Analysis of Glucose Concentration in Interstitial Fluid by Micro Surface Plasmon Resonance Sensor

A novel minimally invasive way to measure blood glucose concentration is proposed by combining interstitial fluid (ISF) transdermal extraction and surface plasmon resonance (SPR) detection. 55 kHz low-frequency ultrasound pulses are applied for 30 seconds to enhance the skin permeability and then interstitial fluid is extracted out of skin by vacuum. The glucose concentration in the interstitial fluid is determined using an optical SPR sensor that measures the refractive index. A protein-glucose binding technology using D- galactose/D-glucose binding protein for specific absorption of glucose is also employed to increase SPR measurement precision. The mathematical model to express the correlation between interstitial fluid glucose and blood glucose is also developed by considering the changes of the skin conductivity. The feasibility of this method is validated for clinical application with the requirements of bloodless, painless, continuous glucose monitoring and a prototype microfluidic diabetes-monitoring device is under development with a current glucose resolution of approximately 1 mg/l.