Comprehensive Review on Wearable Sweat-Glucose Sensors for Continuous Glucose Monitoring

Hima Zafar, Asma Channa, Varun Jeoti, Goran M Stojanović, Hima Zafar, Asma Channa, Varun Jeoti, Goran M Stojanović

Abstract

The incidence of diabetes is increasing at an alarming rate, and regular glucose monitoring is critical in order to manage diabetes. Currently, glucose in the body is measured by an invasive method of blood sugar testing. Blood glucose (BG) monitoring devices measure the amount of sugar in a small sample of blood, usually drawn from pricking the fingertip, and placed on a disposable test strip. Therefore, there is a need for non-invasive continuous glucose monitoring, which is possible using a sweat sensor-based approach. As sweat sensors have garnered much interest in recent years, this study attempts to summarize recent developments in non-invasive continuous glucose monitoring using sweat sensors based on different approaches with an emphasis on the devices that can potentially be integrated into a wearable platform. Numerous research entities have been developing wearable sensors for continuous blood glucose monitoring, however, there are no commercially viable, non-invasive glucose monitors on the market at the moment. This review article provides the state-of-the-art in sweat glucose monitoring, particularly keeping in sight the prospect of its commercialization. The challenges relating to sweat collection, sweat sample degradation, person to person sweat amount variation, various detection methods, and their glucose detection sensitivity, and also the commercial viability are thoroughly covered.

Keywords: biosensor; diabetes; hypoglycemia; non-invasive glucose monitoring; sweat based sensing; wearable electronics.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of the numerous approaches for the measuring of glucose for intense insulin therapy. The figure concept adapted from [3].
Figure 2
Figure 2
Working of biosensors: A close relationship between certain bio-recognition layers and electrical signal transaction. The figure concept adapted from [16].
Figure 3
Figure 3
History of biosensor development for wearables from the beginning to the present.
Figure 4
Figure 4
The direct application of sensors to skin, e.g., (a) Tattoo [54] (Reused with the permission of Copyright 2019, Elsevier), (b) Epidermal Microfluidic Electrochemical Detection System [55] (Reprinted with permission of Copyright© 2017, American Chemical Society), (c) Wearable Tattoo-Based Iontophoretic-Biosensing System for detecting Alcohol in Sweat [56] (Reused with permission of Copyright© 2016, American Chemical Society), (d) A passive wireless capacitive sensor [50] (Reused with the permission of Copyright 2014, John Wiley and Sons), addresses several difficulties in history. The technology is mechanically compatible with the skin, and all of the examples are important as a first step towards reducing perspiration between the skin and the sensors.
Figure 5
Figure 5
(a) The average sweat gland density illustration (glands/cm2) on different areas of the body [57,58]. (b) Scale illustrating the approximate range of levels for several sweat analytes reported in [59,60,61,62,63].
Figure 6
Figure 6
Technique for detecting analytes in sweat as it is released onto skin using multi-analyte RFID patches. The figure concept adapted from [59,65].
Figure 7
Figure 7
(a) A typical commercial non-invasive glucose monitoring (GM) system is depicted. (b) The sensing component of the GM system is being implemented, integrated, and placed directly on the skin. A cross-section of the created GM device inserted into the skin is shown. (c) Illustration of the sensing layers of non-invasive sensors is shown in larger view; the final layer is dependent on different sensing materials which respond to specific analytes, i.e., sweat, and a protective layer to confine the reaction compartment. (d) The integration of a electronic device/system for signal processing and transmission wirelessly.
Figure 8
Figure 8
Various sensing materials employed in electrochemical wearable sweat glucose sensors based on their bio-compatibility with catalysts.
Figure 9
Figure 9
Techniques for sweat collection.
Figure 10
Figure 10
The wearable sweat colorimetric sensor: (a) Optical pictures of flexible, soft microfluidic equipment used for colorimetric skin sweat analysis and mechanical bending (bottom left) and twisting (top left) deformation (bottom right); (b) Microfluidic channels filled with blue-dyed water from the top; (c) A gadget and its interaction with the skin in exploded view; (d) The sweat sample collection process and color analysis of the device’s digital pictures. Reprinted with permission from [104]. Copyright 2019 American Chemical Society.
Figure 11
Figure 11
Textile based wearable sweat colorimetric sensor, using knitted cotton fabric material, for simultaneously detecting sweat pH and lactate, using three layers: (1) chitosan, (2) sodium carboxymethyl cellouse, and (3) indicator dye(methyl orange(MO)), bromocresol green (BCG). Reprinted with permission from [110]. Copyright 2018, Elsevier B.V. All rights reserved.
Figure 12
Figure 12
(a) The screen-printed electrochemically based tattoo, (Path I) for environment, (Path II) for analyte monitoring. Image (b) shows the clear protective sheet is removed, and in (c) the tattoo base paper is softly applied on human skin after dabbing with water for tattoo appliances. Image (d,e) illustrates the level of mechanical stress and strain that a tattoo is used to twist the underlying skin on a human subject. The figure concept adapted from [111,117].
Figure 13
Figure 13
Schematic of a Enzymatic Chrono Amperometric biosensor with mediators, i.e., Prussian blue, nanozymes, etc., interacting with glucose oxidase to detect glucose in sweat. Adapted from [14].
Figure 14
Figure 14
The “Eversense” CGM System from Ascensia Diabetes Care Group is a device that measures glucose levels utilizing sensor technology based on fluorescence: Image taken from https://www.ascensiadiabetes.com (accessed on 10 November 2021).
Figure 15
Figure 15
The basic configuration of photoacoustic spectroscopy (PAS) sensing is shown here. The laser beam from tunable and pulsed QCL laser is irradiated on skin, producing a thermal expansion in the skin to generate the ultrasonic wave. The thermal absorption and thus the ultrasound produced is dependent on ISF constituents such as glucose. The ultrasonic wave is amplified in the acoustic resonator, also known as the cell, and detected through a piezoelectric transducer such as a microphone. After that, the electrical signal corresponding to photoacoustic signal at the piezo sensor’s output is amplified, digitized, and forwarded to the computer for analysis. As the near- or mid-IR wavelengths are tuned one at a time, the amplitude of the corresponding photoacoustic signal indicates which wavelengths are absorbed more efficiently than others. Using ED-QCL, higher-order glucose wavelengths between 1 and 1.25 microns can be easily detected.
Figure 16
Figure 16
Effects of (a) the skin and sweat glands gap on (b) time necessary to fill the new sweat sample under a sensor. The figure concept adapted from [59].
Figure 17
Figure 17
Wearable devices introduced by some companies that aspire to commercialize wearable sweat-sensing devices. (a) The BACtrack Skyn is a wearable alcohol monitor patch device for monitoring transdermal alcohol in real time. This product is for research only and is not yet commercially available; image taken from https://skyn.bactrack.com (accessed on 15 November 2021). (b) Sweat collection patch for drug testing developed and sold by Alcopro; image taken from https://www.alcopro.com (accessed on 15 November 2021). (c) The SCRAM CAM, an ankle bracelet for alcohol testing; image taken from https://www.scramsystems.com (accessed on 15 November 2021). (d) The ELITechGroup proposed a macroduct sweat collection system by ELITechGroup for diagnosis of cystic fibrosis; image taken from https://www.elitechgroup.com (accessed on 15 November 2021).

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