Mechanics and bio-interface engineering in flexible biosensors for continuous health monitoring
Source abstract
Abstract
Flexible biosensors enable real-time, point-of-care health monitoring through wearable systems and must withstand complex mechanical deformation during use. Their performance is governed by coupled material properties, structural design, and fabrication strategies. This review integrates mechanistic insights, bio-interface design, data handling, fabrication methods, and hybrid material strategies, and outlines pathways toward advanced biosensors capable of maintaining structural integrity and high performance in real-world applications.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Advanced Sensor and Energy Harvesting Materials · 2D Materials and Applications · Electrochemical sensors and biosensors
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (100+)
Show source-provided references
1. Chen, S. et al. Starfish-inspired wearable bioelectronic systems for physiological signal monitoring during motion and real-time heart disease diagnosis. Sci. Adv. 11, eadv2406 (2025).10.1126/sciadv.adv2406 ↗
2. Fullenkamp, D. E. et al. Simultaneous electromechanical monitoring in engineered heart tissues using a mesoscale framework. Sci. Adv. 10, eado7089 (2024).10.1126/sciadv.ado7089 ↗
3. Imani, S. et al. A wearable chemical-electrophysiological hybrid biosensing system for real-time health and fitness monitoring. Nat. Commun. 7, 11650 (2016).10.1038/ncomms11650 ↗
4. Jin, X. et al. Fully integrated flexible biosensor for wearable continuous glucose monitoring. Biosens. Bioelectron. 196, 113760 (2022).10.1016/j.bios.2021.113760 ↗
5. Tzavelis, A. et al. Development of a miniaturized mechanoacoustic sensor for continuous, objective cough detection, characterization and physiologic monitoring in children with cystic fibrosis. IEEE J. Biomed. Health Inf. 28, 5941–5952 (2024).10.1109/JBHI.2024.3415479 ↗
6. Botonis, P. G., Arsoniadis, G. G., Smilios, I. & Toubekis, A. G. In-season training load variation - heart rate recovery, perceived recovery status, and performance in elite male water polo players: a pilot study. Sports Health 17, 144–149 (2024).10.1177/19417381241245348 ↗
7. Gadaleta, M. et al. Passive detection of COVID-19 with wearable sensors and explainable machine learning algorithms. NPJ Digit Med. 4, 166 (2021).10.1038/s41746-021-00533-1 ↗
8. Cho, S. I. et al. Engineering TALE-linked deaminases to facilitate precision adenine base editing in mitochondrial DNA. Cell 187, 95–109.e126 (2024).10.1016/j.cell.2023.11.035 ↗
9. Krishnan, S. K., Prokhorov, E., Bahena, D., Esparza, R. & Meyyappan, M. Chitosan-covered Pd@Pt core-shell nanocubes for direct electron transfer in electrochemical enzymatic glucose biosensor. ACS Omega 2, 1896–1904 (2017).10.1021/acsomega.7b00060 ↗
10. Ling, W., Shang, X., Liu, J. & Tang, T. A skin-mountable flexible biosensor based on Cu-MOF/PEDOT composites for sweat ascorbic acid monitoring. Biosens. Bioelectron. 267, 116852 (2025).10.1016/j.bios.2024.116852 ↗
11. Madhvapathy, S. R. et al. Implantable bioelectronics and wearable sensors for kidney health and disease. Nat. Rev. Nephrol. 21, 443–463 (2025).10.1038/s41581-025-00961-2 ↗
12. 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).10.1126/sciadv.aaw9906 ↗
