Skin-Interfaced Wearable Sweat Sensors for Precision Medicine

Abstract

Wearable sensors hold great potential in empowering personalized health monitoring, predictive analytics, and timely intervention toward personalized healthcare. Advances in flexible electronics, materials science, and electrochemistry have spurred the development of wearable sweat sensors that enable the continuous and noninvasive screening of analytes indicative of health status. Existing major challenges in wearable sensors include: improving the sweat extraction and sweat sensing capabilities, improving the form factor of the wearable device for minimal discomfort and reliable measurements when worn, and understanding the clinical value of sweat analytes toward biomarker discovery. This review provides a comprehensive review of wearable sweat sensors and outlines state-of-the-art technologies and research that strive to bridge these gaps. The physiology of sweat, materials, biosensing mechanisms and advances, and approaches for sweat induction and sampling are introduced. Additionally, design considerations for the system-level development of wearable sweat sensing devices, spanning from strategies for prolonged sweat extraction to efficient powering of wearables, are discussed. Furthermore, the applications, data analytics, commercialization efforts, challenges, and prospects of wearable sweat sensors for precision medicine are discussed.

Figure 1.. Overview of skin-interfaced wearable sweat sensors for personalized and precision healthcare.

Created with BioRender.com.

Figure 2.. Physiology of sweat glands and eccrine sweat secretion.

a, Structure of the skin, including apocrine and eccrine sweat glands. b, The eccrine sweat gland can be broken down into two primary components: the secretory coil and the sweat duct where isotonic secretion and reabsorption occur, respectively, to produce a hypotonic aqueous fluid. c, Sweat is stimulated primarily through β-adrenergic and muscarinic innervation. β-adrenergic and muscarinic signaling pathways use cAMP and Ca²⁺ as second messengers, respectively, to activate chloride channels. Activation of nicotinic receptors may amplify the sweating response beyond the localized region via the sudomotor axon reflex. d, Several membrane channels are involved in the secretion of electrolytes and the subsequent osmotic flow into the lumen. Created with BioRender.com.

Figure 3.. Electrochemical potentiometric sweat sensors.

a, Schematic of potentiometry operating mechanism and sensor configurations. b, Schematic showing the redox capacitance-based ISEs using electroactive materials as ion-to-electron transducers. c, Schematic showing the double-layer capacitance-based ISEs using nanomaterials as ion-to-electron transducers. d, An epidermal potentiometric sodium sensor on a subject performing exercise activities. e, Sensor response to varying sodium concentrations over 0.1–100 mM range. d,e, Reproduced with permission from ref . Copyright 2014 Elsevier. f, An epidermal potentiometric ammonium sensor with a PVB-based reference electrode. g, Sensor response to varying sodium concentrations over 0.1–100 mM range. f,g, Reproduced with permission from ref . Copyright 2013 Royal Society of Chemistry. h, A wearable sweat sensor platform based on gold nanodendrite array. i, Real-time on-body sodium data using the sweatband sensor over a period of repetitive indoor cycling. h,i, Reproduced with permission from ref . Copyright 2017 American Chemical Society. j, A fully-integrated wearable wristband that could detect Ca²⁺ and pH at the same time. k, A representative sensitivity and repeatability performance test of Ca²⁺ sensors. j,k, Reproduced with permission from ref . Copyright 2016 American Chemical Society.

Figure 4.. Electrochemical amperometric sweat sensors.

a, Schematic of amperometry operating mechanism and sensor configurations. b, Schematic showing the 3 generations of amperometric enzymatic sensors. c, A 1^st generation wearable mediator-free enzymatic sensor with capability to detect glucose, lactate, and choline. Reproduced with permission from ref . Copyright 2019 Wiley. d, A 2^nd generation wearable glucose sensor with porous membrane that enables long-term glucose monitoring for up to 20 h. Reproduced with permission from ref . Copyright 2019 Wiley. e, A wearable lactate tattoo sensor was built for lactate sensing in human perspiration during exercise. Reproduced with permission from ref . Copyright 2013 American Chemical Society. f, A wearable alcohol sensor for noninvasive alcohol monitoring in iontophoresis-induced sweat. Reproduced with permission from ref . Copyright 2016 American Chemical Society. g, A flexible tattoo patch for vitamin C detection to keep track of nutrients level in the body and guide dietary interventions. Reproduced with permission from ref . Copyright 2020 American Chemical Society. h, A wearable sweat band for noninvasive levodopa drug monitoring for Parkinson’s disease. Reproduced with permission from ref . Copyright 2019 American Chemical Society. i, A wearable sweat band using nicotine-oxidizing enzyme, cytochrome P450 2B6 for noninvasive nicotine detection. Reproduced with permission from ref . Copyright 2020 American Chemical Society. j, A fully-integrated wearable wristband that could detect metabolites and electrolytes at the same time. Reproduced with permission from ref . Copyright 2016 Springer Nature.

