86 results on '"L., Businaro"'
Search Results
2. ICT and the New Urban Development.
- Author
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Ugo L. Businaro
- Published
- 1994
3. A photonic smart system for food quality and safety sensing: first integration and measurement results
- Author
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F. R. Bertani, P. Bourgos, L. Businaro, L. Gambacorta, A. Gerardino, S. Hintschich, G. Koutalieris, M. Logothetis, E. Martinelli, G.J. Nychas, M. Solfrizzo, M. Tosic, Y.Weesepoel, and G. Wunder
- Subjects
food safety ,aflatoxins ,spectroscopy based sensors ,smart system integration ,spoliage - Abstract
The food safety issue is among the cornerstones of the environmental protection schemes worldwide and beside hazard issues, there is great concern about monitoring of food spoilage in a reliable way. Current practices of assessment of food spoilage still relies heavily on regulatory inspection and sampling regimes. A portable photonic multisensor device for the detection of food contaminations, spoilage and fraud is the objective of the EU PhasmaFOOD project. It will integrate different capabilities: spectroscopic detection (VIS/ NIR), imaging, smart signal processing, data analysis and comparison with updated models on cloud platform hosting data set for training and calibration of food analysis algorithms, user friendly interfaces by smartphone/tablet/PC also through wireless connection.
- Published
- 2017
4. Production, characterization and modeling of hard-FM and soft-FM nanostructures for exchange coupled sub-50nm dots
- Author
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P. Alippi, S. Laureti, E. Agostinelli, V. Foglietti, A. Gerardino, L. Businaro, D. Peddis, A. M. Testa, G. Varvaro, and D. Fiorani
- Published
- 2014
5. Wet sample confinement by superhydrophobic patterned surfaces for combined X-ray fluorescence and X-ray phase contrast imaging
- Author
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G. Ciasca (1, L. Businaro (1), A. De Ninno (1), A. Cedola (1), A. Notargiacomo (1), G. Campi (2), M. Papi (3), A. Ranieri (2), S. Carta (1), E. Giovine (1), and A. Gerardino (1)
- Subjects
Diffraction ,Chemistry ,business.industry ,Drop (liquid) ,Phase-contrast imaging ,X-ray fluorescence ,Superhydrophobic patterned surfaces ,X-ray phase contrast imaging ,Analyte enrichment ,Condensed Matter Physics ,Settore FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA) ,Fluorescence ,Microanalysis ,Atomic and Molecular Physics, and Optics ,Spectral line ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Optics ,X-Ray Phase-Contrast Imaging ,Electrical and Electronic Engineering ,business - Abstract
In this work we propose a wet sample handling technique which enables the simultaneous collection of X-ray fluorescence (XRF) spectra and X-ray phase contrast imaging (XPCI) using a few microliters drop confined on a superhydrophobic surface. To this purpose, we fabricated and tested a superhydrophobic patterned surface entailing an hydrophilic region which leads to pinning of the drop, enabling X-ray beam effortless alignment and measuring in liquid phase. Our technique allows to acquire capillary-free XRF spectra, resulting in a significant fluorescence detection gain, which is particularly interesting for light elements. Simultaneous XPCI provides sample geometry assuring a fine control of the experimental conditions and allowing real time monitoring of the drop during measurements. As an additional advantage - after solvent evaporation - the solute is deposited on a precise spot, greatly increasing its concentration allowing further measurements, such as X-ray microanalysis and X-ray diffraction. These results could have potential applications in the study of blood proteins, such as ferritin and low density lipoprotein, which are usually available in very limited quantity.
- Published
- 2013
6. Production, characterization and modeling of exchange coupled hard-FM/soft-FM nanostructures
- Author
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S. Laureti[1], E. Agostinelli[1], P. Alippi[1], V. Foglietti[1], A. Gerardino[2], L. Businaro[2], D. Peddis[1], A. M. Testa[1], G. Varvaro[1], and D. Fiorani[1]
- Published
- 2013
7. Fabrication by means of X-Ray lithography of 2D GaAs/AlGaAs photonic crystals with unconventional unit cell
- Author
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F. ROMANATO, L. BUSINARO E. DI FABRIZIO, A. PASSASEO, M. DE VITTORIO AND R. CINGOLANI, M. PATRINI, M. GALLI, D. BAJONI, DE VITTORIO, Massimo, F., Romanato, L. BUSINARO E., DI FABRIZIO, A., Passaseo, M. DE VITTORIO AND R., Cingolani, M., Patrini, M., Galli, D., Bajoni, and DE VITTORIO, Massimo
- Abstract
Two-dimensional photonic crystals have been fabricated by x-ray lithography and reactive ion etching on an air/GaAs/AlGaAs asymmetric waveguide. The shape of the lattice unit cell has been varied by exploiting x-ray diffraction effects and nonlinear response of resists during the development process. Rings with or without a central pillar have been fabricated with a resolution down to 50 nm. Lithographic details are described to show the accuracy of this fabrication technique. Optical characterization has been performed showing the presence of a well defined photonic band structure as well as band anti-crossing. The results are discussed and compared with theoretical calculations of the photonic band dispersion. Structures with high dielectric fraction are shown to yield photonic modes with small line widths and low propagation losses. The reliability and the precise control of the fabricated sample structures make this lithographic method useful for a full investigation of optical properties on the dependence of the lattice unit cell shape.
- Published
- 2002
8. 'Optimization of Microfluidic Systems for IRMS long term measurement'
- Author
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G. Grenci, G. Birarda, E. Mitri, L. Businaro, S. Pacor, L. Vaccari, and M. Tormen
- Subjects
FTIR ,Synchrotron radiation ,Microfluidics ,Living cells spectroscopy - Abstract
Infrared Microspectroscopy (IRMS) has been proposed as a powerful diagnostic tool in biology, due to the rich molecular, structural and conformational information contained in IR spectra of cells and tissues. In particular, IRMS of live cells in microfluidic devices has to cope with the strong water absorption in the medium infrared spectral region and the scarce knowledge about fabrication protocols suitable for microstructuring infrared-transparent materials. Based on these motivations we are developing and testing a class of microfluidic devices consisting of a patterned photoresist sandwiched between two CaF2 optical windows.In this paper we propose solutions to a few specific issues, namely, (i) the poor resist adhesion during micro-fabrication processes due to the low surface energy of CaF2, (ii) the potentially harmful effects of CaF2 dissolution on interesting cellular lines (such as neurons or stem cells), (iii) the sealing of the devices.Specifically, we modified the surface properties of CaF2 substrates by sputtering a thin layer of Si, as to obtain the following advantages: (a) all lithographic steps can be performed as if they were carried out on silicon wafers; (b) the chemical functionalization and nanostructuring of the surface in contact with cells can be obtained by usual protocols used for Si; (c) the deposited silicon separates living cells and their environment from CaF2. A device sealing process is discussed, based on a polymer bonding protocol, in order to tune the content of residual solvent. Finally, we present IR hyperspectral images acquired on MCF-7 living cells, cultured inside our devices for 48 h.
- Published
- 2012
- Full Text
- View/download PDF
9. Integrated Photonic Micro Logic Gate
- Author
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A. Rudnitsky, A. Shahmoon, M. Nathan, M. Nazarathy, A. Martucci, L. Businaro, A. Gerardino, and Z. Zalevsky
- Published
- 2011
10. Fabrication and characterization of Mn-catalyzed GaAs nanowires
- Author
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F. Martelli, S. Rubini, M. Piccin, G. Bais, F. Jabeen, S. De Franceschi, V. Grillo, E. Carlino, N. Mahne, S. Nannarone, M. Lazzarino, L. Businaro, F. Romanato, and A. Franciosi.
- Abstract
We report on the growth of microns long Mn-catalyzed GaAs nanowires. alpha-Mn is found on top of the wires, demonstrating that Mn acts as the growth catalyst. Transport measurements show that the wires have a p-behavior. Luminescence shows a peak at 1.522 eV. The blue shift with respect to bulk GaAs is not due to quantum effects.
