Stretchable multimodal photonic sensor for wearable healthcare monitoring

Stretchable multimodal photonic sensor for wearable healthcare monitoring | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Stretchable multimodal photonic sensor for wearable healthcare monitoring Jingjing Guo, Jialin Tuo, Zhuozhou Li, Xiaoyan Guo, Yanyan Chen, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4548546/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Stretchable sensors that can conformally interface with the skins for wearable and real-time monitoring of skin deformations, temperature, and sweat biomarkers are of profound significance for early prediction, diagnosis, and treatment of diseases. Integration of multiple modalities in a single stretchable sensor to simultaneously detect these stimuli would be beneficial for more sophisticated understanding of human physiology, but yet, has not been achieved. Here, we report a stretchable multimodal photonic sensor capable of simultaneously detecting and discriminating strain deformations, temperature, and sweat pH in a single sensor architecture. The multimodal sensing abilities are enabled by realization of multiple sensing mechanisms in a hydrogel-coated polydimethylsiloxane (PDMS) optical fiber (HPOF), featured with high flexibility, stretchability, and biocompatibility. The integrated mechanisms are designed to operate at distinct wavelengths to facilitate stimuli decoupling, and adopt a ratiometric detection strategy for improved robustness and accuracy. To achieve simplicity on sensor interrogation, spectrally-resolved multiband emissions are generated upon the excitation of a single-wavelength laser based on upconversion luminescence (UCL) and radiative energy transfer (RET) processes. We show that the sensor allows for simultaneous and sensitive detection of strain deformations, temperature, and pH levels in the physiological range with fast responsiveness, robust repeatability, and reliability. Furthermore, we demonstrate proof-of-concept applications of the sensor for simultaneously detecting artery pulse or cardiopulmonary activities, along with skin temperature and sweat pH with negligible crosstalk, enabling a new paradigm of wearable multiparameter monitoring in healthcare. Physical sciences/Materials science/Materials for devices/Sensors and biosensors Physical sciences/Optics and photonics/Applied optics/Optical sensors Physical sciences/Optics and photonics/Applied optics/Optoelectronic devices and components Physical sciences/Materials science/Soft materials/Polymers Wearable photonic devices multimodal sensor stretchable optics healthcare monitoring Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Skin is the largest organ of human body that not only serves as a protective barrier against external environment, but also acts as a diagnostic interface rich with valuable physiological information originating from dermis/epidermis, blood vessels, and inner organs. Wearable sensor technologies provide an intriguing possibility to interface with the skins for timely prevention, diagnosis, and treatment of diseases, through non-invasive continuous monitoring of those physiological signals [ 1 – 3 ]. In particular, for comfortable wearing and accurate signal detection, wearable sensors should be ideally flexible, stretchable and biocompatible so as to ensure stable, conformal, and long-term attachment onto skin even during body movements [ 4 ]. Moreover, multifunctionalities are also essential considerations to achieve wearable sensors with multiparameter monitoring capabilities, which would enable more comprehensive assessment of an individual’s health status [ 5 , 6 ]. To date, a variety of stretchable multifunctional sensors have already been developed for mechanical (e.g., strain and pressure), thermal, and chemical sensing, with exploitation of resistive [ 7 – 10 ], capacitive [ 11 – 13 ], electrochemical [ 14 , 15 ], or optical sensing mechanisms [ 16 – 20 ]. Application examples of these sensors include on-skin continuous monitoring of vital signs (e.g., pulse rate, body temperature, and respiration) [ 7 , 11 , 17 ], body motion [ 8 , 18 ], and sweat biomarkers [ 15 , 21 ]. Despite their impressive performances and potential applications, most of these sensors rely on electrical or optical properties of functional materials that transform various stimuli into a coupled output signal (resistance, capacitance, or light intensity), making it difficult to discriminate different stimuli. Alternatively, the incorporation of multiple sensors with different sensing modalities into a hybrid sensing platform could enable simultaneous multiparameter monitoring by transducing individual stimuli into separated signals [ 21 – 24 ]. However, different types of sensors may considerably differ in terms of material constitute, structure, and mechanics, posing fundamental barriers for seamless integration of such sensors without compromising structural integrity, stretchability, and functionality. It’s highly desirable, yet considerably challenging to develop wearable multimodal sensors with stimulus discriminability in simple structural architecture (ideally a single sensor unit), while integrating high flexibility, stretchability, and biocompatibility. In this work, we present a flexible, stretchable, and biocompatible multimodal photonic sensor that can simultaneously detect and differentiate mechanical, thermal, and chemical stimuli in single sensor architecture. The integrated sensing modalities are enabled by incorporating three distinct sensing mechanisms in a stretchable hydrogel-coated polydimethylsiloxane (PDMS) optical fiber (HPOF), which shows multi-stimuli responsiveness to strain, temperature, and pH. The three mechanisms share the same HPOF, but operate at different wavelengths to facilitate stimuli decoupling. To achieve system simplicity and compactness for sensor interrogation, lanthanide-based upconversion nanoparticles (Ln-UCNPs) are assembled in the core of HPOF to produce multiband emissions upon single laser excitation based on combined mechanisms of upconversion luminescence (UCL) and radiative energy transfer (RET). The hydrogel coating of the HPOF can assist in constructing a step-index profile for efficient light guiding due to its relatively low refractive index (RI). More importantly, this coating also provides porous hydrophilic matrices that allow facile chemical modifications with functional molecules, and promote analyte exchanges between the hydrogel and aqueous surroundings. The sensing HPOF is also encapsulated in an elastic skin-adhesive patch with elastic polymers and fabric to achieve stable and conformal contact with human skins. Mechanical and cell viability tests were performed to validate the flexibility, stretchability, and biocompatibility of the encapsulated sensor device. Furthermore, we thoroughly investigate the sensing mechanisms and performances of the multimodal sensor upon different stimuli, and as a proof of concept, demonstrate the utility of the sensor for simultaneous monitoring of a person’s heartbeat, respiration, body temperature, and sweat pH in real time. Results and discussion Design, fabrication, and biomechanical compatibility of the multimodal sensor As illustrated in Fig. 1 a, the multimodal photonic sensor enables simultaneous on-skin monitoring of various physiological signals associated with strain, temperature, and pH, providing comprehensive and personalized healthcare information for improved disease diagnosis and treatment. The multimodal sensor primarily consisted of a core/coating HPOF that was encapsulated between two elastic polyurethane layers of a skin-adhesive base and a water-proof protective cover, together with cotton fabric tape to secure the ends of the HPOF. The skin-adhesive base layer was designed with a narrow slit to enable direct contact of the HPOF with skin for sweat monitoring. Silica multimode optical fibers (MMFs) were pigtailed to the HPOF with their central axis aligned for laser coupling and emission collection. The core of the HPOF was made from composites of Ln-UCNPs and PDMS elastomers, and fabricated by approaches of molding and thermally curing (see Figure S1 a, and more details in Materials and Method). Transparent, low-RI polyacrylamide (PAM) hydrogels were chosen as the coating of the HPOF, which endowed the fiber with step-index light guidance and meanwhile introduced abundant active amino groups for functional modifications. Since PDMS is hydrophobic, and the PAM hydrogels are hydrophilic polymers inflated with water, it is hardly to create strong adhesion between the PDMS and PAM via direct physical coating. To achieve a robust hydrogel coating, we chemically anchored the PAM hydrogels on PDMS by using an interfacial interpenetration strategy [ 25 ]. Briefly, the PDMS core was first treated with an ethanol-based organic solution containing hydrophobic photoinitiators (benzophenone) that would swell the PDMS, impelling diffusion and absorption of the photoinitiators into the core surface (Figure S1 b). Afterwards, the treated core was immersed in a PAM precursor that contains hydrophilic photoinitiators (Irgacure 2959). Upon ultraviolet (UV) exposure, the hydrophilic photoinitiators induced polymerization of the PAM monomers while the hydrophobic initiators enabled the PAM networks to covalently crosslink with the PDMS chains, resulting in the formation of a thin hydrogel layer toughly bonded on the PDMS surface. It was found that the hydrogel coating could endure vigorous deformation induced by stretching or scratching with no observable crack or delamination, demonstrating excellent mechanical robustness (Figure S2). The length of the HPOF was optimized at ~ 1.5 cm from the profile of emission decay along the fiber length (Figure S3). The multimodal photonic sensor integrates three distinct sensing mechanisms in a single HPOF to achieve simultaneous detection of strain, temperature, and pH (Fig. 1 b, c). Upon near-infrared (NIR) excitation, the incorporated Ln-UCNPs in the HPOF generate multiband visible emissions via the upconversion process for versatile interrogation of different sensing mechanisms. The UCNPs were comprised of a luminescent core of NaYF 4 :Yb,Er covered by an inert shell of NaYF 4 , which could protect the core from luminescence quenching caused by surface defects and surrounding environments (Figure S4a) [ 26 ]. The morphology and particle size of the UCNPs were examined by transmission electron microscopy (TEM) and scanning electron microscope (SEM), where the UCNPs were uniformly distributed with hexagonal shape and diameter of ~ 57 nm (Fig. 1 d, and Figure S4b-d). The Er 3+ ions of the UCNPs possessed a pair of thermally coupled energy levels ( 2 H 11/2 and 4 S 3/2 ) [ 27 ], and the emission bands originating from these levels showed thermal-dependent behaviors, enabling sensitive temperature measurement from changes of the emission intensities. The PAM coating of the HPOF offers abundant amino groups allow facile chemical modifications with various functional molecules. Hereby, we functionalized the hydrogel coating with pH sensitive fluorescent dyes (pHrodo Red) to achieve pH responsiveness. The pHrodo Red was selected because of the substantial overlap between its absorption spectrum and the emission bands of the UCNPs, thereby enabling radiative energy transfer (RET) from the UCNPs to the pHrodo Red for pH determination (Figure S4e). Besides pH sensitivity, the loaded dye molecules also endowed the HPOF with wavelength-dependent absorption characteristics that could be further harnessed to quantify strain stimuli from the absorption changes of light propagating along the HPOF. Figure 1 e shows a cross-section image of the HPOF (core/coating, 500 µm/553 µm) with red dyes loaded in the hydrogel coating. To avoid leakage of the dye molecules from the coating, the pHrodo Red modified with succinimidyl (NHS) ester was immobilized by covalent bonding to the amino groups of the hydrogel matrix (Figure S5). The sensing HPOF was ultimately encapsulated in an elastic skin-adhesive patch to ensure stable adhesion on skin. Figures 1 f and g show the images of the HPOF-based multimodal sensor conformally attached to the human skin, where the sensor could be freely stretched, compressed, and twisted without any failure. Extensive mechanical test was further conducted that confirmed the skin-like softness (Young’s modulus of 1.14 Mpa) and high stretchability (> 60%) of the sensor (Figure S6). Biological safety is critical for wearable sensors especially when in direct contact with human skins. The multimodal sensor was proven to be nontoxic and biocompatible as verified by a cell viability test with human neuroblastoma cells (SK-N-SH), where a high cell viability of > 98% was observed after 72 h of culture in the presence of the sensor (Figure S7). Figure 1 h shows a typical emission spectrum of the sensor, indicating four separate emission bands generated upon excitation of a single 980-nm laser. The emission at 600 nm was produced by RET from the UCNPs to the pHrodo Red, while the emissions centered at 525, 545, and 655 nm were attributed to the Er 3+ transitions of 2 H 11/2 → 4 I 15/2 , 4 S 3/2 →4I 15/2 , and 4 F 9/2 → 4 I 15/2 levels, respectively (Fig. 2 a). With the distinctive design of materials, structures, and functionalities above, the multimodal sensor holds great promises as a wearable safety device for multi-stimuli sensing in long-term care settings. Temperature sensing performances of the multimodal sensor Temperature is one of the fundamental parameters in monitoring human activities and assessing body abnormalities [ 28 ]. To evaluate the feasibility of the multimodal sensor for temperature sensing, we characterized the temperature response of the sensor with a simplified optical setup as depicted in Figure S8. A fiber-coupled laser at a wavelength of 980 nm and an output power of 15 mW was launched into the sensor through the pigtailed silica MMFs, and the emissions were collected and guided to a compact spectrometer for spectral analysis. Figure 2 b shows the emission spectra of the sensor in response to different temperatures. Because of the thermal coupling of 2 H 11/2 and 4 S 3/2 levels in Er 3+ , the emissions at 525 nm and 545 nm were strongly temperature-dependent and the intensity ratio of these two emissions followed the well-known Boltzmann distribution given by [ 27 ]: $${I_{525}}/{I_{545}}=A\exp ( - \Delta E/kT)$$ 1 Where \({I_{525}}\) and \({I_{545}}\) are emission intensities arising from the transitions of 2 H 11/2 → 4 I 15/2 and 4 S 3/2 →4I 15/2 , respectively; is a constant; \(\Delta E\) denotes the energy gap between the 2 H 11/2 and 4 S 3/2 ; is the Boltzmann’s constant, and is the absolute temperature in the Kelvin scale. Figure 2 c shows a linear plot of \(\ln ({I_{525}}/{I_{545}})\) versus the inverse temperature ( \(1/T\) ) over the temperature range of 25 ℃ (3.35×10 − 3 K − 1 ) to 45 ℃ (3.14×10 − 3 K − 1 ), which agrees well with Eq. ( 1 ). The temperature sensitivity defined as the percent change in \(\ln ({I_{525}}/{I_{545}})\) per unit change in temperature, was calculated to be 0.8% ℃ −1 around 37 ℃ from the response curve, and the limit of detection (LOD) was about \(\pm\) 0.19 ℃, estimated from the noise standard deviation of the temperature readout (Figure S9a). The response speed of the sensor was then studied upon a step change in temperature, where the response and recovery times of the sensor were measured to 3 s and 4 s, respectively (Fig. 2 d). The highly sensitive and fast responding merits enabled the sensor to capture rapid subtle thermal signals produced by human activities such as nose breathing (Figure S9b). To evaluate the repeatability of the sensor, consecutive thermal cycling tests of heating and cooling were performed (Fig. 2 e). The sensor showed reversable and reproducible readout with the cyclic temperature changes, indicating stable and repeatable performances. We further validated the capability of the sensor to quantitatively detect dynamic thermal signals by a real-time temperature monitoring test, where the sensor was treated with water droplet of various temperatures (Fig. 2 f). Figure 2 g shows the temporal evolution of the droplet temperature measured by our sensor and a commercial IR camera. Notably, there was a high consistency between the temperature readout of our sensor and the signal obtained by the IR camera with a root mean square error (RMSE) of 0.46 ℃, demonstrating high reliability and accuracy in real-time temperature measurements. In addition, the influences of strain and pH stimuli on the temperature response of the sensor were also examined (Fig. 2 h). The sensor was treated with different stretching strains and pH, separately, while the applied temperature was kept constant. Remarkably, the temperature readout of the sensor was well maintained despite the changes of strain and pH, indicating high selectivity towards temperature among other stimuli. This unique feature was attributed to the ratiometric detection that made the temperature readout intrinsically self-calibrated and robust to other stimuli interferences. The above results demonstrate our sensor can be used for fast and quantitative temperature monitoring with high selectivity, accuracy, and repeatability. pH sensing performances of the sensor Epidermal pH is an important indicator of human health and illness that can be used for medical diagnosis and health monitoring. For example, the sweat pH of a healthy human normally ranges between 4.5–6.5, whereas the sweat of patients with cystic fibrosis is usually alkaline and can have a pH value beyond 8 [ 29 ]. For pH sensing, we immobilized pH-sensitive fluorescent dyes (pHrodo Red-NHS) into the PAM coating of the HPOF via covalent bonding. The porous nature of the hydrogel matrices facilitated rapid analyte exchanges between the HPOF and aqueous surroundings (e.g., sweat) through passive diffusion. The diffusion of hydrogen ions into the hydrogel coating promotes the protonation of the rhodamine chromophore, resulting in considerably increased fluorescence of the pHrodo Red in acidic pH (Fig. 3 a) [ 30 ]. Figure 3 b shows the emission spectra of the sensor tested with different pH solutions. It was found that the emission of the pHrodo Red at 600 nm was notably increased at lower pH, while the emission band at 650 nm was less affected. The RET process takes place due to the spectral overlap between the UCL emission at 545 nm and the absorption spectrum of the pHrodo Red (Figure S4e). The pH response of the sensor was calibrated in the range of pH 4.0-9.5 by ratiometric dual-wavelength measurements, where the intensity ratio of the pH-sensitive emission at 600 nm and the insensitive UCL emission at 545 nm as a reference signal was calculated (Fig. 3 c). Henderson-Hasselbalch equation was used for fitting of the responsive curve, which indicated an apparent p K a value of ~ 6.6, suitable for physiological pH monitoring. Besides, the sensor displayed a linear pH response with sensitivity of 27% pH − 1 over the pH range of 5.0-7.5, where a low LOD of \(\pm 0.09\) was achieved from the linear fitting (inset of Fig. 3 c). Figure 3 d shows the response of sensor under repeated pH tests, where the sensor exhibited a reversible and reproducible output over multiple cycles with negligible hysteresis. Selectivity is another crucial factor for practical sweat measurements due to the presence of other interference ions in sweat. As revealed in Fig. 3 e, the sensor had a high selectivity towards hydrogen ions over other dominant interference ions in sweat including K + and Na + , due to the selective protonation mechanism. The response time of the sensor to pH was about 34 s, which was sufficiently fast for use in sweat monitoring as the sweat pH generally varied on the order of minutes [ 31 ]. To test the dynamic performance of the sensor for pH determination, the sensor was continuously treated with droplet of different pH solutions. As shown in Fig. 3 f, the sensor exhibited a step-increased behavior in response to solutions of increased pH, and the sensor output was recovered after the pH was returned to the initial value, which validated the reliability of sensor for real-time pH monitoring. Furthermore, the effects of strain and temperature on the pH response of the sensor were investigated in Fig. 3 g. The sensor was kept in a pH 5 buffer solution, and meanwhile tested under various strains and temperatures. It was found that the pH readout was insensitive to strain but slightly affected by temperature. The temperature-dependent effect of the pH response was attributed to the temperature dependence of the fluorescence quantum yield, defined as the ratio of emitted photons to absorbed ones [ 32 ]. The pH response could be calibrated and corrected with the temperature readout to achieve high accuracy for practical use (Figure S10). Strain sensing performances of the sensor Accurate detection of skin strains is critical for a wide variety of applications ranging from healthcare monitoring, sport training to human-machine interfacing [ 33 – 35 ]. Sensitivity and stretchability are the key parameters determining the performance of strain sensors in wearable applications, especially in healthcare monitoring. A high sensitivity is required for monitoring subtle skin deformations caused by vital signs such as artery pulse and heartbeat, which typically induce a strain less than 1% [ 36 ]. Meanwhile, a high stretchability is demanded to enable high mechanical compliance with the elastic skin. We demonstrated highly sensitive strain sensing with the stretchable multimodal sensor by virtue of the wavelength-dependent absorption characteristics of the dye molecules. Upon excitation, the UCNPs generated UCL emissions that propagated in both forward and backward directions along the HPOF (Fig. 4 a, b). The backward emissions were absorbed by the dye molecules distributed in the fiber coating, leading to attenuated emissions detected at the front end. When stretched, the fiber length was increased, which prolonged the interaction length of the backward emission with the dye absorbers, resulting in enlarged absorption. Figure 4 c shows the transmission spectra of the HPOFs with/without dye loading, which confirmed the absorption effect of light propagating through the HPOF in presence of dye molecules. The emission spectra of the sensor under various strains were characterized as presented in Fig. 4 d. Upon stretching, the local stress deformed the coupling joint between the HPOF and the silica MMFs, and induced additional coupling loss that caused decreased intensities at all emission bands. To eliminate the absorption-independent loss effect, a dual-wavelength differential absorption method was employed, for which the emissions at 545 nm (near the absorption peak) and 655 nm (outside the absorption band) were chosen as the probing light and reference light, respectively. Figure 4 e shows the differential attenuation changes at the two wavelengths versus the applied strains ranging from 0–20%. As expected, the sensor displayed increased attenuation with the increasing strain due to the increased light absorption. Notably, the sensor could sensitively detect small-scale strains below 1% with high linearity ( \({{\text{R}}^2}=0.99\) ), and presented a LOD as low as \(\pm 0.07\%\) (inset of Fig. 4 e). The exceptional sensitivity of the sensor makes it a promising candidate to accurately detect subtle skin strains in health monitoring applications. The temporal readout of the sensor in response to step-increased strains was further investigated (Fig. 4 f). The sensor indicated an instant change of signal at each step of strain increase, and its readout was recovered once the loading strain was fully released. To evaluate the response speed, the sensor was loaded with a quasi-transient step strain of ~ 2% (Fig. 4 g). The response and recovery times of the sensor were measured to be 23 ms and 25 ms, which were fast enough to capture almost all the skin strain-related physiological signals (typically < 10 Hz). Figure 4 h shows the sensor readout under a cyclic loading-unloading test of different strains. The sensor exhibited a repeatable response to the sequence of loading-unloading cycles with negligible hysteresis or drift, indicating high stability and reproducibility. Moreover, the crosstalk effects of temperature and pH on the strain response of the multimodal sensor were analyzed under different temperature and pH conditions, where no strain was loaded. As shown in Fig. 4 i, the sensor maintained a stable strain readout at different temperatures in the physiological range of 30–40 ℃, indicating temperature insensitivity of the strain response. In contrast, the changes of pH induced an obvious drift in the strain readout attributed to the pH-dependent absorption of the pHrodo dye. To minimize the interference of pH, the strain readout could be calibrated from the pH value determined by the multimodal sensor as the pH response was not affected by strain. Alternatively, it might be more straightforward to retrieve the strain stimuli by filtering and frequency analysis since the strain-related vital signs possessed a signal frequency much higher than that of the skin pH. In addition, long-term stability of all the sensor readouts were verified by keeping the sensor at constant strain, temperature, and pH levels, where the readout changes were monitored every 24 h for 72 h (Figure S11). No obvious drift was observed in all readouts of the sensor during the monitoring period, suggesting a high stability in long-term operation. Real-time multiparameter monitoring of human health Benefitting from its high stretchability, favorable biocompatibility, and multimodal sensing capabilities, the sensor could be conformally attached onto the human skin for simultaneous monitoring of multiple sets of health indicators. As a proof-of-concept demonstration, the sensor was worn on the human wrist (male, 22 years old) with sweat on the skin to detect artery pulse, skin temperature, and sweat pH in real time (Fig. 5 a). Figure 5 b shows the real-time skin temperature and pH value measured with our sensor. The skin temperature and sweat pH were measured to be around 33.6 ℃ and 4.8, respectively, within the normal physiological ranges. A commercially available IR sensor and pH sensor were also employed to provide reference measurements. The measured results of our sensor were in good agreement with the commercial sensors (relative error < 2%), indicating a high accuracy of the sensor for wearable temperature and pH monitoring. Moreover, artery pulse on the wrist could be simultaneously detected from the strain readout after high-pass filtering (cut-off frequency, 0.1 Hz). The wrist pulse is a weak but crucial physiological signal that can reveal the health status of both heart and arteries. Figure 5 c shows the real-time artery pulse signal captured by the sensor, where each cycle of the pulse involved contraction and relaxation of the heart. The frequency of the pulse signal was observed to be 80 beats per min (bpm), in accordance with the normal range of pulse rates (60–100 bpm for healthy adults [ 37 ]). The inset of Fig. 5 c shows an enlarged view of a typical pulse waveform, where three distinct peaks featured as the percussion (P) wave, tidal (T) wave, and dicrotic (D) wave could be clearly distinguished. The percentage of the T wave height divided by P wave height is defined as the augmentation index (AI), a well-established indicator of arterial stiffness and vascular aging [ 38 ]. From the measured waveform, the AI was calculated to be 0.39, which was a characteristic value expected for a healthy 22-year-old male [ 39 ]. Apart from the wrist, the sensor was further attached onto the skin of chest to detect the chest-wall movement caused by cardiopulmonary activities, and also simultaneously monitor the body temperature and sweat pH (Fig. 5 d). Cardiopulmonary activity monitoring plays a critical role in evaluation of cardiac and pulmonary functions, promoting early detection and prevention of cardiovascular and pulmonary diseases such as atherosclerosis, heart failure, and asthma [ 40 , 41 ]. Abnormal respiratory rate (RR) and heart rate (HR) are often the early signs of serious cardiopulmonary disorders. Figure 5 e shows the original strain readout of the sensor in response to the chest movement. Periodic respiratory activity could be clearly recognized from the original signal, arising from vigorous stretching and releasing of the sensor upon exhaling and inhaling (inset of Fig. 5 e). In contrast, the cardiac activity was much weaker and submerged in the respiratory signal. The two signals could be separated in the frequency domain by filtering strategy due to the different frequency bands of respiration (0.1–0.5 Hz) and cardiac beat (0.8-2Hz). Figure 5 f shows the respiratory and heartbeat signals in the time domain decomposed after band-pass filtering. The obtained signals were further analyzed in the frequency domain by fast Fourier transform (FFT), which indicated a normal RR and HR of 13 bpm and 84 bpm, respectively, demonstrating great