A low power miniaturized CMOS-based continuous glucose monitoring system

This paper presents the design and fabrication of a highly-miniaturized system for continuous glucose monitoring which holds great promise for patients inflicted with diabetes mellitus. To achieve the realization of a truly implantable system, a variety of issues such as robust electrochemical sensor design, miniaturization of the electronic components and counteracting biofouling and negative tissue response need to be addressed. In this report, we present a highly-miniaturized transcutaneous continuous glucose monitoring system which holistically addresses the aforementioned tribulations associated with implantable devices. Specifically, a high performance amperometric electrochemical glucose sensor is integrated with custom designed complementary metal-oxide-semiconductor electronics. The fabricated electrochemical sensor is Clark-based, and employs stratification of five functional layers to achieve a linear response within the physiological range of glucose concentration (2–22 mM). Furthermore, the sensor is encased with a thick polyvinyl alcohol (PVA) hydrogel containing poly(lactic-co-glycolic acid) (PLGA) microspheres which provides continuous, localized delivery of dexamethasone utilized to combat inflammation and fibrosis. Such miniature size (0.665 mm2) and low power operation (140 μW) of the electronic system render it ideal for continuous glucose monitoring devices and other metabolic sensing systems.

[1]  Rosa Villa,et al.  New technology for multi-sensor silicon needles for biomedical applications , 2001 .

[2]  Michael Gerstenberg,et al.  Biocompatibility of an enzyme-based, electrochemical glucose sensor for short-term implantation in the subcutis. , 2006, Diabetes technology & therapeutics.

[3]  Wisniewski,et al.  Methods for reducing biosensor membrane biofouling. , 2000, Colloids and surfaces. B, Biointerfaces.

[4]  Santhisagar Vaddiraju,et al.  Enhanced Glucose Sensor Linearity Using Poly(Vinyl Alcohol) Hydrogels , 2009, Journal of diabetes science and technology.

[5]  Fotios Papadimitrakopoulos,et al.  PLGA/PVA hydrogel composites for long-term inflammation control following s.c. implantation. , 2010, International journal of pharmaceutics.

[6]  Santhisagar Vaddiraju,et al.  Technologies for Continuous Glucose Monitoring: Current Problems and Future Promises , 2010, Journal of diabetes science and technology.

[7]  W. Clarke The original Clarke Error Grid Analysis (EGA). , 2005, Diabetes technology & therapeutics.

[8]  Syed K. Islam,et al.  A low power sensor signal processing circuit for implantable biosensor applications , 2007 .

[9]  Fotios Papadimitrakopoulos,et al.  Controlling Acute Inflammation with Fast Releasing Dexamethasone-PLGA Microsphere/PVA Hydrogel Composites for Implantable Devices , 2007, Journal of diabetes science and technology.

[10]  Pietro Valdastri,et al.  Wireless implantable electronic platform for blood glucose level monitoring , 2009 .

[11]  P Atanasov,et al.  Integrated implantable device for long-term glucose monitoring. , 1995, Biosensors & bioelectronics.

[12]  Boris P Kovatchev,et al.  Graphical and numerical evaluation of continuous glucose sensing time lag. , 2009, Diabetes technology & therapeutics.

[13]  G. S. Wilson,et al.  Biosensors for real-time in vivo measurements. , 2005, Biosensors & bioelectronics.

[14]  Yan Wang,et al.  Design and Fabrication of a High-Performance Electrochemical Glucose Sensor , 2011, Journal of diabetes science and technology.

[15]  G. S. Wilson,et al.  Protein interactions with subcutaneously implanted biosensors. , 2006, Biomaterials.