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Cited by 5,087Advanced Sensor and Energy Harvesting MaterialsNon-Invasive Vital Sign MonitoringElectrochemical sensors and biosensors

Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis

Open access
Gao, Wei, Emaminejad, Sam, Nyein, Hnin Yin Yin, Challa, Samyuktha, Chen, Kevin, Peck, Austin, Fahad, Hossain M., Ota, Hiroki +6 more·2016·Nature
DOI 10.1038/nature16521PMC PMC4996079
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Abstract

Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.

AI snapshot

Written from the paper’s full text.

TL;DR

A flexible wearable sensing array with full on-board integration was built to measure sweat glucose, lactate, sodium, potassium, and skin temperature at the same time, with signal conditioning, processing, and Bluetooth transmission. Human exercise trials showed it could track sweat profiles in real time and detect dehydration-related electrolyte changes.

Key findings

  • The platform merged plastic-based sensors with silicon integrated circuits on a flexible printed circuit board, enabling multiplexed sweat analysis without external analysis; five sensors measured metabolites, electrolytes, and skin temperature.
  • In vitro sensitivities were 2.35 nA μM−1 for glucose over 0–200 μM, 220 nA mM−1 for lactate over 0–30 mM, 64.2 mV per decade for Na+ over 10–160 mM, 61.3 mV per decade for K+ over 1–32 mM, and about 0.18% per degree Celsius for temperature over 20–40 °C.
  • Sensors showed negligible interference from non-target species, and temperature compensation corrected enzymatic sensor overestimation; long-term tests indicated stable sensitivities for at least four weeks, with Na+/K+ at about 62.5 and 59.5 mV per decade in ambient conditions and glucose/lactate within 5% of original values when stored at 4 °C.
  • On-body trials with 26 healthy subjects (4 females, 22 males, aged 20–40) tracked sweat during cycling and outdoor running; dehydration trials without water intake showed sweat [Na+] increases after about 80 min and roughly 2.5% body-weight loss, while euhydration with 150 ml water every 5 min kept [Na+] and [K+] stable after initial changes.

Methods

  • Design: a five-sensor array on PET with 3-mm electrodes, including enzymatic amperometric glucose/lactate sensors, ion-selective Na+/K+ sensors, and a resistive temperature sensor, integrated with an FPCB containing analogue conditioning, an ATmega328P microcontroller, and Bluetooth.
  • Data: in vitro characterization in analyte solutions and artificial sweat; on-body testing in constant-load cycling (14 volunteers: 4 females, 10 males), graded cycling (7 males), and outdoor running (12 males), plus ex situ sweat comparisons.
  • Analysis: chronoamperometry for glucose/lactate, open-circuit potentiometry for Na+/K+, resistance for temperature, with on-board calibration/compensation and wireless data relay to a mobile app.

Limitations

  • Stated: glucose and lactate sensor responses degraded after about two hours of use because of reduced enzyme activity, though the sensor array can be replaced via the sensor–FPCB interface.
  • Stated: wearing the plastic-substrate device raised local temperature, which may slightly bias actual skin-temperature readings, but on-board calibration was reported to prevent impact on electrolyte and metabolite measurements; in vitro temperature-compensation tests also had noise from uneven solution heating.
  • Evident: the human sample was small and heavily male-skewed (26 total; 4 females, 22 males; graded and outdoor running trials included only males), and the paper does not report long-term continuous use beyond the exercise sessions for the enzymatic sensors.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/nature16521

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

16 of 42 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Skin temperature is clinically informative of various diseases and skin injuries such as pressure ulcers.

    “skin temperature is clinically informative of a variety of diseases and skin injuries such as pressure ulcers23,24.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [23] Webb, R. C. et al. Ultrathin conformal devices for precise and continuous thermal characterization of human skin. Nature Mater. 12, 938–944 (2013) source

      The Abstract says that skin thermometry can provide clinically relevant information about cardiovascular health, malignancy and other aspects of physiology. It does not link skin temperature to pressure ulcers or establish its clinical value for assessing skin injuries; its mention of wound healing concerns local heating as a possible intervention. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [24] Sprigle, S., Linden, M., McKenna, D., Davis, K. & Riordan, B. Clinical skin temperature measurement to predict incipient pressure ulcers. Adv. Skin Wound Care 14, 133–137 (2001) source
  • Interpretationcitation

    The decreases in sweat lactate and glucose concentrations are expected due to dilution from increased sweat rate as exercise continues.

