Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Wearable flexible microfluidic sensing technologies

Nature Reviews Bioengineering volume 1, pages 950–971 (2023)Cite this article

Subjects

Abstract

Wearable biosensing technologies can provide real-time monitoring of health and disease at the point of care. By integrating flexible microfluidics with wearable biosensors, body fluids can be non-invasively sampled and analysed for reliable, clinically informative, cost-effective and continuous biomedical monitoring. In this Review, we discuss flexible wearable microfluidic sensors for health monitoring and disease diagnosis, highlighting materials and engineering considerations with regard to biofluid collection, analyte calibration, signal interferences reduction, target recognition, and sensor reusability. We outline how such flexible microfluidic-based biosensors can be designed for the analysis of sweat, saliva, tears, interstitial fluid and wound exudate, and examine their applications at the point of care. Finally, we highlight the challenges that remain to be addressed for the clinical translation of wearable flexible microfluidic sensors and discuss future possibilities, including the integration of machine learning and the Internet-of-things.

Key points

  • Flexible microfluidics can be integrated into wearable flexible sensors to facilitate biofluid sampling and sensing.

  • Flexible microfluidic sensors for sweat, interstitial fluid, tears, saliva and wound exudate may advance personalized health care, in particular for metabolic, eye, oral cavity, gastrointestinal and infectious disease management.

  • Continuous monitoring by flexible microfluidic sensors can be achieved by exploiting direct or enzyme-based redox reactions or bioaffinity and by applying sensor-regeneration strategies such as programmed electrical stimuli.

  • Artificial intelligence can be integrated into flexible microfluidic sensors to design smart point-of-care systems that can aid in medical decision-making by leveraging the Internet-of-things in medicine.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Flexible microfluidic biosensors for biomedical applications.
Fig. 2: Building blocks of flexible microfluidic biosensors.
Fig. 3: Functions of flexible microfluidics.
Fig. 4: Sampling and sensing strategies of flexible microfluidic sensors.

Similar content being viewed by others

References

  1. Sackmann, E. K., Fulton, A. L. & Beebe, D. J. The present and future role of microfluidics in biomedical research. Nature 507, 181–189 (2014).

    Article  Google Scholar 

  2. Whitesides, G. M. The origins and the future of microfluidics. Nature 442, 368–373 (2006).

    Article  Google Scholar 

  3. Yeo, J. C., Kenry & Lim, C. T. Emergence of microfluidic wearable technologies. Lab Chip 16, 4082–4090 (2016).

    Article  Google Scholar 

  4. Li, S., Ma, Z., Cao, Z., Pan, L. & Shi, Y. Advanced wearable microfluidic sensors for healthcare monitoring. Small 16, e1903822 (2020).

    Article  Google Scholar 

  5. Ghaffari, R. et al. Soft wearable systems for colorimetric and electrochemical analysis of biofluids. Adv. Funct. Mater. 30, 1907269 (2019).

    Article  Google Scholar 

  6. Nguyen, N.-T., Wereley, S. T. & Shaegh, S. A. M. Fundamentals and applications of microfluidics (Artech House, 2019).

  7. Gao, W., Ota, H., Kiriya, D., Takei, K. & Javey, A. Flexible electronics toward wearable sensing. Acc. Chem. Res. 52, 523–533 (2019).

    Article  Google Scholar 

  8. Min, J. et al. Skin-interfaced wearable sweat sensors for precision medicine. Chem. Rev. 123, 5049–5138 (2023).

    Article  Google Scholar 

  9. Wu, J., Liu, H., Chen, W., Ma, B. & Ju, H. Device integration of electrochemical biosensors. Nat. Rev. Bioeng. 1, 346–360 (2023).

    Article  Google Scholar 

  10. Sempionatto, J. R., Lasalde-Ramirez, J. A., Mahato, K., Wang, J. & Gao, W. Wearable chemical sensors for biomarker discovery in the omics era. Nat. Rev. Chem. 6, 899–915 (2022).

    Article  Google Scholar 

  11. Lin, M., Hu, H., Zhou, S. & Xu, S. Soft wearable devices for deep-tissue sensing. Nat. Rev. Mater. 7, 850–869 (2022).

    Article  Google Scholar 

  12. Ates, H. C. et al. End-to-end design of wearable sensors. Nat. Rev. Mater. 7, 887–907 (2022).

    Article  Google Scholar 

  13. Kim, J., Campbell, A. S., de Ávila, B. E.-F. & Wang, J. Wearable biosensors for healthcare monitoring. Nat. Biotechnol. 37, 389–406 (2019).

    Article  Google Scholar 

  14. He, T. et al. Emerging wearable chemical sensors enabling advanced integrated systems toward personalized and preventive medicine. Anal. Chem. 95, 490–514 (2023).

    Article  Google Scholar 

  15. Luo, Y. et al. Technology roadmap for flexible sensors. ACS Nano 17, 5211–5295 (2023).

    Article  Google Scholar 

  16. Chen, G., Zheng, J., Liu, L. & Xu, L. Application of microfluidics in wearable devices. Small Methods 3, 1900688 (2019).

    Article  Google Scholar 

  17. Jeerapan, I., Moonla, C., Thavarungkul, P. & Kanatharana, P. Lab on a body for biomedical electrochemical sensing applications: the next generation of microfluidic devices. Prog. Mol. Biol. Transl. Sci. 187, 249–279 (2022).

    Article  Google Scholar 

  18. Nyein, H. Y. Y. et al. A wearable patch for continuous analysis of thermoregulatory sweat at rest. Nat. Commun. 12, 1823 (2021). This article reports a wearable patch that contains hydrophilic fillers for rapid sweat uptake, enabling continuous sweat monitoring at rest, including pH, Cl−, levodopa and sweat rate sensing.

    Article  Google Scholar 

  19. Lin, H. et al. A programmable epidermal microfluidic valving system for wearable biofluid management and contextual biomarker analysis. Nat. Commun. 11, 4405–4405 (2020).

    Article  Google Scholar 

  20. Wang, M. et al. A wearable electrochemical biosensor for the monitoring of metabolites and nutrients. Nat. Biomed. Eng. 6, 1225–1235 (2022). This article reports a wearable electrochemical biosensor for continuous metabolite and nutrient analysis, which integrates iontophoresis-based sweat stimulation and potential-initiated in situ electrode regeneration, achieving detection of all essential amino acids and vitamins during physical exercise and at rest.

    Article  Google Scholar 

  21. Kim, S. et al. Soft, skin-interfaced microfluidic systems with integrated immunoassays, fluorometric sensors, and impedance measurement capabilities. Proc. Natl Acad. Sci. USA 117, 27906–27915 (2020).

    Article  Google Scholar 

  22. Fallahi, H., Zhang, J., Phan, H. P. & Nguyen, N. T. Flexible microfluidics: fundamentals, recent developments, and applications. Micromachines https://doi.org/10.3390/mi10120830 (2019).

    Article  Google Scholar 

  23. Coyle, S. et al. Bio-sensing textiles-wearable chemical biosensors for health monitoring. 4th International Workshop on Wearable and Implantable Body Sensor Networks (BSN 2007) March 26–28, 2007 RWTH Aachen University, Germany, 35–39 (Aachen University, 2007).

