A selection of patents

Biodegradable micro-needle for transdermal drug delivery and the 3D printing method to realize the device

S. Coppola, R. Vecchione, E. Esposito, C. Casale, V. Vespini, S. Grilli, P. Ferraro, P. Netti, “Electro-drawn drug-loaded biodegradable polymer microneedles as a viable route to hypodermic injection” Advanced Functional Materials 24, 3515-3523 (2014).

Hypodermic needle injection is still the most common method of drug delivery despite its numerous limitations and drawbacks, such as pain, one shot administration, and risk of infection. The technology proposed can be used for the fabrication of arrays of micro-needles made by biodegradable materials. The process  developed  possesses great flexibility in shaping sharp biodegradable microneedles with the mechanical properties needed for indentation. The micro-needles are formed directly onto a flexible patches, a disposable strip that is inserted into a cuff, overcoming the technological limitations of both microcasting and drawing lithography and opening new frontiers in the field of transdermal delivery. Upon stimulation, the cartridge of drug-encapsulated, biodegradable polymer microneedles, is able to deliver into hypodermic tissue both hydrophobic and hydrophilic bioactive agents, according to a predefined chrono-programme. The  proposed method overcomes all the limitations deriving from the micro-casting and the drawing lithography approach, since no hazardous temperatures, no multi-step filling process and no UV are required. In fact, biopolymers are processed directly from solution at room temperatures and are shaped directly into microneedles in a single step. This is a further advantage respect to the conventional technique where the temperature involved in the process is usually high, widening the types of drug that could be inserted in the polymeric needle. The method proposed is fast, simple, repeatable, contact-free, it avoids the use of moulds allowing the fabrication of biodegradable polymer microneedles into a ready-to-use configuration. TRL 3 – experimental proof of concept

EP2956203A2, US20150374966A1, US 9221047 B2 

Contact email  ipr.dsftm@cnr.it , p.ferraro@isasi.cnr.it ,  sara.coppola@cnr.it

3D Microstructured Substrates for Culturing Stem Cells

Cell-based therapies represent an important strategy to restore the function of injured cells, tissues and organs. However, the limited availability of functional cells has hampered the success of this strategy. The recent advances in stem cell biology offer an opportunity to address this challenge. Embryonic stem (ES) cells have a great potential because they can proliferate indefinitely and, at the same time, retain the developing potential to generate cells of all three embryonic germ layers. However, ES cells do not maintain their pluripotency during expansion passages on standard plastic culture, but tend to differentiate spontaneously. A feeder layer or different growth factors, are routinely used to counteract spontaneous differentiation and to promote ES cell self-renewal. Such feeder has been the major obstacle to obtain clinically significant cells due to safety issues (e.g. pathogen contamination, immunogenicity of the feeder layer), difficulty in quality control, and high expense. A great challenge lies in identifying simple, repeatable, cost-effective, and optimum substrates capable of feeder- and serum-free culture conditions of stem cells.

Our invention consists in the fabrication of 3D microstructured substrates for the expansion of stem cells while keeping their pluripotency. The microstructuring is produced by two-photon polymerization, an additive manufacturing technique based on femtosecond laser irradiation, that can produce structures at the nano/micro-scale. A 3D scaffold with an engineered layout is fabricated on a glass substrate, covering most of its surface. The implemented scaffold is a matrix of artificial niches that induce a physical confinement to the stem cells as that experienced in physiological niches. Thanks to the 3D layout of the scaffolds, we have proven that stem cells can proliferate without differentiating.

Italian patent n° 102015000048704,  PCT/EP2016/070500

Contact email  ipr.dsftm@cnr.it , roberto.osellame@ifn.cnr.it

Detecting the concentration of combustion products emitted by internal combustion engines

M. Mello, M. De Vittorio, A. Passaseo, M. Lomascolo, A. de Risi, “Optical system for CO and NO gas detection in the exhaust manifold of combustion engines” Energy Conversion and Management 48 (2007) 2911–2917.

The real-time control of gas emitted by internal combustion engines, is a well-known problem in the automotive field. The possibility of a real-time feedback and control adjustment of the combustion parameters inside the combustion chamber would allow the optimisation of the entire process, also in transient condition. Nowadays the only sensor mounted on vehicles is the lambda-sensor, that allows the real-time O2-control, while the emission control COx and NOx exhausted gases is done in a labs or garages, where chemiluminescence and absorption instruments are used. Today testing regulated by the European Union is based on CO2 and Pollutants (substances like CO, HC, NOx and particles) to ensure cars do not emit over the limits allowed. After the Dieselgate, new test will be complemented by the ‘Real Driving Emissions’ (RDE) test to ensure that vehicles deliver low pollutant emissions, not only in the laboratory but also on the road. WLTP (Worldwide Harmonised Light Vehicle Test Procedure) will apply for new types of cars from September 2017 and for all car registrations from September 2018.

The invention relates to a new optical system able to detect the concentration of gaseous species, and more specifically combustion products. A working prototype implements the invention of a new optical sensor for exhausted gases, such as COx and NOx and O2, which overcomes the disadvantages of the known current techniques. It is resistant to high temperatures and permits real-time monitoring of the parameters in a combustion process. It is based on the photodetection of said products, adopting some particular nitride compounds as active material. The operating temperature of the sensor preferably lies between 400°C and 700°C, but the resistance of the active material permits to be used at even higher temperatures. This system can be used to measure the concentration of chemical species present in combustion products directly at their outlet, where its high operating temperature makes it possible to avoid fouling of the sensor caused by carbonaceous and non-carbonaceous deposits.

EP 1749200 B1 , US 7543565 B2

Contact email  ipr.dsftm@cnr.it , adriana.passaseo@nanotec.cnr.it