Figure 5.. Electrochemical sweat sensors using direct oxidation.

a, Schematic of differential pulse voltammetry (DPV)/square wave voltammetry (SWV) operating mechanism and sensor configurations. b, Detection of uric acid and tyrosine in sweat based on a laser-engraved sensor. c, Quantitative analysis of uric acid and tyrosine is based on oxidation peak height in DPV curve. b,c, Reproduced with permission from ref . Copyright 2019 Springer Nature. d, Detection of sweat caffeine levels using a wearable sweatband after drug intake. Scale bar, 5 mm. e, Characterization of a caffeine sensor with a linear response between peak height and caffeine concentrations with a high sensitivity. d,e, Reproduced with permission from ref . Copyright 2018 Wiley. f, Monitoring of circulating drugs’ pharmacokinetics using an aptamer immobilized sweat sensor. g, Detection of antibiotics dynamics such as tobramycin and vancomycin that do not have natural recognition elements. f,g, Reproduced with permission from ref . Copyright 2022 The American Association for the Advancement of Science. h, Electrokinetic preconcentration of the neuropeptide Y using negative dielectrophoretic (nDEP) trapping. i, Electrochemical detection of neuropeptide Y and Orexin A at picomolar levels from subnanoliter solution samples with dielectrophoresis preconcentration. h,i, Reproduced with permission from ref . Copyright 2014 American Chemical Society. j, Detection of heavy metals from body fluids such as sweat using electrochemical square wave anodic stripping voltammetry. k, Simultaneous detection of Pb, Au, and Hg on a Au working microelectrode. j,k, Reproduced with permission from ref . Copyright 2016 American Chemical Society.

Figure 6.. Wearable sweat sensors based on transistors.

a, A transistor-based inorganic pH chemical sensor with ultrahigh sensitivity beyond Nernst limit. b, Optical image of the pH transistor using flexible polimide as substrate. c, pH monitoring with a sensitivity of around 240 millivolts per pH unit. a–c, Reproduced with permission from ref . Copyright 2018 Springer Nature. d, A lab-on-skin system with microfluidics on top of an ISE-functionalized FET chip. e, Optical image of the microfluidics system, which aligned on the top gate of the FET array. f, Real-time measurement of Na⁺ and K⁺ ions with steep variations of the drain current using ion-selective FET. Scale bar, 3 cm. d–f, Reproduced with permission from ref . Copyright 2018 American Chemical Society. g, A wearable In₂O₃ nanoribbon transistor with a fully integrated on-chip gate for glucose detection in sweat. h, The sensor source and drain electrode were immobilized with GOx, using sweat as the liquid gate dielectric. i, A wide detection range from nM level to mM level and a detection limit down to 10 nM was obtained using nanoribbon FET. g–i, Reproduced with permission from ref . Copyright 2018 American Chemical Society. j, Schematic of the organic electrochemical transistor to detect glucose and power generation from biofluids. Scale bar, 200 μm. k, Schematic of enzymatic reaction transferring electrons to the channel when gate voltage is smaller than source-drain bias. l, Real-time response of the mediator-free enzyme-coupled organic FET to successively added glucose in biofluids. j–l, Reproduced with permission from ref . Copyright 2019 Springer Nature.

Figure 7.. Wearable optical sweat sensors.

a, An integrated platform that contains colorimetric assay arrays and sweat microfluidics that detects glucose, lactate, H⁺ and Na⁺. b, A smart phone app for image capture and RGB analysis to read the concentration quantitatively. a,b, Reproduced with permission from ref . Copyright 2016 The American Association for the Advancement of Science. c, A microfluidics design of a colorimetric sensor array that consists of a check valve to prevent backflow. d, Chromogenic reaction of colorimetric glucose sensor and colorimetric response various glucose concentrations from 0.1 to 0.5 mM. c,d, Reproduced with permission from ref . Copyright 2019 American Chemical Society. e, Chemically modified carbon nitride-chitin-acetic acid hybrid that displayed glucose oxidase-like activity. f, Ultraviolet–visible (UV-Vis) absorption of chromogenic indicator 3,30,5,50-tetramethylbenzidine in chemically modified nanozyme with varying glucose concentration (0–1000 μM). e,f, Reproduced with permission from ref . Copyright 2020 Elsevier. g, A soft microfluidic system pre-filled with fluorescent probes for sweat chloride, sodium and zinc detection. h, Fluorescent probe response to analyte concentration under visible light illumination. g,h, Reproduced with permission from ref . Copyright 2018 Royal Society of Chemistry. i, A wearable plasmonic paper-based microfluidic system for sweat rate and metabolite detection. j, Quantitative measurement of uric acid based on surface-enhanced Raman spectroscopy (SERS) spectrum. i,j, Reproduced with permission from ref . Copyright 2022 The American Association for the Advancement of Science. k, SERS sensing of plasmonic metafilm based on ordered silver nanocube superlattice as the sensing component. l, Detection of a wide range of drugs within the human sweat sample using SERS. k,l, Reproduced with permission from ref . Copyright 2021 The American Association for the Advancement of Science.

