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Cited by 3,373Advanced Sensor and Energy Harvesting MaterialsElectrochemical sensors and biosensorsBiosensors and Analytical Detection

Wearable biosensors for healthcare monitoring

Open access
Kim, Jayoung, Campbell, Alan S., de Ávila, Berta Esteban-Fernández, Wang, Joseph·2019·Nature Biotechnology
DOI 10.1038/s41587-019-0045-yPMC PMC8183422
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Abstract

Wearable biosensors are garnering substantial interest due to their potential to provide continuous, real-time physiological information via dynamic, noninvasive measurements of biochemical markers in biofluids, such as sweat, tears, saliva and interstitial fluid. Recent developments have focused on electrochemical and optical biosensors, together with advances in the noninvasive monitoring of biomarkers including metabolites, bacteria and hormones. A combination of multiplexed biosensing, microfluidic sampling and transport systems have been integrated, miniaturized and combined with flexible materials for improved wearability and ease of operation. Although wearable biosensors hold promise, a better understanding of the correlations between analyte concentrations in the blood and noninvasive biofluids is needed to improve reliability. An expanded set of on-body bioaffinity assays and more sensing strategies are needed to make more biomarkers accessible to monitoring. Large-cohort validation studies of wearable biosensor performance will be needed to underpin clinical acceptance. Accurate and reliable real-time sensing of physiological information using wearable biosensor technologies would have a broad impact on our daily lives.

AI snapshot

Written from the paper’s full text.

TL;DR

This review surveys recent advances in wearable biosensors for non-invasive healthcare monitoring, focusing on electrochemical and optical platforms that measure biomarkers in sweat, tears, saliva, and interstitial fluid. It concludes that despite rapid proof-of-concept progress, clinical and commercial translation requires better blood–biofluid correlation, large-population validation, and improved accuracy and stability under uncontrolled conditions.

Key findings

  • Wearable biosensors have expanded from physical activity and vital-sign tracking to non-invasive chemical monitoring in sweat, tears, saliva, and ISF, with representative platforms including multiplexed sweat patches for glucose, lactate, Na⁺, K⁺, and temperature; contact-lens tear glucose sensors; and mouthguard sensors for salivary lactate, uric acid, and glucose.
  • Reported quantitative examples include sweat glands at more than 100 glands/cm² of skin; the GlucoWatch Biographer as an FDA-approved non-invasive glucose monitor over 12 h with 6 measurements per hour, later withdrawn due to skin irritation, a 2–3 h warm-up, and calibration needs; salivary glucose–blood correlation of R = 0.64 in healthy subjects and R = 0.95 in diabetic subjects; iontophoretic tattoo sweat alcohol measurement within 10 min; artificial-saliva glucose range of 5–1000 μM; cortisol/IL-6 immunosensor antibody stability up to 96 h; RI glucose monitoring over 6 h; and iontophoretic sweat generation limited to 60 min.
  • Major technical advances include multiplexed sensing, microfluidic sampling/transport, flexible and stretchable materials, wireless electronics, self-powered or energy-harvesting designs, and closed-loop “sense-act” systems such as sweat glucose monitoring coupled with microneedle metformin delivery in a mouse model.
  • The global wearable sensors market was valued at roughly $150 million in 2016 and projected to reach $2.86 billion by 2025, with non-invasive glucose monitoring expected to make up a large portion of future wearable biosensor market share.

Methods

  • Review article synthesizing key advances from the past 2 years, with emphasis on electrochemical and optical transduction, across epidermal (sweat and ISF), ocular (tears), and oral-cavity (saliva) wearable biosensing platforms.
  • Discusses representative proof-of-concept and clinical/commercial examples, including multiplexed patches, contact lenses, mouthguards, iontophoresis/reverse iontophoresis, microfluidics, and integrated wireless electronics; no new experimental data or systematic meta-analysis are reported.

Limitations

  • The paper states that a limited understanding of correlations between analyte concentrations in blood and non-invasive biofluids remains a major obstacle, and that extensive large-population validation through multidisciplinary collaboration is required for medical and commercial acceptance.
  • The paper states that accuracy and stability under uncontrolled conditions, reproducible sample transport, biofouling, bioreceptor stability, calibration, and immunosensor regeneration remain unresolved challenges; many devices rely on exercise for sweat generation or have limited continuous operation, and saliva and tear sampling face low analyte concentrations, contamination, evaporation, and variability.
  • Evident from the text: as a review, it does not provide primary experimental validation or a systematic quantitative synthesis, and commercial translation remains limited despite numerous proof-of-concept demonstrations.

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

Integrity signals

Registry

Crossref · 10.1038/s41587-019-0045-y

Cites

196 of 196 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 184 cited sources checked · 0 supported · 0 flagged

  • Findingnone given

    Reported epidermal biosensor devices have been limited to analysis of a single sampled biofluid.

    “Despite the tremendous advances in epidermal biosensors, the reported devices have been limited to analysis of a single sampled biofluid.”
    Quote in the paperSubstantial claim
  • Findingcitation

    The system allows on-demand, controlled simultaneous sampling of two biofluids at physically separated locations on a single wearable tattoo platform.

    “The system allows on-demand, controlled simultaneous sampling of two biofluids at physically separated locations on a single wearable tattoo platform.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [93] Kim, J. et al. Simultaneous monitoring of sweat and interstitial fluid using a single wearable biosensor platform. Adv. Sci. (Weinh.) 5, 1800880 (2018).

      Not checked in the free run.

  • Findingcitation

    The authors' group demonstrated a new concept for simultaneous sampling and analysis of two different epidermal biofluids with a single wearable platform through combined iontophoresis.

    “However, our group (J.K., A.S.C., J.W. et al.)93 recently demonstrated a new concept for the simultaneous sampling and analysis of two different epidermal biofluids with a single wearable platform through combined iontophoresis (Fig. 4f).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [93] Kim, J. et al. Simultaneous monitoring of sweat and interstitial fluid using a single wearable biosensor platform. Adv. Sci. (Weinh.) 5, 1800880 (2018).

      Not checked in the free run.

  • Findingcitation

    The biosensing performance of the dual-biofluid platform has been demonstrated by measuring sweat alcohol and ISF glucose as model analytes with human subjects consuming food and alcoholic drink.

    “The biosensing performance has been demonstrated by measuring sweat alcohol and ISF glucose as model analytes with human subjects consuming food and alcoholic drink.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [93] Kim, J. et al. Simultaneous monitoring of sweat and interstitial fluid using a single wearable biosensor platform. Adv. Sci. (Weinh.) 5, 1800880 (2018).

      Not checked in the free run.

  • Findingcitation

    The dual-biofluid platform was accomplished by coupling sweat stimulation (iontophoretic drug delivery) with ISF extraction (via RI), enabling concurrent analysis of biomarkers in each biofluid.

    “This was accomplished by coupling sweat stimulation (iontophoretic drug delivery) with ISF extraction (via RI), enabling concurrent analysis of biomarkers in each biofluid.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [93] Kim, J. et al. Simultaneous monitoring of sweat and interstitial fluid using a single wearable biosensor platform. Adv. Sci. (Weinh.) 5, 1800880 (2018).