promise of our sensor for wearable cardiopulmonary monitoring in different healthcare and clinical settings. Furthermore, other vital indicators of health including skin temperature and sweat pH could be accurately detected from the calibrated temperature and pH readout. As validated in Fig. 5 g, the sensor could simultaneously and continuously monitor heartbeat, respiration, skin temperature, and sweat pH without any crosstalk, and the results showed good consistency with the reference data. To our knowledge, this is the first demonstration of simultaneous monitoring of cardiopulmonary activities, body temperature, and sweat biomarker with only a single sensor. Conclusions In summary, we have demonstrated a wearable multimodal photonic sensor that unite the merits of simultaneous multi-stimuli sensing including strain, temperature, and pH, as well as high flexibility, stretchability, and biocompatibility. The multimodal sensor was made by a stretchable HPOF that was constructed with a step-index light guidance profile. To achieve multi-stimuli sensing with stimulus discriminability, multiple sensing mechanisms were integrated in the HPOF with distinct operation wavelengths. Spectrally-resolved multiband emissions were generated based on the combined mechanisms of upconversion luminescence and RET, which enabled the interrogation of the sensor with a single laser diode. To enable conformal contact and adhesion to human skins, the fabricated HPOF was further encapsulated in an elastic skin-adhesive patch with elastic polymers and fabric. Detailed characterizations were performed that validated the high sensitivity, selectivity, and fast response of the sensor performances towards different stimuli. Furthermore, we demonstrated that the sensor enabled simultaneous and continuous monitoring of mechanical stimuli induced by artery pulsation or cardiopulmonary activities, along with skin temperature and sweat pH, providing thorough insights into the status of human health. We compared the major features of our sensor with previously reported wearable sensors in table S1 and S2. Our work appeared as the only design that implemented simultaneous mechanical, thermal, and chemical sensing in a single sensor structure, while achieving stimulus discriminability, stretchability, and biocompatibility. Moreover, the proposed sensor was also advantageous in aspects including response time, LOD, sensitivity, and electromagnetic interference (EMI) immunity as compared with others. Especially, EMI immunity is crucial for applications in clinical utility, and the intrinsic EMI immunity of the photonic sensor allows for stable and real-time monitoring of patient's physiological status with the presence of EMI-generating medical equipment such as MRI during therapeutic or diagnostic procedures. The hydrogel coating of the HPOF offers abundant active sites that facilitate versatile functional modification, making it possible to detect other sweat biomarkers with different functional molecules. The sensing modalities could be further expanded by using fluorophores with narrow band emissions such as quantum dots (QDs) instead of fluorescent dyes, which enables more stimuli to be spectrally encoded within the HPOF. Emission intensity ratios were employed to achieve robust sensing of different stimuli, for which a compact spectrometer was used to extract the emission intensities at specific wavelengths. For future miniaturization of the demodulation system, an electronic-photonic integrated circuits (EPICs) could be developed with on-chip light sources, spectral filters, photodetectors, and signal processing unit, benefitting from the well-developed integrated circuit technologies. Our sensor represents an important first step towards the realization of wearable multimodal sensors that integrate mechanical, thermal, and chemical sensing modalities for more comprehensive understanding of human physiology. Materials and Methods Fabrication of the Multimodal Photonic Sensor . The multimodal sensor primarily consisted of a core/coating HPOF that was loaded with core-shell NaYF 4 :Yb,Er@NaYF 4 UCNPs and pHrodo red in the core and coating, respectively. The core-shell UCNPs were synthesized according to a previously reported solvothermal strategy [ 42 , 43 ], and the as-obtained nanoparticles were dispersed in cyclohexane for further use. To fabricate the core of HPOF, precursor solution containing 3 wt% UCNPs was prepared by mixing with PDMS (Sylgard 184, Dow Corning) at base to curing agent ratio of 10:1. After vigorous stirring and carefully degassing, the precursor solution was injected into a polyethylene tube mold (inner diameter, 500 µm) via a syringe. Followed by thermal curing at 80°C for about 40 min, the polymerized fiber core was demolded through water pressure. For hydrogel coating, the fiber core was first cleaned with ethanol followed by drying at 80°C. Then, the cleaned fiber core was treated with an ethanol solution of benzophenone (10 wt%, Aladdin) for 1 min. After wipe removal of the excess solution, the fiber core was subsequently immersed in a hydrogel precursor prepared with 30 wt% acrylamide (Aladdin) and 1 wt% Irgacure 2959 (Aladdin) in deionized water. The hydrogel precursor was exposed to UV irradiation (365 nm, 5 mW cm − 2 ) for 50 min to photocrosslink the hydrogel monomer on the fiber core, and the obtained core/coating HPOF was rinsed with deionized water to remove additional unreacted reagents. To immobilize dye molecules into the hydrogel matrix, the HPOF was first immersed in a solution of pHrodo Red-NHS (5×10 − 3 wt%, ThermoFisher Scientific) for 1min, and then treated with NaHCO 3 (100 mM, pH 8.5) for 12 h. The resulting HPOF was finally rinsed with deionized water and stored in phosphate buffer (pH 7.4) for later use. For light coupling, silica MMFs were pigtailed to the fabricated HPOF and aligned along the central axes. The coupling joint of the fibers was protected with a loose tube and secured by UV glue. For skin attachment, the MMFs-pigtailed HPOF was further encapsulated in an elastic skin-adhesive patch by sandwiching it between two elastic polyurethane layers of a skin-adhesive base and a water-proof protective cover. Cotton fabric tape was used to secure the ends of the HPOF on the base layer, which was cut with a narrow slit (~ 0.2 cm width, 1.5 cm length) in the center to allow direct contact of the HPOF with skin. The size of the encapsulated sensor was 60 mm long by 24 mm wide by 0.6 mm thick. Interrogation Setup . A fiber-coupled laser at 980 nm (~ 15 mW) was launched into the multimodal sensor through the pigtailed silica MMFs, which were fiber bundles consisting of a single central fiber for laser excitation and six receiving fibers surrounding the central fiber for emission collection. Each of the fibers had a core/cladding diameter of 200/220 µm with a NA of 0.22. The backward emissions from the multimodal sensor were collected by the six receiving fibers and guided to a compact spectrometer (CCS100, Thorlabs) for spectral analysis. A short-pass filter at 850 nm was used prior to the spectrometer to eliminate the excitation laser. Instruments and Characterizations . TEM and SEM analyses of the UCNPs were performed with a JEM-2100F TEM (JOL) and a Gemini SEM 560 (ZEISS). The emission spectra of the UCNPs and the pHrodo Red were measured by a spectrometer (CCS100, Thorlabs) upon 980 nm and 532 nm excitations, respectively. The absorption spectrum of the pHrodo Red was measured using a UV-Vis-NIR spectrophotometer (UV-3600, Shimadzu). The transmission spectra of the HPOF were characterized by launching the fiber with a halogen light source (Ocean optics, HL-2000). The molecular components of the HPOF were investigated by Fourier transform infrared (FTIR) spectroscopy using a FTIR spectrometer (Nicolet 6700). Mechanical properties of the multimodal sensor were characterized by using a tensile machine (Handpi Instruments) equipped with a 10 N load cell. The thermal response of the sensor was studied by immersing the sensor in a water bath heated to discrete temperatures and the water temperature was read from a digital thermometer with a resolution of 0.1℃. To investigate the pH response, Tris HCl and Tris base (Aladdin) were used to prepare pH buffers with pH range of 4.0-10.5. For strain sensing characterization, the sensor was mounted and stretched by a translation stage (Thorlabs, 10 µm resolution). The loading strain was calculated as the deformed length divided by initial length of the sensor. Biocompatibility Assessment . Cell viability assays were performed to confirm the biocompatibility of the multimodal sensor. The human neuroblastoma cell line SK-N-SH cells were seeded on coverslips in 6-well plates, and cultured in presence of the sensor for 24 h, 48 h, and 72 h. The cells were then incubated with a mixed solution of Hoechst 33342 and PI (P0137, Beyotime), and imaged with a confocal fluorescence microscopy (Dragonfly, Andor). The microscopic images were quantified using ImageJ software. Cell viability was quantified by computing the ratio of the number of red nuclei to that of blue nuclei. Declarations Author contributions statement J.G., and L.X. conceived the idea. J.T., and Z. L. performed the experiments. J.T., J.G., R. C., and J.Z. analyzed the data. J.G., and J.T. wrote the original draft. X.G. and Y. C. assisted with the experiments. All authors contributed to the editing of the manuscript. Competing financial interests The authors declare no competing financial interests. Acknowledgements J.G. acknowledges the funding from the National Natural Science Foundation of China (No. 62175008) and the Fundamental Research Funds for the Central Universities. Data availability All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. References C. Xu, Y. Yang, W. Gao, Skin-interfaced sensors in digital medicine: from materials to applications. Matter 2, 1414–1445 (2020). A. K. Yetisen, J. L. Martinez-Hurtado, B. Ünal, A. Khademhosseini, H. Butt, Wearables in medicine. Adv. Mater. 30, 1706910 (2018). H. C. Ates, P. Q. Nguyen, L. Gonzalez-Macia, E. Morales-Narváez, F. Güder, J. J. Collins, C. Dincer, End-to-end design of wearable sensors. Nat. Rev. Mater. 7, 887–907 (2022). T. Q. Trung, N. E. Lee, Flexible and stretchable physical sensor integrated platforms for wearable human-activity monitoring and personal healthcare. Adv. Mater. 28, 4338–4372 (2016). G. H. Lee, H. Moon, H. Kim, G. H. Lee, W. Kwon, S. Yoo, D. Myung, S. H. Yun, Z. Bao, S. K. Hahn, Multifunctional materials for implantable and wearable photonic healthcare devices. Nat. Rev. Mater. 5, 149–165 (2020). T. Li, Y. Li, T. Zhang, Materials, structures, and functions for flexible and stretchable biomimetic sensors. Accounts Chem. Res. 52, 288–296 (2019). C. Pang, G. Y. Lee, T. I. Kim, S. M. Kim, H. N. Kim, S. H. Ahn, K. Y. Suh, A flexible and highly sensitive strain-gauge sensor using reversible interlocking of nanofibres. Nat. Mater. 11, 795–801 (2012). M. Cao, M. Leng, W. Pan, Y. Wang, S. Tan, Y. Jiao, S. Yu, S. Fan, T. Xu, T. Liu, L. Li, J. Su, 3D wearable piezoresistive sensor with waterproof and antibacterial activity for multimodal smart sensing. Nano Energy 112, 108492 (2023). S. Gong, X. Zhang, X. A. Nguyen, Q. Shi, F. Lin, S. Chauhan, Z. Ge, W. Cheng, Hierarchically resistive skins as specific and multimetric on-throat wearable biosensors. Nat. Nanotechnol. 18, 889–897 (2023). P. Wang, W. Yu, G. Li, C. Meng, S. Guo, Printable, flexible, breathable and sweatproof bifunctional sensors based on an all-nanofiber platform for fully decoupled pressure-temperature sensing application. Chem. Eng. J. 452, 139174 (2023) M. Kang, H. Jeong, S. W. Park, J. Hong, H. Lee, Y. Chae, S. Yang, J. H. Ahn, Wireless graphene-based thermal patch for obtaining temperature distribution and performing thermography. Sci. Adv. 8, eabm6693 (2022). S. Masihi, M. Panahi, D. Maddipatla, A. J. Hanson, A. K. Bose, S. Hajian, V. Palaniappan, B. B. Narakathu, B. J. Bazuin, M. Z. Atashbar, Highly sensitive porous PDMS-based capacitive pressure sensors fabricated on fabric platform for wearable applications. ACS Sens. 6, 938–949 (2021). X. Huang, L. Liu, Y. H. Lin, R. Feng, Y. Shen, Y. Chang, H. Zhao, High-stretchability and low-hysteresis strain sensors using origami-inspired 3D mesostructures. Sci. Adv. 9, eadh9799 (2023). A. Ghoorchian, M. Kamalabadi, M. Moradi, T. Madrakian, A. Afkhami, H. Bagheri, M. Ahmadi, H. Khoshsafar, Wearable potentiometric sensor based on Na 0.44 MnO 2 for non-invasive monitoring of sodium ions in sweat. Anal. Chem. 94, 2263–2270 (2022). M. Bariya, H. Y. Y. Nyein, A. Javey, Wearable sweat sensors. Nat. Electron. 1, 160–171 (2018). J. Guo, X. Liu, N. Jiang, A. K. Yetisen, H. Yuk, C. Yang, Prof. A. Khademhosseini, X. Zhao, S. H. Yun, Highly stretchable, strain sensing hydrogel optical fibers. Adv. Mater. 28, 10244 (2016). J. Guo, B. Zhou, C. Yang, Q. Dai, L. Kong, Stretchable and temperature-sensitive polymer optical fibers for wearable health monitoring. Adv. Funct. Mater. 29, 1902898 (2019). H. Bai, S. Li, J. Barreiros, Y. Tu, C. R. Pollock, R. F. Shepherd, Stretchable distributed fiber-optic sensors. Science 370, 848–852 (2020). M. Elsherif, F. Alam, A. E. Salih, B. AlQattan, A. K. Yetisen, H. Butt, Wearable bifocal contact lens for continual glucose monitoring integrated with smartphone readers. Small 17, 2102876 (2021). A. Leal-Junior, J. Guo, R. Min, A. J. Fernandes, A. Frizera, C. Marques, Photonic smart bandage for wound healing assessment. Photonics Res. 9, 272–280 (2021). S. Nakata, M. Shiomi, Y. Fujita, T. Arie, S. Akita, K. Takei, A wearable pH sensor with high sensitivity based on a flexible charge-coupled device. Nat. Electron. 1, 596–603. (2018). H. Zhao, K. O’Brien, S. Li, R. F. Shepherd, Optoelectronically innervated soft prosthetic hand via stretchable optical waveguides. Sci. Robot. 1, eaai7529 (2016). D. H. Kim, N. Lu, R. Ma, Y. S. Kim, R. H. Kim, S. Wang, J. Wu, S. M. Won, H. Tao, A. Islam, Epidermal Electronics. Science 333, 838–843 (2011). N.T. Tien, S. Jeon, D. I. Kim, T. Q. Trung, M. Jang, B. U. Hwang, K. E. Byun, J. Bae, E. Lee, J. B. H. Tok, A Flexible Bimodal Sensor Array for Simultaneous Sensing of Pressure and Temperature. Adv. Mater. 26, 796–804 (2014). Y. Yu, H. Yuk, G. A. Parada, Y. Wu, X. Liu, C. S. Nabzdyk, K. Youcef-Toumi, J. Zang, X. Zhao, Multifunctional “hydrogel skins” on diverse polymers with arbitrary shapes. Adv. Mater. 