Figure 8.. Wearable sweat rate sensor.

a, An impedance sensor embedded in sweat microfluidics to monitor resting thermoregulatory sweat. b, Dependance of impedance on varying salt concentrations. a,b, Reproduced with permission from ref under CC BY 4.0. Copyright 2021 Nyein et al. c, Sweat rate monitoring based on digitized microbubble detection mechanism by calculating microliter-scale bubbles generated by electrolysis. Reproduced with permission from ref . Copyright 2022 Royal Society of Chemistry. d, A thermal sweat flow sensing module based on a short and straight fluid channel with a flow sensor. e, Detection of sweat rate by temperature difference with varying flow rate under different heater power. d,e, Reproduced with permission from ref . Copyright 2021 Springer Nature. f, Capacitance-based sweat rate sensors. g, Measurement mechanism by capacitance difference of the microfluidic area between those filled with sweat from that of air. h, On-body trial with the capacitance sensor being measured using an LCR meter continuously. f–h, Reproduced with permission from ref . Copyright 2020 American Chemical Society. i, A resettable visual sweat rate sensor with functionalities of collecting sweat, purging collected sweat, and chemesthetic ejection. Scale bar, 1 cm. j, Optical image showing the sweat collection system being reset by the user after rehydration. i,j, Reproduced with permission from ref under CC BY 4.0. Copyright 2019 Reeder et al.

Figure 9.. Wearable sweat sensor based on piezoelectric and other methods.

a, A piezoelectric sweat pH sensor based on pH sensitive hydrogels. b, Optical images of a pH-sensitive hydrogel in acidic, neutral and basic solutions. c, Resonant frequency shift of piezoelectric membrane in response to pH. a–c, Reproduced with permission from ref under CC BY 4.0. Copyright 2020 Scarpa et al. d, Optical image of a piezoelectric patch for multimodal metabolites monitoring. e, Mechanism of coupling effect between the surface enzymatic reaction and piezoelectric characteristic of ZnO nanowire. f, Multimodal signals including glucose, lactate, uric acid and urea could be obtained using the piezoelectric sensor. d–f, Reproduced with permission from ref . Copyright 2017 American Chemical Society. g, A chip-less wireless sensor system using surface acoustic wave sensors for sweat ion sensing. Scale bar, 200 μm. h, Sensing mechanism of ISM-coated surface acoustic wave sensors. i, Dynamic response of surface acoustic wave sensors to different sweat ion concentrations. g–i, Reproduced with permission from ref . Copyright 2022 The American Association for the Advancement of Science.

Figure 10.. Major components of a bioaffinity sensor.

Bioaffinity detects analytes including proteins, nucleic acids and small molecules. A bioaffinity sensor recognizes an analyte via affinity interactions with a receptor (aptamer, antibody or molecularly imprinted polymer) and converts the interactions into measurable signals via a transducer. Transducers employed for epidermal sweat sensing are either electrochemical or optical. SWV, square wave voltammetry; DPV, differential pulse voltammetry; LSV, linear sweep voltammetry; I, current; V, potential; R_CT, charge transfer resistance; C_dl, double layer capacitance; R_s, solution resistance; Z_w, Warburg element; Z’, real impedance; Z”, imaginary impedance; nf-EIS, non-faradaic electrochemical impedance spectroscopy. f-EIS, faradaic impedance spectroscopy; S, substrate; P, product; I-T, chronoamperometry; D, drain; S, source; Vds, drain-source voltage; Vgs, gate-source voltage; FET, field effect transistor; Abs, absorbance; Em, emission; I (a.u.), intensity; λ, wavelength; LFA, lateral flow assay; Δν, Raman shift. Created with BioRender.com.

Figure 11.. Wearable immunosensors.

a, Non-faradaic impedance sensor mediated with room temperature ionic liquid (RTIL) to enhance the stability of sweat cortisol detection. Reproduced with permission from ref under CC BY 4.0. Copyright 2017 Munje et al. b, Microfluidic faradaic impedance sensor whose detection is initiated by manually pushing redox molecules in the reagent chamber to the detection chamber. Reproduced with permission from ref . Copyright 2020 Elsevier. c, Amperometric cortisol sensor on flexible laser-engraved graphene substrate. Reproduced with permission from ref . Copyright 2020 Elsevier. d, Colorimetric detection of cortisol based on a lateral flow strip embedded in a soft, microfluidic patch. Reproduced with permission from ref under CC BY 4.0. Copyright 2020 Proceedings of the National Academy of Sciences.