      Not checked in the free run.

  • May combine two claims. 47
  • Classified as probably not a substantial claim. 48

  • May combine two claims.

    Findingcitation

    Although the smart contact lens device is capable of multiplexed sensing, the simultaneous demonstration of two functionalities has not yet been evaluated.

    “Although this device is capable of multiplexed sensing, the simultaneous demonstration of two functionalities has not yet been evaluated.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [117] Kim, J. et al. Wearable smart sensor systems integrated on soft contact lenses for wireless ocular diagnostics. Nat. Commun. 8, 14997 (2017). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The mouthguard lactate device is capable of detecting salivary lactate electrochemically in connection to selectivity imparted by the lactate oxidase enzyme; protection against biofouling in undiluted human salivary samples was conferred by electro-polymerized ortho-phenylenediamine (OPD) for continuous, non-invasive physiological monitoring of an individual's fitness state.

    “This device is capable of detecting salivary lactate electrochemically in connection to selectivity imparted by the lactate oxidase enzyme; protection against biofouling in undiluted human salivary samples was conferred by electro-polymerized ortho-phenylenediamine (OPD) for continuous, non-invasive physiological monitoring of an individual’s fitness state.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [145] Kim, J. et al. Non-invasive mouthguard biosensor for continuous salivary monitoring of metabolites. Analyst 139, 1632–1636 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The mouthguard uric acid platform enables non-invasive monitoring of blood uric acid levels, which is a biomarker for various diseases (e.g., hyperuricemia, gout and renal syndrome), and it displays highly sensitive, selective, stable and rapid response toward obtaining dynamic chemical data on salivary biomarkers in the oral cavity.

    “This platform enables non-invasive monitoring of blood uric acid levels, which is a biomarker for various diseases (e.g., hyperuricemia, gout and renal syndrome), and it displays highly sensitive, selective, stable and rapid response toward obtaining dynamic chemical data on salivary biomarkers in the oral cavity.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Kim, J. et al. Wearable salivary uric acid mouthguard biosensor with integrated wireless electronics. Biosens. Bioelectron. 74, 1061–1068 (2015). source

      Not checked in the free run.

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

    Findingreasoning

    Few studies have focused on developing wearable oral cavity biosensors, likely due to potential biofouling effects caused by the rich salivary protein content and the very low concentration of some target biomarkers.

    “However, few studies have focused on developing wearable oral cavity biosensors, likely due to potential biofouling effects caused by the rich salivary protein content and the very low concentration of some target biomarkers.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The toxicity of the sodium monitoring device was evaluated without the chemical sensing layer, and hence practical oral-cavity applications would require further critical assessment along with a biocompatible recognition layer.

    “However, the toxicity of the device was evaluated without the chemical sensing layer, and hence practical oral-cavity applications would require further critical assessment along with a biocompatible recognition layer.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [156] Lee, Y. et al. Wireless, intraoral hybrid electronics for real-time quantification of sodium intake toward hypertension management. Proc. Natl Acad. Sci. USA 115, 5377–5382 (2018). source

      Not checked in the free run.

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

    Findingnone given

    Compared with other non-invasively sampled biofluids, saliva can be readily sampled without complicated procedures, but is composed of a rich matrix of constituents that can also be easily contaminated by external factors (e.g., food and drink).

    “Compared with other non-invasively sampled biofluids, saliva can be readily sampled without complicated procedures, but is composed of a rich matrix of constituents that can also be easily contaminated by external factors (e.g., food and drink).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Wearable biosensors face many fundamental challenges and technological gaps related to the scope, validation, stability and accuracy, along with power, communication and security/privacy issues.

    “Wearable biosensors face many fundamental challenges and technological gaps related to the scope, validation, stability and accuracy, along with power (Box 1)1,42,157-167, communication (Box 2)1,168 and security/privacy issues (Box 3)1,169-172”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [1] Bandodkar, A. J., Jeerapan, I. & Wang, J. Wearable chemical sensors: present challenges and future prospects. ACS Sens. 1, 464–482 (2016). source

      Not checked in the free run.

    • cites [42] Jeerapan, I., Sempionatto, J. R., Pavinatto, A., You, J. M. & Wang, J. Stretchable biofuel cells as wearable textile-based self-powered sensors. J. Mater. Chem. A Mater. Energy Sustain. 4, 18342–18353 (2016). source

      Not checked in the free run.

    • cites [157] Sarpeshkar, R. Universal principles for ultra low power and energy efficient design. IEEE Trans. Circuits Syst. II 59, 193–198 (2012). source

      Not checked in the free run.

    • cites [158] De Marcellis, A., Depari, A., Ferri, G., Flammini, A. & Sisinni, E. A CMOS integrated low-voltage low-power time-controlled interface for chemical resistive sensors. Sens. Actuators B Chem. 179, 313–318 (2013). source

      Not checked in the free run.

    • cites [159] Zhang, Y. et al. Realizing both high energy and high power densities by twisting three carbon-nanotube-based hybrid fibers. Angew. Chem. Int. Ed. Engl. 54, 11177–11182 (2015). source

      Not checked in the free run.

    • cites [160] Huang, Y. et al. Weavable, conductive yarn-based NiCo//Zn textile battery with high energy density and rate capability. ACS Nano 11, 8953–8961 (2017). source

      Not checked in the free run.

    • cites [161] Mesin, L. A neural algorithm for the non-uniform and adaptive sampling of biomedical data. Comput. Biol. Med. 71, 223–230 (2016). source

      Not checked in the free run.

    • cites [162] Zi, Y. et al. Triboelectric-pyroelectric-piezoelectric hybrid cell for high-efficiency energy-harvesting and self-powered sensing. Adv. Mater. 27, 2340–2347 (2015). source

      Not checked in the free run.

    • cites [163] Zhang, K. & Yang, Y. Thermo-phototronic effect enhanced InP/ZnO nanorod heterojunction solar cells for self-powered wearable electronics. Adv. Funct. Mater. 27, 1703331 (2017). source

      Not checked in the free run.

    • cites [164] Wen, Z. et al. Self-powered textile for wearable electronics by hybridizing fiber-shaped nanogenerators, solar cells, and supercapacitors. Sci. Adv. 2, e1600097 (2016). source

      Not checked in the free run.

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

    Findingnone given

    Most current wearable biosensing devices measure a small number of biomarkers.

    “Most current wearable biosensing devices measure a small number of biomarkers.”
    Quote in the paperNot a substantial claim

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

    Findingnone given

    Biofouling is driven by the accumulation of proteins, cells or macromolecules on the sensor surface through non-specific binding.

    “Biofouling is driven by the accumulation of proteins, cells or macromolecules on the sensor surface through non-specific binding.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    A plethora of innovative wearable biosensing devices have already been demonstrated in diverse applications, ranging from the detection of metabolites (e.g., lactate or glucose) to the monitoring of electrolytes (e.g., sodium, potassium or calcium) in fluids, such as sweat, ISF, saliva or tears in connection to enzymatic and ion-recognition reactions.