- Published
- 2007
11. X-ray lithography patterning of magnetic material and their characterization
- Author
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E. Di Fabrizio, P. Candeloro, R. Kumar, A. Gerardino, L. Vaccari, M. Altissimo, S. Cabrini, L. Businaro, D. Cojoc, F. Feri, F. Romanato, G. Carlotti, and G. Gubbiotti
- Published
- 2003
12. Fabrication of 3D metallic photonic crystals by X-ray lithography
- Author
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a F. Romanato, L. Businaro, L. Vaccari, S. Cabrini, P. Candeloro, E. Di Fabrizio b M. De Vittorio, A. Passaseo, M.T. Todaro, R. Cingolani c E. Cattaruzza d M. Galli, and C. Andreani
- Abstract
Photonic crystals (3D) represent one of the most important building blocks towards the achievement of a full optics communication technology. So far the largest interest has been attracted by two-dimensional photonic crystals because they are potentially more amenable to fabrication and much closer to application. Straightforward application of the photonic band gap concept is generally thought to require three-dimensional (3D) photonic crystals that, however, represent a challenge from a fabrication point of view. Recent works have shown that 3D metallic PC can be fabricated and that they can be advantageous in the low frequency region where the metals become almost completely reflectors. In this work we show the possibility to fabricate 3D PC structures by X-ray lithography. Gold and nickel 3D photonic crystals with threefold (Yablonovite) and fourfold rotation symmetry have been fabricated with a lattice parameter ranging from 1 ?m down to 300 nm. The total thickness of the 3D PC is of the order of 10 ?m, a value which should allow to achieve a complete bulk behavior. This is supported by variable angle reflectance measurements, which have shown clear indications for true 3D dimensionality of our samples.
- Published
- 2003
13. Nanofabrication of high refractive index contrast two-dimensional photonic crystal waveguides
- Author
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a M.T. Todaro, T. Stomeo, V. Vitale, M. De Vittorio, A. Passaseo, R. Cingolani b F. Romanato, L. Businaro, and E. Di Fabrizio
- Subjects
Condensed Matter::Materials Science ,Physics::Optics ,Condensed Matter::Mesoscopic Systems and Quantum Hall Effect - Abstract
We present the fabrication of high refractive index contrast two-dimensional photonic crystal (2D-PC) slab waveguides. 2D photonic crystal structures, consisting of a periodic array of holes in a GaAs matrix, are obtained by nanopatterning of epitaxially grown GaAs/AlGaAs heterostructures. Two different PC structures will be described in detail: (i) an asymmetric 2D-PC slab waveguide obtained by selective oxidation which transforms the Al-rich AlGaAs cladding layer underneath the PCs into aluminium oxide and (ii) a symmetric 2D-PC slab waveguide obtained by removing the oxide (free standing structure).
- Published
- 2003
14. Fabrication by means of X-Ray lithography of 2D GaAs/AlGaAs photonic crystals with unconventional unit cell
- Author
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CINGOLANI, Roberto, F. ROMANATO, L. BUSINARO, E. DI FABRIZIO, A. PASSASEO, M. DE VITTORIO, M. PATRINI, M. GALLI, D. BAJONI, L. . C. ANDREANI, Cingolani, Roberto, Romanato, F., Businaro, L., DI FABRIZIO, E., Passaseo, A., DE VITTORIO, M., Patrini, M., Galli, M., Bajoni, D., and Andreani, L. . C.
- Published
- 2002
15. Laser diagnostics developed for conservation and restoration of cultural inheritance
- Author
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E. Bacchi, Andrea Bordone, Antonio Palucci, Roberta Fantoni, C. Poggi, Michele Arturo Caponero, S. Ribezzo, L. Businaro, G. Fornetti, Mario Ferri De Collibus, and Ilaria Borgia
- Subjects
Conservation ,Engineering drawing ,Materials science ,Optics ,business.industry ,law ,Speckle imaging ,3d sensor ,business ,Laser ,Cultural inheritance ,law.invention ,Characterization (materials science) - Abstract
Different laser induced diagnostics, originally developed for different purposes including material characterization and environmental monitoring, have been applied in the field of Cultural Inheritance preservation with the aim to facilitate successive conservation and restoration actions. In this paper results relevant to three different techniques are reviewed. The use of topologic laser and 3D sensor in checking small artifacts and large surfaces is discussed, the application of Speckle interferometry to defect analysis of ceramic artwork is represented, a demonstration of the capabilities of a time resolved LIF system in the characterization of surface composition of ancient ceramics and frescoes is finally given.
- Published
- 2000
16. Coherent laser sensor for robotic applications
- Author
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Mario Ferri De Collibus, L. Businaro, G. Fornetti, L. Morici, Andrea Bordone, C. Poggi, and L. Bartolini
- Subjects
Range (mathematics) ,Engineering ,Signal-to-noise ratio ,Laser sensor ,law ,business.industry ,Electronic engineering ,Laser ,business ,law.invention - Abstract
A coherent laser sensor, able to achieve measurement of absolute and relative distance of real targets, has been developed for advanced robotic applications. A brief theoretical description of the expected behavior of such system is reported for static and dynamic targets; the theoretical range error dependence from the signal to noise ratio is also described. Experimental results for measurements of static and vibrating real targets are discussed.
- Published
- 1998
17. Focused ion beam fabrication of one-dimensional photonic crystals onSi3N4/SiO2 channel waveguides.
- Author
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S Cabrini, L Businaro, M Prasciolu, A Carpentiro, D Gerace, M Galli, L C Andreani, F Riboli, L Pavesi, and E Di Fabrizio
- Published
- 2006
18. Resonant second-harmonic generation and mode dispersion in photonic crystal waveguides.
- Author
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L. C. Andreani, G. Guizzetti, M. Patrini, G. Vecchi, A. M. Malvezzi, L. Businaro, F. Romanato, E. Di Fabrizio, and A. Passaseo
- Published
- 2003
- Full Text
- View/download PDF
19. The Automotive Industry Needs Research
- Author
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Ugo L. Businaro
- Subjects
Energy conservation ,University community ,Engineering ,History and Philosophy of Science ,business.industry ,Basic research ,Control (management) ,Automotive industry ,Robot ,Instrumentation (computer programming) ,business ,Social Sciences (miscellaneous) ,Manufacturing engineering - Abstract
There is now an increasing need for research to meet the objectives of vehicle energy conservation and the case for this is presented here. It illustrates the need for basic research in areas such as heat transfer and combustion in alternative engines, instrumentation control, rheology and manufacturing processes for vehicle components and materials. Car manufacture needs research on thermomechanical treatments application of optimization theory, acoustic diagnostics and assembly of mechanical parts by robots. The best way of attracting the attention of the university community to such research are also discussed, emphasizing the role of establishing good communication channels.
