newsletter - AIRI / Nanotec IT

nanotec IT
newsletter
Numero 13 aprile 2012
3
Editoriale
Ricerca & Sviluppo
Advances in Optical and MRI-based Theranostic Nanomedicine Smart Supramolecular Architectures for Industrial and Nanomedicine Applications
Aptamer-based protein recognition using CMOS single-photon detector arrays for time-resolved analysis
From Microwave to TeraHertz NanoAmplifiers for Sustainable Applications
Nanostructured metal oxide gas sensors and Electronic nose at SENSOR
Responsive Development of Nanotechnology
Supersonic Cluster Beam Implantation: a novel process for biocompatible and stretchable metallization of elastomers
Nanoparticle imaging at the Mario Negri Institute: an innovative approach to verify the impact of nanomaterials
from the sub-cellular organelles to the whole organism
RF MEMS Phase Shifters For New Generation Phased Array Antennas
X-ray MicroImaging Laboratory (XMI-LAB)
Notizie da NanotechItaly 2011
Notizie
49
49
49
50
51
52
53
54
The Horizon 2020 programme
Partecipazione italiana ai bandi VII PQ ObservatoryNano Project final outcomes
ObservatoryNANO Briefings
The ObservatoryNANO 2012 Regulation & Standards Report
Nanocode final outcomes
Confermata l’edizione 2012 di Nanochallenge& Polymerchallenge
Seminari & Convegni
Altri eventi
nanotec IT
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37
40
42
42
43
44
45
46
European Projects
Networking Event
European Nanotechnology Landscape Report
Cold & Thermal Spray Symposium
Sviluppo responsabile e Nanotossicologia Airi
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5
11
15
19
24
27
31
55
57
Supplemento a Notizie Airi
n. 177 gennaio-aprile 2012
Anno XXVII - 2012
Quadrimestrale
Abbonamento annuo
• Soci Euro 25,00
• Non soci Euro 40,00
Spedizione in abb. postale
comma 20 lett. B art. 2
L. 23.12.96 n. 662
Roma/Romanina
Pubblicità 45%
Autorizzazione Tribunale
di Roma n. 216
del 29 aprile 1986
Redazione AIRI:
00198 Roma
Viale Gorizia, 25/c
tel. 06.8848831, 06.8546662
fax 06.8552949
e-mail: [email protected]
www.airi.it - www.nanotec.it
Immagine Università di
Trieste - Libro Nanomondi,
area Science Park, 2007
FIRST ANNOUNCEMENT: CALL FOR PAPERS & CALL FOR WORKSHOPS
NanotechITALY2012
INTERNATIONAL SHOWCASE FOR NANOTECHNOLOGIES
TING
PROMO
E
RESPONASTIBI OLN
INNOV
International Conference, Venice, November, 21-23, 2012
Nanotechnologies, in connection with the other EU Key Enabling Technologies (KETs), are recognized
as the drivers to address the challenges indicated by the Europe 2020 Agenda and also by the Italian
National Research Programme.
The three day event will highlight how nanotechnologies can contribute to answer these challenges and
promote competitiveness and responsible innovation in a variety of strategic sectors that will shape
future growth. The leading themes of the conference will be:
aAdvanced materials for improved use of resources: industrial manufacturing, processes and
production; multifunctional, lightweight materials; multisector sustainable solutions
aHealth Care: improving the lifelong health and wellbeing of all
aIntelligent and connected world: developing next generation nanodevices and nanosystems
aEnergy and environment: greener products and processes for a sustainable development
aMade in Italy: nanotechnology to support national leading hedge sectors, reshape traditional productions and preserve and protect the cultural heritage
aSafety, ethics and societal impacts
Call for papers deadline: June 15th, 2012
Contributions should address scientific and industrial developments in the above areas and can be in
the form of an oral presentation or a poster.
Call for workshops deadline: June 15th, 2012
Contributions should aim to present, during a dedicated workshop, activity and results of EU, national,
regional research and innovation projects addressing the themes of the Conference. The proponents
are expected to define the workshop program (duration about 2 hours), invite and follow-up with speakers, collect abstracts and coordinate the workshop onsite.
Info and guidance for submission: www.nanotechitaly.it
Organizers:
Airi
nanotec IT
p r i m o
p i a n o
Editoriale
T
he present issue of this Newsletter is in large part devoted to
NanotechItaly 2011, that took place in Venice on the 23-25 of
November 2011. The Conference, at its 4th edition, has become
the National event of reference for nanotechnologies, showcasing, with the contribution of well known Italian and International
experts coming from both academia and industry, the most recent advances of nanotechnology research and application and
the activities going on in this field in Italy.
The three days event has confirmed that nanotechnologies can
bring about unprecedented advantages in a variety of strategic
fields that span from health care, to communication, to transportation or energy and it has shown that in Italy R&D in this field is
rather intense, with University, the major public research institutions and industry actively involved.
This interest is amply justified for nanotechnologies, together with
micro and nano electronics, advanced materials, photonics, industrial biotechnology and advanced manufacturing systems, are
amongst the so called Key Enabling Technologies (KETs) that the
European Commission has indicated in the Europe 2020 Agenda
as the drivers that will propel the future European growth.
It is strategically important for a country, like Italy, to build on these technologies and this commitment must continue also under
the present financial pressure and budget cuts, for nanotechnologies can be one of the tools to secure a competitive position and
a long lasting growth.
A key element must, however, accompany the efforts. Today expectations, in fact, require for the growth to be sustainable and
attentive of the ethical and societal issues and, as a consequence,
Responsible Research and Innovation (RRI) must characterize all
activities undertaken. Europe is particularly aware of this need
and RRI is one of the pillars of the Europe 2020 Agenda. Italy
cannot avoid this challenge and AIRI/Nanotec IT considers a priority in its mission to keep high the attention on the need of RRI
that is also the red line going through NanotechItaly since the
beginning.
The 2011 edition has followed suit as shown by a session dedicated to the theme and by many of the contributions presented
in the various sessions. This feature will be a distinctive character
also of the next edition of the Conference and it will remain a key
feature of the action of AIRI/Nanotec IT.
Elvio Mantovani
Director of AIRI/Nanotec IT
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Advances in Optical and MRIbased Theranostic Nanomedicine
Gregory M. Lanza, Shelton D. Caruthers, Anne H. Schmieder,
Samuel A. Wickline, Dipanjan Pan
Washington University Medical School, Department of Medicine,
Saint Louis, Missouri, USA
N
anomedicine offers unique tools to address intractable medical problems in cancer and cardiovascular disease from entirely
new perspectives.
Molecular imaging, twenty years ago the purview of nuclear medicine, has expanded to all clinically relevant modalities as well
as several new emergent technologies, such as photoacoustic
tomography (PAT)1-3 and spectral (multicolored) computed tomography (CT).4,5
Many of these nanotechnologies are considered “theranostic”,
since they present opportunites for diagnostic imaging and or
drug delivery on the same platform.
Theranostics have shown robust potential in vivo for diagnosing,
characterizing, treating and following proliferating cancers, progressive atherosclerosis, rheumatoid arthritis and much more.
Photoacoustic Tomography and Gold Nanobeacons
Of late photoacoustic imaging (PAI) and tomography have been
of particular interest because of their high spatial resolution and
soft tissue contrast.2 The advantages of optical and ultrasonic
imaging methods are combined in this novel, hybrid, and nonionizing imaging modality.
The tissue is irradiated with a short-pulsed laser beam in the
near-infrared (NIR) and absorption of optical energy, such as by
hemoglobin in erythrocytes, causes thermoelastic expansion and
radiation of photoacoustic (PA) waves.
A wide-band ultrasonic transducer is employed to receive the PA
waves, which are then used to locate and quantify the optical
absorption distribution in the tissue.
PAT has the potential to provide both functional and molecular
imaging in vivo since optical absorption is sensitive to physiological parameters, such as the concentration and oxygenation of
hemoglobin.
PAT has been used for imaging and quantifying the levels of vascularization and oxygen saturation in tumors.
Gold nanoparticles are an obvious choice, pursued by many, for
optical imaging applications because of their excellent optical
properties.3,8-10
Gold particles are excitable in NIR range within the “optical transmission window” of the biological tissues (λ=650-900 nm),
which allows for deeper light penetration, lower autofluorescence, and reduced light scattering.
A major advantage of gold particles is the resistance to photobleaching, unlike small molecule fluorophores that can be excited in
the NIR range.
We have developed colloidal gold nanobeacons (GNB),3 which
represent a nanomedicinal platform that has a “soft” compliant
nature and which are amenable to bio-elimination.
These are essential features for in vivo efficacy and safety for ultimate clinical translation.
Gold nanobeacons incorporate tiny 2-4nm gold nanoparticles
within a bigger (90-250nm), amphiline encapsulated colloidal
suspension.
Depending on the nature of the application, the component gold
nanoparticles can be chosen as either spherical or rod shaped and
tuned to have a more near infrared absorption.
Neovessel formation (i.e., angiogenesis) is an important biosignature of cancer.
One molecular signature, αvβ3-integrin, has received prominent
attention for angiogenic-targeting applications because it is expressed on the luminal surface of activated endothelial cells but
not on mature quiescent cells.
The αvβ3-integrins, heterodimeric transmembrane glycoproteins,
are expressed by numerous activated and proliferating cell types.
Fortunately, the steric constraint of nanoparticles (150nm to
300nm) within the vasculature precludes significant interaction
with nonendothelial integrin-expressing cells, which greatly enhances neovascular target specificity.
αvβ3-GNB were evaluated in a mouse Matrigel™ plug model of
angiogenesis using dynamic PAT imaging over 5 hours.
αvβ3-integrin targeted GNB penetrated the matrigel plug and
bound to nascent, forming vessels still in the process of development (Figure 1).1
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Figure 1.
Top: (A) Digital photograph of a mouse implanted with Matrigel™ plug.
Blue arrow points to the plug. The black dotted area was imaged.
(B) Digital photograph after with skin removed to show the Matrigel™ plug (blue
arrow). Bottom: (B) Photoacoustic (PA) maximum amplitude projection image of
the dotted area. This is a control baseline image (C,D) PA images 3- and 5-hour
post-injection αvβ3-integrin targeted GNB PA. Red arrows point to the angiogenic
sprouts (not visible in B). Reproduced with permission1
Figure 2.
Microscopic examination of FGF Matrigel subcutaneous explant from FVB/NTgN(TIE2LacZ)182Sato mice following injection (IV) of αvβ3-targeted rhodamine labelled GNB
nanoparticles. Panel A presents a low power H&E stained example of an excised Matrigel™ plug with the muscle and skin labeled for orientation.
Fluorescent microscopy revealed the marked accumulation of rhodamine αvβ3-GNB nanoparticles in the immediate Matrigel™ periphery (panel B) that was not
appreciated in the adjacent subcutaneous tissue (panel E). PECAM staining demonstrated abundant microvascularity in both the red (panel C) and blue (panel F) tissue
regions. PECAM distribution in panel B was closely aligned with the targeted rhodamine αvβ3-GNB but microvessels evident in panel F showed no decoration with
rhodamine nanoparticles. Lac-Z staining, which was regulated by the Tie-2 promoter, was negligible in panel D where αvβ3-GNBs were prevalent.
Conversely, Tie-2 staining in panel G closely corresponded to the PECAM signal in panel F. Reproduced with permission 1
These data indicate that the PA signal observed with αvβ3-GNB
was from the forming (PECAM-positive, Tie-2-negative) angiogenic endothelium induced by the Matrigel™ growth factors and
not from mature microvessels (PECAM-positive, Tie-2-positive) in
the plug periphery. While PAT alone cannot differentiate PA signal
derived from forming and stabilized neovessels, with αvβ3-GNB
contrast enhancement, the PAT sensitively discriminates angiogenesis and microvasculature.
Microscopic characterization and confirmation of the Matrigel™
PA imaging result was pursued using a separate cohort of
Rag1tm1Mom Tg(TIE-2-lacZ)182-Sato mice.
Matrigel™ plug angiogenesis was targeted with rhodamine-labeled αvβ3-GNB in vivo then the plug was excised for fluorescent
and light microscopy visualization 2 hours later (Figure 2).
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Perfluorocarbon Nanoparticles
αvβ3-integrin-targeted perfluorocarbon (PFC) nanoparticles (NP)
are a multifunctional theranostic technology with versatile potential demonstrated in a variety of preclinical animal cancer and
atherosclerotic models.11-15
These particles (200 - 300 nm) encapsulate a PFC core with a
monolayer of phospholipids. The biocompatibility of perfluorooctylbromide core is welldocumented, even at large doses, with no
toxicity, carcinogenicity, mutagenicity or teratogenic effects and
it is eliminated unmetabolized through exhalation with a 3-day
biological half-life.16
PFC NPs, like GNBs, are constrained within the vasculature during the targeting phase, which makes them ideal candidates for
specific homing to intravascular biosignatures, such as integrins,
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selectins, or adhesion molecules. We have shown αvβ3-integrintargeted paramagnetic nanoparticles sensitively detect histologically-corroborated angiogenic endothelium using 1.5 T MRI in
New Zealand White rabbits bearing Vx-2 tumors (<1.0 cm) implanted into the hind-limb 12 days previously17, which confirmed
and significantly extended the previous report of Sipkins et al. in
the same model.18 αvβ3-integrin competition studies markedly diminished signal in animals receiving αvβ3-targeted nanoparticles,
supporting the specificity of the nanosystem in vivo.
In a more challenging follow-on study, MR signal enhancement
from the targeted angiogenic vasculature was apparent 0.5 hours
following IV administration of αvβ3-integrin-targeted PFC nanoparticles to athymic mice implanted with human melanoma xenografts (C-32, ATCC, <40mm3); the signal became progressively more prominent over 2 hours (177%).19 The molecular imaging
results were corroborated microscopically.
Later, αvβ3-targeted nanoparticles incorporating minute dosages
of fumagillin, an antiangiogenic therapeutic, were shown to diminish the development of neovasculature and to reduce Vx-2
tumor growth in rabbits. 7 (Figure 3) Neither nontargeted fumagillin nanoparticles nor αvβ3-targeted nanoparticles without drug
reduced angiogenesis or diminished tumor growth.
Figure 3.
Diminished αvβ3-integrin contrast enhancement in T1-weighted, fat suppressed,
3D gradient echo MR, single slice images (250 x 250 μm, 500 μm slices, TR/TE =
40/5.6 ms, 65o flip angle, 1.5T) in rabbits administered αvβ3-targeted fumagillin
nanoparticles (top) versus those given αvβ3-targeted nanoparticles without drug
(bottom).
Left: Enhancing pixels, color coded in yellow (arrows), demonstrate sparse areas
of angiogenesis in fumagillin treated animal (top).
Right: 3D neovascular maps of example Vx-2 tumors on day 16 following αvβ3targeted fumagillin nanoparticles (top) versus αvβ3-nanoparticles without drug
(bottom).
Note the asymmetric distribution of angiogenic signal (color coded in blue) over
the tumor surface in both the control and treated animals.
Neovessel dense islands and the interspersed fine network of angiogenic
proliferation over the tumor surface are diminished in rabbits receiving the
targeted fumagillin treatment.
Reproduced with permission.7
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Quantitative MR molecular imaging with αvβ3-targeted paramagnetic nanoparticles further revealed that the neovasculature was
distributed predominately in the peripheral aspects of the tumor
accounting for seven percent of that volume.
High-resolution three-dimensional neovascular maps illustrated
the coherent asymmetric expression of angiogenesis as a few
confluent regions of high-density neovascularity with an interspersed reticular network of enhancing voxels.(Figure 3) We have
reported effective in vivo delivery of fumagillin with αvβ3- targeted perfluorocarbon (PFC) nanoparticles at a fraction of the
dosage required systemically for TNP-470 in previous preclinical
and clinical studies.7, 20-24 In these studies, fumagillin was hydrophobically entrapped in the phospholipid surfactant, targeted to
angiogenic endothelial cells, and delivered through a mechanism we described as “contact facilitated drug delivery” (CFDD).13
Tethering of the nanoparticle to the target cell surface facilitated the interaction and hemifusion of the two lipid membranes,
which facilitates the passive transfer of the drug and phospholipids from the nanoparticle surface to the outer leaflet of the
target cell membrane.
The drug is then translocated to the inner leaflet through an ATP
dependent mechanism.25, 26 CFDD eliminates the need for particle
internalization with subsequent endosomal drug payload escape
or extracellular particle release with diffusion into the cell.
αvβ3-targeted fumagillin PFC nanoparticles have been shown to
prolong the pharmacodynamic antiangiogenic effect in preclinical models of atherosclerosis and arthritis.7,20,23,24
Lipase-labile Prodrugs
Despite these promising in vivo results, the “drugability” of native fumagillin is compromised by chemical instability associated
with two highly reactive epoxide rings at the active site and a
photosensitive conjugated decatetraenedioic tail.
The fumagillin chromophore is reported to be photolytically and
stoichiometrically transformed by first-order rates to new chromophoric analogs (“neofumagillin (s)”) for which the apparent
absorptivities are diminished and maxima are shifted into the violet region.
Moreover, parallel pharmacokinetic tracking of αvβ3-targeted fumagillin PFC nanoparticle components revealed substantial premature loss of the drug during circulation to the target despite
its low aqueous solubility and high in vitro retention during dissolution studies.
Although academically the principles of theranostic nanomedicine could be pursued, pharmaceutical development and clinical
translation of the concept was compromised, which inspired the
de novo design and development of the Sn-2 phospholipase labile fumagillin prodrugs in combination with integrin targeted PFC
nanoparticles.6
The synthesis of fumagillin into the prodrug involved saponifying
fumagillin to fumagilol, which preserved the critical di-epoxide
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active moiety of the molecule while eliminating the photosensitive conjugated decatetraenedioic tail group.
This tail group was effectively substituted by the seven-carbon
Sn-2 acyl group of the phosphatidylcholine backbone, i.e.,
PazPC.
The removal of fumagillin’s photosensitivity created a pharmaceutically relevant API (active pharmaceutical ingredient) with acceptable storage and handling properties.
As a phospholipid component, the self assembly of the prodrug
into lipid surfactant of the PFC nanoparticles, or any similar lipid
particle, was easily accomplished.
The resultant particle was very stable, and essentially unchanged
physicochemically from the drug free particles at API inclusion
levels up to 2 mole% of the surfactant.
The retention of the fumagillin prodrug in the particle during in
vitro dissolution was excellent, very similar to the results obtained
with the native fumagillin.
Moreover, Sn-2 phospholipase prodrugs incorporated into PFC
nanoparticles were stable in serum alone or after enrichment
with exogeneous phospholipase A2.
Lipase liberation of the drug in vitro required the addition of isopropyl alcohol to “crack” or destroy the emulsion in order to expose the surfactant components to the enzyme.
Thus, in αvβ3- fumagillin-prodrug NP (αvβ3-Fum-PD NP) the API
is nestled into the hydrophobic phospholipids layer where it is
“protected” from hydrolysis and lipase activation in transit to the
target.6
Upon reaching the target cell, binding of the particle to surface
receptor brings the drug-rich surfactant and cell membrane into
close proximity (i.e., CFDD), which favors hemi fusion and translation of the surfactant components into the outer membrane
leaflet.
Phospholipids from PFC nanoparticles transfer into the inner cell
membranes, in an ATP dependent process, and distribute throughout the interconnected internal membrane architecture.
Once the Sn-2 fumagillin prodrug has entered the cell, the liberation by intracellular enzymes resulted in equivalent bioavailability
of native API and the prodrug API, perhaps numerically favoring
the prodrug.
Using the MatrigelTM plug model of angiogenesis discussed above, the effectiveness of the integrin-targeted fumagillin prodrug
(αvβ3-Fum-PD NP) was clearly demonstrated to be superior to the
nontargeted prodrug (nontargeted (NT)-Fum-PD NP), targeted
fumagillin (αvβ3-Fum (native) NP) and control (αvβ3- no drug (ND)NP) nanoparticles based on MR angiogenesis molecular imaging.
(Figure 4) The very poor effectiveness of the αvβ3-Fum NP was
related to the more rapid clearance of the PFC nanoparticles in
rodents than rabbits 27 and the anticipated premature loss of
the API. These data emphasized the benefits of the αvβ3-Fum-PD
NP formulation in vivo, which experienced the same pharmacokinetics but retained and delivered the prodrug payload at effica8
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cious dosages to the target cells.6 Although the concept of Sn-2
phospholipid prodrugs has never been considered for targeted
drug delivery as presented here, a precedence for the formation
of Sn-2 phospholipid prodrugs was found for two compounds,
indomethacin and valproic acid.28,29
Figure. 4
In vivo MR signal enhancement post treatment with targeted fumagillin or
fumagillin prodrug nanoparticles.
Reproduced with permission 6
Unfortunately, oral administration of an indomethacin prodrug
decreased the total amount of drug absorbed in comparison to
the administration of free indomethacin.
When the prodrug was administered intravenously as an untargeted liposome, the bioavailability of the prodrug was further reduced relative to oral administration of the phospholipid prodrug
and free drug.
Analogous results were obtained for valproic acid prodrug studied similarly.28 Jorgensen pursued the use of untargeted liposomes containing a Sn-2 prodrugs anticipating that increased
secretory phospholipase liberated by cancers would facilitate the
release of the API in the proximity of a tumor increasing the local
drug concentration.30-34 However, the effectiveness of this approach was modest.30 In general, the efficacy of the liposomal Sn-2
prodrugs to liberation by secretory phospholipases was dependent on water accessibility to the bond, which was less available
for the synthetic ether-lipid prodrugs than natural lipids.
For the targeted PFC nanoparticles, the reduced water accessibility of the Sn-2 fumagillin prodrug is highly desirable, preventing
premature release or metabolism until the ligand directed CFDD
mechanism of drug delivery ensues.
Conclusion
Nanomedicine is an evolving field, which has begun to overcome the numerous barriers that previously prevented translation
to the clinic.
Although the path to routine use remains long, the light at the
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end of the tunnel is now visible.
New agents for diagnostic imaging and targeted treatment have
reached the clinic and are winding through the complicated but
thorough multiphasic evaluation process.
Next generation nanosystems tuned to emerging modalities are
now reaching the preclinical safety and stability testing under
good laboratory practices today and will be in the clinic in the
next two to three years.
Indeed, our approach to medicine will slowly begin to change as
physicians are entrusted to use and optimize the clinical nanosystems in the most prudent manner to attack intractable problems
from a new angle.
References
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SA, Wang LV, Lanza GM. Molecular photoacoustic imaging
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2. Yao J, Wang LV. Photoacoustic tomography: fundamentals, advances and prospects. Contrast Media Mol Imaging.
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3. Pan D, Pramanik M, Wickline SA, Wang LV, Lanza GM.
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4. Roessl E, Proksa R. K-edge imaging in x-ray computed tomography using multi-bin photon counting detectors. Phys
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5. Pan D, Roessl E, Schlomka J-P, Caruthers S, Senpan A, Scott
M, Allen J, Zhang H, Hu G, Gaffney P, Choi E, Rasche V,
Wickline S, Proksa R, Lanza G. Computed tomography in color: NanoK-enhanced spectral CT molecular imaging. Angew
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Christy D, Sharkey A, Miller J, Gaffney P, Wickline S. A novel
site-targeted ultrasonic contrast agent with broad biomedical application. Circulation. 1996;94:3334-3340
12. Flacke S, Fischer S, Scott M, Fuhrhop R, Allen J, Mc Lean M,
Winter P, Sicard G, Gaffney P, Wickline S, Lanza G. A novel MRI
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for detecting vulnerable plaques. Circulation. 2001;104:1280
-1285
13. Lanza GM, Yu X, Winter PM, Abendschein DR, Karukstis KK,
Scott MJ, Chinen LK, Fuhrhop RW, Scherrer DE, Wickline SA.
