Intertwined with concepts of telehealth, internet of medical things, and precision medicine, wearable sensors offer attractive features to actively and remotely monitor physiological parameters. Wearable sensors can generate data continuously without causing any discomfort 1,2 or interruptions to daily activity, thus enhancing wearer’s self-monitoring compliance and improving patient care quality.2–4 The monitoring of physical parameters, such as electrocardiogram (ECG)5–7 and blood pressure (BP),8–10 and of biochemical parameters, such as glucose,11–15 using non-invasive wearable sensors has been reported. Recent efforts have led to the integration of physical and chemical sensors into a single wearable device, such as sensors for ECG with lactate16 or glucose17 for monitoring athlete’s performance, and temperature with metabolites and electrolytes for signal calibration.12,18 Yet, to the best of our knowledge, the in-depth study of the correlation of cardiovascular parameters, particularly BP and heart rate (HR), with biomarker levels using an integrated hybrid wearable sensor, remains unexplored.
BP and HR, two of the most important vital signs, can dynamically and directly reflect the physiological status of the body. These cardiovascular parameters can be affected by fluctuations of various biomarker concentrations originated from activities, such as movement, stress, or intake of food, drinks, and drugs. Multimodal BP-chemical sensing could thus have a tremendous clinical value, especially for people with underlying health conditions, such as the elderlies, obese individuals, diabetic and cardiovascular patients, as their physiological response to normal day-to-day activities might differ from healthy people. Further, the prevention, diagnosis, and treatment of many diseases can greatly benefit from the simultaneous monitoring of cardiovascular parameters and biomarker levels. These include acute and deadly septic shock, which commonly involves sudden drops in BP accompanied by rapidly increasing blood lactate levels19 and hypo/hyperglycemia-induced hypo/hypertension which increases the risks of stroke, cardiac diseases, retinopathy, and nephropathy in diabetic patients.20–23 The recent global pandemic has also highlighted the urgent needs for remote self-monitoring devices, with particular attention to the management of high BP and diabetes, which are the major factors in the deaths of COVID-19 patients.24 A comprehensive cardiovascular/biomarker self-monitoring platform would enhance users’ self-awareness to their health conditions, and alert them and their caregivers to the occurrence of abnormal physiological changes.
Herein, we present for the first time, a conformal, stretchable, and integrated wearable sensor that can simultaneously monitor BP, HR, and levels of glucose, lactate, caffeine, and alcohol, toward dynamic and comprehensive health self-monitoring. We use ultrasonic transducers for monitoring the BP and HR, and electrochemical sensors for measuring the levels of biomarkers. Through strategic material selection, layout design, and fabrication innovation, we integrated rigid and soft sensor components, namely customized piezoelectric lead zirconate titanate (PZT) ultrasound transducers and printed polymer composites via innovative solvent-soldering process, into a single wearable conformal platform with high mechanical resiliency and free of sensor crosstalk. Such rational design overcomes engineering challenges related to the integration of the different sensing modalities and materials to allow real-time monitoring of cardiovascular parameters and biomarker levels, in connection to parallel sampling of the interstitial fluid (ISF) and sweat biofluids. The resulting epidermal hybrid device can emit ultrasonic pulses and sense echoes from arteries, while stimulating sweat and extracting ISF through iontophoresis (IP), allowing simultaneous measurements of BP and HR, along with multiple biomarkers in these biofluids. We carried out on-body trials with multiple human subjects experiencing diverse activities and stimuli (exercising, having alcohol, food, and caffeine) (Fig. 1d). The correlations between metabolic variations and hemodynamic activities, under these stimuli, were monitored and evaluated. The improved sensor assembly process, leveraging the SEBS-based stretchable materials, allows the fast and reliable fabrication of a stretchable and conformal epidermal sensor for simultaneous acoustic and electrochemical sensing. Such device offers (i) comprehensive tracking of the effect of daily activities and stimuli upon the users’ physiological status, and (ii) enables the collection of previously unavailable data towards understanding of the body response to such stimuli, while addressing the critical post-pandemic needs for remote telemetric patient monitoring.
The multimodal sensing platform is depicted in Fig. 1a. Styrene-ethylene-butylene-styrene block copolymer (SEBS) was used as the stretchable and conformal substrate to support the electrodes and connections printed with customized inks (Fig. 1e, Supplementary Fig. 1). The stretchable substrate and inks allow the high conformity, flexibility (Fig. 1f-i) and stretchability (Fig. 1f-ii) required for wearable devices. The BP sensor consists of an array of eight piezoelectric transducers, which are aligned with the carotid artery upon applying on the neck to obtain optimal ultrasonic signals (Supplementary Figs. 2–4). During sensing, the piezoelectric transducers were activated with electrical pulses, transmitting ultrasound beams to the artery, and the time of flight of the echoes from the anterior and the posterior walls of the artery was analyzed to gauge the dilation and contraction of arteries (Fig. 1c, h). Detailed information regarding the fabrication of the multimodal sensor is discussed in Fig. 2m and Supplementary Note 1. The BP sensor characterization is discussed in Supplementary Note 3 and Supplementary Fig. 10. The chemical sensing has been realized through non-invasive sweat stimulation (via transdermal pilocarpine delivery) at the IP anode, alongside with ISF extraction at the IP cathode. (Fig. 1b). Chronoamperometry (CA) was used for electrochemical detection of the hydrogen peroxide product of the glucose oxidase (GOx), lactate oxidase (LOx), and alcohol oxidase (AOx) enzymatic reactions, while differential pulse voltammetry (DPV) was used for the detection of caffeine. Detailed electrode modification and reaction mechanisms are discussed in Supplementary Fig. 5. The analytical performance of each chemical sensor is shown in Fig. 1g, Supplementary Figs. 6–9, and Supplementary Note 2.