- Published
- 1983
20. Nuclear reactor physics
- Author
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G. Caglioti, K. Sahai, U. L. Businaro, A. M. Weinberg, and B. L. Youtz
- Subjects
Nuclear and High Energy Physics ,Materials science ,Nuclear reactor physics ,Nuclear reactor core ,law ,Uranium-233 ,Nuclear engineering ,Astronomy and Astrophysics ,Nuclear reactor ,Nuclear reactor safety systems ,Liquid fluoride thorium reactor ,Atomic and Molecular Physics, and Optics ,law.invention - Published
- 1956
21. Collective aspects of nuclear photoeffect
- Author
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U. L. Businaro and S. Gallone
- Subjects
Nuclear physics ,Physics ,Nuclear and High Energy Physics ,Astronomy and Astrophysics ,Atomic and Molecular Physics, and Optics - Published
- 1955
22. Libri ricevuti e Recensioni
- Author
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F. A. Levi, P. Caldirola, S. Gallone, and U. L. Businaro
- Subjects
Nuclear and High Energy Physics ,Astronomy and Astrophysics ,Atomic and Molecular Physics, and Optics - Published
- 1955
23. Asymmetric equilibrium shapes in the liquid drop model
- Author
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S. Gallone and U. L. Businaro
- Subjects
Physics ,Nuclear and High Energy Physics ,Character (mathematics) ,Semi-empirical mass formula ,Computation ,Mathematical analysis ,Spinning drop method ,Astronomy and Astrophysics ,Type (model theory) ,Potential energy ,Ellipsoid ,Atomic and Molecular Physics, and Optics ,Ion - Abstract
In some recent papers (1-3) methods have been given for calculating the potential energy of strongly deformed nuclei under the usual assumptions of the liquid drop model. These methods have been applied to the calculation of the symmetric saddle shape (2), giving results in good accordance with the ENIAC computat ions of FRASKEL and METROi'OL~S (% Also these computations show (~-3) tha t sufficiently elongated shapes might be unstable with respect to asymmetric deformations. We will here apply the formulae already derived in (~,z) to the problem of the existence and character of asymmetric equilibrium shapes. Considering deformations of P2 and Pa type, only, superimposed on the basic ellipsoid, one may write for the potential energy, in a compact form
- Published
- 1957
24. Saddle shapes, threshold energies and fission asymmetry on the liquid drop model
- Author
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U. L. Businaro and S. Gallone
- Subjects
Physics ,Nuclear and High Energy Physics ,Fission products ,Cold fission ,Deformation (mechanics) ,Fission ,media_common.quotation_subject ,Astronomy and Astrophysics ,Asymmetry ,Atomic and Molecular Physics, and Optics ,Symmetry (physics) ,Semi-empirical mass formula ,Atomic physics ,Saddle ,media_common - Published
- 1955
25. X-ray lithography patterning of magnetic materials and their characterization
- Author
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Annamaria Gerardino, P. Candeloro, F. Romanato, Dan Cojoc, Lisa Vaccari, Giovanni Carlotti, S. Cabrini, Matteo Altissimo, Gianluca Gubbiotti, F. Feri, E. Di Fabrizio, L. Businaro, and R. Kumar
- Subjects
Materials science ,Physics and Astronomy (miscellaneous) ,business.industry ,Demagnetizing field ,General Engineering ,Magnetic storage ,General Physics and Astronomy ,Pattern formation ,X-ray lithography ,Permalloy material ,micromagnetic simulation ,magneto-optical Kerr effect ,Characterization (materials science) ,law.invention ,Magnetic Phenomena ,law ,Magnet ,Optoelectronics ,Point (geometry) ,business - Abstract
Patterned arrays of magnetic wires, dots and anti-dots have attracted a lot of interest both for their potential applications in magnetic data-storage devices and for the investigation of magnetic phenomena in low-dimensional systems. However the employment of micro- and nano-structures in magnetic high density recording media and non-volatile RAM is not trivial: compared to the case of a continuous film, the small size of the islands increases the effects of the demagnetizing field, affecting the static and dynamic magnetic properties. Moreover, some new effects arise due to the lateral confinement of the structures, e.g.: quantized spin-wave modes. These latter effects are of great interest also from a fundamental point of view.
26. Recent advances in superhydrophobic surfaces and their relevance to biology and medicine.
- Author
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G Ciasca, M Papi, L Businaro, G Campi, M Ortolani, V Palmieri, A Cedola, A De Ninno, A Gerardino, G Maulucci, and M De Spirito
- Published
- 2016
- Full Text
- View/download PDF
27. Shaping X-rays by diffractive coded nano-optics
- Author
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Burkhard Kaulich, Filippo Romanato, Dan Cojoc, E. Vitale, Giuseppe Gigli, Thomas Wilhein, Luca Businaro, J. Susini, R. Cingolani, M. Altissimo, M. De Vittorio, Stefano Cabrini, E. Di Fabrizio, E., Di Fabrizio, S., Cabrini, D., Cojoc, F., Romanato, L., Businaro, M., Altissimo, B., Kaulich, T., Wilhein, J., Susini, DE VITTORIO, Massimo, E., Vitale, G., Gigli, and Cingolani, Roberto
- Subjects
Diffraction ,Physics ,Fabrication ,business.industry ,Nanophotonics ,Physics::Optics ,Radiation ,Condensed Matter Physics ,Atomic and Molecular Physics, and Optics ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,X-ray optical elements ,Optics ,Cardinal point ,Extreme ultraviolet ,Optoelectronics ,Electrical and Electronic Engineering ,business ,Lithography ,Maskless lithography - Abstract
In this paper we report results obtained in the fabrication and use of novel coded diffractive nano-optics that, beyond focusing, can perform new optical functions. In particular, the intensity of light in the space beyond the optical elements can be redistributed with almost complete freedom. These novel X-ray optical elements have been tested and found to perform multi-focusing in single or multiple focal planes and beam shaping of a generic monochromatic beam into a desired continuous geometrical pattern. Already available extreme ultraviolet and X-ray sources are suitable as ideal sources for such diffractive optical elements. Their new optical functions have been tested in differential interference contrast microscopy and we suggest their use also in maskless lithography and chemical vapour deposition induced by extreme ultraviolet and X-ray radiation.
- Published
- 2003
28. Second-harmonic generation measured on a GaAs photonic crystal planar waveguide
- Author
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A. M. Malvezzi, Maddalena Patrini, Luca Businaro, Lucio Claudio Andreani, Giorgio Guizzetti, G. Vecchi, Adriana Passaseo, F. Romanato, E. Di Fabrizio, M. De Vittorio, F Cattaneo, L. C., Andreani, F., Cattaneo, G., Guizzetti, A. M., Malvezzi, M., Patrini, G., Vecchi, F., Romanato, L., Businaro, E., Di Fabrizio, A., Passaseo, and DE VITTORIO, Massimo
- Subjects
Diffraction ,Materials science ,business.industry ,Guided-mode resonance ,GaAs ,Photonic integrated circuit ,Physics::Optics ,Second-harmonic generation ,Nonlinear optics ,Condensed Matter Physics ,Yablonovite ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials ,Optics ,photonic crystals ,second-harmonic generation ,Optoelectronics ,Photonics ,business ,Photonic crystal - Abstract
Second-harmonic (SH) reflection and diffraction measurements are performed, at the wavelengths of a Ti:sapphire laser on a GaAs/AlGaAs photonic crystal waveguide patterned with a square lattice, the basis consisting of rings of air in the dielectric matrix. The measured angles of diffracted SH beams agree with those predicted from nonlinear diffraction conditions. Results for reflected and diffracted SH intensities as a function of incidence angle, polarization, and pump wavelength show that, due to the low air fraction of the photonic crystal, the reflected one is dominated by the crystalline symmetry of GaAs, while the diffracted one is related to the photonic crystal structure. The large diffraction-to-reflection ratio points to the importance of nonlinear diffraction in photonic crystals. Preliminary measurements in the 1500nm range reveal explicit features related to photonic modes.