31, 1807101 (2019). M. Chen, Y. Ma, M. Li, Facile one-pot synthesis of hydrophilic NaYF 4 : Yb, Er@ NaYF 4 : Yb active-core/active-shell nanoparticles with enhanced upconversion luminescence. Mater. Lett. 114, 80–83 (2014). F. Vetrone, R. Naccache, A. Zamarrón, A. Juarranz de la Fuente, F. Sanz-Rodríguez, L. Martinez Maestro, E. M. Rodriguez, D. Jaque, J. G. Solé, J. A. Capobianco, Temperature sensing using fluorescent nanothermometers. ACS Nano 4, 3254–3258 (2010). T. Q. Trung, N. E. Lee, Flexible and stretchable physical sensor integrated platforms for wearable human-activity monitoring and personal healthcare. Adv. Mater. 28, 4338–4372 (2016). W. Dang, L. Manjakkal, W. T. Navara, L. Lorenzelli, V. Vinciguerra, R. Dahiya, Stretchable wireless system for sweat pH monitoring. Biosens. Bioelectron. 107, 192–202 (2018). R. Arppe, T. Näreoja, S. Nylund, L. Mattsson, S. Koho, J. M. Rosenholm, T. Soukka, M. Schäferling. Photon upconversion sensitized nanoprobes for sensing and imaging of pH. Nanoscale 6, 6837–6843 (2014). H. Y. Y. Nyein, W. Gao, Z. Shahpar, S. Emaminejad, S. Challa, K. Chen, H. M. Fahad, L. Tai, H. Ota, R. W. Davis, A. Javey, A wearable electrochemical platform for noninvasive simultaneous monitoring of Ca 2+ and pH. ACS Nano 10, 7216–7224 (2016). J. Ferguson, A. W. H. Mau, Spontaneous and stimulated emission from dyes. Spectroscopy of the neutral molecules of acridine orange, proflavine, and rhodamine B. Aust. J. Chem. 26, 1617–1624 (1973). D. Son, J. Lee, S. Qiao, R. Ghaffari, J. Kim, J. E. Lee, C. Song, S. J. Kim, D. J. Lee, S. W. Jun, S. Yang, M. Park, J. Shin, K. Do, M. Lee, K. Kang, C. S. Hwang, N. Lu, T. Hyeon, D. H. Kim, Multifunctional Wearable Devices for Diagnosis and Therapy of Movement Disorders. Nat. Nanotechnol. 9, 397–404 (2014). J. Guo, B. Zhou, R. Zong, L. Pan, X. Li, X. Yu, C. Yang, L. Kong, Q. Dai, Stretchable and highly sensitive optical strain sensors for human-activity monitoring and healthcare. ACS Appl. Mater. Interfaces 11, 33589–33598 (2019). M. Amjadi, K. U. Kyung, I. Park, M. Sitti, Stretchable, skin-mountable, and wearable strain sensors and their potential applications: a review. Adv. Funct. Mater. 26, 1678–1698 (2016). Y. R. Jeong, H. Park, S. W. Jin, S. Y. Hong, S. S. Lee, J. S. Ha, Highly stretchable and sensitive strain sensors using fragmentized graphene foam. Adv. Funct. Mater. 25, 4228–4236 (2015). J. Hart, Normal resting pulse rate ranges. J. Nurs. Educ. Pract. 5, 95–98 (2015). K. Kohara, Y. Tabara, A. Oshiumi, Y. Miyawaki, T. Kobayashi, T. Miki, Radial augmentation index: a useful and easily obtainable parameter for vascular aging. Am. J. Hypertens. 18, 11S-14S (2005). W. Nichols, Clinical Measurement of Arterial Stiffness Obtained from Noninvasive Pressure Waveforms. Am. J. Hypertens. 18, 3–10 (2005). A. Mizuno, S. Changolkar, M. S. Patel, Wearable devices to monitor and reduce the risk of cardiovascular disease: evidence and opportunities. Annu. Rev. Med. 72, 459–471 (2021). S. H. Li, B. S. Lin, C. A. Wang, C. T. Yang, B. S. Lin, Design of wearable and wireless multi-parameter monitoring system for evaluating cardiopulmonary function. Med. Eng. Phys. 47, 144–150 (2017). X. Zhu, W. Feng, J. Chang, Y. W. Tan, J. Li, M. Chen, Y. Sun, F. Li, Temperature-feedback upconversion nanocomposite for accurate photothermal therapy at facile temperature. Nat. Commun. 7, 1–10 (2016). Z. Li, Y. Zhang, An efficient and user-friendly method for the synthesis of hexagonal-phase NaYF4:Yb, Er/Tm nanocrystals with controllable shape and upconversion fluorescence. Nanotechnology 19, 345606 (2008). Additional Declarations There is NO Competing Interest. Supplementary Files SupportinginformationG.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4548546","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":315990730,"identity":"f5ffa9ef-0856-4748-aca2-8083a8befd16","order_by":0,"name":"Jingjing Guo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIiWNgGAWjYJACAwmDGjkDCJuZWC0Fx4xJ08LA8IE5cQPRWuQjkg8UWBiwpW+XSH74gaHCOrGB/ewBvFoMb6QlAP0ik7tzRpqxBMOZ9MQGnrwE/Fpm5BgAtbDlbrgB1MrYdjixQYLHgBgtzOkGN9I//2D8R4QWeQmIlgSDGzlmEowNRGgx4HkG8ssxw509b8osEo6lG7fx5BCwpT35mLHEnxp5c/b0zTc+1FjL9rOfIWDLAQY2YEhBQQIQs+FVD7KlgYEZGB+jYBSMglEwCvAAAL1SQYq1+zxGAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-3893-2319","institution":"Beihang University","correspondingAuthor":true,"prefix":"","firstName":"Jingjing","middleName":"","lastName":"Guo","suffix":""},{"id":315990731,"identity":"9caf291c-7470-4f90-927b-c01e149f2e1f","order_by":1,"name":"Jialin Tuo","email":"","orcid":"","institution":"Beihang University","correspondingAuthor":false,"prefix":"","firstName":"Jialin","middleName":"","lastName":"Tuo","suffix":""},{"id":315990732,"identity":"53e64531-17bb-46f2-baa1-1f7a3feb6260","order_by":2,"name":"Zhuozhou Li","email":"","orcid":"","institution":"Beihang University","correspondingAuthor":false,"prefix":"","firstName":"Zhuozhou","middleName":"","lastName":"Li","suffix":""},{"id":315990733,"identity":"4a227883-9224-4b36-8dad-301642ce276b","order_by":3,"name":"Xiaoyan Guo","email":"","orcid":"","institution":"Beihang University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyan","middleName":"","lastName":"Guo","suffix":""},{"id":315990734,"identity":"6b088c7f-67dc-4219-8ba8-0612f74c582b","order_by":4,"name":"Yanyan Chen","email":"","orcid":"","institution":"Beihang University","correspondingAuthor":false,"prefix":"","firstName":"Yanyan","middleName":"","lastName":"Chen","suffix":""},{"id":315990735,"identity":"a91d5fd6-085a-4981-a5db-09b328e3d3d2","order_by":5,"name":"Rong Cai","email":"","orcid":"","institution":"Beihang University","correspondingAuthor":false,"prefix":"","firstName":"Rong","middleName":"","lastName":"Cai","suffix":""},{"id":315990736,"identity":"0be7b0a3-20b0-4212-a937-c519bcec2a7e","order_by":6,"name":"Jing Zhong","email":"","orcid":"","institution":"Beihang University","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Zhong","suffix":""},{"id":315990737,"identity":"9ea391d6-5dd4-44eb-8c16-386c3a4ec729","order_by":7,"name":"Lijun Xu","email":"","orcid":"","institution":"Beihang University","correspondingAuthor":false,"prefix":"","firstName":"Lijun","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2024-06-08 02:40:08","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-4548546/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4548546/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":61464233,"identity":"94141fb1-8e82-4312-9c02-af3a808211c2","added_by":"auto","created_at":"2024-07-31 05:25:08","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2904461,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDesign, structure, and functionality of the stretchable multimodal photonic sensor for wearable healthcare monitoring.\u003c/strong\u003e \u003cstrong\u003ea\u003c/strong\u003e, Illustration of the multimodal sensor attached to human skin to simultaneously and continuously monitor various physiological signals associated with strain, temperature, and pH. Inset shows the sensor structure. \u003cstrong\u003eb\u003c/strong\u003e, Excitation mechanisms of the sensor based on upconversion luminescence and radiative energy transfer. \u003cstrong\u003ec\u003c/strong\u003e, Material and structural design of the HPOF with integrated functionalities. \u003cstrong\u003ed\u003c/strong\u003e, SEM image of the core-shell UCNPs. \u003cstrong\u003ee\u003c/strong\u003e, Cross-section microscope image of the HPOF with red dyes loaded with in the hydrogel coating. \u003cstrong\u003ef\u003c/strong\u003e, Photographs of the sensor conformally attached to the human skin. \u003cstrong\u003eg\u003c/strong\u003e, Mechanical flexibility and stretchability. \u003cstrong\u003eh\u003c/strong\u003e, Emission spectrum of the multimodal sensor upon 980-nm excitation.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4548546/v1/2a3aa3e2cc17d13009818779.jpeg"},{"id":61464239,"identity":"8c3f1f72-50b9-4e5c-81b5-2b58d1626bbb","added_by":"auto","created_at":"2024-07-31 05:25:09","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2707454,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTemperature sensing performances of the multimodal sensor.\u003c/strong\u003e \u003cstrong\u003ea\u003c/strong\u003e, Schematic energy diagram of the UCNPs. \u003cstrong\u003eb\u003c/strong\u003e, Emission spectra of the sensor under different temperatures ranging from 25 ℃ to 45 ℃ . \u003cstrong\u003ec\u003c/strong\u003e, Linear plot of \u0026nbsp;ln(\u003cem\u003eI\u003c/em\u003e\u003csub\u003e525\u003c/sub\u003e/\u003cem\u003eI\u003c/em\u003e\u003csub\u003e545\u003c/sub\u003e) versus \u0026nbsp;\u0026nbsp;retrieved from the emission spectra. \u003cstrong\u003ed\u003c/strong\u003e, Response and recovery times of the sensor upon a step change in temperature. \u003cstrong\u003ee\u003c/strong\u003e, Response of the sensor to cyclic temperature changes between 25 ℃and 45 ℃. \u003cstrong\u003ef\u003c/strong\u003e, Photograph and IR thermograms of the sensor treated with water droplet of various temperatures. \u003cstrong\u003eg\u003c/strong\u003e, Time-lapse changes of the droplet temperature measured by our sensor and a commercial IR camera. Inset shows the measurement deviation between our sensor and the IR camera sensor, indicating a root mean square error (RMSE) of 0.46 ℃. \u003cstrong\u003eh\u003c/strong\u003e, Influences of strain and pH on the temperature response of the sensor.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4548546/v1/6391958af83cc953ae19e1ba.jpeg"},{"id":61464234,"identity":"3e74f2a9-b25b-4d5c-b628-f6be9b568f0c","added_by":"auto","created_at":"2024-07-31 05:25:08","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2354755,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003epH sensing performances of the multimodal sensor.\u003c/strong\u003e \u003cstrong\u003ea\u003c/strong\u003e, Mechanism of the sensor for pH sensing. Protonation/deprotonation of the chromophore results in dynamic fluorescent/non-fluorescent behaviors of the pHrodo Red. \u003cstrong\u003eb\u003c/strong\u003e, Emission spectra of the sensor under different pH. Inset shows an enlarged view of the pHrodo Red emission around 600 nm. \u0026nbsp;\u003cstrong\u003ec\u003c/strong\u003e, Ratiometric pH response of the sensor calibrated in the range of pH 4.0-9.5. The red line is a fit of the Henderson-Hasselbalch equation, and the inset shows a linear pH response over the pH range of 5.0-7.5. \u003cstrong\u003ed\u003c/strong\u003e, Response of the sensor upon repeated cycling between two buffer solutions of pH 4 and pH 6.5. \u003cstrong\u003ee\u003c/strong\u003e, Selectivity of the sensor towards H\u003csup\u003e+\u003c/sup\u003e in presence of 0.1 M Na\u003csup\u003e+\u003c/sup\u003e and 0.1 M K\u003csup\u003e+\u003c/sup\u003e. \u003cstrong\u003ef\u003c/strong\u003e, Real-time pH readout of the sensor upon treatment with different pH solutions. \u003cstrong\u003eg\u003c/strong\u003e, Dependences of the pH response on strain and temperature stimuli.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4548546/v1/506010def0a9f6098a83a6a2.jpeg"},{"id":61464831,"identity":"7c12f45b-67f1-4bb6-8d2c-3f81f9713926","added_by":"auto","created_at":"2024-07-31 05:33:09","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2833855,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStrain sensing performances of the multimodal sensor.\u003c/strong\u003e \u003cstrong\u003ea\u003c/strong\u003e, Mechanism of the sensor for strain sensing. \u003cstrong\u003eb\u003c/strong\u003e, Photographs of the HPOF under relaxed and stretched states. \u003cstrong\u003ec\u003c/strong\u003e, Transmission spectra of the HPOFs with/without dye loading upon white light illumination.\u003cstrong\u003e d\u003c/strong\u003e, Emission spectra of the sensor under different strains. \u003cstrong\u003ee\u003c/strong\u003e, Differential attenuation changes at 545 nm and 655 nm versus the applied strains ranging from 0% to 20%. The inset shows a linear fit of the sensor response over small strains below 1%.\u003cstrong\u003e f\u003c/strong\u003e, Temporal readout of the sensor in response to step-increased strains. The loaded strain was fully released after stretching. \u003cstrong\u003eg\u003c/strong\u003e, Response and recovery behaviors of the sensor upon a quasi-transient step strain of ~2%.\u003cstrong\u003e h\u003c/strong\u003e, Response of the sensor under a cyclic loading-unloading test at different strains. \u003cstrong\u003ei\u003c/strong\u003e, Temperature and pH dependences of the strain readout.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4548546/v1/66cd3482bbdc5f7c5ac5d9cc.jpeg"},{"id":61464236,"identity":"078a9773-9322-44d0-a203-03e6e1763b09","added_by":"auto","created_at":"2024-07-31 05:25:09","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":3001051,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eReal-time multiparameter monitoring of human health.\u003c/strong\u003e \u003cstrong\u003ea\u003c/strong\u003e, Illustration of the multimodal sensor attached onto the human wrist for simultaneous monitoring of artery pulse, skin temperature, and sweat pH in real time. \u003cstrong\u003eb\u003c/strong\u003e, Results of real-time skin temperature and sweat pH monitoring. As references, the skin temperature and sweat pH were also measured by a commercially available IR sensor and pH sensor, respectively.\u003cstrong\u003e c\u003c/strong\u003e, Wrist pulse simultaneously monitored from the strain readout of the sensor.\u003cstrong\u003e d\u003c/strong\u003e, Illustration of the sensor attached onto chest to simultaneously detect chest movements induced by cardiopulmonary activities, as well as body temperature and sweat pH. \u003cstrong\u003ee\u003c/strong\u003e, Original signal of the strain readout corresponding to the chest movements. The inset shows an enlarged view of the obtained signal, indicating clearly distinguished respiration pattern. \u003cstrong\u003ef\u003c/strong\u003e, Respiratory and heartbeat signals in the time domain decomposed after band-pass filtering. The insets show the fast Fourier transform of the temporal signals. \u003cstrong\u003eg\u003c/strong\u003e, Results of simultaneous and continuous monitoring of heartbeat, respiration, skin temperature, and sweat pH with our sensor. The reference results of heartbeat and respiration rates were measured by manual counting, while the reference skin temperature and sweat pH were provided by the commercial IR sensor and pH sensor.