Skin-interfaced systems for sweat collection and analytics

Abstract

Recent interdisciplinary advances in materials, mechanics, and microsystem designs for biocompatible electronics, soft microfluidics, and electrochemical biosensors establish the foundations for emerging classes of thin, skin-interfaced platforms capable of capturing, storing, and performing quantitative, spatiotemporal measurements of sweat chemistry, instantaneous local sweat rate, and total sweat loss. This review summarizes scientific and technical progress in this area and highlights the implications in real time and ambulatory modes of deployment during physical activities across a broad range of contexts in clinical health, physiology research, fitness/wellness, and athletic performance.

Fig. 1. Flexible, skin-integrated electrochemical systems for measuring the chemical composition of sweat.

(A) Schematic illustration of an array of electrochemical sensors for analyzing the concentration of glucose, lactate, potassium, and sodium in sweat. GOx, glucose oxidase, LOx, lactate oxidase; PVB, polyvinyl butyral. (B) Image of a thin, flexible embodiment of the system in (A). (C) Wrist-mounted platform that combines the array of sensors in (B) with battery-powered electronics for digital signal acquisition and Bluetooth wireless data transmission. (D) Flexible, skin-integrated device for analyzing the concentration of sodium in sweat with a wireless interface to a smartphone based on NFC protocols. (E) Image of a stretchable electrochemical sensor under mechanical stress. (F) Results from continuous analysis of local sweat glucose, lactate, sodium, and potassium (and skin temperature) with the electrochemical system in (C). (G) Alcohol sensing based on a device similar to that in (E) (70). BAC, blood alcohol concentration. (H) Heavy metal ion sensing with a stripping voltammetric system (platform not shown) (76). ICP, inductively coupled plasma (mass spectrometry). Figures were reproduced with permission from Gao et al. (46) (A to C and F), Rose et al. (45) (D), Bandodkar et al. (80) (E), Kim et al. (70) (G), and Gao et al. (76) (H).

Fig. 2. Epifluidic devices with integrated wireless electronics and colorimetric chemical reagents for capture, storage, and chemical analysis of sweat.

(A) Exploded view schematic illustration of an epifluidic system and its interface with the skin; this device includes microfluidic channels, reservoirs, colorimetric chemical assays, NFC capabilities, and a soft adhesive layer that serves as a water-tight interface to the skin with localized openings that define access of microfluidic inlets to underlying sweat glands. PDMS, polydimethylsiloxane. (B) Optical image of a device, with magnified views (insets) of the different regions that provide colorimetric response: a serpentine channel to define sweat rate and total sweat loss (blue; labeled “water”); reservoirs to determine the concentration of lactate, glucose, pH, and chloride ions. (C) Optical image of a freestanding device (without electronics) while twisted and stretched to illustrate its low-modulus, elastic mechanical properties. (D) Epifluidic system on the skin during sweating, as an illustration of its colorimetric readout for sweat loss, sweat rate, and sweat chemistry. Figures were reproduced with permission from Koh et al. (53) (A to D).

Fig. 3. Epifluidic systems with CBVs for time-sequential microsampling of sweat and for measuring the surface pressure associated with the action of eccrine sweat glands.

(A) Time series images of artificial sweat entering a region of an epifluidic system with three CBVs, an isolated microreservoir, and an interconnecting microchannel, (i) just before entering the microreservoir after passing through CBV #1, (ii) just after filling the microreservoir and before passing through CBV #2, and (iii) just after passing through CBV #2 and moving to the next microreservoir. (B) In vitro demonstration of time-sequential microsampling with a device that consists of a circular array of 12 microreservoirs using water dyed with different colors to illustrate the capability for sampling without mixing. (C) Concentrations of lactate, potassium, and sodium measured by ex situ analysis of sweat volumes extracted from separate microreservoirs in an epifluidic system mounted on the forearm after a running exercise. (D) Schematic drawing of an epifluidic system that contains a collection of CBVs, microchannels, and microreservoirs designed for measuring surface SPSG by eccrine sweat glands. (E) Optical images of the colorimetric measurement of surface SPSG from the forearm and chest during exercise, as determined by the maximum bursting pressure among the CBVs that burst during filling. (F) Surface SPSG measured under different conditions (cycling, elliptical, treadmill, and thermal exposure in the sauna) and from different regions of the body showing little to no variation in SPSG with the exception of exercise on the elliptical. Exercise duration was limited to 20 min across different exercise conditions, and the relative intensities were not controlled. Figures were reproduced with permission from Choi et al. (54) (A to C) and Choi et al. (55) (D to F).

Fig. 4. Multifunctional, colorimetric epifluidic systems for time-sequential measurements of sweat loss and chemistry.

(A) Epifluidic system that includes multiple colorimetric assays integrated with CBVs for analyzing sweat composition and sweat rate in a time-sequential manner. (B) Optical image of a related device that also includes liquid crystal sensors for temperature. (C) Colorimetric responses and color calibration markers for analysis of sweat biomarkers and skin/sweat temperature. (D) Optical image of an epifluidic device spotted with blue dye that mixes with sweat. The extent of blue dye in the channel during sweat provides a measure of total sweat volume at any given instant in time. (E) Correlation of sweat collection for an epifluidic device from the anterior forearm versus the normalized total body loss (based on initial weigh-in and final weigh-out with no fluid intake or restroom use during exercise). (F) Correlation of sweat collection for an epifluidic device versus an absorbent patch. (G) Cumulative local sweat loss versus time measured from the forearm with an epifluidic device during exercise, while at rest, and during a subsequent exercise session.

Fig. 5. Skin-interfaced devices with capabilities for stimulating release of sweat, analyzing sweat chemistry, and delivering pharmacological agents through the surface of the skin.

(A) Schematic drawing of strategies for stimulating release of sweat by iontophoresis and for electrochemically analyzing the chemistry of this sweat. (B) Optical image of a wearable device with capabilities illustrated in (A), where the sensing involves electrochemical determination of the concentration of chloride and sodium ions (left). Magnified view of electrodes for iontophoresis, chloride, and sodium ISEs and a PVB-coated reference electrode (right). FPCB, flexible printed circuit board. Comparison of concentrations of Na⁺ and Cl⁻ in sweat for (C) a healthy subject and (D) a patient with CF. (E) Schematic drawings of a platform for sweat monitoring and pharmacological delivery. (F) Optical image of such a system connected to an electrochemical analyzer that is wirelessly controlled with a smartphone. (G) Average glucose concentrations before and after correction, accounting for changes in measured pH. (H) Optical image of microheaters integrated with microneedles laminated on the skin near the abdomen of a mouse model. (I) Blood glucose concentrations associated with mice in a treated group (with drug) and a control group (without the patch and without drug). Figures were reproduced with permission from Emaminejad et al. (63) (A to D) and Lee et al. (61) (E to I).