- Published
- 2003
29. Fabrication of a microfluidic platform for investigating dynamic biochemical processes in living samples by FTIR microspectroscopy
- Author
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Benedetta Marmiroli, Sabrina Pacor, Lisa Vaccari, Giovanni Birarda, Gianluca Grenci, Luca Businaro, G., Birarda, G., Grenci, L., Businaro, B., Marmiroli, Pacor, Sabrina, and L., Vaccari
- Subjects
Materials science ,Fabrication ,Microfluidics ,Substrate (chemistry) ,Nanotechnology ,Photoresist ,Condensed Matter Physics ,Atomic and Molecular Physics, and Optics ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,law.invention ,law ,Globar ,Biophysics ,Electrical and Electronic Engineering ,Fourier transform infrared spectroscopy ,Photolithography ,FTIR microspectroscopy ,Microfabrication - Abstract
Here we present the optimization of fabrication steps for realizing an infrared-visible microfluidic chip to study single-living cell behaviour in physiological environment by synchrotron radiation FTIR microspectroscopy. We optimized subtractive and additive lithographic processes on CaF"2 substrate, employing X-ARP 3100/10 photoresist both as etching-mask and for the device fabrication. Using prototype microfabricated liquid cells 9 and [email protected] thick, we measured the response of small groups of THP1 monocytic cells to mechanical compression and chemical stimulation with fMLP using conventional IR globar source, aiming to evaluate biochemical rearrangements of leukocytes during the capillary circulation or recruitment processes. Stimulated monocytes have spectral features recognizable, differentiating them from un-stimulated, especially affecting the spectral region 1280-1000cm^-^1, characteristic of nucleic acids and carbohydrates, and specific band ratios, such as proteins on lipids and methylene on methyl. Spectra variations have been correlated with biochemical events such as transcription, synthesis of new-proteins and variations in membrane fluidity.
- Published
- 2010
30. Infrared microspectroscopy of biochemical response of living cells in microfabricated devices
- Author
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Benedetta Marmiroli, Sabrina Pacor, Federica Piccirilli, Giovanni Birarda, Lisa Vaccari, Gianluca Grenci, Luca Businaro, Birarda, G, Grenci, G, Businaro, L, Marmiroli, B, Pacor, S, Piccirilli, F, Vaccari, L, G., Birarda, G., Grenci, L., Businaro, B., Marmiroli, Pacor, Sabrina, F., Piccirilli, and L., Vaccari
- Subjects
Materials science ,business.industry ,Infrared ,Microfluidics ,Analytical chemistry ,Synchrotron radiation ,Photoresist ,chemistry.chemical_compound ,symbols.namesake ,microfabricated device ,Fourier transform ,FTIR ,chemistry ,Settore BIO/10 - Biochimica ,Amide ,microscopy ,symbols ,Optoelectronics ,Fluidics ,FTIR microspectroscopy ,business ,living cells ,Spectroscopy ,Microfabrication - Abstract
First experiments demonstrating the suitability of novel microfabricated fluidic devices for measuring living cells in physiological environment by synchrotron radiation (SR) Fourier Transform Infrared microspectroscopy (μ-FTIR) are presented. The devices were fabricated on CaF 2 windows, using the photoresist XARP 3100/10 to define the liquid cell lay-out. Therefore, the sample holder is transparent to both visible and infrared light, robust, completely recyclable and with a precise spacing. Using prototype devices of thicknesses 9, 5 and 3 μm, we studied the response of the U937 monocytic cell line to mechanical compression. The temporal evolution of the FTIR spectra, characteristic for the status of living cells, was used to monitor the cellular system stability in time. Protein biosynthesis and lipid metabolism alterations upon deformation have been identified by monitoring specific cell band ratios such as amide I to amide II, amide I to lipids, methylene to methyl and asymmetric to symmetric stretching of phosphates. Taking advantage of the high brilliance of the synchrotron radiation, chemical maps of monocyte cells were collected, demonstrating the versatility of the device.
- Published
- 2010
31. Manganese-induced growth of GaAs nanowires
- Author
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Silvia Rubini, Federico Boscherini, Faustino Martelli, Francesco d'Acapito, Elvio Carlino, Luca Businaro, Filippo Romanato, Marco Lazzarino, Silvano de Franceschi, F. Jabeen, A. Franciosi, V. Grillo, G. Bais, S. Cabrini, M. Piccin, F. Martelli, S. Rubini, M. Piccin, G. Bai, F. Jabeen, S. De Franceschi, V. Grillo, E. Carlino, F. D’Acapito, F. Boscherini, S. Cabrini, M. Lazzarino, L. Businaro, F. Romanato, A. Franciosi, Martelli, F, Rubini, S, Piccin, M, Bais, G, Jabeen, F, DE FRANCESCHI, S, Grillo, V, Carlino, E, Dacapito, F, Boscherini, F, Cabrini, S, Lazzarino, M, Businaro, L, Romanato, F, and Franciosi, Alfonso
- Subjects
X-ray absorption fine structure ,GaAs nanowires ,congenital, hereditary, and neonatal diseases and abnormalities ,Nanostructure ,Surface Properties ,Nanowire ,Analytical chemistry ,Molecular Conformation ,chemistry.chemical_element ,Bioengineering ,Gallium ,Manganese ,NANOSTRUCTURES ,Arsenicals ,TRANSPORT-PROPERTIES ,MOLECULAR-BEAM EPITAXY ,Materials Testing ,MOLECULAR BEAM EPITAXY ,General Materials Science ,Particle Size ,SEMICONDUCTOR NANOWIRES ,Nanotubes ,Extended X-ray absorption fine structure ,business.industry ,Mechanical Engineering ,Doping ,Electric Conductivity ,nutritional and metabolic diseases ,General Chemistry ,Condensed Matter Physics ,Crystallography ,Semiconductor ,chemistry ,Semiconductors ,Transmission electron microscopy ,SYNCHROTRON RADIATION ,business ,Crystallization ,Molecular beam epitaxy - Abstract
GaAs nanowires have been grown on SiO2 and GaAs by molecular beam epitaxy using manganese as growth catalyst. Transmission electron microscopy shows that the wires have a wurtzite-type lattice and that alpha-Mn particles are found at the free end of the wires. X-ray absorption fine structure measurements reveal the presence of a significant fraction of Mn-As bonds, suggesting Mn diffusion and incorporation during wire growth. Transport measurements indicate that the wires are p-type, as expected from doping of GaAs with Mn.
- Published
- 2006
32. Design and fabrication of on-fiber diffractive elements for fiber-waveguide coupling by means of e-beam lithography
- Author
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Annamaria Gerardino, Dan Cojoc, R. Kumar, Massimo Tormen, R. Cingolani, Giuseppe Gigli, Mauro Prasciolu, Luca Businaro, Carlo Liberale, Vittorio Degiorgio, E. Di Fabrizio, P. Candeloro, Dario Pisignano, Stefano Cabrini, M., Prasciolu, D., Cojoc, S., Cabrini, L., Businaro, P., Candeloro, M., Tormen, R., Kumar, C., Liberale, V., Degiorgio, A., Gerardino, G., Gigli, Pisignano, Dario, E., DI FABRIZIO, and R., Cingolani
- Subjects
Materials science ,Optical fiber ,business.industry ,Single-mode optical fiber ,Physics::Optics ,Condensed Matter Physics ,Diffraction efficiency ,Waveguide (optics) ,Atomic and Molecular Physics, and Optics ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,law.invention ,Optics ,law ,X-ray lithography ,Electrical and Electronic Engineering ,business ,Lithography ,Electron-beam lithography ,Gaussian beam - Abstract
The aim of this paper is to demonstrate that efficient fiber-waveguide optical coupling can be achieved using a multilevel phase diffractive element (PDE) fabricated directly on the top of the fiber by means of e-beam lithography. The diffractive phase element is calculated to focus and reshape the gaussian symmetric beam exiting a single-mode fiber into a desired asymmetric intensity distribution at the waveguide input plane. Phase modulation is obtained by multilevel profiling a polymeric material coated on the top of the fiber by means of a specific fabrication process including e-beam lithography and chemical etching. Experimental results obtained for fiber-waveguide coupling with a 20-µm diameter diffractive element are also presented.