Figure 12.. Wearable aptasensors.

a, A wearable tuning circuit–inspired wireless aptasensor on gold electrode for serotonin detection in biofluids. Reproduced with permission from ref . Copyright 2022 The American Association for the Advancement of Science. b, Multiplexed aptamer array based on two different methylene labeled aptamer array for common drugs of abuse detection in artificial sweat. Reproduced with permission from ref . Copyright 2022 American Chemical Society. c, Field effect transistor-based aptasensor thin In₂O₃ for the detection of sweat cortisol. Reproduced with permission from ref . Copyright 2022 The American Association for the Advancement of Science.

Figure 13.. Wearable MIP-based sensors.

a, Touch-based amperometric MIP sensor for cortisol. Reproduced with permission from ref . Copyright 2021 Wiley. b, wearable electrochemical MIP sensor for the detection of electroactive (tyrosine) and non-electroactive (leucine) targets. Reproduced with permission from ref . Copyright 2022 Springer Nature. c, Organic electrochemical transistor integrated with a molecularly selective membrane for sweat cortisol detection. Reproduced with permission from ref . Copyright 2018 The American Association for the Advancement of Science. d, MIP based self-powered triboelectric sensor for the label-free detection of lactate. Reproduced with permission from ref . Copyright 2022 Elsevier.

Figure 14.. Scheme of iontophoresis-based sweat induction.

AXR: Axon-reflex mediated sweating. DIR: direct stimulated sweating.

Figure 15.. Iontophoresis-based sweat induction.

a–c, An iontophoresis patch (a) and sweating responses to different cholinergic agents (b,c). Reproduced with permission from ref . Copyright 2017 Proceedings of the National Academy of Sciences. d–f, A microneedle-based iontophoresis device (d) and in vivo sweat responses of the device (e,f). Reproduced with permission from ref under CC BY 4.0. Copyright 2021 Wiley. g, A carbachol-based iontophoresis sensing device. Reproduced with permission from ref . Copyright 2018 Royal Society of Chemistry. h,i, High sweat rate (h) and low sweat rate (i) duration of carbachol and pilocarpine iontophoresis stimulation, respectively. Reproduced with permission from ref . Copyright 2018 Elsevier. j, A flexible laser-engraved iontophoresis sensing patch. Scale bar, 5 mm. k,l, Localized sweat rates measured from the stimulated (k) and surrounding (l) skin areas after a 5-min iontophoresis with pilocarpine and carbachol. j–l, Reproduced with permission from ref . Copyright 2022 Springer Nature.

Figure 16.. Sweat sampling without microfluidic systems.

a, Rayon pad to direct exercise sweat to sensors in a fully-integrated sweat band. Reproduced with permission from ref . Copyright 2016 Springer Nature. b, Absorbent sponge for sweat wicking from the skin to sweat sensing by the gold electrodes patterned facing outward. Reproduced with permission from ref . Copyright 2014 Wiley. c, Silicone headband with a channel for gravity-facilitated sweat flow through the chip. Reproduced with permission from ref . Copyright 2017 American Chemical Society. d, Touched-based hydrogel for sweat capture from a fingertip. Reproduced with permission from ref . Copyright 2021 American Chemical Society. e, Nitrile glove-based and cot-based system for natural sweat analysis. Reproduced with permission from ref . Copyright 2020 The American Association for the Advancement of Science. f, Fiber-based platform for sweat capture from the skin. Reproduced with permission from ref . Copyright 2019 American Chemical Society.

Figure 17.. Sweat sampling with pressure driven microfluidics.

a, PDMS-based sweat harvesting system. Reproduced with permission from ref . Copyright 2016 The American Association for the Advancement of Science. b, PDMS microfluidic with hydrophilic fillers for natural sweat collection and transport. Reproduced with permission from ref under CC BY 4.0. Copyright 2021 Nyein et al. c, PDMS-based wearable SERS microfluidic platform. Reproduced with permission from 249 under CC BY 4.0. Copyright 2022 He et al. d, Laser-patterned 3D microfluidic system. Reproduced with permission from ref . Copyright 2019 Royal Society of Chemistry. e, Laser-engraved microfluidic patch with fast sweat refreshing. Reproduced with permission from ref . Copyright 2019 Springer Nature. f, Hex-wick for fast and low-volume sweat sampling. Reproduced with permission from ref . Copyright 2018 Royal Society of Chemistry.

Figure 18.. Sweat sampling with fluid actuation.

a, Passive actuation based on capillary bursting valves. Reproduced with permission from ref . Copyright 2017 Wiley. b–d, Active actuation based on super absorbent polymer (SAP) (b), thermal-responsive hydrogel (PNIPAM) (c), and electrowetting valves (d). b, Reproduced with permission from ref . Copyright 2018 Wiley. c, Reproduced with permission from ref under CC BY 4.0. Copyright 2020 Lin et al. d, Reproduced with permission from ref . Copyright 2021 Springer Nature.

