Abstract
Transdermal extraction of interstitial fluid (ISF) offers an attractive method for minimally invasive blood glucose monitoring. However, only a minute volume of ISF could be transdermally extracted, which is required to be diluted to form a manipulable volume of fluid for easy collection, transportation, and glucose detection. Therefore, a high-resolution glucose detection method is required for detecting glucose concentration in diluted ISF. In this paper, an optical surface plasmon resonance (SPR) sensor modified by the glucose/galactose-binding (GGB) protein which has good affinity to glucose molecules was presented for specific and sensitive glucose detection. The GGB protein was mutated at different sites for thiol coupling with the SPR surface and adjusting the affinity between glucose molecules and GGB protein. And the immobilization process of the GGB protein onto the surface of SPR sensor was optimized. Then, the stability of the SPR sensor modified with GGB protein was tested immediately and two weeks after immobilization. The coefficient of variation for glucose concentration measurement was less than 4.5%. By further mutation of the GGB protein at the A213S and L238S sites, the measurement range of the SPR sensor was adjusted to 0.1-100 mg/dL, which matches the glucose concentration range of 5-10 times diluted ISF (3-100 mg/dL). These results suggest that the SPR biosensor immobilized with GGB protein has the potential for continuous glucose monitoring by integrating into the microfluidic ISF extraction chip.