A Flexible Microfluidic Chip-Based Universal Fully Integrated Nanoelectronic System with Point-of-Care Raw Sweat, Tears, or Saliva Glucose Monitoring for Potential Noninvasive Glucose Management.

ABSTRACT

By combining the distinctive noninvasive feature with the peculiar complete functional implementation trait, fully integrated raw noninvasive biofluid glucose biosensors offer active and remote glucose monitoring while posing minimal harm or infection risks compared to the traditional invasive manner. However, each previously reported fully integrated raw noninvasive biofluid glucose biosensor is solely focused on single-type raw noninvasive biofluid analysis. Given the diversity and complexity of subjects' physical conditions, single-type raw noninvasive biofluids are inappropriate to all crowds (e.g., sweat collection/analysis could be inapplicable for dermatopathic subjects). Here, we demonstrate the first example of a universal fully integrated nanoelectronic system with the unique capability to point-of-care and universally monitor diverse raw noninvasive biofluid (i.e., sweat, tears, and saliva) glucose by combining a flexible and disposable microfluidic enzymatic biosensor (named iezSlice) for raw biofluid pump-free sampling and measurement with a customized, handheld, and reusable wireless electronic device (named iezBar) for electrical signal transduction, conditioning, processing, and wireless transmission. We employed the specially designed high-concentration-buffer powder-loaded Kimwipes (HBP-KWs) as the microfluidic channel (microchannel) of iezSlice, guaranteeing a high-accuracy glucose analysis in various raw noninvasive biofluids. We also evaluated the potential utility of the universal fully integrated nanoelectronic system for noninvasive glucose management in healthy and diabetic subjects with the assistance of the proposed volatility-derived blood glucose concentration-free protocol. Although we focus on raw noninvasive biofluid glucose analysis in this work, the universal fully integrated nanoelectronic system may readily realize accurate monitoring of various biomolecules in raw noninvasive biofluids by introducing corresponding bioreceptors.