Advances in Biosensors for Continuous Glucose Monitoring Towards Wearables

Abstract

Continuous glucose monitors (CGMs) for the non-invasive monitoring of diabetes are constantly being developed and improved. Although there are multiple biosensing platforms for monitoring glucose available on the market, there is still a strong need to enhance their precision, repeatability, wearability, and accessibility to end-users. Biosensing technologies are being increasingly explored that use different bodily fluids such as sweat and tear fluid, etc., that can be calibrated to and therefore used to measure blood glucose concentrations accurately. To improve the wearability of these devices, exploring different fluids as testing mediums is essential and opens the door to various implants and wearables that in turn have the potential to be less inhibiting to the wearer. Recent developments have surfaced in the form of contact lenses or mouthguards for instance. Challenges still present themselves in the form of sensitivity, especially at very high or low glucose concentrations, which is critical for a diabetic person to monitor. This review summarises advances in wearable glucose biosensors over the past 5 years, comparing the different types as well as the fluid they use to detect glucose, including the CGMs currently available on the market. Perspectives on the development of wearables for glucose biosensing are discussed.

Keywords: continuous monitoring; diabetes; glucose biosensors; point-of-care detection; wearables.

GRAPHICAL ABSTRACT

FIGURE 1

The process of the design and fabrication for the urine glucose test paper (Shitanda et al., 2019).

FIGURE 2

The schematic and profile map of the interstitial fluid-based CGMs. (A) Two methods (Microneedle array electrode && commercially CGM) detected the concentration of the blood glucose from the interstitial fluid (Sharma et al., 2016). (B) The photographs of insertion test of the sensor on (1) guinea pig, (2) rat, and (3) rabbit, and (4) the senor after being attached and partially inserted into a rabbit (Lee et al., 2016). (C) Semi-implantable device (1) a rodent worn the semi-implantable CGM. (2) the cross-section view of the device. (3), (4) Progress of oxidation reaction on nPt surface (glucose and interferences) and TEM graph (Yoon et al., 2018).

FIGURE 3

Saliva & tear fluid-based CGMs. (A) Mouthguard glucose sensor: structure, calibration curve and android app (Arakawa et al., 2020). (B) Eyeglasses glucose sensor was used in rabbit experiment and the calibration curve (Zou et al., 2019). (C) Eye implantable CGMs impacted on eyes. A: Baseline evaluation. The eye suffered mechanical rubbing and redness. B–D: Before/middle/after the trial, the eye did not show redness or damage (Kownacka et al., 2018). (D) Schematic illustration and properties of the CGMs. (1), (2) the tear fluid entered the device. (3) the structure of the tear glucose device. (4) Mechanism the glucose detection. Reaction for the GOD and glucose (Kownacka et al., 2018).

FIGURE 4

Serum-based CGMs (Cai et al., 2020). (A) The structure of the glucose sensor, including polyethylene terephthalate (PET) substrate, working electrode, a counter electrode and insulating material. (B) The array of the electrodes. (C) The shape of the electrodes. (D) Photograph of the electrodes binding at 90°. (E) The glucose monitoring tested on a rat.

FIGURE 5

Schematics and mechanism of sweat-based CGMs. (A,B) Structure of the sensor and the sketch for the device applying on the skin (Xuan et al., 2018). (C,D) The reaction mechanism and the exploded view for the sensor (Xuan et al., 2018). (E) optimization of the device, minimum the temperature and PH impact on the result (Wiorek et al., 2020).