Figure 19.. Sweat sampling with material-enhanced fluid transport.

a–c, Sweat transport improved with paper (a), hydrogel (b) and Zwitterionic polymer grafting (c). a, Reproduced with permission from ref . Copyright 2022 The American Association for the Advancement of Science. b, Reproduced with permission from ref . Copyright 2021 American Chemical Society. c, Reproduced with permission from ref . Copyright 2021 Wiley. d, Sweat collection by patterned superhydrophobic-superhydrophilic band. Reproduced with permission from ref . Copyright 2019 American Chemical Society. e, Cactus-spine-inspired directional sweat sampling. Reproduced with permission from ref . Copyright 2021 Wiley. f, Janus textile for directional sweat transport across layers. Reproduced with permission from ref . Copyright 2019 Wiley.

Figure 20.. Sweat sampling with induction.

a, Iontophoresis with Rayon-based sweat sampling. Reproduced with permission from ref . Copyright 2017 Proceedings of the National Academy of Sciences. b,c, Pilocarpine-iontophoresis induction with tattoo-based sensing platform (b) and multi-compartment laser-patterned microfluidic systems (c). b, Reproduced with permission from ref under CC BY 4.0. Copyright 2018 Wiley. c, Reproduced with permission from ref . Copyright 2020 Royal Society of Chemistry. d, Carbachol-iontophoresis with laser-engraved microfluidics. Reproduced with permission from ref . Copyright 2022 Springer Nature.

Figure 21.. Biofuel cells for harvesting chemical energy from sweat.

a, Epidermal tattoo-based biofuel cell for harvesting energy from sweat lactate. Reproduced with permission from ref . Copyright 2013 Wiley. b, Island-bridge-based lactate biofuel cell for enhanced performance under strain. Scale bar, 5 mm. Reproduced with permission from ref . Copyright 2017 Royal Society of Chemistry. c, A fully perspiration-powered electronic skin (PPES) for battery-free and wireless multiplexed sweat sensing. Reproduced with permission from ref . Copyright 2020 The American Association for the Advancement of Science. d, Ethanol biofuel cell for harvesting energy from sweat after alcohol consumption. Reproduced with permission from ref . Copyright 2021 Elsevier. e, Microbial fuel cell-based skin-interfaced microfluidic system for harvesting energy from bacteria in sweat. Reproduced with permission from ref . Copyright 2020 Elsevier.

Figure 22.. Nanogenerators for harvesting physical energy from the body.

a–d, Skin-interfaced wearable devices for harvesting energy via the thermoelectric effect (a), the piezoelectric effect (b), the magnetoelastic effect (c), and the triboelectric effect (d). a, Reproduced with permission from ref . Copyright 2020 Elsevier. b, Reproduced with permission from ref . Copyright 2018 Wiley. c, Reproduced with permission from . Copyright 2021 Springer Nature. d, Reproduced with permission from ref . Copyright 2020 The American Association for the Advancement of Science.

Figure 23.. Photovoltaic cells for harvesting energy from the environment.

a, An ultrathin organic photovoltaic cell integrated with an organic electrochemical transistor for wearable self-powered cardiac signal recording. Reproduced with permission from ref . Copyright 2018 Springer Nature. b, A flexible perovskite solar cell paired with a flexible lithium ion capacitor to self-power wearable strain sensors. Reproduced with permission from ref . Copyright 2019 Elsevier. c, A fully integrated smartwatch powered by a commercial flexible solar cell and a flexible battery for the continuous monitoring of sweat glucose. Reproduced with permission from ref . Copyright 2019 American Chemical Society.

Figure 24.. Hybrid energy harvesting from multiple energy sources.

a, A hybrid energy harvester integrating a lactate biofuel cell and a piezoelectric nanogenerator for harvesting energy from natural fingertip sweat and finger tapping. Reproduced with permission from ref . Copyright 2021 Elsevier. b, A textile bioenergy microgrid integrating a biofuel cell and a triboelectric nanogenerator for harvesting energy from exercise induced sweat lactate and arm swinging motions. Reproduced with permission from ref under CC BY 4.0. Copyright 2021 Yin et al. c, A spring-mass coupled hybrid generator integrating a triboelectric nanogenerator and electromagnetic nanogenerator for harvesting energy from exercise induced low-frequency vibrations. Reproduced with permission from ref . Copyright 2022 Wiley.

Figure 25.. Wireless energy harvesting from the mobile phone.

a, A bandage-like RFID sensor patch for the monitoring sweat Na⁺. Reproduced with permission from ref . Copyright 2015 IEEE. b, A soft epidermal microfluidic device integrating an NFC-based wireless monitoring of sweat glucose and lactate. Reproduced with permission from ref . Copyright 2019 The American Association for the Advancement of Science. c, An NFC-based wireless sweat sensor system with a stretchable electrode array for the multiplexed monitoring of sweat Na⁺, K⁺, pH, and glucose. Reproduced with permission from ref . Copyright 2019 Wiley.