    “A plethora of innovative wearable biosensing devices have already been demonstrated in diverse applications, ranging from the detection of metabolites (e.g., lactate or glucose) to the monitoring of electrolytes (e.g., sodium, potassium or calcium) in fluids, such as sweat, ISF, saliva or tears in connection to enzymatic and ion-recognition reactions.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Findingnone given

    The concentrations of many important biomarkers in saliva are substantially lower than in blood, requiring highly sensitive sensing systems for accurate monitoring.

    “The concentrations of many important biomarkers in saliva are substantially lower than in blood, requiring highly sensitive sensing systems for accurate monitoring.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Despite tremendous recent progress in wearable biosensors, the state-of-the-art in this field remains at demonstrating proof-of-concept wearable biosensing platforms for detecting several representative biomarkers, and only small steps can be taken to practical applications in the field.

    “Despite tremendous recent progress in wearable biosensors, the state-of-the-art in this field remains at demonstrating proof-of-concept wearable biosensing platforms for detecting several representative biomarkers, and only small steps can be taken to practical applications in the field.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Wearable batteries have been developed on stretchable and flexible materials for greater wearability, but have not yet demonstrated sufficient energy density for long-term use.

    “Alternatively, wearable batteries have been developed on stretchable and flexible materials for greater wearability, but have not yet demonstrated sufficient energy density for long-term use177-179.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [177] Xu, S. et al. Stretchable batteries with self-similar serpentine interconnects and integrated wireless recharging systems. Nat. Commun. 4, 1543 (2013). source

      Not checked in the free run.

    • cites [178] Berchmans, S. et al. An epidermal alkaline rechargeable Ag-Zn printable tattoo battery for wearable electronics. J. Mater. Chem. A Mater. 2, 15788–15795 (2014). source

      Not checked in the free run.

    • cites [179] Kumar, R. et al. All-printed, stretchable Zn-Ag2O rechargeable battery via hyperelastic binder for self-powering wearable electronics. Adv. Energy Mater. 7, 1–8 (2017). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    New data mining algorithms are being developed for making sense of the large amount of data and predicting patterns in connection to specific applications.

    “New data mining algorithms are being developed for making sense of the large amount of data and predicting patterns in connection to specific applications.”
    Quote in the paperNot a substantial claim

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

    Findingnone given

    The provision of power to wearable biosensing platforms can be accomplished in several ways, with the most common approach being lithium ion or alkaline batteries.

    “The provision of power to wearable biosensing platforms (see Box 1) can be accomplished in several ways, with the most common approach being lithium ion or alkaline batteries.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Lithium ion or alkaline batteries exhibit long lifetimes for extended biosensor operation; however, they are relatively bulky and can pose toxicity issues, particularly lithium ion-based systems.

    “These devices exhibit long lifetimes for extended biosensor operation; however, they are relatively bulky and can pose toxicity issues, particularly lithium ion-based systems175,176.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [175] Hammami, A., Raymond, N. & Armand, M. Lithium-ion batteries: runaway risk of forming toxic compounds. Nature 424, 635–636 (2003). source

      Not checked in the free run.

    • cites [176] Lisbona, D. & Snee, T. A review of hazards associated with primary lithium and lithium-ion batteries. Process Saf. Environ. Prot. 89, 434–442 (2011). source

      Not checked in the free run.

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

    Findingnone given

    Unlike traditional (lab-based) biosensors, wearable biosensors can be exposed to harsh and fluctuating conditions (e.g., temperature) during prolonged outdoor activities in uncontrolled environments.

    “Unlike traditional (lab-based) biosensors, wearable biosensors can be exposed to harsh and fluctuating conditions (e.g., temperature) during prolonged outdoor activities in uncontrolled environments.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Wearable biosensors can obviate painful and risky blood sampling procedures and can be readily blended with a wearer's daily routine.

    “Wearable biosensors can obviate painful and risky blood sampling procedures and can be readily blended with a wearer’s daily routine.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Sweat contains metabolites, electrolytes, trace elements, and small amounts of large molecules.

    “Generally, sweat contains metabolites (e.g., lactate, glucose, urea, ethanol or cortisol) along with electrolytes (e.g., sodium, potassium, chloride or ammonium), trace elements (e.g., zinc or copper), and small amounts of large molecules (e.g., proteins, nucleic acids, neuropeptides or cytokines)64.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [64] Sonner, Z. et al. The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications. Biomicrofluidics 9, 031301 (2015). source

      Not checked in the free run.

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

    Interpretationnone given

    Robust reliable measurement of wearable bioanalyte sensors must overcome challenges including gradual surface biofouling, inefficient sample transport, limited bioreceptor stability, complexity of multi-step bioaffinity assays and receptor regeneration, and calibration issues.

    “Robust, reliable measurement also must overcome such challenges as gradual surface biofouling at the body–sensor interface, inefficient transport of sample over the sensor, limited stability of many bioreceptors, the complexity of multi-step bioaffinity assays and related receptor regeneration, and issues posed by calibration for on-body biosensors.”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    Limited understanding of the correlations between analyte concentrations in blood and non-invasive biofluids remains a major obstacle.

    “Even so, our limited understanding of the correlations between analyte concentrations in the blood and non-invasive biofluids remains a major obstacle.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Sweat, tears, saliva and interstitial fluid can be sampled non-invasively without disrupting the stratum corneum and without contacting blood, posing minimal risk of harm or infection and being more user-friendly.

    “Sweat, tears, saliva and ISF have been targeted as they can be sampled in a non-invasive manner, meaning that they can be readily accessed without disrupting the outermost protecting layers of the body’s skin (i.e., stratum corneum) and without contacting blood. As such, non-invasive sensing methods pose minimal risk of harm or infection and are generally more user-friendly.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Sweat lactate does not directly reflect concurrent blood levels, but it indicates the level of physical exertion during prolonged exercise and can be used as a marker for athletic efficiency without invasive blood sampling.

    “Although sweat lactate does not directly reflect the concurrent blood levels, it indicates the level of physical exertion experienced during prolonged exercise and can be used as a marker for athletic efficiency without invasive blood sampling.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [58] Jia, W. et al. Electrochemical tattoo biosensors for real-time noninvasive lactate monitoring in human perspiration. Anal. Chem. 85, 6553–6560 (2013). source

      Not checked in the free run.

    • Rests on an assumption: Sweat lactate is a byproduct of local sweat gland metabolism and intense physical activity induces higher generation rates.

  • May combine two claims.

    Interpretationcitation

    The reported multiplexed sweat biosensor system proved advantageous for monitoring fitness parameters during exercise, but its utility would be limited in continuous monitoring applications due to its reliance on physical exertion for sweat generation.

    “The reported system proved advantageous for monitoring fitness parameters during exercise, but its utility would be limited in continuous monitoring applications due to its reliance on physical exertion for sweat generation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Gao, W. et al. Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis. Nature 529, 509–514 (2016). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The duration of sweat generation in a patch-type iontophoretic sweat sensor was limited to 60 min, with varying rates over that time, which could hinder continuous monitoring applications.

