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 biomolecular sensing nanotechnologies in chronic disease management

Nature Nanotechnology (2025)Cite this article

Subjects

Abstract

Over the past decade, consumer wearable sensors have become increasingly ubiquitous in health monitoring, enabling the widespread tracking of key biophysical parameters. The transition towards next-generation body-interfaced biomolecular sensing technologies, fuelled by the integration of reagentless sensing strategies with advanced nanomaterials, marks the next substantial leap forward. These innovations enable unobtrusive, multimodal monitoring of both physiological parameters and biochemical disease markers in real time. This Review examines the current generation of body-interfaced biomolecular sensing technologies, with a particular emphasis on materials innovation and nanotechnological advancements, and discusses their pivotal role in chronic disease monitoring. The discussion extends to the challenges and prospects in this rapidly evolving field, highlighting the potential for materials-focused approaches to transform the landscape of chronic disease monitoring and management with body-interfaced bioelectronics. By harnessing the power of materials and nanotechnological innovations, these biomolecular sensing technologies promise to enhance diagnostic capabilities and foster a more proactive, personalized approach to combating these diseases.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Fig. 1: Molecular signatures of chronic diseases.
Fig. 2: Introduction of nanomaterials and nanotechnologies in body-interfaced monitoring.
Fig. 3: Body-interfaced sensor devices for chronic disease care applications.
Fig. 4: Clinical translation sieve for body-interfaced sensing technologies.

Similar content being viewed by others

References

  1. The top 10 causes of death. WHO https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death (2020).

  2. Zhao, C., Park, J., Root, S. E. & Bao, Z. Skin-inspired soft bioelectronic materials, devices and systems. Nat. Rev. Bioeng. 2, 671–690 (2024).

    Article  CAS  Google Scholar 

  3. Lee, G.-H. et al. Multifunctional materials for implantable and wearable photonic healthcare devices. Nat. Rev. Mater. 5, 149–165 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Flynn, C. D. et al. Biomolecular sensors for advanced physiological monitoring. Nat. Rev. Bioeng. 1, 560–575 (2023).

    Article  CAS  Google Scholar 

  5. Townsend, N. et al. Epidemiology of cardiovascular disease in Europe. Nat. Rev. Cardiol. 19, 133–143 (2022).

    Article  PubMed  Google Scholar 

  6. Mahmud, A. et al. Monitoring cardiac biomarkers with aptamer-based molecular pendulum sensors. Angew. Chem. Int. Ed. 62, e202213567 (2023).

    Article  CAS  Google Scholar 

  7. Saenger, A. K. A tale of two biomarkers: the use of troponin and CK-MB in contemporary practice. Am. Soc. Clin. Lab. Sci. 23, 134–140 (2010).

    Article  Google Scholar 

  8. Libby, P. et al. Atherosclerosis. Nat. Rev. Dis. Prim. 5, 56 (2019).

    Article  PubMed  Google Scholar 

  9. Wang, H., Rosendaal, F. R., Cushman, M. & Van Hylckama Vlieg, A. D‐dimer, thrombin generation, and risk of a first venous thrombosis in the elderly. Res. Pract. Thromb. Haemost. 5, e12536 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Pan, X. et al. Associations of circulating choline and its related metabolites with cardiometabolic biomarkers: an international pooled analysis. Am. J. Clin. Nutr. 114, 893–906 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Tousoulis, D. et al. Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease. Int. J. Cardiol. 167, 1924–1928 (2013).

    Article  PubMed  Google Scholar 

  12. Tomic, D., Shaw, J. E. & Magliano, D. J. The burden and risks of emerging complications of diabetes mellitus. Nat. Rev. Endocrinol. 18, 525–539 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lee, M. et al. β-hydroxybutyrate as a biomarker of β-cell function in new-onset type 2 diabetes and its association with treatment response at 6 months. Diabetes Metab. 49, 101427 (2023).