Figure 26.. Energy storage: next generation batteries for powering wearable sweat sensors.

a, A fiber-based e-textile lithium-ion battery for powering a wearable sweat sensor system that monitors and displays sweat Na⁺ and Ca²⁺ levels. Scale bar, 2 cm. Reproduced with permission from ref . Copyright 2021 Springer Nature. b, Screen-printed stretchable AgO-Zn battery powered epidermal sweat sensor patch for monitoring and displaying various sweat metabolite and electrolyte levels. Reproduced with permission from ref . Copyright 2022 Springer Nature. c,d, Epidermal sweat activated batteries for monitoring heartrate (c) and sweat biomarkers (pH, glucose, and Na⁺) (d). c, Reproduced with permission from ref . Copyright 2020 Springer Nature. d, Reproduced with permission from ref under CC BY 4.0. Copyright 2022 Liu et al. e,f, Textile-based sweat activated batteries prepared on fabric (e) and on a cotton yarn (f). Scale bar, 3 cm. e, Reproduced with permission from ref . Copyright 2021 The American Association for the Advancement of Science. f, Reproduced with permission from ref under CC BY 4.0. Copyright 2022 Xiao et al.

Figure 27.. Energy storage: next generation sweat activated supercapacitors for powering wearable sweat sensors.

a, A textile-based wearable supercapacitor based on a PEDOT:PSS-coated cloth using sweat as the electrolyte. Reproduced with permission from ref under CC BY 4.0. Copyright 2020 Manjakkal et al. b, A twisted carbon threads-based supercapacitor using sweat as the electrolyte. Reproduced with permission from ref under CC BY 4.0. Copyright 2020 Lima et al. c, Hybrid textile-based supercapacitor-biofuel system with a supercapacitor and biofuel cell on each side of a sweatband. Reproduced with permission from ref . Copyright 2018 Royal Society of Chemistry. d, An all-printed biosupercapacitor integrating a biofuel cell and a supercapacitor in a single footprint for harvesting and storing energy from sweat. Scale bar, 2 cm. Reproduced with permission from ref . Copyright 2021 Wiley.

Figure 28.. Electronic system block diagram of wearable sweat sensors.

Control amplifier (CA), digital to analog converter (DAC), transimpedance amplifier (TIA), analog to digital converter (ADC), instrumentation amplifier (InAmp), serial peripheral interface (SPI), universal asynchronous receiver-transmitter (UART), general-purpose input/output (GPIO), direct current (DC).

Figure 29.. Strategies for choosing which types of integrated circuits to use for designing a wearable electronic device.

a–c, Electronic components can be categorized based on degree of integration as general purpose integrated circuits (GPICs) (a), application specific standard products (ASSPs) (b), and application specific integrated circuits (ASICs) (c).

Figure 30.. Approaches for designing a printed circuit board that can conform to skin.

a–d, Printed circuit boards (PCBs) can be classified based on degree of deformability as commercial FPCBs (a), ultrathin FPCBs (b), rigid islands stretchable PCBs (SPCBs) (c), and chip-less SPCBs (d). Scale bars in a,b, 1 cm; scale bar in d, 500 μm. a, Reproduced with permission from ref . Copyright 2022 Springer Nature. b, Reproduced with permission from ref . Copyright 2020 The American Association for the Advancement of Science. c, Reproduced with permission from ref under CC BY 4.0. Copyright 2019 The American Association for the Advancement of Science. d, Reproduced with permission from ref . Copyright 2022 The American Association for the Advancement of Science.

Figure 31.. Wearable sensors for fitness and human performance monitoring.

a, FISA enables multiplexed sweat analysis for dehydration identification during exercise. Reproduced with permission from ref . Copyright 2016 Springer Nature. b, Whole-body sweat rate versus regional sweat rate measured with microfluidic patches (left) and whole-body sweat chloride concentration versus regional sweat chloride measured with microfluidic patches. Reproduced with permission from ref . Copyright 2020 The American Association for the Advancement of Science. c, Thermistors-based flow sensor for wireless sweat rate monitoring validated with visual quantitation of sweat flow. Reproduced with permission from ref . Copyright 2021 Springer Nature. d, Sweat lactate concentration was found to be inversely related to sweat rate. Reproduced with permission from ref under CC BY 4.0. Copyright 2010 Springer Nature. e, Wearable lactate sensor that tracked sweat lactate threshold in conjunction with ventilatory threshold. Reproduced with permission from ref under CC BY 4.0. Copyright 2021 Seki et al. f, Correlations in variation rates of lactate concentrations between sweat from thigh (open circles), working muscle area or arm (closed circles), latent muscle area and blood. Reproduced with permission from ref . Copyright 2020 Wiley.