    “However, the duration of sweat generation was limited to 60 min, with varying rates over that time, which could hinder continuous monitoring applications.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Emaminejad, S. et al. Autonomous sweat extraction and analysis applied to cystic fibrosis and glucose monitoring using a fully integrated wearable platform. Proc. Natl Acad. Sci. USA 114, 4625–4630 (2017). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    The efficiency of glucose extraction by reverse iontophoresis is difficult to control, which can lead to inconsistent volumes of sampled ISF and thus variations in glucose concentration.

    “However, the efficiency of glucose extraction by RI is difficult to control, which can lead to inconsistent volumes of sampled ISF and thus variations in glucose concentration.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Antibody-based bioassays hold great promise for expanding the scope of epidermal wearable biosensors, but their successful on-body evaluation has yet to be demonstrated.

    “Although such antibody-based bioassays hold great promise for expanding the scope of epidermal wearable biosensors, which focus primarily on enzymatic metabolite detection, their successful on-body evaluation has yet to be demonstrated.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Although several studies have indicated that sweat glucose concentrations can correlate with concurrent blood levels, the limitations of uncontrolled conditions, contamination, irregular sampling, and low volumes can significantly impact the accuracy of collected data.

    “Although several studies have indicated that sweat glucose concentrations can correlate with concurrent blood levels, these limitations can significantly impact the accuracy of collected data 64, 76,77.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [64] Sonner, Z. et al. The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications. Biomicrofluidics 9, 031301 (2015). source

      Not checked in the free run.

    • cites [76] Moyer, J., Wilson, D., Finkelshtein, I., Wong, B. & Potts, R. Correlation between sweat glucose and blood glucose in subjects with diabetes. Diabetes Technol. Ther. 14, 398–402 (2012). source

      Not checked in the free run.

    • cites [77] Sakaguchi, K. et al. Evaluation of a minimally invasive system for measuring glucose area under the curve during oral glucose tolerance tests: usefulness of sweat monitoring for precise measurement. J. Diabetes Sci. Technol. 7, 678–688 (2013). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Unlike epidermal enzyme-based biosensors, immunosensors cannot be readily regenerated toward continuous monitoring applications, and along with other challenges of multi-step affinity bioassays, require further efforts and innovations.

    “Unlike epidermal enzyme-based biosensors, such immunosensors cannot be readily regenerated toward continuous monitoring applications, and along with other challenges of multi-step affinity bioassays, these devices require further efforts and innovations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Patch-type sweat biosensors require physical exercise for their operation and are thus not compatible with continuous glucose monitoring in daily-life without exercise.

    “Yet, these devices require physical exercise for their operation, and are thus not compatible with continuous glucose monitoring in daily-life without exercise.”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    Iontophoresis-induced sweat generation obviates the need to exercise for sweat sampling.

    “Iontophoresis-induced sweat generation obviates the need to exercise for sweat sampling.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The GlucoWatch Biographer was an FDA-approved device capable of non-invasive glucose monitoring over a 12 hour period with 6 measurements per hour.

    “This US Food and Drug Administration (FDA)-approved device is capable of non-invasive glucose monitoring over a 12 hour period with 6 measurements per hour.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Tierney, M. J., Tamada, J. A., Potts, R. O., Jovanovic, L. & Garg, S. Clinical evaluation of the GlucoWatch biographer: a continual, non-invasive glucose monitor for patients with diabetes. Biosens. Bioelectron. 16, 621–629 (2001). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The caffeine sensing device was not integrated with the sweat generation device, but was coupled to a commercially available Macroduct sweat collector using pilocarpine delivery.

    “Even so, as described, the sensing device was not integrated with the sweat generation device, but rather coupled to a commercially available Macroduct sweat collector using pilocarpine delivery.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [92] Tai, L. C. et al. Methylxanthine drug monitoring with wearable sweat sensors. Adv. Mater. 30, e1707442 (2018). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Biomarker molecules in tears diffuse directly from the blood and exhibit close tear-blood concentration correlations.

    “Not only do biomarker molecules in tears diffuse directly from the blood and exhibit close tear–blood concentration correlations, but also tear analysis presents opportunities for the diagnosis of ocular disease.”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [94] Farandos, N. M., Yetisen, A. K., Monteiro, M. J., Lowe, C. R. & Yun, S. H. Contact lens sensors in ocular diagnostics. Adv. Healthc. Mater. 4, 792–810 (2015). source

      Not checked in the free run.

    • cites [95] Baca, J. T., Finegold, D. N. & Asher, S. A. Tear glucose analysis for the noninvasive detection and monitoring of diabetes mellitus. Ocul. Surf. 5, 280–293 (2007). source

      Not checked in the free run.

    • cites [96] Thaysen, J. H. & Thorn, N. A. Excretion of urea, sodium, potassium and chloride in human tears. Am. J. Physiol. 178, 160–164 (1954). source

      Not checked in the free run.

    • cites [97] Mitsubayashi, K. & Arakawa, T. Cavitas sensors: contact lens type sensors & mouthguard sensors. Electroanalysis 28, 1170–1187 (2016). source

      Not checked in the free run.

    • cites [98] Pankratov, D., Gonzalez-Arribas, E., Blum, Z. & Shleev, S. Tear based bioelectronics. Electroanalysis 28, 1250–1266 (2016). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tear glucose concentrations have been demonstrated to exhibit good correlation with blood glucose levels, reflecting diffusion from the lachrymal artery when tears are sampled without eye irritation or stimulation, which can compromise the relationship.

    “In particular, tear glucose concentrations have been demonstrated to exhibit good correlation with blood glucose levels, reflecting the diffusion from the lachrymal artery when the tears are sampled without any eye irritation or stimulation, which can compromise the relationship94, 95, 99-101.”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [94] Farandos, N. M., Yetisen, A. K., Monteiro, M. J., Lowe, C. R. & Yun, S. H. Contact lens sensors in ocular diagnostics. Adv. Healthc. Mater. 4, 792–810 (2015). source

      Not checked in the free run.

    • cites [95] Baca, J. T., Finegold, D. N. & Asher, S. A. Tear glucose analysis for the noninvasive detection and monitoring of diabetes mellitus. Ocul. Surf. 5, 280–293 (2007). source

      Not checked in the free run.

    • cites [99] Sen, D. K. & Sarin, G. S. Tear glucose levels in normal people and in diabetic patients. Br. J. Ophthalmol. 64, 693–695 (1980). source

      Not checked in the free run.

    • cites [100] Chu, M. X. et al. Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment. Talanta 83, 960–965 (2011). source

      Not checked in the free run.

    • cites [101] Chu, M. et al. Biomedical soft contact-lens sensor for in situ ocular biomonitoring of tear contents. Biomed. Microdevices 13, 603–611 (2011). source

      Not checked in the free run.

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

    Premisecitation

    Contact lens-based sensors were initially introduced utilizing optical detection of tear glucose levels based on the interaction of glucose with concanavalin A or phenylboronic acid derivatives.

    “Contact lens-based sensors were initially introduced utilizing optical detection of tear glucose levels based on the interaction of glucose with concanavalin A or phenylboronic acid derivatives107,108.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [107] Alexeev, V. L., Das, S., Finegold, D. N. & Asher, S. A. Photonic crystal glucose-sensing material for noninvasive monitoring of glucose in tear fluid. Clin. Chem. 50, 2353–2360 (2004). source

      Not checked in the free run.