    “The decreases in concentration of lactate and glucose in sweat are expected, owing to the dilution effect caused by an increase in sweat rate, which is visually observed as exercise continues13.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [13] Sonner, Z. et al. The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications. Biomicrofluidics 9, 031301 (2015) source

      The Introduction (page not available in our copy) explains that increasing sweat flow can dilute biomarkers whose transport into sweat is slower than the flow. It does not establish that lactate and glucose concentrations both decrease as exercise continues; instead, it says high-exertion tests can show a spike in sweat lactate associated with sweat rate. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Interpretationcitation

    The relatively stable [K+] behavior is explained by passive ion partitioning.

    “The relatively stable behaviour of [K+] is explained by its passive ion partitioning mechanism13.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [13] Sonner, Z. et al. The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications. Biomicrofluidics 9, 031301 (2015) source

      The section headed “Passive ion partitioning: Potassium (mM)” reports that sweat K+ concentration is independent of sweat rate, supporting the description of relatively stable behavior. But it says the precise partitioning mechanism has not been fully confirmed, so it does not establish passive partitioning as the explanation. No page number is available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Interpretationcitation

    With a single-centred flow model, the shortest sampling interval is under 1 min, calculated from the sweat rate (~3-4 mg min−1 cm−2) and the pad dimensions (1.5 cm × 2 cm × 50 μm).

    “Assuming a single-centred flow model13, the best-case sampling interval can be calculated to be less than 1 min, based on the sweat rate (~3–4 mg min−1 cm−2)39 and the pad size (1.5 cm × 2 cm × 50 μm).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [13] Sonner, Z. et al. The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications. Biomicrofluidics 9, 031301 (2015) source
    • cites [39] Vimieiro-Gomes, A. C. Comparison of sweat rate during graded exercise and the local rate induced by pilocarpine. Braz. J. Med. Biol. Res. 38, 1133–1139 (2005) source

      The Abstract (page unavailable) reports local exercise-induced sweat rates of 2.1 ± 1.4 and 2.7 ± 1.2 mg cm−2 min−1 in nine young men. That supports using a sweat rate on the order of 3 for an estimate, but not the cited value of approximately 3–4 as a reported rate. The citation is attached to the sweat-rate input, not to the flow model, pad dimensions, or calculated interval. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • The authors state this as an assumption: Sweat flow can be modeled as a single-centred flow.
  • Interpretationcitation

    Lactate concentration becomes relatively stable after 1,100 s, indicating stabilization of physiological responses to continuous sub-maximal constant-exercise power output.

    “However, lactate concentration becomes relatively stable after 1,100 s, indicating the stabilization of physiological responses to continuous, sub-maximal constant-exercise power output22.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [22] Derbyshire, P. J., Barr, H., Davis, F. & Higson, S. P. Lactate in human sweat: a critical review of research to the present day. J. Physiol. Sci. 62, 429–440 (2012) source

      The review’s “Sweat lactate variation with exercise intensity” section (page unavailable) reports that sweat lactate decayed and then reached a plateau during incremental cycling. It does not give 1,100 s as the time of stabilization or interpret the plateau as stabilization of physiological responses during continuous, sub-maximal constant-power exercise. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Classified as probably not a substantial claim. 22
  • May combine two claims. 30
  • The quote only partly states this claim. 1

  • Probably not a substantial claim: may not pass S2 (checkable).

    Premisecitation

    Wearable sensor technologies are essential for personalized medicine through continuous monitoring of an individual's health.

    “Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health1–12.”
    Quote in the paperNot a substantial claim3 of 10 sources checked
    • cites [1] Kim, D. H. et al. Epidermal electronics. Science 333, 838–843 (2011) source

      The paper’s Abstract describes skin-integrated sensors for physiological-status monitoring, and its ECG, EMG and EEG demonstrations show that they can measure an individual’s signals. It does not establish that wearable sensors are essential to personalized medicine or demonstrate continuous health monitoring; it notes that long-term use requires further work (Abstract; page unavailable). (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [2] Lipomi, D. J. et al. Skin-like pressure and strain sensors based on transparent elastic films of carbon nanotubes. Nature Nanotechnol. 6, 788–792 (2011) source
    • cites [3] Takei, K. et al. Nanowire active-matrix circuitry for low-voltage macroscale artificial skin. Nature Mater. 9, 821–826 (2010) source
    • cites [4] Wu, W. et al. Piezoelectricity of single-atomic-layer MoS2 for energy conversion and piezotronics. Nature 514, 470–474 (2014) source
    • cites [5] McAlpine, M. C., Ahmad, H., Wang, D. & Heath, J. R. Highly ordered nanowire arrays on plastic substrates for ultrasensitive flexible chemical sensors. Nature Mater. 6, 379–384 (2007) source