Targeted antiproliferative drug delivery to vascular smooth
muscle cells with a magnetic resonance imaging nanoparticle contrast agent: implications for rational therapy of restenosis. Circulation. 2002;106:2842-2847
14. Winter PM, Shukla HP, Caruthers SD, Scott MJ, Fuhrhop RW,
Robertson JD, Gaffney PJ, Wickline SA, Lanza GM. Molecular
imaging of human thrombus with computed tomography.
Acad Radiol. 2005;12(Suppl 1):9-13
15. u X, Song S-K, Chen J, Scott M, Fuhrhop R, Hall C, Gaffney P,
Wickline S, Lanza G. High-resolution MRI characterization of
human thrombus using a novel fibrin-targeted paramagnetic
nanoparticle contrast agent. Mag Reson Med. 2000;44:867872
16. Krafft M. Fluorocarbons and fluorinated amphiphiles in
drug delivery and biomedical research. Adv Drug Del Rev.
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17. Winter PM, Caruthers SD, Kassner A, Harris TD, Chinen LK,
Allen JS, Lacy EK, Zhang H, Robertson JD, Wickline SA, Lanza
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20. Winter P, Neubauer A, Caruthers S, Harris T, Robertson J,
Williams T, Schmieder A, Hu G, Allen J, Lacy E, Wickline S,
Lanza G. Endothelial alpha(nu)beta(3)-Integrin targeted fumagillin nanoparticles inhibit angiogenesis in atherosclerosis. Arterioscler Thromb Vasc Biol 2006;26:2103 - 2109
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Robertson JD, Wickline SA, Lanza GM. Three-dimensional
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MR mapping of angiogenesis with {alpha}5{beta}1({alpha}
{nu}{beta}3)-targeted theranostic nanoparticles in the MDAMB- 435 xenograft mouse model. FASEB J. 2008;22:41794189
22. Winter P, Caruthers S, Zhang H, Williams T, Wickline S, Lanza
G. Antiangiogenic synergism of integrin-targeted fumagillin
nanoparticles and atorvastatin in atherosclerosis. J Am Coll
Cardiol Img 2008;1:624-634
23. Zhou HF, Chan HW, Wickline SA, Lanza GM, Pham CT.
Alphavbeta3-targeted nanotherapy suppresses inflammatory arthritis in mice. FASEB J. 2009;23:2978-2985
24. Zhou HF, Hu G, Wickline SA, Lanza GM, Pham CT. Synergistic
effect of antiangiogenic nanotherapy combined with methotrexate in the treatment of experimental inflammatory
arthritis. Nanomedicine (Lond). 2010;5:1065-1074
25. Partlow K, Lanza G, Wickline S. Exploiting lipid raft transport with membrane targeted nanoparticles: A strategy
for cytosolic drug delivery. Biomaterials 2008;29:3367-3375
26. Soman N, Baldwin S, Hu G, Marsh J, Lanza G, Heuser J,
Arbeit J, Wickline S, Schlesinger P. A platform of molecularly
targeted nanostructures for anticancer therapy with cytolytic
peptides. J Clin Invest. 2009;119:2830-2842
27. Hu G, Lijowski M, Zhang H, Partlow KC, Caruthers SD, Kiefer
G, Gulyas G, Athey P, Scott MJ, Wickline SA, Lanza GM.
Imaging of Vx-2 rabbit tumors with alpha(nu)beta3- integrintargeted 111In nanoparticles. Int J Cancer. 2007;120:19511957
28. Arik D, Duvdevani R, Shapiro I, Elmann A, Finkelstein E,
Hoffman A. The oral absorption of phospholipid prodrugs:
In vivo and in vitro mechanistic investigation of trafficking of
a lecithin-valproic acid conjugate following oral administration. J Control Release. 2008;126:1-9
29. Dahan A, Duvdevani R, Dvir E, Elmann A, Hoffman A. A novel mechanism for oral controlled release of drugs by continuous degradation of a phospholipid prodrug along the
intestine: In-vivo and in-vitro evaluation of an indomethacin–
lecithin conjugate. J Control Release. 2007;119:86-93
30. Davidsen J, Jørgensen K, Andresen TL, Mouritsen OG.
Secreted phospholipase A2 as a new enzymatic trigger
mechanism for localised liposomal drug release and absorption in diseased tissue. Biochimica et Biophysica Acta Biomembranes. 2003;1609:95-101
31.Andresen TL, Davidsen J, Begtrup M, Mouritsen OG,
Jørgensen K. Enzymatic release of antitumor ether lipids by
specific phospholipase A2 activation of liposome-forming
prodrugs. J Med Chem. 2004;47:1694-1703
32. Jensen SS, Andresen TL, Davidsen J, Høyrup P, Shnyder SD,
Bibby MC, Gill JH, Jørgensen K. Secretory phospholipase A2
as tumor-specific trigger for targeted delivery of a novel class
of liposomal prodrug anticancer etherlipids. Mol Cancer
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activation and release of liposomal prodrugs and drugs in
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34. Peters G, Møller M, Jørgensen K, Rönnholm P, Mikkelsen M,
Andresen T. Secretory phospholipase A2 hydrolysis of phospholipid analogues is dependent on water accessibility to the
active site. J Am Chem Soc 2007;129:5451-5461
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Smart Supramolecular
Architectures for Industrial
and Nanomedicine Applications
M. Ambrosi*, S. Nappini*, M. Bonini*, E. Fratini* and P. Baglioni*
*University of Florence, Chemistry Department and CSGI
C
SGI, the Italian Center for Colloid and Nanoscience, was
founded in 1993 with the mission of developing new smart supramolecular, colloidal and nano-systems, both as fundamental
research and for specific industrial applications. CSGI scientific
activity concerns all those systems whose large interface confers to them peculiar properties, so spanning from soft matter
to nanotechnology. In this article we highlight some meaningful
examples of how soft matter can join nanoscience for the development of innovative high-performing devices. The potential applications range from expected areas, such as nanomedicine, to
novel fields, such as the conservation of works of art, to sectors
that, in spite of being perceived as more traditional, can represent
opportunities of real application of surface and nano-science for
the production of advanced materials with conventional uses.
Magnetoliposomes for controlled drug release in the presence of low-frequency magnetic field.
In the past few years, we extensively described the synthesis and
characterization of several types of nanomaterials, including ferrite nanoparticles[1-3]. Magnetic nanoparticles can be successfully
encapsulated into drug carriers (such as liposomes or polymeric
microcapsules) to produce a class of targeted drug delivery systems that can be driven to the specific location in the body and,
once at the target site, release the embedded drug by simply
applying an external oscillating magnetic field (Figure 1). Among
all possible drug vectors, liposomes have attracted growing interest thanks to their biocompatibility, flexibility in composition and
size, the easy modification of surface properties, and their ability
to encapsulate both hydrophilic and hydrophobic molecules into
the aqueous pool or in the lipid bilayer, respectively. We, therefore, loaded cobalt-ferrite nanoparticles, either naked or differently surface functionalized, both into the inner pool[4,5] or in
the membrane[6] of liposomes. A model fluorescent compound
(carboxyfluorescein) was also loaded into the aqueous pool in
order to investigate the release mechanism and kinetics. Despite
a high-frequency alternating magnetic field is usually employed
to promote local heating of nanoparticles located in the tumor
cells (magnetic fluid hyperthermia) leading to thermal ablation
of such cells, a low-frequency alternating magnetic field should
be preferred for in vivo applications. Thus, we proceeded by investigating the effect of a low-frequency field on the behavior of
the prepared magnetoliposomes, so minimizing the hyperthermic
contribution.
Figure 1. Sketch of CoFe2O4 nanoparticle-embedded liposomes containing
carboxyfluorescein and subsequent release of the fluorescent compound upon
application of a low-frequency alternating magnetic field (LF-AMF). Adapted from
ref.[4] with permission from Royal Society of Chemistry.
The release efficiency, mechanism and kinetics were found to
strongly depend on the presence of the magnetic nanoparticles.
The application of the magnetic field promoted nanoparticles’
motions, such as flipping and shaking, which partially destabilized the membrane with formation of pores and/or defects that
favored the release of the fluorescent molecules. The release occurred without rupture of the vesicles, as confirmed by confocal
microscopy investigations[7] (Figure 2).
It is worthwhile to note that we were able to control and modulate both the loading efficiency and the release profile by modifying the surface functionalization of nanoparticles, for example
by coating with citrate[5] or oleic acid[6]. Particles coated with
oleic acid were physisorbed on the lipid bilayer instead of being
loaded in the inner aqueous pool. After application of the field,
their presence was found to induce a strong perturbation of the
bilayer structure, followed by the disruption of some vesicles. This
heavy structural rearrangement was also confirmed by differential scanning calorimetry measurements, which indicated that
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the lipid bilayer progressively lost its original structure (lamellar
gel phase Lβ) to completely transform into a liquid crystalline (Lα)
phase 8 hours after the application of the field.
Figure 2. Confocal microscopy images of fluorescent dye-loaded vesicles
containing citrate-coated magnetic nanoparticles (a) in the absence of magnetic
field at time zero and (b) after 30 min. Vesicles (c) exposed for 5 min and (d) 10
min to the magnetic field and (e) 10 min after the field application. Vesicles again
exposed to magnetic field for (f) 5 min and (g) 10 min and (h) 10 min after the
last field application. Adapted from ref.[5] with permission from Royal Society of
Chemistry.
The release curve obtained for nanoparticles coated by oleic acid
(physisorbed on the bilayer) was significantly different from curves obtained for naked and citrate-coated nanoparticles embedded into the pool of the vesicles (Figure 3).
Figure 3. Release curves of control sample (liposomes without magnetic
nanoparticles) and magnetoliposomes loaded respectively with naked, citratecoated and oleic acid-coated nanoparticles (NPs) after exposure to an alternating
magnetic field at 5.2 kHz for 50 minutes. Adapted from ref.[6] with permission of
the Royal Society of Chemistry.
The presence of hydrophobically modified nanoparticles within
the bilayer hampered the diffusion of the fluorescent molecules
in the first 6 hours. Afterwards, the magnetic field effect started to cause the membrane destabilization and, after 8 hours,
a structural change of the membrane occurred which favored
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the release. The leakage reached a value of about 90% after 30
hours, indicating that some liposomes broke during time.
Therefore, magnetic nanoparticles could be efficiently loaded
into liposomes to form drug carriers whose release profile could
be modulated and triggered by functionalizing the embedded
particles. Carriers prepared with particles coated by oleic acid,
for example, possessed a “lag time” that could be employed to
achieve a complete release at the target site with no loss of drug
during the transport.
Magnetic Nanosponges for the Cleaning of Works of Art
Synthetic polymers have been largely used in the past for the
protection of paintings and they are nowadays recognized as deleterious to the preservation of the artwork. Unfortunately, their
selective removal without damage of the underlying paint layer
can be very difficult to attain. Pure organic solvents, in fact, can
cause losses by penetrating the paint layer. The use of solvents in
their gelated state partially overcomes this drawback: the capillary
penetration of the solvent into the artifact is strongly decreased
through its immobilization within the gel network. In the past,
we proposed the use of oil-in-water microemulsions to remove
polymer coatings, such as aged Paraloid B72 resin, from wall
paintings[8-10]. Due to their large interface, the use of microemulsions allowed exploiting the lowest possible amount of toxic
organic solvent. The polymer could be efficiently solubilized in
the oil- nanostructured phase, so leading to an effective and safe
cleaning procedure with low environmental impact. We further
developed the technique by associating the o/w microemulsion
to a nanomagnetic sponge obtained by incorporating magnetic
nanoparticles into a polyacrylamide-based gel (Figure 4)[11]. The
magnetic nanoparticles were homogeneously distributed into the
gel and slightly affected its water retention properties[12].
Figure 4. Schematic representation of the process of loading the microemulsion
into the nanomagnetic sponge structure. Adapted from ref.[11] with permission of
the American Chemical Society.
The microemulsion was easily loaded into the gel porous structure and, through the pores, it could migrate towards the surface
of the gel, coming in contact with the artwork, solubilize the
polymer into the droplet and transfer it to the gel structure. Then,
it could be removed by simply applying an anisotropic magnetic
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field with the aid of a permanent magnet and the gel could be
dried and reused.
Importantly, the gel could be shaped as desired with a fine spatial control and then removed by using for example a permanent
magnet, with no need of direct contact of the magnet with the
precious artifact surface.
Infrared spectroscopy (not shown) and microscopy investigations
provided evidence of a complete removal of the polymer coating
with no residuals of magnetic gel and nanoparticles on the treated surface (Figure 5).
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order to tailor the dimension and structure of the final product. A
stringy-looking gelatinous precipitate was first obtained by addition of sodium hydroxide to a zirconyl chloride aqueous solution
(bottom-up step). The initially formed solid was constituted by
branched clusters with a mass fractal structure. The clusters slowly de-aggregated to finally form primary units with radius of gyration of 6 Å, passing through intermediate structures constituted
by clusters with lower fractal dimensions and elongated objects
(top-down step) (Figure 6).
Figure 5. Application of the nanomagnetic gel to a fresco painting coated by
Paraloid B72. Left), Fresco coated by Paraloid, the circle shows the area that will
be treated with the gel; Center), Gel treatment; Right), The area treated by the gel
appeared clean.
In conclusion, we developed a new magnetic gel that could be loaded by microemulsions or micellar solutions, easily manipulated
and shaped and magnetically removed from the application area.
This system allows cleaning works of art without any side effects,
so representing a breakthrough in conservation science.
Nanogres®: An innovative nanostructured zirconia-based
coating to produce ceramic tiles with enhanced mechanical
and stain resistance.
Porcelain stoneware tiles are widely used due to their technological characteristics such as the high hardness, wear resistance, fracture toughness and bending strength. Nevertheless, the
presence of micro- and mesopores on the surface make both
polished and as-fired tiles susceptible to dirt penetration, with
formation of stains and halos that can be very difficult to remove.
Reducing the porosity of porcelanized tiles could be very onerous,
especially from an economical point of view, since all step of the
manufacturing process should be taken into account and opportunely varied.
We developed a versatile and cost-effective treatment that allowed addressing the stain resistance issue with simultaneous
enhancement of mechanical properties and without altering the
original aesthetical qualities. The green compacts were treated by
a mixture of micronized ceramic oxides and nanosized zirconium
hydroxide and a protective coating was formed upon firing.
Zirconium hydroxide nanoparticles were synthesized by a bottom-up/top-down combined route that could be finely tuned in
Figure 6. SAXS profiles of samples after addition of sodium hydroxide with
different degree of aging (from 4 h to 5640 h). The broken line represents q-2
power-law while the dotted one refers to q-1. Continuous red lines represent the
best fitting results. Original data and corresponding fitting have been offset for
graphical purposes. Inset): Pictures and schematic representations of the initially
formed precipitate containing mass fractals, intermediate objects and the clear
solution containing the primary units.
A transparent solution was formed in about 2 weeks after the initial formation of the precipitate. It was mixed with a micronized
glass frit opportunely chosen in order not to alter the color and
roughness of the tile. The glass component melted upon firing,
totally or partially filling the surface pores and embedding the
formed zirconium oxide. The nanoparticles of zirconium hydroxide, in fact, acted as nucleation centers for the crystallization of
nanostructured zirconia in situ. The so developed zirconia was
small enough not to alter the appearance of the tile, but it could
still enhance the tile hardness up to three times. For example,
Vickers hardness increased from about 700 before treatment
to 2100 after treatment. The treated tiles appeared completely
stain resistant, as evidenced by tests performed both following
the standard procedure (ISO-10545-14) and by using an indelible
pen (Figure 7).
We set up a versatile, cheap and environmentally friendly treatment able to confer to ceramic tiles both stain and mechanical
resistance. The treatment can be easily extended on an industrial
scale to a wide variety of ceramic tiles, ranging from porcelain stoN e w s l e t t e r
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neware to “cotto”. The described synthetic procedure and overall
treatment were patented [13,14] and the used ceramic oxide mixture is now a registered trademark called NANOGRES®.
(a)
(b)
Figure 7. Tile (a) before and (b) after the treatment by NANOGRES®. The stain,
still visible after cleaning on the tile before treatment, was produced by an
indelible pen and cleaned by ethyl alcohol.
References
[1] Bonini, M.; Wiedenmann, A.; Baglioni, P. Physica A 2004, 339,
86-91.
[2] Bonini, M.; Wiedenmann, A.; Baglioni, P. J. Phys. Chem. B
2004, 108, 14901-14906.
[3] Bonini, M.; Wiedenmann, A.; Baglioni, P. J. Appl. Cryst.
2007, 40, s254-s258.
[4] Nappini, S.; Baldelli Bombelli, F.; Bonini, M.; Nordèn, B.;
Baglioni, P. Soft Matter 2010, 6, 154-162.
[5] Nappini, S.; Bonini, M.; Baldelli Bombelli, F.; Pineider, F.;
Sangregorio, C.; Baglioni, P.; Nordèn, B. Soft Matter 2011,
7, 1025-1037.
[6] Nappini, S.; Bonini, M.; Ridi, F.; Baglioni, P. Soft Matter 2011,
7, 4801-4811.
[7] Nappini, S.; Al Kayal, T.; Berti, D.; Nordèn, B.; Baglioni, P. J.
Phys. Chem. Lett. 2011, 2, 713-718.
[8]Carretti, E.; Dei, L.; Baglioni, P. Langmuir 2003, 19.
[9]Carretti, E.; Giorgi, R.; Berti, D.; Baglioni, P. Langmuir 2007,
23, 6396-6403.
[10]Carretti, E.; Salvadori, B.; Baglioni, P.; Dei, L. Stud. Conserv.
2005, 50, 1-8.
[11]Bonini, M.; Lenz, S.; Giorgi, R.; Baglioni, P. Langmuir 2007,
23, 8681-8685.
[12]Bonini, M.; Lenz, S.; Falletta, E.; Ridi, F.; Carretti, E.; Fratini,
E.; Wiedenmann, A.; Baglioni, P. Langmuir 2008, 24, 1264412650.
[13]Ambrosi, M.; Baglioni, P.; Bonini, M.; Fratini, E. Italian Patent
2006, IT2006FI00313.
[14]Baglioni, P.; Ambrosi, M.; Dei, L.; Faneschi, M.; Mancioli, L.;
Santoni, S. International Patent 2007, WO2007EP53351.
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Contact
Piero Baglioni
Department of Chemistry and CSGI
University of Florence
Via della Lastruccia, 3 – 50019, Sesto Fiorentino, Firenze
Tel. +390554573033
[email protected]
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Aptamer-based protein
recognition using CMOS
single-photon detector arrays
for time-resolved analysis
Cecilia Pederzolli
FBK - Bruno Kessler Foundation, Center for Materials and Microsystems
Coordinator of “A NAno on MIcro approach to a multispectral analysis system for
protein essays (NAoMI)” project
Introduction
M
odern medicine approaches diagnosis calling for detailed,
specific and fast detection of molecular markers. Early diagnosis,
generalized screening and patient follow up are some benefits
that such approach allows. However, this detailed detection, identification and quantification can be very complex, expensive and
time consuming if realized with traditional laboratory methods.
To overcome such issues, small portable lab-on-a-chip systems
are continuously developed and improved, increasing sensitivity,
specificity and implementing automated devices that could also
be utilized on field.
In this context, NAoMI (NAno on MIcro) develops lab-on-chip devices and new materials that represent an innovative approach
for performing prognostic tests in non-specialized infrastructures
(e.g. Point of Care). Particularly, NAoMI aims to develop highperformance, multi-wells optical biosensors, which will be used
for detecting small concentrations of blood biomarkers.
The project activity has been focused on the study and development of monolithic silicon-based CMOS-compatible micro and
nano systems that integrate different functional layers: photonic,
fluidic and biofunctional.
NAoMI has been developing two different main configurations:
i) the first one (transparent microarray sensor - TMS) is built enclosing a transparent array with direct far-field illumination of
the biorecognition layer (that is discussed in detail in this paper);
ii) a second, more advanced configuration utilizes a photonic
layer (waveguide) with biomolecular receptors immobilized on
its surface and with an evanescent field for fluorophores excitation. The second configuration confines and guides the light in a
submicrometer-size channel, therefore enhancing the interaction
between an optical probe and biomolecular complexes (aptamer/
protein). Our approach replaces the microscope system used for
measurements of the fluorescence with a matrix of SPAD (Single
Photon Avalanche Diode) detectors developed in the silicon microelectronic technology and miniaturized pulsed light sources. Each
element of the SPAD can detect single photons with high quantum efficiency and low noise; the number of elements match the
number of biofunctional spots in a microarray. The detection of
human thrombin using thrombin-binding aptamers has been selected as a proof of principle of the NAoMI innovative approach.
DNA aptamers in particular have been selected as specific biorecognition elements for their advantages over antibodies: they are
obtained by synthesis, allowing their facile and controlled linking
on surfaces; they can be very specific and robust, permitting also
the regeneration and reutilization of the bioactive layer.
The TMS configuration (transparent microarray sensor) has shown
an optimal detectable range of 5–1000 nM protein concentration
with good sensitivity and selectivity. Furthermore, the sensor can
be possibly improved and standardized for direct detection of
other blood proteins of clinical interest, such as growth factors
(i.e. VEGF).
A summary of the main achievements and technical innovations
is reported (see Scheme 1):
• High sensitivity, multi-well sensor for protein detection; stateof-the-art detection limit for biosensors.
• Novel optical sensors based on an innovative monolithic matrix
detector (i.e. SPAD detectors) and on bioaffinity reactors (aptamer/protein).
• Development of a diagnostic test which exceeds the antibody/
antigen mechanism with the use of DNA aptamers, synthetic
molecules able to recognize only one type of molecule in the
blood.
• Polymeric microfluidic devices which enable the direct injection
of the biological samples.
• Integrated approach (photonics, fluidics, biochemistry).
• Development of a portable platform.
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Scheme 1. Main achievements of the NAoMI project.
Development of a fluorescence-based aptasensor
A biosensor based on fluorescence was designed and realized.
It consists of three different layers: i) a detection layer, ii) a microfluidic layer, and iii) a biorecognition layer. The excitation and
emission system is orthogonal to the chip surface, for the direct
far-field illumination of the biorecognition layer made of 256
aptamer spots. The device includes a disposable part (the biorecognition layer and the microfluidic layer) and a portable, reusable
part for direct reading. Figure 1 depicts the prototype system on
the lab bench, describing its main parts.
Detection layer
The sensor is based on a 32x32 pixel CMOS SPAD array [L.
Pancheri et al. Proc. International Image Sensor Workshop,
Hokkaido, Japan, 2011], having 25µm pixel pitch and 20.8% fill
factor. Each pixel is composed of a SPAD and a time-gated analog
counter, and is capable of nanosecond gating at up to 80MHz
pulse repetition rate. The compact in-pixel analog counter is used
to accumulate the photon-detection events without needing a
high frame rate array readout, while maintaining a shot-noise
limited operation.
A pulsed LED is used as fluorescence excitation source, collimated
and filtered in order to reduce its spectral bandwidth. Pulsed operation is used together with sensor gating to reduce the effect
of detector dark counts on the measurement precision, while allowing the use of a small average excitation power. Four time16
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windows have been implemented in this architecture, with a time
width that can be set within the range 800ps-100ns and with a
resolution of 200ps, allowing the measurement of the lifetime of
the fluorophores.
Microfluidic layer
The reaction chamber is realized on silicon and consists of an
array of micro-wells closed with an optically transparent, 2µm
thick, glass membrane made of a SiO2/Si3N4/SiO2 multilayer. The
array is mounted on a fluidic layer completely made of PDMS. The
fluidic layer consists of a peristaltic pump and integrated pneumatic valves. On-chip reservoirs and microchannels are used to
deliver the different solutions to the reaction sites in a controlled
manner.
Biorecognition layer
The primary aptamer layer was immobilized onto the micro-wells
silicon oxide surface as an array of 256 spots, using a functional
silane intermediate layer, deposited in wet conditions.