    • cites [108] Ben-Moshe, M., Alexeev, V. L. & Asher, S. A. Fast responsive crystalline colloidal array photonic crystal glucose sensors. Anal. Chem. 78, 5149–5157 (2006). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Sampling tears for in vitro diagnoses is associated with errors due to small sample volumes, ease of evaporation during sample collection, variations in tear production among individuals and throughout the day, and challenging collection methods that can affect sampled analyte concentrations.

    “Despite the demonstrated correlations, sampling tears for in vitro diagnoses is associated with several errors that are due to the following: first, small sample volumes102; second, ease of evaporation during sample collection; third, variations in tear production among individuals and throughout the day103; and lastly, challenging collection methods that can affect the sampled analyte concentra”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [102] Mishima, S., Gasset, A., Klyce, S. D. Jr. & Baum, J. L. Determination of tear volume and tear flow. Invest. Ophthalmol. 5, 264–276 (1966).

      Not checked in the free run.

    • cites [103] Fullard, R. J. & Carney, L. G. Diurnal variation in human tear enzymes. Exp. Eye Res. 38, 15–26 (1984). source

      Not checked in the free run.

    • cites [104] Yan, Q. et al. Measurement of tear glucose levels with amperometric glucose biosensor/capillary tube configuration. Anal. Chem. 83, 8341–8346 (2011). source

      Not checked in the free run.

    • cites [105] Stuchell, R. N., Feldman, J. J., Farris, R. L. & Mandel, I. D. The effect of collection technique on tear composition. Invest. Ophthalmol. Vis. Sci. 25, 374–377 (1984).

      Not checked in the free run.

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

    Premisecitation

    Other contact lens-based optical sensors have involved the use of photonic crystal materials in combination with responsive hydrogels or fluorescent dyes for measuring glucose and other target analytes in tears.

    “Other contact lens-based optical sensors have involved the use of photonic crystal materials in combination with responsive hydrogels or fluorescent dyes for measuring glucose and other target analytes in tears110-113.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [110] Khalil, O. S. Noninvasive photonic-crystal material for sensing glucose in tears. Clin. Chem. 50, 2236–2237 (2004). source

      Not checked in the free run.

    • cites [111] Cai, Z., Smith, N. L., Zhang, J. T. & Asher, S. A. Two-dimensional photonic crystal chemical and biomolecular sensors. Anal. Chem. 87, 5013–5025 (2015). source

      Not checked in the free run.

    • cites [112] Elsherif, M., Hassan, M. U., Yetisen, A. K. & Butt, H. Wearable contact lens biosensors for continuous glucose monitoring using smartphones. ACS Nano 12, 5452–5462 (2018). source

      Not checked in the free run.

    • cites [113] Sung, Y., Campa, F. & Shih, W. C. Open-source do-it-yourself multi-color fluorescence smartphone microscopy. Biomed. Opt. Express 8, 5075–5086 (2017). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The Parviz team demonstrated electrochemical biosensing and investigated different biosensing strategies to achieve good sensitivity, linearity and accuracy.

    “Further advances for the field came with the demonstration of electrochemical biosensing by the Parviz team114-116. This group investigated different biosensing strategies to achieve good sensitivity, linearity and accuracy.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [114] Yao, H., Afanasiev, A., Lahdesmaki, I. & Parviz, B. A. A dual microscale glucose sensor on a contact lens, tested in conditions mimicking the eye. Proc. IEEE Micro. Electro. Mech. Syst. 2011, 25–28 (2011).

      Not checked in the free run.

    • cites [115] Yao, H. et al. A contact lens with integrated telecommunication circuit and sensors for wireless and continuous tear glucose monitoring. J. Micromech. Microeng. 22, 075007 (2012). source

      Not checked in the free run.

    • cites [116] Liao, Y. T., Yao, H. F., Lingley, A., Parviz, B. & Otis, B. P. A. 3-µW CMOS glucose sensor for wireless contact-lens tear glucose monitoring. IEEE J. Solid-State Circuits 47, 335–344 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Such sensor placement at the base of the eye provides continuously accessible tear glucose measurements when coupled with wireless data transmission, without causing discomfort.

    “Such sensor placement at the base of the eye (behind the eyelid) provides continuously accessible tear glucose measurements when coupled with wireless data transmission, without causing discomfort.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [119] Kownacka, A. E. et al. Clinical evidence for use of a noninvasive biosensor for tear glucose as an alternative to painful finger-prick for diabetes management utilizing biopolymer coating. Biomacromolecules 19, 4504–4511 (2018). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The hydrogel-based contact lens device offers fast and easy fabrication along with a rapid and sensitive glucose response.

    “This device offers fast and easy fabrication along with a rapid and sensitive glucose response.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [112] Elsherif, M., Hassan, M. U., Yetisen, A. K. & Butt, H. Wearable contact lens biosensors for continuous glucose monitoring using smartphones. ACS Nano 12, 5452–5462 (2018). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Tear-based sensors have been focused primarily on glucose monitoring but show considerable promise for non-invasive sensing of other physiologically important biomarkers.

    “Overall, tear-based sensors have been focused primarily on glucose monitoring but show considerable promise for non-invasive sensing of other physiologically important biomarkers.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Further progress was made by embedding a wireless read out chip (2.4 GHz) and by powering with far-field electromagnetic radiation (3μW within 15 cm).

    “Further progress has since been made by embedding a wireless read out chip (2.4 GHz) and by powering with far-field electromagnetic radiation (3μW within 15 cm)116.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Liao, Y. T., Yao, H. F., Lingley, A., Parviz, B. & Otis, B. P. A. 3-µW CMOS glucose sensor for wireless contact-lens tear glucose monitoring. IEEE J. Solid-State Circuits 47, 335–344 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The advanced contact lens device focused on ensuring wearer comfort without hindrance to vision through transparent soft materials, while integrating wireless electronics to eliminate the need for an external power source.

    “This advanced device focused on ensuring wearer comfort without hindrance to vision through the use of transparent soft materials, while integrating wireless electronics to eliminate the need for an external power source.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [118] Park, J. et al. Soft, smart contact lenses with integrations of wireless circuits, glucose sensors, and displays. Sci. Adv. 4, eaap9841 (2018). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tear fluid contains thousands of proteins-the most abundant of which are lysozyme, lactoferrin and albumin.

    “As tear fluid contains thousands of proteins—the most abundant of which are lysozyme, lactoferrin and albumin—non-invasive tear monitoring could also be used to detect protein biomarkers correlated with disease121.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [121] Zhou, L. et al. In-depth analysis of the human tear proteome. J. Proteomics 75, 3877–3885 (2012). source

      Not checked in the free run.

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

    Premisenone given

    The high protein content of saliva makes it attractive for detecting disease and stress biomarkers toward biomedical and fitness monitoring.

    “The high protein content of saliva makes it attractive for detecting disease and stress biomarkers toward biomedical and fitness monitoring.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Compared with epidermally focused wearable biosensors, tear-based systems benefit from the advantage of continuous access to the target biofluid without the need for induction or extraction.