13. Qaiser, N. et al. A robust wearable point-of-care CNT-based strain sensor for wirelessly monitoring throat-related illnesses. Adv. Funct. Mater. 31, 2103375 (2021).10.1002/adfm.202103375 ↗
14. Trung, T. Q. & Lee, N. E. Flexible and stretchable physical sensor integrated platforms for wearable human-activity monitoringand personal healthcare. Adv. Mater. 28, 4338–4372 (2016).10.1002/adma.201504244 ↗
15. Wu, S. J. & Zhao, X. Bioadhesive technology platforms. Chem. Rev. 123, 14084–14118 (2023).10.1021/acs.chemrev.3c00380 ↗
16. Min, J. et al. Skin-interfaced wearable sweat sensors for precision medicine. Chem. Rev. 123, 5049–5138 (2023).10.1021/acs.chemrev.2c00823 ↗
17. O’Brien, M. K., Hohl, K., Lieber, R. L. & Jayaraman, A. Automate, illuminate, predict: a universal framework for integrating wearable sensors in healthcare. Digit Biomark. 8, 149–158 (2024).10.1159/000540492 ↗
18. Qaiser, N., Khan, S. M. & Hussain, M. M. In-plane and out-of-plane structural response of spiral interconnects for highly stretchable electronics. J. Appl Phys. 124, 034905 (2018).10.1063/1.5031176 ↗
19. Bandodkar, A. J. et al. Tattoo-based noninvasive glucose monitoring: a proof-of-concept study. Anal. Chem. 87, 394–398 (2015).10.1021/ac504300n ↗
20. Choi, M. K. et al. cephalopod-inspired miniaturized suction cups for smart medical skin. Adv. Health. Mater. 5, 80–87 (2016).10.1002/adhm.201500285 ↗
21. Derkus, B. Applying the miniaturization technologies for biosensor design. Biosens. Bioelectron. 79, 901–913 (2016).10.1016/j.bios.2016.01.033 ↗
22. Kim, J. Y. et al. Continuous glucose monitoring with structured education in adults with type 2 diabetes managed by multiple daily insulin injections: a multicentre randomised controlled trial. Diabetology 67, 1223–1234 (2024).10.1007/s00125-024-06152-1 ↗
23. Vora, L. K. et al. Artificial intelligence in pharmaceutical technology and drug delivery design. Pharmaceutics 15, 1916 (2023).10.3390/pharmaceutics15071916 ↗
24. Sharma, A., Badea, M., Tiwari, S. & Marty, J. L. Wearable biosensors: an alternative and practical approach in healthcare and disease monitoring. Molecules 26, 748 (2021).10.3390/molecules26030748 ↗
25. Yoon, J. et al. Nanotechnology-based wearable electrochemical biosensor for disease diagnosis. ACS Sens. 10, 1675–1689 (2025).10.1021/acssensors.4c03371 ↗
26. 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).10.1126/sciadv.aav3294 ↗
27. Bandodkar, A. J. & Wang, J. Non-invasive wearable electrochemical sensors: a review. Trends Biotechnol. 32, 363–371 (2014).10.1016/j.tibtech.2014.04.005 ↗
28. Meng, J. et al. A tonically active master neuron modulates mutually exclusive motor states at two timescales. Sci. Adv. 10, eadk0002 (2024).10.1126/sciadv.adk0002 ↗
29. Ayçiçek, S., Cevher, S. u. C. k. & Acar, S. Recent trends in hydrogel-based biosensor technology for the diagnosis of neurodegenerative diseases. ACS Appl. Bio Mater. 8, 5424–5444 (2025).10.1021/acsabm.5c00420 ↗
30. Keles, G., Derici, U. S., Altunay, B. B., Yilgor, P. & Kurbanoglu, S. Applications of 3D-printed electrochemical sensors in medical diagnostics. in Additively Manufactured Electrochemical Sensors: Design, Performance, and Applications, 177–250 (Wiley, 2025).10.1002/9781394303434.ch8 ↗
