ISLET CHIP: Quality Control of Islets for Transplantation – ISLET CHIP

1. Design and assess the biosensor based on our existing prototype with improvement of the commercial micro-electrodes, design of microfluidics and experimental validation
2. Conceive data synopsis by designing algorithms to extract relevant information in the signals recorded from MEAs, implement real-time processing of multiple and parallel channels, asses the validity of obtained data by modeling in an in-silico patient, and design a read-out summary with diagnostics on the characteristics of islet preparations
3. Provide aliquots (ca. 0.1%) of transplantable islets for multi-parametric analysis either on the current prototype (DiaBchip in Bordeaux) or on ISLETchip and gather patient data
4. Validate the experimental platforms and protocols, provide hands-on training of clinicians to ISLETchip usage, perform user acceptance testing and feedback to designers. This step will provide technology transfer and distribution of the ISLETchip system to the clinical laboratories.
5. Examine data for correlation of parameters with clinical outcome

As a major outcome, this multi-parametric approach will allow objective quality control to enhance the success in transplantation and may establish a widely used standard. It shall first help to monitor and improve islet preparation.

Second, it will provide an objective criterion for the use of preparations in transplantation and finally it may provide criteria to predict clinical outcome . Thus, the deliverables (ISLETchip and correlative study) are destined to improve patient care in this area of transplantation medicine (but are not phase I !). The approach will remain valid in the case transplantations will be performed using stem-cells as similar functional quality controls should be applied. Our approach will also advance algorithms in the field of continuous glucose monitoring.

The approach has been patented three years ago and we will decide on the precise further dissemination in agreement with all partners and with the SATT Aquitaine (University Technical Transfer Office) especially in view of potential licensing to an industrial or creation of a start-up.

Destruction of pancreatic beta-cells leads to absolute insulin deficiency in type 1 diabetes and concerns some 15 to 30 million patients. Chronic insulin treatment is mandatory and transplantation represents one therapeutic choice in patients with serious progressive complications of diabetes. Islet cell transplantation is still under development and currently no method has been established to test and evaluate the quality of the islets and their preparation within the short time span (few hours) prior to their transplantation.

Our project bridges this important gap in a multidisciplinary approach (diabetology-transplantation medicine/biology-electrophysiology/microelectronics) from bench to bed and bed to bench implying two research groups from CNRS laboratories (Bordeaux), two clinical groups in France (Grenoble, Montpellier) and a third one in neighboring Switzerland (Geneva). The project is innovative, as it employs a novel bio-sensing approach (extracellular recordings of islets on multi-electrode arrays) and relies on real-time data filtering and time-frequency analysis we developed recently and that is capable to provide an extensive analysis in a short time span. The project addresses technological, biological and signal processing challenges that will be of benefit for other biosensor applications, for example rehabilitation of neuronal motor control.
The device (ISLETchip) delivered during the project will be able to examine in-vitro a small aliquot (<0.1%) of the islets preparation to be transplanted, to conduct a multi-parametric on-line real-time analysis and to display a diagnostic read-out prior to transplantation. Moreover, the use of such a device will be compatible with the degree of specialization of a general clinical laboratory. Systematic exchange between clinical and fundamental groups will ensure that specifications are exchanged and adapted to the clinical needs. We will provide such a novel bio-microelectronic device for the Health Sciences based on our recently published proofs of principle including an international patent.

Within the work packages we will:
1. design and assess the biosensor based on our existing prototype with improvement of the commercial micro-electrodes, design of microfluidics and experimental validation
2. conceive data synopsis by designing algorithms to extract relevant information in the signals recorded from MEAs, implement real-time processing of multiple and parallel channels, asses the validity of obtained data by modeling in an in-silico patient, and design a read-out summary with diagnostics on the characteristics of islet preparations
3. provide aliquots (ca. 0.1%) of transplantable islets for multi-parametric analysis either on the current prototype (DiaBchip in Bordeaux) or on ISLETchip and gather patient data
4. validate the experimental platforms and protocols, provide hands-on training of clinicians to ISLETchip usage, perform user acceptance testing and feedback to designers. This step will provide technology transfer and distribution of the ISLETchip system to the clinical laboratories.
5. Examine data for correlation of parameters with clinical outcome

As a major outcome, this multi-parametric approach will allow objective quality control to enhance the success in transplantation and may establish a widely used standard. It shall first help to monitor and improve islet preparation. Second, it will provide an objective criterion for the use of preparations in transplantation and finally it may provide criteria to predict clinical outcome . Thus, the deliverables (ISLETchip and correlative study) are destined to improve patient care in this area of transplantation medicine (but are not phase I !). The approach will remain valid in the case transplantations will be performed using stem-cells as similar functional quality controls should be applied. Our approach will also advance algorithms in the field of continuous glucose monitoring.