Figure 32.. Wearable sensors for cystic fibrosis diagnostics.

a, A commercial sweat test device for cystic fibrosis diagnosis. b, Correlation between chloride concentration obtained in sweat from CF (closed circles) and non-CF (open circles) subjects using Macroduct^® and from the QPIT method. Reproduced with permission from ref . Copyright 1994 Elsevier. c, Correlation between sweat chloride levels in CF (red circles) and non-CF (blue circles) subjects measured with a wearable sensor and with laboratory measurement. Reproduced with permission from ref . Copyright 2018 Elsevier. d, A soft epidermal microfluidic device for the in situ colorimetric quantitation of chloride in sweat. Scale bars, 5 mm. Reproduced with permission from ref . Copyright 2021 The American Association for the Advancement of Science. e, An integrated single battery-powered wearable device for localized sweat stimulation and sweat chloride analysis in situ. Reproduced with permission from ref . Copyright 2017 Proceedings of the National Academy of Sciences.

Figure 33.. Wearable sensors for metabolic syndrome diagnostics.

a, A wearable diabetes monitoring and feedback therapy patch consisting of a multimodal sensor patch for sweat glucose detection and a polymeric microneedles array for thermally-activated drug delivery. Reproduced with permission from ref . Copyright 2016 Springer Nature. b, A roll-to-roll fabricated microfluidic patch with a regional sweat rate sensor and sweat glucose sensor demonstrate inconsistent correlation between sweat glucose or glucose secretion rate and blood glucose in healthy and diabetic subjects. Reproduced with permission from ref . Copyright 2019 The American Association for the Advancement of Science. c, The rates of glucose concentration increase in capillary blood and in iontophoretic sweat after glucose intake for 90 minutes demonstrate good correlation (r=0.75). Reproduced with permission from ref . Copyright 2019 American Chemical Society. d, A wearable MIP-based biosensor for the metabolic profiling of various amino acids and nutrients. Sweat Leucine/BCAAs demonstrate good correlation with blood with elevations observed in obese and diabetic subjects. Scale bars, 1 cm (top) and 5 cm (bottom). Reproduced with permission from ref . Copyright 2022 Springer Nature.

Figure 34.. Wearable sensors for nutrition tracking.

a, Vitamin C profiles in iontophoretic sweat and urine after vitamin C consumption for two consecutive days obtained with a wearable sensor. Reproduced with permission from ref . Copyright 2020 Wiley. b, Temporal profile of vitamin C and alcohol in natural thermoregulatory sweat after intake using a glove-based sensor for natural sweat accumulation and in situ analysis. Reproduced with permission from ref . Copyright 2020 The American Association for the Advancement of Science. c, A miniaturized for the colorimetric assessment of vitamin C, calcium, zinc, and iron, and transdermal nutrients delivery. Reproduced with permission from ref under CC BY 4.0. Copyright 2021 Kim et al. d, A controlled purine-diet study of uric acid levels in subjects with gout, hyperuricemia, and healthy subjects using a wearable laser-engraved platform. Scale bar, 1 cm. Reproduced with permission from ref . Copyright 2019 Springer Nature.

Figure 35.. Wearable sensors for stress monitoring.

a, A fully integrated, flexible, and wireless mHealth device, for stress response monitoring in sweat cortisol. Reproduced with permission from ref . Copyright 2020 Elsevier. b, A wearable aptamer-field-effect transistor-based smartwatch with signal correction algorithm for sweat cortisol detection. Reproduced with permission from ref . Copyright 2022 The American Association for the Advancement of Science.

Figure 36.. Wearable sensors for therapeutic drug monitoring.

a, Therapeutic window based on pharmacokinetics and pharmacodynamics of drug concentrations in blood and alternative biofluids like sweat. Reproduced with permission from ref . Copyright 2020 Proceedings of the National Academy of Sciences. b, Catabolic products of caffeine found in fingertip sweat and metabolic networks facilitated discovery of dynamic metabolic patterns. Reproduced with permission from ref under CC BY 4.0. Copyright 2021 Brunmair et al. c, A wearable sensor for the detection of electroactive methylxanthine drug, caffeine. Reproduced with permission from ref . Copyright 2018 Wiley. d, Chronological profile of levodopa in natural sweat after intake using a wearable microfluidic fingertip patch. Reproduced with permission from ref . Copyright 2021 Wiley. e, Absorption and elimination kinetics of acetaminophen in sweat obtained with a wearable smart watch. Reproduced with permission from ref . Copyright 2020 Proceedings of the National Academy of Sciences.

Figure 37.. Wearable sensors for substance monitoring.

a, Photo of a commercial continuous remote alcohol monitor. Reproduced with permission from ref . Copyright 2020 Elsevier. b, Pharmacokinetics of TAC and BrAC after intake. Reproduced with permission from ref . Copyright 2006 Wiley. c, Tracking of TAC for the contingency management of alcohol disorder. Reproduced with permission from ref . Copyright 2011 Elsevier. d, A flexible tattoo device with sweat induction electrodes for in situ epidermal sweat stimulation and alcohol sensing. Reproduced with permission from ref . Copyright 2016 American Chemical Society. e, A wearable sweat sensing device that combined an iontophoresis module with commercial screen-printed carbon electrodes for alcohol detection and comparison with blood alcohol metabolism. Reproduced with permission from ref . Copyright 2018 Royal Society of Chemistry.