      The Abstract (p. 1) says flexible chemical and biological sensors could enable wearable monitoring systems. It does not establish that wearable sensors are essential to personalized medicine or that they continuously monitor an individual's health; those claims are stronger and more specific than the paper's proposed application. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [6] Kaltenbrunner, M. et al. An ultra-lightweight design for imperceptible plastic electronics. Nature 499, 458–463 (2013) source
    • cites [7] Xu, S. et al. Soft microfluidic assemblies of sensors, circuits, and radios for the skin. Science 344, 70–74 (2014) source

      The Abstract says skin-mounted sensors can provide clinical-quality health monitoring for continuous use and that continuous physiological monitoring is needed to treat many medical conditions. It does not say wearable sensors are essential to the realization of personalized medicine; that part overstates what the paper supports. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [8] Wang, C. et al. User-interactive electronic skin for instantaneous pressure visualization. Nature Mater. 12, 899–904 (2013) source
    • cites [9] Liang, J., Li, L., Niu, X., Yu, Z. & Pei, Q. Elastomeric polymer light-emitting devices and displays. Nature Photon. 7, 817–824 (2013) source
    • cites [10] Kim, D. H., Ghaffari, R. & Rogers, J. A. Flexible and stretchable electronics for biointegrated devices. Annu. Rev. Biomed. Eng. 14, 113–128 (2012) source

  • May combine two claims.

    Premisecitation

    Previously reported sweat-based and other non-invasive biosensors either monitor only one analyte at a time or lack on-site signal processing and calibration for accurate physiological analysis.

    “Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state14–18.”
    Quote in the paperSubstantial claim2 of 5 sources checked
    • cites [14] Schazmann, B. et al. A wearable electrochemical sensor for the real-time measurement of sweat sodium concentration. Anal. Methods 2, 342–348 (2010) source
    • cites [15] Jia, W. et al. Electrochemical tattoo biosensors for real-time noninvasive lactate monitoring in human perspiration. Anal. Chem. 85, 6553–6560 (2013) source
    • cites [16] Coyle, S. et al. BIOTEX—biosensing textiles for personalised healthcare management. IEEE Trans. Inf. Technol. Biomed. 14, 364–370 (2010) source

      The Introduction describes limitations of earlier sweat-collection methods, but does not say that previously reported biosensors were restricted to one analyte or lacked on-site processing and calibration. It instead describes BIOTEX’s multiparametric patch; the sensor and control-electronics sections discuss calibration before trials and signal processing, without establishing the claimed either-or limitation of prior devices. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [17] Bandodkar, A. J. et al. Epidermal tattoo potentiometric sodium sensors with wireless signal transduction for continuous non-invasive sweat monitoring. Biosens. Bioelectron. 54, 603–609 (2014) source
    • cites [18] Rose, D. P. et al. Adhesive RFID sensor patch for monitoring of sweat electrolytes. IEEE Trans. Biomed. Eng. 62, 1457–1465 (2015) source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Sweat lactate can potentially serve as a sensitive marker of pressure ischaemia.

    “sweat lactate can potentially serve as a sensitive marker of pressure ischaemia22;”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [22] Derbyshire, P. J., Barr, H., Davis, F. & Higson, S. P. Lactate in human sweat: a critical review of research to the present day. J. Physiol. Sci. 62, 429–440 (2012) source

  • May combine two claims.

    Premisecitation

    Human sweat contains physiologically rich information, and sampling it could enable non-invasive monitoring.

    “Sampling human sweat, which is rich in physiological information13, could enable non-invasive monitoring.”
    • Also stated in: § Abstract · plain
      “Measurements of human sweat could enable such insight, because it contains physiologically and metabolically rich information that can be retrieved non-invasively13.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [13] Sonner, Z. et al. The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications. Biomicrofluidics 9, 031301 (2015) source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A two-electrode configuration using Ag/AgCl as both reference and counter electrode is a standard approach for low-current electrochemical sensing.