\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4548546/v1/34e17d44227fbf807f685349.jpeg"},{"id":61465914,"identity":"dfafd5a0-841a-466e-973d-441468ba504d","added_by":"auto","created_at":"2024-07-31 05:49:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":14393770,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4548546/v1/cdfc63ad-3a23-407e-b5ba-ce356c587ce4.pdf"},{"id":61464237,"identity":"7e4c8818-3430-44d9-aaa6-d00dd4b007ce","added_by":"auto","created_at":"2024-07-31 05:25:09","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":12205380,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"SupportinginformationG.docx","url":"https://assets-eu.researchsquare.com/files/rs-4548546/v1/9755bd63c07d3ac59b4419f4.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Stretchable multimodal photonic sensor for wearable healthcare monitoring","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSkin is the largest organ of human body that not only serves as a protective barrier against external environment, but also acts as a diagnostic interface rich with valuable physiological information originating from dermis/epidermis, blood vessels, and inner organs. Wearable sensor technologies provide an intriguing possibility to interface with the skins for timely prevention, diagnosis, and treatment of diseases, through non-invasive continuous monitoring of those physiological signals [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In particular, for comfortable wearing and accurate signal detection, wearable sensors should be ideally flexible, stretchable and biocompatible so as to ensure stable, conformal, and long-term attachment onto skin even during body movements [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Moreover, multifunctionalities are also essential considerations to achieve wearable sensors with multiparameter monitoring capabilities, which would enable more comprehensive assessment of an individual\u0026rsquo;s health status [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. To date, a variety of stretchable multifunctional sensors have already been developed for mechanical (e.g., strain and pressure), thermal, and chemical sensing, with exploitation of resistive [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], capacitive [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], electrochemical [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], or optical sensing mechanisms [\u003cspan additionalcitationids=\"CR17 CR18 CR19\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Application examples of these sensors include on-skin continuous monitoring of vital signs (e.g., pulse rate, body temperature, and respiration) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], body motion [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], and sweat biomarkers [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Despite their impressive performances and potential applications, most of these sensors rely on electrical or optical properties of functional materials that transform various stimuli into a coupled output signal (resistance, capacitance, or light intensity), making it difficult to discriminate different stimuli. Alternatively, the incorporation of multiple sensors with different sensing modalities into a hybrid sensing platform could enable simultaneous multiparameter monitoring by transducing individual stimuli into separated signals [\u003cspan additionalcitationids=\"CR22 CR23\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. However, different types of sensors may considerably differ in terms of material constitute, structure, and mechanics, posing fundamental barriers for seamless integration of such sensors without compromising structural integrity, stretchability, and functionality. It\u0026rsquo;s highly desirable, yet considerably challenging to develop wearable multimodal sensors with stimulus discriminability in simple structural architecture (ideally a single sensor unit), while integrating high flexibility, stretchability, and biocompatibility.\u003c/p\u003e \u003cp\u003eIn this work, we present a flexible, stretchable, and biocompatible multimodal photonic sensor that can simultaneously detect and differentiate mechanical, thermal, and chemical stimuli in single sensor architecture. The integrated sensing modalities are enabled by incorporating three distinct sensing mechanisms in a stretchable hydrogel-coated polydimethylsiloxane (PDMS) optical fiber (HPOF), which shows multi-stimuli responsiveness to strain, temperature, and pH. The three mechanisms share the same HPOF, but operate at different wavelengths to facilitate stimuli decoupling. To achieve system simplicity and compactness for sensor interrogation, lanthanide-based upconversion nanoparticles (Ln-UCNPs) are assembled in the core of HPOF to produce multiband emissions upon single laser excitation based on combined mechanisms of upconversion luminescence (UCL) and radiative energy transfer (RET). The hydrogel coating of the HPOF can assist in constructing a step-index profile for efficient light guiding due to its relatively low refractive index (RI). More importantly, this coating also provides porous hydrophilic matrices that allow facile chemical modifications with functional molecules, and promote analyte exchanges between the hydrogel and aqueous surroundings. The sensing HPOF is also encapsulated in an elastic skin-adhesive patch with elastic polymers and fabric to achieve stable and conformal contact with human skins. Mechanical and cell viability tests were performed to validate the flexibility, stretchability, and biocompatibility of the encapsulated sensor device. Furthermore, we thoroughly investigate the sensing mechanisms and performances of the multimodal sensor upon different stimuli, and as a proof of concept, demonstrate the utility of the sensor for simultaneous monitoring of a person\u0026rsquo;s heartbeat, respiration, body temperature, and sweat pH in real time.\u003c/p\u003e"},{"header":"Results and discussion","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDesign, fabrication, and biomechanical compatibility of the multimodal sensor\u003c/h2\u003e \u003cp\u003eAs illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea, the multimodal photonic sensor enables simultaneous on-skin monitoring of various physiological signals associated with strain, temperature, and pH, providing comprehensive and personalized healthcare information for improved disease diagnosis and treatment. The multimodal sensor primarily consisted of a core/coating HPOF that was encapsulated between two elastic polyurethane layers of a skin-adhesive base and a water-proof protective cover, together with cotton fabric tape to secure the ends of the HPOF. The skin-adhesive base layer was designed with a narrow slit to enable direct contact of the HPOF with skin for sweat monitoring. Silica multimode optical fibers (MMFs) were pigtailed to the HPOF with their central axis aligned for laser coupling and emission collection. The core of the HPOF was made from composites of Ln-UCNPs and PDMS elastomers, and fabricated by approaches of molding and thermally curing (see Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003ea, and more details in Materials and Method). Transparent, low-RI polyacrylamide (PAM) hydrogels were chosen as the coating of the HPOF, which endowed the fiber with step-index light guidance and meanwhile introduced abundant active amino groups for functional modifications. Since PDMS is hydrophobic, and the PAM hydrogels are hydrophilic polymers inflated with water, it is hardly to create strong adhesion between the PDMS and PAM via direct physical coating. To achieve a robust hydrogel coating, we chemically anchored the PAM hydrogels on PDMS by using an interfacial interpenetration strategy [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Briefly, the PDMS core was first treated with an ethanol-based organic solution containing hydrophobic photoinitiators (benzophenone) that would swell the PDMS, impelling diffusion and absorption of the photoinitiators into the core surface (Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003eb). Afterwards, the treated core was immersed in a PAM precursor that contains hydrophilic photoinitiators (Irgacure 2959). Upon ultraviolet (UV) exposure, the hydrophilic photoinitiators induced polymerization of the PAM monomers while the hydrophobic initiators enabled the PAM networks to covalently crosslink with the PDMS chains, resulting in the formation of a thin hydrogel layer toughly bonded on the PDMS surface. It was found that the hydrogel coating could endure vigorous deformation induced by stretching or scratching with no observable crack or delamination, demonstrating excellent mechanical robustness (Figure S2). The length of the HPOF was optimized at ~\u0026thinsp;1.5 cm from the profile of emission decay along the fiber length (Figure S3).\u003c/p\u003e \u003cp\u003eThe multimodal photonic sensor integrates three distinct sensing mechanisms in a single HPOF to achieve simultaneous detection of strain, temperature, and pH (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb, c). Upon near-infrared (NIR) excitation, the incorporated Ln-UCNPs in the HPOF generate multiband visible emissions via the upconversion process for versatile interrogation of different sensing mechanisms. The UCNPs were comprised of a luminescent core of NaYF\u003csub\u003e4\u003c/sub\u003e:Yb,Er covered by an inert shell of NaYF\u003csub\u003e4\u003c/sub\u003e, which could protect the core from luminescence quenching caused by surface defects and surrounding environments (Figure S4a) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The morphology and particle size of the UCNPs were examined by transmission electron microscopy (TEM) and scanning electron microscope (SEM), where the UCNPs were uniformly distributed with hexagonal shape and diameter of ~\u0026thinsp;57 nm (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed, and Figure S4b-d). The Er\u003csup\u003e3+\u003c/sup\u003e ions of the UCNPs possessed a pair of thermally coupled energy levels (\u003csup\u003e2\u003c/sup\u003eH\u003csub\u003e11/2\u003c/sub\u003e and \u003csup\u003e4\u003c/sup\u003eS\u003csub\u003e3/2\u003c/sub\u003e) [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], and the emission bands originating from these levels showed thermal-dependent behaviors, enabling sensitive temperature measurement from changes of the emission intensities. The PAM coating of the HPOF offers abundant amino groups allow facile chemical modifications with various functional molecules. Hereby, we functionalized the hydrogel coating with pH sensitive fluorescent dyes (pHrodo Red) to achieve pH responsiveness. The pHrodo Red was selected because of the substantial overlap between its absorption spectrum and the emission bands of the UCNPs, thereby enabling radiative energy transfer (RET) from the UCNPs to the pHrodo Red for pH determination (Figure S4e). Besides pH sensitivity, the loaded dye molecules also endowed the HPOF with wavelength-dependent absorption characteristics that could be further harnessed to quantify strain stimuli from the absorption changes of light propagating along the HPOF. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ee shows a cross-section image of the HPOF (core/coating, 500 \u0026micro;m/553 \u0026micro;m) with red dyes loaded in the hydrogel coating. To avoid leakage of the dye molecules from the coating, the pHrodo Red modified with succinimidyl (NHS) ester was immobilized by covalent bonding to the amino groups of the hydrogel matrix (Figure S5).\u003c/p\u003e \u003cp\u003eThe sensing HPOF was ultimately encapsulated in an elastic skin-adhesive patch to ensure stable adhesion on skin. Figures\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ef and g show the images of the HPOF-based multimodal sensor conformally attached to the human skin, where the sensor could be freely stretched, compressed, and twisted without any failure. Extensive mechanical test was further conducted that confirmed the skin-like softness (Young\u0026rsquo;s modulus of 1.14 Mpa) and high stretchability (\u0026gt;\u0026thinsp;60%) of the sensor (Figure S6). Biological safety is critical for wearable sensors especially when in direct contact with human skins. The multimodal sensor was proven to be nontoxic and biocompatible as verified by a cell viability test with human neuroblastoma cells (SK-N-SH), where a high cell viability of \u0026gt;\u0026thinsp;98% was observed after 72 h of culture in the presence of the sensor (Figure S7). Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eh shows a typical emission spectrum of the sensor, indicating four separate emission bands generated upon excitation of a single 980-nm laser. The emission at 600 nm was produced by RET from the UCNPs to the pHrodo Red, while the emissions centered at 525, 545, and 655 nm were attributed to the Er\u003csup\u003e3+\u003c/sup\u003e transitions of \u003csup\u003e2\u003c/sup\u003eH\u003csub\u003e11/2\u003c/sub\u003e\u0026rarr;\u003csup\u003e4\u003c/sup\u003eI\u003csub\u003e15/2\u003c/sub\u003e, \u003csup\u003e4\u003c/sup\u003eS\u003csub\u003e3/2\u003c/sub\u003e\u0026rarr;4I\u003csub\u003e15/2\u003c/sub\u003e, and \u003csup\u003e4\u003c/sup\u003eF\u003csub\u003e9/2\u003c/sub\u003e\u0026rarr;\u003csup\u003e4\u003c/sup\u003eI\u003csub\u003e15/2\u003c/sub\u003e levels, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). With the distinctive design of materials, structures, and functionalities above, the multimodal sensor holds great promises as a wearable safety device for multi-stimuli sensing in long-term care settings.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eTemperature sensing performances of the multimodal sensor\u003c/h2\u003e \u003cp\u003eTemperature is one of the fundamental parameters in monitoring human activities and assessing body abnormalities [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. To evaluate the feasibility of the multimodal sensor for temperature sensing, we characterized the temperature response of the sensor with a simplified optical setup as depicted in Figure S8. A fiber-coupled laser at a wavelength of 980 nm and an output power of 15 mW was launched into the sensor through the pigtailed silica MMFs, and the emissions were collected and guided to a compact spectrometer for spectral analysis. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb shows the emission spectra of the sensor in response to different temperatures. Because of the thermal coupling of \u003csup\u003e2\u003c/sup\u003eH\u003csub\u003e11/2\u003c/sub\u003e and \u003csup\u003e4\u003c/sup\u003eS\u003csub\u003e3/2\u003c/sub\u003e levels in Er\u003csup\u003e3+\u003c/sup\u003e, the emissions at 525 nm and 545 nm were strongly temperature-dependent and the intensity ratio of these two emissions followed the well-known Boltzmann distribution given by [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]:\u003cdiv id=\"Equ1\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equ1\" name=\"EquationSource\"\u003e\n$${I_{525}}/{I_{545}}=A\\exp ( - \\Delta E/kT)$$\u003c/div\u003e\u003cdiv class=\"EquationNumber\"\u003e1\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eWhere \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({I_{525}}\\)\u003c/span\u003e\u003c/span\u003eand \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({I_{545}}\\)\u003c/span\u003e\u003c/span\u003e are emission intensities arising from the transitions of \u003csup\u003e2\u003c/sup\u003eH\u003csub\u003e11/2\u003c/sub\u003e\u0026rarr;\u003csup\u003e4\u003c/sup\u003eI\u003csub\u003e15/2\u003c/sub\u003e and \u003csup\u003e4\u003c/sup\u003eS\u003csub\u003e3/2\u003c/sub\u003e\u0026rarr;4I\u003csub\u003e15/2\u003c/sub\u003e, respectively; \u003cspan class=\"InlineEquation\"\u003e\u003c/span\u003eis a constant; \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\Delta E\\)\u003c/span\u003e\u003c/span\u003edenotes the energy gap between the \u003csup\u003e2\u003c/sup\u003eH\u003csub\u003e11/2\u003c/sub\u003e and \u003csup\u003e4\u003c/sup\u003eS\u003csub\u003e3/2\u003c/sub\u003e;\u003cspan class=\"InlineEquation\"\u003e\u003c/span\u003eis the Boltzmann\u0026rsquo;s constant, and \u003cspan class=\"InlineEquation\"\u003e\u003c/span\u003e is the absolute temperature in the Kelvin scale. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec shows a linear plot of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\ln ({I_{525}}/{I_{545}})\\)\u003c/span\u003e\u003c/span\u003e versus the inverse temperature (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(1/T\\)\u003c/span\u003e\u003c/span\u003e) over the temperature range of 25 ℃ (3.35\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003e K\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e) to 45 ℃ (3.14\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003e K\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e), which agrees well with Eq.\u0026nbsp;(\u003cspan refid=\"Equ1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The temperature sensitivity defined as the percent change in \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\ln ({I_{525}}/{I_{545}})\\)\u003c/span\u003e\u003c/span\u003e per unit change in temperature, was calculated to be 0.8% ℃\u003csup\u003e\u0026minus;1\u003c/sup\u003e around 37 ℃ from the response curve, and the limit of detection (LOD) was about \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\pm\\)\u003c/span\u003e\u003c/span\u003e0.19 ℃, estimated from the noise standard deviation of the temperature readout (Figure S9a). The response speed of the sensor was then studied upon a step change in temperature, where the response and recovery times of the sensor were measured to 3 s and 4 s, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed). The highly sensitive and fast responding merits enabled the sensor to capture rapid subtle thermal signals produced by human activities such as nose breathing (Figure S9b). To evaluate the repeatability of the sensor, consecutive thermal cycling tests of heating and cooling were performed (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee). The sensor showed reversable and reproducible readout with the cyclic temperature changes, indicating stable and repeatable performances.\u003c/p\u003e \u003cp\u003eWe further validated the capability of the sensor to quantitatively detect dynamic thermal signals by a real-time temperature monitoring test, where the sensor was treated with water droplet of various temperatures (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ef). Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eg shows the temporal evolution of the droplet temperature measured by our sensor and a commercial IR camera. Notably, there was a high consistency between the temperature readout of our sensor and the signal obtained by the IR camera with a root mean square error (RMSE) of 0.46 ℃, demonstrating high reliability and accuracy in real-time temperature measurements. In addition, the influences of strain and pH stimuli on the temperature response of the sensor were also examined (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eh). The sensor was treated with different stretching strains and pH, separately, while the applied temperature was kept constant. Remarkably, the temperature readout of the sensor was well maintained despite the changes of strain and pH, indicating high selectivity towards temperature among other stimuli. This unique feature was attributed to the ratiometric detection that made the temperature readout intrinsically self-calibrated and robust to other stimuli interferences. The above results demonstrate our sensor can be used for fast and quantitative temperature monitoring with high selectivity, accuracy, and repeatability.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003epH sensing performances of the sensor\u003c/h2\u003e \u003cp\u003eEpidermal pH is an important indicator of human health and illness that can be used for medical diagnosis and health monitoring. For example, the sweat pH of a healthy human normally ranges between 4.5\u0026ndash;6.5, whereas the sweat of patients with cystic fibrosis is usually alkaline and can have a pH value beyond 8 [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. For pH sensing, we immobilized pH-sensitive fluorescent dyes (pHrodo Red-NHS) into the PAM coating of the HPOF via covalent bonding. The porous nature of the hydrogel matrices facilitated rapid analyte exchanges between the HPOF and aqueous surroundings (e.g., sweat) through passive diffusion. The diffusion of hydrogen ions into the hydrogel coating promotes the protonation of the rhodamine chromophore, resulting in considerably increased fluorescence of the pHrodo Red in acidic pH (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea) [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb shows the emission spectra of the sensor tested with different pH solutions. It was found that the emission of the pHrodo Red at 600 nm was notably increased at lower pH, while the emission band at 650 nm was less affected. The RET process takes place due to the spectral overlap between the UCL emission at 545 nm and the absorption spectrum of the pHrodo Red (Figure S4e). The pH response of the sensor was calibrated in the range of pH 4.0-9.5 by ratiometric dual-wavelength measurements, where the intensity ratio of the pH-sensitive emission at 600 nm and the insensitive UCL emission at 545 nm as a reference signal was calculated (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec). Henderson-Hasselbalch equation was used for fitting of the responsive curve, which indicated an apparent p\u003cem\u003eK\u003c/em\u003e\u003csub\u003ea\u003c/sub\u003e value of ~\u0026thinsp;6.6, suitable for physiological pH monitoring. Besides, the sensor displayed a linear pH response with sensitivity of 27% pH\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e over the pH range of 5.0-7.5, where a low LOD of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\pm 0.09\\)\u003c/span\u003e\u003c/span\u003e was achieved from the linear fitting (inset of Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec). Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed shows the response of sensor under repeated pH tests, where the sensor exhibited a reversible and reproducible output over multiple cycles with negligible hysteresis.\u003c/p\u003e \u003cp\u003eSelectivity is another crucial factor for practical sweat measurements due to the presence of other interference ions in sweat. As revealed in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ee, the sensor had a high selectivity towards hydrogen ions over other dominant interference ions in sweat including K\u003csup\u003e+\u003c/sup\u003e and Na\u003csup\u003e+\u003c/sup\u003e, due to the selective protonation mechanism. The response time of the sensor to pH was about 34 s, which was sufficiently fast for use in sweat monitoring as the sweat pH generally varied on the order of minutes [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. To test the dynamic performance of the sensor for pH determination, the sensor was continuously treated with droplet of different pH solutions. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ef, the sensor exhibited a step-increased behavior in response to solutions of increased pH, and the sensor output was recovered after the pH was returned to the initial value, which validated the reliability of sensor for real-time pH monitoring. Furthermore, the effects of strain and temperature on the pH response of the sensor were investigated in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eg. The sensor was kept in a pH 5 buffer solution, and meanwhile tested under various strains and temperatures. It was found that the pH readout was insensitive to strain but slightly affected by temperature. The temperature-dependent effect of the pH response was attributed to the temperature dependence of the fluorescence quantum yield, defined as the ratio of emitted photons to absorbed ones [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. The pH response could be calibrated and corrected with the temperature readout to achieve high accuracy for practical use (Figure S10).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStrain sensing performances of the sensor\u003c/h2\u003e \u003cp\u003eAccurate detection of skin strains is critical for a wide variety of applications ranging from healthcare monitoring, sport training to human-machine interfacing [\u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Sensitivity and stretchability are the key parameters determining the performance of strain sensors in wearable applications, especially in healthcare monitoring. A high sensitivity is required for monitoring subtle skin deformations caused by vital signs such as artery pulse and heartbeat, which typically induce a strain less than 1% [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Meanwhile, a high stretchability is demanded to enable high mechanical compliance with the elastic skin. We demonstrated highly sensitive strain sensing with the stretchable multimodal sensor by virtue of the wavelength-dependent absorption characteristics of the dye molecules. Upon excitation, the UCNPs generated UCL emissions that propagated in both forward and backward directions along the HPOF (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea, b). The backward emissions were absorbed by the dye molecules distributed in the fiber coating, leading to attenuated emissions detected at the front end. When stretched, the fiber length was increased, which prolonged the interaction length of the backward emission with the dye absorbers, resulting in enlarged absorption. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ec shows the transmission spectra of the HPOFs with/without dye loading, which confirmed the absorption effect of light propagating through the HPOF in presence of dye molecules. The emission spectra of the sensor under various strains were characterized as presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ed. Upon stretching, the local stress deformed the coupling joint between the HPOF and the silica MMFs, and induced additional coupling loss that caused decreased intensities at all emission bands. To eliminate the absorption-independent loss effect, a dual-wavelength differential absorption method was employed, for which the emissions at 545 nm (near the absorption peak) and 655 nm (outside the absorption band) were chosen as the probing light and reference light, respectively. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ee shows the differential attenuation changes at the two wavelengths versus the applied strains ranging from 0\u0026ndash;20%. As expected, the sensor displayed increased attenuation with the increasing strain due to the increased light absorption. Notably, the sensor could sensitively detect small-scale strains below 1% with high linearity (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({{\\text{R}}^2}=0.99\\)\u003c/span\u003e\u003c/span\u003e), and presented a LOD as low as \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\pm 0.07\\%\\)\u003c/span\u003e\u003c/span\u003e (inset of Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ee). The exceptional sensitivity of the sensor makes it a promising candidate to accurately detect subtle skin strains in health monitoring applications.\u003c/p\u003e \u003cp\u003eThe temporal readout of the sensor in response to step-increased strains was further investigated (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ef). The sensor indicated an instant change of signal at each step of strain increase, and its readout was recovered once the loading strain was fully released. To evaluate the response speed, the sensor was loaded with a quasi-transient step strain of ~\u0026thinsp;2% (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eg). The response and recovery times of the sensor were measured to be 23 ms and 25 ms, which were fast enough to capture almost all the skin strain-related physiological signals (typically\u0026thinsp;\u0026lt;\u0026thinsp;10 Hz). Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eh shows the sensor readout under a cyclic loading-unloading test of different strains. The sensor exhibited a repeatable response to the sequence of loading-unloading cycles with negligible hysteresis or drift, indicating high stability and reproducibility. Moreover, the crosstalk effects of temperature and pH on the strain response of the multimodal sensor were analyzed under different temperature and pH conditions, where no strain was loaded. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ei, the sensor maintained a stable strain readout at different temperatures in the physiological range of 30\u0026ndash;40 ℃, indicating temperature insensitivity of the strain response. In contrast, the changes of pH induced an obvious drift in the strain readout attributed to the pH-dependent absorption of the pHrodo dye. To minimize the interference of pH, the strain readout could be calibrated from the pH value determined by the multimodal sensor as the pH response was not affected by strain. Alternatively, it might be more straightforward to retrieve the strain stimuli by filtering and frequency analysis since the strain-related vital signs possessed a signal frequency much higher than that of the skin pH. In addition, long-term stability of all the sensor readouts were verified by keeping the sensor at constant strain, temperature, and pH levels, where the readout changes were monitored every 24 h for 72 h (Figure S11). No obvious drift was observed in all readouts of the sensor during the monitoring period, suggesting a high stability in long-term operation.