Briefly, after a piranha activation, the substrate was placed in a
mercaptopropyltrimethoxysilane (MPTMS) toluene solution (1%
v/v) at 60°C for 10 minutes. The primary DNA aptamer (5’-HO(CH2)3-S-S-GGT TGG TGT GGT TGG-3’), carrying a dithiol chemical group at the 5’ end was then immobilized on the sensor surface in carbonate buffer. After a washing step, the surface was
passivated with 1mM mercaptoethanol for 2 hours.
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a lifetime measure of the fluorescein molecule were obtained as
reported in Figure 3, panel a and panel b respectively.
Figure 1: Measurement setup with a closed view of the microfluidic network and
the bioreactors.
Results
Before testing the integrated aptamer-based protein chip, the
separate functional layers were analyzed and optimized. First
of all, the SPAD detector performances were evaluated using a
microarray of fluorescently labelled avidin and Evidots-quantum
dots deposited on a microscope slide in an alternated pattern
(Figure 2, panel a). The built sensor was able to discriminate the
two fluorophores thanks to their different lifetime, namely about
4ns and 16ns for AlexaFluor488 and Evidots, respectively (Figure
2, panel c).
Figure 2: Spotted microarray of AlexaFluor 488-avidin and quantum dots. Scale
bar 300 µm. Panel a: fluorescence microscopy image of the deposited array, avidin
spots are green, quantum dots red. SPAD acquisition of the same sample is shown
in panels b (intensity) and c (lifetime).
The detector was also tested in terms of sensibility. A 20 µM concentration of fluorescent derivative of the primary DNA aptamer
was spotted on silanizated silicon surface; after washing, an aptamer monolayer remained on the surface. An intensity signal and
Figure 3: Spotted microarray of 20µM fluorescein-labelled DNA aptamer
immobilized on silanizated silicon oxide surface measured by SPAD detector as
intensity (panel a) and lifetime (panel b). Scale bar 300 µm.
A characterization of the biorecognition layer was then performed. The silanization efficacy was evaluated chemically and
morphologically using XPS (X-ray Photoelectron Spectroscopy)
and AFM (Atomic Force Microscopy) measurements. The AFM
characterization of MPTMS deposited on silicon oxide samples revealed uniformly distributed features, with a moderate increment
in the initial surface roughness. The XPS analysis showed an increase in the carbon content due to the silane aliphatic chain and
the presence of a sulphur peak compatible with the thiol group
of the aptamer. The immobilization of the fluorescent primary
DNA aptamer on silanated surfaces was evaluated in terms of
density and homogeneity via spectrofluorimetric and microscopy
analysis, obtaining an immobilized DNA aptamer density ranging
from 0.5 to 7.5 x 1012 molecules/cm2.
The peristaltic pumps present in the microfluidic layer were also
tested with complex biological solutions such as serum and whole
blood, demonstrating an efficient transport of biological samples
toward reaction sites and an efficient washing procedure.
After testing the separate functional layers, an aptamer-functionalized microwells array was mounted on the microfluidic platform.
A 300 nM thrombin protein was incubated for 20 minutes on the
aptamer- functionalized microwells; after washing, a further incubation with a secondary fluorescent labelled DNA aptamer (5’AlexaFluor488-AGTCCGTGGTAGGGCAGGTTGGGGTGACT-3’)
was performed. The fluorescence was measured with the SPAD
detector placed below the microfluidic cartridge (Figure 1), collecting the signal through the microwells. The fluorescent signal
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deriving from protein recognition was efficiently measured, as
reported in Figure 4.
Figure 4: Fluorescence image (left) captured with the SPAD matrix of a portion of
the array after incubation with AlexaFluor488-labelled secondary aptamer. On the
right a plot of the photon counts on the 15th pixel column (red line in the image
on the left) is reported.
At the moment we are working on the system integration at two
different levels: on one side by designing a disposable unit including the fluidic layer and the reaction chamber with the aptamerfunctionalized microwells array, and on the other side designing
an assembly including excitation, detection and fluidic control
functions. The aim is to develop a low cost, rapid and sensitive
diagnostic tool. The possibility to selectively functionalize each
microwell with a different aptamer sequence offers a simultaneous detection of several proteins, contributing to identify at
one time potential disease biomarkers.
Acknowledgements
This work is accomplished in the framework of the NAoMI Project
funded by the Province of Trento (http://naomi.science.unitn.it/).
Project partners besides FBK: University of Trento (Nano Science
Laboratory, Dept. Materials Engineering, Dept. Information
Engineering and Computer Science), CNR (Dept. of Materials
and Devices: Institute for Photonics and Nanotechnologies
and Institute of Applied Physics “Nello Carrara”), CIVEN
(Coordinamento Interuniversitario Veneto per le Nanotecnologie),
Scuola Superiore S. Anna and OPTOi Group.
Contact
Cecilia Pederzolli
via Sommarive, 18, 38123 Povo (Trento)
tel. 0461 314494
e-mail. [email protected]
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From Microwave to TeraHertz
NanoAmplifiers for Sustainable
Applications
Massimiliano Dispenza, Carlo Falessi, Anna Maria Fiorello: SELEX sistemi
Integrati;
F. Brunetti, G. Ulisse, M. Mineo, C. Paoloni, A. Di Carlo: UniRoma2
Introduction
T
(THz) radiation is electromagnetic radiation whose
frequency lies between the microwave and infrared regions of
the spectrum. The THz band is usually included in the spectral
region between 0.3 and 3 THz.
The roots of terahertz science go back to more than 100 years
to the days when the earliest experimenters in electromagnetics were producing and detecting radiation emitted from spark
gaps that undoubtedly contained frequencies in the tenths of
GHz close to the THz range [1]. Modern terahertz science dates
back to the mid 1970’s when far-infrared Fourier transform spectrometers and fast semiconductor diode detectors were first introduced. This early period is well covered in many review articles
and texts, a large number of which are referenced in [2].
Usually the THz region is called THz gap due to the lack of electronic or optoelectronic source with sufficient output power(see
Figure 1) [3].
erahertz
Figure 1. THz gap
Over the last two decades, strong efforts have been done in the
development of THz technologies, in different scientific disciplines such as ultrafast spectroscopy, semiconductor device fabrication, vacuum devices, laser science and bio-medical imaging.
Technological advances in optics and electronics have resulted in
many different types of THz sources and sensors. Typically THz
sources are based on up-conversion of electronic source or down
conversion of optoelectronic source. The third possibility is represented by quantum cascade lasers. Due to the low conversion
efficiency both in down- and in up- conversion, output power
cannot reach typically high values. In this context vacuum devices, such as traveling wave tubes (TWT) or klystrons, represent
a good solution due to their better performance respect to solid
state devices in terms of output power [4]. As main drawback,
vacuum tubes in the THz frequency range requires sophisticated
engineering of the device.
For the application point of view, THz technology has become
attractive due to the low energy content and non-ionizing nature
of the signal. This property makes it suitable for imaging and
sensing applications. The potential of THz radiation is impressive
in many fields, such as space communication, security, medical,
biology and microscopy.
One of the primary motivations for the development of THz sources and spectroscopy systems is the potential to extract material
characteristics that are unavailable when using other frequency
bands. As shown in figure 2, THz radiation strongly interacts
with molecules inducing vibrational and rotational movements.
Consequently much information can then be extracted from the
molecular response to THz frequency signals.
Astronomy and space research were one of the strongest drivers for THz research because of the vast amount of information
available concerning the presence of abundant molecules such as
oxygen, water and carbon monoxide in stellar dust clouds, comets and planets. In recent years, THz spectroscopy systems have
been applied to a huge variety of materials both to aid the basic
understanding of the material properties, and to demonstrate
potential applications in sensing and diagnostics [5].
Strong terahertz signatures can be ascribed to a very wide range
of rotational and vibrational motions that take place between
atomic or molecular collisions. These quantum transitions can
both be computed and directly measured as either absorption or
emission peaks that occur over very narrow spectral windows.
In interstellar space, the outer atmospheres of planets and deep
within the heart of galaxies, these thermal emission signatures
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can be readily measured against the background of cold space
(3K). The specific spectral signatures provide a vast amount of
information on the abundance, distribution, temperature, pressure and velocity of the gases involved; and provide the basis for
modern cosmology, atmospheric dynamics, star formation and
evolution, and galactic structure .
tion path a communication link has to tackle. The attenuation due
to the dissipation of the radiated energy between a transmitter
and a receiver and the high absorption of some molecules such as
H2O and O2 (see Figure 3) are the most important problem..
Figure 2 Molecular interactions with THz radiation
When strong magnetic fields are present around hot and fast moving electrons, terahertz energy is naturally generated. This is the
basis for interest from the plasma diagnostics community. In particle accelerators (also at the surface of the Sun), the energy and
magnetic field levels are high enough to induce strong coherent
terahertz emission either through electron cyclotron resonance
(ECR), Bremsstrahlung or Bethe-Bloch deceleration effects. The
measure of wavelength and power level of the emitted ECR terahertz photons from plasma translates directly into information
about the temperature and magnetic field strength in the core of
a fusion reaction, something that is difficult to do in situ.
Several accelerator facilities around the world have also taken
advantage of their synchrotron beams to produce high power
(many kW and even MW) terahertz pulses through ComptonScattering and free electron laser beam bunching techniques.
Jefferson Labs in the US now boasts a THz beam dump with sufficient energy for even the most demanding ionization or pump
probe applications . Apart from studies in the field of astronomy
and particle physics another field of application is represented by
telecommunication. The increasing demand of unoccupied and
unregulated bandwidth for wireless communication systems will
inevitably lead in fact to the extension of operation frequencies
toward the lower THz frequency range. Higher carrier frequencies
will allow for fast transmission of huge amounts of data as needed for new emerging applications. THz communication could
have broad potential applications in space telecommunications,
and are particularly attractive for extremely high bandwidth intersatellite links due to the absence of atmospheric attenuation
problems. A THz communication system has to overcome certain
technological and general hurdles. The technological hurdles are
strictly related to the low output power of THz source and to the
complicated system to detect THz signals. The general problems
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Figure 3 Attenuation between transmitter and receiver plotted over frequency and
distance including freespace
THz systems have broad applicability also in a biomedical context.
Active fields of research range from cancer detection to genetic
analysis. Biomedical applications of THz spectroscopy are facilitated by the fact that the collective vibrational modes of many
proteins and DNA molecules are predicted to occur in the THz
range. THz spectroscopy has also been heralded for its potential ability to infer information on a biomolecule’s conformational
state. Very famous is the picture shown in figure 4 where THz
spectroscopy is used to detect an internal cavity of a tooth [6]. In
figure 5 the THz image of a chip is reported [7].
Figure 4 Terahertz images of tooth with an internal cavity
Figure 5 (Top) Visible image and (bottom) THz image of an IC with plastic
packaging.
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THz systems can be used also for security applications such as
imaging and sensing of explosives, weapons and drugs . For
example in particular figure 6 shows an absorption spectra of C4
explosive, as it is possible to see there are six absorption peaks
located near 0.8, 1.1, 1.3, 1.5, 2.0 and 2.2 THz that could be
used to identify the material [8].
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bon nanotubes or nanowires, are formed in the cavities. Typically,
the cutoff frequency of a standard Spindt-type microtriode value,
that is the frequency at which the current gain assumes unitary,
is strongly limited from the cathode-gate capacitance. The other
parameter which influences the cutoff frequency is the transconductance which mainly depends on the tip radius and on the
distance between the grid and the tip. Other parameter such as
the electron mobility and transit time can be neglected in microminiaturized vacuum devices [14].
The activity developed in the SELEX-SI project NMP in collaboration with the University of Rome Tor Vergata, has been mainly
focused in the design of an innovative nanotriode able to reach
frequency of more than one order of magnitude higher respect
to standard Spindt type microtriodes whose maximum frequency
operation is in the range of GHz.
Figure 6 Absorption spectra of C4 explosive.
In this context, a great deal of attention has been deserved to vacuum tube technology for its ability to reach higher output power
with respect to solid state devices. The main problem for vacuum
devices at THz frequencies is the request of very small feature
sizes and tolerances.
TeraHz NanoAmplifier
SELEX-SI, in collaboration with the University of Rome Tor Vergata,
is involved in two main projects related to vacuum electronics.
The first is the PNRM NanoTechnology MultiScale Project - NMP
for which a nanotriode based on field emission is going to be
realized. Field emitter arrays triodes are interesting devices for
the use in microwave amplification both as guns in vacuum tubes
and as integrated devices [9,10,11]. The possibility to use Spindt
Type microtriodes (figure 7) as amplifiers in the range of few GHz
has been already demonstrated [12,13]. Microtriodes are vacuum
triode realized with micromachining techniques based on field
emitting cathodes.
They are realized on a conductive substrate and have a thin-film
sandwich structure, consisting of an insulating layer between
two conductors, the substrate and the gate. The gate is formed
on the substrate with arrays of holes in the top conducting film
and the insulating layer. The cathode is usually fabricated on a
high-conductivity silicon substrate. The silicon substrate is covered with a 1 µm thick insulating layer of thermally grown silicon
dioxide (SiO2). The SiO2 is then coated with a thin film of molybdenum (gate), in which an array of holes is patterned. The
holes are then etched through the SiO2 to the silicon substrate.
Finally emitting tips, that could be molybdenum nanocones, car-
Figure. 7. Spindt type microtriodes
The main limitation of Spindt type microtriodes is the high cathode-gate capacitance therefore, within NMP project, a different
microtriode geometry has been proposed to reduce this capacitance. The new crossbar structure, that has been patented, is
shown in figure 8 [14].
Figure 8. Cross-bar geometry
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The main difference between this new microtriode and the Spindt
type is that the cathode and the gate are metallic striplines that
can be patterned. This allows to reduce their overlap, in fact, the
cathode and the gate line are designed with an angle of 90°. A
dielectric layer is present between the cathode and gate line. For
clarity in figure 8 the dielectric between the cathode and the gate
is transparent.
The frequency dependent simulations of the device have been
performed with the PIC (Particle In Cell) simulator Magic Tool
Suite.
In the simulations variable dielectric thickness have been considered. As we expected the cutoff frequency is increased with the
increase of the dielectric thickness. The maximum dielectric thickness has been fixed arbitrary at some tenth of microns.
With the reduction of the overlap between cathode and gate
the capacitance between the two electrodes is strongly reduced
leading to a device cutoff frequency of 130 GHz that is one order
of magnitude higher than the standard Spindt Type devices.
The second activity related with the vacuum THz electronics, is
a European project OPTHER (Optically Driven THz Amplifier), for
which SELEX-SI is a partner involved in the technological development and Tor Vergata is the coordinator. OPTHER project was
born with the purpose to establish a breakthrough in technology
by the realization of the first THz vacuum amplifier ever built (figure 9).
Figure. 9. Cross-bar geometry
The availability of amplifiers at THz frequencies is strategic for the
implementation of a wide number of THz applications in many
fields such as imaging, security, and early diagnostic.
The complexity of the task has stressed the OPTHER partner expertise at the maximum level to get the final result and established new knowledge at the state of the art.
A backward wave amplifier configuration was chosen for the first
prototype at 1 THz. This configuration is based on a first spatial
harmonic allowing larger dimensions than to operate at the fundamental harmonic. A gain of 10 dB and about 8 mW output
power, with 10 kV beam voltage, are expected.
This kind of amplifier device is composed of four main parts:
• a Cathode acting as an electron gun where electrons are emitted, accelerated towards the anode by the high voltage, and
a shape matched to the Slow Wave Structure is given to the
electron beam by a grid electrode.
• a Slow Wave Structure where the e-beam transfer part of its
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energy to the input THz travelling wave radiation, thus causing
its amplification.
• a Collector in which the residual non-transferred beam energy
is converted into heat.
• Input/Output coupling sections for THz I/O radiation.
Carbon nanotube cold cathode gun is under test to be used in
cold cathode electron gun (Figure 10). A micro gun optimized for
reducing the effect of the transverse electron velocity was designed. A micro thermionic gun is considered as first choice to test
the amplifier. Cold cathodes are expected to reduce power consumption, weight and size and increase lifetime of the device.
Figure 10. CNT based electron gun
Double corrugation waveguide was adopted as slow wave structure to make possible an effective interaction with a cylindrical
electron beam.
Both a LIGA process and a low cost alternative UV process (developed in SELEX-SI), based on high aspect ratio photopolymers (figure 11) are used for Slow Wave Structure realization. It is worth
to highlight that the very small wavelength of the THz radiation
imposes hard constraints to the machining technology needed
for fabrication of the Slow Wave Structure.
Figure 11. Slow Wave Structures fabricated by UV process based on high aspect
ratio photopolymers
Finally Input-Output couplers compatible with requirements for
minimum return loss have been designed and fabricated.
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Future works
Another fundamental activity in the THZ vacuum electronics field
for SELEX-SI is the participation in a joint Startup company with
the University of Rome Tor Vergata called THERATIS. The main
purpose of the THERATIS is to design and build compact and low
cost THz sources that can be the enabler of imaging systems,
communications, spectroscopy, early detection and safety systems. Such sources are currently only conceivable as a prototype
and therefore are impractical to be realized on a large scale fabrication. The idea of the start-up is focused on the design and
realization of vacuum electronic devices in particular on backward wave oscillator. In this context, the big experience, in vacuum devices, accumulated by proposing start-up people would
be dedicated to the design and implementation of THz source
backward oscillator type. The benefits provided by such devices
and their flexibility of use allow their implementation in many
systems and applications, thus paving the way to a wide range of
business opportunities, once a diversified portfolio of THz sources
is built up. The low cost of the sources would be guaranteed by
UV photolithographic realization technology and use of carbon
nanotubes cold cathodes. A range of design features, developed
through years of experience in the field, will be applied in order
to reduce weight and cost of used materials, in particular of the
magnetic beam focusing system. The start-up proponents have
developed expertise in the design of THz vacuum electronic devices, both amplifiers and oscillators. The design methodologies
have been developed with great precision, both in the management of simulation software and the transition from simulation
to implementation phase. All these skills developed in this way
will then be fundamental for the finalization of the THz vacuum
sources, which aims to realize the core business of THERATIS.
References
[1]M. Kimmett, “Restrahlen to T-Rays – 100 Years of Terahertz
Radiation,” Journal of Biological Physics, vol. 29, no. 2-3, pp.
77-85, June 2003.
[2]P.H. Siegel, “THz Technology,” IEEE Trans. MTT, vol. 50, no. 3,
pp. 910-928, March 2002 and P.H. Siegel, “THz Technology
in Biology and Medicine,” IEEE Trans. MTT, vol. 52, no. 10,
pp. 2438-2448, Oct. 2004.
[3] V. Krozer, B. Leone, H. Roskos, T. Löffler, G. Loata, G. Döhler,
F. Renner, S. Eckardt, S. Malzer, A. Schwanhäusser, T. O.
Klaassen, A. Adam, P. Lugli, A. Di Carlo, M. Manenti, G.
Scamarcio, M. S. Vitiello, M. Feiginov, “Optical far-IR wave
generation - state-of-the-art and advanced device structures” Proc. SPIE Intern. Optical Eng, vol. 5466: Microwave
and Terahertz photonics 2004.
[4] Qiu, J.X.; Levush, B.; Pasour, J.; Katz, A.; Armstrong, C.M.;
Whaley, D.R.; Tucek, J.; Kreischer, K.; Gallagher, D. “Vacuum
tube amplifiers” Microwave Magazine, IEEE, 10, 2009
[5] B. FERGUSON, XI-CHENG ZHANG “Materials for terahertz
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science and technology”, nature materials, Vol. 1, 2002
[6] http://www.teraview.com/terahertz/applications/medical/
oral-healthcare.html
[7] B. Hu and M. Nuss, “Imaging with terahertz waves,” Opt.
Lett, vol. 20, no. 16, pp. 1716–1718, 1995.
[8]Schecklman et al. “Terahertz material detection from diffuse
surface scattering”, J. Appl. Phys. vol. 109, 094902, 2011
[9]A. Di Carlo et Al “European research on THz vacuum amplifiers” 35th International Conference on Infrared Millimeter
and Terahertz Waves (IRMMW-THz), 2010
[10]Whaley, D.R.; Duggal, R.; Armstrong, C.M.; Bellew, C.L.;
Holland, C.E.; Spindt, C.A.; “100 W Operation of a Cold
Cathode TWT “ IEEE Transactions on Electron Devices, 2009
pp 896-905
[11]Manohara, H.M.; Siegel, P.H.; Marrese, C.; Baohe Chang; Xu,
J.; “ Fabrication and emitter measurements for a nanoklystron: A novel THz micro-tube source” Third IEEE International
Vacuum Electronics Conference, 2002, pp. 28-29
[12]C. A. Spindt, C. E. Holland, A. Rosengreen, I. Brodie “Fieldemitter-array development for high-frequency operation” J.
Vac. Sci. Technol. B Volume 11, Issue 2,1993, pp. 468-473
[13]Baoqing Zeng, Ning Liu and Zhonghai Yang “Simulation
of Vacuum Microelectronic Triode Made of Single Carbon
Nanotube” International Journal of Infrared and Millimeter
Waves, Vol. 25, No. 11, November 2004
[14]A. Di Carlo, C. Paoloni, E.Petrolati, F.Brunetti, R.Riccitelli
”High frequency triode-type field emission device and process for manufacturing the same” Pat. WO200984054
[15]Chuanhong Jina, Jingyun Wangb, Mingshen Wangb, Jun Sua
and Lian-Mao Peng “In-situ studies of electron field emission
of single carbon nanotubes inside the TEM” Carbon Volume
43, Issue 5, 2005, pp 1026-1031.
[16]Chuanhong Jina, Jingyun Wangb, Mingshen Wangb, Jun Sua
and Lian-Mao Peng “In-situ studies of electron field emission
of single carbon nanotubes inside the TEM” Carbon Volume
43, Issue 5, 2005, pp 1026-1031.
[17]M. Sveningsson, K. Hansen, K. Svensson, E. Olsson, and E. E.
B. Campbell “Quantifying temperature-enhanced electron
field emission from individual carbon nanotubes” Phys. Rev.
B 72 2005 085429
Contacts
F..Brunetti, University of Rome Tor Vergata,
viale del Politecnico 1, 00133 Rome, Italy.
e-mail:[email protected]
G.Ulisse, University of Rome Tor Vergata
e-mail:[email protected]
M.Mineo, University of Rome Tor Vergata,
e-mail:[email protected]
C.Paoloni, University of Rome Tor Vergata
e-mail:[email protected]
A.Di Carlo, University of Rome Tor Vergata
e-mail: [email protected]
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Nanostructured metal oxide gas
sensors and Electronic nose at
SENSOR
G. Sberveglieri*, C. Baratto*, E. Comini*, I. Concina*, G. Faglia*,
M. Falasconi*, M. Ferroni*, E. Gobbi*, A. Ponzoni*, V. Sberveglieri **,
A. Vomiero*, D. Zappa*
* Department of Chemistry and Physics University of Brescia and CNR National
Research Council-IDASC, Brescia
** Dept. of Agricultural and Food Sciences, Modena and Reggio Emilia University,
Reggio Emilia, Italy
The SENSOR Laboratory
Established since 2003, SENSOR joins the activity of researchers
from the Brescia University and the CNR -IDASC Institute and is
located in Brescia, at the Engineering Faculty of the university and
at the CNR building. The main scientific research lines address the
preparation and functional characterization of semiconducting
oxides for application in the field of sensing, photovoltaic, solid
state lighting. In addition, the tasks of SENSOR are the preparation and functional characterization of gas/flavor sensors based
on semiconducting thin-films / nanowires and the development
of Artificial Olfactive Systems (AOS).
Metal oxide gas sensors
Conductometric semiconductor are the most promising devices
among solid state chemical sensors, due to their small dimension, low cost, low power consumption, on-line operation and
high compatibility with microelectronic processing. The progress
made on Si technology for micromachining and micro fabrication
foreshadows the development of low cost, small size and low
power consumption devices, suitable to be introduced in portable instruments and possibly in biomedical systems. The materials for chemical sensing that were investigated covered a wide
spectrum of metal oxides (MOX): SnO2, In2O3, WO3, MoO3, TiO2,
Ga2O3, and several mixed oxides like SnO2-In2O3, TiO2-Fe2O3 and
TiO2-WO3. The sensing layers were prepared by physical vapor deposition (PVD) techniques, in particular RF magnetron sputtering,
which are easily scalable on the industrial scale, and deposited
both on alumina and silicon micromachined substrates. Novel
activities point towards nanostructured systems with reduced dimensionality like metal-oxide nanowires and nanostructures, and
to their implementation in functional devices.