  24. Coyle, S. et al. BIOTEX-Biosensing textiles for personalised healthcare management. IEEE Trans. Inf. Technol. Biomed. 14, 364–370 (2010).

    Article  Google Scholar 

  25. Curto, V. F. et al. Real-time sweat pH monitoring based on a wearable chemical barcode micro-fluidic platform incorporating ionic liquids. Sens. Actuators B Chem. 171, 1327–1334 (2012).

    Article  Google Scholar 

  26. Rose, D. P. et al. Adhesive RFID sensor patch for monitoring of sweat electrolytes. IEEE Trans. Biomed. Eng. 62, 1457–1465 (2015).

    Article  Google Scholar 

  27. Koh, A. et al. A soft, wearable microfluidic device for the capture, storage, and colorimetric sensing of sweat. Sci. Transl Med. 8, 366ra165 (2016). This article reports the first integrated PDMS-based wearable microfluidic colourimetric sweat monitoring system for analysis of multiple analytes with wireless communication powering modules.

    Article  Google Scholar 

  28. Wang, B. et al. Wearable aptamer-field-effect transistor sensing system for noninvasive cortisol monitoring. Sci. Adv. 8, eabk0967 (2022). This article reports the accurate detection of cortisol using a label-free field-effect transistor-based sweat sensor.

    Article  Google Scholar 

  29. Gao, Y. et al. A flexible multiplexed immunosensor for point-of-care in situ wound monitoring. Sci. Adv. 7, eabg9614 (2021). This article reports a wireless wound patch with a biomimetic microfluidic exudate collector for multiplexed wound profiling through monitoring of inflammatory mediators, Staphylococcus aureus, temperature and pH.

    Article  Google Scholar 

  30. Klode, J. et al. Investigation of adhesion of modern wound dressings: a comparative analysis of 56 different wound dressings. J. Eur. Acad. Dermatol. Venereol. 25, 933–939 (2011).

    Article  Google Scholar 

  31. Reeder, J. T. et al. Waterproof, electronics-enabled, epidermal microfluidic devices for sweat collection, biomarker analysis, and thermography in aquatic settings. Sci. Adv. 5, eaau6356 (2019).

    Article  Google Scholar 

  32. Choi, J.-Y., Park, D.-W. & Oh, T. S. Variation of elastic stiffness of polydimethylsiloxane (PDMS) stretchable substrates for wearable packaging applications. J. Microelectron. Electron. Packag. 21, 125–131 (2014).

    Article  Google Scholar 

  33. Olanrewaju, A., Beaugrand, M., Yafia, M. & Juncker, D. Capillary microfluidics in microchannels: from microfluidic networks to capillaric circuits. Lab Chip 18, 2323–2347 (2018).

    Article  Google Scholar 

  34. Zhang, Y. et al. Skin-interfaced microfluidic devices with one-opening chambers and hydrophobic valves for sweat collection and analysis. Lab Chip 20, 2635–2645 (2020).

    Article  Google Scholar 

  35. Lim, H., Jafry, A. T. & Lee, J. Fabrication, flow control, and applications of microfluidic paper-based analytical devices. Molecules 24, 2869 (2019).

    Article  Google Scholar 

  36. Shen, L. L., Zhang, G. R. & Etzold, B. J. M. Paper-based microfluidics for electrochemical applications. ChemElectroChem 7, 10–30 (2020).

    Article  Google Scholar 

  37. Zhao, Z. et al. A thread/fabric-based band as a flexible and wearable microfluidic device for sweat sensing and monitoring. Lab Chip 21, 916–932 (2021).

    Article  Google Scholar 

  38. Agustini, D. et al. Microfluidic devices based on textile threads for analytical applications: state of the art and prospects. Anal. Methods 13, 4830–4857 (2021).

    Article  Google Scholar 

  39. Gong, M. M. & Sinton, D. Turning the page: advancing paper-based microfluidics for broad diagnostic application. Chem. Rev. 117, 8447–8480 (2017).

    Article  Google Scholar 

  40. Deroco, P. B., Wachholz Junior, D. & Kubota, L. T. Paper‐based wearable electrochemical sensors: a new generation of analytical devices. Electroanalysis 35, e202200177 (2022).

    Article  Google Scholar 

  41. Abbasiasl, T., Mirlou, F., Istif, E., Ceylan Koydemir, H. & Beker, L. A wearable paper-integrated microfluidic device for sequential analysis of sweat based on capillary action. Sens. Diagn. 1, 775–786 (2022).

    Article  Google Scholar 

  42. Tang, R. H. et al. A review on advances in methods for modification of paper supports for use in point-of-care testing. Mikrochim. Acta 186, 521 (2019).

    Article  Google Scholar 

  43. Li, M. et al. A highly integrated sensing paper for wearable electrochemical sweat analysis. Biosens. Bioelectron. 174, 112828 (2021).

    Article  Google Scholar 

  44. Cao, Q. et al. Three-dimensional paper-based microfluidic electrochemical integrated devices (3D-PMED) for wearable electrochemical glucose detection. RSC Adv. 9, 5674–5681 (2019).

    Article  Google Scholar 

  45. Choi, J., Kang, D., Han, S., Kim, S. B. & Rogers, J. A. Thin, soft, skin-mounted microfluidic networks with capillary bursting valves for chrono-sampling of sweat. Adv. Healthc. Mater. 6, 1601355 (2017).

    Article  Google Scholar 

  46. Kim, S. B. et al. Super‐absorbent polymer valves and colorimetric chemistries for time‐sequenced discrete sampling and chloride analysis of sweat via skin‐mounted soft microfluidics. Small 14, 1703334 (2018).

    Article  Google Scholar 

  47. Choi, J. et al. Soft, skin-integrated multifunctional microfluidic systems for accurate colorimetric analysis of sweat biomarkers and temperature. ACS Sens. 4, 379–388 (2019).

    Article  Google Scholar 

  48. Bandodkar, A. J. et al. Soft, skin‐interfaced microfluidic systems with passive galvanic stopwatches for precise chronometric sampling of sweat. Adv. Mater. 31, 1902109 (2019).

    Article  Google Scholar 

  49. Xiao, J. et al. Microfluidic chip-based wearable colorimetric sensor for simple and facile detection of sweat glucose. Anal. Chem. 91, 14803–14807 (2019).

    Article  Google Scholar 

  50. Mishra, N. et al. A soft wearable microfluidic patch with finger-actuated pumps and valves for on-demand, longitudinal, and multianalyte sweat sensing. ACS Sens. 7, 3169–3180 (2022).

    Article  Google Scholar 

  51. Reeder, J. T. et al. Resettable skin interfaced microfluidic sweat collection devices with chemesthetic hydration feedback. Nat. Commun. 10, 5513 (2019). This article reports a reusable skin-mounted microfluidic sensor, which includes a pinch valve and a suction pump to reset the microfluidics, and an effervescent pump and a chemaesthetic agent for automated warnings of excessive sweat loss.

    Article  Google Scholar 

  52. Zhong, B., Jiang, K., Wang, L. & Shen, G. Wearable sweat loss measuring devices: from the role of sweat loss to advanced mechanisms and designs. Adv. Sci. 9, e2103257 (2022).

