Wearable Sweat Sensor for Personalized Metabolic and Nutritional Management
Metabolic syndrome, a metabolic disorder defined as glucose intolerance, obesity, hypertension and dyslipidemia, is a risk factor for atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes (T2DB). The prevalence of metabolic syndrome ranges from 10% to 40% worldwide, with a prevalence of 33% in US.[1] Despite chronic screening of the metabolic diseases, it is still of urgent need to detect and monitor the metabolic biomarkers, and an effective nutritional treatment could be personalized from different dietary interventions to ameliorate symptoms such as inflammation, glucose intolerance, etc. [1] Sampling of circulating metabolites and nutrients in serum could provide useful insights in metabolic health management and treatment evaluation, but the process is episodic, requiring frequent clinic visits and invasive blood-drawing procedures.
Wearable electronics for non-invasive metabolic monitoring
Wearables biosensors provide great outlook for non-invasive continuous monitoring of human health and provide great potentials for personalized medicine with the large data sets collected. However, existing commercial wearables are limited to physical sensing (e.g. heart rate). Human sweat serves as an attractive biofluid for non-invasive metabolic monitoring, as it contains a wealth of chemicals reflective of metabolic condition.[2] The transition from plasma to sweat analyses could provide an innovative and noninvasive means of metabolic and nutritional monitoring based on sweat molecular data collected continuously from a wearable device. Despite burgeoning research studies on wearable sweat sensors, there was limited progress on detecting more chemical targets in human in vivo. [2,3] My research focuses on developing highly sensitive wearable sweat sensors which could perform continuous metabolic monitoring and enable personalized nutritional intervention.
Materials and chemistry innovation for high performance biosensing
Most of the metabolites are of ultralow levels in human sweat after partitioning from blood, and commercially available electrodes such as glassy carbon and screen-printed electrodes could barely achieve micromolar-level sensitivity. While modification of nanomaterials could improve the sensitivity, modifying the sensing electrode individually with nanomaterials through a drop-casting method is time-consuming and could result in large sensor variations. We recently developed a massproducible laser-engraved wearable microfluidic system that consists of laser-engraved graphene (LEG)- based sensors for highly sensitive sweat analysis and multiplexed vital sign monitoring (Fig. 1).[4] Laserengraved medical adhesives with microchannel patterns were mass-produced and assembled to create the sweatsampling microfluidics. The multi-inlet design enabled a much faster and efficient sweat sampling (2~3min filling
Fig. 1. Laser-engraved microfluidic sensor patch.[4] LEG-based sensors enable highly sensitive metabolic and nutritional sensing in human sweat.
and refreshing time). As polyimide was etched by laser, it underwent a photothermal process and yields graphene structure at optimized laser settings. Owing to unique electrochemical properties arising from the fast electron mobility, high current density, and ultra large surface area, our LEG sensor enables the first ever demonstration of ultra-low-level uric acid (UA) and tyrosine (Tyr) monitoring in human sweat through differential pulse voltammetry. The LEG-based approach could be easily adapted to other sensing strategies for targets such as Fig. 1. Laser-engraved microfluidic sensor patch.[4] LEG-based sensors enable highly sensitive metabolic and nutritional sensing in human sweat. amino acids, vitamins, hormones, etc. For example, we developed a highly sensitive cortisol sensor using LEG and achieved accurate and sensitive cortisol measurements in human sweat, saliva and serum. [5] We have also developed a fast and accurate COVID antibody test sensor with the LEG. [6]
Fully integrated wireless wearable sensing systems
a c
b
Fig. 2. Fully integrated wireless system for dynamic molecular sensing. a. UA and amino acid sensing.[4] b. stress hormone cortisol sensing.[5] c. urea and ammonium sensing.[7] Scale bar, 1 cm.
In order to achieve accurate and continuous wearable sensing, system-level integration is necessary. We have developed fully integrated wireless systems for realtime signal conditioning, processing and wireless data transmission. The metabolic information could be wirelessly sent to a user interface and displayed on a custom developed cellphone app. The patches can be attached to skin conformally and could provide real-time and non-invasive sensing of various metabolites and nutrients (Fig. 2). [4-7]
Validation of wearable biosensor for the management of metabolic disorders
Fig. 3. Evaluation of the wearable sensor for non-invasive gout management by continuously monitoring sweat UA.[4]
In collaboration with Prof. Zhaoping Li at UCLA Medical Center (chief of Clinical Nutrition), we are evaluating our wearable systems for personalized management of various metabolic disorders. For example, considering that elevated UA is a hallmark biomarker for gout (a common metabolic disease associated with high prevalence of metabolic syndrome and affecting millions of people globally), we have successfully applied our wearable UA sensor in healthy individuals as well as patients with gout and hyperuricemia (Fig. 3).[4]
The high sweat-serum UA correlation obtained with the LEG sensor has shown promising potentials of using the wearable LEG sensor for continuous UA monitoring for metabolic health monitoring (Fig. 3).[4] Right now, we are integrating more biosensors for monitor a broad range of metabolic risk factors and evaluate our sensors in patients with metabolic syndrome (with 3 active IRB protocols at UCLA and Caltech). Summary. My research thrusts include fundamental chemistry and materials innovations with practical device and system level applications toward personalized metabolic and nutritional management. With the continuing technical innovations and working closely with our clinical nutrition collaborators, I believe our wearable biosensing technology could play a crucial role in future personalized metabolic and nutritional management.
Summary
My research thrusts include fundamental chemistry and materials innovations with practical device and system level applications toward personalized metabolic and nutritional management. With the continuing technical innovations and working closely with our clinical nutrition collaborators, I believe our wearable biosensing technology could play a crucial role in future personalized metabolic and nutritional management.
Reference
1. Grundy, S. M. JAMA. 2015,313.19,1973-1974.
2. Yang, Y. and Gao, W. Chem. Soc. Rev. 2019, 48.6, 1465-1491.
3. Xu, C.; Yang, Y.; Gao, W. Matter 2020, 2.6, 1414-1445.
4. Yang, Y. et al. Nat. Biotechnol. 2020, 38.2, 217-224.
5. Torrente-Rodríguez, R. M.; Tu, J.; Yang, Y. et al. Matter, 2020, 2, 921-937.
6. Torrente-Rodríguez, R. M.; Lukas, H.; Tu, J.; Min, J.; Yang, Y. et al. Matter, 2020, 3, 1–18.
7. Yu, Y.; Nassar, J.; Xu, C.; Min J.; Yang Y. et al. Science Robotics, 2020, 5, eaaz7946.