- Published
- 2003
33. Fabrication of 3D metallic photonic crystal by X-ray lithography
- Author
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R. Cingolani, S. Cabrini, Patrizio Candeloro, M. De Vittorio, C. Andreani, Elti Cattaruzza, A. Passaseo, Luca Businaro, E. Di Fabrizio, Filippo Romanato, Maria Teresa Todaro, Lisa Vaccari, Matteo Galli, F., Romanato, L., Businaro, S., Cabrini, DE VITTORIO, Massimo, A., Passaseo, M. T., Todaro, R., Cingolani, C., Andreani, and E., DI FABRIZIO
- Subjects
Materials science ,Fabrication ,business.industry ,Optical communication ,Condensed Matter Physics ,Yablonovite ,X-ray lithography ,Atomic and Molecular Physics, and Optics ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,law.invention ,Lattice constant ,Optics ,law ,photonic crystals ,Electrical and Electronic Engineering ,Photolithography ,business ,Lithography ,Photonic crystal - Abstract
Photonic crystals (3D) represent one of the most important building blocks towards the achievement of a full optics communication technology. So far the largest interest has been attracted by two-dimensional photonic crystals because they are potentially more amenable to fabrication and much closer to application. Straightforward application of the photonic band gap concept is generally thought to require three-dimensional (3D) photonic crystals that, however, represent a challenge from a fabrication point of view. Recent works have shown that 3D metallic PC can be fabricated and that they can be advantageous in the low frequency region where the metals become almost completely reflectors. In this work we show the possibility to fabricate 3D PC structures by X-ray lithography. Gold and nickel 3D photonic crystals with threefold (Yablonovite) and fourfold rotation symmetry have been fabricated with a lattice parameter ranging from 1 μm down to 300 nm. The total thickness of the 3D PC is of the order of 10 μm, a value which should allow to achieve a complete bulk behavior. This is supported by variable angle reflectance measurements, which have shown clear indications for true 3D dimensionality of our samples.
- Published
- 2003
34. Nanofabrication of high refractive index contrast two-dimensional photonic crystal waveguides
- Author
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Luca Businaro, R. Cingolani, Maria Teresa Todaro, V. Vitale, E. Di Fabrizio, Adriana Passaseo, Tiziana Stomeo, F. Romanato, M. DeVittorio, M. T., Todaro, T., Stomeo, V., Vitale, DE VITTORIO, Massimo, A., Passaseo, R., Cingolani, F., Romanato, L., Businaro, and E., Difabrizio
- Subjects
Materials science ,High-refractive-index polymer ,business.industry ,heterostructures ,photonic crystal waveguides ,Oxide ,Physics::Optics ,Heterojunction ,Condensed Matter::Mesoscopic Systems and Quantum Hall Effect ,Condensed Matter Physics ,Cladding (fiber optics) ,Waveguide (optics) ,Atomic and Molecular Physics, and Optics ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Condensed Matter::Materials Science ,chemistry.chemical_compound ,Optics ,chemistry ,Slab ,Electrical and Electronic Engineering ,business ,Refractive index ,Photonic crystal - Abstract
We present the fabrication of high refractive index contrast two-dimensional photonic crystal (2D-PC) slab waveguides. 2D photonic crystal structures, consisting of a periodic array of holes in a GaAs matrix, are obtained by nanopatterning of epitaxially grown GaAs/AlGaAs heterostructures. Two different PC structures will be described in detail: (i) an asymmetric 2D-PC slab waveguide obtained by selective oxidation which transforms the Al-rich AlGaAs cladding layer underneath the PCs into aluminium oxide and (ii) a symmetric 2D-PC slab waveguide obtained by removing the oxide (free standing structure).
- Published
- 2003
35. Fabrication of diffractive optical elements for photonic applications by nanolithography
- Author
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Dan Cojoc, C. Liberae, R. Cingolani, Giuseppe Gigli, R. Kumar, S. Cabrini, Dario Pisignano, Vittorio Degiorgio, Mauro Prasciolu, E. Di Fabrizio, Luca Businaro, E., Di Fabrizio, M., Prasciolu, R., Kumar, S., Cabrini, L., Businaro, D., Cojoc, C., Liberae, V., Degiorgio, Gigli, Giuseppe, Pisignano, Dario, and Cingolani, Roberto
- Subjects
Materials science ,Optical fiber ,business.industry ,Physics::Optics ,Zone plate ,Laser ,Waveguide (optics) ,law.invention ,Optics ,Nanolithography ,law ,Optoelectronics ,Photonics ,business ,Lithography ,Photonic crystal - Abstract
The present research work is devoted to the realization of an efficient optical coupling between single-mode fiber and rectangular waveguide. The outcoming laser beam exiting from the fiber has a gaussian transversal field distribution. On the contrary, the single-mode waveguide has an asymmetric transversal field distribution in X and Y-axis. The problem of transforming the outcoming circular laser beam onto a rectangular, size adjusted, spot can be solved realizing directly on the top of the fiber a diffractive optical element. This optic element is able to redistribute the diffractive electromagnetic field on a selected area by a suitable phase modulation of the light, in analogy with what happens for Fresnel zone plate lenses. Phase modulation is obtained by a multilevel profiling of a polymeric material coating the top of the fiber by means of e-beam lithography. The design of diffractive optical elements has been realized using our own algorithm and code. Focalization experiments have been made with the use of a 1550nm wavelength laser. Description of the lithography and fabrication processes are shown as well.
- Published
- 2002
36. High-resolution complex structures for two-dimensional photonic crystals realized by x-ray diffraction lithography
- Author
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P. Candeloro, Adriana Passaseo, Matteo Galli, F. Romanato, E. Di Fabrizio, M. De Vittorio, Luca Businaro, Maddalena Patrini, C. Andreani, L., Businaro, F., Romanato, P., Candeloro, C., Andreani, M., Galli, M., Patrini, A., Passaseo, DE VITTORIO, Massimo, and E., DI FABRIZIO
- Subjects
Diffraction ,Fabrication ,Materials science ,business.industry ,photonic crystals ,X-ray diffraction lithography ,high resolution structures ,General Engineering ,Physics::Optics ,Multiphoton lithography ,Optics ,Resist ,Etching (microfabrication) ,Optoelectronics ,X-ray lithography ,business ,Lithography ,Photonic crystal - Abstract
Two-dimensional photonic band gap structures were fabricated by x-ray lithography combined with, ion etching on metalorganic chemical vapor deposition grown GaAs/AlGaAs waveguides. Such structures, more amenable to fabrication than fully three-dimensional photonic crystals, allow the confinement of light in the third direction using index guiding. The feasibility of complex high-resolution (down to 50 nm) unit cell fabrication has been demonstrated by exploiting x-ray diffraction and nonlinear resist response during the development process. Optical characterizations of some samples were performed. These characterizations show the presence of well-defined photonic band gap structures and second harmonic property generation. The results have been discussed and compared with theoretical simulation
37. Second-harmonic generation in reflection and diffraction by a GaAs photonic-crystal waveguide
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Giorgio Guizzetti, A. M. Malvezzi, Massimo De Vittorio, Luca Businaro, A. Passaseo, Enzo Di Fabrizio, Francesco Cattaneo, Matteo Falasconi, Filippo Romanato, G. Vecchi, Lucio Claudio Andreani, A. M., Malvezzi, F., Cattaneo, G., Vecchi, M., Falasconi, G., Guizzetti, L. C., Andreani, F., Romanato, L., Businaro, E., DI FABRIZIO, A., Passaseo, and DE VITTORIO, Massimo
- Subjects
Physics ,Diffraction ,business.industry ,photonic crystal waveguides ,Physics::Optics ,Second-harmonic generation ,Nonlinear optics ,Statistical and Nonlinear Physics ,Diffraction efficiency ,Waveguide (optics) ,Atomic and Molecular Physics, and Optics ,Optics ,second-harmonic generation ,Crystal optics ,Reflection coefficient ,business ,Diffraction grating - Abstract
Nonlinear reflection and diffraction measurements have been performed on a GaAs/AlGaAs photonic-crystal waveguide patterned with a square lattice: The basis in the two-dimensional unit cell consists of rings of air in the dielectric matrix. The measured angles of diffracted second-harmonic beams agree with those predicted for nonlinear diffraction conditions, Results for second-harmonic intensities as a function of incidence angle, polarization, and pump wavelength show that the reflected second-harmonic signal is dominated by the crystalline symmetry of GaAs, whereas nonlinear diffraction is determined by the photonic-crystal structure.