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eReal-time multiparameter monitoring of human health\u003c/h2\u003e \u003cp\u003eBenefitting from its high stretchability, favorable biocompatibility, and multimodal sensing capabilities, the sensor could be conformally attached onto the human skin for simultaneous monitoring of multiple sets of health indicators. As a proof-of-concept demonstration, the sensor was worn on the human wrist (male, 22 years old) with sweat on the skin to detect artery pulse, skin temperature, and sweat pH in real time (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ea). Figure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eb shows the real-time skin temperature and pH value measured with our sensor. The skin temperature and sweat pH were measured to be around 33.6 ℃ and 4.8, respectively, within the normal physiological ranges. A commercially available IR sensor and pH sensor were also employed to provide reference measurements. The measured results of our sensor were in good agreement with the commercial sensors (relative error\u0026thinsp;\u0026lt;\u0026thinsp;2%), indicating a high accuracy of the sensor for wearable temperature and pH monitoring. Moreover, artery pulse on the wrist could be simultaneously detected from the strain readout after high-pass filtering (cut-off frequency, 0.1 Hz). The wrist pulse is a weak but crucial physiological signal that can reveal the health status of both heart and arteries. Figure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ec shows the real-time artery pulse signal captured by the sensor, where each cycle of the pulse involved contraction and relaxation of the heart. The frequency of the pulse signal was observed to be 80 beats per min (bpm), in accordance with the normal range of pulse rates (60\u0026ndash;100 bpm for healthy adults [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]). The inset of Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ec shows an enlarged view of a typical pulse waveform, where three distinct peaks featured as the percussion (P) wave, tidal (T) wave, and dicrotic (D) wave could be clearly distinguished. The percentage of the T wave height divided by P wave height is defined as the augmentation index (AI), a well-established indicator of arterial stiffness and vascular aging [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. From the measured waveform, the AI was calculated to be 0.39, which was a characteristic value expected for a healthy 22-year-old male [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eApart from the wrist, the sensor was further attached onto the skin of chest to detect the chest-wall movement caused by cardiopulmonary activities, and also simultaneously monitor the body temperature and sweat pH (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ed). Cardiopulmonary activity monitoring plays a critical role in evaluation of cardiac and pulmonary functions, promoting early detection and prevention of cardiovascular and pulmonary diseases such as atherosclerosis, heart failure, and asthma [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Abnormal respiratory rate (RR) and heart rate (HR) are often the early signs of serious cardiopulmonary disorders. Figure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ee shows the original strain readout of the sensor in response to the chest movement. Periodic respiratory activity could be clearly recognized from the original signal, arising from vigorous stretching and releasing of the sensor upon exhaling and inhaling (inset of Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ee). In contrast, the cardiac activity was much weaker and submerged in the respiratory signal. The two signals could be separated in the frequency domain by filtering strategy due to the different frequency bands of respiration (0.1\u0026ndash;0.5 Hz) and cardiac beat (0.8-2Hz). Figure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ef shows the respiratory and heartbeat signals in the time domain decomposed after band-pass filtering. The obtained signals were further analyzed in the frequency domain by fast Fourier transform (FFT), which indicated a normal RR and HR of 13 bpm and 84 bpm, respectively, demonstrating great promise of our sensor for wearable cardiopulmonary monitoring in different healthcare and clinical settings. Furthermore, other vital indicators of health including skin temperature and sweat pH could be accurately detected from the calibrated temperature and pH readout. As validated in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eg, the sensor could simultaneously and continuously monitor heartbeat, respiration, skin temperature, and sweat pH without any crosstalk, and the results showed good consistency with the reference data. To our knowledge, this is the first demonstration of simultaneous monitoring of cardiopulmonary activities, body temperature, and sweat biomarker with only a single sensor.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn summary, we have demonstrated a wearable multimodal photonic sensor that unite the merits of simultaneous multi-stimuli sensing including strain, temperature, and pH, as well as high flexibility, stretchability, and biocompatibility. The multimodal sensor was made by a stretchable HPOF that was constructed with a step-index light guidance profile. To achieve multi-stimuli sensing with stimulus discriminability, multiple sensing mechanisms were integrated in the HPOF with distinct operation wavelengths. Spectrally-resolved multiband emissions were generated based on the combined mechanisms of upconversion luminescence and RET, which enabled the interrogation of the sensor with a single laser diode. To enable conformal contact and adhesion to human skins, the fabricated HPOF was further encapsulated in an elastic skin-adhesive patch with elastic polymers and fabric. Detailed characterizations were performed that validated the high sensitivity, selectivity, and fast response of the sensor performances towards different stimuli. Furthermore, we demonstrated that the sensor enabled simultaneous and continuous monitoring of mechanical stimuli induced by artery pulsation or cardiopulmonary activities, along with skin temperature and sweat pH, providing thorough insights into the status of human health.\u003c/p\u003e \u003cp\u003eWe compared the major features of our sensor with previously reported wearable sensors in table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e and S2. Our work appeared as the only design that implemented simultaneous mechanical, thermal, and chemical sensing in a single sensor structure, while achieving stimulus discriminability, stretchability, and biocompatibility. Moreover, the proposed sensor was also advantageous in aspects including response time, LOD, sensitivity, and electromagnetic interference (EMI) immunity as compared with others. Especially, EMI immunity is crucial for applications in clinical utility, and the intrinsic EMI immunity of the photonic sensor allows for stable and real-time monitoring of patient's physiological status with the presence of EMI-generating medical equipment such as MRI during therapeutic or diagnostic procedures. The hydrogel coating of the HPOF offers abundant active sites that facilitate versatile functional modification, making it possible to detect other sweat biomarkers with different functional molecules. The sensing modalities could be further expanded by using fluorophores with narrow band emissions such as quantum dots (QDs) instead of fluorescent dyes, which enables more stimuli to be spectrally encoded within the HPOF. Emission intensity ratios were employed to achieve robust sensing of different stimuli, for which a compact spectrometer was used to extract the emission intensities at specific wavelengths. For future miniaturization of the demodulation system, an electronic-photonic integrated circuits (EPICs) could be developed with on-chip light sources, spectral filters, photodetectors, and signal processing unit, benefitting from the well-developed integrated circuit technologies. Our sensor represents an important first step towards the realization of wearable multimodal sensors that integrate mechanical, thermal, and chemical sensing modalities for more comprehensive understanding of human physiology.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e \u003cem\u003eFabrication of the Multimodal Photonic Sensor\u003c/em\u003e. The multimodal sensor primarily consisted of a core/coating HPOF that was loaded with core-shell NaYF\u003csub\u003e4\u003c/sub\u003e:Yb,Er@NaYF\u003csub\u003e4\u003c/sub\u003e UCNPs and pHrodo red in the core and coating, respectively. The core-shell UCNPs were synthesized according to a previously reported solvothermal strategy [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e], and the as-obtained nanoparticles were dispersed in cyclohexane for further use. To fabricate the core of HPOF, precursor solution containing 3 wt% UCNPs was prepared by mixing with PDMS (Sylgard 184, Dow Corning) at base to curing agent ratio of 10:1. After vigorous stirring and carefully degassing, the precursor solution was injected into a polyethylene tube mold (inner diameter, 500 \u0026micro;m) via a syringe. Followed by thermal curing at 80\u0026deg;C for about 40 min, the polymerized fiber core was demolded through water pressure. For hydrogel coating, the fiber core was first cleaned with ethanol followed by drying at 80\u0026deg;C. Then, the cleaned fiber core was treated with an ethanol solution of benzophenone (10 wt%, Aladdin) for 1 min. After wipe removal of the excess solution, the fiber core was subsequently immersed in a hydrogel precursor prepared with 30 wt% acrylamide (Aladdin) and 1 wt% Irgacure 2959 (Aladdin) in deionized water. The hydrogel precursor was exposed to UV irradiation (365 nm, 5 mW cm\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003e) for 50 min to photocrosslink the hydrogel monomer on the fiber core, and the obtained core/coating HPOF was rinsed with deionized water to remove additional unreacted reagents. To immobilize dye molecules into the hydrogel matrix, the HPOF was first immersed in a solution of pHrodo Red-NHS (5\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003e wt%, ThermoFisher Scientific) for 1min, and then treated with NaHCO\u003csub\u003e3\u003c/sub\u003e (100 mM, pH 8.5) for 12 h. The resulting HPOF was finally rinsed with deionized water and stored in phosphate buffer (pH 7.4) for later use. For light coupling, silica MMFs were pigtailed to the fabricated HPOF and aligned along the central axes. The coupling joint of the fibers was protected with a loose tube and secured by UV glue. For skin attachment, the MMFs-pigtailed HPOF was further encapsulated in an elastic skin-adhesive patch by sandwiching it between two elastic polyurethane layers of a skin-adhesive base and a water-proof protective cover. Cotton fabric tape was used to secure the ends of the HPOF on the base layer, which was cut with a narrow slit (~\u0026thinsp;0.2 cm width, 1.5 cm length) in the center to allow direct contact of the HPOF with skin. The size of the encapsulated sensor was 60 mm long by 24 mm wide by 0.6 mm thick.\u003c/p\u003e \u003cp\u003e \u003cem\u003eInterrogation Setup\u003c/em\u003e. A fiber-coupled laser at 980 nm (~\u0026thinsp;15 mW) was launched into the multimodal sensor through the pigtailed silica MMFs, which were fiber bundles consisting of a single central fiber for laser excitation and six receiving fibers surrounding the central fiber for emission collection. Each of the fibers had a core/cladding diameter of 200/220 \u0026micro;m with a NA of 0.22. The backward emissions from the multimodal sensor were collected by the six receiving fibers and guided to a compact spectrometer (CCS100, Thorlabs) for spectral analysis. A short-pass filter at 850 nm was used prior to the spectrometer to eliminate the excitation laser.\u003c/p\u003e \u003cp\u003e \u003cem\u003eInstruments and Characterizations\u003c/em\u003e. TEM and SEM analyses of the UCNPs were performed with a JEM-2100F TEM (JOL) and a Gemini SEM 560 (ZEISS). The emission spectra of the UCNPs and the pHrodo Red were measured by a spectrometer (CCS100, Thorlabs) upon 980 nm and 532 nm excitations, respectively. The absorption spectrum of the pHrodo Red was measured using a UV-Vis-NIR spectrophotometer (UV-3600, Shimadzu). The transmission spectra of the HPOF were characterized by launching the fiber with a halogen light source (Ocean optics, HL-2000). The molecular components of the HPOF were investigated by Fourier transform infrared (FTIR) spectroscopy using a FTIR spectrometer (Nicolet 6700). Mechanical properties of the multimodal sensor were characterized by using a tensile machine (Handpi Instruments) equipped with a 10 N load cell. The thermal response of the sensor was studied by immersing the sensor in a water bath heated to discrete temperatures and the water temperature was read from a digital thermometer with a resolution of 0.1℃. To investigate the pH response, Tris HCl and Tris base (Aladdin) were used to prepare pH buffers with pH range of 4.0-10.5. For strain sensing characterization, the sensor was mounted and stretched by a translation stage (Thorlabs, 10 \u0026micro;m resolution). The loading strain was calculated as the deformed length divided by initial length of the sensor.\u003c/p\u003e \u003cp\u003e \u003cem\u003eBiocompatibility Assessment\u003c/em\u003e. Cell viability assays were performed to confirm the biocompatibility of the multimodal sensor. The human neuroblastoma cell line SK-N-SH cells were seeded on coverslips in 6-well plates, and cultured in presence of the sensor for 24 h, 48 h, and 72 h. The cells were then incubated with a mixed solution of Hoechst 33342 and PI (P0137, Beyotime), and imaged with a confocal fluorescence microscopy (Dragonfly, Andor). The microscopic images were quantified using ImageJ software. Cell viability was quantified by computing the ratio of the number of red nuclei to that of blue nuclei.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor contributions statement\u003c/h2\u003e \u003cp\u003eJ.G., and L.X. conceived the idea. J.T., and Z. L. performed the experiments. J.T., J.G., R. C., and J.Z. analyzed the data. J.G., and J.T. wrote the original draft. X.G. and Y. C. assisted with the experiments. All authors contributed to the editing of the manuscript.