    “The two-electrode system is a common strategy for low-current electrochemical sensing34,35.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [34] Kudo, H. et al. A flexible and wearable glucose sensor based on functional polymers with Soft-MEMS techniques. Biosens. Bioelectron. 22, 558–562 (2006) source
    • cites [35] Bandodkar, A. J. et al. Tattoo-based noninvasive glucose monitoring: a proof-of-concept study. Anal. Chem. 87, 394–398 (2015) source

      The Results and Discussion section describes this tattoo glucose sensor using an Ag/AgCl electrode as a combined counter/reference electrode alongside a working electrode (page unavailable). It does not say that this two-electrode configuration is a common or standard strategy for low-current electrochemical sensing; its discussion of lower current density concerns glucose extraction by reverse iontophoresis, not the sensing configuration. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationcitation

    The dehydration trends are probably caused by increased blood serum [Na+] and [K+] with dehydration and increased neural stimulation, agreeing with previous ex situ sweat analyses.

    “These trends are probably caused by increased blood serum [Na+] and [K+] with dehydration and increased neural stimulation, a conclusion in agreement with previous ex situ sweat analyses33.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [33] Morgan, R. M., Patterson, M. J. & Nimmo, M. A. Acute effects of dehydration on sweat composition in men during prolonged exercise in the heat. Acta Physiol. Scand. 182, 37–43 (2004) source

      The Results report higher serum Na+ and K+ during dehydration, and the Discussion proposes greater extracellular Na+ and sympathetic nervous activity as possible explanations for higher sweat Na+. The Discussion’s concluding mechanism emphasizes Na+ and Cl−, aldosterone, and sympathetic activity; it does not identify increased serum K+ as a specific cause. The Experimental procedures describe sweat collected from a forearm patch and analyzed after collection, consistent with ex situ analysis. Page numbers are unavailable in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingnone given

    The paper presents a mechanically flexible, fully integrated sensor array for multiplexed in situ perspiration analysis that simultaneously and selectively measures sweat metabolites such as glucose and lactate, electrolytes such as sodium and potassium, and skin temperature for sensor calibration.

    “Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors).”
    • Also stated in: § Abstract · plain
      “Here we present a wearable flexible integrated sensing array (FISA) for simultaneous and selective screening of a panel of biomarkers in sweat (Fig. 1a).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    The wearable system measures detailed sweat profiles of human subjects during prolonged indoor and outdoor physical activities and makes real-time assessments of their physiological state.

    “The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Prussian blue mediator minimizes reduction potentials to approximately 0 V versus Ag/AgCl, eliminating the need for an external power source to activate the sensors.

    “The use of Prussian blue dye as a mediator minimizes the reduction potentials to approximately 0 V (versus Ag/AgCl) (Extended Data Fig. 2a), and thus eliminates the need for an external power source to activate the sensors.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The water-absorbent rayon pad could hold about 10 μl of sweat, enough to give stable sensor readings.

    “The pad could absorb about 10 μl of sweat, which was sufficient to provide stable sensor readings.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Sweat [Na+] increases and [K+] decreases at the beginning of perspiration, consistent with previous ex situ studies.

    “Sweat [Na+] increases and [K+] decreases in the beginning of perspiration, in line with the previous ex situ studies from the collected sweat samples28,29.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [28] Cage, G. W., Wolfe, S. M., Thompson, R. H. & Gordon, R. S. Jr. Effects of water intake on composition of thermal sweat in normal human volunteers. J. Appl. Physiol. 29, 687–690 (1970) source
    • cites [29] Patterson, M. J., Galloway, S. D. R. & Nimmo, M. A. Variations in regional sweat composition in normal human males. Exp. Physiol. 85, 869–875 (2000) source

  • May combine two claims.

    Findingown data

    The entire system is mechanically flexible, making it a practical wearable sensor technology for prolonged indoor and outdoor physical activities.

    “Importantly, the entire system is mechanically flexible, thus delivering a practical wearable sensor technology that can be used for prolonged indoor and outdoor physical activities.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingreasoning

    Conditioning the ion-selective sensors with a solution containing 0.1-M NaCl and 0.01-M KCl for 1 h before measurements further minimizes potential drift.

    “This conditioning process was important to minimize the potential drift further.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    No apparent difference in glucose concentration is observed at different power output settings, consistent with blood glucose response to graded short-term exercise.