    Article  Google Scholar 

  53. Baker, L. B. & Wolfe, A. S. Physiological mechanisms determining eccrine sweat composition. Eur. J. Appl. Physiol. 120, 719–752 (2020).

    Article  Google Scholar 

  54. Sonner, Z. et al. The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications. Biomicrofluidics 9, 031301 (2015).

    Article  Google Scholar 

  55. Baker, L. B. et al. Skin-interfaced microfluidic system with personalized sweating rate and sweat chloride analytics for sports science applications. Sci. Adv. 6, eabe3929 (2020). This article presents the systematic validation of a wearable microfluidic sweat sensor by testing the device on 312 athletes in various conditions.

    Article  Google Scholar 

  56. Kim, S. B. et al. Soft, skin-interfaced microfluidic systems with wireless, battery-free electronics for digital, real-time tracking of sweat loss and electrolyte composition. Small 14, 1802876 (2018).

    Article  Google Scholar 

  57. Kwon, K. et al. An on-skin platform for wireless monitoring of flow rate, cumulative loss and temperature of sweat in real time. Nat. Electron. 4, 302–312 (2021).

    Article  Google Scholar 

  58. Pu, Z. et al. A thermal activated and differential self-calibrated flexible epidermal biomicrofluidic device for wearable accurate blood glucose monitoring. Sci. Adv. https://doi.org/10.1126/sciadv.abd0199 (2021).

    Article  Google Scholar 

  59. Bariya, M., Nyein, H. Y. Y. & Javey, A. Wearable sweat sensors. Nat. Electron. 1, 160–171 (2018).

    Article  Google Scholar 

  60. Naik, A. R. et al. Printed microfluidic sweat sensing platform for cortisol and glucose detection. Lab Chip 22, 156–169 (2021).

    Article  Google Scholar 

  61. Kim, J. et al. A skin-interfaced, miniaturized microfluidic analysis and delivery system for colorimetric measurements of nutrients in sweat and supply of vitamins through the skin. Adv. Sci. 9, e2103331 (2022).

    Article  Google Scholar 

  62. Choi, J. et al. Skin-interfaced microfluidic systems that combine hard and soft materials for demanding applications in sweat capture and analysis. Adv. Healthc. Mater. 10, e2000722 (2021).

    Article  Google Scholar 

  63. Zhao, Y. et al. A wearable freestanding electrochemical sensing system. Sci. Adv. 6, eaaz0007 (2020). This article introduces an out-of-plain strain-isolated pathway in microfluidic sensor design, achieving high-fidelity data acquisition.

    Article  Google Scholar 

  64. Dourado, A. H. B. Electric double layer: the good, the bad, and the beauty. Electrochem 3, 789–808 (2022).

    Article  Google Scholar 

  65. Schmickler, W. Electronic effects in the electric double layer. Chem. Rev. 96, 3177–3200 (1996).

    Article  Google Scholar 

  66. Xu, G. et al. Battery-free and wireless epidermal electrochemical system with all-printed stretchable electrode array for multiplexed in situ sweat analysis. Adv. Mater. Technol. 4, 1800658 (2019).

    Article  Google Scholar 

  67. Zhao, Y. et al. Soft strain-insensitive bioelectronics featuring brittle materials. Science 378, 1222–1227 (2022).

    Article  Google Scholar 

  68. Bae, C. W. et al. Fully stretchable capillary microfluidics-integrated nanoporous gold electrochemical sensor for wearable continuous glucose monitoring. ACS Appl. Mater. Interfaces 11, 14567–14575 (2019).

    Article  Google Scholar 

  69. Ji, S. et al. Water-resistant conformal hybrid electrodes for aquatic endurable electrocardiographic monitoring. Adv. Mater. 32, e2001496 (2020).

    Article  Google Scholar 

  70. Xu, S. et al. Soft microfluidic assemblies of sensors, circuits, and radios for the skin. Science 344, 70–74 (2014).

    Article  Google Scholar 

  71. Lee, H. et al. Wearable/disposable sweat-based glucose monitoring device with multistage transdermal drug delivery module. Sci. Adv. 3, e1601314 (2017).

    Article  Google Scholar 

  72. Hong, Y. J. et al. Multifunctional wearable system that integrates sweat-based sensing and vital-sign monitoring to estimate pre-/post-exercise glucose levels. Adv. Funct. Mater. 28, 1805754 (2018).

    Article  Google Scholar 

  73. Xie, W. et al. Ultra-stretchable, bio-inspired ionic skins that work stably in various harsh environments. J. Mater. Chem. A 6, 24114–24119 (2018).

    Article  Google Scholar 

  74. Sabate Del Rio, J., Henry, O. Y. F., Jolly, P. & Ingber, D. E. An antifouling coating that enables affinity-based electrochemical biosensing in complex biological fluids. Nat. Nanotechnol. 14, 1143–1149 (2019).

    Article  Google Scholar 

  75. Wisniewski, N. & Reichert, M. Methods for reducing biosensor membrane biofouling. Colloids Surf. B 18, 197–219 (2000).

    Article  Google Scholar 

  76. Xu, J. & Lee, H. Anti-biofouling strategies for long-term continuous use of implantable biosensors. Chemosensors https://doi.org/10.3390/chemosensors8030066 (2020).

    Article  Google Scholar 

  77. Lee, H.-B., Meeseepong, M., Trung, T. Q., Kim, B.-Y. & Lee, N.-E. A wearable lab-on-a-patch platform with stretchable nanostructured biosensor for non-invasive immunodetection of biomarker in sweat. Biosens. Bioelectron. 156, 112133 (2020).

    Article  Google Scholar 

  78. Huynh, V. L. et al. Hollow microfibers of elastomeric nanocomposites for fully stretchable and highly sensitive microfluidic immunobiosensor patch. Adv. Funct. Mater. 30, 2004684 (2020).

    Article  Google Scholar 

  79. Xi, W. et al. Soft tubular microfluidics for 2D and 3D applications. Proc. Natl Acad. Sci. USA 114, 10590–10595 (2017).

    Article  Google Scholar 

  80. Xi, W., Yeo, J. C., Yu, L., Zhang, S. & Lim, C. T. Ultrathin and wearable microtubular epidermal sensor for real-time physiological pulse monitoring. Adv. Mater. Technol. 2, 1700016 (2017).

    Article  Google Scholar 

  81. Choi, D. Y. et al. Highly stretchable, hysteresis-free ionic liquid -based strain sensor for precise human motion monitoring. ACS Appl. Mater. Interfaces 9, 1770–1780 (2017).

    Article  Google Scholar 

  82. Bariya, M. et al. Resettable microfluidics for broad-range and prolonged sweat rate sensing. ACS Sens. 7, 1156–1164 (2022).

    Article  Google Scholar 

  83. Li, J. et al. Designing biomimetic liquid diodes. Soft Matter 15, 1902–1915 (2019).

    Article  Google Scholar 

  84. Wang, S. et al. A review of capillary pressure control valves in microfluidics. Biosensors 11, 10 (2021).

    Article  Google Scholar 

  85. Naeimirad, M., Abuzade, R., Babaahmadi, V. & Dabirian, F. Microfluidic through fibrous structures: recent developments and future trends. Mater. Des. Process. Commun. https://doi.org/10.1002/mdp2.78 (2019).