    “Compared with epidermally focused wearable biosensors, tear-based systems benefit from the advantage of continuous access to the target biofluid without the need for induction or extraction.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    Difficult sampling procedures complicate reliable tear-based sensing platforms while contact lens-type systems suffer from design constraints imposed by the nature of their operating environment.

    “However, difficult sampling procedures complicate reliable tear-based sensing platforms while contact lens-type systems suffer from design constraints imposed by the nature of their operating environment.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Several saliva biomarkers (e.g., drug, hormones, metabolites or antibodies) have been used in clinical settings as they offer meaningful diagnostic information.

    “Several of these saliva biomarkers (e.g., drug, hormones, metabolites or antibodies) have been used in clinical settings as they offer meaningful diagnostic information140-144.”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [140] Malon, R. S. P., Sadir, S., Balakrishnan, M. & Córcoles, E. P. Saliva-based biosensors: noninvasive monitoring tool for clinical diagnostics. Biomed Res. Int. 2014, 962903 (2014). source

      Not checked in the free run.

    • cites [141] Chicharro, J. L., Lucía, A., Pérez, M., Vaquero, A. F. & Ureña, R. Saliva composition and exercise. Sports Med. 26, 17–27 (1998). source

      Not checked in the free run.

    • cites [142] Singh, M. Non invasive diagnostic tool for pathological conditions salivary biomarkers. Int. J. Pharm. Biol. Arch. 5, 1–12 (2014).

      Not checked in the free run.

    • cites [143] Gatti, R. & De Palo, E. F. An update: salivary hormones and physical exercise. Scand. J. Med. Sci. Sports 21, 157–169 (2011). source

      Not checked in the free run.

    • cites [144] Viswanath, B., Choi, C. S., Lee, K. & Kim, S. Recent trends in the development of diagnostic tools for diabetes mellitus using patient saliva. Trends Analyt. Chem. 89, 60–67 (2017). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A fluidic platform was suggested by the Butt group for integration with an optical monitoring system, but has not been demonstrated for biosensing applications.

    “Such a fluidic platform was suggested by the Butt group112 for integration with an optical monitoring system, but has not been demonstrated for biosensing applications.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [112] Elsherif, M., Hassan, M. U., Yetisen, A. K. & Butt, H. Wearable contact lens biosensors for continuous glucose monitoring using smartphones. ACS Nano 12, 5452–5462 (2018). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Wearable contact lens tear monitoring platforms do not cause any eye irritation and yield a relatively consistent tear fluid composition.

    “Wearable contact lens tear monitoring platforms are highly advantageous as they do not cause any eye irritation and yield a relatively consistent tear fluid composition.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Many biomarkers in saliva pass directly from the bloodstream via transcellular or paracellular paths, making saliva the "mirror of the human body" that reflects the body's physiological state to offer a non-invasive alternative to blood analysis.

    “Many of the biomarkers in saliva pass directly from the bloodstream via transcellular or paracellular paths, making saliva the “mirror of the human body” that reflects the body’s physiological state to offer a non-invasive alternative to blood analysis.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Saliva is a complex oral fluid, produced mainly by the parotid gland and composed of numerous constituents, such as metabolites, enzymes, hormones, proteins, microorganisms and ions.

    “Saliva is a complex oral fluid, which is produced mainly by the parotid gland and is composed of numerous constituents, such as metabolites, enzymes, hormones, proteins, microorganisms and ions125,135-140.”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [125] Campuzano, S., Yanez-Sedeno, P. & Pingarron, J. M. Electrochemical bioaffinity sensors for salivary biomarkers detection. Trends Analyt. Chem. 86, 14–24 (2017). source

      Not checked in the free run.

    • cites [135] Aguirre, A. et al. Sialochemistry: a diagnostic tool? Crit. Rev. Oral Biol. Med. 4, 343–350 (1993). source

      Not checked in the free run.

    • cites [136] Kaufman, E. & Lamster, I. B. The diagnostic applications of saliva—a review. Crit. Rev. Oral Biol. Med. 13, 197–212 (2002). source

      Not checked in the free run.

    • cites [137] Chiappin, S., Antonelli, G., Gatti, R. & De Palo, E. F. Saliva specimen: a new laboratory tool for diagnostic and basic investigation. Clin. Chim. Acta 383, 30–40 (2007). source

      Not checked in the free run.

    • cites [138] Streckfus, C. F. & Bigler, L. R. Saliva as a diagnostic fluid. Oral Dis. 8, 69–76 (2002). source

      Not checked in the free run.

    • cites [139] Mandel, I. D. The diagnostic uses of saliva. J. Oral Pathol. Med. 19, 119–125 (1990). source

      Not checked in the free run.

    • cites [140] Malon, R. S. P., Sadir, S., Balakrishnan, M. & Córcoles, E. P. Saliva-based biosensors: noninvasive monitoring tool for clinical diagnostics. Biomed Res. Int. 2014, 962903 (2014). source

      Not checked in the free run.

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

    Premisenone given

    Such in-mouth operation required the replacement of several teeth by the sensors and was subject to risks associated with potential leakage of the internal sensor solution.

    “However, such in-mouth operation required the replacement of several teeth by the sensors and was subject to risks associated with potential leakage of the internal sensor solution.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    These oral-cavity sensors were integrated with a resonant coil for battery-free operation and were capable of detecting salivary bacteria at the single cell level in vitro using a naturally occurring antimicrobial peptide (AMP) biorecognition element along with label-free impedance transduction.

    “These oral-cavity sensors were integrated with a resonant coil for battery-free operation and were capable of detecting salivary bacteria at the single cell level in vitro using a naturally occurring antimicrobial peptide (AMP) biorecognition element along with label-free impedance transduction.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Mannoor, M. S. et al. Graphene-based wireless bacteria detection on tooth enamel. Nat. Commun. 3, 763 (2012). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    In-mouth biosensing platforms can offer an attractive painless route for obtaining dynamic chemical information from saliva.

    “Despite these challenges, in-mouth biosensing platforms can offer an attractive painless route for obtaining dynamic chemical information from saliva.”
    Quote in the paperSubstantial claim

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

    Premisenone given

    The first example of a wearable oral sensor was demonstrated in the 1960s and was based on a partial denture platform for monitoring mastication, monitoring plaque pH and fluoride concentrations.

    “The first example of a wearable oral sensor was demonstrated in the 1960s and was based on a partial denture platform for monitoring mastication monitoring plaque pH and fluoride concentrations.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    In diabetes, changes in hormonal and neural balance may impact the salivary glands, which act as a filter from the blood, and lead to increased secretion of salivary glucose.

    “In the case of diabetes, changes in hormonal and neural balance may impact the salivary glands, which act as a filter from the blood, and lead to increased secretion of salivary glucose.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The developed cavitas sensors are based on a GOX-modified poly(ethylene terephthalate) glycol (PETG) surface, and the device is seamlessly integrated with a wireless transmitter on a custom-fitted monolithic mouthguard platform.