Figure 38.. Wearable sensors for drug abuse detection.

a, A wearable nicotine sensor for sweat nicotine levels monitoring during exercise. Reproduced with permission from ref . Copyright 2020 American Chemical Society. b, Detection of methadone, methamphetamine, amphetamine, and tetrahydrocannabinol spiked in artificial sweat with a rapid quantitative competitive immunoassay-based capillary array. Reproduced with permission from ref . Copyright 2020 Royal Society of Chemistry. c, Latent fingerprints containing narcotic drug metabolites fluorescently labeled with antibodies. Scale bars, 2 mm. Reproduced with permission from refs ,. Copyright 2007 Wiley. Copyright 2010 American Chemical Society. d, A wearable electrochemical for the detection of psychoactive drugs in artificial sweat. Reproduced with permission from ref . Copyright 2022 American Chemical Society.

Figure 39.

Multimodal data acquisition. a, Multimodal ECG and sweat lactate measuring device. Reproduced with permission from ref under CC BY 4.0. Copyright 2016 Imani et al. b, Laser engraved biosensor with multiple sensing modalities and a high degree of flexibility. Scale bar, 1 cm. Reproduced with permission from ref . Copyright 2022 The American Association for the Advancement of Science. c, Wearable device with both sweat and ISF sensing capabilities. Reproduced with permission from ref under CC BY 4.0. Copyright 2018 Wiley. d, Colorimetric wearable device with glucose and lactate sensors. Reproduced with permission from ref . Copyright 2019 The American Association for the Advancement of Science. e, Stress detecting wearable device integrated with lateral flow immunoassay. Reproduced with permission from ref under CC BY 4.0. Copyright 2020 Proceedings of the National Academy of Sciences.

Figure 40.. Sensor crosstalk and calibration.

a, Influence of temperature on glucose and lactate sensors. Reproduced with permission from ref . Copyright 2016 Springer Nature. b, Influence of electrolyte (Na⁺) level on tryptophan biosensor response. Reproduced with permission from ref . Copyright 2022 Springer Nature. c, Influence of ammonium (NH₄⁺) on urea biosensors. Reproduced with permission from ref . Copyright 2020 The American Association for the Advancement of Science. d, Influence of pH on glucose biosensors. Reproduced with permission from ref . Copyright 2016 Springer Nature.

Figure 41.. Data processing and machine learning.

a, Broad overview of the machine learning experimental pipeline from biosensor fabrication to industry application. Reproduced with permission from ref . Copyright 2021 Wiley. b, Principal component analysis (PCA) analysis that can categorize different cell lines based on gene expression. Reproduced with permission from ref under CC BY 4.0. Copyright 2016 Lenz et al. c, Shapley additive explanations (SHAP) analysis of two kinase inhibitors, displaying functional groups that help (red) or hurt (blue) its potency. Reproduced with permission from ref under CC BY 4.0. Copyright 2020 Rodríguez-Pérez et al. d, Flow chart for extracting features from electrochemical measurements, training a model, and predicting analyte concentrations. Reproduced with permission from ref . Copyright 2022 Elsevier. e, Generic training process for a neural network. Reproduced with permission from ref . Copyright 2020 American Chemical Society.

Figure 42.. Exponential growth of feature space with input dimension.

a–c, An evenly spaced sampling across a 1-dimensional feature space (4 data points) (a), a 2-dimensional feature space (16 data points) (b), and a 3-dimensional feature space (64 data points) (c).

Figure 43.. Wearable device product life cycle.

Reproduced with permission from refs ,. Copyright 2020 The American Association for the Advancement of Science. Copyright 2016 Wiley.

Figure 44.. Mass manufacturing techniques for low-cost wearable electronics and microfluidic patches.

a, Screen printed electrode fabrication and flexible graphene ink formulation. Reproduced with permission from refs ,. Copyright 2022 American Chemical Society. Copyright 2019 Wiley. b, Inkjet printing of electrodes and bioink enzyme functionalization. Scale bar, 1 cm. Reproduced with permission from ref . Copyright 2022 The American Association for the Advancement of Science. c, Roll-to-roll electrode fabrication. Reproduced with permission from ref . Copyright 2018 American Chemical Society. d, Roll-to-roll lab-on-a-chip fabrication. Reproduced with permission from ref . Copyright 2019 The American Association for the Advancement of Science. e, Laser-engraved lab on the skin. Scale bar, 1 cm. Reproduced with permission from ref . Copyright 2019 Springer Nature.

Figure 45.

Number of annual publications and citations on ‘sweat sensing’ from 2011 to 2021 according to Web of Science.