    Article  Google Scholar 

  86. Hu, L., Zhang, Q., Li, X. & Serpe, M. J. Stimuli-responsive polymers for sensing and actuation. Mater. Horiz. 6, 1774–1793 (2019).

    Article  Google Scholar 

  87. Takashima, A., Kojima, K. & Suzuki, H. Autonomous microfluidic control by chemically actuated micropumps and its application to chemical analyses. Anal. Chem. 82, 6870–6876 (2010).

    Article  Google Scholar 

  88. Park, J. & Park, J. K. Integrated microfluidic pumps and valves operated by finger actuation. Lab Chip 19, 2973–2977 (2019).

    Article  Google Scholar 

  89. Bacchin, P., Leng, J. & Salmon, J. B. Microfluidic evaporation, pervaporation, and osmosis: from passive pumping to solute concentration. Chem. Rev. 122, 6938–6985 (2022).

    Article  Google Scholar 

  90. Saha, T., Fang, J., Mukherjee, S., Dickey, M. D. & Velev, O. D. Wearable osmotic-capillary patch for prolonged sweat harvesting and sensing. ACS Appl. Mater. Interfaces 13, 8071–8081 (2021).

    Article  Google Scholar 

  91. Jeon, N. L. et al. Microfluidics section: design and fabrication of integrated passive valves and pumps for flexible polymer 3-dimensional microfluidic systems. Biomed. Microdevices 4, 117–121 (2002).

    Article  Google Scholar 

  92. Gomez, M., Moulton, D. E. & Vella, D. Passive control of viscous flow via elastic snap-through. Phys. Rev. Lett. 119, 144502 (2017).

    Article  Google Scholar 

  93. Cho, H., Kim, H. Y., Kang, J. Y. & Kim, T. S. How the capillary burst microvalve works. J. Colloid Interface Sci. 306, 379–385 (2007).

    Article  Google Scholar 

  94. Jiang, Y. et al. Wireless, closed-loop, smart bandage with integrated sensors and stimulators for advanced wound care and accelerated healing. Nat. Biotechnol. https://doi.org/10.1038/s41587-022-01528-3 (2022).

    Article  Google Scholar 

  95. Moreddu, R., Wolffsohn, J. S., Vigolo, D. & Yetisen, A. K. Laser-inscribed contact lens sensors for the detection of analytes in the tear fluid. Sens. Actuators B Chem. 317, 128183 (2020).

    Article  Google Scholar 

  96. Sempionatto, J. R. et al. Eyeglasses-based tear biosensing system: non-invasive detection of alcohol, vitamins and glucose. Biosens. Bioelectron. 137, 161–170 (2019).

    Article  Google Scholar 

  97. García-Carmona, L. et al. Pacifier biosensor: toward noninvasive saliva biomarker monitoring. Anal. Chem. 91, 13883–13891 (2019).

    Article  Google Scholar 

  98. Hou, B. et al. An interactive mouthguard based on mechanoluminescence-powered optical fibre sensors for bite-controlled device operation. Nat. Electron. 5, 682–693 (2022).

    Article  Google Scholar 

  99. Teymourian, H., Tehrani, F., Mahato, K. & Wang, J. Lab under the skin: microneedle based wearable devices. Adv. Healthc. Mater. 10, e2002255 (2021).

    Article  Google Scholar 

  100. Yang, Y. et al. A laser-engraved wearable sensor for sensitive detection of uric acid and tyrosine in sweat. Nat. Biotechnol. 38, 217–224 (2020).

    Article  Google Scholar 

  101. Tehrani, F. et al. An integrated wearable microneedle array for the continuous monitoring of multiple biomarkers in interstitial fluid. Nat. Biomed. Eng. 6, 1214–1224 (2022).

    Article  Google Scholar 

  102. Gao, W. et al. Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis. Nature 529, 509–514 (2016).

    Article  Google Scholar 

  103. Tai, L.-C. et al. Methylxanthine drug monitoring with wearable sweat sensors. Adv. Mater. 30, e1707442 (2018).

    Article  Google Scholar 

  104. Simmers, P., Li, S. K., Kasting, G. & Heikenfeld, J. Prolonged and localized sweat stimulation by iontophoretic delivery of the slowly-metabolized cholinergic agent carbachol. J. Dermatol. Sci. 89, 40–51 (2018).

    Article  Google Scholar 

  105. Hauke, A. et al. Complete validation of a continuous and blood-correlated sweat biosensing device with integrated sweat stimulation. Lab Chip 18, 3750–3759 (2018).

    Article  Google Scholar 

  106. Martin, A. et al. Epidermal microfluidic electrochemical detection system: enhanced sweat sampling and metabolite detection. ACS Sens. 2, 1860–1868 (2017).

    Article  Google Scholar 

  107. Shirzaei Sani, E. et al. A stretchable wireless wearable bioelectronic system for multiplexed monitoring and combination treatment of infected chronic wounds. Sci. Adv. 9, eadf7388 (2023).

    Article  Google Scholar 

  108. Pal, A. et al. Early detection and monitoring of chronic wounds using low-cost, omniphobic paper-based smart bandages. Biosens. Bioelectron. 117, 696–705 (2018).

    Article  Google Scholar 

  109. Mostafalu, P. et al. A toolkit of thread-based microfluidics, sensors, and electronics for 3D tissue embedding for medical diagnostics. Microsyst. Nanoeng. 2, 16039 (2016).

    Article  Google Scholar 

  110. Liu, W.-T., Cao, Y.-P., Zhou, X.-H. & Han, D. Interstitial fluid behavior and diseases. Adv. Sci. 9, 2100617 (2022).

    Article  Google Scholar 

  111. Friedel, M. et al. Opportunities and challenges in the diagnostic utility of dermal interstitial fluid. Nat. Biomed. Eng. 7, https://doi.org/10.1038/s41551-022-00998-9 (2023).

  112. Saifullah, K. M. & Faraji Rad, Z. Sampling dermal interstitial fluid using microneedles: a review of recent developments in sampling methods and microneedle‐based biosensors. Adv. Mater. Interfaces 10, 2201763 (2023).

    Article  Google Scholar 

  113. Samant, P. P. et al. Sampling interstitial fluid from human skin using a microneedle patch. Sci. Transl Med. 12, eaaw0285 (2020).

    Article  Google Scholar 

  114. Li, X. et al. A fully integrated closed‐loop system based on mesoporous microneedles‐iontophoresis for diabetes treatment. Adv. Sci. 8, 2100827 (2021).

    Article  Google Scholar 

  115. Yang, B., Kong, J. & Fang, X. Programmable CRISPR-Cas9 microneedle patch for long-term capture and real-time monitoring of universal cell-free DNA. Nat. Commun. 13, 3999 (2022).

    Article  Google Scholar 

  116. Wang, Z. et al. Microneedle patch for the ultrasensitive quantification of protein biomarkers in interstitial fluid. Nat. Biomed. Eng. 5, 64–76 (2021).

    Article  Google Scholar 

  117. Ribet, F., Stemme, G. & Roxhed, N. Real-time intradermal continuous glucose monitoring using a minimally invasive microneedle-based system. Biomed. Microdevices 20, 101 (2018).

