1246 JOURNAL OF MICROELECTROMECHANICAL SYSTEMS, VOL. 18, NO. 6, DECEMBER 2009A Capacitive MEMS Viscometric Sensorfor Affinity Detection of GlucoseXian Huang, Siqi Li, Jerome Schultz, Qian Wang, and Qiao LinAbstract—This paper presents a capacitively based mi-croelectromechanical systems affinity sensor for continuousglucose monitoring (CGM) applications. This sensor consists ofa vibrating Parylene diaphragm, which is remotely driven bya magnetic field and situated inside a microchamber. A so-lution of poly(acrylamide-ran-3-acrylamidophenylboronic acid)(PAA-ran-PAAPBA), a biocompatible glucose-sensitive polymer,fills the microchamber, which is separated from its surroundingsby a semipermeable membrane. Glucose permeates through themembrane and binds reversibly to the phenylboronic acid moietyof the polymer. This results in a viscosity change of the sensingsolution, causing a detectable change in the Parylene diaphragmvibration which can be measured capacitively. Experimental re-sults demonstrate that the device is capable of detecting glucoseat physiologically relevant concentrations ranging from 30 to360 mg/dL. The response time of the sensor to glucose concen-tration changes is approximately 1.5 min, which can be furtherimproved with optimized device designs. Excellent reversibilityand stability are observed in sensor responses, as highly desiredfor long-term CGM. [2009-0171]Index Terms—Affinity binding, biocompatibility, biosensor,continuous glucose monitoring (CGM), diabetes, viscometry.I. INTRODUCTIONDIABETES mellitus is a metabolic disease characterizedby persistent hyperglycemia (high blood sugar levels).Close monitoring of daily blood sugar levels reduces the riskof diabetes-related complications by allowing timely identifica-tion and correction of hyperglycemia as well as hypoglycemia(low blood sugar levels), a condition that typically results fromexcessive insulin uptake or inadequate glucose intake. This canbe most effectively achieved by continuous glucose monitoring(CGM), which involves constantly repetitive measurements ofphysiological glucose levels.Currently, subcutaneously implanted enzymatic electro-chemical detection is the prevailing CGM technique and isthe basis for several commercially available devices, such asManuscript received July 8, 2009; revised September 22, 2009. First pub-lished November 13, 2009; current version published December 1, 2009.This work was supported in part by the National Science Foundation underGrant ECCS-0702101 and in part by the Columbia Diabetes and EndocrinologyResearch Center under NIH Grant DK63068-05. The work of X. Huang wassupported in part by a national scholarship program from the China ScholarshipCouncil. Subject Editor A. J. Ricco.X. Huang and Q. Lin are with the Department of Mechanical Engineering,Columbia University, New York, NY 10027 USA (e-mail: [email protected]).S. Li and Q. Wang are with the Department of Chemistry and Biochemistryand Nanocenter, University of South Carolina, Columbia, SC 29208 USA.J. Schultz is with the Department of Bioengineering, University ofCalifornia, Riverside, CA 92521 USA.Color versions of one or more of the figures in this paper are available onlineat http://ieeexplore.ieee.org.Digital Object Identifier 10.1109/JMEMS.2009.2034869Medtronic MiniMed Paradigm [1], Freestyle Navigator [2], andDexCom Seven Plus [3]. Electrochemical methods are capableof sensitive and specific glucose detection but suffer fromsome significant drawbacks. The irreversible consumption ofglucose in electrochemical detection induces a potential changein the equilibrium glucose concentration in the tissue and thusaffects the actual measured glucose level. In addition, the rateof glucose consumption is diffusion limited. Any changes indiffusion layers due to biofouling (e.g., by protein adsorption,cell deposition, and capsule formation) on the sensor surfaceaffect the diffusion rate and, thus, the device sensitivity. More-over, drift from hydrogen peroxide production and interfer-ence from electrode-active chemicals may cause erosion ofthe sensor electrodes and deactivation of functional enzymes,compromising the device accuracy, reliability, and longevity[4]. As a result, electrochemical CGM sensors generally exhibitlarge drifts over time and require frequent calibration by fingerpricks (typically at least once every 12 h) [1], [3]. This lackof reliability has been severely hindering CGM applications topractical diabetes management.To overcome the drawbacks of electrochemical detection,alternative subcutaneously based glucose sensing techniqueshave been under active investigation. In particular, methodsthat use equilibrium affinity binding of glucose have showngreat promise [5]–[8]. These methods, in which glucose isnot consumed, do not carry the risk of interfering with thelocal glucose concentration in the tissue or generating erosivereaction products. More importantly, affinity sensing is consid-erably more stable and low drift in the face of biofouling, asthe deposition of biological material on the implanted sensorsurface results only in an increased equilibration time withoutany changes in measurement accuracy. A widely used affin-ity sensing technique is based on concanavalin A (Con A),whose specific binding to glucose can be detected via methodssuch as fluorescence [5], [6] and viscosity [7]. Unfortunately,Con A is immunogenic and cytotoxic [9] and degrades withtime [10]. Alternatively, affinity sensing systems utilizing syn-thetic glucose-binding polymers have the potential to addressthese issues [11]. In particular, polymers containing boronicacid groups bind to glucose specifically at physiological pHvalues [12] and have been developed to enable a variety ofglucose detection methods such as fluorescence [13], volumechange [14], and conductometry [15]. Recently, we developeda novel boronic-acid-based affinity sensing system that usesthe polymer poly(acrylamide-ran-3-acrylamidophenylboronicacid) (PAA-ran-PAAPBA) [16], [17]. In the system, glucosereversibly forms strong ester bonds with the phenylboronic acidmoiety on the backbone of PAA-ran-PAAPBA, resulting in1057-7157/$26.00 © 2009 IEEEAuthorized licensed use limited to: Columbia University. Downloaded on January 19, 2010 at 13:06 from IEEE Xplore. Restrictions apply.HUANG et al.: CAPACITIVE MEMS VISCOMETRIC SENSOR FOR AFFINITY DETECTION OF GLUCOSE 1247cross-linking of the polymer and an increase in the viscosityof the