The framework of our 3-years’ project encompasses the synthesis and engineering of bistable, nano-patterned metal-organic-framework (MOF) materials with predictable and controllable physical properties. To this aim, MOF thin-films will be designed, synthesized and patterned on surfaces using various state-of-the-art methods. These nano-objects will be functionalized through the spin-crossover (SCO) properties of the bulk materials that can be maintained in miniaturized systems. Our project seeks to explore the spin-state switching phenomena, triggered by chemical stimuli, and associated optical properties in these nano-objects from both fundamental and applied scientific points of view in a multidisciplinary integrated approach. These nanostructures have the perspective to attain industrial applications, in particular that for (1) chemical sensors based on optical detection, and - at a more exploratory level - in (2) switchable photonic devices (filters, waveguides, addressable gratings, …). The initial results have convinced an SME (Innopsys SA) to participate in this project so as to ensure that it seeks to develop high added-value products for sensor applications.

Biosoft is a joint research lab from Occitanie region associating an academic research team of LAAS-CNRS institution (Laboratory for Analysis and Architecture of Systems of French National Research Center) and SME Innopsys. It is an original Public/Private partnership, where we develop new methods of soft lithography (mainly Micro-Contact Printing) for the biomedical field. Micro-Contact Printing allows to deposit biomolecules of interest along micrometric patterns on any analytical supporting substrate. For the research team of LAAS, this labcom aimed at transferring some research processes and to deploy them for specific applications in biology and medical diagnostic. For Innopsys company, this joint lab targeted a diversification of its commercial products and a new strategic orientation towards instruments dedicated to the fabrication of micro-patterned analytical substrates with highly relevant biological content. The joint program focused around the Innostamp instrument, a semi-automatic system of Micro-Contact Printing, allowing the printing of biomolecular features on analytical slides with a sub-micrometric accuracy. We have explored, with an industrial vision, all the benefits offered by this technology and this instrument in the biomedical field. We have developed a competitive technology for the biofunctionalization of biochips and biosensors from the micrometric to the nanometric scale. After the first period of activity of this joint lab (2014-2016) we have strategically oriented our innovation towards the fabrication of Cell Micro-Arrays (CMAs), for which a growing market exist centered on academics and industrial end-users of the pharmaceutical field. The instrument at the core of our joint lab indeed enables the fabrication of very competitive CMAs (Solid supports on which living cells can be deterministically immobilized in a precise, reproducible and controlled manner). For this purpose, a dedicated automated Micro-Contact Printing process has been developed in order to print patterns of proteins of the Extra Cellular matrix of cells. In this consolidation phase of our joint lab our objective will be to qualify the instruments in term of quality and reproducibility, to adapt the process to different supports used nowadays in cellular biologie (titration plates, glass slides, hydrogels thin layers) and to apply this process in collaboration with prestigious biological teams to original problematics of current cell biology. At the end of this consolidation phase, we hope to demonstrate : - The advantages of our fabrication system with respect to concurrent solutions - The versatility of our process with respect to some specific issues interesting our "end-users" guests - The acceptation of our technology by some research teams acting as key opinion leaders in the field - the complementary of the instruments commercialized by Innopsys along the whole value chain (Innostamp for the production of the CMAs and Innoscan for their characterization at high throughput.

