Wearable and flexible electrochemical sensors for sweat analysis: a review

The review addresses the need for noninvasive, continuous, real-time health monitoring that can detect suboptimal health before overt disease. Traditional care relies on symptomatic presentation and clinic-based diagnostics. Wearable biosensors promise dynamic monitoring of biochemical markers in accessible biofluids. While vital-sign wearables are mature, they reflect biophysical rather than biochemical states. Among biofluids, sweat is highlighted for its noninvasive access, analyte richness, and correlations with blood levels (e.g., glucose, lactate, ethanol). The purpose of the review is to summarize advances enabling wearable electrochemical sweat sensing—including sweat stimulation/collection, sensor modalities and materials, electronics and power systems—and to outline applications, challenges, and future directions toward personalized, intelligent medicine.

The paper surveys prior work across: (1) comparative analysis of biofluids for wearable sensing, noting limitations of blood (invasive), urine (non-continuous), tears (collection irritation), saliva (contamination), and interstitial fluid (invasive collection), positioning sweat as advantageous for noninvasive, body-wide sampling with molecular-level insight; (2) sweat biomarker landscape spanning electrolytes (Na+, K+, Cl−, Ca2+, NH4+, pH), metabolites (glucose, lactate, ethanol, uric acid), drugs (e.g., caffeine, levodopa), trace metals (Zn2+, Cu2+), and small molecules (cortisol, IL-6, NPY, tyrosine), with linked physiological/clinical relevance (e.g., CF diagnosis via chloride; dehydration/electrolyte imbalance; diabetes; kidney and liver disorders; stress and immune monitoring); (3) sweat stimulation methods, especially iontophoresis and improvements to reduce irritation, enable dual-fluid (sweat + ISF) sampling, and maintain data integrity; (4) microfluidic sweat collection strategies using capillarity, osmotic hydrogels, evaporation micropumps, and integrated electrochemical reservoirs, including scalable manufacturing (roll-to-roll, laser engraving) and advances for low-rate resting sweat monitoring; (5) electrochemical detection modalities—potentiometry (ISEs for ions/pH and immunosensing), amperometry (enzyme-based glucose, lactate, alcohol), voltammetry (DPV, CV, SWASV for drugs and trace metals), with notes on emerging contactless gas-based and photoelectrochemical approaches; (6) flexible/stretchable materials for substrates (PET, PI, PDMS, PU, PMMA), textiles and threads, and paper microfluidics, and active electrode materials (graphene, MXenes like Ti3C2Tx, silk-derived N-doped carbon textiles) and fabrication (screen/gravure printing, lithography, laser engraving); (7) electronics for signal conditioning, ADC, microcontroller calibration, and wireless links (BLE, NFC, RFID), with considerations of power, bandwidth, and user interaction; (8) power sources including flexible batteries, safer zinc–Mn systems, and energy harvesting (solar PV, biofuel cells from sweat metabolites, triboelectric nanogenerators), supercapacitor buffering, and hybrid microgrid strategies; (9) milestone devices from single-analyte tattoo sensors (2013) to fully integrated multiplexed arrays (2016), microfluidic-iontophoretic platforms (2017), eyewear and smartwatch form factors, battery-free NFC systems, and multimodal platforms combining chemical and physical sensing.

This is a narrative review synthesizing recent advances in wearable electrochemical sweat sensing. The authors organize the field by: (1) profiling sweat’s analytical advantages and biomarker relevance; (2) detailing sweat stimulation (e.g., iontophoresis) and microfluidic collection approaches; (3) describing sensor components—electrochemical modalities (potentiometry, amperometry, voltammetry), materials and fabrication, electronics, and wireless interfaces; (4) discussing power strategies (batteries, biofuel cells, TENGs, PV, supercapacitors, hybrid microgrids); (5) highlighting representative platforms for electrolytes, metabolites, drugs, trace metals, and other small molecules (e.g., cytokines, hormones); and (6) analyzing challenges and future directions. No systematic search strategy or meta-analysis is reported; examples are drawn from seminal and recent publications to illustrate technological progress and application scope.