    “No apparent difference is observed for glucose concentration at different power output settings, a finding consistent with the response of blood glucose to graded, short-term exercise30.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Messonnier, L. A. et al. Lactate kinetics at the lactate threshold in trained and untrained men. J. Appl. Physiol. 114, 1593–1602 (2013) source

  • May combine two claims.

    Findingown data

    The sensitivity relative standard deviation was roughly 1% for Na+ and K+ sensors and roughly 5% for glucose and lactate sensors.

    “Extended Data Fig. 6a–d show that Na+ and K+ sensors had a relative standard deviation of ~1% in sensitivity while glucose and lactate sensors had a relative standard deviation of ~5% in sensitivity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Temperature has minimal effect on potentiometric sensors but greatly influences enzymatic sensor performance.

    “Although temperature has a minimal effect on the potentiometric sensors, it greatly influences the performance of the enzymatic sensors.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    After power is raised, sweat rate visibly increases, followed by sharp increases in skin temperature and sweat [Na+] and a slight increase in [K+], with [K+] remaining stable in three of seven subjects.

    “After the power is raised, the sweat rate visibly increases, followed by a sharp increase in skin temperature and sweat [Na+] as well as a slight increase in [K+] (in three of the seven subjects, [K+] remained stable).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingnone given

    A parylene insulating layer ensures reliable sensor reading by preventing electrical contact of metal lines with skin and sweat.

    “Parylene is used as an insulating layer to ensure reliable sensor reading by preventing electrical contact of the metal lines with skin and sweat.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    Both sweat [Na+] and [K+] stabilize as cycling continues.

    “Both [Na+] and [K+] stabilize as the cycling continues.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Without temperature compensation, increasing temperature leads to substantial overestimation of glucose and lactate concentrations; with compensation, readings are accurate and consistent.

    “Figure 2h illustrates that with the increase of temperature, the uncompensated sensor readouts can lead to substantial overestimation of the actual concentration of the given glucose and lactate solutions; however, the temperature compensation allows for accurate and consistent readings.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Sweat analyte levels on the wrist follow similar trends to those on the forehead but with different concentrations.

    “Sweat analyte levels on the wrist follow similar trends but with concentrations different from those obtained at the forehead (Extended Data Fig. 9).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    During constant-load exercise, heart rate, oxygen consumption, and pulmonary minute ventilation increased proportionally with increasing power output.

    “During the exercise, the heart rate, oxygen consumption (VO2), and pulmonary minute ventilation were measured using external monitoring instruments, and were found to increase proportionally with increasing power output as shown in Fig. 3c.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In dehydration trials without water intake, after 80 min when subjects lost about 2.5% of body weight, sweat [Na+] substantially increases and sweat [K+] increases less, with no clear increase in two of six subjects.

    “On the other hand, a substantial increase in sweat [Na+] and a smaller increase in sweat [K+] (no clear increase in [K+] was observed in two out of six subjects) were observed in dehydration trials (without water intake) after 80 min when subjects had lost a large amount of water (~2.5% of body weight) (Fig. 4d and e).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    With continued perspiration, skin temperature rises at about 400 s due to muscle heat conductance to skin and then remains stable, while sweat lactate and glucose concentrations decrease gradually.

    “With continued perspiration, the skin temperature rises at about 400 s because of muscle heat conductance to skin and then remains stable, while the concentration of both lactate and glucose in sweat decrease gradually.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Lactate sensors show a linear current response in 0-30 mM lactate solutions with a sensitivity of 220 nA mM−1.

    “A linear relationship between current and analyte concentrations with sensitivities of 2.35 nA μM−1 for glucose sensors and 220 nA mM−1 for lactate sensors was observed.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    The sensor-FPCB interface permits convenient replacement of fresh sensor arrays for later use.

    “The sensor–FPCB interface allows for convenient replacement of the fresh sensor arrays for subsequent use.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    With cessation of exercise, these physiological responses decrease and then remain stable.

    “With the cessation of exercise, these physiological responses decrease and then remain stable.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    The Na+ and K+ ion-selective sensors can be used without preconditioning, with a drift of about 2-3 mV per hour.

    “The sensors could be used without pre-conditioning (with a small drift of ~2–3 mV h−1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The current-sensing signal paths had a detection capability down to 1 nA, well below the smallest signal observed in the measurements (tens of nanoamperes).