31. Atabay, M., Inci, F. & Saylan, Y. Computational studies for the development of extracellular vesicle-based biosensors. Biosens. Bioelectron. 277, 117275 (2025).10.1016/j.bios.2025.117275 ↗
32. Song, J. K. et al. Wearable force touch sensor array using a flexible and transparent electrode. Adv. Funct. Mater. 27, 1605286 (2017).10.1002/adfm.201605286 ↗
33. Wang, S., Chinnasamy, T., Lifson, M. A., Inci, F. & Demirci, U. Flexible substrate-based devices for point-of-care diagnostics. Trends Biotechnol. 34, 909–921 (2016).10.1016/j.tibtech.2016.05.009 ↗
34. Kumar, R. & Parashar, A. Atomistic simulations of pristine and nanoparticle reinforced hydrogels: a review. Wiley Interdiscip. Rev. Comput. Mol. Sci. 13, e1655 (2023).10.1002/wcms.1655 ↗
35. Yan, Z. et al. Mechanical assembly of complex, 3D mesostructures from releasable multilayers of advanced materials. Sci. Adv. 2, e1601014 (2016).10.1126/sciadv.1601014 ↗
36. Zhu, Y. & Lu, N. Mechanics of Flexible and Stretchable Electronics (Wiley-VCH, 2025).10.1002/9783527842308 ↗
37. Cui, X., Wu, L., Zhang, C. & Li, Z. Implantable self-powered systems for electrical stimulation medical devices. Adv. Sci. 12, e2412044 (2025).10.1002/advs.202412044 ↗
38. Yang, Y. et al. Ultrafine graphene nanomesh with large on/off ratio for high-performance flexible biosensors. Adv. Funct. Mater. 27, 1604096 (2016).10.1002/adfm.201604096 ↗
39. Bocchetta, P. et al. Soft materials for wearable/flexible electrochemical energy conversion, storage, and biosensor devices. Materials 13, 2733 (2020).10.3390/ma13122733 ↗
40. Shetti, N. P. et al. Skin-patchable electrodes for biosensor applications: a review. ACS Biomater. Sci. Eng. 6, 1823–1835 (2020).10.1021/acsbiomaterials.9b01659 ↗
41. Vedadghavami, A. et al. Manufacturing of hydrogel biomaterials with controlled mechanical properties for tissue engineering applications. Acta Biomater. 62, 42–63 (2017).10.1016/j.actbio.2017.07.028 ↗
42. Ates, H. C. et al. End-to-end design of wearable sensors. Nat. Rev. Mater. 7, 887–907 (2022).10.1038/s41578-022-00460-x ↗
43. Carpinteri, A. Decrease of apparent tensile and bending strength with specimen size: two different explanations based on fracture mechanics. Int. J. Solid Struct. 25, 407–429 (1989).10.1016/0020-7683(89)90056-5 ↗
44. Kenry, Yeo, J. C. & Lim, C. T. Emerging flexible and wearable physical sensing platforms for healthcare and biomedical applications. Microsyst. Nanoeng. 2, 16043 (2016).10.1038/micronano.2016.43 ↗
45. Vaghasiya, J. V., Mayorga-Martinez, C. C. & Pumera, M. Wearable sensors for telehealth based on emerging materials and nanoarchitectonics. npj Flex. Electron. 7, 26 (2023).10.1038/s41528-023-00261-4 ↗
46. Himmelhaus, M. & Francois, A. In-vitro sensing of biomechanical forces in live cells by a whispering gallery mode biosensor. Biosens. Bioelectron. 25, 418–427 (2009).10.1016/j.bios.2009.07.021 ↗
47. Prasad, S. et al. 3D nanorhombus nickel nitride as stable and cost-effective counter electrodes for dye-sensitized solar cells and supercapacitor applications. RSC Adv. 8, 8828–8835 (2018).10.1039/C8RA00347E ↗
48. Ge, Z., Yang, F., Goh, J. C., Ramakrishna, S. & Lee, E. H. Biomaterials and scaffolds for ligament tissue engineering. J. Biomed. Mater. Res. A 77, 639–652 (2006).10.1002/jbm.a.30578 ↗