    Article  PubMed  CAS  Google Scholar 

  14. Zheng, X. et al. Hyocholic acid species as novel biomarkers for metabolic disorders. Nat. Commun. 12, 1487 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Katsiki, N., Mikhailidis, D. P. & Banach, M. Leptin, cardiovascular diseases and type 2 diabetes mellitus. Acta Pharmacol. Sin. 39, 1176–1188 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Theofilopoulos, A. N., Kono, D. H. & Baccala, R. The multiple pathways to autoimmunity. Nat. Immunol. 18, 716–724 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Kolarz, B., Podgorska, D. & Podgorski, R. Insights of rheumatoid arthritis biomarkers. Biomarkers 26, 185–195 (2021).

    Article  PubMed  CAS  Google Scholar 

  18. Pisetsky, D. S. Anti-DNA antibodies—quintessential biomarkers of SLE. Nat. Rev. Rheumatol. 12, 102–110 (2016).

    Article  PubMed  CAS  Google Scholar 

  19. 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  PubMed  PubMed Central  Google Scholar 

  20. Colhoun, H. M. & Marcovecchio, M. L. Biomarkers of diabetic kidney disease. Diabetologia 61, 996–1011 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Khalil, M. et al. Neurofilaments as biomarkers in neurological disorders. Nat. Rev. Neurol. 14, 577–589 (2018).

    Article  PubMed  CAS  Google Scholar 

  22. Hagberg, L., Edén, A., Zetterberg, H., Price, R. W. & Gisslén, M. Blood biomarkers for HIV infection with focus on neurologic complications—a review. Acta Neurol. Scand. 146, 56–60 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Busche, M. A. & Hyman, B. T. Synergy between amyloid-β and tau in Alzheimer’s disease. Nat. Neurosci. 23, 1183–1193 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Emin, D. et al. Small soluble α-synuclein aggregates are the toxic species in Parkinson’s disease. Nat. Commun. 13, 5512 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Sarkar, S. et al. Expression of microRNA-34a in Alzheimer’s disease brain targets genes linked to synaptic plasticity, energy metabolism, and resting state network activity. Brain Res. 1646, 139–151 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Martinez, B. & Peplow, P. MicroRNAs in Parkinson’s disease and emerging therapeutic targets. Neural Regen. Res. 12, 1945–1959 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Otani, N., Hoshiyama, E., Ouchi, M., Takekawa, H. & Suzuki, K. Uric acid and neurological disease: a narrative review. Front. Neurol. 14, 1164756 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Moustafa, A. A., Hewedi, D. H., Eissa, A. M., Frydecka, D. & Misiak, B. in Diet and Exercise in Cognitive Function and Neurological Diseases (eds. Farooqui, T. & Farooqui, A. A.) 73–81 (Wiley, 2015).

  29. Wang, L., Hu, Y., Jiang, N. & Yetisen, A. K. Biosensors for psychiatric biomarkers in mental health monitoring. Biosens. Bioelectron. 256, 116242 (2024).

    Article  PubMed  CAS  Google Scholar 

  30. Zamani, M., Wilhelm, T. & Furst, A. L. Perspective—electrochemical sensors for neurotransmitters and psychiatrics: steps toward physiological mental health monitoring. J. Electrochem. Soc. 169, 047513 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Schumann, G. et al. Stratified medicine for mental disorders. Eur. Neuropsychopharmacol. 24, 5–50 (2014).

    Article  PubMed  CAS  Google Scholar 

  32. Rutsch, A., Kantsjö, J. B. & Ronchi, F. The gut–brain axis: how microbiota and host inflammasome influence brain physiology and pathology. Front. Immunol. 11, 604179 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Roomruangwong, C. et al. Menstruation distress is strongly associated with hormone–immune–metabolic biomarkers. J. Psychosom. Res. 142, 110355 (2021).

    Article  PubMed  Google Scholar 

  34. Ciebiera, M. et al. Nutrition in gynecological diseases: current perspectives. Nutrients 13, 1178 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Mavreli, D., Theodora, M. & Kolialexi, A. Known biomarkers for monitoring pregnancy complications. Expert Rev. Mol. Diagn. 21, 1115–1117 (2021).