    “The current sensing signal paths were capable of measuring current levels as low as 1 nA, which was much lower than the minimum signal in our measurements (tens of nanoamperes).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Wearing the smart headband or smart wristband increased temperature because of the plastic substrate on the skin.

    “An increase in temperature was observed when the ‘smart headband’ or ‘smart wristband’ was worn owing to the use of the plastic substrate on skin.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The platform enables a wide range of personalized diagnostic and physiological monitoring applications.

    “This platform enables a wide range of personalized diagnostic and physiological monitoring applications.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Excessive loss of sodium and potassium in sweat could result in hyponatremia, hypokalemia, muscle cramps, or dehydration.

    “For example, excessive loss of sodium and potassium in sweat could result in hyponatremia, hypokalemia, muscle cramps or dehydration20;”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Speedy, D. B., Noakes, T. D. & Schneider, C. Exercise-associated hyponatremia: a review. Emerg. Med. 13, 17–27 (2001) source

  • May combine two claims.

    Premisecitation

    For current sweat analysis applications, sample collection and analysis are performed separately, preventing real-time sweat content profiling and requiring bulky laboratory instrumentation.

    “For these applications, the sample collection and analysis are performed separately, failing to provide a real-time profile of sweat content secretion, while requiring extensive laboratory analysis using bulky instrumentation19.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Boysen, T. C., Yanagawa, S., Sato, F. & Sato, K. A modified anaerobic method of sweat collection. J. Appl. Physiol. 56, 1302–1307 (1984) source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisereasoning

    Because sweat secretion is complex, simultaneous multiplexed screening of target biomarkers is critical and requires full system integration to ensure measurement accuracy.

    “Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Sweat secretion involves multivariate mechanisms and is complex.

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Skin temperature measurements are needed to compensate for and eliminate temperature variation effects on chemical sensor readings through a built-in signal processor.

    “Additionally, skin temperature measurements are needed to compensate for and eliminate the influence of temperature variation in the readings of the chemical sensors through a built-in signal processor.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The approach decouples stringent mechanical requirements at the sensor level from electrical requirements at signal conditioning, processing, and transmission levels, while exploiting the strengths of the underlying technologies.

    “This approach decouples the stringent mechanical requirements at the sensor level and electrical requirements at the signal conditioning, processing and transmission levels, and at the same time exploits the strengths of the underlying technologies.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Convection and uneven solution temperature distributions could cause noticeable noise in signal measurements.

    “The convection and non-uniform distributions of solution temperature could result in noticeable noise in the signal measurements.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    The platform could be exploited or reconfigured for in situ analyses of other biomarkers in sweat and other human fluid samples to facilitate personalized and real-time physiological and clinical investigations.

    “This platform could be exploited or reconfigured for in situ analyses of other biomarkers within sweat and other human fluid samples to facilitate personalized and real-time physiological and clinical investigations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    During on-body tests, fresh sweat refilled the pad and washed away older sweat.

    “During on-body tests, the newly generated sweat would refill the pad and ‘rinse away’ the old sweat.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisereasoning

    Silicon integrated-circuit technology does not provide sufficiently large active areas nor the intimate skin contact required for stable and sensitive on-body measurements.

    “On the other hand, the silicon integrated-circuit technology does not provide sufficiently large active areas nor the intimate skin contact required to achieve stable and sensitive on-body measurements.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Because the subject had a lower sweat rate at the wrist, the sensors were activated later there.

    “In this case, because the subject had a lower sweat rate at the wrist29, the sensors were activated at a later time.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Patterson, M. J., Galloway, S. D. R. & Nimmo, M. A. Variations in regional sweat composition in normal human males. Exp. Physiol. 85, 869–875 (2000) source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Fluid deficit impairs endurance performance and increases carbohydrate reliance, making hydration monitoring important for athletes.

    “Monitoring hydration status is of the utmost importance to athletes because fluid deficit impairs endurance performance and increases carbohydrate reliance32.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Barr, S. I. Effects of dehydration on exercise performance. Can. J. Appl. Physiol. 24, 164–172 (1999) source

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationnone given

    The authors believe the wearable platform may enable new fundamental physiology studies through further on-body evaluation.

    “We believe that this wearable platform may enable new fundamental physiology studies through further on-body evaluation.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    To ensure fidelity, data collection for each channel occurred when sufficient sweat was present, indicated by stabilization of sensor readings within the physiologically relevant range.