38. Resonant second-harmonic generation in a GaAs photonic crystal waveguide
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Luca Businaro, Lucio Claudio Andreani, M. De Vittorio, Giorgio Guizzetti, Maddalena Patrini, Filippo Romanato, G. Vecchi, A. Passaseo, E. Di Fabrizio, A. M. Malvezzi, A. M., Malvezzi, G., Vecchi, M., Patrini, G., Guizzetti, L. C., Andreani, F., Romanato, L., Businaro, E., DI FABRIZIO, A., Passaseo, and DE VITTORIO, Massimo
- Subjects
Physics ,business.industry ,Resonant second-harmonic generation ,GaAs ,photonic crystal waveguides ,Second-harmonic generation ,Physics::Optics ,Spectral line ,Momentum ,Reflection (mathematics) ,Dispersion (optics) ,Optoelectronics ,Photonics ,Atomic physics ,business ,Anisotropy ,Photonic crystal - Abstract
Second-harmonic generation (SHG) measurements in reflection on a ${\mathrm{G}\mathrm{a}\mathrm{A}\mathrm{s}/\mathrm{A}\mathrm{l}}_{0.25}{\mathrm{Ga}}_{0.75}\mathrm{As}$ photonic crystal waveguide show a resonant enhancement when the pump beam is frequency and momentum matched with the photonic modes in the slab. The enhanced SH signal is observed in the form of resonant peaks, unlike in linear reflectance spectra. The observations are in very good agreement with a full 3D calculation of the anisotropic mode dispersion in the photonic crystal slab. The present results open the way towards realizing the extraordinary enhancement of SHG which was recently predicted [A. R. Cowan and J. F. Young, Phys. Rev. B $65,$ 085106 (2002)], and also demonstrate the potential of SHG as a nonlinear spectroscopic tool for optical studies of photonic crystals.
39. Author Correction: Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B.
- Author
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Musella M, Guarracino A, Manduca N, Galassi C, Ruggiero E, Potenza A, Maccafeo E, Manic G, Mattiello L, Soliman Abdel Rehim S, Signore M, Pietrosanto M, Helmer-Citterich M, Pallocca M, Fanciulli M, Bruno T, De Nicola F, Corleone G, Di Benedetto A, Ercolani C, Pescarmona E, Pizzuti L, Guidi F, Sperati F, Vitale S, Macchia D, Spada M, Schiavoni G, Mattei F, De Ninno A, Businaro L, Lucarini V, Bracci L, Aricò E, Ziccheddu G, Facchiano F, Rossi S, Sanchez M, Boe A, Biffoni M, De Maria R, Vitale I, and Sistigu A
- Published
- 2024
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40. Crosstalk and communication of cancer-associated fibroblasts with natural killer and dendritic cells: New frontiers and unveiled opportunities for cancer immunotherapy.
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Ielpo S, Barberini F, Dabbagh Moghaddam F, Pesce S, Cencioni C, Spallotta F, De Ninno A, Businaro L, Marcenaro E, Bei R, Cifaldi L, Barillari G, and Melaiu O
- Subjects
- Humans, Animals, Dendritic Cells immunology, Killer Cells, Natural immunology, Cancer-Associated Fibroblasts immunology, Neoplasms immunology, Neoplasms therapy, Immunotherapy methods, Tumor Microenvironment immunology, Cell Communication immunology
- Abstract
Natural killer (NK) cells and dendritic cells (DCs) are critical mediators of anti-cancer immune responses. In addition to their individual roles, NK cells and DCs are involved in intercellular crosstalk which is essential for the initiation and coordination of adaptive immunity against cancer. However, NK cell and DC activity is often compromised in the tumor microenvironment (TME). Recently, much attention has been paid to one of the major components of the TME, the cancer-associated fibroblasts (CAFs), which not only contribute to extracellular matrix (ECM) deposition and tumor progression but also suppress immune cell functions. It is now well established that CAFs support T cell exclusion from tumor nests and regulate their cytotoxic activity. In contrast, little is currently known about their interaction with NK cells, and DCs. In this review, we describe the interaction of CAFs with NK cells and DCs, by secreting and expressing various mediators in the TME of adult solid tumors. We also provide a detailed overview of ongoing clinical studies evaluating the targeting of stromal factors alone or in combination with immunotherapy based on immune checkpoint inhibitors. Finally, we discuss currently available strategies for the selective depletion of detrimental CAFs and for a better understanding of their interaction with NK cells and DCs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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41. IL-33 stimulates the anticancer activities of eosinophils through extracellular vesicle-driven reprogramming of tumor cells.
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Gambardella AR, Antonucci C, Zanetti C, Noto F, Andreone S, Vacca D, Pellerito V, Sicignano C, Parrottino G, Tirelli V, Tinari A, Falchi M, De Ninno A, Businaro L, Loffredo S, Varricchi G, Tripodo C, Afferni C, Parolini I, Mattei F, and Schiavoni G
- Subjects
- Animals, Mice, Humans, Cell Line, Tumor, Cell Proliferation, Cellular Reprogramming, Interleukin-33 metabolism, Eosinophils metabolism, Extracellular Vesicles metabolism
- Abstract
Immune cell-derived extracellular vesicles (EV) affect tumor progression and hold promise for therapeutic applications. Eosinophils are major effectors in Th2-related pathologies recently implied in cancer. Here, we evaluated the anti-tumor activities of eosinophil-derived EV following activation with the alarmin IL-33. We demonstrate that IL-33-activated mouse and human eosinophils produce higher quantities of EV with respect to eosinophils stimulated with IL-5. Following incorporation of EV from IL-33-activated eosinophils (Eo33-EV), but not EV from IL-5-treated eosinophils (Eo5-EV), mouse and human tumor cells increased the expression of cyclin-dependent kinase inhibitor (CDKI)-related genes resulting in cell cycle arrest in G0/G1, reduced proliferation and inhibited tumor spheroid formation. Moreover, tumor cells incorporating Eo33-EV acquired an epithelial-like phenotype characterized by E-Cadherin up-regulation, N-Cadherin downregulation, reduced cell elongation and migratory extent in vitro, and impaired capacity to metastasize to lungs when injected in syngeneic mice. RNA sequencing revealed distinct mRNA signatures in Eo33-EV and Eo5-EV with increased presence of tumor suppressor genes and enrichment in pathways related to epithelial phenotypes and negative regulation of cellular processes in Eo33-EV compared to Eo5-EV. Our studies underscore novel IL-33-stimulated anticancer activities of eosinophils through EV-mediated reprogramming of tumor cells opening perspectives on the use of eosinophil-derived EV in cancer therapy., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
42. Kinetic Detection of Apoptosis Events Via Caspase 3/7 Activation in a Tumor-Immune Microenvironment on a Chip.
- Author
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Bertani FR, Moghaddam FD, Panella C, Giannitelli SM, Peluzzi V, Gerardino A, Rainer A, Roscilli G, De Ninno A, and Businaro L
- Subjects
- Animals, Humans, Mice, Caspase 3, Microfluidics methods, Apoptosis, Lab-On-A-Chip Devices, Tumor Microenvironment, Neoplasms pathology
- Abstract
The development of advanced biological models like microphysiological systems, able to rebuild the complexity of the physiological and/or pathological environments at a single-cell detail level in an in-vivo-like approach, is proving to be a promising tool to understand the mechanisms of interactions between different cell populations and main features of several diseases. In this frame, the tumor-immune microenvironment on a chip represents a powerful tool to profile key aspects of cancer progression, immune activation, and response to therapy in several immuno-oncology applications. In the present chapter, we provide a protocol to identify and characterize the time evolution of apoptosis by time-lapse fluorescence and confocal imaging in a 3D microfluidic coculture murine model including cancer and spleen cells., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
43. Rapid Assessment of Susceptibility of Bacteria and Erythrocytes to Antimicrobial Peptides by Single-Cell Impedance Cytometry.