Metal oxides (MOxs) represent a vast class of materials of interest
for various scientific communities, ranging from physics to chemistry, from material science to engineering. [1, 2, 3, 4] There exist
a large variety of metal oxides compounds, mostly depending on
the type of metals used along with oxygen. To the latter, most of
the properties characterizing those types of materials, are related.
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For decades now, metal oxides have been successfully used in various forms in the field of gas sensing, where the conductometric
properties of those materials are exploited based principally on
the induced variation of the electrical resistance upon interaction
(absorption, chemisorption or physisorption) of a gas molecule
on the oxide surface. Due to their small dimension, low cost, low
power consumption, on-line operation and high compatibility
with microelectronic processing, conductometric semiconductor
thin films are between the most promising devices in the field of
solid state chemical sensors (see Fig. 1).
Figure 1. Picture of a MOX sensor, showing its very small size.
The fundamental sensing mechanism of semiconductor gas sensors relies on a change in electrical conductivity due to the interaction process between the surface complexes and the gas
molecules to be detected. Unfortunately, sensors still suffer from
lack of selectivity and long-term stability: they are not able to
recognize single chemical compounds, their analytical approach
being based on unspecific chemical interactions (redox processes
on semiconductor surface). However, the mentioned limits have
not restricted the interest and the use of these tools. ENs have
indeed found applications in many field, from environmental monitoring to medical diagnostic and food analysis.
Electronic Nose
AOS, or Electronic Noses (EN), are useful in applications domain
like environmental monitoring and food processing control. ENs
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analyze gaseous mixtures for discriminating between different
(but similar) mixtures and, in the case of simple mixtures, quantifying the constituents’ concentration. There is in fact a strong
and growing request from the market for artificial olfactory systems dedicated to environmental monitoring and food processing control Electronic Noses (ENs) are instruments simulating the
mammalian olfaction by means of a semi-selective chemical gas
sensor array that can identify differences in volatile patterns for
different samples [5]. ENs do not separate a complex mixture in
its single constituents: the interaction of the global sample headspace on the surface of the sensor sensitive layer induces a variation on a physical characteristic of the sensor.
Over the last years, SENSOR has been especially working on food
quality and safety evaluation and on security application [6]. The
ability in food analysis relies on recognition of the differences in
the volatile headspace of a sample induced by an adulteration
with respect to the native composition. Since most food adulterations are reflected on volatile chemical profile, ENs appear
as excellent candidates for process monitoring, freshness evaluation, shelf-life investigation, sensory and authenticity assessment,
microbial contamination diagnosis, providing for rapid and objective analysis [7]. Among the advantages in using artificial olfactory systems it is worth to remind their flexibility, easiness of use,
low-cost, no or minimal sample pre-treatment demanding and
the possibility to work completely stand-alone once trained.
ENs consist of four main building blocks (Figure 2). The first block
is represented by the sample headspace generation. The generated sample headspace is carried through the sensor chamber,
whose temperature and relative humidity are constantly monitored by means of dedicated sensors. A computer manages the
overall system operation. Finally, data analysis is carried out by
means of statistical techniques that reconstruct the olfactory fingerprint of the analysed samples.
The use of ENs envisages two main steps, being the first the instrument training, during which EN is taught to recognize the
characteristics under study. The training consists in randomly submitting to EN’s analysis a certain number of samples belonging to
different classes and verifying the skill in separating that classes
by means of supervised analysis. The second step is the validation
of the analytical protocol: unknown samples are smelt by the EN
and classified by means of unsupervised statistical analysis.
Three paradigmatic applications of ENs in food field are here described. The fraudulent adulteration of high quality extra virgin
olive oil (EVOO) with low quality hazelnut oil is heavily damaging the European olive oil market and posing a threat on customers’health [8]. Due to the very similar composition as respect
to fatty acids content, this fraud is extremely difficult to identify.
EN revealed a noteworthy capability in discriminating between
pure and hazelnut-diluted EVOO samples (Figure 3), even at very
low dilution levels. This result suggests that ENs can be used as
monitoring tool for a fast evaluation of EVOO.
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Figure 2. Schematic layout of an EN.
The impressive ability shown by Alicyclobacillus spp. (ACB) in contaminating drinks, without at present any effective early diagnostic tool, has qualified these as major quality control target microorganisms [9, 10]. EN demonstrated a surprising skill in identifying beverages contaminated by ACB (Figure 4), with correct
classification rates up to 100%, both for peach-and pear-based
soft drinks and fruit juices [10, 11], even before the production of
secondary taint metabolites, usually exploited as contamination
markers by traditional analytical techniques. A noteworthy exception was however constituted by apple-based drinks toward
which all the sensors in the array were blind (data not shown),
without any trivial explanation [12].
This means that ENs can find application as ACB diagnostic tools
for drinks, after a careful evaluation of response of the matrix
under study. Sensory damage caused in tomato-derived products
because of errors during the process of the raw matter is often
reflected in product rejection by consumers and thus in economical losses for producers.
Figure 3. PCA score plot of pure EVOO (+) and EVOO diluted with 5% (x), 10%
(x) and 25 (x) of hazelnut oil. The arrow indicates the data drift over the time.
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EN was able to separate in-standard (regular sterilization) from
out-of-standard (oversterilisation) tomato pulps with a 100%
classification rate. Currently, this evaluation is performed by humans smelling the products, with all the drawbacks related to
the human sensory panel test (such as nose saturation and low
sample throughput ): ENs can be used instead, thus rendering
faster and more objective the analysis.
Figure 4. Biplot reporting the principal component analysis and the loading
evaluation for the early diagnosis of ACB contamination in peach-based soft drink
(o: contaminated and x: uncontaminated samples).
Figure 5. PCA score plot showing the discrimination along the PC1 axis of instandard tomato pulp (•) and oversterilised product (x).
Reported examples clearly show that, although ENs can be widely applied
in the field of food analysis, the sensor technology appears promising for
implementation in the industrial level, even though an higher degree of reliability
should be achieved for long term operation.
References
1. J. L. G. Fierro in Metal Oxides: Chemistry and Applications
CRC Press, Florida, 2006.
2. V. E. Henrich and P. A. Cox in The Surface Chemistry of Metal
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Oxides Cambridge University Press, Cambridge, UK, 1994.
3. C. Noguera in Physics and Chemistry at Oxide Surfaces
Cambridge University Press, Cambridge, UK, 1996.
4. A. R. José and F.-G. Marcos in Synthesis, Properties, and
Applications of Oxide Nanomaterials Wiley, New Jersey,
2007.
5. Persaud & Dodd, Nature 299 (1982) 352–355.
6. T Pearce, S Schiffman, H Nagle, J W Gardner in Handbook of
Machine Olfaction, 2006 Wiley-VCH.
7. M. Peris and L. Escuder-Gilabert, Analytica Chimica Acta,
638, 1-15 (2009).
8. M. Arlorio, J.D. Coisson, M. Bordiga, F. Travaglia, C. Garino,
L. Zuidmeer, (2010). Food Addiditives And Contaminants A,
27, 11-18 (2010).
9. J.D. Wisotzkey, P. Jurtshuk, G.E. Fox, G. Deinhard, and K.
Poralla, International Journal of Systematic Bacteriology, 42,
263-269 (1992).
10. I. Walls and R Chuyate, Dairy Food Environmental Sanit., 18,
499-503 (1998).
11. I. Concina, M. Borsnek, S. Baccelliere, M. Falasconi, E. Gobbi,
and G. Sberveglieri, Food Res. Int., 43, 2108-2114 (2010)
12. E. Gobbi, M. Falasconi, I. Concina, G. Mantero, F. Bianchi, M.
Mattarozzi, et al., Food Control, 21, 1374-1382 (2010).
Contacts
Prof. Giorgio Sberveglieri, University of Brescia
Via Valotti, 9, 25133 BRESCIA , Italy web site http://sensor.ing.unibs.it
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Responsive Development
of Nanotechnology
Kai Savolainen
Nanosafety Research Centre, Finnish Institute of Occupational Health
Helsinki, Finland
Introduction
I
n its 2020 Strategy, the European Union highlights nanotechnology as one of the key novel technologies enabling smart, sustainable and inclusive growth throughout the European Union
to promote the Union as the most competitive knowledge-based
society globally providing prosperity and social stability to its citizens [1]. Engineered nanomaterials (ENM) and nanotechnologies, belonging to the key enabling technologies such as the biotechnology, and information and communication technologies,
remarkably contribute to the goals put forward in the European
Union 2020 Strategy. However, the safety of ENM has given rise
to increasing concerns, not only for the public and regulators, but
also for the industries using these materials. In fact, uncertainties
related to safety of ENM and associated technologies represent,
according to the European Commission, a major obstacle to marketing and innovations based on these technologies [2]. Hence,
it is of the utmost importance to develop a sound science-based
foundation on which to build a reliable and affordable safety classification of ENM and nanotechnologies. For example, one needs
a clear understanding of the relationship between ENM characteristics, such as their surface chemistry, and biological changes
they may evoke in living organisms, across species, and through
the life cycle of ENM used in different products. Reaching these
goals would remove one major obstacle, of global importance,
for realizing the full potential of these materials and technologies
[1,3].
The essence of engineered nanomaterials enabling nanotechnologies
Engineered nanomaterials constitute a large number of classes
and subclasses of diverse materials which have features in common: one, two or three of their dimensions are 1-100 nm. If only
one dimension equals or is less than 100 nm, one deals with
nanoflakes, whereas two such dimensions suggest a fibrous or
a tubular structure, and three dimensions equaling or being less
than 100 nm mean a ball-like structure. An example of the first
case is graphene, of the second case single-walled (SWCNT) or
multi-walled (MWCNT) carbon nanotubes, and ENM with three
dimensions equaling or being less than 100 nm include various
metal oxide and metal nanoparticles [3].
ENM typically have small size, large surface are, and large surface to volume ratio. ENM, due to their large surface area, render them much more reactive than their larger but chemically
identical counterparts. They exhibit unique properties not found
in larger particles, and also exhibit unusual behavior in aerosols
as well as liquid dispersions and other matrices for example in
environmental compartments or synthetic matrices such as different polymers [3, 4]. For example, carbon nanotubes have tensile
strengths better than that of stainless steel, and better electrical
conductivity than copper [3]. Also organic materials, such as nanocellulose fibers, exhibit unique properties including excellent
electrical conductivity. It is, hence, not surprising, that these unique materials, in combination with existing technologies such as
electronics, energy production, textiles, information storage and
car making, not forgetting food industry, provide huge technological benefits and high economic expectations. The number of
nanotechnology patents has grown from around 100 annually in
1991 to about 12000 in 2008. Likewise, the expected market of
final products incorporating ENM has been expected to be about
3 trillion US dollars on 2020 [3].
Many of the properties of ENM that enable their technological
benefits may though cause harm when in contact with living organisms, i.e. with bio-molecules, cells, organs and whole organisms [5,6]. Such properties include large surface area to mass
ratio, and a large surface area as such associated with a high
reactivity in biological and other environments. Small size is often
associated with the potential of these minute particles to cross
biological barriers and the ability to enter almost any organ or
cell in the body. Subsequent to inhalational exposure these minute particles in many cases are able to penetrate the alveolar
wall and thus have a ready access to the systemic circulation,
and hence to organs and cells in the body [6]. One of the striking
features of some of the ENM, especially carbon nanotubes (CNT),
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is the high aspect ratio (fiber length to diameter ratio) meaning
that they resemble asbestos fibers [7, 8]. In addition, it has been
demonstrated that for example manganese oxide nanoparticles,
when exposure takes place through the nose, are taken up by the
olfactory nerve endings in the olfactory epithelium hence proving
an access to the olfactory bulb at the bottom of the forebrain
potentially providing a pathway to other parts of the brain [9].
It is not surprising that these novel materials have evoked concerns among workers, consumers and regulators. This has become an obstacle for investments on nanotechnology-based innovations in many industry sectors which are concerned about
the potential health effects of these materials. Even the absence of such demonstrated health effects concerns easily leads to
unwanted consequences on the use of ENM in nanotechnology
applications provide that a general uncertainty surrounds these
materials and technologies and causes suspicions in the potential
user communities of such ENM-enabled products, whether single
consumer and down-stream industry sectors in the value chain of
these materials [2,3].
Knowledge gaps hampering the risk assessment of engineered nanomaterials
The fundamental equation in toxicology is as follows: hazard x exposure = risk. If one can prevent hazards or exposure from occurring, there is no risk [10]. The current challenge in assessing the
potential health risks of ENM is the lack of knowledge on health
effects of and exposure to the very different classes and a great
diversity of ENM. There is not a systematic database on hazards
or exposure, or systematic delineation of dose-effects relationship
for any given ENM. National Institute for Occupational Safety and
Health (NIOSH) has drafted a proposal for occupational exposure
level (OEL) for nano-sized (0.1 mg/m3) and micro-sized (2.4 mg/
m3) titanium dioxide based on their potential to increase the risk
of lung tumors in experimental animals [11]. Likewise, NIOSH has
proposed a draft OEL of 7 μg/m3 for CNT based on their ability
to produce inflammation and interstitial fibrosis after pulmonary
exposure [12]. There have also been European attempts to define
precautionary based benchmark levels for different types of ENM
based to the technical ability to assess exposure to these materials [13]. None of these proposed draft OELs or benchmark levels
have been implemented, or none of them have legislative power,
due to limited evidence justifying the use of these values.
There have also been attempts to identify the routes of exposure
in the occupational environments, the release of these materials
into environmental compartments such as air, soil, and ground
and surface waters leading to exposure of consumers through air,
water and food, as well as release from products incorporating
ENM [4, 14]. These attempts have provided further insight and
understanding of the potential human and environmental exposures, and of exposure routes throughout the entire life-cycle of
ENM. However, none of these activities have provided quantita28
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tive exposure information required for the risk assessment of different potential target species of ENM. Furthermore, our understanding of the effects of ENM on environmental species remains
very limited. In conclusion, knowledge, our first defense against
the potential hazards and risks such as ENM, is lacking.
Analysis of assessing risks of engineered nanomaterials,
and the way forward
Exposure to ENM
Exposure of workers and the environment to ENM is possible in
all stages of production, transport, storage, and incorporating
ENM into the products. This possibility also includes recycling of
these materials. Workers have the greatest likelihood of becoming exposed to different doses of ENM, preferentially through
the pulmonary route, because ENM infrequently occur as aerosols
in the occupational environment. However, consumers may also
become exposed in these materials though consumer products
incorporating ENM [15].
In all the above stages, production, transport, storage, incorporation into product, and recycling of ENM, also leaks of these
materials into different environmental compartments, air, soil,
and surface and groundwater, may take place. This may allow
transportation of ENM into drinking water, inhaled air, and food
through contamination of crops and production animals. This
may, in turn, lead to exposure of consumers. They may also be
exposed through the skin due to the consumption of cosmetics and sun-block creams. Further, as the medical applications of
ENM have become more widespread, exposure via intravenous
route has become possible. However, for the time being, occupational exposure through the lungs predominates, and merits most
attention [15, 16].
Identification of workplaces where exposure to ENM takes place requires a thorough analysis of those occupational environments in which these materials are being used. Schulte et al. [16]
considered that such workplaces include at least the following:
1) research laboratories; 2) start up and scale up operations; 3)
manufacturing of ENM at industrial scale; 4) incorporating of
ENM into products by their down-stream users (e.g. cosmetics
industry); 5) disposal and end-of-life; and 6) recycling of ENM
when they again become raw materials. The challenge is how to
use the limited amount of exposure information to develop risk
assessment and risk management guidance for the great diversity of ENM. Another challenge is the currently lacking ability to
separate the process-derived ENM from nano-sized background
nanoparticles. Without this information for example the setting
of occupational exposure limits for ENM is not possible [17].
Health hazards of ENM
Because it is not possible to discuss all the various ENM groups
and their health effects, carbon nanotubes (CNT) will be used as
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an example in this context. The best known classes of CNT are
single-walled carbon nanotubes (SWCNT) and multi-walled carbon nanotubes (MWCNT).
Recently, Poland et al. [7] showed that a single intra-peritoneal
injection of low doses of long, stiff, and agglomerated MWCNT,
resembling asbestos fibers, induced during a 7-day follow-up
asbestos-like changes in the mesothelial lining of mouse peritoneal cavity. Takagi et al. [18] demonstrated that the administration of a high single dose of the same material into the peritoneal
cavity of p53 deficient know-out mice, a cancer sensitive mouse
model, induced a high incidence of mesotheliomas in the peritioneal cavity, exceeding that induced by a corresponding dose
of crocidolite asbestos through the same route. The results of
these studies support each other [19] but are not suitable for risk
assessment.
In later studies, Ryman-Rasmussen et al. [20] demonstrated that
MWCNT, when mice were exposed through inhalation, reach
subpleural space in the pulmonary cavity. In this study, the material also induced subpleural fibrosis resembling that induced
by asbestos. Ma-Hock et al. [21] demonstrated that CNT at low
doses induce interstitial fibrosis and granulomas in the lungs of
exposed animals. Based on several studies with a relevant inhalational exposure route and toxic endpoints including interstitial
fibrosis, NIOSH [12] proposed a draft OEL for CNT, notably 7.0
μg/m3. Also other proposals for different CNT that vary between
1-2 and 210 μg/m3 have been proposed [22, 23]. So far, there
are no OELs used to control exposure to CNT, or exposure to
any other ENM either due to the lack of relevant and systematic
knowledge justifying the implementation of such OELs. A remarkable challenge that remains is the development of intelligent
testing strategies and safety assessment paradigms. They should
allow the evaluation the safety of increasing numbers of ENM,
and classes of ENM [15].
Management and governance of risks of engineered nanomaterials
Adequate risk assessment is an important prerequisite for risk
management of ENM. Furthermore, trustworthy risk governance
of ENM requires the dissemination of safety culture within the
main communities dealing with ENM, notably the regulators, the
industry, the labor unions, the research community, and the public at large. Trust is important both for successful management
and governance of risks of ENM.
Risk management approaches used in the EU are in general terms
based on REACH regulation [24]. This novel regulation does not,
however, provide reliable and practical enough guidance on
how to assess potential risks of ENM, and, hence, the support of
REACH for the ENM risk management and governance is limited.
Recent approaches to further develop risk management of ENM
are based on precaution in the absence of sufficient knowledge
on exposure to and effects of ENM. They include among others
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the German Benchmark Values [13] and the Dutch Provisional
Nano-Reference Values. Both include proposals for acceptable
exposure levels for ENM expressing the ENM exposure levels in
number concentrations in the air, and are hence suited mainly for
occupational environment.
Most recent approaches include the promotion of safe-by-design
thinking through the whole life cycle of these materials starting
with the planning, design, and production. Including safety as
an integral element in the business thinking would mean enhanced understanding of the benefits of safety for the promises of
nanotechnologies. Incorporation of safety as an integral part of
nanotechnology business would reduce the pressure on safety
assessment of and regulatory activities of ENM. Supported by EU
FP7 CP-IP 211464 (NANODEVICE).
References
[1]EU Strategy 2020. Communication from the Commission:
EUROPE 2020 - A strategy for smart, sustainable and inclusive growth. European Commission 2010.
[2]Impact of Engineered Nanomaterials on Health:
Considerations for benefit-risk assessment. Joint EASACJRC (European Academies Science Advisory Council-Joint
Research Centre) Report. September 2011.
[3]Roco MC, Mirkin CA, Hersam MC. Nanotechnology research directions for societal needs in 2020: retrospective and
outlook summary. NSF/WTEC (National Science Foundation/
World Technology Evaluation Center) report. 2010. [summary of the full report published by Springer].
[4]Maynard AD, Aitken RJ. Assessing exposure to airborne
nanomaterials: current abilities and future requirements.
Nanotoxicology 2007;1:26–41.
[5] Borm PJA, Robbins D, Haubold S, Kuhlbusch T, Fissan H,
Donaldson K, Schins R, Stone V, Kreyling W, Lademann J,
Krutmann J, Warheit D, Oberdörster E. The potential risks of
nanomaterials: a review carried out for ECETOC. Part. Fibre
Toxicol. 2006;3 11.
[6] Nel AE, Mädler L, Velegol D, Xia T, Hoek EM, Somasundaran
P, Klaessig F, Castranova V, Thompson M. Understanding
biophysicochemical interactions at the nano-bio interface.
Nat. Mater. 2009;7:543-57.
[7]Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WAH,
Seaton A, Stone V, Brown S, MacNee W, Donaldson K.
Carbon nanotubes introduced into the abdominal cavity
of mice show asbestos-like pathogenicity in a pilot study.
Nature Nanotech. 2008;3:423-8.
[8] Donaldson K, Murphy FA, Duffin R, Poland CA: Asbestos,
carbon nanotubes and the pleural mesothelium: a review of
the hypothesis regarding the role of long fibre retention in
the parietal pleura, inflammation and mesothelioma. Part.
Fibre Toxicol. 2010;7:5
[9]Oberdörster G, Sharp Z, Atudorei V, Elder A, Gelein R,
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Kreyling W, Cox C. Translocation of inhaled ultrafine particles to the brain. Inhal. Toxicol. 2004;16(6-7):437-45.
[10]NRC. Risk Assessment in the Federal Government:
Managing the Process. National Academy of Sciences. 1983.
Washington, DC.
[11]NIOSH. Approaches to Safe Nanotechnology: Managing the
Health and Safety Concerns with Engineered Nanomaterials:
Publication No. 2009-125. 2009. CDC. www.cdc.gov/niosh/
docs/2099-125/Report.
[12]NIOSH. Occupational Exposure to Carbon Naotubes and
Nanofibers. Department of Health and Human Services,
CDC. External review draft, November 2010. www.cdc.gov/
niosh/docket/review/docket161A/Report.
[13]IFA. Criteria for assessment of the effectiveness of protective
measures. 2009. Available from: http://www.dguv.de/ifa/en/
fac/nanopartikel/beurteilungsmassstaebe/index.jsp
[14]Savolainen K, Alenius H, Norppa H, Pylkkanen L, Tuomi T,
Kasper G. Risk assessment of engineered nanomaterials and
nanotechnologies-A review. Toxicology. 2010;269:92-104.
[15]Elder A, Lynch I, Grieger K, Chan-Remillard S, Gatti A,
Gnewuch H, Kenawy E, Korenstein R, Kuhlbusch T, Linker
F. Human health risks of engineered nanomaterials: critical
knowledge gaps in nanomaterials risk assessment. In: Linkov,
I., Steevens, J. (Eds.), Nanomaterials: Risks and Benefits.
2009. Springer, Dordrecht, pp. 3–29.
[16]Schulte PA, Murashov V, Zumwalde R, Kuempel ED, Geraci
CL. Occupational exposure limits for nanomaterials: state of
the art. J. Nanopart. Res 2010;12:1971-87.
[17]Kuhlbusch TA, Asbach C, Fissan H, Göhler D, Stintz M. Part.
Nanoparticle exposure at nanotechnology workplaces: a review. Part. Fibre Toxicol. 2011;8:22.
[18]Takagi A, Hirose A, Nishimura T, et al. Induction of mesothelioma in p53+/- mouse by intraperitoneal application of
multi-wall carbon nanotube. J. Toxicol. Sci. 2008;33(1):10516.
[19]Kane AB, Hurt RH. Nanotoxicology: The asbestos analogy
revisited. Nature Nanotech. 2008;3:378-9.
[20]Ryman-Rasmussen, J.P., Cesta, M.F., Brody, A.R., ShipleyPhillips, J.K., Everitt, J.I., Tewksbury, E.W., Moss, O.R., Wong,
B.A., Dodd, D.E., Andersen, M.E., Bonner, J.C. Inhaled carbon nanotubes reach the subpleural tissue in mice. Nature
Nanotech. 2009;4:747-51.
