A miniaturized transcutaneous system for continuous glucose monitoring

Abstract

Implantable sensors for continuous glucose monitoring hold great potential for optimal diabetes management. This is often undermined by a variety of issues associated with: (1) negative tissue response; (2) poor sensor performance; and (3) lack of device miniaturization needed to reduce implantation trauma. Herein, we report our initial results towards constructing an implantable device that simultaneously address all three aforementioned issues. In terms of device miniaturization, a highly miniaturized CMOS (complementary metal-oxide-semiconductor) potentiostat and signal processing unit was employed (with a combined area of 0.665 mm2). The signal processing unit converts the current generated by a transcutaneous, Clark-type amperometric sensor to output frequency in a linear fashion. The Clark-type amperometric sensor employs stratification of five functional layers to attain a well-balanced mass transfer which in turn yields a linear sensor response from 0 to 25 mM of glucose concentration, well beyond the physiologically observed (2 to 22 mM) range. In addition, it is coated with a thick polyvinyl alcohol (PVA) hydrogel with embedded poly(lactic-co-glycolic acid) (PLGA) microspheres intended to provide continuous, localized delivery of dexamethasone to suppress inflammation and fibrosis. In vivo evaluation in rat model has shown that the transcutaneous sensor system reproducibly tracks repeated glycemic events. Clarke’s error grid analysis on the as –obtained glycemic data has indicated that all of the measured glucose readings fell in the desired Zones A & B and none fell in the erroneous Zones C, D and E. Such reproducible operation of the transcutaneous sensor system, together with low power (140 μW) consumption and capability for current-to-frequency conversion renders this a versatile platform for continuous glucose monitoring and other biomedical sensing devices.

A Highly Miniaturized Low-Power CMOS-Based pH Monitoring Platform

“…The Ag/AgCl quasi-reference electrode, which is a well-known and FDA approved reference electrode [28], was then fabricated by coiling silver (Ag) wire in close proximity to the working electrode, followed by converting the surface to AgCl via galvanometry (at 0.4 V vs. standard calomel electrode for 5 min) in a stirred 0.1 M HCl solution [8], [27]. The resulting sensor has a radius and length of ca.…”

“…More specifically, implantable devices for continuous glucose [7], [8], [11]- [13], lactate [14] and oxygen [11], [15], [16] monitoring have started to emerge due to the coupling of advanced electrochemical sensors with complementary metal-oxide semiconductor (CMOS)-based circuits [8], [17]- [19] to attain extreme miniaturization and reduce the overall power consumption of the implantable system. This interdisciplinary integration of miniaturized chemical and biological sensors with CMOS microelectronic devices is proving to address the core issues of 1530-437X © 2014 IEEE.…”

Biosensor Design with Molecular Engineering and Nanotechnology

“…For all in vivo measurements, the implanted device perturbs the environment initiating an inflammatory response in the host [89]. Significant efforts have been made to minimise this in biosensors for intravascular and subcutaneous application [86,91]. Three different processes can give incorrect analytical results for sensors implanted within the vasculature using a catheter.…”

“…In addition, the biocompatible material should be free from cytotoxic, irritant, sensitising and carcinogenic effects. Polyurethane, Nafion, cellulose acetate, various hydrogels, surfactants, polytetrafluoroethylene, polyvinyl chloride and other materials have been used with varying degrees of effectiveness [89,91]. Kerner et al [94] proposed polyurethane as an outer protective membrane for glucose biosensor and showed the ability to monitor glucose for up to 7 h. Poor performance was associated with loss of sensitivity of the sensor caused by low molecular weight substances from the sample diffusing across the polyurethane biocompatible coating.…”

“…Another interesting approach to minimise the foreign body response to the implantable sensor was employed by Croce et al [91]. It is speculated that the by-product of the catalytic reaction between the enzyme and the glucosehydrogen peroxide -is released from the implantable sensors at a dosage that enhances the foreign body response.…”