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 highconcentration-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.

Flexible microfluidic nanoplasmonic sensors for refreshable and portable recognition of sweat biochemical fingerprint

“…Wearable colorimetric [17][18][19] and fluorescent [20][21][22] sweat sensors have offered visual sensing access via observation of color/absorbance/fluorescence depth related to the chromogenic/luminous reaction between indicator and analytes. Electrochemical sensors are widely adopted for sweat analysis by transducing target contents into currents or potential signals at miniature and specific electrode surfaces [23][24][25][26][27][28] . Electrochemical techniques are featured with high sensitivity and selectivity, where the electrodes can also be flexibly designed into different shapes and sizes.…”

Recent Advancement in Biofluid-Based Glucose Sensors Using Invasive, Minimally Invasive, and Non-Invasive Technologies: A Review

“…In diabetic patients, glucose levels in other biofluids (such as urine, saliva, tears, breath sweat, and interstitial fluids) and blood are correlated to some degree. Moreover, their ease of production and collection have led to extensive research and development on biofluid-based glucose sensors, making the glucose level detection and monitoring process more patient-friendly [ 42 ].…”

Biosensors and Chemical Sensors for Healthcare Monitoring: A Review

“…Sun et al . [68] demonstrated a fully integrated point‐of‐care system with the capability to noninvasively monitor glucose concentration in various biofluids such as sweat, tears, and saliva glucose by combining a flexible and disposable microfluidic enzymatic biosensor.…”

“…When sweat concentration was compared with a commercial blood-glucose system, it showed a good blood-sweat glucose correlation in healthy subjects. Sun et al [68] demonstrated a fully integrated point-of-care system with the capability to noninvasively monitor glucose concentration in various biofluids such as sweat, tears, and saliva glucose by combining a flexible and disposable microfluidic enzymatic biosensor.…”