4.8 Article

Bioelectronic organ-based sensor for microfluidic real-time analysis of the demand in insulin

Journal

BIOSENSORS & BIOELECTRONICS
Volume 117, Issue -, Pages 253-259

Publisher

ELSEVIER ADVANCED TECHNOLOGY
DOI: 10.1016/j.bios.2018.06.015

Keywords

Diabetes; Islets; Continuous glucose monitoring; Micro-electrode arrays; On-line real-time analysis; Field programmable gate array

Funding

  1. French National research Agency ANR [ISLET CHIP] [ANR-13-PRTS-0017]
  2. Aquitaine Regional Government
  3. Fonds Europeen de Developpement Regional [FEDER BIODIA 38352, FEDER DIAGLYC 3538510]
  4. Aquitaine Technical Transfer Office [SATT, DIABETACHIP]

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On-line and real-time analysis of micro-organ activity permits to use the endogenous analytical power of cellular signal transduction algorithms as biosensors. We have developed here such a sensor using only a few pancreatic endocrine islets and the avoidance of transgenes or chemical probes reduces bias and procures general usage. Nutrient and hormone-induced changes in islet ion fluxes through channels provide the first integrative read-out of micro-organ activity. Using extracellular electrodes we captured this read-out non-invasively as slow potentials which reflect glucose concentration-dependent (3-15 mM) micro-organ activation and coupling. Custom-made PDMS-based microfluidics with platinum black micro-electrode arrays required only some tens of islets and functioned at flow rates of 1-10 mu l/min which are compatible with microdialysis. We developed hardware solutions for on-line real-time analysis on a reconfigurable Field-Programmable Gate Array (FPGA) that offered resource-efficient architecture and storage of intermediary processing stages. Moreover, real-time adaptive and reconfigurable algorithms accounted for signal disparities and noise distribution. Based on islet slow potentials, this integrated set-up allowed within less than 40 ps the discrimination and precise automatic ranking of small increases (2 mM steps) of glucose concentrations in real time and within the physiological glucose range. This approach shall permit further development in continuous monitoring of the demand for insulin in type 1 diabetes as well as monitoring of organs-on-chip or maturation of stem-cell derived islets.

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