    Article  PubMed  CAS  Google Scholar 

  36. Eastell, R. & Hannon, R. A. Biomarkers of bone health and osteoporosis risk. Proc. Nutr. Soc. 67, 157–162 (2008).

    Article  PubMed  Google Scholar 

  37. Amin, M. N. et al. Inflammatory cytokines in the pathogenesis of cardiovascular disease and cancer. SAGE Open Med. 8, 205031212096575 (2020).

    Article  Google Scholar 

  38. Jain, K. K. in The Handbook of Biomarkers 27–238 (Springer, 2017).

  39. Liu, C. H. et al. Biomarkers of chronic inflammation in disease development and prevention: challenges and opportunities. Nat. Immunol. 18, 1175–1180 (2017).

    Article  PubMed  CAS  Google Scholar 

  40. Tu, J. et al. A wireless patch for the monitoring of C-reactive protein in sweat. Nat. Biomed. Eng. 7, 1293–1306 (2023). This paper introduces a wearable, wireless patch that enables real-time, non-invasive monitoring of the inflammatory biomarker C-reactive protein in sweat, correlating with serum levels and demonstrating high translation potential for the point-of-care management of chronic diseases.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Liu, Y. et al. Revolutionizing precision medicine: exploring wearable sensors for therapeutic drug monitoring and personalized therapy. Biosensors 13, 726 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Sempionatto, J. R., Montiel, V. R.-V., Vargas, E., Teymourian, H. & Wang, J. Wearable and mobile sensors for personalized nutrition. ACS Sens. 6, 1745–1760 (2021).

    Article  PubMed  CAS  Google Scholar 

  43. Wang, M. et al. A wearable electrochemical biosensor for the monitoring of metabolites and nutrients. Nat. Biomed. Eng. 6, 1225–1235 (2022). This study reports on a wearable electrochemical biosensor capable of continuously monitoring multiple non-electroactive metabolites and nutrients, including all essential amino acids and vitamins, in sweat during both exercise and rest, utilizing innovative MIPs, redox-active nanoparticles and integrated sweat induction and sampling technologies.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Güttler, N. et al. Omega-3 fatty acids and vitamin D in cardiology. Cardiol. Res. Pract. 2012, 729670 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Kevadiya, B. D. et al. Diagnostics for SARS-CoV-2 infections. Nat. Mater. 20, 593–605 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Wang, C. et al. Wound management materials and technologies from bench to bedside and beyond. Nat. Rev. Mater. 9, 550–566 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Cappon, G., Vettoretti, M., Sparacino, G. & Facchinetti, A. Continuous glucose monitoring sensors for diabetes management: a review of technologies and applications. Diabetes Metab. J. 43, 383–397 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Arlett, J. L., Myers, E. B. & Roukes, M. L. Comparative advantages of mechanical biosensors. Nat. Nanotechnol. 6, 203–215 (2011).

    Article  PubMed  CAS  Google Scholar 

  49. Zhang, Y. et al. Nanozymes for nanohealthcare. Nat. Rev. Methods Prim. 4, 36 (2024).

    Article  CAS  Google Scholar 

  50. Wu, X., Ge, J., Yang, C., Hou, M. & Liu, Z. Facile synthesis of multiple enzyme-containing metal–organic frameworks in a biomolecule-friendly environment. Chem. Commun. 51, 13408–13411 (2015).

    Article  CAS  Google Scholar 

  51. Wang, M. et al. Printable molecule-selective core–shell nanoparticles for wearable and implantable sensing. Nat. Mater. 24, 589–598 (2025). This study reports on a skin-interfaced, printable wearable sensor leveraging core–shell nanoparticles with MIP shells for customizable and selective sweat analysis, featuring electrochemical regeneration via electrical pulses for repeated use without performance loss.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Yao, J., Yang, M. & Duan, Y. Chemistry, biology, and medicine of fluorescent nanomaterials and related systems: new insights into biosensing, bioimaging, genomics, diagnostics, and therapy. Chem. Rev. 114, 6130–6178 (2014).