    Article  Google Scholar 

  118. Jiang, X. & Lillehoj, P. B. Microneedle-based skin patch for blood-free rapid diagnostic testing. Microsyst. Nanoeng. 6, 96 (2020).

    Article  Google Scholar 

  119. Parrilla, M., Detamornrat, U., Dominguez-Robles, J., Donnelly, R. F. & De Wael, K. Wearable hollow microneedle sensing patches for the transdermal electrochemical monitoring of glucose. Talanta 249, 123695 (2022).

    Article  Google Scholar 

  120. Lee, H. et al. Porous microneedles on a paper for screening test of prediabetes. Med. Devices Sens. 3, e10109 (2020).

    Article  Google Scholar 

  121. Kusama, S. et al. Transdermal electroosmotic flow generated by a porous microneedle array patch. Nat. Commun. 12, 658 (2021).

    Article  Google Scholar 

  122. 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).

    Article  Google Scholar 

  123. Mishra, R. K. et al. Simultaneous detection of salivary Δ9-tetrahydrocannabinol and alcohol using a wearable electrochemical ring sensor. Talanta 211, 120757 (2020).

    Article  Google Scholar 

  124. de Castro, L. F. et al. Salivary diagnostics on paper microfluidic devices and their use as wearable sensors for glucose monitoring. Anal. Bioanal. Chem. 411, 4919–4928 (2019).

    Article  Google Scholar 

  125. Lim, H. R. et al. Smart bioelectronic pacifier for real-time continuous monitoring of salivary electrolytes. Biosens. Bioelectron. 210, 114329 (2022). This article reports the first integrated smart pacifier using a hydrophilic microfluidics channel for neonatal intensive care unit monitoring.

    Article  Google Scholar 

  126. Yetisen, A. K. et al. Scleral lens sensor for ocular electrolyte analysis. Adv. Mater. 32, e1906762 (2020).

    Article  Google Scholar 

  127. Yang, X. et al. Flexible, wearable microfluidic contact lens with capillary networks for tear diagnostics. J. Mater. Sci. 55, 9551–9561 (2020).

    Article  Google Scholar 

  128. An, H. et al. Microfluidic contact lenses for unpowered, continuous and non-invasive intraocular pressure monitoring. Sens. Actuators A Phys. 295, 177–187 (2019).

    Article  Google Scholar 

  129. Araci, I. E., Su, B., Quake, S. R. & Mandel, Y. An implantable microfluidic device for self-monitoring of intraocular pressure. Nat. Med. 20, 1074–1078 (2014).

    Article  Google Scholar 

  130. Agaoglu, S. et al. Ultra-sensitive microfluidic wearable strain sensor for intraocular pressure monitoring. Lab Chip 18, 3471–3483 (2018).

    Article  Google Scholar 

  131. Naresh, V. & Lee, N. A review on biosensors and recent development of nanostructured materials-enabled biosensors. Sensors 21, 1906713 (2021).

    Article  Google Scholar 

  132. Campuzano, S., Pedrero, M., Torrente‐Rodríguez, R. M. & Pingarrón, J. M. Affinity‐based wearable electrochemical biosensors: natural versus biomimetic receptors. Anal. Sens. https://doi.org/10.1002/anse.202200087 (2022).

    Article  Google Scholar 

  133. Tu, J. B., Torrente-Rodriguez, R. M., Wang, M. Q. & Gao, W. The era of digital health: a review of portable and wearable affinity biosensors. Adv. Funct. Mater. https://doi.org/10.1002/adfm.201906713 (2020).

    Article  Google Scholar 

  134. Monošík, R., Streďanský, M. & Šturdík, E. Biosensors - classification, characterization and new trends. Acta Chim. Slov. 5, 109–120 (2012).

    Article  Google Scholar 

  135. Ronkainen, N. J., Halsall, H. B. & Heineman, W. R. Electrochemical biosensors. Chem. Soc. Rev. 39, 1747–1763 (2010).

    Article  Google Scholar 

  136. Fiore, L. et al. Microfluidic paper-based wearable electrochemical biosensor for reliable cortisol detection in sweat. Sens. Actuators B Chem. 379, 133258 (2023).

    Article  Google Scholar 

  137. Mazur, F., Tjandra, A. D., Zhou, Y., Gao, Y. & Chandrawati, R. Paper-based sensors for bacteria detection. Nat. Rev. Bioeng. https://doi.org/10.1038/s44222-023-00024-w (2023).

    Article  Google Scholar 

  138. Sadana, A. A kinetic study of analyte-receptor binding and dissociation, and dissociation alone, for biosensor applications: a fractal analysis. Anal. Biochem. 291, 34–47 (2001).

    Article  Google Scholar 

  139. Wu, Y. et al. Microneedle aptamer-based sensors for continuous, real-time therapeutic drug monitoring. Anal. Chem. 94, 8335–8345 (2022).

    Article  Google Scholar 

  140. Singh, N. K., Chung, S., Chang, A. Y., Wang, J. & Hall, D. A. A non-invasive wearable stress patch for real-time cortisol monitoring using a pseudoknot-assisted aptamer. Biosens. Bioelectron. 227, 115097 (2023).

    Article  Google Scholar 

  141. Fercher, C., Jones, M. L., Mahler, S. M. & Corrie, S. R. Recombinant antibody engineering enables reversible binding for continuous protein biosensing. ACS Sens. 6, 764–776 (2021).

    Article  Google Scholar 

  142. Lin, S. et al. Wearable microneedle-based electrochemical aptamer biosensing for precision dosing of drugs with narrow therapeutic windows. Sci. Adv. 8, eabq4539 (2022).

    Article  Google Scholar 

  143. Wang, Z. R. et al. A flexible and regenerative aptameric graphene-nafion biosensor for cytokine storm biomarker monitoring in undiluted biofluids toward wearable applications. Adv. Funct. Mater. 31, 2005958 (2020).

    Article  Google Scholar 

  144. Goode, J. A., Rushworth, J. V. & Millner, P. A. Biosensor regeneration: a review of common techniques and outcomes. Langmuir 31, 6267–6276 (2015).

    Article  Google Scholar 

  145. Flynn, C. D. et al. Biomolecular sensors for advanced physiological monitoring. Nat. Rev. Bioeng. https://doi.org/10.1038/s44222-023-00067-z (2023).

    Article  Google Scholar 

  146. Gosai, A., Ma, X., Balasubramanian, G. & Shrotriya, P. Electrical stimulus controlled binding/unbinding of human thrombin-aptamer complex. Sci. Rep. 6, 37449 (2016).

    Article  Google Scholar 

  147. Aleman, J., Kilic, T., Mille, L. S., Shin, S. R. & Zhang, Y. S. Microfluidic integration of regeneratable electrochemical affinity-based biosensors for continual monitoring of organ-on-a-chip devices. Nat. Protoc. 16, 2564–2593 (2021).

    Article  Google Scholar 

  148. Shin, S. R. et al. Label-free and regenerative electrochemical microfluidic biosensors for continual monitoring of cell secretomes. Adv. Sci. 4, 1600522 (2017).

