This paper reports a flexible electronics-based epidermal biomicrofluidics technique for clinical continuous blood glucose monitoring, overcoming the drawback of the present wearables, unreliable measurements. A thermal activation method is proposed to improve the efficiency of transdermal interstitial fluid (ISF) extraction, enabling extraction with a low current density to notably reduce skin irritation. An Na+ sensor and a correction model are proposed to eliminate the effect of individual differences, which leads to fluctuations in the amount of ISF extraction. An electrochemical sensor with a 3D nanostructured working electrode surface is designed to enable precise in situ glucose measurement. A differential structure is proposed to eliminate the effect of passive perspiration, which leads to inaccurate blood glucose prediction. Fabrications of the epidermal biomicrofluidic device including formation of flexible electrodes, nanomaterial modification, and enzyme immobilization are fully realized by inkjet printing to enable facile manufacturing with low cost, which benefits practical production.

A novel flexible enzyme-electrode sensor was fabricated with a big cylindrical working electrode which, cooperating with the surface-modified 3D nanostructure, significantly improved the sensitivity.

Step emulsification for micro- and nano-droplet generation is reviewed in brief, including the emulsion mechanisms and microfluidic devices.

This paper presents a continuous glucose monitoring microsystem consisting of a three-electrode electrochemical sensor integrated into a microfluidic chip. The microfluidic chip, which was used to transdermally extract and collect subcutaneous interstitial fluid, was fabricated from five polydimethylsiloxane layers using micromolding techniques. The electrochemical sensor was integrated into the chip for continuous detection of glucose. Specifically, a single-layer graphene and gold nanoparticles (AuNPs) were decorated onto the working electrode (WE) of the sensor to construct a composite nanostructured surface and improve the resolution of the glucose measurements. Graphene was transferred onto the WE surface to improve the electroactive nature of the electrode to enable measurements of low levels of glucose. The AuNPs were directly electrodeposited onto the graphene layer to improve the electron transfer rate from the activity center of the enzyme to the electrode to enhance the sensitivity of the sensor. Glucose oxidase (GOx) was immobilized onto the composite nanostructured surface to specifically detect glucose. The factors required for AuNPs deposition and GOx immobilization were also investigated, and the optimized parameters were obtained. The experimental results displayed that the proposed sensor could precisely measure glucose in the linear range from 0 to 162 mg/dl with a detection limit of 1.44 mg/dl (S/N = 3). The proposed sensor exhibited the potential to detect hypoglycemia which is still a major challenge for continuous glucose monitoring in clinics. Unlike implantable glucose sensors, the wearable device enabled external continuous monitoring of glucose without interference from foreign body reaction and bioelectricity.

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