    Article  PubMed  CAS  Google Scholar 

  53. Biswas, A. et al. Advances in top-down and bottom-up surface nanofabrication: techniques, applications & future prospects. Adv. Colloid Interface Sci. 170, 2–27 (2012).

    Article  PubMed  CAS  Google Scholar 

  54. Wang, P. et al. DNA origami guided self-assembly of plasmonic polymers with robust long-range plasmonic resonance. Nano Lett. 20, 8926–8932 (2020).

    Article  PubMed  CAS  Google Scholar 

  55. Fu, K. et al. Accelerated electron transfer in nanostructured electrodes improves the sensitivity of electrochemical biosensors. Adv. Sci. 8, 2102495 (2021).

    Article  CAS  Google Scholar 

  56. Altug, H., Oh, S.-H., Maier, S. A. & Homola, J. Advances and applications of nanophotonic biosensors. Nat. Nanotechnol. 17, 5–16 (2022).

    Article  PubMed  CAS  Google Scholar 

  57. Bauch, M., Toma, K., Toma, M., Zhang, Q. & Dostalek, J. Plasmon-enhanced fluorescence biosensors: a review. Plasmonics 9, 781–799 (2014).

    Article  PubMed  CAS  Google Scholar 

  58. Fu, W. et al. Efficient optical plasmonic tweezer-controlled single-molecule SERS characterization of pH-dependent amylin species in aqueous milieus. Nat. Commun. 14, 6996 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Xu, Y. et al. In-ear integrated sensor array for the continuous monitoring of brain activity and of lactate in sweat. Nat. Biomed. Eng. 7, 1307–1320 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Arwani, R. T. et al. Stretchable ionic–electronic bilayer hydrogel electronics enable in situ detection of solid-state epidermal biomarkers. Nat. Mater. 23, 1115–1122 (2024). This article reports on a stretchable ionic–electronic bilayer hydrogel sensor capable of detecting solid-state epidermal biomarkers, including cholesterol and lactate, directly on the skin surface without the need for fluid sampling, combining innovative materials science with electrochemical sensing for non-invasive, continuous health monitoring.

    Article  PubMed  CAS  Google Scholar 

  62. Ye, C. et al. A wearable aptamer nanobiosensor for non-invasive female hormone monitoring. Nat. Nanotechnol. 19, 330–337 (2024).

    Article  PubMed  CAS  Google Scholar 

  63. Wu, Z. et al. Interstitial fluid-based wearable biosensors for minimally invasive healthcare and biomedical applications. Commun. Mater. 5, 33 (2024).

    Article  CAS  Google Scholar 

  64. Friedel, M. et al. Opportunities and challenges in the diagnostic utility of dermal interstitial fluid. Nat. Biomed. Eng. 7, 1541–1555 (2023).

    Article  PubMed  Google Scholar 

  65. 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). In this study, multiple biomarkers were continuously monitored using a fully integrated wearable microneedle array in ISF during daily activities.

    Article  PubMed  CAS  Google Scholar 

  66. Lipani, L. et al. Non-invasive, transdermal, path-selective and specific glucose monitoring via a graphene-based platform. Nat. Nanotechnol. 13, 504–511 (2018).

    Article  PubMed  CAS  Google Scholar 

  67. Gao, Y. et al. A flexible multiplexed immunosensor for point-of-care in situ wound monitoring. Sci. Adv. 7, eabg9614 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. 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  PubMed  PubMed Central  CAS  Google Scholar 

  70. Mannoor, M. S. et al. Graphene-based wireless bacteria detection on tooth enamel. Nat. Commun. 3, 763 (2012).

    Article  PubMed  Google Scholar 

  71. Kim, J. et al. Wearable salivary uric acid mouthguard biosensor with integrated wireless electronics. Biosens. Bioelectron. 74, 1061–1068 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Güntner, A. T. et al. Breath sensors for health monitoring. ACS Sens. 4, 268–280 (2019).