\u003c/p\u003e\u003ch2\u003eCompeting financial interests\u003c/h2\u003e \u003cp\u003eThe authors declare no competing financial interests.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eJ.G. acknowledges the funding from the National Natural Science Foundation of China (No. 62175008) and the Fundamental Research Funds for the Central Universities.\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e \u003cp\u003eAll data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eC. Xu, Y. Yang, W. Gao, Skin-interfaced sensors in digital medicine: from materials to applications. Matter 2, 1414\u0026ndash;1445 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eA. K. Yetisen, J. L. Martinez-Hurtado, B. \u0026Uuml;nal, A. Khademhosseini, H. Butt, Wearables in medicine. Adv. Mater. 30, 1706910 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eH. C. Ates, P. Q. Nguyen, L. Gonzalez-Macia, E. Morales-Narv\u0026aacute;ez, F. G\u0026uuml;der, J. J. Collins, C. Dincer, End-to-end design of wearable sensors. Nat. Rev. Mater. 7, 887\u0026ndash;907 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eT. Q. Trung, N. E. Lee, Flexible and stretchable physical sensor integrated platforms for wearable human-activity monitoring and personal healthcare. Adv. Mater. 28, 4338\u0026ndash;4372 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eG. H. Lee, H. Moon, H. Kim, G. H. Lee, W. Kwon, S. Yoo, D. Myung, S. H. Yun, Z. Bao, S. K. Hahn, Multifunctional materials for implantable and wearable photonic healthcare devices. Nat. Rev. Mater. 5, 149\u0026ndash;165 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eT. Li, Y. Li, T. Zhang, Materials, structures, and functions for flexible and stretchable biomimetic sensors. Accounts Chem. Res. 52, 288\u0026ndash;296 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eC. Pang, G. Y. Lee, T. I. Kim, S. M. Kim, H. N. Kim, S. H. Ahn, K. Y. Suh, A flexible and highly sensitive strain-gauge sensor using reversible interlocking of nanofibres. Nat. Mater. 11, 795\u0026ndash;801 (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eM. Cao, M. Leng, W. Pan, Y. Wang, S. Tan, Y. Jiao, S. Yu, S. Fan, T. Xu, T. Liu, L. Li, J. Su, 3D wearable piezoresistive sensor with waterproof and antibacterial activity for multimodal smart sensing. \u003cem\u003eNano Energy\u003c/em\u003e 112, 108492 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS. Gong, X. Zhang, X. A. Nguyen, Q. Shi, F. Lin, S. Chauhan, Z. Ge, W. Cheng, Hierarchically resistive skins as specific and multimetric on-throat wearable biosensors. Nat. Nanotechnol. 18, 889\u0026ndash;897 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eP. Wang, W. Yu, G. Li, C. Meng, S. Guo, Printable, flexible, breathable and sweatproof bifunctional sensors based on an all-nanofiber platform for fully decoupled pressure-temperature sensing application. Chem. Eng. J. 452, 139174 (2023)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eM. Kang, H. Jeong, S. W. Park, J. Hong, H. Lee, Y. Chae, S. Yang, J. H. Ahn, Wireless graphene-based thermal patch for obtaining temperature distribution and performing thermography. Sci. Adv. 8, eabm6693 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS. Masihi, M. Panahi, D. Maddipatla, A. J. Hanson, A. K. Bose, S. Hajian, V. Palaniappan, B. B. Narakathu, B. J. Bazuin, M. Z. Atashbar, Highly sensitive porous PDMS-based capacitive pressure sensors fabricated on fabric platform for wearable applications. ACS Sens. 6, 938\u0026ndash;949 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eX. Huang, L. Liu, Y. H. Lin, R. Feng, Y. Shen, Y. Chang, H. Zhao, High-stretchability and low-hysteresis strain sensors using origami-inspired 3D mesostructures. Sci. Adv. 9, eadh9799 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eA. Ghoorchian, M. Kamalabadi, M. Moradi, T. Madrakian, A. Afkhami, H. Bagheri, M. Ahmadi, H. Khoshsafar, Wearable potentiometric sensor based on Na\u003csub\u003e0.44\u003c/sub\u003eMnO\u003csub\u003e2\u003c/sub\u003e for non-invasive monitoring of sodium ions in sweat. Anal. Chem. 94, 2263\u0026ndash;2270 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eM. Bariya, H. Y. Y. Nyein, A. Javey, Wearable sweat sensors. Nat. Electron. 1, 160\u0026ndash;171 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJ. Guo, X. Liu, N. Jiang, A. K. Yetisen, H. Yuk, C. Yang, Prof. A. Khademhosseini, X. Zhao, S. H. Yun, Highly stretchable, strain sensing hydrogel optical fibers. Adv. Mater. 28, 10244 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJ. Guo, B. Zhou, C. Yang, Q. Dai, L. Kong, Stretchable and temperature-sensitive polymer optical fibers for wearable health monitoring. Adv. Funct. Mater. 29, 1902898 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eH. Bai, S. Li, J. Barreiros, Y. Tu, C. R. Pollock, R. F. Shepherd, Stretchable distributed fiber-optic sensors. Science 370, 848\u0026ndash;852 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eM. Elsherif, F. Alam, A. E. Salih, B. AlQattan, A. K. Yetisen, H. Butt, Wearable bifocal contact lens for continual glucose monitoring integrated with smartphone readers. Small 17, 2102876 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eA. Leal-Junior, J. Guo, R. Min, A. J. Fernandes, A. Frizera, C. Marques, Photonic smart bandage for wound healing assessment. Photonics Res. 9, 272\u0026ndash;280 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS. Nakata, M. Shiomi, Y. Fujita, T. Arie, S. Akita, K. Takei, A wearable pH sensor with high sensitivity based on a flexible charge-coupled device. Nat. Electron. 1, 596\u0026ndash;603. (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eH. Zhao, K. O\u0026rsquo;Brien, S. Li, R. F. Shepherd, Optoelectronically innervated soft prosthetic hand via stretchable optical waveguides. Sci. Robot. 1, eaai7529 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eD. H. Kim, N. Lu, R. Ma, Y. S. Kim, R. H. Kim, S. Wang, J. Wu, S. M. Won, H. Tao, A. Islam, Epidermal Electronics. Science 333, 838\u0026ndash;843 (2011).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eN.T. Tien, S. Jeon, D. I. Kim, T. Q. Trung, M. Jang, B. U. Hwang, K. E. Byun, J. Bae, E. Lee, J. B. H. Tok, A Flexible Bimodal Sensor Array for Simultaneous Sensing of Pressure and Temperature. Adv. Mater. 26, 796\u0026ndash;804 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eY. Yu, H. Yuk, G. A. Parada, Y. Wu, X. Liu, C. S. Nabzdyk, K. Youcef-Toumi, J. Zang, X. Zhao, Multifunctional \u0026ldquo;hydrogel skins\u0026rdquo; on diverse polymers with arbitrary shapes. Adv. Mater. 31, 1807101 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eM. Chen, Y. Ma, M. Li, Facile one-pot synthesis of hydrophilic NaYF\u003csub\u003e4\u003c/sub\u003e: Yb, Er@ NaYF\u003csub\u003e4\u003c/sub\u003e: Yb active-core/active-shell nanoparticles with enhanced upconversion luminescence. Mater. Lett. 114, 80\u0026ndash;83 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eF. Vetrone, R. Naccache, A. Zamarr\u0026oacute;n, A. Juarranz de la Fuente, F. Sanz-Rodr\u0026iacute;guez, L. Martinez Maestro, E. M. Rodriguez, D. Jaque, J. G. Sol\u0026eacute;, J. A. Capobianco, Temperature sensing using fluorescent nanothermometers. ACS Nano 4, 3254\u0026ndash;3258 (2010).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eT. Q. Trung, N. E. Lee, Flexible and stretchable physical sensor integrated platforms for wearable human-activity monitoring and personal healthcare. Adv. Mater. 28, 4338\u0026ndash;4372 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eW. Dang, L. Manjakkal, W. T. Navara, L. Lorenzelli, V. Vinciguerra, R. Dahiya, Stretchable wireless system for sweat pH monitoring. Biosens. Bioelectron. 107, 192\u0026ndash;202 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eR. Arppe, T. N\u0026auml;reoja, S. Nylund, L. Mattsson, S. Koho, J. M. Rosenholm, T. Soukka, M. Sch\u0026auml;ferling. Photon upconversion sensitized nanoprobes for sensing and imaging of pH. Nanoscale 6, 6837\u0026ndash;6843 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eH. Y. Y. Nyein, W. Gao, Z. Shahpar, S. Emaminejad, S. Challa, K. Chen, H. M. Fahad, L. Tai, H. Ota, R. W. Davis, A. Javey, A wearable electrochemical platform for noninvasive simultaneous monitoring of Ca\u003csup\u003e2+\u003c/sup\u003e and pH. ACS Nano 10, 7216\u0026ndash;7224 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJ. Ferguson, A. W. H. Mau, Spontaneous and stimulated emission from dyes. Spectroscopy of the neutral molecules of acridine orange, proflavine, and rhodamine B. Aust. J. Chem. 26, 1617\u0026ndash;1624 (1973).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eD. Son, J. Lee, S. Qiao, R. Ghaffari, J. Kim, J. E. Lee, C. Song, S. J. Kim, D. J. Lee, S. W. Jun, S. Yang, M. Park, J. Shin, K. Do, M. Lee, K. Kang, C. S. Hwang, N. Lu, T. Hyeon, D. H. Kim, Multifunctional Wearable Devices for Diagnosis and Therapy of Movement Disorders. Nat. Nanotechnol. 9, 397\u0026ndash;404 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJ. Guo, B. Zhou, R. Zong, L. Pan, X. Li, X. Yu, C. Yang, L. Kong, Q. Dai, Stretchable and highly sensitive optical strain sensors for human-activity monitoring and healthcare. ACS Appl. Mater. Interfaces 11, 33589\u0026ndash;33598 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eM. Amjadi, K. U. Kyung, I. Park, M. Sitti, Stretchable, skin-mountable, and wearable strain sensors and their potential applications: a review. Adv. Funct. Mater. 26, 1678\u0026ndash;1698 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eY. R. Jeong, H. Park, S. W. Jin, S. Y. Hong, S. S. Lee, J. S. Ha, Highly stretchable and sensitive strain sensors using fragmentized graphene foam. Adv. Funct. Mater. 25, 4228\u0026ndash;4236 (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJ. Hart, Normal resting pulse rate ranges. J. Nurs. Educ. Pract. 5, 95\u0026ndash;98 (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eK. Kohara, Y. Tabara, A. Oshiumi, Y. Miyawaki, T. Kobayashi, T. Miki, Radial augmentation index: a useful and easily obtainable parameter for vascular aging. Am. J. Hypertens. 18, 11S-14S (2005).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eW. Nichols, Clinical Measurement of Arterial Stiffness Obtained from Noninvasive Pressure Waveforms. Am. J. Hypertens. 18, 3\u0026ndash;10 (2005).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eA. Mizuno, S. Changolkar, M. S. Patel, Wearable devices to monitor and reduce the risk of cardiovascular disease: evidence and opportunities. Annu. Rev. Med. 72, 459\u0026ndash;471 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS. H. Li, B. S. Lin, C. A. Wang, C. T. Yang, B. S. Lin, Design of wearable and wireless multi-parameter monitoring system for evaluating cardiopulmonary function. Med. Eng. Phys. 47, 144\u0026ndash;150 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eX. Zhu, W. Feng, J. Chang, Y. W. Tan, J. Li, M. Chen, Y. Sun, F. Li, Temperature-feedback upconversion nanocomposite for accurate photothermal therapy at facile temperature. Nat. Commun. 7, 1\u0026ndash;10 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZ. Li, Y. Zhang, An efficient and user-friendly method for the synthesis of hexagonal-phase NaYF4:Yb, Er/Tm nanocrystals with controllable shape and upconversion fluorescence. Nanotechnology 19, 345606 (2008).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Wearable photonic devices, multimodal sensor, stretchable optics, healthcare monitoring","lastPublishedDoi":"10.21203/rs.3.rs-4548546/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4548546/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eStretchable sensors that can conformally interface with the skins for wearable and real-time monitoring of skin deformations, temperature, and sweat biomarkers are of profound significance for early prediction, diagnosis, and treatment of diseases. Integration of multiple modalities in a single stretchable sensor to simultaneously detect these stimuli would be beneficial for more sophisticated understanding of human physiology, but yet, has not been achieved. Here, we report a stretchable multimodal photonic sensor capable of simultaneously detecting and discriminating strain deformations, temperature, and sweat pH in a single sensor architecture. The multimodal sensing abilities are enabled by realization of multiple sensing mechanisms in a hydrogel-coated polydimethylsiloxane (PDMS) optical fiber (HPOF), featured with high flexibility, stretchability, and biocompatibility. The integrated mechanisms are designed to operate at distinct wavelengths to facilitate stimuli decoupling, and adopt a ratiometric detection strategy for improved robustness and accuracy. To achieve simplicity on sensor interrogation, spectrally-resolved multiband emissions are generated upon the excitation of a single-wavelength laser based on upconversion luminescence (UCL) and radiative energy transfer (RET) processes. We show that the sensor allows for simultaneous and sensitive detection of strain deformations, temperature, and pH levels in the physiological range with fast responsiveness, robust repeatability, and reliability. Furthermore, we demonstrate proof-of-concept applications of the sensor for simultaneously detecting artery pulse or cardiopulmonary activities, along with skin temperature and sweat pH with negligible crosstalk, enabling a new paradigm of wearable multiparameter monitoring in healthcare.\u003c/p\u003e","manuscriptTitle":"Stretchable multimodal photonic sensor for wearable healthcare monitoring","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-31 05:25:04","doi":"10.21203/rs.3.rs-4548546/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a530025e-2271-4239-9e60-cc891c9091c6","owner":[],"postedDate":"July 31st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":33415824,"name":"Physical sciences/Materials science/Materials for devices/Sensors and biosensors"},{"id":33415825,"name":"Physical sciences/Optics and photonics/Applied optics/Optical sensors"},{"id":33415826,"name":"Physical sciences/Optics and photonics/Applied optics/Optoelectronic devices and components"},{"id":33415827,"name":"Physical sciences/Materials science/Soft materials/Polymers"}],"tags":[],"updatedAt":"2024-07-31T05:25:06+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-31 05:25:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4548546","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4548546","identity":"rs-4548546","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}