    Article  Google Scholar 

  149. Ota, H. et al. Highly deformable liquid-state heterojunction sensors. Nat. Commun. 5, 5032 (2014).

    Article  Google Scholar 

  150. Yeo, J. C., Yu, J., Koh, Z. M., Wang, Z. & Lim, C. T. Wearable tactile sensor based on flexible microfluidics. Lab Chip 16, 3244–3250 (2016).

    Article  Google Scholar 

  151. Bandodkar, A. J. et al. Battery-free, skin-interfaced microfluidic/electronic systems for simultaneous electrochemical, colorimetric, and volumetric analysis of sweat. Sci. Adv. 5, eaav3294 (2019).

    Article  Google Scholar 

  152. Sekine, Y. et al. A fluorometric skin-interfaced microfluidic device and smartphone imaging module for in situ quantitative analysis of sweat chemistry. Lab Chip 18, 2178–2186 (2018).

    Article  Google Scholar 

  153. He, X., Fan, C., Luo, Y., Xu, T. & Zhang, X. Flexible microfluidic nanoplasmonic sensors for refreshable and portable recognition of sweat biochemical fingerprint. NPJ Flex. Electron. 6, 1 (2022).

    Article  Google Scholar 

  154. Mogera, U. et al. Wearable plasmonic paper-based microfluidics for continuous sweat analysis. Sci. Adv. 8, eabn1736 (2022).

    Article  Google Scholar 

  155. Mei, X., Yang, J., Liu, J. & Li, Y. Wearable, nanofiber-based microfluidic systems with integrated electrochemical and colorimetric sensing arrays for multiplex sweat analysis. Chem. Eng. J. https://doi.org/10.1016/j.cej.2022.140248 (2023).

    Article  Google Scholar 

  156. Schäferling, M. The art of fluorescence imaging with chemical sensors. Angew. Chem. Int. Ed. 51, 3532–3554 (2012).

    Article  Google Scholar 

  157. Stiles, P. L., Dieringer, J. A., Shah, N. C. & Van Duyne, R. P. Surface-enhanced Raman spectroscopy. Annu. Rev. Anal. Chem. 1, 601–626 (2008).

    Article  Google Scholar 

  158. Vinoth, R., Nakagawa, T., Mathiyarasu, J. & Mohan, A. M. V. Fully printed wearable microfluidic devices for high-throughput sweat sampling and multiplexed electrochemical analysis. ACS Sens. 6, 1174–1186 (2021).

    Article  Google Scholar 

  159. Nyein, H. Y. Y. et al. A wearable microfluidic sensing patch for dynamic sweat secretion analysis. ACS Sens. 3, 944–952 (2018).

    Article  Google Scholar 

  160. Elgrishi, N. et al. A practical beginner’s guide to cyclic voltammetry. J. Chem. Educ. 95, 197–206 (2018).

    Article  Google Scholar 

  161. Chen, A. & Shah, B. Electrochemical sensing and biosensing based on square wave voltammetry. Anal. Methods 5, 2158–2173 (2013).

    Article  Google Scholar 

  162. Singh, A., Chowdhury, D. R. & Paul, A. A kinetic study of ferrocenium cation decomposition utilizing an integrated electrochemical methodology composed of cyclic voltammetry and amperometry. Analyst 139, 5747–5754 (2014).

    Article  Google Scholar 

  163. Shaver, A. & Arroyo-Curras, N. The challenge of long-term stability for nucleic acid-based electrochemical sensors. Curr. Opin. Electrochem. https://doi.org/10.1016/j.coelec.2021.100902 (2022).

    Article  Google Scholar 

  164. Daniels, J. S. & Pourmand, N. Label-free impedance biosensors: opportunities and challenges. Electroanalysis 19, 1239–1257 (2007).

    Article  Google Scholar 

  165. Araci, I. E. et al. Flow stabilization in wearable microfluidic sensors enables noise suppression. Lab Chip 19, 3899–3908 (2019).

    Article  Google Scholar 

  166. Bae, C. W., Chinnamani, M. V., Lee, E. H. & Lee, N. E. Stretchable non‐enzymatic fuel cell‐based sensor patch integrated with thread‐embedded microfluidics for self‐powered wearable glucose monitoring. Adv. Mater. Interfaces 9, 2200492 (2022).

    Article  Google Scholar 

  167. Bandodkar, A. J. et al. Sweat-activated biocompatible batteries for epidermal electronic and microfluidic systems. Nat. Electron. 3, 554–562 (2020).

    Article  Google Scholar 

  168. Huang, X. et al. Garment embedded sweat-activated batteries in wearable electronics for continuous sweat monitoring. NPJ Flex. Electron. 6, 1 (2022).

    Article  Google Scholar 

  169. Liu, Y. et al. Stretchable sweat-activated battery in skin-integrated electronics for continuous wireless sweat monitoring. Adv. Sci. 9, e2104635 (2022).

    Article  MathSciNet  Google Scholar 

  170. Xiao, G. et al. A weavable and scalable cotton-yarn-based battery activated by human sweat for textile electronics. Adv. Sci. 9, e2103822 (2022).

    Article  MathSciNet  Google Scholar 

  171. Baker, L. B. et al. Skin‐interfaced microfluidic system with machine learning‐enabled image processing of sweat biomarkers in remote settings. Adv. Mater. Technol. 7, 2200249 (2022).

    Article  Google Scholar 

  172. Mohr, D. C., Zhang, M. & Schueller, S. M. Personal sensing: understanding mental health using ubiquitous sensors and machine learning. Annu. Rev. Clin. Psychol. 13, 23–47 (2017).

    Article  Google Scholar 

  173. Bohr, A. & Memarzadeh, K. in Artificial Intelligence in Healthcare 25–60 (Elsevier, 2020).

  174. Yang, D. S., Ghaffari, R. & Rogers, J. A. Sweat as a diagnostic biofluid. Science 379, 760–761 (2023).

    Article  Google Scholar 

  175. Oh, S. Y. et al. Skin-attachable, stretchable electrochemical sweat sensor for glucose and pH detection. ACS Appl. Mater. Interfaces 10, 13729–13740 (2018).

    Article  Google Scholar 

  176. Lee, H. et al. A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy. Nat. Nanotechnol. 11, 566–572 (2016).

    Article  Google Scholar 

  177. Brothers, M. C. et al. Achievements and challenges for real-time sensing of analytes in sweat within wearable platforms. Acc. Chem. Res. 52, 297–306 (2019).

    Article  Google Scholar 

  178. Jagannath, B. et al. A sweat-based wearable enabling technology for real-time monitoring of IL-1β and CRP as potential markers for inflammatory bowel disease. Inflamm. Bowel Dis. 26, 1533–1542 (2020).

    Article  Google Scholar 

  179. Tai, L. C. et al. Wearable sweat band for noninvasive levodopa monitoring. Nano Lett. 19, 6346–6351 (2019).

    Article  Google Scholar 

  180. Raymundo-Pereira, P. A., Gomes, N. O., Machado, S. A. S. & Oliveira, O. N. Wearable glove-embedded sensors for therapeutic drug monitoring in sweat for personalized medicine. Chem. Eng. J. 435, 135047 (2022).