[21]Ma-Hock L, Treumann S, Strauss V, Brill S, Luizi F, Mertler
M, Wiench K, Gamer AO, van Ravenzwaay B, Landsiedel R.
Inhalation toxicity of multiwall carbon nanotubes in rats exposed for 3 months. Toxicol. Sci. 2009;112(2):468-81.
[22]Kobayashi N, Ogura I, Gamo M, Kishimoto A, Nakanishi J.
Risk assessment of manufactured nanomaterials: carbon nanotubes (CNTs). Interim report issued on October 16, 2009.
Available from: http://goodnanoguide.org/tiki-download_
wiki_attachment.php?attId=31.
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[23]Pauluhn J. Multi-walled carbon nanotubes (Baytubes): approach for derivation of occupational exposure limit. Regul.
Toxicol. Pharmacol. 2010;57(1):78-89.
[24]REACH. Nanomaterials in REACH. European Commision.
CA/59/2008 rev.; 2008.
Contacts
Kai Savolainen
Nanosafety Research Centre, Creating Solutions
Finnish Institute of Occupational Health
Topeliuksenkatu 41 a A, FI-00250 Helsinki, Finland
Tel: +358 30 474 2200
Email: [email protected]
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Supersonic Cluster Beam
Implantation: a novel process
for biocompatible and
stretchable metallization of
elastomers
G. Corbelli1,2, C. Ghisleri1,2, P. Milani1,2, L. Ravagnan1
1
WISE s.r.l.,Via Boschetti 1 – 20121 Milano – Italy, www.wisebiotech.com
2
Physics Department and CIMAINA, Università degli Studi di Milano, Via Celoria
16 – 20133 Milano - Italy
I
ncreasingly, many applications in biomedicine, prosthetics, wearable electronics and robotics require the integration of electronic, optical and actuation capabilities on soft and conformable
polymeric substrates.[1] Much progress has been made in this
area, especially in the fabrication of circuits and devices on flexible substrates[2] and that utilize mass production manufacturing processes in the production of flexible solar cells,[3] flexible
displays,[4] smart clothing,[5] sensors and actuators.[6] Despite
these achievements, stretchable electrodes consisting of metallic paths on elastomeric substrates are still plagued by drawbacks and failures that prevent their use, especially for biomedical applications. Implantable devices for neurostimulation and
neuroprosthetics[7] could for instance strongly enhance their performances and enlarge their field of application by the possibility
of printing metallic microcircuits on biocompatible and conformable substrates: this would benefit significantly the treatment
of several pathologies such as chronic pain, Parkinson’s disease,
essential tremor, dystonia, and epilepsy.[8]
Efforts to fabricate stretchable metallic circuits and electrodes
are concentrated on the direct metallization of polydimethylsiloxane (PDMS) which couples biocompatibility with mechanical
properties and machinability suitable for rapid prototyping.[9]
At present the metallization of PDMS to produce micrometric
and well-defined conductive pathways is obtained by metal vapor deposition[10] or metal ion implantation.[11] Unfortunately,
these standard approaches have many drawbacks in terms of
layer adhesion, electrical functionality under stretching, attainable lateral resolution, sample heating and charging, and lack of
biocompatibility of the obtained materials. Here we demonstrate
that stretchable and compliant electrodes on PDMS can be efficiently fabricated by the implantation in the elastomeric substrate
of neutral metallic clusters aerodynamically accelerated by a supersonic expansion.[12]
Supersonic cluster beam implantation (SCBI) consists in directing
a highly collimated beam of neutral (i.e. with null electric charge)
metallic clusters, having a size distribution range of 3 nm to 10
nm and kinetic energy of about 0.5 eV atom-1, towards a polymeric substrate (Figure 1a). Although the kinetic energy per atom
of clusters is four orders of magnitude lower than in the case of
ion implantation, clusters (made of several thousands of atoms)
have sufficient inertia to penetrate inside the polymeric target
(kept at room temperature) and to form a nanocomposite layer,
avoiding charging and carbonization of the polymeric substrate.
[12,13]
Figure 1b and 1c show transmission electron microscope (TEM)
images of cross sections of a PDMS substrate implanted at
room temperature with Au clusters at corresponding equivalent thicknesses[13] of 35 nm and 210 nm respectively[12].
Remarkably, the penetration depth of the Au clusters in PDMS
(90 nm – 136 nm, see Figure 1b and 1c) is approximately twice
the penetration depth that was previously observed for Pd cluster
in Poly(methyl methacrylate),[13] as was expected due to the lower hardness of PDMS in comparison to PMMA.
We tested the performances of conductive PDMS/gold nanocomposite obtained by SCBI against extensive uni-axial strain cycles
by means of a custom-built, computer-controlled, motorized uniaxial stretcher, allowing automatic acquisition of the nanocomposite electrical resistance (R) with cyclic strain (ε). At each strain
cycle, the maximum applied strain was 40%.[12]
Figure 2a shows the resulting R evolutions recorded during cycle
2, 10, 100, 1000, 10000 and 50000. During cycle 2 the nanocomposite electrical resistance grows, almost linearly, from an
initial value of 23 Ω (at 0% strain, Rin) up 420 Ω when the maximum strain is reached (i.e. at 40% strain, Rfin), recovering its
initial resistance when the strain is released. Remarkably, as the
number of strain cycles grows, the increase of R with ε remains
monotonous also after 50000 cycles, keeping an almost triangular response: this is a first significant departure from the typical
behavior observed for evaporated metal films on polymers, where a non-monotonous increase of R with ε is reported after a few
thousand strain cycles[10] Furthermore, the value of Rin for the
nanocomposite has only a slow increase as the number of cycle
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increases and, most remarkably, the value of Rfin progressively
decreases. As shown in Figure 2b the value of Rfin becomes, after
50000 strain cycles, almost half the initial value, completely at
odds with the usual huge increase (by orders of magnitudes) of
Rfin observed for evaporated metal films.[10] Those differences
can be explained by the nanocomposite nature of the conductive
film: indeed the increase of the R with strain application is due to
the increase of the mean distance between the metal nanoparticles in the nanocomposite, which is anyway reversed when the
stress is released (recovering the initial conductivity). Moreover,
the repetition of uni-axial strain cycles allows the nanoparticles
embedded in the nanocomposite to progressively reorganize
themselves, leading to a percolating network less affected by the
strain and consequently to the decrease of Rfin.[12] Furthermore,
as shown in Figure 2c, the nanocomposite is not characterized by
the supervening of an abrupt electrical failure at a critical applied
strain (as for evaporated metal films[14]): for any tested film, the
occurrence of an electrical failure is observed only when the mechanical failure of the polymer film (i.e. its breakage) occurs.
SCBI is not only an efficient method for the production of
stretchable and durable metallic circuits but it also functions as a
micropatterning tool: by exploiting the high collimation typical of
supersonic cluster beams,[15] micrometric patterns can be easily
obtained by interposing a stencil mask in front of the PDMS substrate (Figure 3a). Figure 3b and 3c show two example of gold
micropatterns obtained using as stencil masks two TEM grid not
in contact with the substrate.
In summary, SCBI is a novel fabrication process enabling to obtain
metallic electrodes and micropatterns on stretchable substrates.
[12] The produced structures are characterized by their superior capability to sustain very large deformation with electrical
conductance which improves with cyclical deformation.[12] Our
approach substantially overcomes the many limitations typical
of standard metallization approaches, in terms of performances
(delamination, etc.) and processing (sample heating, electrical
charging, carbonization, use of solvents, use of adhesion layers).
Microfabrication of conductive nanocomposite patterns on elastomers provide new perspectives for stretchable and conformable electrodes for biomedicine and smart prosthetics.
The WISE s.r.l. company: from nanotechnology to biomedical applications
WISE S.r.l. (Wiringless Implantable Stretchable Electronics – www.
wisebiotech.com) is a start-up company created in 2011 by the
four authors of the present paper (three of them under-35) and
a seed capital company Agite! S.p.A. The scientific team has a
strong background in the nano- and bio-technology fields.
WISE has the mission of producing and marketing Implantable
Medical Devices through the proprietary SCBI technology. WISE
will produce a completely new family of leads for neuromodulation (implanted in the spinal cord or brain of patients for treating
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neurodegenerative disease like chronic pain and Parkinson) that
will be more reliable, less invasive and cheaper compared to existing products.
During 2011 WISE and its founders have received the following
Technology Innovation Awards and Business Plan competition
prizes: the “TR35-Young Innovators” prize (awarded by the
Technology Review magazine and the RIE Forum), the 2nd place
for the “Medical Bisiness Idea 2011” (awarded by the Charité
Entrepreneurship Summit 2011 - Berlin), the “Isimbardi – Young
Talents” prize (awarded by the Province of Milan), the “What’s
Up Young Talent” prize (awarded by the Journal “What’s Up”),
the first prize for the Life Sciences at the “Start Cup Milano
Lombardia 2011” and the “Nanochallenge 2011” prize (awarded by Veneto Nanotech).
Figure 1. (a) Schematic view of the apparatus used for SCBI (not to scale). The
collimated supersonic beam of neutrally charged Au nanoparticles impact on the
PDMS substrate forming an Au/PDMS nanocomposite layer. (b) and (c): TEM
micrographs of cross-sections (cut by crio-ultramicrotomy, thickness 300 nm) of
the produced Au/PDMS nanocomposite samples.
Figure 2. (a) Electrical resistance as a function of applied strain recorded on the
Au/PDMS nanocomposite film during cycle 2, 10, 100, 1000, 10000 and 50000
(maximum elongation 40%). (b) Electrical resistance at 0% strain (Rin) and at
40% strain (Rfin) as a function of the number of stretching cycle to 40% strain. (c)
Electrical resistance as a function of applied uni-axial strain: the failure at 97%
strain is due to the mechanical breakage of the PDMS substrate.[12]
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Contacts of corresponding author
Luca Ravagnan (Ph.D), C.E.O.
WISE S.r.l. - Via Boschetti, 1 - 20121 MILANO
E-mail: [email protected]
Mobile: +39 3337657189 WebSite: www.wisebiotech.com
Figure 3. (a) Schematic view of the process of stencil mask lithography: a TEM
grid is interposed between the cluster beam and the PDMS substrate. (b) and (c)
The micrographs of the Au/PDMS nanocomposite micropatterns obtained using
two TEM grids Agar G215N and Agar G2760N respectively.
Acknowledgments
WISE S.r.l. is pleased to acknowledge Regione Lombardia and
Regione Sardegna for their financial support to the project
“ELDABI - Elettronica Deformabile per Applicazioni Biomediche”
(project n. 26599138).
References
[1] J.A. Rogers, T. Someya, Y. Huang, Science 2010, 327, 1603.
[2] G. P. Collins, Sci. Am. 2004, 291, 74.
[3] K. Shiu, J. Zimmerman, H. Wang, S. R. Forrest, Appl. Phys.
Lett. 2009, 95, 223503.
[4]S. R. Forrest, Nature, 2004, 428, 911.
[5]M. B. Schbert, J. H. Werner, Mater. Today, 2006, 9(6), 42.
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[7]R. J. Coffey, Artif. Organs, 2008, 33(3), 208.
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[9] G. M. Whitesides, Nature, 2006, 442, 368.
[10]I. M. Graz, D. P. J. Cotton, S. P. Lacour, Appl. Phys. Lett. 2009,
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[11]S. Rosset, M. Niklaus, P. Dubois, H. R. Shea, Adv. Funct.
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[12]G. Corbelli, C. Ghisleri, M. Marelli, P. Milani, L. Ravagnan,
Advanced Materials 2011, 23, 4504.
[13]L. Ravagnan, G. Divitini, S. Rebasti, M. Marelli, P. Piseri, P.
Milani, J. Phys. D: Appl. Phys., 2009, 42, 082002.
[14]T. Adrega, S. P. Lacour, J. Micromech. Microeng., 2010, 20,
055025.
[15]E. Barborini, S. Vinati, M. Leccardi, P. Repetto, G. Bertolini,
O. Rorato, L. Lorenzelli, M. decarli, V. Guarnieri, C. Ducati, P.
Milani, J. Micromech. Microeng., 2008, 18, 055015.
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Nanoparticle imaging at the
Mario Negri Institute: an
innovative approach to verify
the impact of nanomaterials
from the sub-cellular organelles
to the whole organism
Paolo Bigini1, Leopoldo Sitia1, Davide Moscatelli2, Massimo Morbidelli3
and Mario Salmona1
1
Istituto di Ricerche Farmacologiche Mario Negri, Department of
Biochemistry and Molecular Pharmacology,
Via La Masa 19, 20158 Milan, Italy
2
Politecnico di Milano, Department of Chimica, Materiali ed Ingegneria Chimica
G. Natta, Via Mancinelli 7, 20131 Milan, Italy
3
Department of Chemistry and Applied Biosciences, Institute for
Chemical- and Bioengineering,
Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland
Introduction
O
ne of the main goal of the modern toxicology is the translation of results obtained from the bench (cells and animals) to
the bedside. The development of preclinical analyses similar to
those routinely used at the clinical level is fundamental to satisfy
to this need. In this context, the exploitation of in vivo diagnostics
(by non invasive instruments of imaging) in rodents and other
small animals is required for therapeutic, pharmacological and
toxicological purposes. In recent years, the use of non invasive
instruments of screening in the field of nanotechnology has been
taking place either for the theranostic purposes or to verify the
possible risks associated with the interaction between nanoparticles and host tissues. To achieve exhaustive information about
the risk-benefit balance associated with acute/chronic exposure
to nanoparticles represents a priority for both scientific community and the public opinion. In spite of the abundant literature
existing on this issue, the survey of the risks for many different
types of nanomaterials is far from to be unveiled.
It has been demonstrated that a wide range of physico-chemical
features may concur to confer cytotoxicity to Nps, affecting their
interaction with cells and organs, and their subsequent uptake
and intracellular trafficking/fate. Such features include particle size, agglomeration state, shape, crystal structure, chemical
composition, surface area, surface chemistry, surface charge, and
porosity. An additional source of variability stems from the nonspecific adsorption of proteins on NP surface.
For this reason, the modern strategy of “in vivo nanotoxicology” needs to the development of new instruments for in vivo
imaging for small rodents. This approach enables to follow the
fate of nanoparticles in each experimental subject: 1) at diffe-
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rent interval of times after administration; 2) after different serial
administrations; 3) in different organs and 4) following different
ways of administration. On the overall, these studies can be crucial to provide information about the distribution, accumulation,
biodegradability, metabolism, localization in specific targets, of
different types of nanoparticles.
In July 2007 the Institute moved to a new building where a
“mouse clinic” has been set up. The access to animal rooms and
laboratory animals is exclusively allowed to Specific Pathogen
Free animals. Modern instruments for experiments of in vivo imaging in rodents are available in the “mouse clinic”. This large and
heterogeneous range of possibility allows to our groups to investigate about important items related to the nanomedicine (distribution, accumulation in target organs, interaction with different
organs, permanence in the bloodstream, passage of biological
barriers). Moreover the employment of diagnostic and therapeutic screenings, largely utilized at the clinical level, contribute to
the improvement of translation research. A large series of investigations, by using neo-synthesized polymeric nanoparticles loaded
with fluo-paramagentic tracers, have been carried out in the last
year at the Mario Negri Institue and further studies with different
types of nanomaterials are in progress.
Experimental procedures
Nanoimaging can be roughly divided in four different serial steps:
1) In vitro determination; 2) Cellular assessment; 3) In vivo imaging; 4) Ex vivo analyses.
A brief description of the potentials of the Mario Negri in the field
of Nanoimaging is summarized below.
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1. In vitro determination
The morphology, size, distribution and the external surface charge of Fluo-SPIO Nps can be determined by Dynamic Laser Light
Scattering (DLLS) at different times and in different conditions
(e.g. distilled water, saline solution, cell culture medium, blood
and tissue homogenates).
Atomic Force Microscopy (AFM) allows to determine the shape
and the degree of monodispersion of Fluo-SPIO Nps.
Fluorimetric analysis is employed to verify if the internalization
of dyes into the Nps might somehow modify the peaks of excitation and emission and reduce the intensity of the fluorescence
(Figures 1 and 2).
By Electron Spetroscopic Imaging (ESI) it is possible to verify the
presence of SPIO Nps in each single nanoparticle and the spatial
distribution of the Iron domains (Figures 1 and 2).
By the combination of these techniques we are able to determine
the main physico-chemical parameters of ne-synthesized Nps and
their interaction with biological samples. This approach could be
extremely interesting to determine and predict the behaviour of
many nanomaterials either in the environmental area or in nanomedicine.
is important to underline that the Mario Negri introduced this
criteria of non invasive investigation also to drastically reduce the
number of animals for each single research and to minimize their
stress during the investigation. In addition the Mario Negri has recently started in vivo study with an alternative and simpler model
of pluricellular organism, the nematode chaenorabditis elegans
( c. elegans). The c. elegans is an efficient and reliable model to
study basic mechanisms on the interaction between Nps and host
tissues (Figure 2).
2. Cellular assessment
Time lapse recording experiments can be carried out to determine
the dynamic of internalization of Fluo-SPIO Nps in dependence of
nanoparticle concentration, time of incubation and cell types.
Confocal microscopy and Transmission Electron Microscopy (TEM)
is commonly utilized to better investigate the distribution of fluorescent or paramagnetic component in cells (Figures 1).
Moreover, quantitative parameter of Fluo-SPIO Nps internalization at any different experimental condition can be easily achieved by TissueQuest analysis software (TissueGnostics, Vienna,
Austria). All these approaches enabled us to evaluate the main
parameters of viability and cell functionality at different times
after Fluorescent and –paramagnetic Nps in amniotic stem cells
(Figures 1 and 2) and can be utilized to study the same mechanisms for pollutant Nps or Nps loaded with different drugs.
Conclusions
The possibility to utilize the same instruments for all investigations, to avoid the delivery of materials and to maintain the same
“environmental conditions”, greatly contributes to the reliability
of a such complex and multi-step characterization not only in
the field of nanotoxicology but also for the development of new
therapeutic strategies based on Np-dependent delivery of drugs,
small peptides or nucleic acid. It is in fact important to underline
that, since the early 60s, the Mario Negri Institute has been involving in many projects related to the advancement of pharmacological strategies for the overall improvement of public health.
The modernity of the infrastructure, the high level of pharmacologists and technicians and the past and present experience in the
field of pharmacokinetics, pharmacotherapy make the Institute
as an attractive and reliable centre for to collaborative projects
with academic Institutions and Industrial partners. In particular,
we believe that our ability to carry out investigation of a very wide
range of materials particles from the single nanoparticle synthesized to its effect in healthy animals and/or models of human
disorders, may pave the way for innovative studies in the field of
nanotechnology.
3. In vivo imaging
By Two-Photon Confocal Microscopy is possible to determine the
presence of systemically injected Fluo-SPIO Nps in the bloodstream at different times and their possible diffusion to neighbouring
areas (Figure 3).
A detailed investigation about the biodistribution of Fluo-SPIO
Nps in host tissues can be performed both by experiments of
Fluorescent Molecular Tomography (FMT) and analyses of
Magnetic Resonance Imaging (MRI). This combined strategy of
scanning allows to visualize nanoparticles by coupling the high
sensitivity and relative rate of image acquisition achieved by FMT
to the anatomical resolution and the lack of background (due to
the autofluorescence of tissues) provided from MRI (Figure 4). It
4. Ex vivo analyses
We previously stated that not-invasive procedures of imaging are
indispensable to improve the translation between preclinical and
clinical studies. However, it is important to underline that, the exploitation of ex vivo analyses in animal models are still required to
further validate the in vivo studies and to provide a more detailed
characterization on the cellular distribution of Fluo-SPIO Nps in
different organs and at different times after administration.
In this context, we are able to visualize fluorescent spots in different organs by histological analyses and confocal microscopy
(Figure 3).
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Figure 1
Representative pictures showing the main features of paramagnetic Nps and their
interaction with human amniotic fluid cells (hACFs).
A: Atomic force microscopy image, demonstrates the monodispersity of Nps
and the homogeneity of shape and size (further confirmed by DLLS analysis) B.
Electron Spectrometer Imaging, reveals the spatial disposition of SPIO domains
(red pixels) in the gray spheres, which correspond to the PLA-coating. C-D: Neosynthesized paramagnetic nanoparticles efficiently internalized in all types of
hACFs (C) and selectively localized within the cell cytoplasm (D). E-F: Transmission
electron microscopy reveals that paramagnetic nanoparticles are rapidly
internalized (E- red arrows) and accumulate in vesicular structures close to the
perinuclear area (F- red arrows).
Figure 2
Representative pictures showing the main features of fluorescent Nps (Rhodamine
B is covalently linked to the polymer) and their interaction with human amniotic
fluid cells (hACFs).
A: Atomic force microscopy image, demonstrating the monodispersity of
fluorescent Nps and the homogeneity of shape and size (further confirmed
by DLLS analysis) B. Fluorimetric analysis demonstrates that conjugation with
the polymer does not modify the optical properties of Rhodamine (the peak of
fluorescence intensity is typical of that found for unconjugated Rhodamine C:
Time-lapse recording experiments reveal that hACFs (phase-contrast, left columns)
efficiently internalize fluorescent PLA-Nps (red staining, middle columns).
Incubation with the vital nuclear dye Hoechst33258 (blue staining) shows that,
similarly to paramagnetic Nps, the process of internalization is confined to the
cytoplasm. The panels show the same frame monitored at different times (0-72
hours). Similarly to SPIO-loaded Nps, fluorescent Nps progressively accumulate in
cells Nps (red staining). D: High magnification picture showing the endocytosis of
Nps in hACFs.
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Figure 3
Representative pictures showing the tracking of fluorescent nanoparticles, injected
in the tail vein of healthy mice, by in vivo (A-B) and ex vivo (C-H) imaging.
A: Two-photon confocal microscopy allows us to visualize cerebral vessels by
intravenously injecting dextran coupled to a fluorescein (green signal), B: High
magnification picture reveals the presence of fluorescent Nps intravenously
injected after dextran administration (the red signal is associated with Rhodamine
B). Similarly to the dextran, the staining associated with nanoparticles is confined
to the vasculature and does not cross the blood brain barrier. C-D Histology of the
liver (C) and spleen (D) of a mouse sacrificed shortly after two-photon microscopy;
E-F: Merge between the green (FITC) and red (Rhodamine B) signals in the liver
and spleen a few hours after intravenous administration of nanoparticles; G-H.
High magnification pictures of liver (D) and spleen (F) in which it is possible to
observe that nanoparticles are not exclusively associated with the bloodstream
but are also localized in the parenchyma.
Figure 4
Representative MRI showing sagittal cerebral slices six hours after administration,
in lateral brain ventricles of healthy mice, of saline solution (A) or saline solution
+ paramagnetic Nps (B-D). A: The administration of saline solution into ventricles
slightly increases the water volume and increase the brightness of MRI signal
in the ventricular system by T2* acquisition; B-D: The presence of paramagnetic
Nps is clearly detectable in both representative sagittal (B) and coronal (C)
slices 6 hours after administration (red arrows). This darkening phenomenon is
dependent upon the concentration of iron superoxide in the brain ventricles. D:
The positive signal is almost completely recovered 48 hours after parmagnetic Nps
administration. This suggests a rapid removal of Nps from brain ventricles and/
or their internalization by macrophages surrounding the ventricle layer. Figure E:
Histological section showing the positive signal for Prussian blue staining in the
lateral ventricle of a mouse mouse sacrificed eight hours after Nps administration.
The presence of iron oxide was previously revealed by MRI axial slice (F).
