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1. An autonomous wearable system for diurnal sweat biomarker data acquisition

   https://doi.org/10.1039/d0lc00820f  

   Hojaiji, Hannaneh; Zhao, Yichao; Gong, Max C.; Mallajosyula, Mudith; Tan, Jiawei; Lin, Haisong; Hojaiji, Amir M.; Lin, Shuyu; Milla, Carlos; Madni, Asad M.; et al (December 2020, Lab on a Chip)

   To track dynamically varying and physiologically relevant biomarker profiles in sweat, autonomous wearable platforms are required to periodically sample and analyze sweat with minimal or no user intervention. Previously reported sweat sensors are functionally limited to capturing biomarker information at one time-point/period, thereby necessitating repeated user intervention to increase the temporal granularity of biomarker data. Accordingly, we present a compact multi-compartment wearable system, where each compartment can be activated to autonomously induce/modulate sweat secretion ( via iontophoretic actuation) and analyze sweat at set time points. This system was developed following a hybrid-flex design and a vertical integration scheme—integrating the required functional modules: miniaturized iontophoresis interfaces, adhesive thin film microfluidic-sensing module, and control/readout electronics. The system was deployed in a human subject study to track the diurnal variation of sweat glucose levels in relation to the daily food intake. The demonstrated autonomous operation for diurnal sweat biomarker data acquisition illustrates the system's suitability for large-scale and longitudinal personal health monitoring applications. 

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2. Wearable aptamer-field-effect transistor sensing system for noninvasive cortisol monitoring

   https://doi.org/10.1126/sciadv.abk0967  

   Wang, Bo; Zhao, Chuanzhen; Wang, Zhaoqing; Yang, Kyung-Ae; Cheng, Xuanbing; Liu, Wenfei; Yu, Wenzhuo; Lin, Shuyu; Zhao, Yichao; Cheung, Kevin M.; et al (January 2022, Science Advances)

   Wearable technologies for personalized monitoring require sensors that track biomarkers often present at low levels. Cortisol—a key stress biomarker—is present in sweat at low nanomolar concentrations. Previous wearable sensing systems are limited to analytes in the micromolar-millimolar ranges. To overcome this and other limitations, we developed a flexible field-effect transistor (FET) biosensor array that exploits a previously unreported cortisol aptamer coupled to nanometer-thin-film In 2 O 3 FETs. Cortisol levels were determined via molecular recognition by aptamers where binding was transduced to electrical signals on FETs. The physiological relevance of cortisol as a stress biomarker was demonstrated by tracking salivary cortisol levels in participants in a Trier Social Stress Test and establishing correlations between cortisol in diurnal saliva and sweat samples. These correlations motivated the development and on-body validation of an aptamer-FET array–based smartwatch equipped with a custom, multichannel, self-referencing, and autonomous source measurement unit enabling seamless, real-time cortisol sweat sensing. 

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3. A programmable epidermal microfluidic valving system for wearable biofluid management and contextual biomarker analysis

   https://doi.org/10.1038/s41467-020-18238-6  

   Lin, Haisong; Tan, Jiawei; Zhu, Jialun; Lin, Shuyu; Zhao, Yichao; Yu, Wenzhuo; Hojaiji, Hannaneh; Wang, Bo; Yang, Siyang; Cheng, Xuanbing; et al (September 2020, Nature Communications)

   Abstract Active biofluid management is central to the realization of wearable bioanalytical platforms that are poised to autonomously provide frequent, real-time, and accurate measures of biomarkers in epidermally-retrievable biofluids (e.g., sweat). Accordingly, here, a programmable epidermal microfluidic valving system is devised, which is capable of biofluid sampling, routing, and compartmentalization for biomarker analysis. At its core, the system is a network of individually-addressable microheater-controlled thermo-responsive hydrogel valves, augmented with a pressure regulation mechanism to accommodate pressure built-up, when interfacing sweat glands. The active biofluid control achieved by this system is harnessed to create unprecedented wearable bioanalytical capabilities at both the sensor level (decoupling the confounding influence of flow rate variability on sensor response) and the system level (facilitating context-based sensor selection/protection). Through integration with a wireless flexible printed circuit board and seamless bilateral communication with consumer electronics (e.g., smartwatch), contextually-relevant (scheduled/on-demand) on-body biomarker data acquisition/display was achieved. 

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4. A Computationally Assisted Approach for Designing Wearable Biosensors toward Non‐Invasive Personalized Molecular Analysis

   https://doi.org/10.1002/adma.202212161  

   Mukasa, Daniel; Wang, Minqiang; Min, Jihong; Yang, Yiran; Solomon, Samuel_A; Han, Hong; Ye, Cui; Gao, Wei (July 2023, Advanced Materials)

   Abstract Wearable sweat sensors have the potential to revolutionize precision medicine as they can non‐invasively collect molecular information closely associated with an individual's health status. However, the majority of clinically relevant biomarkers cannot be continuously detected in situ using existing wearable approaches. Molecularly imprinted polymers (MIPs) are a promising candidate to address this challenge but haven't yet gained widespread use due to their complex design and optimization process yielding variable selectivity. Here, QuantumDock is introduced, an automated computational framework for universal MIP development toward wearable applications. QuantumDock utilizes density functional theory to probe molecular interactions between monomers and the target/interferent molecules to optimize selectivity, a fundamentally limiting factor for MIP development toward wearable sensing. A molecular docking approach is employed to explore a wide range of known and unknown monomers, and to identify the optimal monomer/cross‐linker choice for subsequent MIP fabrication. Using an essential amino acid phenylalanine as the exemplar, experimental validation of QuantumDock is performed successfully using solution‐synthesized MIP nanoparticles coupled with ultraviolet–visible spectroscopy. Moreover, a QuantumDock‐optimized graphene‐based wearable device is designed that can perform autonomous sweat induction, sampling, and sensing. For the first time, wearable non‐invasive phenylalanine monitoring is demonstrated in human subjects toward personalized healthcare applications. 

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5. Skin-interfaced microfluidic systems with spatially engineered 3D fluidics for sweat capture and analysis

   https://doi.org/10.1126/sciadv.adg4272  

   Wu, Chung-Han; Ma, Howin_Jian Hing; Baessler, Paul; Balanay, Roxanne Kate; Ray, Tyler R (May 2023, Science Advances)

   Skin-interfaced wearable systems with integrated microfluidic structures and sensing capabilities offer powerful platforms for monitoring the signals arising from natural physiological processes. This paper introduces a set of strategies, processing approaches, and microfluidic designs that harness recent advances in additive manufacturing [three-dimensional (3D) printing] to establish a unique class of epidermal microfluidic (“epifluidic”) devices. A 3D printed epifluidic platform, called a “sweatainer,” demonstrates the potential of a true 3D design space for microfluidics through the fabrication of fluidic components with previously inaccessible complex architectures. These concepts support integration of colorimetric assays to facilitate in situ biomarker analysis operating in a mode analogous to traditional epifluidic systems. The sweatainer system enables a new mode of sweat collection, termed multidraw, which facilitates the collection of multiple, independent sweat samples for either on-body or external analysis. Field studies of the sweatainer system demonstrate the practical potential of these concepts. 

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