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ISLET CELLS AS BIOSENSORS (Diachip™; Dia▀sensor)

Sensors for artificial organs and rapid on-line diagnostics are major issues in regenerative medicine including diabetes. The introduction of electrochemical glucose sensors in type I diabetes has presented a major breakthrough in diabetes therapy. The continuous monitoring of glucose levels and injection of the corresponding amounts of insulin thus became feasible. However, this approach captures only part of the information the organism uses for physiological regulation of homeostasis. Within the body a group of specialized cells, the so-called alpha-, beta- and delta-cells, are arranged in a micro-organ to sense the nutrient levels and demand in the hormone insulin. Biological sensors, such as pancreatic islets, have been shaped during half a billion years of evolution and in contrast to currently available medical devices, they rely on a number of different relevant signals, not only glucose but also several hormones and nutrients other than glucose.

The integration of information about the presence of these molecules by pancreatic beta-cells subsequently provides a precisely tuned signal to regulate cellular actions, such as the release of the potent hormone insulin into the bloodstream. Islet cells, including beta-cells, are excitable cells similar as nerve cells. They relate signals by changing their electrical properties and this represents the first signal integration step in these cells. Therefore the electrical properties relate precisely the information obtained through different signals and reflects the activity of these cells and the demand of the body for insulin. Electrical signals can be captured by extracellular electrodes and the corresponding devices are easy to miniaturize and do not produce heat, considerations that are important in the case of implantation.

A device extracting information on the activity of beta-cells may serve as a novel sensor for the demand in insulin and regulate an insulin infusion pump in patients suffering from type 1 diabetes. Such a device may also bypass the shortcoming of currently used sensors, i.e. their incapacity to work in a closed-loop configuration and the ensuing requirement of complex algorithms and user interventions. Moreover, we propose that such a device may also serve rapidly to monitor the activity of islet-cells prior to their transplantation, in the field of tissue engineering to follow the differentiation of stem-cells into islet cells in a non-destructive manner or to be used in drug screening. We have previously shown the general feasibility of this approach that is capturing the electrical signals by the use of extracellular electrodes and extracting the relevant information on-line which reflects the ambient levels of glucose and hormones.

Our arrangement of smart MEAs will serve
- First as a device for as tool for cellular diagnostics and drug investigations (automated functional islet screening for pre-transplantation quality tests,        drug and toxicology tests, real-time analysis during regeneration of islet cells from stem cells).
- In the long-term we intend to extend this modular device to a low power implantable bio-microelectronic hybrid sensor of insulin demand.

diabchip



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Current prototype (Feb 2013):
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References:

Original work
Jeandidier N, Riveline JP, Tubiana-Rufi N, Vambergue A, Catargi B, et al. 2008. Treatment of diabetes mellitus using an external insulin pump in clinical practice. Diabetes Metab 34: 425-38
Raoux M, Bornat Y, Quotb A, Catargi B, Renaud S, Lang J. 2012. Non-invasive long-term and real-time analysis of endocrine cells on micro-electrode arrays. J Physiol 590: 1085-91
 
Book Chapters
Raoux M, Bontorin G, Bornat Y, Lang J, Renaud S. 2011. Bioelectronic Sensing of Insulin Demand. In Biohybrid Systems: Nerves, Interfaces, and Machines, ed. R Jung, pp. 191-202. Berlin: Wiley – VCH
 
Patent
Lang, J., B. Catargi, S. Renaud, M. Raoux, G. Charpentier, and Y. Bornat. 2011. SENSOR FOR MEASURING THE ACTIVITY OF BETA-PANCREATIC CELLS OR OF ISLETS OF LANGERHANS, MANUFACTURE AND USE OF SUCH A SENSOR, PCT/EP2011/050359
 

Communications with Proceedings
Bornat Y, Raoux M, Boutaib Y, Morin FO, Charpentier G, et al. 2010. Detection of electrical activity of pancreatic β-cells using micro-electrode arrays. Presented at 5th IEEE Int. Symposium on Electronic Design, Test & Applications - DELTA 2010, Ho Chi Minh City, VietNam
Quotb, Adam; Bornat, Yannick; Raoux, Matthieu; Lang, Jochen; Renaud, Sylvie. NeuroBetaMed: A re-configurable wavelet-based event detection circuit for in vitro biological signals. Circuits and Systems (ISCAS), 2012 IEEE International Symposium on , vol., no., pp.1532-1535, 20-23 May 2012
Quotb A, Floderer JB, Bollengier T, Fabre R, Bornat Y, Renaud S 2012. Real-time wavelet spike detection with in-vitro biological signals : the NeuroBetaMed setup. 2012. Biomedical Circuits and Systems Conference (BioCAS 2012), Taiwan (ROC).
 
Communications w/o Proceedings
Raoux M, Bornat Y, Quotb A, Catargi B, Renaud S, Lang J. 2012. Biocapteur hybride destinÚ au suivi fonctionnel Ó long terme et au criblage sur les ţlots de Langerhans. Diabetes & Metabolism
Lebreton F, Caro A, Quotb A, Gaitan J, Laloum J, et al. 2012. Multi-electrode arrays reveal glucose-dependent action potentials and slow waves that differ by their calcium sensitivity in mouse islet cells. Diabetologia
Raoux M, Bornat Y, Quotb A, Catargi B, Renaud S, Lang J. 2011. Hybrid bioelectronic sensor development for long-term functional screening on islets and insulin therapy improvement. Diabetologia 54: P480
Raoux M, Vacher P, Papin J, Chevallier S, Charpentier G, et al. 2010. A new noninvasive method for long-term study of cells - pancreatic islets and intact - Extracellular recording of electrical activity on micro-electrode arrays. Diabetes & Metabolism 36: A30-A

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