    Article  PubMed  Google Scholar 

  73. Ates, H. C. & Dincer, C. Wearable breath analysis. Nat. Rev. Bioeng. 1, 80–82 (2023).

    Article  CAS  Google Scholar 

  74. Nguyen, P. Q. et al. Wearable materials with embedded synthetic biology sensors for biomolecule detection. Nat. Biotechnol. 39, 1366–1374 (2021). In this study, freeze-dried, cell-free synthetic biology circuits were successfully integrated into wearable materials, enabling the non-invasive detection of various biomolecules, chemicals and pathogens, including SARS-CoV-2, without the need for living cells or complex instrumentation.

    Article  PubMed  CAS  Google Scholar 

  75. Heng, W. et al. A smart mask for exhaled breath condensate harvesting and analysis. Science 385, 954–961 (2024). This work demonstrates continuous breath condensate sampling and accurate electrochemical monitoring of metabolites and inflammatory biomarkers in exhaled breath, offering practical applications in both daily life and clinical settings.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Ye, Y. et al. Smart contact lens with dual-sensing platform for monitoring intraocular pressure and matrix metalloproteinase-9. Adv. Sci. 9, 2104738 (2022).

    Article  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. 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  PubMed  PubMed Central  CAS  Google Scholar 

  80. Seo, H. et al. Smart contact lenses as wearable ophthalmic devices for disease monitoring and health management. Chem. Rev. 123, 11488–11558 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Park, W. et al. In-depth correlation analysis between tear glucose and blood glucose using a wireless smart contact lens. Nat. Commun. 15, 2828 (2024). In this study, a wireless smart contact lens was successfully developed and validated for continuous, real-time monitoring of tear glucose, establishing a strong correlation with blood glucose through the concept of personalized lag time across multiple species and diabetic conditions.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Kalantar-Zadeh, K. et al. A human pilot trial of ingestible electronic capsules capable of sensing different gases in the gut. Nat. Electron. 1, 79–87 (2018). This article demonstrates a human pilot trial of ingestible electronic capsules capable of sensing oxygen, hydrogen and carbon dioxide in the gut, providing real-time data on gastrointestinal gas profiles and transit times.

    Article  Google Scholar 

  83. Belknap, R. et al. Feasibility of an ingestible sensor-based system for monitoring adherence to tuberculosis therapy. PLoS ONE 8, e53373 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Siddiqui, I., Majid, H. & Abid, S. Update on clinical and research application of fecal biomarkers for gastrointestinal diseases. World J. Gastrointest. Pharmacol. Ther. 8, 39–46 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Steiger, C. et al. Ingestible electronics for diagnostics and therapy. Nat. Rev. Mater. 4, 83–98 (2019).

    Article  PubMed  CAS  Google Scholar 

  86. De la Paz, E. et al. A self-powered ingestible wireless biosensing system for real-time in situ monitoring of gastrointestinal tract metabolites. Nat. Commun. 13, 7405 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Mimee, M. et al. An ingestible bacterial–electronic system to monitor gastrointestinal health. Science 360, 915–918 (2018). This study reports on the development of an ingestible micro-bio-electronic device that combines engineered probiotic bacteria with miniaturized electronics for the in situ detection of gastrointestinal biomarkers, as validated in both in vitro and in vivo porcine models.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Inda-Webb, M. E. et al. Sub-1.4 cm3 capsule for detecting labile inflammatory biomarkers in situ. Nature 620, 386–392 (2023).

    Article  PubMed  CAS  Google Scholar 

  89. Li, J. et al. A tissue-like neurotransmitter sensor for the brain and gut. Nature 606, 94–101 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Wang, L. et al. Functionalized helical fibre bundles of carbon nanotubes as electrochemical sensors for long-term in vivo monitoring of multiple disease biomarkers. Nat. Biomed. Eng. 4, 159–171 (2020).

    Article  PubMed  CAS  Google Scholar 

  91. Li, R. et al. A flexible and physically transient electrochemical sensor for real-time wireless nitric oxide monitoring. Nat. Commun. 11, 3207 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Ferguson, B. S. et al. Real-time, aptamer-based tracking of circulating therapeutic agents in living animals. Sci. Transl. Med. 5, 213ra165 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Arroyo-Currás, N. et al. Real-time measurement of small molecules directly in awake, ambulatory animals. Proc. Natl Acad. Sci. USA 114, 645–650 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Holmström, N., Nilsson, P., Carlsten, J. & Bowald, S. Long-term in vivo experience of an electrochemical sensor using the potential step technique for measurement of mixed venous oxygen pressure. Biosens. Bioelectron. 13, 1287–1295 (1998).