    “The developed sensors are based on a GOX-modified poly(ethylene terephthalate) glycol (PETG) surface, and the device is seamlessly integrated with a wireless transmitter on a custom-fitted monolithic mouthguard platform.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [148] Arakawa, T. et al. Mouthguard biosensor with telemetry system for monitoring of saliva glucose: a novel cavitas sensor. Biosens. Bioelectron. 84, 106–111 (2016). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Soni et al. demonstrated the correlation between blood and saliva glucose concentrations to be R = 0.64 in healthy subjects, whereas diabetic subjects show a much closer relationship with R = 0.95.

    “Soni et al.126 have demonstrated the correlation between blood and saliva glucose concentrations to be R = 0.64 in healthy subjects, whereas diabetic subjects show a much closer relationship with R = 0.95.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [126] Soni, A. & Jha, S. K. A paper strip based non-invasive glucose biosensor for salivary analysis. Biosens. Bioelectron. 67, 763–768 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This configuration enables the telemetric measurement of salivary glucose in artificial saliva over the relevant physiological range (5-1000 μM) and the device has been further characterized through connection to a phantom jaw that mimics the human oral cavity with a saliva flow system.

    “This configuration enables the telemetric measurement of salivary glucose in artificial saliva over the relevant physiological range (5–1000 μM) and the device has been further characterized through connection to a phantom jaw that mimics the human oral cavity with a saliva flow system.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [148] Arakawa, T. et al. Mouthguard biosensor with telemetry system for monitoring of saliva glucose: a novel cavitas sensor. Biosens. Bioelectron. 84, 106–111 (2016). source

      Not checked in the free run.

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

    Interpretationreasoning

    These advances have greatly enhanced the reliability of wearable biosensor, the analyte monitoring capabilities and wearability.

    “These advances have greatly enhanced the reliability of wearable biosensor, the analyte monitoring capabilities and wearability.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    Some of these challenges are specific to the individual platforms or target analytes, whereas others are shared by all wearable biosensing systems.

    “Some of these challenges are specific to the individual platforms or target analytes, whereas others are shared by all wearable biosensing systems.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    These demonstrations have shown that wearable biosensors have immense potential for real-world applications.

    “These demonstrations have shown that wearable biosensors have immense potential for real-world applications.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Fouling of the surface of wearable biosensors, particularly those operating in sweat or tears over short durations, is expected to be less severe compared with that observed with implantable or minimally-invasive sensors.

    “Fouling of the surface of wearable biosensors, particularly those operating in sweat or tears over short durations, is expected to be less severe compared with that observed with implantable or minimally-invasive sensors.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Such dramatic progress has benefited from the refinement of multiplexed-sensing platforms, improved biofluid sampling and advances in flexible materials and wireless electronics.

    “Such dramatic progress has benefited from the refinement of multiplexed-sensing platforms, improved biofluid sampling and advances in flexible materials and wireless electronics.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    A wireless electronic printed circuit board (PCB) containing a fully functional microcontroller is a widely used platform for wireless electronics due to its flexibility and cost-effectiveness.

    “A wireless electronic printed circuit board (PCB) containing a fully functional microcontroller is a widely used platform for wireless electronics due to its flexibility and cost-effectiveness.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Such severe conditions may affect the stability of their fragile bioreceptors.

    “Such severe conditions may affect the stability of their fragile bioreceptors.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    These issues can be partially addressed using proper microfluidic sampling systems and optimization of surface coating techniques.

    “These issues can be partially addressed using proper microfluidic sampling systems and optimization of surface coating techniques.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Multiplexed sensing, including both biosensors and physical sensors, could provide active calibration for variations in temperature, pH and humidity.

    “Multiplexed sensing, including both biosensors and physical sensors, could provide active calibration for variations in temperature, pH and humidity.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Energy can be harvested from motion with piezoelectric or triboelectric devices.

    “motion with piezoelectric or triboelectric devices185,186”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [185] Yang, J.H. et al. Effect of garment design on piezoelectricity harvesting from joint movement. Smart Mater. Struct. 25, 1–15 (2016). source

      Not checked in the free run.

    • cites [186] Pu, X. et al. Wearable self-charging power textile based on flexible yarn supercapacitors and fabric nanogenerators. Adv. Mater. 28, 98–105 (2016). source

      Not checked in the free run.

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

    Premisecitation

    Energy can be harvested from heat with thermoelectric materials.

    “heat with thermoelectric materials187,188”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [187] Oh, J. Y. et al. Chemically exfoliated transition metal dichalcogenide nanosheet-based wearable thermoelectric generators. Energy Environ. Sci. 9, 1696–1705 (2016). source

      Not checked in the free run.

    • cites [188] Lu, Z. S., Zhang, H. H., Mao, C. P. & Li, C. M. Silk fabric-based wearable thermoelectric generator for energy harvesting from the human body. Appl. Energy 164, 57–63 (2016). source

      Not checked in the free run.

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

    Premisecitation

    Energy can be harvested from light with wearable solar cells.

    “Energy can be harvested from light with wearable solar cells183,184”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [183] O’Connor, T. F. et al. Wearable organic solar cells with high cyclic bending stability: materials selection criteria. Sol. Energy Mater. Sol. Cells 144, 438–444 (2016). source

      Not checked in the free run.

    • cites [184] Kim, B. J. et al. Highly efficient and bending durable perovskite solar cells: toward a wearable power source. Energy Environ. Sci. 8, 916–921 (2015). source

      Not checked in the free run.

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

    Interpretationreasoning

    Advances in wearable power sources are a significant need, particularly with increases in energy demands caused by multiplexed sensing platforms.

    “Advances in wearable power sources are a significant need, particularly with increases in energy demands caused by multiplexed sensing platforms.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The global wearable sensors market was valued at roughly $150 million in 2016 and is projected to reach $2.86 billion by 2025.

    “The global wearable sensors market was valued at roughly $150 million in 2016 and is projected to reach $2.86 billion by 2025, according to a recent market report (https://www.grandviewresearch.com/industry-analysis/global-wearable-sensor-market).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites https://www.grandviewresearch.com/industry-analysis/global-wearable-sensor-market

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationnone given

    The acceptance of non-invasive biosensors by the medical community will require extensive and successful validation in human testing and improved understanding of the clinical relevancy of sensor information.

    “The acceptance of these non-invasive biosensors by the medical community will require extensive and successful validation in human testing and improved understanding of the clinical relevancy of sensor information.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationnone given

    Future advances, breakthroughs and growth in wearable biosensors will require close multidisciplinary collaboration among the engineering, scientific and medical communities.

    “Such future advances, breakthroughs and growth will require close multidisciplinary collaboration among the engineering, scientific and medical communities.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Sensor preparation must ensure high bioreceptor stability for maintaining accuracy and reliability of the response.

    “The sensor preparation thus must ensure high bioreceptor stability for maintaining accuracy and reliability of the response.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Fully integrated wearable biosensing platforms would require incorporation of wireless electronics (integrated with energy source) to facilitate data processing and secured signal transmission.

    “Fully integrated wearable biosensing platforms would require incorporation of wireless electronics (integrated with energy source) to facilitate the data processing and secured signal transmission.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The regeneration issue of immunosensors is a major challenge to overcome if prolonged use of wearables is to be attained.

