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Viscometric MEMS affinity glucose sensors for continuous glucose monitoring

 

The MEMS affinity glucose sensors we have developed primarily measure viscosity changes of glucose-sensitive polymer solution. The glucose-sensitive solution was initially based on concanavalin A (Con A), a protein that binds specifically to glucose. To overcome the lack of biocompatibility and stability of Con A, we have recently been using poly(acrylamide-ran-3-acrylamidophenylboronic acid) (PAA-ran-PAAPBA), a synthetic, biocompatible, glucose-specific polymer that was developed in the lab of Professor Qian Wang specifically for this project. The MEMS viscometric glucose sensors consist of a magnetically vibrational element (a cantilever or diaphragm) inside a microchamber that is equipped with a semi-permeable membrane and filled with a PAA-ran-PAAPBA solution. Glucose permeates through the semi-permeable membrane and binds reversibly to the polymer, causing crosslinking of the polymer and changing the viscosity of the solution. The viscosity change causes variations in the viscous damping on the cantilever or diaphragm vibration. Vibration measurements by optical or capacitive methods thus allow determination of the ISF glucose concentration. Our experimental results show that the devices are capable of accurately determining glucose concentrations with excellent repeatability and reversibility as well as minimal drifts. The use of magnetic vibration generation and capacitive sensing is amenable to making the device fully implantable, wirelessly interrogated for long-term glucose monitoring, which is being pursued in ongoing work.

 

Fig1

MEMS affinity glucose sensing for continuous glucose monitoring. The glucose sensor is implanted in subcutaneous tissue; glucose permeates into and out of the device through a semi-permeable membrane, allowing measurement of the glucose level in interstitial fluid.

Fig2

A MEMS viscometric glucose sensor. A Parylene diaphragm, embedded with permalloy, is set in vibration by a remotely applied magnetic field. The upper side of the diaphragm is exposed to a solution of PAA-ran-PAAPBA, a synthetic, biocompatible, glucose-specific polymer. A moving electrode is embedded in the diaphragm, forming a capacitive sensor with a ground electrode. As glucose binding with the polymer changes the solution viscosity and the viscous vibration damping, capacitive measurement of the diaphragm vibration allows determination of the glucose concentration.

Fig3

Frequency-dependent behavior of the harmonically driven vibration of the sensor diaphragm at physiologically relevant glucose concentrations: (a) amplitude, and (b) phase shift.

Fig4

A 1-DOF mass-spring-damper model fitted to the experimental data obtained at a glucose concentration of 90 mg/dL. A single set of parameters(vibration amplitude expressed in circuit output voltage = 0.38 V, natural frequency in vacuum = 1190 Hz, and damping ratio = 0.39) allow the model to fit two sets of data, which are experimentally determined values of the real and imaginary parts of the complex vibration amplitude.

Researcher:

Junyi Shang, Ph.D Student (Mechanical Engineering)

Zhixing Zhang, Ph.D Student (Mechanical Engineering)

Collaborators:

Dr. Qian Wang, Departments of Chemistry and Biochemistry, University of South Carolina

Dr. Jerome Schultz, Department of Bioengineering, University of California, Riverside

Representative Journal Publications:

1. X. Huang, S. Li, J. Schultz, Q. Wang and Q. Lin, "A Capacitive MEMS Viscometric Sensor for Affinity Detection of Glucose," J. of Microelectromechanical Systems. In Press.

2. S. Li, E. Davis, J. Anderson, Q. Lin and Q. Wang, "Development of Boronic Acid Grafted Random Copolymers for Continuous Glucose Monitoring," Biomacromolecules, 10: 113-118, 2009.

3. Y. Zhao, S. Li, A. Davidson, B. Yang, Q. Wang, and Q. Lin, "A MEMS Viscometric Sensor for Continuous Glucose Monitoring," Journal of Micromechanics and Microengineering, vol. 17, pp. 2528-2537, 2007.

4. Siqi Li, Xian Huang, Erin N. Davis, Qiao Lin, and Qian Wang, "Development of Novel Glucose Sensing Fluids with Potential Application to Microelectromechanical Systems-Based Continuous Glucose Monitoring," Journal of Diabetes Science and Technology, November 2008, Volume 2, Issue 6: Page 1066-1074.

5. X. Huang, S. Li, J. Schultz, Q. Wang, and Q. Lin, "A MEMS affinity glucose sensor using a biocompatible glucose-responsive polymer" Sensors and Actuators B: Chemical, vol. 140, pp. 603-609 2009.


Representative Conference Publications:

1. X. Huang, S. Li, J. Schultz, Q. Wang, and Q. Lin, "A Capacitively Based MEMS Affinity Glucose Sensor," The 15th International Conference on Solid State Sensors, Actuators & Microsystems (Transducers 2009), Denver, CO, USA, 2009.

2. X. Huang, S. Li, J. Schultz, Q. Wang, and Q. Lin, "A MEMS Sensor for Continuous Monitoring of Glucose in Subcutaneous Tissue," IEEE Int. Conf. Micro Electro Mechanical Systems (MEMS '09), Sorrento, Italy, 2009.

3. X. Huang, S. Li, J. Schultz, Q. Wang, and Q. Lin, "A Biocompatible Affinity MEMS Sensor for Continuous Monitoring of Glucose," IEEE Int. Conf. on Nano/Micro Engineered and Molecular Systems (NEMS'09), Shenzhen, China, 2009.