The recurrence of the kidney stones (or urinary lithiasis) increases in all industrialized countries implying an increasing cost for healthcare systems. In this project, we propose to reduce it by developing a new connected auto-test monitoring the urinary composition. This device is composed of two modules. The first one is based on colorimetric and refractometric sensors enabling a long term nutrition follow-up to prevent the fabrication of kidney stone formation. Therefore, it is of particular importance for the patient to understand and measure the impact of its food on its stone recurrence risk.The second one is a turbidimetric sensor (more precisely we will use nephelometry) used as a short term warning system. It will detect the first steps of kidney stone formation by quantifying the crystals in urine (named crystalluria) through the turbidimetric measurement. The coupling of these two modules (short and long-term prevention) is the main innovative feature of the proposed system. The second point is that the analyses are carried out at home at an affordable cost by the general public. A software application enables the patient to access to the analyses follow-up and to contextualize its data. As the generated data are classified as health data, their security will be taken into account throughout the instrumental and software chain. The first objective of this project is to develop a urinary auto-test with a high reliability compatible for urinary lithiasis prevention. The second objective is to show that the biomarkers integrated into the device are relevant for early detection of an increased risk of kidney stone production and alerting the patient to this fact, which can very quickly modify his diet. The third objective is to prove that this auto-test can be integrated into a long-term prevention by detecting the causes of the urinary lithiasis, coaching the patient about his food and improving the interaction between the doctor and the patient. To this end, the various technologies (nephelometry, colorimetry and refractometry) will be developed separately and then integrated, for the first time, into a single, portable device. The latter will then be validated by comparing it with reference methods applied in hospitals in the context of laboratory handling and then in real situations. In the latter case, the prototypes developed will be handled by users who have no link with the project, thus allowing their operational validation. The first expected impact of the URITRACK project in the long term is to reduce the severe pain caused by renal colic to patients. Indeed, reducing the recurrence of kidney stones reduces the occurrence of these kidney attacks, which are known to cause one of the most severe pain. The second impact concerns reducing the cost of this disease by targeting an innovative and effective preventive strategy. Indeed, the trend in industrialized countries is towards an increase in the costs generated by kidney stones due to increased prevalence and incidence. The origin of this evolution is mainly in the diet, which requires nutrition education and is the main objective of this project. Finally, the third expected impact is to allow epidemiological monitoring studies of this disease by public authorities and the medical community, following anonymization of the data.

This project comprises two innovative aspects : A new label free method to detect biomolecular interactions based on light diffraction that uses the latest developments in nanotechnology; and the application of such method to the development of new microRNA and protein biochipsA new detection methodBiochip technology has been used mainly in laboratories for research purposes. However, this technology is expected to expand in the near future to the diagnostic field. In most cases, fluorescence-labelling of the samples to be analyzed on biochips is the method of choice to measure biomolecular interactions. Fluorescence labelling greatly adds to the costs of biochip processing, hampering the implementation of diagnostic biochips as routine tests in hospitals and health care centers.The present project aims at developing a new detection method of biomolecular interactions without a need for fluorescence labelling. This innovative method relies on a light diffraction procedure from a biomolecular grating structured at the nanoscale by soft lithography.Diffraction based detection relies on the patterning of the probe that will recognize the target molecules into a periodic grating. Such grating diffracts incident light at specific angles determined by the light wavelength and the inverse of the pitch (periodic distance between two identical structures). If a probe-target complex is formed, the diffracted intensity will change.New microRNA and protein biochips for cancer diagnosisDetection of cancer-derived proteins present in bodily fluids or detection of cancer-associated microRNAs constitute direct ways to diagnose a number of cancer types. Simultaneous detection of multiple such proteins or microRNAs by means of biochips (microarrays) results in an enhanced diagnostic power. Our goal is to apply light diffraction technology to the detection of interaction between probes on the biochip (antibodies or oligonucleotides) and cancer-derived products (proteins or microRNAs, respectively).Economic impact :Innopsys is an SME developing biotechnology instrumentation. Its last product is a scanner for biochip. The development on diffractive detection has been defined as a priority program with the objective of having a new biochip platform to be commercialized in three years. A doctoral studend has already started to work on this project in collaboration with the LAAS. The result of this technology transfer from LAAS to Innopsys will be a new highly competitive biochip platform that will a have a huge economic impact for Innopsys by increasing its sales and technology portfolio.Proteomika designs and produces antibody biochips (microarrays) for the detection of cancerderived proteins. Detection of antibody-protein interactions relies on fluorescence labeling, often a costly procedure. By using light diffraction as a detection method Proteomika expects to reduce expenses and consequently, reduce the price of its products, which in turn is expected to result in a wider implementation of its diagnostic systems in the clinic.Actigenics designs and produces microRNA biochips together with the Biochip platform (PBGT), for the detection of molecular biomarkers involved in disease tissues (cancer, immune diseases).MicroRNA detection using current labeling fluorochrome methods has some limitations. Indeed one of the major challenges in microRNA detection is the fact that microRNA only represent 0.1% of total RNA, which requires at least 5ug of total RNA to start with. By using light diffraction we expect to reduce both the costs associated to current labeling methods but also to increase sensitivity and allow for the development of novel microRNA chips able that need lower quantities of microRNA.More precise and cost-effective diagnostic methods will also result in a reduction in patient management costs, and therefore in a direct benefit for health care systems.