    “The regeneration issue of immunosensors is another major challenge to overcome if prolonged use of wearables is to be attained.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    For completely reliable use, wearable devices must overcome stability issues caused by prolonged operation under uncontrolled conditions, biofouling from constituents present in the sampled biofluids, and intrinsic instabilities of the biological recognition components themselves.

    “For completely reliable use, wearable devices must overcome stability issues caused by prolonged operation under uncontrolled conditions, biofouling from constituents present in the sampled biofluids, and intrinsic instabilities of the biological recognition components themselves.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The use of mobile devices and smartphone-based microscopes, including algorithm-based applications, is expected to facilitate the readout of the response in optical wearable biosensors.

    “Furthermore, the use of mobile devices and smartphone-based microscopes, including algorithm-based applications, is expected to facilitate the readout of the response in optical wearable biosensors112,113,195.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [112] Elsherif, M., Hassan, M. U., Yetisen, A. K. & Butt, H. Wearable contact lens biosensors for continuous glucose monitoring using smartphones. ACS Nano 12, 5452–5462 (2018). source

      Not checked in the free run.

    • cites [113] Sung, Y., Campa, F. & Shih, W. C. Open-source do-it-yourself multi-color fluorescence smartphone microscopy. Biomed. Opt. Express 8, 5075–5086 (2017). source

      Not checked in the free run.

    • cites [195] Yetisen, A. K., Martinez-Hurtado, J. L., Garcia-Melendrez, A., Vasconcellos, F. D. & Lowe, C. R. A smartphone algorithm with inter-phone repeatability for the analysis of colorimetric tests. Sens. Actuators B Chem. 196, 156–160 (2014). source

      Not checked in the free run.

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

    Premisecitation

    A large portion of the future wearable sensors market share is expected to be made up of wearable biosensors, primarily non-invasive glucose monitoring.

    “A large portion of this future market share is expected to be made up of wearable biosensors, primarily non-invasive glucose monitoring2.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Heikenfeld, J. et al. Wearable sensors: modalities, challenges, and prospects. Lab Chip 18, 217–248 (2018). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    Wearable devices must be capable of robust operation without the need for constant (re)calibration.

    “Furthermore, the devices must be capable of robust operation without the need for constant (re)calibration (common in laboratory settings).”
    Quote in the paperNot a substantial claim
84 of 84

  • The paper relies on this without support.

    Sweat glands are distributed across the entire body with more than 100 glands/cm2 of skin.

    “Sweat is the most readily obtainable biofluid for chemical sensing applications since sweat glands are distributed across the entire body with more than 100 glands/cm2 of skin.”

  • The paper relies on this without support.

    Sweat lactate is a byproduct of local sweat gland metabolism and intense physical activity induces higher generation rates.

    “Sweat lactate is a byproduct of local sweat gland metabolism and intense physical activity induces higher generation rates.”

  • The paper relies on this without support.

    ISF components diffuse directly from the capillary endothelium.

    “Within the viable skin tissue, skin cells are surrounded by ISF, which provides nutrients that diffuse directly from the capillary endothelium.”

  • The paper relies on this without support.

    Wearable biosensor technologies can improve health and performance.

    “Considering all the above challenges, we are only at the beginning of understanding how wearable biosensor technologies can improve our health and performance.”
4 of 4

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?

  • Biosensing technology is increasingly being used to provide real-time physiological information using dynamic non-invasive measurements of markers including but not limited to heart rate.

    “Biosensing technology is increasingly being used to provide real-time physiological information using dynamic non-invasive measurements of markers including but not limited to heart rate (Kim et al. 2019).”

    From Effects of a Personalized Stress Management Intervention on Maternal Mental Health: A Randomized Clinical Trial. (2025) · cites this paper as Kim et al. 2019

  • Despite some efforts, several challenges remain for tear biosensors, such as difficulty in sampling tears, small sample volumes, issues with fast evaporation, dependence of tear composition on emotional or mechanical stimulation, and reliable operation of fully integrated wireless sensing platforms.

    “Despite some efforts, several challenges remain, such as difficulty in sampling tears, small sample volumes, issues with fast evaporation, dependence of tear composition on emotional or mechanical stimulation, and reliable operation of fully integrated wireless sensing platforms [126,152].”

    From The emergence of AI-based wearable sensors for digital health technology: a review (2023) · cites this paper as [126]

  • Biochemical sensors can measure body fluid electrolytes with electrochemical transducers, offering valuable information about plasma volume status and analyte concentrations.

    “Biochemical sensors can measure body fluid electrolytes with the use of electrochemical transducers, offering valuable information about plasma volume status and analyte concentrations30.”

    From Smart wearable devices in cardiovascular care: Where we are and how to move forward (2021) · cites this paper as [30]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Iontophoretic alcohol biosensor cites an unrelated paper

    Minor

    Reference 75 concerns sensing fibers woven into fabric, whereas the cited passage describes an iontophoretic tattoo biosensor for sweat alcohol.

  • Piezoelectric biosensor description cites an optical-sensor paper

    Minor

    The cited reference 56 describes a textile patch with optical detection, not the piezoelectric electronic-skin biosensor described in the text.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. Singh, M. Non invasive diagnostic tool for pathological conditions salivary biomarkers. Int. J. Pharm. Biol. Arch. 5, 1–12 (2014).
  2. Imani, S., Mercier, P.P., Bandodkar, A.J., Kim, J. & Wang, J. in 2016 IEEE International Symposium on Circuits and Systems (ISCAS) 1122–1125 (IEEE, 2016).
  3. Dimitriou, T. & Ioannis, K. in First International Symposium on Applied Sciences on Biomedical and Communication Technologies, 2008 ISABEL’08 1–5 (IEEE, 2008).

Cited by

Sorted by citations

Related

Authors
Kim, J., Campbell, A. S., de Ávila, B. E.-F., & Wang, J.
Affiliations
University of California San Diego (US)
Corresponding author
Wang, Joseph
ORCID
Venue
Nature Biotechnology
Publisher
Springer Science and Business Media LLC
Published
2019-02-25
Volume
37
Issue
4
Pages
389-406
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
DOI
10.1038/s41587-019-0045-y
PMC
PMC8183422
OpenAlex
W2917386416
Cited by
3,373
References
196
Citations by year
2026: 424 · 2025: 544 · 2024: 557 · 2023: 511 · 2022: 472 · 2021: 418 · 2020: 340 · 2019: 106
FWCI
26.94
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Biotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Alcohol Abuse and Alcoholism (T32AA013525)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Advanced Sensor and Energy Harvesting Materials
  • Physical Sciences › Engineering › Electrical and Electronic Engineering › Electrochemical sensors and biosensors
  • Physical Sciences › Engineering › Biomedical Engineering › Biosensors and Analytical Detection
Keywords
wearable biosensors, biological fluids, sweat, saliva, tears, interstitial fluid, electrochemical biosensor, optical biosensors, multiplexed biosensing, flexible materials, real-time physiological monitoring, wearable healthcare
MeSH terms
Wearable Electronic Devices, Biotechnology, Body Fluids, Computer Systems, Humans, Iontophoresis, Monitoring, Physiologic, Saliva, Sweat, Tears, Biosensing Techniques, Lab-On-A-Chip Devices

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 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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