    Article  PubMed  Google Scholar 

  95. Theuns, D. A. M. J. et al. Prognostic role of high‐sensitivity C‐reactive protein and B‐type natriuretic peptide in implantable cardioverter‐defibrillator patients. Pacing Clin. Electrophysiol. 35, 275–282 (2012).

    Article  PubMed  Google Scholar 

  96. Abbassy, M. et al. Biosensors with left ventricular assist devices. Heart Fail. Rev. 29, 957–967 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Neubeck, L. et al. The mobile revolution—using smartphone apps to prevent cardiovascular disease. Nat. Rev. Cardiol. 12, 350–360 (2015).

    Article  PubMed  Google Scholar 

  98. Xu, C. et al. A physicochemical-sensing electronic skin for stress response monitoring. Nat. Electron. 7, 168–179 (2024).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Torrente-Rodríguez, R. M. et al. Investigation of cortisol dynamics in human sweat using a graphene-based wireless mHealth system. Matter 2, 921–937 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Song, Y. et al. 3D-printed epifluidic electronic skin for machine learning-powered multimodal health surveillance. Sci. Adv. 9, eadi6492 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Sundhoro, M. et al. Rapid and accurate electrochemical sensor for food allergen detection in complex foods. Sci. Rep. 11, 20831 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Criscuolo, F., Cantù, F., Taurino, I., Carrara, S. & De Micheli, G. A wearable electrochemical sensing system for non-invasive monitoring of lithium drug in bipolar disorder. IEEE Sens. J. 21, 9649–9656 (2021).

    Article  CAS  Google Scholar 

  103. 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  PubMed  CAS  Google Scholar 

  104. Alipour, A., Gabrielson, S. & Patel, P. B. Ingestible sensors and medication adherence: focus on use in serious mental illness. Pharmacy 8, 103 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  105. Kane, J. M. et al. First experience with a wireless system incorporating physiologic assessments and direct confirmation of digital tablet ingestions in ambulatory patients with schizophrenia or bipolar disorder. J. Clin. Psychiatry 74, e533–e540 (2013).

    Article  PubMed  Google Scholar 

  106. Sempionatto, J. R., Lasalde-Ramírez, 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  PubMed  PubMed Central  Google Scholar 

  107. Xu, C., Solomon, S. A. & Gao, W. Artificial intelligence-powered electronic skin. Nat. Mach. Intell. 5, 1344–1355 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Flynn, C. D. & Chang, D. Artificial intelligence in point-of-care biosensing: challenges and opportunities. Diagnostics 14, 1100 (2024).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Rodbard, D. Continuous glucose monitoring: a review of recent studies demonstrating improved glycemic outcomes. Diabetes Technol. Ther. 19, S25–S37 (2017).

    Article  PubMed  Google Scholar 

  110. Soto, R. J., Hall, J. R., Brown, M. D., Taylor, J. B. & Schoenfisch, M. H. In vivo chemical sensors: role of biocompatibility on performance and utility. Anal. Chem. 89, 276–299 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  111. Chang, D. et al. A high-dimensional microfluidic approach for selection of aptamers with programmable binding affinities. Nat. Chem. 15, 773–780 (2023).

    Article  PubMed  CAS  Google Scholar 

  112. Zhu, Y. et al. Lab-on-a-contact lens: recent advances and future opportunities in diagnostics and therapeutics. Adv. Mat. 34, 2108389 (2022).

    Article  CAS  Google Scholar 

  113. Smith, J. L. & Rice, M. J. Why have so many intravascular glucose monitoring devices failed? J. Diabetes Sci. Technol. 9, 782–791 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  114. Sideri, K. et al. Digital pills for the remote monitoring of medication intake: a stakeholder analysis and assessment of marketing approval and patent granting policies. J. Law Biosci. 9, lsac029 (2022).