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RF MEMS Phase Shifters For
New Generation Phased Array
Antennas
I. Pomona*, F. Di Maggio*, M. Dispenza**, P. Farinelli***, B. Margesin#,
E. Carpentieri§, U. D’Elia§, M. Barbato$, G. Meneghesso$, M. Tului^, E.
Chiuppesi***, R. Sorrentino***
* Selex Elsag Spa, Via A. Agosta, Zona Industriale Pantano d’Arci - 95121 Catania,
**Selex Sistemi Integrati S.p.A., Via Tiburtina 1231, 00100 – Roma,
***University of Perugia, DIEI, Via G. Duranti 93, 06125 Perugia,
#
MEMS Research Unit, FBK-irst, Via Somarive 18, 38123 Trento,
$
University of Padova, via 8 Febbraio, 2 - 35122 Padova
§
MBDA Italia SPA, Via Tiburtina Km.12400, 00131 - Roma,
^
Centro Sviluppo Materiali SpA, via di Castel Romano 100 -00128 Roma,
M
icro-Electro-Mechanical Systems (MEMS) are miniaturized
devices combining together electrical and mechanical functionalities, realized by technological processes compliant with those
devoted to the fabrication of standard integrated CMOS circuits.
With the increased demand for faster, smaller, highly tuneable
and cheaper communication systems that consume less power
and have wider bandwidths for increased data rates, MEMS devices have found a great deal of attention, thanks to their ability to
bring reconfigurability in practically any passive RF device.
The growing interest on RF MEMS technology led Finmeccanica
to approve the CONFIRM [reCONFIgurable circuits by Rf Mems]
corporate project within the activities of the Advanced Materials
& Enabling Technologies Community, Mems Focus Group, in
MindSh@re project. The aim of CONFIRM was to demonstrate
the capability of RF-MEMS technology to realize RF reconfigurable circuits (Phase shifters, True Time Delay lines, Wideband
Switches) to be applied on the new generation of Phased Array
Antennas for SatCom, Radar and Missile systems. Integration on
RF modules and packaging solutions have been analyzed with a
focus on low-cost production.
The team of CONFIRM project is composed of Selex Elsag (formerly Selex Communications), playing the role of team leader,
Selex Sistemi Integrati, MBDA, CSM, along with Padova and
Perugia Universities as Academic Centers.
The MEMS realization is coordinated by RF Microtech, a spinoff of Perugia University participated by FBK (Fondazione Bruno
Kessler - Trento), one of the most appreciated MEMS foundry in
Europe. Packaging and assembly is carried out by Optoi (Trento).
Phase Shifter was the most important element selected by the
team in order to have a better understanding of MEMS technology capability for RF applications. Military and Governmental
applications are increasingly interested in Satellite On The Move
(SOTM) terminals requiring both transmitting and receiving antenna systems with the capability to track different targets during
motion with high resolution and low probability of interception.
Electronically steerable antennas offer many advantages over
conventional mechanically scanned arrays such as fast scanning
rate, low weight and beam shaping capability. The electronic
beam steering is realized by using variable loads, phase shifters
or true time delay (TTD) networks to control the phase of the
individual radiating element of the antenna array without any
mechanical motion. Micro-Electro-Mechanical Systems (MEMS)
represent an extremely attractive technology for the realization
of TTD and programmable phase shifters due to the low loss,
low-power consumption, and excellent linearity compared to the
traditional monolithic microwave integrated circuit (MMIC). [1]
[2] [3].
In the framework of CONFIRM project three compact 5-bit K-band
MEMS phase shifters to be used in Phased Array Antennas for
SOTM Terminals and ESA (Electronically Scanned Antenna) seekers, have been designed, manufactured and tested. The operating bandwidths are 20.2-21.2GHz, 30-31GHz and 33.9-36
.1GHz.
All devices have been designed in microstrip technology using
properly developed RF-MEMS ohmic cantilever switches as basic components. A hybrid architecture based on switched and
loaded line sections has been adopted in order to get the best
compromise among phase shift, low loss and reduced space occupation in the selected area. Each bit has been separately designed and optimized by using the full wave EM ADS Momentum
[4]. The three 5 bit phase shifters as well as the device single bits
have been monolithically manufactured on 200µm thick HR Si
[High Resistivity Silicon] substrate by using the eight-mask surface
micro-machining process available at FBK [5].
The devices have characterized on-wafer and on-board; some
significant reliability tests have been carried out. Excellent performance has been obtained for all devices, demonstrating the
great potentiality of RF MEMS technology. For the 20.2-21.2GHz
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device return loss better than 15dB and insertion loss better than
3 dB have been measured for all 32 states [6].
Such a high performance devices will allow to reduce the complexity of the RF beamforming network and the amplification
stage in the Phased Array Antenna Architecture and consequently to significantly reduce the production cost of the whole system.
Few types of phase shifters (non-MEMS) Ka-band are available
only in bare GaAs chips with higher losses [typically> 7dB], only
in the USA market with possible restrictions on end users. With
MEMS technology we use Silicon, less expensive than GaAs, with
lower losses and in which also active RF components (amplifier
stages) can be integrated at low cost, on the same chip.
Figure 1: Photo of the packaged 5-bit K-band MEMS phase shifter
Figure 4: Phase Shifters in ESA (Electronically Scanned Antennas) seekers.
Figure 5: Phase Shifters Beam forming Network in SOTM (Satellite On The Move).
Figure 6: Multifunction / Multirole Electronically Scanned Antenna for Defense
Systems.
Figure 2: Photo of the manufactured 4’’ HR Si wafer
Figure 3: Photo of the manufactured 35GHz Phase Shifter in the microstrip test
board and comparison between theorethical and measured phase shift for the 32
states of the 35GHz device.
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References
[1]P. Farinelli, E. Chiuppesi, F. Di Maggio, B. Margesin, S. Colpo,
A. Ocera, M. Russo, I. Pomona, “Development of different
K-band integrated MEMS phase shifters for satellite COTM
terminals”, International Journal of Microwave and Wireless
Technologies 2010, volume 2, issue 3-4, pp. 263-271
[2]Wexler, R.S.; Ho, D.; Jones, D.N.; , “Medium data rate (MDR)
satellite communications (SATCOM) on the move (SOTM)
prototype terminal for the army warfighters,” Military
Communications Conference, 2005. MILCOM 2005. IEEE ,
vol., no., pp.1734-1739 Vol. 3, 17-20 Oct. 2005
[3]Topalli, K.; Civi, O.A.; Demir, S.; Koc, S.; Akin, T.; “A
Monolithic Phased Array Using 3-bit Distributed RF MEMS
Phase Shifters”, Microwave Theory and Techniques, IEEE
Transactions on, Volume 56, Issue 2, Feb. 2008 Page(s):270
– 277.
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[4]ADS Agilent Momentum www.agilent.com
[5]A. Ocera, P. Farinelli, F. Cherubini, P. Mezzanotte, R. Sorrentino,
B. Margesin, F. Giacomozzi, “A MEMS-Reconfigurable Power
Divider on High Resistivity Silicon Substrate”, IEEE MTT-S
International Microwave Symposium, Honolulu, 3-8 June
2007
[6] F. Casini et al., “RF MEMS based microwave 5-bit phase shifters for Phased Array Antenna Systems” MEMSWAVE 2011
Conference Proceedings
Contacts
Ignazio Pomona
Selex Elsag Catania
mail: [email protected]
telephone number: +390957576328
mobile: +393357379375.
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X-ray MicroImaging Laboratory
(XMI-LAB)
Cinzia Giannini, Davide Altamura, Rocco Lassandro, Liberato De Caro,
Dritan Siliqi, Massimo Ladisa
Istituto di Cristallografia – Consiglio Nazionale delle Ricerche
via Amendola 122/O, BARI
T
he SEED project ‘X-ray synchrotron-class rotating anode microsource for the structural micro imaging of nanomaterials and
enginereed biotissues has been financed by the Italian Institute
of Technology (IIT) – Genova. The project officially started the
23.02.2010. Main goal of the project was the realization of a
forefront laboratory in the national and international frame.
The X-ray micro Imaging laboratory (XMI-LAB) was aimed at the
structural (atomic models), micro-structural (domain size and lattice strain) and morphological (domain shape) characterization of
new materials (nanomaterials and biomaterials). Delivery of the
instrument and its installation was carried out in spring 2011. An
opening workshop, dated 14.10.2011, launched the instrument
in the Italian scientific community. The XMI-LAB is illustrated in
Fig. 1.
a SAXS/WAXS (SWAXS) [1] three pinholes camera (Fig. 1c). The
Fr-E+ SuperBrigth microsource is quite unique in terms of brilliance as laboratory source, being the flux comparable to a bending
magnet synchrotron light source.
Fig. 2 shows the other Fr-E+ SuperBrigth rotating anode microsources present in the world (only 10, including the present
one).
Figure 2: world map of the Fr-E+ SuperBrigth rotating copper anode microsources
The XMI-LAB can be used either as a scanning less-less SWAXS
microscope or for GISAXS-GIWAXS [2] data collection. The X-ray
scanning microscope allows to load the sample onto a scanning
stage and the sample is measured in transmission mode. For
GISAXS and GIWAXS sample is mounted in reflection mode.
Figure 1 (a) Scheme of the XMI-LAB; (b) SuperBright rotating copper anode
microsource (45 kV/55 mA; Cu-Kα, λ = 0.15405 nm); (c) SAXS/WAXS (SWAXS) three
pinholes camera.
The laboratory is equipped with a Fr-E+ SuperBrigth rotating copper anode microsource (45 kV/55 mA; Cu-Kα, λ = 0.15405 nm,
4*109 photons/sec/mm2/mR2, 2475 W) shown in Fig. 1b, and
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WAXS-GIWAXS data contain information on the NP atomic crystalline structure and its deformation (strain). Information can
be extracted from higher order peak shifts (strain), peak width
anisotropy (domain size and shape) or peak positions and relative
intensities (crystal structure). Being several effects all convoluted
in the same profile, it is quite helpful to determine size&shape
separately from SAXS-GISAXS data, especially if measured simul-
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taneously on the same sample, as possible with this SWAXS microscope at CNR-IC.
SAXS-GISAXS are used to study the NP morphology at the nanoscale; in case of known shape it is possible to find the size distribution. The specimen to be studied can be either onto a surface,
or embedded in a matrix. Besides the morphological analysis
(shape&size), these techniques can provide precise structural information on a nanometric scale (nanometric periodicities) when
present. Fig. 3 shows how the SAXS pattern changes for NPs of
different shapes (sphere, rod, platelet, shell).
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- Smart Materials, where the long lasting and fruitful collaborations, established by the CNR-IC with several Italian laboratories involved in the synthesis of nanocrystalline materials and
nanostructured films, will all benefit of the instrumentation.
Indeed, almost any type of nanocrystalline or nanostructured
sample, either in form of powder, or dispersed in solution, or
embedded into a ~100µ thin support, if transparent to X-rays.
Nanostructures can be studied also if laying on top of surfaces or
buried underneath.
Figure 3. SAXS pattern of NPs of different shapes
Figure 4. SWAXS microscopy of a bone biopsy (b,c,d) compared with CPL (a).
The structural complexity of a novel materials can be studied at
three different length scales:
- Atomic scale (type, positions and symmetry relation of the atoms in the unit cell, unit cell size, space group, domain size)
- Nanometric scale (morphological conformation: NP shape and
size, NP assembly)
- Micrometric scale: the atomic or nanometric sample information can be mapped every 70 μm, which is the X-ray spot size
at the sample position of the scanning lens-less SWAXS microscope (this possibility is feasible only for sample measured in
transmission mode).
In line with Horizon 2020 proposals, the XMI-LAB will be intensively involved in studies of:
In this latter case, mm2 sample areas can be inspected. As an
example, scanning SWAXS data were collected on bone biopsies.
Bone is a complex biomaterials formed by an inorganic conterpart (hydroxyaapatite nanocrystals) embedded into a polymetric
matrix (collagen fibrils). Data were converted, by means of robust
crystallographic analytic methods, into direct images (radiographies) of the mineral nanocrystals contribution (size/shape and
orientation of hydroxyapatite nanocrystals) to be directly compared with Circularly Polarized Light (CPL) microscopy. This combination of SWAXS and CPL microscopies allowed us to image
the complex architecture of the cross-linked type I collagen fibrils
mineralized with hydroxyapatite nanocrystals (see Fig. 4).
- Health, where the CNR-IC has started a promising collaboration
with Dr. Fabio Baruffaldi (Lab. Tec. Med., Rizzoli-BO) for studies
of pathologic and healthy bone biopsies, aimed at imaging the
mineral nanocrystalline phase within the collagen fibril at subosteon resolution.
The XMI-LAB, that will become fully operational by the end of
2012 (end of the commissioning), is available to consider possible collaborations and use of facilities with other organizations
(research, industry).
[1]SAXS is the acronymous of Small Angle X-ray Scattering;
WAXS is the acronymous of Wide Angle X-ray Scattering
[2] GISAXS is the acronymous of Grazing Incidence Small Angle
X-ray Scattering; GIWAXS is the acronymous of Grazing
Incidence Wide Angle X-ray Scattering
Contacts
Dr. Cinzia Giannini
Istituto di Cristallografia (IC) Consiglio Nazionale delle Ricerche
via Amendola 122/O 70126 Bari - Italy
web: www.ic.cnr.it Phone: 0039 - 080 - 592 9167 (9154,9151)
fax: 0039 - 080 - 592 9170 E-mail: [email protected]
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European Projects
NanotechItaly 2011 in its fourth edition hosted specific events
within the meeting dedicated to European Projects.
The main EU projects presented at the Conference were:
KEEN-Regions, NanoSustain, NanoCom, Nanofutures and
NanoCode.
KEEN-Regions
Info: www.keen-regions.eu
NanoSustain Project is a EU project focused on topics concerning the materials characterisation, the toxicity aspects (mainly
concerning the hazard and impact assessment), the preliminary
results of the Life Cycle Assessment. A main topic of the workoshop was the evaluation of the possibility of recycling/reusing
nano-doped material.
Rudolf Reuther introduced the NanoSustain Project, followed
by the presentatios by:
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Stefano Pozzi Muccelli – NanoSustain: Material
Characterization
Anne Thoustrup Saber – NanoSustain WP3: Hazard
Characterization and impact assessment
Michael Steinfeldt – NanoSustain WP4: Life Cycle assessment
of nanotechnology-based products
Ulrika Backman – NanoSustain WP5: Reuse/Recycling, final treatment and disposal of nanotechnology-based products.
Info:www.nanosustain.eu
(Knowledge and Excellence in European Nanotechnology Regions)
is one of the Regions of Knowledge projects and it is supported
by the European Commission through its Seventh Framework
Programme. It aims to expand and deepen the collaboration
between three European regions - Veneto, Rhone Alpes and the
Basque Country – drawing a joint action plan for the development of nanotechnologies. The project gathers stakeholders representing researchers, businesses and local authorities from the
three Regions.
KEEN-Regions organized a specific workshop on “Governance
and development of nanotechnologies: a regional joint action plan” in order to spread information on the activities and
opportunities on nanotechnologies which are the focus of the
project itself.
The workshop was divided in two parts. The first was moderated by Dr. Ivan Boesso (Veneto Innovazione), who presented
the main actions and goals of KEEN-Regions and introduced the
three speakers:
Gerd Meier Zu Kocker - Clusters Policies in a European perspective
Simone Arnaldi - Perceptions, narratives and debates about nanotechnologies
Jean Chabbal – A simple and interactive way to present new
technologies to the general public
The second session was organized as a round table and panellists
discussed on the actual governance for nanotechnologies and
future developments with the audience.
The panellists, moderated by Emily Wise (Vinnova), were people
from institutions and research centres,:
Michele De Ruos, Veneto Region
Diego Basset, CIVEN and NANOFAB
Zita Zombori, Gedeon Richter
Germàn Cabañero Sevillano, CIDETEC
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NanoCom Project
is funded by the EU 7th Framework Programme with the scope
to analyzing the best practices to lower the barriers for commercialisation of nanotechnology. NanoCom organized a training module with the aim to foster the
transfer and draw upon knowledge from analysing the barriers
to, and best practices in, the commercialisation of nanotechnology. The module included also material related to finance, open
innovation and business development.
The session was chaired by Enzo Sisti and the presentations
were by:
Frank T. Piller – Fundamental understanding of Open Innovation;
Fundamental understanding of Open Collaboration
Jozef Cenens – Practical training; Best practices; tools for effective collaboration and open innovation; innovation Project
Mamanagement
Info:www.nanocom-eu.org NANOfutures
is an ETIP European Technology Integrating and Innovation
Platform, multi-sectorial, cross-ETP, integrating platform with
the objective of connecting and establishing cooperation and
representation of European Technology Platforms that require nanotechnologies in their industrial sector and products.
NANOfutures, aims to be a long-lasting nanotechnology hub,
coordinating all relevant nanotechnology stakeholders (industry,
SMEs, NGOs, financial institutions, research institutions, universities, civil society with an involvement from Member States at
national and regional level). The Conference session presented
objectives and current outcomes at European level as well as the
activity of the Italian Nanofutures Platform. It is an environment
where all these different entities are able to interact and come
out with a shared vision on nanotechnology futures.
The workshop chaired by Paolo Matteazzi hosted the presentations by:
Paolo Matteazzi – Nanofutures, European integrating and
Innovation Platform on Nanotechnology
Vito Lambertini – Nanofutures Key Nodes
Brian Winans – The ObservatoryNANO European Nanotechnology
Landscape Report
Donato Zangani and Pierluigi Bellutti – The Italian Platform
n o t i z i e
d a
for Nanotechnology – Industrial and research Cluster
Info:www.nanofutures.eu NanoCode Project
The FP7 Nanocode Project (January 2010-November 2011) has
facilitated a broad stakeholders dialogue in Member States and
other selected countries aimed at identifying perspective and attitudes, opportunities and limits of the European Code of Conduct
for Responsible Nanosciences and Nanotechnologies Research,
considered key to support responsible innovation. NanoCode
main outcomes are: the “MasterPlan: issues and options on
the path forward with the Code” and the CodeMeter, a practical tool to help stakeholder assess their compliance with the
Code’s principles. These documents, illustrated during a presentation in the session on Responsible Development and shown at
the NanoCode project booth, are available for download on the
project website.
Info:www.nanocode.eu
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Networking Event
A special Networking Event was organized, with the support of
APRE (Agency for the Promotion of European Research), in the
framework of the Conference. The networking, free of charge
for the Conference participants, offered the possibility to businessmen, entrepreneurs, researchers and innovators to actively
establish contacts during face-to-face meetings. They made
possible sharing and discussing ideas with other highly qualified people, promoting knowledge and exchange of information
among participants, evaluating collaboration opportunities at the
national and international level, meeting potential business or
project partners.
The meetings were designed in “all against all”, i.e. each participant was allowed to actively select profiles to meet and could be
required by other participants for a meeting. Participants had the
opportunity to select at least 7 meetings for each session lasting
a maximum of 30 minutes.
The Networking Event, saw 65 participants, representatives of
both academia and industry (see Fig.1). Representatives also
from third countries to the European Union, as U.S. and Russia,
have actively participated in the networking and interacted with
European and Italian researchers.
Besides the official participants, other meetings were informally held on time for some researchers participating in the
Conference.
After the Networking participants were asked to fill in a feedback
form via the website to assess the encounters that took place,
assess the degree of satisfaction of each meeting, and the nature
of possible future collaborations between the parties.
The data obtained from the general assessment of the event
were very positive, with the average value amounted to “good”
(Fig.2).
Fig.1 Types of Participant Institutions
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European Nanotechnology
Landscape Report
In the frame of the NanoFutures Project Session, Brian Winans
(Bax&Willems, Spain) has illustrated the emerging highlights of
the “European Nanotechnology Landscape Report” produced
within the FP7 ObservatoryNANO Project. The introduction to the
document is reported below.
Fig. 2 General Evaluation of the Event
The average of the responses on expectations about future collaborations were also positive, with a majority ( 37%) on the average value of “Further Planned Contact “ (Fig.3).
Fig. 3 Evaluation of face to face meeting
For further questions: Serena Borgna ([email protected])
APRE - Agency for the Promotion of European Research - www.apre.it
Europe faces a number of ‘Grand Challenges’, outlined in the
Lund Declaration 2009, such as global warming, tightening supplies of energy, water and food, ageing societies, public health,
pandemics and security. Nanotechnologies offer the potential to
help address a number of these challenges leading to an ecoefficient European economy, which competes effectively with
other world regions.
In order to achieve these goals policy makers must ensure that
European research is world leading.
However, the innovation pathway from basic research, through
development, to commercialisation must also be highly effective.
With this need in mind the FP7 ObservatoryNANO project has
undertaken to provide policy makers at all levels, from local governments up to the European Commission (EC) and European
Parliament (EP), with an overview of the nanotechnology landscape in Europe. This has involved monitoring of new technology
developments and their market impacts through desk research
and extensive expert engagement together with a company survey to identify and gather information on European nanotechnology business activity. The survey has built upon the patent,
publication, and funding analysis that has been ongoing since the
project’s inception in 2008. It already includes direct input from
over one hundred nanotechnology businesses across Europe, as
well as basic data on over 1500 nanotech companies identified
by the ObservatoryNANO through objective criteria.
The first part of this report looks at the European Nanotechnology
Innovation Landscape. The methodology utilised to identify nanotechnologies companies will be outlined before the results are
presented.
An analysis of EU innovation tools is presented that illustrates
which innovation stimulation instruments are available to policy
makers, and what a balanced portfolio of such instruments might
look like, from a nanotechnology specific science-to-market perspective.
The second part of the report will take five of the Grand
Challenges identified and provide a snapshot of the wide-ranging
development are outlined. Further, the obstacles being faced in
the development of the relevant technologies are evaluated including EHS and ELSA issues, Regulations & Standards, and also
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economic and technological barriers. Finally two case studies of
specific developments and their impacts, market potential, and
barriers to success are highlighted.
Organisations involved in the manufacture, supply or use of any
material have a duty to understand any risks that it may pose to
the health of their workforce, customers and the environment,
and to put in place such measures that are needed to manage
these risks. This requires them to address any evident gaps in
knowledge in order to gain a better understanding of the risks
associated with their materials, whether to show compliance
with regulation, pre-empt regulatory changes, and (particularly
where no regulation exists) demonstrate responsibility. ELSA,
EHS, and Regulations & Standards issues are obviously very important considerations when addressing the future development
of nanotechnologies within Europe. Aspects relevant to each of
the grand challenges featured above are outlined within this report but considerably more in-depth analysis has been conducted
within the ObservatoryNANO consortium.
This information together with all other outputs of the project,
including annual factsheets, Briefings, and more in-depth technical reports, can be found on the ObservatoryNANO website.
Info: www.observatorynano.eu
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Cold & Thermal Spray
Symposium
Simone Vezzù - CIVEN
Le tradizionali tecniche di spruzzatura termica, alle quali più recentemente si è aggiunta la tecnica Cold Spray, hanno una importanza rilevante nel panorama scientifico ed industriale soprattutto legato al mondo della meccanica, meccatronica, aeronautica e
navale. Tuttavia, la sempre maggiore richiesta ed impiego nell’industria di rivestimenti superficiali e tecniche di ingegnerizzazione
delle superfici sta espandendo l’interesse di oggi (e quindi si prevede l’utilizzo di domani) anche ad altri settori quali ad esempio il
chimico, biomedicale, agroalimentare e manifatturiero.
L’Italia dispone di una importante competenza nell’ambito del
thermal spray sia dal punto di vista universitario ed accademico
che dal punto di vista industriale. Tuttavia, come in molti casi
avviene nel nostro paese, non esiste una vera e propria comunità scientifica in questo settore, le occasioni di disseminazione
e condivisione del know how sono limitate e le collaborazioni
tra le diverse realtà operanti nel settore (nei casi in cui non ci sia
una concorrenza diretta) sono limitate ad iniziative e conoscenze
personali. In questo ambito, Veneto Nanotech è operativo “solamente” dal 2007 tramite la facility di Cold Spray installata presso
Nanofab nel parco scientifico VEGA situato nell’ex area di porto
Marghera ed attualmente diretta da Simone Vezzù, organizzatore del simposio. Lo scopo di questo primo Cold & Thermal Spray
Symposium è proprio quello di offrire un’occasione per il confronto tra diverse realtà operanti nel settore, fornendo un aggiornamento sulle nuove tecnologie, condividendo esperienze dirette su
attività di R&D e illustrando casi specifici di studio in applicazioni
industriali e cercando quindi in questo modo di favorire il networking tra ricerca ed impresa.