49. Niinomi, M. & Nakai, M. Titanium-based biomaterials for preventing stress shielding between implant devices and bone. Int. J. Biomater. 2011, 836587 (2011).10.1155/2011/836587 ↗
50. Pena, A. E. et al. Mechanical fatigue resistance of an implantable branched lead system for a distributed set of longitudinal intrafascicular electrodes. J. Neural Eng. 14, 066014 (2017).10.1088/1741-2552/aa814d ↗
51. Mousavi, A., Rahimnejad, M., Azimzadeh, M., Akbari, M. & Savoji, H. Recent advances in smart wearable sensors as electronic skin. J. Mater. Chem. B 11, 10332–10354 (2023).10.1039/D3TB01373A ↗
52. Zeng, Q. & Huang, Z. Challenges and opportunities of implantable neural interfaces: from material, electrochemical and biological perspectives. Adv. Funct. Mater. 33, 2301223 (2023).10.1002/adfm.202301223 ↗
53. Park, B., Jeong, C., Ok, J. & Kim, T.-i. Materials and structural designs toward motion artifact-free bioelectronics. Chem. Rev. 124, 6148-6197 (2024).10.1021/acs.chemrev.3c00374 ↗
54. Gong, S., Lu, Y., Yin, J., Levin, A. & Cheng, W. Materials-driven soft wearable bioelectronics for connected healthcare. Chem. Rev. 124, 455–553 (2024).10.1021/acs.chemrev.3c00502 ↗
55. Tan, E. L. et al. Implantable biosensors for real-time strain and pressure monitoring. Sensors 8, 6396–6406 (2008).10.3390/s8106396 ↗
56. Wang, L. & Beebe, D. J. Characterization of a silicon-based shear-force sensor on human subjects. IEEE Trans. Biomed. Eng. 49, 1340–1347 (2002).10.1109/TBME.2002.804586 ↗
57. Yamagishi, K., Zhou, W., Ching, T., Huang, S. Y. & Hashimoto, M. Ultra-deformable and tissue-adhesive liquid metal antennas with high wireless powering efficiency. Adv. Mater. 33, e2008062 (2021).10.1002/adma.202008062 ↗
58. Guo, Z. et al. A flexible neural implant with ultrathin substrate for low-invasive brain-computer interface applications. Microsyst. Nanoeng. 8, 133 (2022).10.1038/s41378-022-00464-1 ↗
59. Shen, K. et al. Nanocomposite conductive hydrogels with Robust elasticity and multifunctional responsiveness for flexible sensing and wound monitoring. Mater. Horiz. 10, 2096–2108 (2023).10.1039/D3MH00192J ↗
60. Zhao, L. et al. On-demand contact-mode switchable cerebral cortex biosensors enhanced by magnetic actuation. ACS Appl. Mater. Interfaces 17, 20671–20684 (2025).10.1021/acsami.4c21235 ↗
61. Roy, A. et al. A highly stretchable, conductive, and transparent bioadhesive hydrogel as a flexible sensor for enhanced real-time human health monitoring. Adv. Mater. 36, e2404225 (2024).10.1002/adma.202404225 ↗
62. Zhai, Q. & Cheng, W. Soft and stretchable electrochemical biosensors. Mater. Today Nano 7, 100041 (2019).10.1016/j.mtnano.2019.100041 ↗
63. Hu, B. et al. Ultrathin crystalline silicon–based omnidirectional strain gauges for implantable/wearable characterization of soft tissue biomechanics. Sci. Adv. 10, eadp8804 (2024).10.1126/sciadv.adp8804 ↗
64. Deo, K. A. et al. Nanoengineered ink for designing 3 d printable flexible bioelectronics. ACS Nano 16, 8798–8811 (2022).10.1021/acsnano.1c09386 ↗
65. Wang, C., Sani, E. S. & Gao, W. Wearable bioelectronics for chronic wound management. Adv. Funct. Mater. 32 https://doi.org/10.1002/adfm.202111022 (2022).10.1002/adfm.202111022 ↗
66. Shao, Y. et al. Multi-functional, conformal systems with ultrathin crystalline-silicon-based bioelectronics for characterization of intraocular pressure and ocular surface temperature. Biosens. Bioelectron. 267, 116786 (2025).10.1016/j.bios.2024.116786 ↗
67. Su, X. et al. Integrated wearable sensors with bending/stretching selectivity and extremely enhanced sensitivity derived from agarose-based ionic conductor and its 3D-shaping. Chem. Eng. J. 389, 124503 (2020).10.1016/j.cej.2020.124503 ↗
68. Brooks, A. K., Chakravarty, S., Ali, M. & Yadavalli, V. K. Kirigami-inspired biodesign for applications in healthcare. Adv. Mater. 34, e2109550 (2022).10.1002/adma.202109550 ↗
69. Gideon, O., Samuel, H. S. & Okino, I. A. Biocompatible materials for next-generation biosensors. Discov. Chem. 1, 34 (2024).10.1007/s44371-024-00042-6 ↗
70. Ashok, A. et al. Flexible nanoarchitectonics for biosensing and physiological monitoring applications. Small 19, e2204946 (2023).10.1002/smll.202204946 ↗
71. Bae, W. G. et al. Enhanced skin adhesive patch with modulus-tunable composite micropillars. Adv. Health. Mater. 2, 109–113 (2013).10.1002/adhm.201200098 ↗
72. Choi, S., Lee, H., Ghaffari, R., Hyeon, T. & Kim, D. H. Recent advances in flexible and stretchable bio-electronic devices integrated with nanomaterials. Adv. Mater. 28, 4203–4218 (2016).10.1002/adma.201504150 ↗
73. Ling, H., Liu, S., Zheng, Z. & Yan, F. Organic flexible electronics. Small Methods 2, 1800070 (2018).10.1002/smtd.201800070 ↗
74. Choi, C. K., English, A. E., Jun, S. I., Kihm, K. D. & Rack, P. D. An endothelial cell compatible biosensor fabricated using optically thin indium tin oxide silicon nitride electrodes. Biosens. Bioelectron. 22, 2585–2590 (2007).10.1016/j.bios.2006.10.006 ↗
75. Miao, J. & Fan, T. Flexible and stretchable transparent conductive graphene-based electrodes for emerging wearable electronics. Carbon 202, 495–527 (2023).10.1016/j.carbon.2022.11.018 ↗
76. Liu, X. et al. Bioinspired, microstructured silk fibroin adhesives for flexible skin sensors. ACS Appl Mater. Interfaces 12, 5601–5609 (2020).10.1021/acsami.9b21197 ↗
77. Kim, D. H. et al. Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics. Nat. Mater. 9, 511–517 (2010).10.1038/nmat2745 ↗
78. Shi, Z. et al. Silk-enabled conformal multifunctional bioelectronics for investigation of spatiotemporal epileptiform activities and multimodal neural encoding/decoding. Adv. Sci. 6, 1801617 (2019).10.1002/advs.201801617 ↗
79. Sang, M., Kim, K., Shin, J. & Yu, K. J. Ultra-thin flexible encapsulating materials for soft bio-integrated electronics. Adv. Sci. 9, e2202980 (2022).10.1002/advs.202202980 ↗
80. Bovone, G., Dudaryeva, O. Y., Marco-Dufort, B. & Tibbitt, M. W. Engineering hydrogel adhesion for biomedical applications via chemical design of the junction. ACS Biomater. Sci. Eng. 7, 4048–4076 (2021).10.1021/acsbiomaterials.0c01677 ↗
81. Li, Y., Veronica, A., Ma, J. & Nyein, H. Y. Y. Materials, structure, and interface of stretchable interconnects for wearable bioelectronics. Adv. Mater. 37, e2408456 (2025).10.1002/adma.202408456 ↗
82. Morikawa, Y. et al. Ultrastretchable kirigami bioprobes. Adv. Health. Mater. 7, 1701100 (2018).10.1002/adhm.201701100 ↗
83. Han, W. B. et al. Ultra-stretchable and biodegradable elastomers for soft, transient electronics. Nat. Commun. 14, 2263 (2023).
84. Wu, H., Huang, Y., Xu, F., Duan, Y. & Yin, Z. Energy harvesters for wearable and stretchable electronics: from flexibility to stretchability. Adv. Mater. 28, 9881–9919 (2016).10.1002/adma.201602251 ↗
85. Xu, R. et al. Kirigami-inspired, highly stretchable micro-supercapacitor patches fabricated by laser conversion and cutting. Microsyst. Nanoeng. 4, 36 (2018).10.1038/s41378-018-0036-z ↗
86. Xiao, Y. et al. High-adhesive flexible electrodes and their manufacture: a review. Micromachines 12, 1505 (2021).10.3390/mi12121505 ↗
87. Zhang, Y. Stretchable Bioelectronics for Medical Devices and Systems (eds John A. R., Roozbeh, G. & Kim, D. H.) 53–68 (Springer International Publishing, 2016).10.1007/978-3-319-28694-5_3 ↗
88. Yuan, C. et al. Bionic design and performance of electrode for bioelectrical signal monitoring. Adv. Mater. Interfaces 9, 2200532 (2022).10.1002/admi.202200532 ↗
89. Yeh, C. et al. Bioinspired shark skin-based liquid metal triboelectric nanogenerator for self-powered gait analysis and long-term rehabilitation monitoring. Nano Energy 104, 107852 (2022).10.1016/j.nanoen.2022.107852 ↗
90. Narasimhan, V. et al. Multifunctional biophotonic nanostructures inspired by the longtail glasswing butterfly for medical devices. Nat. Nanotechnol. 13, 512–519 (2018).10.1038/s41565-018-0111-5 ↗
91. Lan, T. et al. Treefrog-inspired flexible electrode with high permeability, stable adhesion, and robust durability. Adv. Mater. 36, e2404761 (2024).10.1002/adma.202404761 ↗
92. Pettinelli, S. et al. High-performance bioelectronic tongue for the simultaneous analysis of phenols, sugars and organic acids in wines. J. Sci. Food Agric. 105, 1430–1438 (2025).10.1002/jsfa.13174 ↗
93. Khan, M. R., Khalilian, A. & Kang, S. W. A high sensitivity idc-electronic tongue using dielectric/sensing membranes with solvatochromic dyes. Sensors 16, 668 (2016).10.3390/s16050668 ↗
94. Pal, S., Kumar, D., Ulucan-Karnak, F., Narang, J. & Shukla, S. K. Bio-inspired electronic sensors for healthcare applications. Chem. Eng. J. 499, 155894 (2024).10.1016/j.cej.2024.155894 ↗
95. Alam, F. et al. Prospects for additive manufacturing in contact lens devices. Adv. Eng. Mater. 23. https://doi.org/10.1002/adem.202000941 (2020).10.1002/adem.202000941 ↗
96. Chen, Y. et al. A biochemical sensor with continuous extended stability in vivo. Nat. Biomed. Eng. 9, 1517–1530 (2025).10.1038/s41551-025-01389-6 ↗
97. Liu, Y. et al. Soft and elastic hydrogel-based microelectronics for localized low-voltage neuromodulation. Nat. Biomed. Eng. 3, 58–68 (2019).10.1038/s41551-018-0335-6 ↗
98. Zhao, K., Yuan, Y., Wang, S. & Cui, L. Effect of parylene coating on the performance of implantable pressure sensor. IEEE Sens. J. 24, 24593–24599 (2024).10.1109/JSEN.2024.3410538 ↗
99. Hashemi, S. et al. Ultra-sensitive wireless capacitive nanocomposite-based pressure sensors for health monitoring. Adv. Mater. Technol. 10, e01316 (2025).10.1002/admt.202501316 ↗
100. Li, Z. et al. An all-solid-state fluorinated ion-conductive elastomer with outstanding mechanical properties and high environmental stability for flexible electronics. Chem. Eng. J. 505, 159437 (2025).10.1016/j.cej.2025.159437 ↗