    Article  Google Scholar 

  181. Kim, Y. & Prausnitz, M. R. Sensitive sensing of biomarkers in interstitial fluid. Nat. Biomed. Eng. 5, 3–5 (2021).

    Article  Google Scholar 

  182. Heikenfeld, J. et al. Accessing analytes in biofluids for peripheral biochemical monitoring. Nat. Biotechnol. 37, 407–419 (2019).

    Article  Google Scholar 

  183. Goud, K. Y. et al. Wearable electrochemical microneedle sensor for continuous monitoring of levodopa: toward Parkinson management. ACS Sens. 4, 2196–2204 (2019).

    Article  Google Scholar 

  184. Liu, G. S. et al. Microneedles for transdermal diagnostics: recent advances and new horizons. Biomaterials 232, 119740 (2020).

    Article  Google Scholar 

  185. Himawan, A. et al. Where microneedle meets biomarkers: futuristic application for diagnosing and monitoring localized external organ diseases. Adv. Healthc. Mater. 12, e2202066 (2023).

    Article  Google Scholar 

  186. Loffler, M. W., Schuster, H., Buhler, S. & Beckert, S. Wound fluid in diabetic foot ulceration: more than just an undefined soup? Int. J. Low. Extrem. Wounds 12, 113–129 (2013).

    Article  Google Scholar 

  187. White, R. & Cutting, K. F. Modern exudate management: a review of wound treatments. World Wide Wounds http://www.worldwidewounds.com/2006/september/White/Modern-Exudate-Mgt.html (2006).

  188. Cutting, K. F. Wound exudate: composition and functions. Br. J. Community Nurs. 8, 4–9 (2003).

    Article  Google Scholar 

  189. Fernandez, M. L., Upton, Z., Edwards, H., Finlayson, K. & Shooter, G. K. Elevated uric acid correlates with wound severity. Int. Wound J. 9, 139–149 (2012).

    Article  Google Scholar 

  190. Wang, C., Shirzaei Sani, E. & Gao, W. Wearable bioelectronics for chronic wound management. Adv. Funct. Mater. 32, 2111022 (2021).

    Article  Google Scholar 

  191. Xiong, Z. et al. A wireless and battery-free wound infection sensor based on DNA hydrogel. Sci. Adv. 7, eabj1617 (2021).

    Article  Google Scholar 

  192. Kang, S. M. et al. A matrix metalloproteinase sensing biosensor for the evaluation of chronic wounds. BioChip J. 13, 323–332 (2019).

    Article  Google Scholar 

  193. Xue, M., Le, N. T. & Jackson, C. J. Targeting matrix metalloproteases to improve cutaneous wound healing. Expert Opin. Ther. Targets 10, 143–155 (2006).

    Article  Google Scholar 

  194. Xu, G. et al. Battery‐free and wireless smart wound dressing for wound infection monitoring and electrically controlled on‐demand drug delivery. Adv. Funct. Mater. 31, 2100852 (2021).

    Article  Google Scholar 

  195. Pedersen, A. M. L., Sorensen, C. E., Proctor, G. B., Carpenter, G. H. & Ekstrom, J. Salivary secretion in health and disease. J. Oral. Rehabil. 45, 730–746 (2018).

    Article  Google Scholar 

  196. Li, Y. et al. Oral wearable sensors: health management based on the oral cavity. Biosens. Bioelectron. X 10, 100135 (2022).

    Google Scholar 

  197. Dave, P. K., Rojas-Cessa, R., Dong, Z. & Umpaichitra, V. Survey of saliva components and virus sensors for prevention of COVID-19 and infectious diseases. Biosensors https://doi.org/10.3390/bios11010014 (2020).

    Article  Google Scholar 

  198. Iorgulescu, G. Saliva between normal and pathological. Important factors in determining systemic and oral health. J. Med. Life 2, 303 (2009).

    Google Scholar 

  199. Fan, Y. et al. Dynamic changes in salivary cortisol and secretory immunoglobulin A response to acute stress. Stress Health 25, 189–194 (2009).

    Article  Google Scholar 

  200. Dong, T., Matos Pires, N. M., Yang, Z. & Jiang, Z. Advances in electrochemical biosensors based on nanomaterials for protein biomarker detection in saliva. Adv. Sci. 10, e2205429 (2023).

    Article  Google Scholar 

  201. Moonla, C. et al. Review—Lab-in-a-Mouth and advanced point-of-care sensing systems: detecting bioinformation from the oral cavity and saliva. ECS Sens. Plus 1, 021603 (2022).

    Article  Google Scholar 

  202. Hong, W. & Lee, W. G. Wearable sensors for continuous oral cavity and dietary monitoring toward personalized healthcare and digital medicine. Analyst 145, 7796–7808 (2021).

    Article  Google Scholar 

  203. Esmaeelpour, M., Watts, P. O., Boulton, M. E., Cai, J. & Murphy, P. J. Tear film volume and protein analysis in full-term newborn infants. Cornea 30, 400–404 (2011).

    Article  Google Scholar 

  204. Van Haeringen, N. J. Clinical biochemistry of tears. Surv. Ophthalmol. 26, 84–96 (1981).

    Article  Google Scholar 

  205. Pankratov, D., Gonzalez-Arribas, E., Blum, Z. & Shleev, S. Tear based bioelectronics. Electroanalysis 28, 1250–1266 (2016).

    Article  Google Scholar 

  206. 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).

    Article  Google Scholar 

  207. Occhiutto, M. L., Freitas, F. R., Maranhao, R. C. & Costa, V. P. Breakdown of the blood-ocular barrier as a strategy for the systemic use of nanosystems. Pharmaceutics 4, 252–275 (2012).

    Article  Google Scholar 

  208. Hagan, S., Martin, E. & Enríquez-de-Salamanca, A. Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine. EPMA J. 7, 15 (2016).

    Article  Google Scholar 

  209. Çomoğlu, S. S., Güven, H., Acar, M., Öztürk, G. & Koçer, B. Tear levels of tumor necrosis factor-alpha in patients with Parkinson’s disease. Neurosci. Lett. 553, 63–67 (2013).

    Article  Google Scholar 

  210. Li, M. S. et al. Current and future perspectives on microfluidic tear analytic devices. ACS Sens. 7, 1300–1314 (2022).

    Article  Google Scholar 

  211. Keum, D. et al. Wireless smart contact lens for diabetic diagnosis and therapy. Sci. Adv. 6, eaba3252 (2020).

    Article  Google Scholar 

  212. Kim, J. et al. Wearable smart sensor systems integrated on soft contact lenses for wireless ocular diagnostics. Nat. Commun. 8, 14997 (2017).

    Article  Google Scholar 

  213. Ku, M. et al. Smart, soft contact lens for wireless immunosensing of cortisol. Sci. Adv. 6, eabb2891 (2020).

    Article  Google Scholar 

  214. Ma, X. et al. Smart contact lenses for biosensing applications. Adv. Intell. Syst. 3, 2000263 (2021).

    Article  Google Scholar 

  215. Khoshmanesh, K. et al. Liquid metal enabled microfluidics. Lab Chip 17, 974–993 (2017).

    Article  Google Scholar 

  216. Wu, C.-Y., Liao, W.-H. & Tung, Y.-C. Integrated ionic liquid-based electrofluidic circuits for pressure sensing within polydimethylsiloxane microfluidic systems. Lab Chip 11, 1740–1746 (2011).