    “To ensure the fidelity of sensor readings, the data collection of each channel took place when a sufficient sweat sample was present, as shown by stabilization of sensor readings within the physiologically relevant range (see Methods).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The ergometer's power output was calibrated and monitored.

    “The power output was calibrated and monitored through the ergometer.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    All participants provided written informed consent before joining the study.

    “All subjects gave written, informed consent before participation in the study.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The on-body evaluation of the FISA followed a protocol approved by the University of California, Berkeley institutional review board (CPHS 2014-08-6636).

    “The on-body evaluation of the FISA was performed in compliance with the protocol that was approved by the institutional review board at the University of California, Berkeley (CPHS 2014-08-6636).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    Although the temperature increase may slightly bias actual skin temperature measurement, it does not affect electrolyte and metabolite measurements because of on-board temperature calibration.

    “Although this may result in a small error in measuring the actual skin temperature, it should be noted that this does not have an impact on the measurement of the electrolytes and metabolites, owing to the on-board temperature calibration.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Before on-body wear, sensor arrays were calibrated and subjects' foreheads and wrists were cleaned with alcohol swabs and gauze.

    “The sensor arrays were calibrated, and the subjects’ foreheads and wrists were cleaned with alcohol swabs and gauze before sensors were worn on-body.”
    Quote in the paperNot a substantial claim
49 of 49

  • The paper relies on this without support.

    Commercially available wearable sensors only track physical activities and vital signs and fail to provide molecular-level health insight.

    “At present, commercially available wearable sensors are only capable of tracking an individual's physical activities and vital signs (such as heart rate), and fail to provide insight into the user's health state at molecular levels.”

  • The paper relies on this without support.

    Sweat secretion involves multivariate mechanisms and is complex.

    “Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements.”
    “Given the multivariate mechanisms that are involved in sweat secretion, an attractive strategy would be to devise a fully integrated multiplexed sensing system to extract the complex information available from sweat.”

  • The paper relies on this without support.

    Amperometric sensors with a larger area produce a larger current signal.

    “It is known that amperometric sensors with larger area provide larger current signal.”

  • The paper relies on this without support.

    A thinner Prussian blue layer provides better sensitivity, which is essential for measuring low glucose levels in sweat.

    “A thinner Prussian blue layer can provide better sensitivity, which is essential for low-glucose-level measurements in sweat.”

  • The paper relies on this without support.

    A thicker Prussian blue layer yields a broader linear response range, which is important for measuring lactate in sweat.

    “A thicker Prussian blue layer can provide a wider linear response range, which is crucial for lactate measurement in sweat.”

  • The authors state this as an assumption.

    Sweat flow can be modeled as a single-centred flow.

    “Assuming a single-centred flow model13, the best-case sampling interval can be calculated to be less than 1 min, based on the sweat rate (~3–4 mg min−1 cm−2)39 and the pad size (1.5 cm × 2 cm × 50 μm).”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The Na+ sensor remains stable throughout the measurement period with a sensitivity of 56.2 mV/decade in 15 to 120 mM NaCl solutions, similar to sensitivities achieved by lithography-based Na+ sensors and close to the Nernstian ideal.

    “The sensor remains stable throughout the measurement period with a sensitivity of 56.2 mV/decade, similar to sensitivities achieved by lithography-based Na+ sensors and close to the Nernstian ideal (23).”

    From Regional and correlative sweat analysis using high-throughput microfluidic sensing patches toward decoding sweat (2019) · cites this paper as [23]

    The sensor-performance passage (Fig. 2c–d; page not provided) describes the Na+ sensor as near-Nernstian, and Methods, 'The characterization of the sensors' (page not provided), reports stability during exercise and over four weeks. But the paper gives Na+ sensitivities of 64.2 and approximately 62.5 mV per decade, not 56.2; it tests 10–160 mM Na+, not 15–120 mM NaCl, and does not make the claimed comparison with lithography-based sensors. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • A fully integrated wearable sensor array for multiplexed in-situ perspiration analysis measured sodium, potassium, lactate, and glucose in sweat simultaneously by electrochemical methods.

    “Recently, a fully integrated wearable sensor array for multiplexed in-situ perspiration analysis was reported, where the sodium, potassium, lactate, and glucose content of sweat can be measured simultaneously by electrochemical methods.”

