Funded research program participation

MIMLIVER ON CHIP

MIMLIVER on CHIP project coordinated by the laboratory of Biomechanics and Bioengineering from UTC/CNRS aims at developing a functional liver-on-chip system to evaluate the toxicity of drugs. It is motivated by the established observation that 90% of potential drug candidates fail in clinical trials due to the lack of relevant models in the early drug development stages. The Liver is a central organ for toxicology assessment as it metabolizes the drugs into compounds that can be more active than the parent drug itself. Prior to being metabolized by hepatocytes, drugs are first filtered across an endothelial barrier which is typical of the liver. This selective barrier loses its properties in pathological conditions.

MIMLIVER on CHIP project Kick Off

• October 18, 2019

Fluigent and our collaborators are pleased to announce that the 1.5 M€ project: MIMLIVER on CHIP has been funded by the French National Research Agency.

This project coordinated by the laboratory of Biomechanics and Bioengineering from UTC/CNRS aims at developing a functional liver-on-chip system to evaluate the toxicity of drugs.

This project is motivated by the established observation that 90% of potential drug candidates fail in clinical trials due to the lack of relevant models in the early drug development stages. The Liver is a central organ for toxicology assessment as it metabolizes the drugs into compounds that can be more active than the parent drug itself. Prior to being metabolized by hepatocytes, drugs are first filtered across an endothelial barrier which is typical of the liver. This selective barrier loses its properties in pathological conditions.

In order to produce more reliable results in preclinical development, the MIMLIVERonCHIP project aims at developing the first in vitro model that reproduces both the liver and its associated vascular system.

Participating in this project are 4 partners with complementary expertise:

• The laboratory of Biomechanics and Bioengineering who have already developed and validated a liver on chip model. They will lead the development the endothelial cell chip and its connection to the liver chip.
• The Laboratory of Integrated Micro Mechatronic Systems who have strong expertise in endothelial cells, angiogenesis and vascular networks. They will grow primary endothelial cells and drive their growth into a relevant cell layer representative of the liver’s vascularisation.
• HCS Pharma is a CRO specialized in the development of innovative 2D and 3D cellular models for pharmacology and toxicology. They will validate the final liver-on-chip model by evaluating the effect of known substances and benchmark it with existing techniques.
• Fluigent will develop an automated instrument that will meet pharma standards in terms of throughput, automation, connection, compactness and ease of use.

The kick-off meeting took place on the 3^rd of October. This project is very innovative and we expect to find significant results on the co-culture of the hepatocytes and LSEC (Liver Specific Endothelial Cells) on our way to the final report.

MYOCHIP FETOPEN PROJECT

The aim of the MyoChip project is to build a 3D human skeletal muscle irrigated by vasculature and innervated by neurons. The reconstituted 3D muscle will mirror the architecture and function found in vivo, namely in shape, contractility and microenvironment, while irrigation by a vascular network and innervation by human motor neurons will bring additional physiologic pertinence to it. This organ-on-a-chip technology will have numerous applications including but not limited to research on muscle building and aging, drug testing and screening, as well as prosthetics and biorobotics. The feasibility of the project relies on the interdisciplinary approach which joins a team of cell biologists, material engineers, experts in microfluidics and mathematical modellers. The architecture of skeletal muscle and its regenerative capabilities make muscle a prime candidate to push the 3D tissue engineering field. As such the project will lay the technical, material and methodological foundations to tackle the next generation of complex organ-on-a-chip systems that the MyoChip consortium can exploit for the generation of highly complex 3D in vitro systems of many organs.

BIO-ART LUNG 2020

The BIOART-LUNG 2020 project aims to develop a long term, autonomous, portable, artificial lung for patients suffering from acute respiratory distress. This innovative therapeutic approach will provide 2 major advantages compared to existing extracorporeal membrane oxygenation:

• Portable device that will increase mobility of patients while waiting for lung transplantation surgery
• Physiologically relevant device which would reduce blood activation and extended blood oxygenation above the current three weeks limitation.

To validate intermediate steps, Fluigent has conceived, developed and made a customized fluidic platform connected to the device that integrates all the functions the final system will have. This fully automated platform allows for testing of the devices under realistic conditions.

HOLIFAB

Microfluidics is currently faced with 2 main difficulties:

• A considerable hindrance to fast prototyping and industrialisation, because system performances rely on complex selection and assembly of numerous fluidic, mechanic, optical, electronic (etc…) components,
• A complex process for setting the system requirements, because constraints and specifications of microfluidic systems cover a huge range in terms of complexity level, materials, dimensions, acceptable costs, without any standardisation and rationalisation of design and production.

The HoliFAB project aims at overcoming these difficulties with a holistic system-oriented and problem-solving approach, starting from the customer’s need, optimising the chip and addressing the question of its environment.
HoliFAB change of paradigm implies:

• A holistic approach at the instrument level: Providing new methods and production tools to instruments manufacturers and new generation of applications to users,
• A holistic approach for the chip production: Using a technology-agnostic strategy integrating both 3D printing and injection moulding technologies for the design of the microfluidic chip.

INDEX

The aim of Project INDEX is to isolate and characterize nanoparticles available in bodily fluids through development and integration of novel technological breakthroughs. The technology will enable the analysis of clinically valuable nanoparticles called exosomes towards new generation diagnostics. Exosomes are known to mediate communication between cells and their effective utilization holds a great promise of revolutionizing the standard of clinical care. However, their detection and molecular profiling is technically challenging. The proposed technology will isolate exosomes that are as small as 30nm in diameter from human plasma with high purity, and provide in-depth, multi-parameter characterization of the particles through digital counting, size determination, and biological phenotyping.

Towards this goal: (1) Novel microfluidics will be developed and used for efficient magnetic enrichment; (2) Isolated particles will be detected and analyzed with a novel biological nanoparticle (BNP) sensor (3) Immune-capture and release chemistries as well as phenotyping assays will be developed; (4) Critically, complete on-chip integration of isolation, detection and analysis will be accomplished; (5) Utility of in-depth exosome characterization will be demonstrated with clinical samples for lung cancer.

Project INDEX requires successful integration of multiple sub-units and assays that each represents technological frontiers, which is extremely challenging. However, the breadth of information on exosomes that will be available with the integrated system is unmatched. Although, the clinical utility of exosomes is still developing, the uncertainty can only be clarified through automated technologies that provide latitude of information. Once completed, Project INDEX can demonstrate a new paradigm in cancer diagnostics, and also present a potential future technology for other applications involving nanoparticles.

MFMANUFACTURING

The objective of the MFManufacturing project is to bring the manufacturing of microfluidic devices to the same level of maturity and industrialisation of electronic devices, enabling them to address more widely in the healthcare needs. Electronic devices, which have been on the market for many years, have benefited from the long going standardization of electronic components, and were therefore easily integrated in the production process of the major foundries.

The anticipated standardization in the microfluidics field – first of all aimed at strengthening Europe’s position will focus on increasing maturity of both functional and fabrication process aspects:

• Gain of maturity in MF functions focusing both on novel functional modules and their interoperability.
• Gain of maturity in manufacturing process: focusing on a distributed pilot line, on novel hybrid integration processes and on increasing maturity of some selected manufacturing processes, which have a good short term commercial perspective.

This will have an effect on availability, reliability as well as accessibility and will result in device cost reduction and improved time-to market. These conditions will enable large scale uptake of microfluidic devices in the markets identified.