    PubMed  PubMed Central  Google Scholar 

  115. De Miguel Beriain, I. & Morla González, M. ‘Digital pills’ for mental diseases: an ethical and social analysis of the issues behind the concept. J. Law Biosci. 7, lsaa040 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Tadikonda, S. HealthVerity: Real World Data and Evidence. Case 824-019 (Harvard Business School, 2023).

  117. Galindo, R. J. et al. Continuous glucose monitors and automated insulin dosing systems in the hospital consensus guideline. J. Diabetes Sci. Technol. 14, 1035–1064 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  118. Tu, J. & Gao, W. Ethical considerations of wearable technologies in human research. Adv. Healthc. Mater. 10, 2100127 (2021).

    Article  CAS  Google Scholar 

  119. Zheng, H. et al. Reverse iontophoresis with the development of flexible electronics: a review. Biosens. Bioelectron. 223, 115036 (2023).

    Article  PubMed  CAS  Google Scholar 

  120. Wang, C. et al. A microfluidic wearable device for wound exudate management and analysis in human chronic wounds. Sci. Transl. Med. 17, eadt0882 (2025).

    Article  PubMed  CAS  Google Scholar 

  121. Shibasaki, K., Kimura, M., Ikarashi, R., Yamaguchi, A. & Watanabe, T. Uric acid concentration in saliva and its changes with the patients receiving treatment for hyperuricemia. Metabolomics 8, 484–491 (2012).

    Article  CAS  Google Scholar 

  122. Daum, K. M. & Hill, R. M. Human tear glucose. Invest. Ophthalmol. Vis. Sci. 22, 509–514 (1982).

    PubMed  CAS  Google Scholar 

  123. Min, J. et al. Continuous biochemical profiling of the gastrointestinal tract using an integrated smart capsule. Nat. Electron. https://doi.org/10.1038/s41928-025-01407-0 (2025).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Barton, M. & Yanagisawa, M. Endothelin: 30 years from discovery to therapy. Hypertension 74, 1232–1265 (2019).

    Article  PubMed  CAS  Google Scholar 

  125. Tektonidou, M. G. & Ward, M. M. Validation of new biomarkers in systemic autoimmune diseases. Nat. Rev. Rheumatol. 7, 708–717 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. PRECISION study: evaluating the accuracy of the LabPatch continuous glucose monitor. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT03262415 (2023).

  127. A study of non-invasive measurement of blood glucose and blood pressure. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT05904769?intr=LIFELEAF&rank=1 (2025).

  128. Epicore Biosystems launches Discovery Patch® Sweat Collection System. Epicore Biosystems https://www.prnewswire.com/news-releases/epicore-biosystems-launches-discovery-patch-sweat-collection-system-301392407.html (2021).

  129. Law, R. Biolinq granted de novo classification for needle-free glucose monitor. Medical Device Network https://www.medicaldevice-network.com/news/biolinq-granted-de-novo-classification-for-needle-free-glucose-monitor (2025).

  130. Eversense E3 Continuous Glucose Monitoring (CGM) System – P160048/S021 FDA https://www.fda.gov/medical-devices/recently-approved-devices/eversense-e3-continuous-glucose-monitoring-cgm-system-p160048s021 (2023).

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Das, J. et al. Reagentless biomolecular analysis using a molecular pendulum. Nat. Chem. 13, 428–434 (2021). This article introduces a novel molecular pendulum sensing mechanism capable of the reagentless detection of diverse protein biomarkers in multiple biofluids, enabling continuous real-time monitoring and in vivo measurements.

    Article  PubMed  CAS  Google Scholar 

  133. Zargartalebi, H. et al. Capillary-assisted molecular pendulum bioanalysis. J. Am. Chem. Soc. 144, 18338–18349 (2022).

