title: Continuous monitoring of glucose in subcutaneous tissue using microfabricated differential affinity sensors.
abstract: OBJECTIVE
  We describe miniaturized differential glucose sensors based on affinity binding between glucose and a synthetic polymer. The sensors possess excellent resistance to environmental disturbances and can potentially allow wireless measurements of glucose concentrations within interstitial fluid in subcutaneous tissue for long-term, stable continuous glucose monitoring (CGM).
  
  
  METHODS
  The sensors are constructed using microelectromechanical systems (MEMS) technology and exploit poly(N-hydroxy-ethyl acrylamide-ran-3-acrylamidophenylboronic acid) (PHEAA-ran-PAAPBA), a glucose-binding polymer with excellent specificity, reversibility, and stability. Two sensing approaches have been investigated, which respectively, use a pair of magnetically actuated diaphragms and perforated electrodes to differentially measure the glucose-binding-induced changes in the viscosity and permittivity of the PHEAA-ran-PAAPBA solution with respect to a reference, glucose-unresponsive polymer solution.
  
  
  RESULTS
  In vivo characterization of the MEMS affinity sensors were performed by controlling blood glucose concentrations of laboratory mice by exogenous glucose and insulin administration. The sensors experienced an 8-30 min initialization period after implantation and then closely tracked commercial capillary glucose meter readings with time lags ranging from 0-15 min during rapid glucose concentration changes. Clarke error grid plots obtained from sensor calibration suggest that, for the viscometric and dielectric sensors, respectively, approximately 95% (in the hyperglycemic range) and 84% (ranging from hypoglycemic to hyperglycemic glucose concentrations) of measurement points were clinically accurate, while 5% and 16% of the points were clinically acceptable.
  
  
  CONCLUSIONS
  The miniaturized MEMS sensors explore differential measurements of affinity glucose recognition. In vivo testing demonstrated excellent accuracy and stability, suggesting that the devices hold the potential to enable long-term and reliable CGM in clinical applications.
authors.affiliation: Department of Mechanical Engineering, Columbia University, New York, NY 10027, USA. xh2123@columbia.edu
authors.forename: Xian
authors.initials: X
authors.lastname: Huang
authors.forename: Charles
authors.initials: C
authors.lastname: Leduc
authors.forename: Yann
authors.initials: Y
authors.lastname: Ravussin
authors.forename: Siqi
authors.initials: S
authors.lastname: Li
authors.forename: Erin
authors.initials: E
authors.lastname: Davis
authors.forename: Bing
authors.initials: B
authors.lastname: Song
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Domenico
authors.initials: D
authors.lastname: Accili
authors.forename: Rudolph
authors.initials: R
authors.lastname: Leibel
authors.forename: Qiao
authors.initials: Q
authors.lastname: Lin
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000295:instrumentation*; D001786:Blood Glucose / Q000032:analysis*; D015190:Blood Glucose Self-Monitoring / Q000295:instrumentation*; D051379:Mice; D008810:Mice, Inbred C57BL; D055616:Microtechnology; D008991:Monitoring, Physiologic / Q000295:instrumentation*; D040521:Subcutaneous Tissue / Q000378:metabolism
chemical_list: D001786:Blood Glucose