    From Flexible Electronics and Devices as Human–Machine Interfaces for Medical Robotics (2022) · cites this paper as [83]

  • Conventional commercially available integrated-circuit components (more than ten chips) can be applied on an FPCB for data processing and transmission.

    “Conventional commercially available integrated-circuit components (more than ten chips) can be applied on a FPCB to serve as data processing and transmission.[83]”

    From Flexible Electronics and Devices as Human–Machine Interfaces for Medical Robotics (2022) · cites this paper as [83]

  • Additional advances are needed to meet the challenging requirements of the NICU, where comprehensive, continuous sensing with wireless functionality, clinical-grade measurement fidelity, and mechanical form factors that eliminate risk of harm to exceptionally fragile neonatal skin are essential.

    “Although such systems can support various types of biophysical measurements of physiological health (8–13), additional advances are needed to meet the challenging requirements of the NICU, where comprehensive, continuous sensing with wireless functionality, clinical-grade measurement fidelity, and mechanical form factors that eliminate risk of harm to exceptionally fragile neonatal skin are essent”

    From Binodal, wireless epidermal electronic systems with in-sensor analytics for neonatal intensive care (2019) · cites this paper as [10]

  • Recently, tactile pressure sensors have been developed in the form of active-matrix arrays consisting of pressure-sensitive graphene transistors with air-dielectric layers.

    “Recently, tactile pressure sensors have been developed in the form of active‐matrix arrays consisting of pressure‐sensitive graphene transistors with air–dielectric layers.33”

    From Wearables in Medicine (2018) · cites this paper as [33]

    The sensor-array description and Methods > Fabrication of electrode arrays describe electrodes for sweat biomarkers and skin temperature, not tactile pressure sensors. Searches for pressure-sensitive graphene transistors, active-matrix tactile arrays, and air-dielectric layers found no passage addressing the claimed design. No page number was available in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Cites

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Related

Authors
Gao, W., Emaminejad, S., Nyein, H. Y. Y., Challa, S., Chen, K., Peck, A., Fahad, H. M., Ota, H., Shiraki, H., Kiriya, D., Lien, D.-H., Brooks, G. A., Davis, R. W., & Javey, A.
Affiliations
  • Lawrence Berkeley National Laboratory (US)
  • Stanford Medicine (US)
  • University of California, Berkeley (US)
Corresponding author
Javey, Ali
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2016-01-27
Volume
529
Issue
7587
Pages
509-514
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature16521
PMC
PMC4996079
OpenAlex
W2266175888
Semantic Scholar
52709f85aaaaea3dbceb33a9666e3cb1dfb932a3
Cited by
5,087
References
39
Citations by year
2026: 462 · 2025: 581 · 2024: 528 · 2023: 543 · 2022: 531 · 2021: 585 · 2020: 538 · 2019: 502 · 2018: 415 · 2017: 282 · 2016: 117 · 2015: 2
FWCI
211.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders
  • National Science Foundation (DEAC02-05CH11231)
  • U.S. Department of Energy (-AC02-05CH11231, 05CH11231, DE AC02 05CH11231, DE-AC02-)
  • National Institutes of Health (DE-AC02–05CH11231, HG000205)
  • Office of Science (DEAC02–05CH11231, AC02-05CH11231, DE-AC02)
  • Japan Society for the Promotion of Science
  • National Human Genome Research Institute (P01HG000205)
  • Basic Energy Sciences (DE-AC02, DE-AC02-05CH11231., AC02–05CH11231)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Advanced Sensor and Energy Harvesting Materials
  • Physical Sciences › Engineering › Biomedical Engineering › Non-Invasive Vital Sign Monitoring
  • Physical Sciences › Engineering › Electrical and Electronic Engineering › Electrochemical sensors and biosensors
Keywords
wearable sensors, sweat analysis, sweat electrolytes, glucose, lactate, sodium, potassium, skin temperature, flexible electronics, silicon integrated circuits, multiplexed biosensing, wireless transmission, real-time physiological monitoring, non-invasive monitoring, wearable biosensors, physical activity monitoring, personalized medicine, drug abuse detection, athletic performance
MeSH terms
Adult, Bicycling, Body Water, Calibration, Electrolytes, Female, Glucose, Humans, Male, Monitoring, Physiologic, Running, Skin, Skin Temperature, Sweat, Reproducibility of Results, Lactic Acid, Young Adult, Precision Medicine, Healthy Volunteers

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

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