Wearable Bioelectronics: Enzyme-Based Body-Worn Electronic Devices

Abstract

In this Account, we detail recent progress in wearable bioelectronic devices and discuss the future challenges and prospects of on-body noninvasive bioelectronic systems. Bioelectronics is a fast-growing interdisciplinary research field that involves interfacing biomaterials with electronics, covering an array of biodevices, encompassing biofuel cells, biosensors, ingestibles, and implantables. In particular, enzyme-based bioelectronics, built on diverse biocatalytic reactions, offers distinct advantages and represents a centerpiece of wearable biodevices. Such wearable bioelectronic devices predominately rely on oxidoreductase enzymes and have already demonstrated considerable promise for on-body applications ranging from highly selective noninvasive biomarker monitoring to epidermal energy harvesting. These systems can thus greatly increase the analytical capability of wearable devices from the ubiquitous monitoring of mobility and vital signs, toward the noninvasive analysis of important chemical biomarkers. Wearable enzyme electrodes offer exciting opportunities to a variety of areas, spanning from healthcare, sport, to the environment or defense. These include real-time noninvasive detection of biomarkers in biofluids (such as sweat, saliva, interstitial fluid and tears), and the monitoring of environmental pollutants and security threats in the immediate surrounding of the wearer. Furthermore, the interface of enzymes with conducting flexible electrode materials can be exploited for developing biofuel cells, which rely on the bioelectrocatalytic oxidation of biological fuels, such as lactate or glucose, for energy harvesting applications. Crucial for such successful application of enzymatic bioelectronics is deep knowledge of enzyme electron-transfer kinetics, enzyme stability, and enzyme immobilization strategies. Such understanding is critical for establishing efficient electrical contacting between the redox enzymes and the conducting electrode supports, which is of fundamental interest for the development of robust and efficient bioelectronic platforms. Furthermore, stretchable and flexible bioelectronic platforms, with mechanical properties similar to those of biological tissues, are essential for handling the rigors of on-body operation. As such, special attention must be given to changes in the behavior of enzymes due to the uncontrolled conditions of on-body operation (including diverse outdoor activities and different biofluids), for maintaining the attractive performance that these bioelectronics devices display in controlled laboratory settings. Therefore, a focus of this Account is on interfacing biocatalytic layers onto wearable electronic devices for creating efficient and stable on-body electrochemical biosensors and biofuel cells. With proper attention to key challenges and by leveraging the advantages of biocatalysis, electrochemistry, and flexible electronics, wearable bioelectronic devices could have a tremendous impact on diverse biomedical, fitness, and defense fields.

Figure 1.

(A) Conceptual illustration of wearable bioelectronics integrated with the human body, consisting of a biosensor, electronic device, energy source, and display. Schematics of wearable enzyme-based bioelectronics, including: (B) biosensor, showing biocatalytic reactions on the transducer surface, (C) biofuel cell (BFC) illustrating bioanode and biocathode, and (D) self-powered biosensor utilizing BFCs that generate power proportional to the analyte concentration.

Figure 2.

Examples of biofuel cells (BFCs). Images and schematics illustrating: (A) Tattoo-based BFC. Adapted with permission from ref. . Copyright 2013 ACS. (B) Highly stretchable BFC. Adapted with permission from ref. . Copyright 2016 ACS. (C) Stretchable electronic skin-based island-bridge BFC. Adapted with permission from ref. . Copyright 2017 RSC. (D) Stretchable textile-based BFC as self-powered sensors. Adapted with permission from ref. . Copyright 2016 RSC. (E) Microneedle-based self-powered glucose sensors. Adapted with permission from ref. . Copyright 2014 Elsevier. (F) Natural extract-based BFC. Adapted with permission from ref. . Copyright 2018 RSC.

Figure 3.

Examples of wearable biosensor devices. Images and schematics illustrating: (A) the first example of a screen-printed non-invasive glucose biosensor based on a tattoo-like iontophoretic system. Adapted with permission from ref. . Copyright 2015 ACS. (B) Alcohol tattoo biosensor integrated with electronic board. Adapted with permission from ref. . Copyright 2016 ACS. (C) Dual biofluid sampling tattoo devices for simultaneous detection of ISF glucose and sweat alcohol. Adapted with permission from ref. . Copyright 2018 John Wiley & Sons. (D) Hybrid sensing system for monitoring sweat lactate and electrophysiological signals. Adapted with permission from ref. . Copyright 2016 Nature. (E) Sweat sampling microfluidic platform for detecting lactate and glucose. Adapted with permission from ref. . Copyright 2017 ACS. (F) Microneedle biosensor platform for continuous subcutaneous alcohol monitoring. Adapted with permission from ref. . Copyright 2017 Elsevier. (G) Bandage-based sensor platform for detecting the melanoma cancer biomarker tyrosinase. Adapted with permission from ref. . Copyright 2018 John Wiley & Sons. (H) Salivary uric acid mouthguard biosensor integrated with wireless amperometric circuit board. Adapted with permission from ref. . Copyright 2015 Elsevier. (I) ‘Lab-on-a-Glove’ based fingertip biosensing of organophosphate nerve agents. Adapted with permission from ref. . Copyright 2017 ACS.