- Sweat is highly suitable for noninvasive, continuous biochemical monitoring: ~99% water content and average pH ~6.3; many analytes show meaningful correlations with blood (e.g., glucose, lactate, ethanol). - Clinically relevant links include: sweat chloride as a gold standard biomarker for cystic fibrosis screening; electrolyte balance (Na+, K+, Ca2+), hydration and thermoregulation; metabolites (glucose for diabetes, lactate for exercise physiology/ischemia risk, ethanol for alcohol monitoring); uric acid for renal/gout assessment; drugs (caffeine, levodopa) for pharmacokinetics; trace metals (Zn2+, Cu2+); stress/inflammatory markers (cortisol, IL-6, NPY, tyrosine). - Stimulation and collection: Iontophoresis enables sedentary sampling but requires safety controls to reduce irritation; dual-fluid (sweat + ISF) sampling has been demonstrated. Microfluidics improves sample integrity and temporal resolution via capillary flow, osmotic hydrogels, and evaporation-driven pumps; scalable R2R and laser engraving manufacturing were demonstrated; novel patches enable continuous analysis of resting thermoregulatory sweat. - Electrochemical modalities: Potentiometry with ISEs for ions/pH; amperometry with enzymes for glucose, lactate, alcohol; voltammetry (SWASV/CV/DPV) for trace metals and drugs. Gas-based contactless and photoelectrochemical sensing are promising future directions. - Materials/fabrication: Flexible polymers (PET, PI, PDMS, PU, PMMA), breathable textiles and thread-based sensors, and paper microfluidics expand wearability and integration. Advanced electrodes (graphene, MXenes like Ti3C2Tx, SilkNCT) enhance sensitivity/stability. Manufacturing via screen/gravure printing and laser engraving supports scalable, high-throughput production. - Electronics/wireless: Integrated AFE, ADC, MCU calibration, and wireless links; BLE offers up to ~100 m range but higher power; NFC enables battery-free close-range operation (<10 cm); RFID patches enable low-component electrolyte and temperature monitoring. - Power/self-sufficiency: Flexible/stretchable batteries and safer zinc–Mn systems; energy harvesting via PV, biofuel cells powered by sweat metabolites (with SC buffering for stability), and triboelectric nanogenerators; hybrid microgrids combining BFC, TENG, and supercapacitors demonstrated autonomous operation. - Representative platforms: From the first tattoo lactate sensor (2013) to fully integrated multiplexed arrays (2016) measuring Na+, K+, glucose, lactate with temperature compensation; iontophoresis-based autonomous platforms for CF and glucose; eyewear and smartwatch form factors; battery-free NFC microfluidics for multiplex analysis; multimodal systems combining ultrasound blood pressure with sweat and ISF biochemical sensing. - Heavy metals and drugs: Real-time wearable SWASV detection of Zn2+ and multiplex heavy metals (Zn, Cd, Pb, Cu, Hg); fully printed microfluidic nanosensor for Cu2+. Drug monitoring via DPV/CV enabled caffeine and levodopa detection in sweat with improved electrode stability. - Other analytes: Affinity-based sensors (antibodies/aptamers, MIPs) and EIS/CV readouts for IL-6 and cortisol; graphene-based wireless cortisol systems mapped circadian and stress responses; thread-based cortisol immunosensors improved sensitivity; laser-engraved DPV platforms detected ultralow uric acid and tyrosine.

The review demonstrates that integrating sweat stimulation, microfluidic collection, advanced electrochemical detection, flexible materials, and low-power electronics enables reliable, real-time, noninvasive biochemical monitoring. These developments address the need for proactive, personalized health assessment by providing molecular-level insights complementary to vital signs. Multiplexed sensing and multimodal integration (with ISF and physical sensors) improve accuracy through cross-calibration and broaden clinical utility. Power autonomy via energy harvesting and storage supports continuous operation. Remaining challenges—sample integrity (evaporation, mixing, contamination), sweat-rate variability, low analyte concentrations, user comfort and safety (iontophoresis irritation), and scalable manufacturing—are clearly articulated, guiding future research toward more robust, accurate, and deployable systems for large-scale clinical and wellness applications.

The paper consolidates the state of wearable electrochemical sweat sensing, covering biomarkers, stimulation/collection, sensing modalities, materials, electronics, power, and application exemplars. It highlights a trajectory from single-analyte demonstrations to integrated, multiplexed, and multimodal platforms with growing potential in health monitoring and disease detection. Future directions include: (1) deeper integration and intelligence (on-device analytics, machine learning; multimodal chemical/physical/electrophysiological sensing); (2) improved sample reliability (real-time sweat-rate monitoring/compensation; collection tailored to context; prevention of evaporation/mixing/contamination); (3) efficient, sustainable power (hybrid energy harvesting, advanced storage and power management; energy-aware sensing); (4) ultra-sensitive detection for low-abundance analytes (advanced microfluidics, affinity/MIP strategies, and potentially photoelectrochemistry); and (5) safer, low-current sedentary sweat induction and improved resting-sweat collection for broader medical use.

- Sweat composition and secretion rate vary widely across individuals, locations, and contexts; analyte partitioning and rate effects complicate calibration and blood correlation. - Evaporation, mixing of fresh/old sweat, and skin contaminants can alter analyte concentrations without proper microfluidic isolation and flow control. - Iontophoresis can irritate skin and corrode electrodes; long-term continuous use is limited without safety controls and low-current designs. - Many clinically relevant targets are at low concentrations and sensitive to pH/temperature, challenging sensitivity and stability of wearable electrochemical sensors. - Powering continuous, multiplexed sensing with wireless communications remains difficult; existing harvesters can be intermittent, requiring buffering and efficient power management. - Manufacturing challenges include achieving uniform, high-throughput, low-cost production with precise microfluidics and electrode architectures on soft, breathable substrates. - As a narrative review, no systematic search protocol is described; coverage may be selective and not exhaustive.