Il simposio è stato strutturato in una doppia sessione, con 12
interventi complessivi, distribuiti dalle 9:30 fino alle 16:00 circa.
L’intervento di apertura tenuto dal prof. Rainer Gadow ha da subito illustrato una interessante panoramica sullo stato del thermal
spray ad oggi ed un focus sulle recenti opportunità offerte dalle
tecnologie emergenti di spruzzatura con sospensioni quali SPS
(Suspension Plasma Spray) e HVSPS (High Velocity Suspension
Plasma Spray) che rappresentano ad oggi l’anello di congiunzione
tra la deposizione di film sottili (indicativamente minore di 0.01
mm) e la deposizione di film spessi (indicativamente superiori a 0.1
mm). Tali tecnologie sono in fase di forte crescita sebbene ad oggi
il loro impatto nell’industria sia ancora limitato. I due interventi
successivi tenuti dal prof. Pedro Poza dell’Università di Madrid e
da Tiziana Marrocco di TWI (The Welding Institute) di York hanno illustrato due potenziali applicazioni della tecnica cold spray
rispettivamente nella deposizione di cer-met per collettori solari e
nel near-net shape manufacturing di componenti in lega di titanio. Maurice Ducos, consulente di CGT gmbh, principale azienda
costruttrice di cold spray nel mondo, ha fornito una ampia panoN e w s l e t t e r
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ramica relativamente alla tecnologia cold spray, partendo da un
breve tutorial della tecnica fino alle più recenti applicazioni nel
mondo industriale. Cases study industriali relativamente all’utilizzo delle tecniche Cold Spray e HVOF (High-Velocity Oxy Fuel) nei
settori dell’aeronautica, dei coating per l’elettronica di potenza,
del biomedicale e dell’industria dello stampaggio del vetro cavo
sono inoltre stati riportati direttamente da speaker provenienti
da aziende operanti nei rispettivi settori, quali ad esempio Avio
spa, obz gmbh, Busellato Glass Moulds. Infine una finestra su
nuove opportunità offerte nello studio di nuovi materiali, nuove
tecniche di ingegnerizzazione delle polveri e nuove metodologie
per la modellizzazione dei processi di deposizione sono stati riportati dal mondo accademico: associazione CIVEN, Università di
Modena e Reggio Emilia, Politecnico di Milano.
La giornata si è chiusa con i consueti ringraziamenti e l’invito a
ripetere il prossimo anno il simposio con l’intento di coinvolgere
ancor più realtà interessate, sia provenienti dal mondo accademico che industriale, per dare continuità ed ulteriore efficacia
all’evento.
Simone Vezzù
Veneto Nanotech scpa - Nanofab Laboratory
Via delle industrie 5, Marghera (VE)
www.venetonanotech.com
[email protected]
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Sviluppo responsabile
e Nanotossicologia
Enrico Sabbioni, ECSIN
Programma scientifico e nanotossicologia. Analizzando
l’evoluzione degli eventi Nanotechitaly realizzati dal 2008 non
c’è dubbio che l’edizione 2011 ha rappresentato una svolta circa la presenza della nanotossicologia nel programma scientifico.
Infatti, il programma del’edizione 2008 ha incluso aspetti di governance (analisi del rischio dei materiali ingegnerizzati) mentre
l’evento 2009 non ha contemplato alcun aspetto di nanotossicologia, e nemmeno di governance. Solo l’edizione 2010, pur mantenendo il focus sulla ricerca per lo sviluppo e le applicazioni dei
nanomateriali, ha iniziato ad ampliare gli obiettivi ed i contenuti
prendendo coscienza della necessità di introdurre nel programma
anche aspetti di nanotossicologia. Infine, è nell’edizione 2011,
con il supporto della Società Italiana di Nanotossicologia-SIN, che
la nanotossicologia è entrata a pieno titolo come una delle sei
tematiche dell’evento (Sviluppo responsabile- nano-tossicologia). Questo fatto costituisce una svolta di cruciale importanza
nell’evoluzione di tale evento sempre più orientato a superare
un’ottica per lo più settoriale e a promuovere il dialogo non solo
tra i rappresentanti della ricerca che sviluppano i nanomateriali
con quelli dell’industria che li producono, ma anche con coloro
che ne studiano la sicurezza, sinergia indispensabile per uno sviluppo sicuro, sostenibile e trasparente delle nanotecnologie.
La giornata Sviluppo responsabile-Nanotossicologia.
Dal programma della giornata sono emersi aspetti generali ed
evidenze importanti sul come concepire il ruolo della nanotossicologia:
(i) A tutt’oggi il panorama sulla sicurezza delle applicazioni dei
nanomateriali è offuscato da molte incertezze e caratterizzato da
due aspetti tra loro contrapposti: da un lato una nanoeuforia per
i grandi potenziali benefici e dall’altro un nanocatastrofismo per i
possibili rischi sanitari. Purtroppo è emerso che la mancanza di attendibili dati nanotossicologici non permette a tutt’oggi un’analisi scientifica del rischio sanitario dei nanomateriali (P.Wick). In tale
situazione non sorprende che la preoccupazione nella comunità
scientifica sui possibili danni alla salute dei nanomateriali possa
raggiungere i media in forma generalizzata di forte avvertimento,
generando nell’opinione pubblica il falso messaggio che tutte le
nanoparticelle sarebbero pericolose a causa della loro dimensione, un aspetto che potrebbe costituire un freno all’innovazione
nanotecnologica. In tale contesto, Nanotechitaly 2011 ha evidenziato la necessità di basare la ricerca nanotossicologica su
una visione equilibrata e non emotiva, adottata tra l’altro anche
dalla Società Italiana di Nanotossicologia-SIN (www.sona-it.
org/) che considera i nanomateriali né “nanoangeli” né “nanodemoni”. In tale contesto, la nanotossicologia non deve essere
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considerata un freno all’innovazione, ma piuttosto una parte essenziale del processo di sviluppo sostenibile delle nanotecnologie
(K. Savolainen, L.Manzo, R. Sa Gaspar, E.Gaffet), aspetto che
analiticamente è stato riassunto nell’equazione di sostenibilità dei
nanomateriali (E.Sabbioni):
Sviluppo sicuro e sostenibile delle nanotecnologie = Ricerca e
produzione dei nanomateriali + (eco) nanotossicologia + nanotossicologia + società (etica)
(ii) E’ stato confermato come le nanoparticelle siano in grado di
interagire in vitro con il sistema immunitario, inducendo effetti
autoimmuni ed allergie, queste ultime probabilmente generate
da un’azione di adiuvante immunologico delle nanoparticelle via induzione di infiammazione allergica (M. DiGioacchino,
Fondazione Università G. D’Annunzio, Chieti). In ogni caso,
la base della immunonanotossicità è supportata da un numero
troppo esiguo di dati sperimentali e clinici e quindi è ribadita l’urgenza di ricerche in tale area.
Un altro aspetto considerato di grande rilievo circa gli effetti biologici dei nanomateriali è il loro potenziale genotossico e cancerogeno. Sebbene queste aree di ricerca siano di elevata priorità,
anche in tal caso i dati disponibili sono limitatissimi, e per lo più
confinati a studi in vitro con colture cellulari o a studi in vivo in cui
però “modi oscuri e non fisiologici” di esposizione (ad es. somministrazione di nanoparticelle per via sottocutanea) rendono tali
risultati irrilevanti per l’analisi dei rischi sanitari. In qualsiasi caso,
non esistono oggi evidenze di effetti cancerogeni indotti nell’uomo da esposizione a nanoparticelle (R.Colognato, GexNano).
(iii) La presentazione del libro bianco “Esposizione a nanomateriali ingegnerizzati ed effetti sulla salute e sicurezza dei lavoratori” è di particolare significato, poiché, in un’ottica di prevenzione sanitaria, è stato di fatto istituzionalizzato tale problema
a livello nazionale da parte dell’INAIL (ex-ISPESL) (S. Iavicoli,
E.Boccuni). Il libro è un passo molto importante al fine di indirizzare uno sviluppo sostenibile della ricerca in nanotecnologia, affinché le applicazioni nanotecnologiche possano portare tutti gli
enormi vantaggi e benefici che promettono in assoluta sicurezza
e sotto scrupoloso e doveroso controllo.
(iv) Di particolare rilievo è stata la presentazione del progetto Nanocode (70PQ) dedicato al Codice di Condotta per le
Nanotecnologie. La ricerca, conclusa a Novembre 2011, è stata
realizzata tramite consultazione di oltre 450 esperti europei ed
extra-europei con l’obiettivo di valutare il ruolo ed il livello di applicazione di misure volontarie quali il Codice nella governance
delle nanotecnologie (E.Mantovani, A.Porcari, AIRI/Nanotec
IT). L’obiettivo finale del progetto è l’implementazione/adozione del Codice e la definizione di uno strumento che permetta la
valutazione/autovalutazione del livello di aderenza ai principi del
Codice (CodeMeter).
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Due importanti organizzazioni di ricerca hanno presentato le loro
attività nel settore della salute e nanomateriali:
(a) l’Istituto Superiore di Sanità (ISS). Oltre a partecipare al
“Working Party on Manufactured Nanomaterials” (WPMN)
dell’OCSE, all’attività istituzionale per il Ministero della Salute e ad
essere coinvolto in parecchie commissioni nazionali sulla valutazione del rischio dovuto alla manipolazione e all’uso di nanomateriali, l’ISS ha istituito l’importante Gruppo di Lavoro Nanomaterials
and Health, interdipartimentale e multidisciplinare, al fine di condividere tecnologie e competenze disponibili nel campo della nanomedicina e della nanotossicologia (L.Musumeci, ISS)
(b) Il Center for Bio-Molecular Nanotechnology, Italian
Institute of Technology (IIT-CBN), che ha presentato la piattaforma di ricerca Environment, Health&Safety dedicata all’identificazione del responso biologico di sistemi biologici in seguito
all’interazione con i materiali su scala nanometrica (P. Pompa).
Oltre alla forte necessità di identificare e categorizzare i responsi biologici sulla base delle dimensioni, forma, composizione e
struttura dei nanomateriali è stata stressato come lo studio dei
meccanismi di interazione debba essere basato su un approccio
multidisciplinare che richiede l’uso combinato di varie tecniche
analitiche includenti nanochimica, nanotossicogenomica, nanoproteomica e tecniche avanzate di imaging.
ECSIN e Nanotechitaly 2011. La giornata Sviluppo responsabile-Nanotossicologia di Nanotechitaly 2011 ha costituito anche un
importante momento di confronto tra le visioni verso i nanomateriali e la funzione della nanotossicologia di ECSIN e quelle corrispondenti emerse dalle presentazioni della giornata. Tali visioni
sono risultate sostanzialmente coincidenti: i nanomateriali non
devono essere considerati né “nanoangeli” né “nanodemoni”, ed
il ruolo della nanotossicologia è di creare i presupposti che invece
di frenare l’innovazione le siano favorevoli, ovvero uno strumento essenziale per promuovere uno sviluppo più celere, sicuro e
mirato dei nanomateriali, per facilitare l’analisi del rischio e per
generare dati utili per gli organi normativi. Inoltre, l’introduzione
della nanotossicologia nel programma scientifico di Nanotechitaly
2011 è anche in linea con l’obiettivo generale di ECSIN per quanto riguarda una più efficace sensibilizzazione dei responsabili dello sviluppo e dell’applicazione dei nanomateriali verso i problemi
di un loro utilizzo sicuro.
Più specificatamente, anche i contenuti e gli sviluppi dei progetti
di ricerca di nanotossicologia di ECSIN sono basati su alcuni punti
chiave emersi da Nanotechitaly 2011, come ad esempio l’inderogabile necessità di una completa caratterizzazione di nanomateriali prima del loro uso per studi nanotossicologici, e di collaborazioni multidisciplinari. In tale contesto, citiamo di seguito alcuni
progetti tra i più significativi in essere ad ECSIN:
Nanovalid, Progetto europeo FP7 per lo sviluppo e la validazione di metodiche per la valutazione del rischio e dell’impatto del
Ciclo di Vita dei nanomateriali. L’obiettivo è sviluppare e validare
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le metodiche di ricerca con cui caratterizzare il pericolo, l’esposizione, il rischio e il ciclo di vita di nanomateriali ingegnerizzati. In
particolare, mediante un approccio di round robin, si vuole valutare il potenziale applicativo di tali metodi a livello di casi studio,
e stilare delle opportune linee guida per il loro corretto utilizzo.
Queste attività sono condotte su una serie di nanomateriali selezionati in base ai relativi volumi di produzione e applicazione
industriale e commerciale, con diverse priorità. Tra gli obiettivi
specifici si annovera l’identificazione di biomarkers per potenziali
effetti genotossici ed immunotossici.
NanoSustain, Progetto europeo FP7 per lo studio dell’impatto
del Ciclo di Vita dei nanomateriali secondo un approccio “dalla
culla alla tomba”. Lo scopo è di studiare soluzioni innovative per
lo sviluppo, l’utilizzo, e lo smaltimento di prodotti industriali basati su nanomateriali. Questo obiettivo viene perseguito mediante
un approccio che comporta un’integrazione di competenze di
caratterizzazione chimico fisica, di analisi di impatto biologico e
ambientale, di integrazione in modelli di valutazione del rischio e
del Ciclo di Vita dei nanomateriali che includono: compositi di nanocellulosa; resine epossidiche contenenti nanotubi di carbonio;
matrici silaniche contenenti ossido di zinco nanometrico e vernici
contenenti diverse forme di biossido di titanio nanostrutturato.
SINA–Silver Nanoparticles. L’obiettivo è di approfondire la conoscenza sui meccanismi di interazione e potenziale tossicità di
nanoparticelle d’argento (AgNP) e materiali contenenti AgNPs,
attualmente presenti sul mercato, in cellule umane, animali e batteriche, al fine di guidare uno sviluppo di AgNPs che abbiano la
massima efficacia in termini di azione antibatterica e allo stesso
tempo che siano le meno tossiche possibile per la salute umana
e per l’ambiente.
COFENI. L’obiettivo è una ricerca comparativa per valutare le proprietà di nanoparticelle (NPs) metalliche zerovalenti (Co,Fe, Ni)
utilizzando un approccio chimico per fornire una chiara risposta
alla possibilità di predire il comportamento tossicologico di una
NP in base a proprietà chimiche pregresse di altre NPs. Questo
tipo di informazione è quanto mai importante per poter velocizzare un processo di analisi del rischio che sia il più ampio possibile
e includa il maggior numero di nanomateriali.
Enrico Sabbioni
ECSIN LAB - European Center for the Sustainable Impact of Nanotechnology
Viale Porta Adige, 45. Rovigo
Tel. +39 0425 377 511 - 377 501
[email protected]
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The Horizon 2020 programme
The European Commission presented its €80-billion research funding programme Horizon 2020 with the aim of boosting research, stimulating innovation and simplifying the way scientists
and smaller businesses can get funding for EU-backed projects.
The Horizon 2020 programme brings together all EU research
and innovation funding under a single scheme running from
2014 to 2020. It replaces the Seventh Framework Programme for
research (FP7), which expires in 2013.
Horizon 2020 is a part of Innovation Union, a Europe 2020
flagship initiative aimed at enhancing global competitiveness.
The European Union leads the world in some technologies, but
faces increasing competition from traditional powers and emerging economies alike. Launched in a time of austerity the programme would serve as a driver for European growth.
Horizon 2020 introduces a simplified reimbursement by introducing a single flat rate for indirect costs and only two funding
rates - for research and for demonstration activities respectively;
a single point of access for participants; less paperwork in preparing proposals; and no unnecessary controls and audits. One key
goal is to reduce the time until funding is received following a
grant application by 100 days on average, meaning projects can
start more quickly.
Horizon 2020 will identify potential centres of excellence in underperforming regions and offer them policy advice and support,
while structural funds can be used to upgrade infrastructure and
equipment. &
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Partecipazione italiana ai bandi
VII PQ
L’Italia ha ottenuto finanziamenti per circa l’ 8,43% sul budget
generale del 7PQ, pari a 2.221 milioni di euro sui circa 27 miliardi
di euro nei bandi già assegnati.
L’Italia, dopo la Germania, ha il più alto numero di proposte inviate alla Commissione (87.000) ma solo il 16,6% è ammesso al
finanziamento (14.478 proposte). Di queste il numero di proposte a coordinamento italiano (5.434) è al primo posto, superando
la Germania, il Regno Unito, e la Spagna, ma il tasso di successo di progetti a coordinamento italiano è più basso della media
(12,3%).
Per quanto riguarda la “Cooperation” tra le migliori performance
di finanziamento a progetti con partecipazione italiana si riscontra il programma inerente le Nanotecnologie, materiali e sistemi
di produzione. La percentuale italiana di finanziamento sul budget generale si attesta al 10,5%
(circa 254 milioni di euro in negoziazione) e si posiziona dietro
alla Germania, 21,46 %
Info: http://ec.europa.eu/research/horizon2020/index_en.cfm
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to italiano. I coordinatori italiani sono al secondo posto dopo la
Germania in sede di presentazione, per scendere al terzo in sede
di negoziazione e scendere poi all’ottavo posto nel rank dei coordinatori vincenti (9,3% rispetto al 16% della Germania).
I coordinatori vincenti appartengono per il 44,29% ai Centri di
Ricerca, per il 34,29% all’Industria, per il 20% all’Università e per
l’1,43% ad Altri.
Fonte Miur: http://www.ricercainternazionale.miur.it/media/1221/
studi_statistiche.pdf
ObservatoryNano Project final
outcomes
The ObservatoryNano Final Workshop
On March 1, 2012 was held in Brussels the final workshop of
the project ObservatoryNANO: the European Observatory on
Nanotechnologies, a 4 years FP7 Support Action finished in
March 2012 and involving 16 European partners.
AIRI/Nanotec IT participated in the project as leader of the
Workpackage dedicated to Regulation & Standards and of the
Technology Sector on Textiles.
The project coordinator Mark Morrison (Institute of
Nanotechnology) presented an overview of the main results of
the project funded under FP7 (April 2008 - March 2012) the aims
of which were:
• Support the EU policy on nanotechnology;
• Produce an objective analysis of developments in nanotechnology - potential opportunities and potential Risks;
• Integrate the analysis of the Technical Areas with economic
data, ELSA, EHS, Regulations & Standards;
• Provide tools for ethical and social responsibility in academia
and industry;
• Interact with other initiatives;
• Evaluate the opportunity to realize a permanent European
Observatory on Nanotechnologies.
The project activity was developed around the following lines:
• Bibliographic search (journal publications, patents, reports, all
information relating to nanotechnology from basic research to
market applications);
• Interim reports;
• Involvement (and selected interview) of experts;
• Annual projects conferences to disseminate results/information (annual overview of analysis and results with contributions
from universities, industries, business, NGOs, policy makers);
• Interviews and reviews, questionnaires, workshops and roundtables
• Publications (Publication of concise and peer-reviewed reports
on the project web site).
10 major technological/market sectors were analyzed, each presented as a series of sub-sectors:
Aerospace, Automotive & Transportation, Food, Chemical &
Materials, Construction, Energy, Environment, Health, Medicine
& Nanobio, Information & Communication, Security, Textiles.
Three types of documents have been produced:
• ”Factsheets” (summaries outlining the most interesting developments of nanotechnology)
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• “Briefings” (four pages documents containing concise wideranging scientific, economic analysis, and social risks on topics
of particular interest.
• “General Sector Reports” (more general reports providing a
detailed scientific and technological analysis for each of the ten
sectors examined).
As a result the four years of activity more than 140 documents
were uploaded on the web site, with three interactive tools and
over 1000 experts involved.
More specifically, the ObservatoryNANO project output has made
available the following products:
• Factsheets on each Technology Sector, on statistical analysis of
Patents and Publications and on nanoethics and ELSA issues.
• 33 Briefings
• Over 70 General Reports. Economic relations and EHS for each
of the Technology Sectors.
• Analysis of Patents and Publications for each of the T.S.
• Reports on public and private funding.
• 4 ELSA reports regarding: responsibility & codes of conduct,
nanobiomedicine, privacy and security, communication nanoethics.
• 4 annual updated reports on the evolving landscape of regulations and standards.
• Analysis of other observatories.
• Basic studies on EHS research in the field.
• Ethical Toolkit, CSR tool and NanoMeter in use.
• The report “European Nanotechnology Landscape Report”.
All documents can be found in the project web site and provide
information about various aspects linked to the development
of these enabling technologies. This knowledge is a crucial tool
when planning the activity in this field both for industry and policy decision makers and therefore it is envisaged that an activity of
this type should be permanent and not remain limited to the life
span of the ObservatoryNANO project.
Visit the Project website: www.observatorynano.eu
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ObservatoryNANO Briefings
A very efficient tool published in the course of the ObservatoryNANO
Project consists in the production of “Briefings”, which are short
documents, of accessible reading to non-specialists, and of potential interest to policy makers, which face both the technological
and the economical point of view, with specific issues concerning the introduction of nanotechnology in areas of relevance and
impact of potential development for the European industry. If the
analysis on technology and market related to the development of
nanotechnology in various fields of application, the project supports specific activities related to cross-cutting issues including
the following: impact on human health and the environment,
regulation and standards, ethical aspects.
Following is a list of the 33 published titles.
ObservatoryNano Briefings
Aerospace,
Automotive
&Transport
Nano-enhanced automotive plastic glazing
Nanotechnology in automotive tyres
Nanotech in next-generation electric batteries: beyond
Li-ion
Agrifood
Biodegradable food packaging
Improving delivery of essential vitamins & minerals
Sensors in food production & processing
Construction
Nano enabled insulation materials
Nanofillers –improving performance and reducing cost
Chemistry &
Materials
Applications of Photocatalysis
From microscope to nanoscope
Addressing critical commodity scarcity
Nanocomposite Materials
Energy
Photocatalysis for water treatment
Organic photovoltaics
Thermoelectricity for energy harvesting
Supercapacitors
Environment
Photocatalysis for water treatment
Nanostructured membranes for water treatment
Nanoenhanced membranes for improved water treatment
Nanosorbents for environmental applications
Health, Medicine
& Nanobio
Next generation sequencing
Bridging diagnosis closer to the patient
Pacemakers and ICDs
Information &
Communication
Universal memory
Nanotechnology for flat panel Displays
Nanotechnology for wireless communications
Security
Nanotechnologies for anti-counterfeiting applications
Nanosensors for explosive detection
Nanotechnology for secure communications
Textiles
Nano-enabled protective textiles
Nano-enabled automotive textiles
Nano-enabled Textiles in Construction and Engineering
Statistical Patent
Analysis
Patents: an indicator of nanotechnology innovation
Publication
analysis
Geographical distribution of nano S&T publications
The above Briefings can be downloaded by the site:
http://www.observatorynano.eu/project/catalogue/B/
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The ObservatoryNANO 2012
Regulation & Standards Report
The 2012 report is the last of a series developed during the 4
years of life of project ObservatoryNANO, to monitor the changes
in the regulatory landscape (and governance more broadly) of
nanotechnologies.
It updates those reports and it includes a detailed description of:
• regulatory actions in the most relevant application areas of nanotechnologies;
• activities on nanoregulation in more than 20 Countries worldwide;
• initiatives related to voluntary measures;
• standards and international cooperation.
The 2012 report, in addition to the highlights of the most relevant developments that have taken place in the period July
2011–March 2012 complementing the information provided in
the three previous reports, includes also a commentary about
the overall evolution of nanotechnologies governance during the
project time.