    Article  Google Scholar 

  217. Gao, Y. et al. Wearable microfluidic diaphragm pressure sensor for health and tactile touch monitoring. Adv. Mater. 29, 1701985 (2017).

    Article  Google Scholar 

  218. Jiang, H. et al. A wireless implantable passive intra-abdominal pressure sensing scheme via ultrasonic imaging of a microfluidic device. IEEE Trans. Biomed. Eng. 68, 747–758 (2021).

    Article  Google Scholar 

  219. Zhang, S. et al. A wearable battery-free wireless and skin-interfaced microfluidics integrated electrochemical sensing patch for on-site biomarkers monitoring in human perspiration. Biosens. Bioelectron. 175, 112844 (2021).

    Article  Google Scholar 

  220. Bolat, G. et al. Wearable soft electrochemical microfluidic device integrated with iontophoresis for sweat biosensing. Anal. Bioanal. Chem. 414, 5411–5421 (2022).

    Article  Google Scholar 

  221. Paul Kunnel, B. & Demuru, S. An epidermal wearable microfluidic patch for simultaneous sampling, storage, and analysis of biofluids with counterion monitoring. Lab Chip 22, 1793–1804 (2022).

    Article  Google Scholar 

  222. Kulkarni, M. B., Ayachit, N. H. & Aminabhavi, T. M. Biosensors and microfluidic biosensors: from fabrication to application. Biosensors 12, 543 (2022).

    Article  Google Scholar 

  223. Whitesides, G. M., Ostuni, E., Takayama, S., Jiang, X. & Ingber, D. E. Soft lithography in biology and biochemistry. Annu. Rev. Biomed. Eng. 3, 335–373 (2001).

    Article  Google Scholar 

  224. Beebe, D. J. et al. Microfluidic tectonics: a comprehensive construction platform for microfluidic systems. Proc. Natl Acad. Sci. USA 97, 13488–13493 (2000).

    Article  Google Scholar 

  225. Borok, A., Laboda, K. & Bonyar, A. PDMS bonding technologies for microfluidic applications: a review. Biosensors 11, 8 (2021).

    Article  Google Scholar 

  226. Poulsen, C. E. et al. Laser ablated micropillar energy directors for ultrasonic welding of microfluidic systems. J. Micromech. Microeng. 26, 067001 (2016).

    Article  Google Scholar 

  227. Faghih, M. M. & Sharp, M. K. Solvent-based bonding of PMMA–PMMA for microfluidic applications. Microsyst. Technol. 25, 3547–3558 (2019).

    Article  Google Scholar 

  228. Nyein, H. Y. Y. et al. Regional and correlative sweat analysis using high-throughput microfluidic sensing patches toward decoding sweat. Sci. Adv. 5, eaaw9906 (2019).

    Article  Google Scholar 

  229. Bariya, M. et al. Roll-to-roll gravure printed electrochemical sensors for wearable and medical devices. ACS Nano 12, 6978–6987 (2018).

    Article  Google Scholar 

  230. Epicore. Gx Sweat Patch Provides Hydration Biomarker Analytics and Recovery Insights. Epicore Biosystems https://www.epicorebiosystems.com/gx-sweat-patch/ (2022).

  231. Nix. Nix Hydration Biosensor. Nix Biosensors https://nixbiosensors.com/pages/product (2022).

  232. L’Oreal Groupe. My Skin Track Ph by La Roche-Posay Won the CES 2019 Innovation Award. Loreal https://www.loreal.com/en/news/research-innovation/my-skin-track-ph-by-la-roche-posay-won-the-ces-2019-innovation-award/ (2019).

  233. Epicore. Continuous real-time hydration monitoring. Epicore Biosystems https://www.epicorebiosystems.com/connected-hydration/ (2023).

  234. FlexoSense. 3D-printed Insole (Diabetes). FlexoSense flexosense.com/product-page/3d-printed-insole-for-diabetes (2023).

Download references

Acknowledgements

This work was supported by the Institute for Health Innovation and Technology (iHealthtech), MechanoBioEngineering Laboratory at the Department of Biomedical Engineering and the Institute for Functional Intelligent Materials (I-FIM) at the National University of Singapore (NUS). We also acknowledge support from the National Research Foundation and Singapore A*STAR under its RIE2020 Industry Alignment Fund – Industry Collaboration Projects (IAF-ICP) Grant (Grant No. I2001E0059) – SIA-NUS Digital Aviation Corp Lab. We also thank Henryk Chan for help in preparing some figure items.

Author information

Authors and Affiliations

  1. Institute for Health Innovation & Technology, National University of Singapore, Singapore, Singapore

    Shuwen Chen, Zheng Qiao, Joo Chuan Yeo, Jiaming Qi, Shicheng Fan, Xiaoyan Liu, Jee Yeon Lee & Chwee Teck Lim

  2. Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore

    Zheng Qiao, Jiaming Qi, Shicheng Fan & Chwee Teck Lim

  3. SIA-NUS Digital Aviation Corporate Lab, National University of Singapore, Singapore, Singapore

    Zheng Qiao & Chwee Teck Lim

  4. School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, China

    Yan Niu

  5. Department of Physics, City University of Hong Kong, Hong Kong SAR, China

    Yuanchao Liu

  6. Mechanobiology Institute, National University of Singapore, Singapore, Singapore

    Chwee Teck Lim

  7. Institute for Functional Intelligent Materials, National University of Singapore, Singapore, Singapore

    Chwee Teck Lim

  8. Institute For Digital Molecular Analytics and Science, Nanyang Technological University, Singapore, Singapore

    Chwee Teck Lim

Authors
  1. Shuwen Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zheng Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan Niu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joo Chuan Yeo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuanchao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jiaming Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shicheng Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaoyan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jee Yeon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chwee Teck Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

C.T.L., J.Y.L. and S.W.C. discussed and conceived the idea for the synopsis. C.T.L. and S.W.C. guided all aspects of the work. C.T.L., J.C.Y. and J.Y.L. refined the manuscript. S.W.C., Z.Q. and Y.N. drew most figures and wrote and finalized the content. J.C.Y., J.Y.L., Y.C.L., X.Y.L., S.C.F. and J.M.Q. contributed to writing the first draft. All authors contributed to discussing, editing and finalizing the article.

Corresponding author

Correspondence to Chwee Teck Lim.

Ethics declarations

Competing interests

C.T.L. is an inventor on patents related to a smart insole from FlexoSense and an ARIS muscle analyser from Microtube Technologies. These patents have been licensed to FlexoSense and Microtube Technologies, respectively. C.T.L. is a scientific founder of the above two companies and holds equity in them. The remaining authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Bioengineering thanks Wei Gao, Roozbeh Ghaffari, Nae-Eung Lee and Tran Quang Trung for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

Microtube Technologies: https://microtube.tech/

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, S., Qiao, Z., Niu, Y. et al. Wearable flexible microfluidic sensing technologies. Nat Rev Bioeng 1, 950–971 (2023). https://doi.org/10.1038/s44222-023-00094-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s44222-023-00094-w

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing