Abstract
Wearable devices with skin-like mechanical properties enable continuous monitoring of the human body. However, wearable device design has mainly focused on recording superficial signals from the skin thus far, which can only reveal limited information about health and disease. Deep-tissue signals, for example, electrophysiologic, metabolic, circulatory, thermal and mechanical signals, often have stronger correlation with disease and can predict the onset of symptoms. In this Review, we discuss the engineering of soft wearable devices that can sense signals in deep tissues. We highlight electrical, electromagnetic, thermal and mechanical sensing approaches, investigating sensing mechanisms, device designs, fabrication processes and sensing performance, with a focus on penetration depth and temporal and spatial resolutions in the human body. Finally, we discuss remaining challenges in the field and highlight strategies to further improve penetration depth and specificity, accuracy and system-level integration.
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References
Ray, T. R. et al. Bio-integrated wearable systems: a comprehensive review. Chem. Rev. 119, 5461–5533 (2019).
Lee, G.-H. et al. Multifunctional materials for implantable and wearable photonic healthcare devices. Nat. Rev. Mater. 5, 149–165 (2020). This review discusses multifunctional materials and healthcare applications for wearable optical sensors.
Someya, T. & Amagai, M. Toward a new generation of smart skins. Nat. Biotechnol. 37, 382–388 (2019).
Kim, J., Campbell, A. S., de Ávila, B. E.-F. & Wang, J. Wearable biosensors for healthcare monitoring. Nat. Biotechnol. 37, 389–406 (2019).
Wang, C., Wang, C., Huang, Z. & Xu, S. Materials and structures toward soft electronics. Adv. Mater. 30, 1801368 (2018).
Ates, H. C., Yetisen, A. K., Güder, F. & Dincer, C. Wearable devices for the detection of COVID-19. Nat. Electron. 4, 13–14 (2021).
Quer, G. et al. Wearable sensor data and self-reported symptoms for COVID-19 detection. Nat. Med. 27, 73–77 (2021).
Mishra, T. et al. Pre-symptomatic detection of COVID-19 from smartwatch data. Nat. Biomed. Eng. 4, 1208–1220 (2020).
Kim, D. H. et al. Epidermal electronics. Science 333, 838–843 (2011).
Lim, H. R. et al. Advanced soft materials, sensor integrations, and applications of wearable flexible hybrid electronics in healthcare, energy, and environment. Adv. Mater. 32, 1901924 (2020).
Gambhir, S. S., Ge, T. J., Vermesh, O., Spitler, R. & Gold, G. E. Continuous health monitoring: an opportunity for precision health. Sci. Transl Med. 13, eabe5383 (2021).
Jung, J., Lee, J., Lee, J. & Kim, Y. T. A smartphone-based U-Healthcare system for real-time monitoring of acute myocardial infarction. Int. J. Commun. Syst. 28, 2311–2325 (2015).
Pu, Z. et al. A thermal activated and differential self-calibrated flexible epidermal biomicrofluidic device for wearable accurate blood glucose monitoring. Sci. Adv. 7, eabd0199 (2021).
Huang, X., Yeo, W.-H., Liu, Y. & Rogers, J. A. Epidermal differential impedance sensor for conformal skin hydration monitoring. Biointerphases 7, 52 (2012).
Anastasova, S. et al. A wearable multisensing patch for continuous sweat monitoring. Biosens. Bioelectron. 93, 139–145 (2017).
Inamori, G. et al. Neonatal wearable device for colorimetry-based real-time detection of jaundice with simultaneous sensing of vitals. Sci. Adv. 7, eabe3793 (2021).
Kim, J. et al. Miniaturized battery-free wireless systems for wearable pulse oximetry. Adv. Funct. Mater. 27, 1604373 (2017).
Gao, L. et al. Epidermal photonic devices for quantitative imaging of temperature and thermal transport characteristics of the skin. Nat. Commun. 5, 4938 (2014).
Nyein, H. Y. Y. et al. A wearable patch for continuous analysis of thermoregulatory sweat at rest. Nat. Commun. 12, 1823 (2021).
Webb, R. C. et al. Epidermal devices for noninvasive, precise, and continuous mapping of macrovascular and microvascular blood flow. Sci. Adv. 1, e1500701 (2015).
Dagdeviren, C. et al. Conformable amplified lead zirconate titanate sensors with enhanced piezoelectric response for cutaneous pressure monitoring. Nat. Commun. 5, 4496 (2014).
Yang, S. et al. “Cut-and-paste” manufacture of multiparametric epidermal sensor systems. Adv. Mater. 27, 6423–6430 (2015).
Wang, Y. et al. Wearable and highly sensitive graphene strain sensors for human motion monitoring. Adv. Funct. Mater. 24, 4666–4670 (2014).
Zhao, Y. et al. Highly sensitive flexible strain sensor based on threadlike spandex substrate coating with conductive nanocomposites for wearable electronic skin. Smart Mater. Struct. 28, 035004 (2019).
Landsberg, L., Young, J. B., Leonard, W. R., Linsenmeier, R. A. & Turek, F. W. Do the obese have lower body temperatures? A new look at a forgotten variable in energy balance. Trans. Am. Clin. Climatol. Assoc. 120, 287–295 (2009).
Leon, L. R. & Helwig, B. G. Heat stroke: role of the systemic inflammatory response. J. Appl. Physiol. 109, 1980–1988 (2010).
Chaudhry, R., Miao, J. H. & Rehman, A. Physiology, Cardiovascular (StatPearls, 2020).
Buchner, T. On the physical nature of biopotentials, their propagation and measurement. Physica A 525, 85–95 (2019).
Mahmood, M. et al. Fully portable and wireless universal brain–machine interfaces enabled by flexible scalp electronics and deep learning algorithm. Nat. Mach. Intell. 1, 412–422 (2019).
Xu, S. et al. Soft microfluidic assemblies of sensors, circuits, and radios for the skin. Science 344, 70–74 (2014).
Huang, Z. et al. Three-dimensional integrated stretchable electronics. Nat. Electron. 1, 473–480 (2018).
Gharibans, A. A. et al. Artifact rejection methodology enables continuous, noninvasive measurement of gastric myoelectric activity in ambulatory subjects. Sci. Rep. 8, 5019 (2018).
Searle, A. & Kirkup, L. A direct comparison of wet, dry and insulating bioelectric recording electrodes. Physiol. Meas. 21, 271–283 (2000).
Krieger, K. J. et al. Development and evaluation of 3D-printed dry microneedle electrodes for surface electromyography. Adv. Mat. Technol. 5, 2000518 (2020).
Lee, S. & Kruse, J. Biopotential electrode sensors in ECG/EEG/EMG systems. Analog Devices https://www.analog.com/en/technical-articles/biopotential-electrode-sensors-ecg-eeg-emg.html (2008).
Ha, S. et al. in Wearable Sensors 2nd edn (ed. Sazonov, E.) 163–199 (Elsevier, 2021).
Chi, Y. M., Jung, T.-P. & Cauwenberghs, G. Dry-contact and noncontact biopotential electrodes: methodological review. IEEE Rev. Biomed. Eng. 3, 106–119 (2010). This review introduces skin–electrode coupling mechanisms and highlights recent developments in dry and non-contact biopotential sensors.
Yao, S. & Zhu, Y. Nanomaterial-enabled dry electrodes for electrophysiological sensing: a review. JOM 68, 1145–1155 (2016).
Zhang, L. et al. Fully organic compliant dry electrodes self-adhesive to skin for long-term motion-robust epidermal biopotential monitoring. Nat. Commun. 11, 4683 (2020).
Rivnay, J. et al. Structural control of mixed ionic and electronic transport in conducting polymers. Nat. Commun. 7, 11287 (2016).
Liu, J. et al. A novel dry-contact electrode for measuring electroencephalography signals. Sens. Actuators A 294, 73–80 (2019).
Wang, Y. et al. Robust, self-adhesive, reinforced polymeric nanofilms enabling gas-permeable dry electrodes for long-term application. Proc. Natl Acad. Sci. USA 118, e2111904118 (2021).
Shad, E. H. T., Molinas, M. & Ytterdal, T. Impedance and noise of passive and active dry eeg electrodes: a review. IEEE Sens. J. 20, 14565–14577 (2020).
Lv, J. et al. Printable elastomeric electrodes with sweat-enhanced conductivity for wearables. Sci. Adv. 7, eabg8433 (2021).
Ershad, F. et al. Ultra-conformal drawn-on-skin electronics for multifunctional motion artifact-free sensing and point-of-care treatment. Nat. Commun. 11, 3823 (2020).
Chen, X. et al. Fabric-substrated capacitive biopotential sensors enhanced by dielectric nanoparticles. Nano Res. 14, 3248–3252 (2021).
Forvi, E. et al. Preliminary technological assessment of microneedles-based dry electrodes for biopotential monitoring in clinical examinations. Sens. Actuators A 180, 177–186 (2012).
Srivastava, A. K., Bhartia, B., Mukhopadhyay, K. & Sharma, A. Long term biopotential recording by body conformable photolithography fabricated low cost polymeric microneedle arrays. Sens. Actuators A 236, 164–172 (2015).
Dabbagh, S. R. et al. 3D-printed microneedles in biomedical applications. Iscience 24, 102012 (2020).
Hedrich, T., Pellegrino, G., Kobayashi, E., Lina, J.-M. & Grova, C. Comparison of the spatial resolution of source imaging techniques in high-density EEG and MEG. Neuroimage 157, 531–544 (2017).
Wang, K. et al. Stretchable dry electrodes with concentric ring geometry for enhancing spatial resolution in electrophysiology. Adv. Healthc. Mater. 6, 1700552 (2017).
Makeyev, O. & Besio, W. G. Improving the accuracy of Laplacian estimation with novel variable inter-ring distances concentric ring electrodes. Sensors 16, 858 (2016).
Victorino, J. A. et al. Imbalances in regional lung ventilation: a validation study on electrical impedance tomography. Am. J. Respir. Crit. Care Med. 169, 791–800 (2004).
Isaacson, D., Mueller, J. L., Newell, J. C. & Siltanen, S. Imaging cardiac activity by the D-bar method for electrical impedance tomography. Physiol. Meas. 27, S43–S50 (2006).
Soni, N. K., Hartov, A., Kogel, C., Poplack, S. P. & Paulsen, K. D. Multi-frequency electrical impedance tomography of the breast: new clinical results. Physiol. Meas. 25, 301 (2004).
Tidswell, T., Gibson, A., Bayford, R. H. & Holder, D. S. Three-dimensional electrical impedance tomography of human brain activity. Neuroimage 13, 283–294 (2001).
Cheney, M., Isaacson, D. & Newell, J. C. Electrical impedance tomography. SIAM Rev. 41, 85–101 (1999).
Khan, T. A. & Ling, S. H. Review on electrical impedance tomography: artificial intelligence methods and its applications. Algorithms 12, 88 (2019).
Barth, A., Harrach, B., Hyvönen, N. & Mustonen, L. Detecting stochastic inclusions in electrical impedance tomography. Inverse Probl. 33, 115012 (2017).
Kelley, C. T. Solving Nonlinear Equations with Newton’s Method (SIAM, 2003).
Adler, A. & Holder, D. S. Electrical Impedance Tomography: Methods, History and Applications (CRC, 2004). This book describes the background science, reconstruction principles and clinical applications of electrical impedance tomography.
Yan, W., Hong, S. & Chaoshi, R. Optimum design of electrode structure and parameters in electrical impedance tomography. Physiol. Meas. 27, 291–306 (2006).
Rezanejad Gatabi, Z., Mohammadpour, R., Rezanejad Gatabi, J., Mirhoseini, M. & Sasanpour, P. A novel composite gold/gold nanoparticles/carbon nanotube electrode for frequency-stable micro-electrical impedance tomography. J. Mater. Sci. Mater. Electron. 31, 10803–10810 (2020).
Oh, T. I. et al. Flexible electrode belt for EIT using nanofiber web dry electrodes. Physiol. Meas. 33, 1603–1616 (2012).
Zhang, X. & Zhong, Y. A silver/silver chloride woven electrode with convex based on electrical impedance tomography. J. Text. Inst. 112, 1067–1079 (2021).
de Castro Martins, T. et al. A review of electrical impedance tomography in lung applications: theory and algorithms for absolute images. Annu. Rev. Control 48, 442–471 (2019).
Sola, J. et al. Non-invasive monitoring of central blood pressure by electrical impedance tomography: first experimental evidence. Med. Biol. Eng. Comput. 49, 409–415 (2011).
Romsauerova, A. et al. Multi-frequency electrical impedance tomography (EIT) of the adult human head: initial findings in brain tumours, arteriovenous malformations and chronic stroke, development of an analysis method and calibration. Physiol. Meas. 27, S147 (2006).
Wang, Q. et al. Exploring respiratory motion tracking through electrical impedance tomography. IEEE Trans. Instrum. Meas. 70, 1–12 (2021).
Metherall, P., Barber, D. C., Smallwood, R. H. & Brown, B. H. Three-dimensional electrical impedance tomography. Nature 380, 509–512 (1996).
Graham, B. & Adler, A. Electrode placement configurations for 3D EIT. Physiol. Meas. 28, S29–S44 (2007).
Lipani, L. et al. Non-invasive, transdermal, path-selective and specific glucose monitoring via a graphene-based platform. Nat. Nanotechnol. 13, 504–511 (2018). This article describes an electrode array with millimetre-sized elements for glucose monitoring, which significantly improves the spatial resolution of reverse iontophoresis.
Jain, S. M., Pandey, K., Lahoti, A. & Rao, P. K. Evaluation of skin and subcutaneous tissue thickness at insulin injection sites in Indian, insulin naïve, type-2 diabetic adult population. Indian J. Endocrinol. Metab. 17, 864–870 (2013).
Yang, Y. & Gao, W. Wearable and flexible electronics for continuous molecular monitoring. Chem. Soc. Rev. 48, 1465–1491 (2019).
Bandodkar, A. J. et al. Tattoo-based noninvasive glucose monitoring: a proof-of-concept study. Anal. Chem. 87, 394–398 (2015).
Sieg, A., Guy, R. H. & Delgado-Charro, M. B. Electroosmosis in transdermal iontophoresis: implications for noninvasive and calibration-free glucose monitoring. Biophys. J. 87, 3344–3350 (2004).
Chen, Y. et al. Skin-like biosensor system via electrochemical channels for noninvasive blood glucose monitoring. Sci. Adv. 3, e1701629 (2017).
Gowers, S. A. et al. Development of a minimally invasive microneedle-based sensor for continuous monitoring of β-lactam antibiotic concentrations in vivo. ACS Sens. 4, 1072–1080 (2019).
Yang, B., Fang, X. & Kong, J. Engineered microneedles for interstitial fluid cell-free DNA capture and sensing using iontophoretic dual-extraction wearable patch. Adv. Funct. Mater. 30, 2000591 (2020).
Wang, Z. et al. Microneedle patch for the ultrasensitive quantification of protein biomarkers in interstitial fluid. Nat. Biomed. Eng. 5, 64–76 (2021).
Lee, C.-K. et al. Non-invasive and transdermal measurement of blood uric acid level in human by electroporation and reverse iontophoresis. Int. J. Nanomed. 5, 991–997 (2010).
Cengiz, E. & Tamborlane, W. V. A tale of two compartments: interstitial versus blood glucose monitoring. Diabetes Technol. Ther. 11, S-11–S-16 (2009).
Giri, T. K., Chakrabarty, S. & Ghosh, B. Transdermal reverse iontophoresis: a novel technique for therapeutic drug monitoring. J. Control. Release 246, 30–38 (2017).
Gade, R. & Moeslund, T. B. Thermal cameras and applications: a survey. Mach. Vis. Appl. 25, 245–262 (2014).
Carpes, F. P. et al. Insights on the use of thermography in human physiology practical classes. Adv. Physiol. Educ. 42, 521–525 (2018).
Best, S. R. in 2011 International Workshop on Antenna Technology 90–93 (IEEE, 2011).
Rossmann, C. & Haemmerich, D. Review of temperature dependence of thermal properties, dielectric properties, and perfusion of biological tissues at hyperthermic and ablation temperatures. Crit. Rev. Biomed. Eng. 42, 467–492 (2014).
Chen, L. Y. et al. Continuous wireless pressure monitoring and mapping with ultra-small passive sensors for health monitoring and critical care. Nat. Commun. 5, 5028 (2014).
Roshni, S. B., Jayakrishnan, M., Mohanan, P. & Surendran, K. P. Design and fabrication of an E-shaped wearable textile antenna on PVB-coated hydrophobic polyester fabric. Smart Mater. Struct. 26, 105011 (2017).
Wang, Y. et al. Flexible RFID tag metal antenna on paper-based substrate by inkjet printing technology. Adv. Funct. Mater. 29, 1902579 (2019).
Tsolis, A., Whittow, W. G., Alexandridis, A. A. & Vardaxoglou, J. Embroidery and related manufacturing techniques for wearable antennas: challenges and opportunities. Electronics 3, 314–338 (2014).
Cluff, K. et al. Passive wearable skin patch sensor measures limb hemodynamics based on electromagnetic resonance. IEEE Trans. Biomed. Eng. 65, 847–856 (2017).
Stauffer, P. R. et al. Stable microwave radiometry system for long term monitoring of deep tissue temperature. Proc. SPIE Int. Soc. Opt. Eng. 8584, 227–237 (2013).
Costanzo, S. & Cioffi, V. in Information Technology and Systems. ICITS 2020 (eds Rocha, Á. et al.) 607–612 (Springer, 2020).
El Gharbi, M., Fernández-García, R., Ahyoud, S. & Gil, I. A review of flexible wearable antenna sensors: design, fabrication methods, and applications. Materials 13, 3781 (2020).
Lee, J. et al. Neural recording and stimulation using wireless networks of microimplants. Nat. Electron. 4, 604–614 (2021).
Dong, Z., Li, Z., Yang, F., Qiu, C.-W. & Ho, J. S. Sensitive readout of implantable microsensors using a wireless system locked to an exceptional point. Nat. Electron. 2, 335–342 (2019).
Boutry, C. M. et al. Biodegradable and flexible arterial-pulse sensor for the wireless monitoring of blood flow. Nat. Biomed. Eng. 3, 47–57 (2019).
Yoo, S. et al. Wireless power transfer and telemetry for implantable bioelectronics. Adv. Healthc. Mater. 10, 2100614 (2021). This review introduces approaches to retrieve deep-tissue signals and deliver power using wearable antennas and electromagnetic transmission.
Karimi, M. J., Schmid, A. & Dehollain, C. Wireless power and data transmission for implanted devices via inductive links: a systematic review. IEEE Sens. J. 21, 7145–7161 (2021).
Gutruf, P. et al. Fully implantable optoelectronic systems for battery-free, multimodal operation in neuroscience research. Nat. Electron. 1, 652–660 (2018).
Laqua, D., Just, T. & Husar, P. in 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology 1437–1440 (IEEE, 2010).
Burton, A. et al. Wireless, battery-free, and fully implantable electrical neurostimulation in freely moving rodents. Microsyst. Nanoeng. 7, 62 (2021).
Ausra, J. et al. Wireless, battery-free, subdermally implantable platforms for transcranial and long-range optogenetics in freely moving animals. Proc. Natl Acad. Sci. USA 118, e2025775118 (2021).
Agrawal, D. R. et al. Conformal phased surfaces for wireless powering of bioelectronic microdevices. Nat. Biomed. Eng. 1, 0043 (2017).
Lee, J. et al. in 2018 IEEE Biomedical Circuits and Systems Conference (IEEE, 2018).
Bahramiabarghouei, H. et al. Flexible 16 antenna array for microwave breast cancer detection. IEEE Trans. Biomed. Eng. 62, 2516–2525 (2015).
Zhang, H. et al. Wireless, battery-free optoelectronic systems as subdermal implants for local tissue oximetry. Sci. Adv. 5, eaaw0873 (2019).
Tremper, K. K. Pulse oximetry. Chest 95, 713–715 (1989).
Weissleder, R. & Ntziachristos, V. Shedding light onto live molecular targets. Nat. Med. 9, 123–128 (2003).
Cohen, L., Salzberg, B. & Grinvald, A. Optical methods for monitoring neuron activity. Annu. Rev. Neurosci. 1, 171–182 (1978).
Anderson, R. R. & Parrish, J. A. The optics of human skin. J. Invest. Dermatol. 77, 13–19 (1981).
Zonios, G. et al. Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection. J. Biomed. Opt. 13, 014017 (2008).
Lister, T., Wright, P. A. & Chappell, P. H. Optical properties of human skin. J. Biomed. Opt. 17, 90901 (2012).
Maeda, Y., Sekine, M. & Tamura, T. The advantages of wearable green reflected photoplethysmography. J. Med. Syst. 35, 829–834 (2011).
Maruo, K., Tsurugi, M., Tamura, M. & Ozaki, Y. In vivo noninvasive measurement of blood glucose by near-infrared diffuse-reflectance spectroscopy. Appl. Spectrosc. 57, 1236–1244 (2003).
Higurashi, E., Sawada, R. & Ito, T. An integrated laser blood flowmeter. J. Light. Technol. 21, 591–595 (2003).
Zhang, H. et al. Biocompatible light guide-assisted wearable devices for enhanced UV light delivery in deep skin. Adv. Funct. Mater. 31, 2100576 (2021).
Temko, A. Accurate heart rate monitoring during physical exercises using PPG. IEEE Trans. Biomed. Eng. 64, 2016–2024 (2017).
Kim, J. et al. Battery-free, stretchable optoelectronic systems for wireless optical characterization of the skin. Sci. Adv. 2, e1600418 (2016).
Lázaro, J., Gil, E., Bailón, R., Mincholé, A. & Laguna, P. Deriving respiration from photoplethysmographic pulse width. Med. Biol. Eng. Comput. 51, 233–242 (2013).
Avci, P. et al. Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring. Semin. Cutan. Med. Surg. 32, 41–52 (2013).
Mickle, A. D. et al. A wireless closed-loop system for optogenetic peripheral neuromodulation. Nature 565, 361–365 (2019).
Choi, S. et al. Highly flexible and efficient fabric-based organic light-emitting devices for clothing-shaped wearable displays. Sci. Rep. 7, 6424 (2017).
Kim, J.-H. & Park, J.-W. Intrinsically stretchable organic light-emitting diodes. Sci. Adv. 7, eabd9715 (2021).
Ash, C., Dubec, M., Donne, K. & Bashford, T. Effect of wavelength and beam width on penetration in light-tissue interaction using computational methods. Lasers Med. Sci. 32, 1909–1918 (2017).
Okamoto, K. Fundamentals of Optical Waveguides (Academic, 2006).
Shabahang, S., Kim, S. & Yun, S. H. Light-guiding biomaterials for biomedical applications. Adv. Funct. Mater. 28, 1706635 (2018).
Choi, M. et al. Light-guiding hydrogels for cell-based sensing and optogenetic synthesis in vivo. Nat. Photonics 7, 987–994 (2013).
Chung, S. H., Mehta, R., Tromberg, B. J. & Yodh, A. G. Non-invasive measurement of deep tissue temperature changes caused by apoptosis during breast cancer neoadjuvant chemotherapy: a case study. J. Innov. Opt. Health Sci. 4, 361–372 (2011).
Pesonen, E. et al. The focus of temperature monitoring with zero-heat-flux technology (3M Bair-Hugger): a clinical study with patients undergoing craniotomy. J. Clin. Monit. Comput. 33, 917–923 (2019).
Gao, X. et al. A photoacoustic patch for three-dimensional imaging of hemoglobin and core temperature. Preprint at Research Square https://doi.org/10.21203/rs.3.rs-558432/v1 (2021).
Tian, L. et al. Flexible and stretchable 3ω sensors for thermal characterization of human skin. Adv. Funct. Mater. 27, 1701282 (2017). This article reports a stretchable device using thermal modulation to interrogate tissue conductivity.
Qiu, L., Ouyang, Y., Feng, Y., Zhang, X. & Wang, X. In vivo skin thermophysical property testing technology using flexible thermosensor-based 3ω method. Int. J. Heat Mass Transf. 163, 120550 (2020).
Hattori, Y. et al. Multifunctional skin-like electronics for quantitative, clinical monitoring of cutaneous wound healing. Adv. Healthc. Mater. 3, 1597–1607 (2014).
Kurz, A. Physiology of thermoregulation. Best Pract. Res. Clin. Anaesthesiol. 22, 627–644 (2008).
Lim, C. L., Byrne, C. & Lee, J. K. Human thermoregulation and measurement of body temperature in exercise and clinical settings. Ann. Acad. Med. Singap. 37, 347 (2008).
Yamakage, M. & Namiki, A. Deep temperature monitoring using a zero-heat-flow method. J. Anesthesia 17, 108–115 (2003).
Huang, M., Tamura, T., Chen, W. & Kanaya, S. Evaluation of structural and thermophysical effects on the measurement accuracy of deep body thermometers based on dual-heat-flux method. J. Therm. Biol. 47, 26–31 (2015).
Feng, J., Zhou, C., He, C., Li, Y. & Ye, X. Development of an improved wearable device for core body temperature monitoring based on the dual heat flux principle. Physiol. Meas. 38, 652 (2017).
Huang, M., Tamura, T., Tang, Z., Chen, W. & Kanaya, S. Structural optimization of a wearable deep body thermometer: from theoretical simulation to experimental verification. J. Sensors 2016, 4828093 (2016).
Zhang, Y. et al. Theoretical and experimental studies of epidermal heat flux sensors for measurements of core body temperature. Adv. Healthc. Mater. 5, 119–127 (2016).
West, N., Cooke, E., Morse, D., Merchant, R. N. & Görges, M. Zero-heat-flux core temperature monitoring system: an observational secondary analysis to evaluate agreement with naso-/oropharyngeal probe during anesthesia. J. Clin. Monit. Comput. 34, 1121–1129 (2019).
Brajkovic, D. & Ducharme, M. B. Confounding factors in the use of the zero-heat-flow method for non-invasive muscle temperature measurement. Eur. J. Appl. Physiol. 94, 386–391 (2005).
Fang, J., Zhou, C. & Ye, X. in IOP Conference Series: Materials Science and Engineering Vol. 667 (IOP, 2019).
Shi, Y. et al. Functional soft composites as thermal protecting substrates for wearable electronics. Adv. Funct. Mater. 29, 1905470 (2019).
Dames, C. & Chen, G. 1ω, 2ω, and 3ω methods for measurements of thermal properties. Rev. Sci. Instrum. 76, 124902 (2005).
Wang, H. & Sen, M. Analysis of the 3-omega method for thermal conductivity measurement. Int. J. Heat Mass Transf. 52, 2102–2109 (2009).
Dagdeviren, C. et al. Conformal piezoelectric energy harvesting and storage from motions of the heart, lung, and diaphragm. Proc. Natl Acad. Sci. USA 111, 1927–1932 (2014).
Cotur, Y. et al. Stretchable composite acoustic transducer for wearable monitoring of vital signs. Adv. Funct. Mater. 30, 1910288 (2020).
Wang, F. et al. A flexible skin-mounted wireless acoustic device for bowel sounds monitoring and evaluation. Sci. China Inf. Sci. 62, 202402 (2019).
Bosco, C. et al. Adaptive respsonses of human skeletal muscle to vibration exposure. Clin. Physiol. 19, 183–187 (1999).
Tao, L. Q. et al. An intelligent artificial throat with sound-sensing ability based on laser induced graphene. Nat. Commun. 8, 14579 (2017).
Li, W. et al. Nanogenerator-based dual-functional and self-powered thin patch loudspeaker or microphone for flexible electronics. Nat. Commun. 8, 15310 (2017).
Song, E. et al. Miniaturized electromechanical devices for the characterization of the biomechanics of deep tissue. Nat. Biomed. Eng. 5, 759–771 (2021).
Dagdeviren, C. et al. Conformal piezoelectric systems for clinical and experimental characterization of soft tissue biomechanics. Nat. Mater. 14, 728–736 (2015).
Fan, X. et al. Ultrathin, rollable, paper-based triboelectric nanogenerator for acoustic energy harvesting and self-powered sound recording. ACS Nano 9, 4236–4243 (2015).
Lee, H. S. et al. Flexible inorganic piezoelectric acoustic nanosensors for biomimetic artificial hair cells. Adv. Funct. Mater. 24, 6914–6921 (2014).
Nayeem, M. O. G. et al. All-nanofiber-based, ultrasensitive, gas-permeable mechanoacoustic sensors for continuous long-term heart monitoring. Proc. Natl Acad. Sci. USA 117, 7063–7070 (2020). This article describes an ultrasensitive, nanofibre-based, passive vibration sensor for continuous cardiac sensing.
Gupta, P., Wen, H., Di Francesco, L. & Ayazi, F. Detection of pathological mechano-acoustic signatures using precision accelerometer contact microphones in patients with pulmonary disorders. Sci. Rep. 11, 13427 (2021).
Hu, Y. & Xu, Y. in 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society 694–697 (IEEE, 2012).
Lee, K. et al. Mechano-acoustic sensing of physiological processes and body motions via a soft wireless device placed at the suprasternal notch. Nat. Biomed. Eng. 4, 148–158 (2020).
Liu, Y. et al. Epidermal mechano-acoustic sensing electronics for cardiovascular diagnostics and human-machine interfaces. Sci. Adv. 2, e1601185 (2016).
Gupta, P. et al. Precision wearable accelerometer contact microphones for longitudinal monitoring of mechano-acoustic cardiopulmonary signals. NPJ Digit. Med. 3, 19 (2020).
Yang, C. & Tavassolian, N. An independent component analysis approach to motion noise cancelation of cardio-mechanical signals. IEEE Trans. Biomed. Eng. 66, 784–793 (2018).
Yu, X. et al. Needle-shaped ultrathin piezoelectric microsystem for guided tissue targeting via mechanical sensing. Nat. Biomed. Eng. 2, 165–172 (2018).
Yu, X. et al. Skin-integrated wireless haptic interfaces for virtual and augmented reality. Nature 575, 473–479 (2019).
Maccabi, A. et al. Quantitative characterization of viscoelastic behavior in tissue-mimicking phantoms and ex vivo animal tissues. PLoS ONE 13, e0191919 (2018).
Shung, K. K. Diagnostic Ultrasound: Imaging and Blood Flow Measurements (CRC, 2005).
Hu, H. et al. Stretchable ultrasonic transducer arrays for three-dimensional imaging on complex surfaces. Sci. Adv. 4, eaar3979 (2018). This article reports a stretchable ultrasound array device that can conform to nondevelopable surfaces for reconstructing 3D structures located deep underneath the surface.
Li, Z. et al. Broadband gradient impedance matching using an acoustic metamaterial for ultrasonic transducers. Sci. Rep. 7, 42863 (2017).
Huang, H. & Paramo, D. Broadband electrical impedance matching for piezoelectric ultrasound transducers. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 58, 2699–2707 (2011).
Wang, C. et al. Continuous monitoring of deep-tissue haemodynamics with stretchable ultrasonic phased arrays. Nat. Biomed. Eng. 5, 749–758 (2021). This article introduces the design of a skin-conformal ultrasonic phased array to sense haemodynamic signals in deep tissue.
Roy, O., Mahaut, S. & Casula, O. in AIP Conference Proceedings 908–914 (American Institute of Physics, 2002).
Frankle, R. S. & Rose, D. N. in Nondestructive Evaluation of Aging Maritime Applications 51–59 (SPIE, 1995).
Wang, C. et al. Monitoring of the central blood pressure waveform via a conformal ultrasonic device. Nat. Biomed. Eng. 2, 687–695 (2018).
Sempionatto, J. R. et al. An epidermal patch for the simultaneous monitoring of haemodynamic and metabolic biomarkers. Nat. Biomed. Eng. 5, 737–748 (2021).
Peng, C., Chen, M., Sim, H. K., Zhu, Y. & Jiang, X. in 15th International Conference on Nano/Micro Engineered and Molecular System 143–146 (IEEE, 2020).
AlMohimeed, I., Turkistani, H. & Ono, Y. In 2013 IEEE International Ultrasonics Symposium 1137–1140 (IEEE, 2013).
Pang, D.-C. & Chang, C.-M. Development of a novel transparent flexible capacitive micromachined ultrasonic transducer. Sensors 17, 1443 (2017).
Powell, D. & Hayward, G. Flexible ultrasonic transducer arrays for nondestructive evaluation applications. II. Performance assessment of different array configurations. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 43, 393–402 (1996).
Li, Z., Chen, A. I., Wong, L. L., Na, S. & Yeow, J. T. in 2015 IEEE International Ultrasonics Symposium (IEEE, 2015).
Qiu, Y. et al. Piezoelectric micromachined ultrasound transducer (PMUT) arrays for integrated sensing, actuation and imaging. Sensors 15, 8020–8041 (2015).
Lee, J.-H. et al. Flexible piezoelectric micromachined ultrasonic transducer (pMUT) for application in brain stimulation. Microsyst. Technol. 23, 2321–2328 (2017).
Duval, F. F., Dorey, R. A., Wright, R. W., Huang, Z. & Whatmore, R. W. Fabrication and modeling of high-frequency PZT composite thick film membrance resonators. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 51, 1255–1261 (2004).
Bowen, C., Bradley, L., Almond, D. & Wilcox, P. Flexible piezoelectric transducer for ultrasonic inspection of non-planar components. Ultrasonics 48, 367–375 (2008).
Pashaei, V. et al. Flexible body-conformal ultrasound patches for image-guided neuromodulation. IEEE Trans. Biomed. Circuits Syst. 14, 305–318 (2019).
Kato, Y. et al. Large-area flexible ultrasonic imaging system with an organic transistor active matrix. IEEE Trans. Electron. Devices 57, 995–1002 (2010).
Chen, Z. et al. High-frequency ultrasonic imaging with lead-free (Na,K)(Nb,Ta)O3 single crystal. Ultrason. Imaging 39, 348–356 (2017).
Hettiarachchi, N., Ju, Z. & Liu, H. in 2015 IEEE International Conference on Systems, Man, and Cybernetics 1415–1420 (IEEE, 2017).
Yang, X., Yan, J. & Liu, H. Comparative analysis of wearable a-mode ultrasound and SEMG for muscle-computer interface. IEEE Trans. Biomed. Eng. 67, 2434–2442 (2019).
Stadler, R. W., Taylor, J. A. & Lees, R. S. Comparison of B-mode, M-mode and echo-tracking methods for measurement of the arterial distension waveform. Ultrasound Med. Biol. 23, 879–887 (1997).
Shung, K. K. Diagnostic Ultrasound: Imaging and Blood Flow Measurements (CRC, 2005).
Ding, H. et al. A pulsed wave Doppler ultrasound blood flowmeter by PMUTs. J. Microelectromech. Syst. 30, 680–682 (2021).
Jiang, J. & Hall, T. J. A coupled subsample displacement estimation method for ultrasound-based strain elastography. Phys. Med. Biol. 60, 8347 (2015).
Kallel, F. & Ophir, J. A least-squares strain estimator for elastography. Ultrason. Imaging 19, 195–208 (1997).
Francois Dord, J. et al. in Ultrasound Elastography for Biomedical Applications and Medicine (eds Nenadic, I. Z. et al.) 129–142 (Wiley, 2018).
Papadacci, C., Bunting, E. A. & Konofagou, E. E. 3D quasi-static ultrasound elastography with plane wave in vivo. IEEE Trans. Med. Imaging 36, 357–365 (2016).
Alam, S. K., Ophir, J. & Varghese, T. Elastographic axial resolution criteria: an experimental study. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 47, 304–309 (2000).
Ramalli, A., Basset, O., Cachard, C., Boni, E. & Tortoli, P. Frequency-domain-based strain estimation and high-frame-rate imaging for quasi-static elastography. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 59, 817–824 (2012).
Chen, H., Varghese, T., Rahko, P. S. & Zagzebski, J. Ultrasound frame rate requirements for cardiac elastography: experimental and in vivo results. Ultrasonics 49, 98–111 (2009).
Schrank, F. et al. Real-time MR elastography for viscoelasticity quantification in skeletal muscle during dynamic exercises. Magn. Reson. Med. 84, 103–114 (2020).
Fink, M. Time reversal of ultrasonic fields. I. Basic principles. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 39, 555–566 (1992).
Turner, B. L. et al. Ultrasound-powered implants: a critical review of piezoelectric material selection and applications. Adv. Healthc. Mater. 10, 2100986 (2021).
Sonmezoglu, S., Fineman, J. R., Maltepe, E. & Maharbiz, M. M. Monitoring deep-tissue oxygenation with a millimeter-scale ultrasonic implant. Nat. Biotechnol. 39, 855–864 (2021).
Shi, C., Costa, T., Elloian, J., Zhang, Y. & Shepard, K. L. A 0.065-mm3 monolithically-integrated ultrasonic wireless sensing mote for real-time physiological temperature monitoring. IEEE Trans. Biomed. Circuits Syst. 14, 412–424 (2020).
Weber, M. J. et al. A miniaturized single-transducer implantable pressure sensor with time-multiplexed ultrasonic data and power links. IEEE J. Solid-State Circuits 53, 1089–1101 (2018).
Jin, P. et al. A flexible, stretchable system for simultaneous acoustic energy transfer and communication. Sci. Adv. 7, eabg2507 (2021).
Lyu, W. et al. Flexible ultrasonic patch for accelerating chronic wound healing. Adv. Healthc. Mater. 10, 2100785 (2021).
Zhou, H. et al. Wearable ultrasound improves motor function in an MPTP mouse model of Parkinson’s disease. IEEE Trans. Biomed. Eng. 66, 3006–3013 (2019).
Xu, S. Closed-loop actuating and sensing epidermal systems. US Patent 16/093,820 (2017).
Manohar, S. & Razansky, D. Photoacoustics: a historical review. Adv. Opt. Photonics 8, 586–617 (2016).
& Lin, J. C. Microwave thermoacoustic tomographic (MTT) imaging. Phys. Med. Biol. 66, 10TR02 (2021).
Hin, J. et al. A flexible optoacoustic blood stethoscope for non-invasive multiparametric cardiovascular monitoring. Preprint at Research Square https://doi.org/10.21203/rs.3.rs-384531/v1 (2021).
Borcea, L. Electrical impedance tomography. Inverse Probl. 18, R99–R126 (2002).
Jibiki, T. Coded excitation medical ultrasound imaging. Igaku Butsuri 21, 136–141 (2001).
Isla, J. & Cegla, F. Coded excitation for pulse-echo systems. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 64, 736–748 (2017).
Beniczky, S., Karoly, P., Nurse, E., Ryvlin, P. & Cook, M. Machine learning and wearable devices of the future. Epilepsia 62, S116–S124 (2021).
Jaber, M. S. H. & Kazemi, A. Noise reduction of signals received from wearable sensors along with integrating their information with machine learning. EurAsian J. Biosci. 14, 5253–5259 (2020).
Zhang, B., Sodickson, D. K. & Cloos, M. A. A high-impedance detector-array glove for magnetic resonance imaging of the hand. Nat. Biomed. Eng. 2, 570–577 (2018).
Wang, J. et al. in 2020 IEEE Symposium on VLSI Circuits (IEEE, 2020).
Chen, K., Lee, H.-S. & Sodini, C. G. in 2014 Symposium on VLSI Circuits Digest of Technical Papers (IEEE, 2014).
Biggs, J. et al. A natively flexible 32-bit Arm microprocessor. Nature 595, 532–536 (2021).
Wang, S. et al. Skin electronics from scalable fabrication of an intrinsically stretchable transistor array. Nature 555, 83–88 (2018).
Lee, Y., Cha, S. H., Kim, Y.-W., Choi, D. & Sun, J.-Y. Transparent and attachable ionic communicators based on self-cleanable triboelectric nanogenerators. Nat. Commun. 9, 1804 (2018).
Niu, S. et al. A wireless body area sensor network based on stretchable passive tags. Nat. Electron. 2, 361–368 (2019).
Lin, M., Gutierrez, N.-G. & Xu, S. Soft sensors form a network. Nat. Electron. 2, 327–328 (2019).
Li, Z., Tian, X., Qiu, C.-W. & Ho, J. S. Metasurfaces for bioelectronics and healthcare. Nat. Electron. 4, 382–391 (2021).
Tian, X. et al. Wireless body sensor networks based on metamaterial textiles. Nat. Electron. 2, 243–251 (2019).
Lim, C. et al. Tissue-like skin-device interface for wearable bioelectronics by using ultrasoft, mass-permeable, and low-impedance hydrogels. Sci. Adv. 7, eabd3716 (2021).
Huang, D., Wang, H., Li, J., Chen, Y. & Li, Z. in 20th International Conference on Solid-State Sensors, Actuators and Microsystems & Eurosensors 298–301 (IEEE, 2019).
Liu, J., Jiang, L., Liu, H. & Cai, X. A bifunctional biosensor for subcutaneous glucose monitoring by reverse iontophoresis. J. Electroanal. Chem. 660, 8–13 (2011).
Alberto, J. et al. Fully untethered battery-free biomonitoring electronic tattoo with wireless energy harvesting. Sci. Rep. 10, 5539 (2020).
Choi, Y. S. et al. Fully implantable and bioresorbable cardiac pacemakers without leads or batteries. Nat. Biotechnol. 39, 1228–1238 (2021).
Choi, M., Humar, M., Kim, S. & Yun, S. H. Step-index optical fiber made of biocompatible hydrogels. Adv. Mater. 27, 4081–4086 (2015).
Schröder, H. et al. in Optoelectronic Integrated Circuits VIII 612407 (SPIE, 2006).
Manocchi, A. K., Domachuk, P., Omenetto, F. G. & Yi, H. Facile fabrication of gelatin-based biopolymeric optical waveguides. Biotechnol. Bioeng. 103, 725–732 (2009).
Hanada, Y., Sugioka, K. & Midorikawa, K. UV waveguides light fabricated in fluoropolymer CYTOP by femtosecond laser direct writing. Opt. Express 18, 446–450 (2010).
Liu, C.-H. & Kenny, T. W. A high-precision, wide-bandwidth micromachined tunneling accelerometer. J. Microelectromech. Syst. 10, 425–433 (2001).
Zhu, H.-T., Chen, Y., Xiong, Y.-F., Xu, F. & Lu, Y.-Q. A flexible wireless dielectric sensor for noninvasive fluid monitoring. Sensors 20, 174 (2020).
Choi, A. & Shin, H. Photoplethysmography sampling frequency: pilot assessment of how low can we go to analyze pulse rate variability with reliability? Physiol. Meas. 38, 586 (2017).
Guschlbauer, M. et al. Zero-heat-flux thermometry for non-invasive measurement of core body temperature in pigs. PLoS ONE 11, e0150759 (2016).
Sharma, S., Huang, Z., Rogers, M., Boutelle, M. & Cass, A. E. Evaluation of a minimally invasive glucose biosensor for continuous tissue monitoring. Anal. Bioanal. Chem. 408, 8427–8435 (2016).
Ren, L. et al. Fabrication of flexible microneedle array electrodes for wearable bio-signal recording. Sensors 18, 1191 (2018).
Acknowledgements
The authors gratefully acknowledge financial support from the National Institutes of Health grants 1R21EB025521-01, 1R21EB027303-01A1 and 3R21EB027303-02S1. The authors thank S. Xiang for valuable discussions and constructive feedback on manuscript preparation, and all authors whose work is reviewed in this article.
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M.L., H.H. and S.Z. contributed equally to the literature review, figure design, manuscript writing and discussion of content. S.X. conceived the article. All authors contributed to reviewing and editing the manuscript.
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Lin, M., Hu, H., Zhou, S. et al. Soft wearable devices for deep-tissue sensing. Nat Rev Mater 7, 850–869 (2022). https://doi.org/10.1038/s41578-022-00427-y
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DOI: https://doi.org/10.1038/s41578-022-00427-y
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