    Article  PubMed  CAS  Google Scholar 

  134. Rivnay, J. et al. Organic electrochemical transistors. Nat. Rev. Mater. 3, 17086 (2018).

    Article  CAS  Google Scholar 

  135. Lu, Z. et al. Biomolecule sensors based on organic electrochemical transistors. NPJ Flex. Electron. 9, 9 (2025).

    Article  Google Scholar 

  136. Koh, A. et al. A soft, wearable microfluidic device for the capture, storage, and colorimetric sensing of sweat. Sci. Transl. Med. 8, 366ra165 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  137. Lee, K. H. et al. Synergistic SERS enhancement in GaN–Ag hybrid system toward label-free and multiplexed detection of antibiotics in aqueous solutions. Adv. Sci. 8, 2100640 (2021).

    Article  CAS  Google Scholar 

  138. Xu, K., Zhou, R., Takei, K. & Hong, M. Toward flexible surface-enhanced Raman scattering (SERS) sensors for point-of-care diagnostics. Adv. Sci. 6, 1900925 (2019).

    Article  Google Scholar 

  139. Wang, Y. et al. Wearable plasmonic-metasurface sensor for noninvasive and universal molecular fingerprint detection on biointerfaces. Sci. Adv. 7, eabe4553 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. Lin, L. & Wang, L. V. The emerging role of photoacoustic imaging in clinical oncology. Nat. Rev. Clin. Oncol. 19, 365–384 (2022).

    Article  PubMed  Google Scholar 

  141. Zargartalebi, H. et al. Active-reset protein sensors enable continuous in vivo monitoring of inflammation. Science 386, 1146–1153 (2024). This article introduces an active-reset methodology that enables receptor regeneration through the application of an alternating electric potential and facilitates continuous protein monitoring.

    Article  PubMed  CAS  Google Scholar 

  142. Sun, N. et al. Aptamer melting biosensors for thousands of signaling and regenerating cycles. Biosens. Bioelectron. 271, 116998 (2025).

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This project was supported by the National Science Foundation (grants 2145802 and 2444815), National Institutes of Health (grants R01HL155815, R01HL165002 and R21DK13266), Army Research Office (grant W911NF-23-1-0041), American Cancer Society Research Scholar (grant RSG-21-181-01-CTPS), US Army Medical Research Acquisition Activity (grant HT9425-24-1-0249), Advanced Research Projects Agency for Health Sprint for Women’s Health (award number ARPA-H-ICHUB-24-101-504), Heritage Medical Research Institute, Natural Sciences and Engineering Research Council of Canada and Chan Zuckerberg Biohub Chicago.

Author information

Author notes

  1. These authors contributed equally: Jiaobing Tu, Connor D. Flynn.

Authors and Affiliations

  1. Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA

    Jiaobing Tu, Jeonghee Yeom & Wei Gao

  2. Department of Chemistry, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL, USA

    Connor D. Flynn & Shana O. Kelley

  3. Chan Zuckerberg Biohub Chicago, Chicago, IL, USA

    Connor D. Flynn, Zhenwei Wu & Shana O. Kelley

  4. Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA

    Zhenwei Wu & Shana O. Kelley

  5. Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada

    Shana O. Kelley

  6. Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Evanston, IL, USA

    Shana O. Kelley

  7. International Institute for Nanotechnology, Northwestern University, Evanston, IL, USA

    Shana O. Kelley

Authors
  1. Jiaobing Tu
    View author publications

    Search author on:PubMed Google Scholar

  2. Connor D. Flynn
    View author publications

    Search author on:PubMed Google Scholar

  3. Jeonghee Yeom
    View author publications

    Search author on:PubMed Google Scholar

  4. Zhenwei Wu
    View author publications

    Search author on:PubMed Google Scholar

  5. Shana O. Kelley
    View author publications

    Search author on:PubMed Google Scholar

  6. Wei Gao
    View author publications

    Search author on:PubMed Google Scholar

Corresponding authors

Correspondence to Shana O. Kelley or Wei Gao.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Nanotechnology thanks the anonymous reviewers 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.

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

Tu, J., Flynn, C.D., Yeom, J. et al. Wearable biomolecular sensing nanotechnologies in chronic disease management. Nat. Nanotechnol. (2025). https://doi.org/10.1038/s41565-025-02010-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41565-025-02010-2

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