A MEMS viscometric sensor for continuous glucose monitoring

We present a MEMS sensor aiming to enable continuous monitoring of glucose levels in diabetes patients. The device features a magnetically-driven vibrating microcantilever, which is situated in a microchamber and separated from the environment by a semi-permeable membrane. Glucose sensing is based on affinity binding principles using a solution of dextran concanavalin-A (Con A) as the sensing fluid. The glucose concentration is determined by detecting viscosity changes induced by the binding of glucose to Con A through the measurement of the cantilever's vibration parameters. The device is capable of measuring physiologically relevant glucose concentrations from 0 to 25 mM with a resolution better than 0.025 mM and a phase sensitivity better than 0.4° mM−1. The response of the sensor to glucose concentration changes has a time constant down to 4.27 min, and can be further improved with optimized device designs.

[1]  Sohrab Mansouri,et al.  A Miniature Optical Glucose Sensor Based on Affinity Binding , 1984, Bio/Technology.

[2]  J. Thain.  Nonequilibrium thermodynamics in biophysics By A. Katchalsky and Peter F. Curran. Pp. x + 248. Harvard University Press, Cambridge, Mass.; Oxford University Press, London. 1965. 68s , 1966 .

[3]  Chuan Pu,et al.  A surface-micromachined optical self-homodyne polarimetric sensor for noninvasive glucose monitoring , 2000, IEEE Photonics Technology Letters.

[4]  A Heller,et al.  Implanted electrochemical glucose sensors for the management of diabetes. , 1999, Annual review of biomedical engineering.

[5]  N. Evans,et al.  Fluorescence-based glucose sensors. , 2005, Biosensors & bioelectronics.

[6]  Wendy D. Bennett,et al.  Microfluidic Devices on Polymer Substrates for Bioanalytical Applications , 1999 .

[7]  J Wang,et al.  Microfabricated electrophoresis chips for simultaneous bioassays of glucose, uric acid, ascorbic acid, and acetaminophen. , 2000, Analytical chemistry.

[8]  David C Klonoff,et al.  Subcutaneous continuous glucose monitoring in severe burn patients. , 2007, Critical care medicine.

[9]  David L. Meadows,et al.  Design, manufacture and characterization of an optical fiber glucose affinity sensor based on an homogeneous fluorescence energy transfer assay system , 1993 .

[10]  R. Ballerstadt,et al.  Suitability of aqueous dispersions of dextran and Concanavalin A for glucose sensing in different variants of the affinity sensor , 1994 .

[11]  A. Katchalsky,et al.  Nonequilibrium Thermodynamics in Biophysics , 1965 .

[12]  Bengt Danielsson,et al.  Mini/micro thermal biosensors and other related devices for biochemical/clinical analysis and monitoring , 2000 .

[13]  P. Bataillard,et al.  Calorimetric sensing in bioanalytical chemistry : principles, applications and trends , 1993 .

[14]  Sang Beom Jun,et al.  Application of a new Cl-plasma-treated Ag/AgCl reference electrode to micromachined glucose sensor , 2003 .

[15]  Ryoji Kurita,et al.  Microfluidic device integrated with pre-reactor and dual enzyme-modified microelectrodes for monitoring in vivo glucose and lactate , 2002 .

[16]  Post‐Stress Thickening of Dextran/Concanavalin A Solutions Used as Sensitive Fluids in a Viscosimetric Affinity Assay for Glucose , 1997 .

[17]  W. Sansen,et al.  The glucose sensor integratable in the microchannel , 2001 .

[18]  J. Schultz,et al.  Affinity sensors for individual metabolites. , 1979, Biotechnology and bioengineering symposium.

[19]  Stephen P. Timoshenko,et al.  Vibration problems in engineering , 1928 .

[20]  Babak Ziaie,et al.  A hydrogel-based implantable micromachined transponder for wireless glucose measurement. , 2006, Diabetes technology & therapeutics.

[21]  Robert C. White,et al.  A PDMS dermal patch for non-intrusive transdermal glucose sensing , 2003 .

[22]  H. Dautzenberg,et al.  Viscosimetric affinity assay. , 1996, Analytical biochemistry.

[23]  U. Haueter,et al.  Recording of subcutaneous glucose dynamics by a viscometric affinity sensor , 2001, Diabetologia.

[24]  U. Haueter,et al.  Clinical performance of a continuous viscometric affinity sensor for glucose. , 2004, Diabetes technology & therapeutics.

[25]  L. Heinemann,et al.  Sensors for glucose monitoring: technical and clinical aspects , 2001, Diabetes/metabolism research and reviews.

[26]  S. Tadigadapa,et al.  Calorimetric biosensors with integrated microfluidic channels. , 2004, Biosensors & bioelectronics.

[27]  Ashok Gowda,et al.  Fluorescence resonance energy transfer-based near-infrared fluorescence sensor for glucose monitoring. , 2004, Diabetes technology & therapeutics.

[28]  U. Beyer,et al.  Compensation of Temperature and Concanavalin A Concentratration Effects for Glucose Determination by the Viscometric Affinity Assay , 2000, Biotechnology progress.

[29]  David Trebotich,et al.  Microfabricated microdialysis microneedles for continuous medical monitoring , 2000, 1st Annual International IEEE-EMBS Special Topic Conference on Microtechnologies in Medicine and Biology. Proceedings (Cat. No.00EX451).

[30]  J. Cooper,et al.  Miniaturized Electroanalytical Sensor Systems in Micromachined Structures , 2000 .

[31]  J. Schultz,et al.  Affinity Sensor: A New Technique for Developing Implantable Sensors for Glucose and Other Metabolites , 1982, Diabetes Care.