The report is prepared by AIRI/Nanotec IT (IT), The Institute of
Nanotechnology (UK) and the National Institute for Public Health
& the Environment (RIVM) (NL)
Activities and initiatives about Environment, Health and Safety
Issues (EHS) as well as Ethical, Legal and Societal Aspects (ELSA)
are not taken into account in the report, except where these activities and initiatives are clearly in the context of regulation and
standards, for within the project they are subject of a dedicated
effort (ObservatoryNano WorkPackage4 and WorkPackage5 reports).
The information gathered indicates that the European Commission
is particularly active in this area and national initiatives tend to
align to its indications, but also that some European countries are
pursuing their own specific initiatives.
The developments in regulation and standards during the period
considered by this report can be summarised as it follows:
• Publication or revision of definitions of nanomaterials for regulatory purposes (European Commission; Canada; International
Cooperation on Cosmetic Regulation, ICCR);
• Publication by the French Government of the final interministerial decree regarding the annual mandatory reporting of “nanoparticulate substances” placed on the market.
• Adoption of the EU Biocidal Products Regulation (BPR) and the
provision of Food Information to Consumers (labelling) by the
European Parliament, including specifications for nanomaterials;
• Developments of tools and guidelines to put in force the novel
Cosmetics Directive in Europe (including specifications for nanomaterials);
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• Pre-market notification rules issued by some regulatory agencies for specific nanomaterials (silver nanoparticles, CNT and
others);
• Ongoing review of the application of chemical legislation to
nanomaterials (EU, USA, Canada, Australia);
• Publication/revision of tools for risk management of nanomaterials (Switzerland, Denmark, Australia, Korea) and sustainability of nano-related products (UK, USA)
• Achievements in the work on standards (ISO TC 229) and the
activities of the OECD–WPMN
The report is complemented by a detailed list of references, organized by regions and countries and its available for download on
the project website.
Download the 2012 report on Developments In Nanotechnologies
Regulation And Standards: http://www.observatorynano.eu
Info: Airi / Naotec IT - e-mail: [email protected]
RICERCA
Nanocode final outcomes
NanoCode is a European project funded under the Programme
Capacities, in the area Science in Society, within the 7th
Framework Program (FP7) led bey AIRI/Nanotec IT. The project
started in January 2010 and end in November 2011.
The objective of NanoCode was to define and develop a framework (MasterPlan) aimed at improving and strengthening
awareness and supporting the successful integration and wider
implementation of the European Commission Code of Conduct
(EU-CoC) for responsible nanosciences and nanotechnologies
(N&N) research at European level and beyond, integrated with an
implementation assistance tool (CodeMeter).
The project rested on four pillars:
Analysis of existing/proposed codes of conduct, voluntary measures and practices for a responsible R&D in N&N and identification of the relevant stakeholders (work package 1 (WP1).
Consultation of stakeholders to assess attitudes, expectations,
needs and objections regarding the EU-CoC through a survey
(electronic questionnaire and structured interviews) to more than
400 stakeholders worldwide (WP2).
Design of a MasterPlan and a performance assessment tool
(CodeMeter) enabling the implementation and articulation of
the EU-CoC, based on the WP2 consultation phase, a series of
National Workshops in partners’ countries and a final international conference (WP3).
Communication in a suitable form and to the widest possible
audience of project objectives, findings and outcomes (WP4).
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intended to:
• Point out the level of awareness as well as criteria and indicators of the level of implementation and application of the
EU-CoC.
• Indicate the need for future changes to the EU-CoC.
• Identify best practices, incentives and disincentives to foster
widespread adoption of the EU-CoC.
The CodeMeter, is a practical tool that breaks the EC-CoC’s general principles and guidelines down into concrete, easily comprehensible criteria which can be answered through a questionnaire.
The tool is designed to enhance the practicability of the EU-CoC,
support reflection and learning and allow individual stakeholders
self-assess their performance in relation to the EC-CoC principles
and guidelines.
The MasterPlan, the CodeMeter and all other reports detailing
outcomes of the different project activities are available on the
project website.
Info: Airi / Naotec IT - e-mail: [email protected] - www.nanocode.eu
The project brought together 11 partners representing 8 European
countries, plus Argentina, South Africa and South Korea (associated member).
The two main final outcomes have been the MasterPlan and
the CodeMeter. They builds on the insights gained from encompassing stakeholder consultations in eight European
countries as well as at international level. The consultations,
made by an electronic survey, structured interviews and focus groups, involved more than 450 stakeholders worldwide, to assess attitudes, expectations, needs and objections regarding the EU-CoC. Results of the consultation were used to
prepare a first draft of the MasterPlan and CodeMeter, that
have been then throughly debated in national workshops in all
partners countries and a final international conference that leads to the designing of the final version of these documents.
The MasterPlan provides a portfolio of options, ideas and recommendations for the further development and implementation, at
European level and beyond, of the EU-CoC. The MasterPlan is
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Confermata l’edizione
2012 di Nanochallenge&
Polymerchallenge
Si svolgerà regolarmente per l’ottavo anno consecutivo,
Nanochallenge&Polymerchallenge, prima competizione
internazionale dedicata al finanziamento di idee imprenditoriali
basate sull’applicazione industriale delle nanotecnologie. La business
plan competition si rivolge a ricercatori, scienziati, meno di tre anni),
italiani e stranieri e a quanti abbiano un’idea innovativa nel settore
delle nanotecnologie e dei materiali compositi.
Creata nel 2005 da Veneto Nanotech, Distretto italiano delle nanotecnologie, grazie ad un finanziamento della Fondazione Cassa di
Risparmio di Padova e Rovigo, ha come obiettivo quello di supportare
la nascita e lo sviluppo di nuova imprenditorialità tecnologica e favorire e sviluppare gli investimenti privati.
Fin dalla prima edizione del 2005, l’iniziativa ha messo in palio
un premio di 300.000 euro. Nel 2007 IMAST, il Distretto campano sui materiali compositi, si unisce alla BPC dando vita così a
Nanochallenge&Polymerchallenge con un premio equivalente.
Complessivamente l’iniziativa ha finanziato 3,3 milioni di euro
per la creazione di 11 startup, di cui 7 in Veneto e 4 in Campania.
Indirettamente ha raccolto quasi 250 proposte progettuali di cui
ne sono state ammesse alla fase finale 87, contribuendo alla realizzazione di numerosi posti di lavoro.
Nel 2010 l’accordo con Banca Intesa Sanpaolo e l’integrazione
di Nanochallenge&Polymerchallenge con la StartUP Initiative
(SUI) ha contribuito a dare ulteriore valore aggiunto alla competizione
in termini di visibilità ed efficacia con l’introduzione del Boot Camp,
momento formativo destinato a tutti i partecipanti grazie al supporto della californiana Maverick Angels.
Per informazioni: www.nanochallenge.com; [email protected]
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SEMINARI & CONVEGNI
Graphene 2012
April 10-13, 2012
Brussels 44 Center (Belgium)
Graphene 2012 International Conference will be the largest
European Event in Graphene. A Plenary session with internationally renowned speakers, extensive thematic workshops in parallel, an important industrial exhibition carried out with the latest
Graphene nanotrends for the future will be some of the features
of this event. Following the overwhelming success of Graphene
2011, Phantoms Foundation is pleased to announce the second
edition of this great event that will gather the Graphene community, including researchers, industry policymakers, investors and
plans to be a reference in Europe in the upcoming years.
Info: Phantoms Foundation; Tel: +34 91 1402145; [email protected]
BioInItaly Investment Forum 2012 & Intesa
Sanpaolo Start-up Initiative
Italian Biotech meets Investors in Milan
The 7th International ECNP Conference
on NANOSTRUCTURED POLYMERS AND
NANOCOMPOSITES
April 24–27, 2012
Prague, Czech Republic
Conference covers polymer science from fundamentals to applications:
synthesis of polymers, polymer architecture, processing, theory
and characterization, interfaces, supramolecular chemistry, and
it will focus on:
Polymer networks and gels; Polymer nanocomposites for biomedical application; Stimuli responsive polymers for optoelectronics,
sensing and actuators; Conductive polymers; Polymer materials
from renewable resources; Nanofillers: carbon nanotubes, graphene and nanofibres; Nanostructured coatings and adesive;
Advanced characterization techniques; Mathematical modelling
of processes and properties.
Info: www.ecnp-eu.org.
April 18-19, 2012
Nanomateriali e Salute
Palazzo Besana Piazza Belgioioso 1 - Milano
May 10-11, 2012
Assobiotec - the Italian Association for the Development of
Biotechnology, together with Innovhub SSI and Intesa Sanpaolo,
present BioInItaly Investment Forum 2012 & Intesa Sanpaolo
Start-up Initiative from April 18 to April 19 in Milan, Italy. This
event will bring together national and international investors,
managers of international corporations and companies from all
sectors of the biotechnology industry. This will welcoming your
organization to our event. This will provide a unique opportunity
for investors to monitor the pulse of the dynamic biotech sector
in Italy. Investors and business development managers will discover in a single meeting the opportunity of investment offered
by some of the most promising biotech companies. Companies,
ranging from start-ups and spin-offs to established companies,
universities and research organizations will present their new
business ideas and projects in the fields of biotech and nanobiotech. The presenting companies and projects will be selected by a
committee of experts in the biotech field.
Istituto Superiore di Sanità - Roma
Il mondo dei nanomateriali abbraccia molteplici aspetti della realtà scientifica e produttiva. Allo stato attuale è uno dei settori
di ricerca e sviluppo con le ricadute più interessanti dal punto
di vista delle innovazioni tecnologiche. In quest’ottica va inquadrato il convegno che il gruppo di lavoro “Nanomateriali e
Salute” dell’ISS propone per illustrare le attività interdisciplinari
dell’Istituto in risposta alla sfida che si sta aprendo, per il mondo
scientifico ed istituzionale, verso un equilibrio tra l’introduzione
di materiali innovativi e la necessità di assicurare un alto livello
di protezione per l’individuo e l’ambiente. L’ISS, con il gruppo
di lavoro “Nanomateriali e Salute” coagula un vasto patrimonio
di esperienze, che vanno dalla ricerca pre-clinica e clinica, allo
sviluppo di metodologie appropriate per la caratterizzazione dei
nanomateriali e la valutazione del rischio ad essi associato, all’attività regolamentatoria per la sicurezza e il controllo di qualità.
Modalità di presentazione al convegno: solo poster.
Info: [email protected]; www.bioinitaly.com; www.startupini-
Info: [email protected]; http://nanomaterialiesalute.it
tiative.com
Nanotechnologies for HealthCare
May 25-26, 2012
Trento, (Italy)
The Workshop will be organized by University of Trento, Bruno
Kessler Foundation, CNR-IBF and CNR-IMEM. The principal topics
will be: Safety and Regulations, Nanomaterials/cells/body interaction, Nanosensing, Nanodiagnostics and Imaging, Nanovectors
and nano-based medication, Tissue engineering and regenerative
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medicine, “Smart” nanomaterials. For medical uses, the interaction of materials and devices with the body occurs at subcellular
level and with a high degree of specificity. This can be achieved
with nanotechnologies for specific cells targeted applications to
prevent, image, control and treat health diseases with fewer side
effects and higher therapeutic efficiency.
The Conference will take place in the Buonconsiglio Castle, a medieval castle in the center of the town.
The number of participants is limited to 80.
Info: http://www.unitn.it/en/dimti
Industrial Technology 2012 – Integrating nano,
materials and production
Jun 19-21, 2012
Aarhus (Denmark)
Industrial Technologies 2012 will offer integrated coverage of
nanoscience and nanotechnology, materials, and new production
processes (NMP). The event programme will highlight the knowledge intensive products and processes driving European growth
to 2020, which identifying solution to improve the framework
conditions for innovation in Europe.
Several sessions will look at those products and processes where
Europe can build or maintain global leadership in the next decade; these may include mass producing low emission vehicles,
making new buildings net energy producers, or offering new
therapies enabled by developments in nanomedicine. These areas will require input from all three streams of NMP, and will bring
together researchers and industry to address both technical and
non-technical challenges.
Info: http://industrialtechnologies2012.eu/event/
ECCM 15 (Fifteenth European Conference on
Composite Materials)
June 24-28, 2012
Venice (Italy)
The Conference is organized by the Department of Management
and Engineering of the University of Padova in cooperation with
the Italian Cluster of Nanotechnology (Veneto Nanotech), under
the patronage of the European Society for Composite Materials
(ESCM). ECCM is the Europe’s leading conference on composite materials and, traditionally, hosts scientists, engineers and
designers, both of Academia and Industry, coming from all the
areas of the world.
The Conference aims to represent a forum for exchanging ideas,
presenting the latest developments and trends, proposing new
solutions and promoting international collaborations.
Info: www.eccm15.org
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Italian Forum on Industrial Biotech and
Bioeconomy - IFIB 2012
Dalle biotecnologie nuove risorse per l’industria
October 23-24, 2012
Palazzo Turati, in via Meravigli 9/b - Milano
Assobiotec, l’Associazione nazionale per lo sviluppo delle biotecnologie, che fa parte di Federchimica, Innovhub SSI e l’Italian
Biocatalysis Center invitano imprese e centri di ricerca a presentare i propri progetti in campo biotecnologico industriale nel corso
di un workshop destinato a una platea di addetti ai lavori, finalizzato a far crescere il network delle biotecnologie industriali in
Italia e a favorire partnership tra imprese diverse e tra imprese e
Università/centri di ricerca.
Il workshop rappresenta la seconda edizione dell’Italian Forum
on Industrial Biotech and Bioeconomy (IFIB). La partecipazione al workshop e la presentazione dei contributi scientifici saranno totalmente gratuite. L’iniziativa è diretta in modo specifico
al mondo delle biotecnologie industriali. Sono pertanto esclusi i
contributi scientifici non pertinenti. La lingua del workshop sarà
l’italiano. I soggetti ammessi saranno le Imprese, le Università, i
Centri di ricerca pubblici e privati.
Info: www.assobiotec.it, www.innovhub.it o www.italianbiocatalysis.eu
RICERCAALTRI
& S V IL
E V UE PPO
N TI
ALTRI EVENTI
Apr 1-Apr 5, 2012
Arcachon (France)
Jun 18-Jun 20, 2012
Varese (Italy)
International meeting on the chemistry of
nanotubes and graphene
8th NanoBio Europe
Apr 3-Apr 4, 2012
Santa Clara, CA (USA)
Berlin (Germany)
Printed Electronics Europe
Apr 16-Apr 19, 2012
Erfurt, Germany
IMAPS/ACerS 8th International Conference and
Exhibition on Ceramic Interconnect and Ceramic
Microsystems Technologies (CICMT 2012)
Apr 16-Apr 19, 2012
Brussels (Belgium)
International Conference on Nanophotonics
Apr 19-Apr 20, 2012
Berlin (Germany)
Nanomedicine: Visions, risks, potential
Apr 10-Apr 13, 2012
Brussels (Belgium)
Graphene 2012
Apr 24-Apr 24, 2012
London (UK)
HiPerNano 2012
Jun 18-Jun 21, 2012
Nanotech 2012
Jul 1-Jul 6, 2012
Genoa (Italy)
16th International Conference on Solid Films and
Surfaces
Jul 2-Jul 4, 2012
Cranfield (UK)
International Conference on Structural Nano
Composites (Nanostruc 2012)
Jul 6, 2012
Edinburgh (UK)
Working Safely with Nanomaterials
Jul 15-Jul 17, 2012
Amsterdam (The Netherlands)
Colloids and Nanomedicine 2012
Jul 23-Jul 27, 2012
Paris (France)
International Conference on Nanoscience +
Technology (ICN+T2012)
May 22-May 24, 2012
Lausanne (Switzerland)
Swiss NanoConvention 2012
Jun 4-Jun 5, 2012
Tokyo (Japan)
Nanofibers 2012
Jun 12-Jun 13, 2012
Dresden (Germany)
Nanofair 2012 - 9th International Nanotechnology
Symposium
Jun 17-Jun 21, 2012
Ancona (Italy)
European Conference on Nanofilms (ECNF 2)
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A V V ISO
PER
I
LETTORI
AVVISO PER I LETTORI
MODALITA’ DI DISTRIBUZIONE DI NANOTEC IT NEWSLETTER
Gentile lettore,
Newsletter Nanotec IT viene distribuita in forma cartacea (e gratuita) alle organizzazioni iscritte ad
AIRI/Nanotec IT ed ai soggetti che collaborano con l’Associazione per la realizzazione di pubblicazioni
ed eventi, in particolare tutte le organizzazioni che hanno risposto al Censimento delle nanotecnologie,
viene inoltre distribuita durante gli eventi organizzati dal Centro.
La rivista è inviata in formato elettronico ad un ampio indirizzario di soggetti a livello italiano ed
internazionale, al fine di favorire una più efficace promozione delle nanotecnologie e la conoscenza
dell’attività in corso, in particolare a livello italiano.
Tutti i numeri della rivista sono scaricabili gratuitamente da www.nanotec.it
Nel caso lo riteniate opportuno o vogliate essere inseriti ex-novo nella mailing list della Newsletter
vi preghiamo di comunicare il vostro attuale indirizzo e-mail a [email protected] o di contattare i nostri
uffici.
Pubblicazione notizie ed articoli sulle nanotecnologie:
Nanotec IT è interessata a ricevere articoli, notizie ed informazioni in genere su attività di ricerca nel
campo delle nanotecnologie da pubblicare su Newsletter Nanotec IT. Quanti volessero sfruttare tale
opportunità sono pregati di contattare la redazione.
Per informazioni:
Andrea Porcari,
tel. 068848831, 068546662 - e-mail: [email protected]
58
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P U B B LICIT à
PUBBLICITà
Listino prezzi (al netto di IVA 21%)
1. NANOTEC IT NEWSLETTER
Sulla Newsletter sono riportate le notizie più importanti (disponibili anche su www.nanotec.it), quali
risultati di ricerche ed applicazioni, eventi, corsi, iniziative di Nanotec IT e degli iscritti, articoli su
tendenze e su risultati di ricerche, su politiche della ricerca, su problematiche connesse alla diffusione
delle nanotecnologie.
Destinatari (attivi o interessati alle nanotecnologie): industrie, istituti universitari, enti pubblici di ricerca,
associazioni industriali e pubbliche amministrazioni.
Gli ordini devono pervenire a AIRI/Nanotec IT entro il 20 settembre 2012 per il secondo numero del
2012.
Gli iscritti ad AIRI / Nanotec IT usufruiscono di uno sconto del 30% sulla tariffe previste.
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AIRI / N A N OTECIT
MEM B ER
AIRI/Nanotec IT Members
INDUSTRY
1. APE RESEARCH
2. BRACCO IMAGING
3. COLOROBBIA
4. CRF - FIAT Research Centre
5. CSM – Centro Sviluppo Materiali
6. CTG - Group Technical Centre– ItalCementi
7. DE NORA Tecnologie Elettrochimiche
8. HITECH 2000
9. ENI
10. FINMECCANICA
11. PIRELLI TYRE
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13. SELEX Elsag
14. SELEX Sistemi Integrati
15. STMICROELECTRONICS
16. TETHIS
17. TRUSTECH
18. SMILAB
19. VENETO NANOTECH
PUBLIC RESEARCH
Universities
1. CHILAB- Polytechnic of Torino
2. INSTM (Inter- University Consortium for Material Sciences and Technologies) - representing 44 Italian Universities
Public Research Institutions
1. Bruno Kessler Foundation - Center for Materials and Microsystems
2. CNR - Molecular Design Department
3. CNR - Materials and Devices Department
4. CNR - Institute of Industrial Technologies and Automation - ITIA
5 ENEA (Nat. Agency for New Technologies, Energy, Environment)
6. INAIL (Italian Workers’ Compensation Authority)
7. Scuola Superiore S.Anna - CRIM (Centre for Applied Research in Micro and Nano Engineering)
8. SINCROTRONE Trieste (Electra lab)
Airi
nanotec IT
Airi
nanotec IT
Third
Italian Nanotechnology
Census
The third edition of the
Italian Nanotechnology Census
(June 2011) is now available
Since 2004 AIRI/Nanotec IT periodically publishes
the Italian Nanotechnology Census, basing on
an extensive survey of organizations active in
nanotechnologies at national level.
The Census is a unique reference for anyone
(scientific community, industry, public and private
planners, financial players, entrepreneurs) looking
for a comprehensive and up-to-date panorama of
nanotechnologies in Italy.
The publication, in English, provides detailed
information on the 189 public and private
structures surveyed, including:
General profile:
Organization description, employees, R&D
Personnel,R&D activities, size and type of company,
revenues, R&D Expenditure
Nanotechnologies:
Funding, R&D activities, publications and patents,
applications and products, cooperative projects,
instrumentation, initiatives related to regulation
and safety issues, education initiatives
Format: A4, 450 pages, English
information and orders:
AIRI-Nanotec IT - Viale Gorizia 25/c - 00198 Roma - Italia
Tel. +39 068848831 +39 068546662 - Fax +39 068552949
E-mail: [email protected] - Web: www.airi.it - www.nanotec.it
www.nanotec.it
AIRI/Nanotec IT
Nanotec IT - Centro Italiano per le Nanotecnologie
Il centro è stato creato nel 2003 da AIRI, Associazione Italiana per la Ricerca Industriale, per farne un punto di riferimento nazionale per le
nanotecnologie per industria, ricerca pubblica, istituzioni governative.
La sua missione è quella di promuovere lo sviluppo e l’applicazione delle nanotecnologie in Italia, al fine di accrescere il posizionamento
competitivo del Paese.
Nanotec IT contribuisce a:
• Raccogliere e diffondere informazioni sulle nanotecnologie circa risultati e tendenze di R&S, applicazioni, dati e previsioni di mercato,
politiche/strategie nazionali
• Indirizzare/stimolare l’interesse e l’attività delle imprese, grandi e PMI, verso queste tecnologie
• Sollecitare azioni nazionali atte a promuovere e sostenere le iniziative in questo campo
• Agevolare contatti e collaborazioni, a livello nazionale ed internazionale, tra ricerca pubblica e imprese, e tra imprese
• Favorire il trasferimento tecnologico
• Perseguire uno sviluppo responsabile delle nanotecnologie
Nanotec IT- Italian Centre for Nanotechnology- started in 2003 by AIRI- Italian Association for Industrial Research – as an internal division,
is a national bridging point connecting industry, public research, and governmental institutions.
Its mission is to promote nanotechnology and its applications in Italy to increase through it the competitive position of the Country.
The Nanotec IT activity aims to:
• Stimulate the interest and the commitment in nanotechnology within the Italian enterprises;
• Inform government, opinion leaders, and the public, to foster correct and timely initiatives for the development of nanotechnology and
its applications
• Favour networking and exchange of information to promote cooperation;
• Facilitate the use of research results and technology transfer;
• Contribute to a responsible development of nanotechnology.
AIRI- Associazione Italiana per la Ricerca Industriale
Nata nel 1974 per promuovere lo sviluppo della ricerca e dell’innovazione industriale e stimolare la collaborazione tra settore privato e
pubblico, AIRI rappresenta oggi un essenziale punto di confluenza per più di 100 Soci:
• Grandi imprese e PMI attive nella ricerca industriale
• Università, Centri di ricerca pubblici e privati
• Associazioni industriali, Parchi scientifici, Istituti finanziari che operano a supporto della R&S
I Soci raccolgono il 45% circa degli addetti alla ricerca in Italia.
Questa larga rappresentatività permette ad AIRI di agire quale interlocutore rilevante per tutti i decisori che sostengono la ricerca
industriale come strategia per lo sviluppo tecnologico del Paese.
AIRI-Italian Association for Industrial Research
Founded in 1974 with the aim of promoting industrial research and enhancing co-operation between private and public sector, today AIRI
is the focal point for more than 100 members:
• Large companies and SMEs operating in R&D
• Universities, public and private research Centers
• Industrial associations, Scientific parks and Banks supporting R&D activities
Researchers from AIRI members represent about the 45% of the country.
Due to this broad representative base, AIRI is a key opinion leader for decision-makers sustaining industrial research as strategy for the
technological development of the Country.
Airi
nanotec IT