- Author
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Troiano C, De Ninno A, Casciaro B, Riccitelli F, Park Y, Businaro L, Massoud R, Mangoni ML, Bisegna P, Stella L, and Caselli F
- Subjects
- Humans, Electric Impedance, Bacteria, Erythrocytes, Antimicrobial Peptides, Antimicrobial Cationic Peptides pharmacology, Antimicrobial Cationic Peptides chemistry
- Abstract
Antimicrobial peptides (AMPs) represent a promising class of compounds to fight antibiotic-resistant infections. In most cases, they kill bacteria by making their membrane permeable and therefore exhibit low propensity to induce bacterial resistance. In addition, they are often selective, killing bacteria at concentrations lower than those at which they are toxic to the host. However, clinical applications of AMPs are hindered by a limited understanding of their interactions with bacteria and human cells. Standard susceptibility testing methods are based on the analysis of the growth of a bacterial population and therefore require several hours. Moreover, different assays are required to assess the toxicity to host cells. In this work, we propose the use of microfluidic impedance cytometry to explore the action of AMPs on both bacteria and host cells in a rapid manner and with single-cell resolution. Impedance measurements are particularly well-suited to detect the effects of AMPs on bacteria, due to the fact that the mechanism of action involves perturbation of the permeability of cell membranes. We show that the electrical signatures of Bacillus megaterium cells and human red blood cells (RBCs) reflect the action of a representative antimicrobial peptide, DNS-PMAP23. In particular, the impedance phase at high frequency (e.g., 11 or 20 MHz) is a reliable label-free metric for monitoring DNS-PMAP23 bactericidal activity and toxicity to RBCs. The impedance-based characterization is validated by comparison with standard antibacterial activity assays and absorbance-based hemolytic activity assays. Furthermore, we demonstrate the applicability of the technique to a mixed sample of B. megaterium cells and RBCs, which paves the way to study AMP selectivity for bacterial versus eukaryotic cells in the presence of both cell types.
- Published
- 2023
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44. Combined mitoxantrone and anti-TGFβ treatment with PD-1 blockade enhances antitumor immunity by remodelling the tumor immune landscape in neuroblastoma.
- Author
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Lucarini V, Melaiu O, D'Amico S, Pastorino F, Tempora P, Scarsella M, Pezzullo M, De Ninno A, D'Oria V, Cilli M, Emionite L, Infante P, Di Marcotullio L, De Ioris MA, Barillari G, Alaggio R, Businaro L, Ponzoni M, Locatelli F, and Fruci D
- Subjects
- Humans, Mice, Animals, Mitoxantrone pharmacology, CD8-Positive T-Lymphocytes, Transforming Growth Factor beta, Cell Line, Tumor, Mice, Transgenic, Tumor Microenvironment, Programmed Cell Death 1 Receptor, Neuroblastoma drug therapy
- Abstract
Background: Poor infiltration of functioning T cells renders tumors unresponsive to checkpoint-blocking immunotherapies. Here, we identified a combinatorial in situ immunomodulation strategy based on the administration of selected immunogenic drugs and immunotherapy to sensitize poorly T-cell-infiltrated neuroblastoma (NB) to the host antitumor immune response., Methods: 975A2 and 9464D NB cell lines derived from spontaneous tumors of TH-MYCN transgenic mice were employed to study drug combinations able of enhancing the antitumor immune response using in vivo and ex vivo approaches. Migration of immune cells towards drug-treated murine-derived organotypic tumor spheroids (MDOTS) were assessed by microfluidic devices. Activation status of immune cells co-cultured with drug-treated MDOTS was evaluated by flow cytometry analysis. The effect of drug treatment on the immune content of subcutaneous or orthotopic tumors was comprehensively analyzed by flow-cytometry, immunohistochemistry and multiplex immunofluorescence. The chemokine array assay was used to detect soluble factors released into the tumor microenvironment. Patient-derived organotypic tumor spheroids (PDOTS) were generated from human NB specimens. Migration and activation status of autologous immune cells to drug-treated PDOTS were performed., Results: We found that treatment with low-doses of mitoxantrone (MTX) recalled immune cells and promoted CD8
+ T and NK cell activation in MDOTS when combined with TGFβ and PD-1 blockade. This combined immunotherapy strategy curbed NB growth resulting in the enrichment of a variety of both lymphoid and myeloid immune cells, especially intratumoral dendritic cells (DC) and IFNγ- and granzyme B-expressing CD8+ T cells and NK cells. A concomitant production of inflammatory chemokines involved in remodelling the tumor immune landscape was also detected. Interestingly, this treatment induced immune cell recruitment against PDOTS and activation of CD8+ T cells and NK cells., Conclusions: Combined treatment with low-dose of MTX and anti-TGFβ treatment with PD-1 blockade improves antitumor immunity by remodelling the tumor immune landscape and overcoming the immunosuppressive microenvironment of aggressive NB., (© 2022. The Author(s).)- Published
- 2022
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- View/download PDF
45. Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B.
- Author
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Musella M, Guarracino A, Manduca N, Galassi C, Ruggiero E, Potenza A, Maccafeo E, Manic G, Mattiello L, Soliman Abdel Rehim S, Signore M, Pietrosanto M, Helmer-Citterich M, Pallocca M, Fanciulli M, Bruno T, De Nicola F, Corleone G, Di Benedetto A, Ercolani C, Pescarmona E, Pizzuti L, Guidi F, Sperati F, Vitale S, Macchia D, Spada M, Schiavoni G, Mattei F, De Ninno A, Businaro L, Lucarini V, Bracci L, Aricò E, Ziccheddu G, Facchiano F, Rossi S, Sanchez M, Boe A, Biffoni M, De Maria R, Vitale I, and Sistigu A
- Subjects
- Anthracyclines metabolism, Anthracyclines therapeutic use, Female, Humans, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Breast Neoplasms pathology, Epigenesis, Genetic, Histone Demethylases metabolism, Interferon Type I metabolism
- Abstract
Cancer stem cells (CSCs) are a subpopulation of cancer cells endowed with high tumorigenic, chemoresistant and metastatic potential. Nongenetic mechanisms of acquired resistance are increasingly being discovered, but molecular insights into the evolutionary process of CSCs are limited. Here, we show that type I interferons (IFNs-I) function as molecular hubs of resistance during immunogenic chemotherapy, triggering the epigenetic regulator demethylase 1B (KDM1B) to promote an adaptive, yet reversible, transcriptional rewiring of cancer cells towards stemness and immune escape. Accordingly, KDM1B inhibition prevents the appearance of IFN-I-induced CSCs, both in vitro and in vivo. Notably, IFN-I-induced CSCs are heterogeneous in terms of multidrug resistance, plasticity, invasiveness and immunogenicity. Moreover, in breast cancer (BC) patients receiving anthracycline-based chemotherapy, KDM1B positively correlated with CSC signatures. Our study identifies an IFN-I → KDM1B axis as a potent engine of cancer cell reprogramming, supporting KDM1B targeting as an attractive adjunctive to immunogenic drugs to prevent CSC expansion and increase the long-term benefit of therapy., (© 2022. The Author(s).)
