Droplet-based Textile Microfluidics for High-Throughput Organoids Screening
The project aims to develop a new type of platform for screening from cellular spheroids. This platform is based on the microfluidic technology of drops, or more precisely of «plugs«, i.e. drops strongly confined in a cylindrical channel. Each channel contains a «train« with several series of drops containing successively cells, drug and reagent, to perform a high throughput screening. To allow a low cost production, it is planned to manufacture the cartridge by a «textile microfluidic« technique. As a backup, an option based on a cartridge made from tubes, less risky, has also been planned. At the application level, we aim to perform a screening of anticancer drugs on cancer cell spheroids (tumoroids). More specifically, we are first addressing lines, then cells from patients («PDX«), in the field of pediatric cancers. <br /><br />Translated with www.DeepL.com/Translator (free version)
Le projet combine deux innovations: d'une part, le fait d'effectuer un criblage de médicaments sur des sphéroides 3D (ici des sphéroides tumoraux ou «tumoroides«), dans un format de microfluidique de gouttes (gouttes fortement confinées ou «plugs«.; D'autre part, une méthode de babrication à bas coût de cartouches microfluidiques, combinant la microfluidique et les techniques de fabrication textile, pour la fabrication de canaux cylindriques. la méthode est validée par criblage de l'effet de drogues anticancéreuses sur des tumoroides de lignées cellulaires et de PDX.
Overall, the project is progressing according to the initial schedule, with even a little advance on certain items. This is notably the case for the prototype and developments relating to cell culture, for which we have been able to establish viability curves (IC50) that are consistent with conventional techniques. The developments in the textile field have, on the other hand, led to contrasting results: the weaving technologies and the development of the impregnation pilot have progressed well, and have made it possible to obtain pilot «chips«. However, difficulties have been encountered with imaging (MS2, M18 milestones), which is hampered by the fibers, and with interfacing.
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It was decided to activate the «mitigation strategy« of «extruded tube arrays«, foreseen in the program, in order to ensure an operational system within the deadline. We also switched to a syringe pump flow control (MS1, M18), to maximize the compatibility with the Inorevia platform, and thus the chances of a commercial product. These choices were planned as options (see table 2 of the project), and therefore do not constitute a major change in the content of the project. For the moment, no change in the schedule is envisaged either. The developments concerning the imaging in textile chips are continued in parallel.
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International conference : ITC Stutgart 2021 (on-line)
Quentin WATEL, Anissa KADDOUCHE, Ya ZHOU, Aurélie CAYLA, Fabien SALAUN, Jean-Louis VIOVY, François BOUSSU, Microfluidic Textile solution for cancer treatment detection, International textile Conference (on line), Stutgart, Germany, November 9 - 10, 2021
Fast progress in genomics and cell biology is uncovering the complexity of the mechanisms underlying diseases and aging. The application of this new understanding in health, however, raises stronger and stronger technological challenges. This slows down the current pace of progress, and leads to an explosion of costs in pharmaceutical research, and to increasing difficulties to choose the right treatment among a constantly increasing choice of possible drugs and therapeutic options. This diversification let to the concept of “precision” or “personalized” medicine, aiming at selecting the best treatment for each patient using a more and more detailed characterization of his/her specific pathology, at the molecular and cellular level.
The DROMOS project aims at helping the development of more powerful, more specific and less costly diagnosis and treatments, by combining two innovative technological fields. The first is “organoids”: it consists in growing, from cells from patients or stem cells, 3D cellular aggregates reproducing the structure of tissues. On can then use them to test drugs, in a more powerful and less expensive way than with previously used animal models. The second technological field is microfluidics: microfluidic systems can be seen as “microprocessors” able to manipulate minute fluid volume, as conventional microprocessors manipulate information. Microfluidic devices allow to considerably increase the number of tests feasible with a sample, and to accelerate testing. Unfortunately, so far the wide transfer of these technologies to daily life was hindered by their cost and their complexity. The project will overcome this limitation using a new technology “Free Flow Textile Microfluidics”, allowing the mass-production of integrated and low-cost microfluidic systems, by textile technologies. These systems use a combination of innovations by the partners, which allow the integration of complex fluidic architectures and functionalities within the textile “chip”. A preliminary study has validated an original approach, in which hundreds of organoids can be cultivated within droplets prepared in the textile chip, and tested individually against various drug combinations. This approach will find applications e.g. in pharmaceutical research or in precision medicine.
The project will develop in parallel the textile microfluidic chips and the instrument allowing their operation and the implementation of assays. This will be followed by a biological and clinical validation, and finally by the development of a commercial instrument, to transfer as fast as possible the project’s results to patients and the society. Validation will focus on a specific problem: the screening of drugs against pediatric cancers. The textile microfluidic technology is very generic, however, and it will be applicable to a number of other biomedical problems, such as the diagnosis of infectious diseases, regenerative medicine or patient’s follow-up by “intelligent” clothing.
This interdisciplinary project will involve close collaboration between: the microfluidics laboratory MMBM, affiliated to Curie Institute, CNRS and IPGG (Pierre-Gilles de Gennes Institute, first European institute fully dedicated to microfluidics); the GEMTEX laboratory of ENSAIT (National Superior School of Textile Arts and Industries), a European leader in textile innovation; the Clinical and fundamental research laboratory U830 Institut Curie/INSERM, who will develop biological and clinical aspects and testing; and finally the biomedical startup INOREVIA, who will develop the pre-industrial prototype, and prepare industrialization and commercialization of the technology after its validation within the project.
Monsieur Jean-louis Viovy (Unite physico-chimie Curie, UMR168)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
CHIP INSTITUT CURIE - SECT DE RECHERCHE
PCC Unite physico-chimie Curie, UMR168
GEMTEX GEnie des Matériaux TEXtiles
Help of the ANR 697,373 euros
Beginning and duration of the scientific project: - 42 Months