- Published
- 2022
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- View/download PDF
46. Electro-Optical Classification of Pollen Grains via Microfluidics and Machine Learning.
- Author
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DaOrazio M, Reale R, De Ninno A, Brighetti MA, Mencattini A, Businaro L, Martinelli E, Bisegna P, Travaglini A, and Caselli F
- Subjects
- Pollen, Machine Learning, Microfluidics
- Abstract
Objective: In aerobiological monitoring and agriculture there is a pressing need for accurate, label-free and automated analysis of pollen grains, in order to reduce the cost, workload and possible errors associated to traditional approaches., Methods: We propose a new multimodal approach that combines electrical sensing and optical imaging to classify pollen grains flowing in a microfluidic chip at a throughput of 150 grains per second. Electrical signals and synchronized optical images are processed by two independent machine learning-based classifiers, whose predictions are then combined to provide the final classification outcome., Results: The applicability of the method is demonstrated in a proof-of-concept classification experiment involving eight pollen classes from different taxa. The average balanced accuracy is 78.7% for the electrical classifier, 76.7% for the optical classifier and 84.2% for the multimodal classifier. The accuracy is 82.8% for the electrical classifier, 84.1% for the optical classifier and 88.3% for the multimodal classifier., Conclusion: The multimodal approach provides better classification results with respect to the analysis based on electrical or optical features alone., Significance: The proposed methodology paves the way for automated multimodal palynology. Moreover, it can be extended to other fields, such as diagnostics and cell therapy, where it could be used for label-free identification of cell populations in heterogeneous samples.
- Published
- 2022
- Full Text
- View/download PDF
47. Microfluidic Co-Culture Models for Dissecting the Immune Response in in vitro Tumor Microenvironments.
- Author
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De Ninno A, Bertani FR, Gerardino A, Schiavoni G, Musella M, Galassi C, Mattei F, Sistigu A, and Businaro L
- Subjects
- Cell Line, Tumor, Humans, Leukocytes, Mononuclear immunology, Coculture Techniques, Microfluidic Analytical Techniques, Tumor Microenvironment immunology
- Abstract
Complex disease models demand cutting-edge tools able to deliver physiologically and pathologically relevant, actionable insights, and unveil otherwise invisible processes. Advanced cell assays closely mimicking in vivo scenery are establishing themselves as novel ways to visualize and measure the bidirectional tumor-host interplay influencing the progression of cancer. Here we describe two versatile protocols to recreate highly controllable 2D and 3D co-cultures in microdevices, mimicking the complexity of the tumor microenvironment (TME), under natural and therapy-induced immunosurveillance. In section 1, an experimental setting is provided to monitor crosstalk between adherent tumor cells and floating immune populations, by bright field time-lapse microscopy. As an applicative scenario, we analyze the effects of anti-cancer treatments, such as the so-called immunogenic cancer cell death inducers on the recruitment and activation of immune cells. In section 2, 3D tumor-immune microenvironments are assembled in a competitive layout. Differential immune infiltration is monitored by fluorescence snapshots up to 72 h, to evaluate combination therapeutic strategies. In both settings, image processing steps are illustrated to extract a plethora of immune cell parameters (e.g., immune cell migration and interaction, response to therapeutic agents). These simple and powerful methods can be further tailored to simulate the complexity of the TME encompassing the heterogeneity and plasticity of cancer, stromal and immune cells subtypes, as well as their reciprocal interactions as drivers of cancer evolution. The compliance of these rapidly evolving technologies with live-cell high-content imaging can lead to the generation of large informative datasets, bringing forth new challenges. Indeed, the triangle ''co-cultures/microscopy/advanced data analysis" sets the path towards a precise problem parametrization that may assist tailor-made therapeutic protocols. We expect that future integration of cancer-immune on-a-chip with artificial intelligence for high-throughput processing will synergize a large step forward in leveraging the capabilities as predictive and preclinical tools for precision and personalized oncology.
- Published
- 2021
- Full Text
- View/download PDF
48. Oncoimmunology Meets Organs-on-Chip.
- Author
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Mattei F, Andreone S, Mencattini A, De Ninno A, Businaro L, Martinelli E, and Schiavoni G
- Abstract
Oncoimmunology represents a biomedical research discipline coined to study the roles of immune system in cancer progression with the aim of discovering novel strategies to arm it against the malignancy. Infiltration of immune cells within the tumor microenvironment is an early event that results in the establishment of a dynamic cross-talk. Here, immune cells sense antigenic cues to mount a specific anti-tumor response while cancer cells emanate inhibitory signals to dampen it. Animals models have led to giant steps in this research context, and several tools to investigate the effect of immune infiltration in the tumor microenvironment are currently available. However, the use of animals represents a challenge due to ethical issues and long duration of experiments. Organs-on-chip are innovative tools not only to study how cells derived from different organs interact with each other, but also to investigate on the crosstalk between immune cells and different types of cancer cells. In this review, we describe the state-of-the-art of microfluidics and the impact of OOC in the field of oncoimmunology underlining the importance of this system in the advancements on the complexity of tumor microenvironment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mattei, Andreone, Mencattini, De Ninno, Businaro, Martinelli and Schiavoni.)
- Published
- 2021
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49. A Bayesian Approach for Coincidence Resolution in Microfluidic Impedance Cytometry.
- Author
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Caselli F, De Ninno A, Reale R, Businaro L, and Bisegna P
- Subjects
- Bayes Theorem, Electric Impedance, Erythrocytes, Flow Cytometry, Lab-On-A-Chip Devices, Microfluidic Analytical Techniques, Microfluidics
- Abstract
Objective: Cell counting and characterization is fundamental for medicine, science and technology. Coulter-type microfluidic devices are effective and automated systems for cell/particle analysis, based on the electrical sensing zone principle. However, their throughput and accuracy are limited by coincidences (i.e., two or more particles passing through the sensing zone nearly simultaneously), which reduce the observed number of particles and may lead to errors in the measured particle properties. In this work, a novel approach for coincidence resolution in microfluidic impedance cytometry is proposed., Methods: The approach relies on: (i) a microchannel comprising two electrical sensing zones and (ii) a model of the signals generated by coinciding particles. Maximum a posteriori probability (MAP) estimation is used to identify the model parameters and therefore characterize individual particle properties., Results: Quantitative performance assessment on synthetic data streams shows a counting sensitivity of 97% and a positive predictive value of 99% at concentrations of 2×10
6 particles/ml. An application to red blood cell analysis shows accurate particle characterization up to a throughput of about 2500 particles/s. An original formula providing the expected number of coinciding particles is derived, and good agreement is found between experimental results and theoretical predictions., Conclusion: The proposed cytometer enables the decomposition of signals generated by coinciding particles into individual particle contributions, by using a Bayesian approach., Significance: This system can be profitably used in applications where accurate counting and characterization of cell/particle suspensions over a broad range of concentrations is required.- Published
- 2021
- Full Text
- View/download PDF
50. Accelerating the experimental responses on cell behaviors: a long-term prediction of cell trajectories using Social Generative Adversarial Network.
- Author
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Comes MC, Filippi J, Mencattini A, Corsi F, Casti P, De Ninno A, Di Giuseppe D, D'Orazio M, Ghibelli L, Mattei F, Schiavoni G, Businaro L, Di Natale C, and Martinelli E
- Subjects
- Algorithms, Cells cytology, Computational Biology methods
- Abstract
The incremented uptake provided by time-lapse microscopy in Organ-on-a-Chip (OoC) devices allowed increased attention to the dynamics of the co-cultured systems. However, the amount of information stored in long-time experiments may constitute a serious bottleneck of the experimental pipeline. Forward long-term prediction of cell trajectories may reduce the spatial-temporal burden of video sequences storage. Cell trajectory prediction becomes crucial especially to increase the trustworthiness in software tools designed to conduct a massive analysis of cell behavior under chemical stimuli. To address this task, we transpose here the exploitation of the presence of "social forces" from the human to the cellular level for motion prediction at microscale by adapting the potential of Social Generative Adversarial Network predictors to cell motility. To demonstrate the effectiveness of the approach, we consider here two case studies: one related to PC-3 prostate cancer cells cultured in 2D Petri dishes under control and treated conditions and one related to an OoC experiment of tumor-immune interaction in fibrosarcoma cells. The goodness of the proposed strategy has been verified by successfully comparing the distributions of common descriptors (kinematic descriptors and mean interaction time for the two scenarios respectively) from the trajectories obtained by video analysis and the predicted counterparts.
- Published
- 2020
- Full Text
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