Wearable biosensors are garnering substantial interest due to their potential to provide continuous, real-time physiological information via dynamic, noninvasive measurements of biochemical markers in biofluids, such as sweat, tears, saliva and interstitial fluid. Recent developments have focused on electrochemical and optical biosensors, together with advances in the noninvasive monitoring of biomarkers including metabolites, bacteria and hormones. A combination of multiplexed biosensing, microfluidic sampling and transport systems have been integrated, miniaturized and combined with flexible materials for improved wearability and ease of operation. Although wearable biosensors hold promise, a better understanding of the correlations between analyte concentrations in the blood and noninvasive biofluids is needed to improve reliability. An expanded set of on-body bioaffinity assays and more sensing strategies are needed to make more biomarkers accessible to monitoring. Large-cohort validation studies of wearable biosensor performance will be needed to underpin clinical acceptance. Accurate and reliable real-time sensing of physiological information using wearable biosensor technologies would have a broad impact on our daily lives.

Wearable biosensors for healthcare monitoring.

Wearable biosensors have received tremendous attention over the past decade owing to their great potential in predictive analytics and treatment toward personalized medicine. Flexible electronics could serve as an ideal platform for personalized wearable devices because of their unique properties such as light weight, low cost, high flexibility and great conformability. Unlike most reported flexible sensors that mainly track physical activities and vital signs, the new generation of wearable and flexible chemical sensors enables real-time, continuous and fast detection of accessible biomarkers from the human body, and allows for the collection of large-scale information about the individual's dynamic health status at the molecular level. In this article, we review and highlight recent advances in wearable and flexible sensors toward continuous and non-invasive molecular analysis in sweat, tears, saliva, interstitial fluid, blood, wound exudate as well as exhaled breath. The flexible platforms, sensing mechanisms, and device and system configurations employed for continuous monitoring are summarized. We also discuss the key challenges and opportunities of the wearable and flexible chemical sensors that lie ahead.

Wearable and flexible electronics for continuous molecular monitoring.

Bio-integrated wearable systems can measure a broad range of biophysical, biochemical, and environmental signals to provide critical insights into overall health status and to quantify human performance. Recent advances in material science, chemical analysis techniques, device designs, and assembly methods form the foundations for a uniquely differentiated type of wearable technology, characterized by noninvasive, intimate integration with the soft, curved, time-dynamic surfaces of the body. This review summarizes the latest advances in this emerging field of “bio-integrated” technologies in a comprehensive manner that connects fundamental developments in chemistry, material science, and engineering with sensing technologies that have the potential for widespread deployment and societal benefit in human health care. An introduction to the chemistries and materials for the active components of these systems contextualizes essential design considerations for sensors and associated platforms that appear in f...

Bio-Integrated Wearable Systems: A Comprehensive Review

Continuous monitoring of the central-blood-pressure waveform from deeply embedded vessels, such as the carotid artery and jugular vein, has clinical value for the prediction of all-cause cardiovascular mortality. However, existing non-invasive approaches, including photoplethysmography and tonometry, only enable access to the superficial peripheral vasculature. Although current ultrasonic technologies allow non-invasive deep-tissue observation, unstable coupling with the tissue surface resulting from the bulkiness and rigidity of conventional ultrasound probes introduces usability constraints. Here, we describe the design and operation of an ultrasonic device that is conformal to the skin and capable of capturing blood-pressure waveforms at deeply embedded arterial and venous sites. The wearable device is ultrathin (240 μm) and stretchable (with strains up to 60%), and enables the non-invasive, continuous and accurate monitoring of cardiovascular events from multiple body locations, which should facilitate its use in a variety of clinical environments.

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Monitoring of the central blood pressure waveform via a conformal ultrasonic device.

Disposable sensors are low-cost and easy-to-use sensing devices intended for short-term or rapid single-point measurements. The growing demand for fast, accessible, and reliable information in a vastly connected world makes disposable sensors increasingly important. The areas of application for such devices are numerous, ranging from pharmaceutical, agricultural, environmental, forensic, and food sciences to wearables and clinical diagnostics, especially in resource-limited settings. The capabilities of disposable sensors can extend beyond measuring traditional physical quantities (for example, temperature or pressure); they can provide critical chemical and biological information (chemo- and biosensors) that can be digitized and made available to users and centralized/decentralized facilities for data storage, remotely. These features could pave the way for new classes of low-cost systems for health, food, and environmental monitoring that can democratize sensing across the globe. Here, a brief insight into the materials and basics of sensors (methods of transduction, molecular recognition, and amplification) is provided followed by a comprehensive and critical overview of the disposable sensors currently used for medical diagnostics, food, and environmental analysis. Finally, views on how the field of disposable sensing devices will continue its evolution are discussed, including the future trends, challenges, and opportunities.

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Disposable Sensors in Diagnostics, Food, and Environmental Monitoring.

Despite tremendous recent efforts, noninvasive sweat monitoring is still far from delivering its early analytical promise. Here, we describe a flexible epidermal microfluidic detection platform fabricated through hybridization of lithographic and screen-printed technologies, for efficient and fast sweat sampling and continuous, real-time electrochemical monitoring of glucose and lactate levels. This soft, skin-mounted device judiciously merges lab-on-a-chip and electrochemical detection technologies, integrated with a miniaturized flexible electronic board for real-time wireless data transmission to a mobile device. Modeling of the device design and sweat flow conditions allowed optimization of the sampling process and the microchannel layout for achieving attractive fluid dynamics and rapid filling of the detection reservoir (within 8 min from starting exercise). The wearable microdevice thus enabled efficient natural sweat pumping to the electrochemical detection chamber containing the enzyme-modified e...

Epidermal Microfluidic Electrochemical Detection System: Enhanced Sweat Sampling and Metabolite Detection

To enable continuous, mobile health monitoring, body worn sensors need to offer comparable performance to clinical devices in a lightweight, unobtrusive package. This work presents a complete wireless electrophysiology data acquisition system (weDAQ) that is demonstrated for in-ear EEG with user-generic dry-contact electrodes made from standard printed circuit boards (PCBs). Each weDAQ device supports 16 channels, driven right leg, impedance scanning, 3-axis accelerometer data, local storage, high sampling rates, and adaptable data transmission modes. The weDAQ wireless platform supports body sensor networks (BSN) capable of aggregating multiple biosignal streams (EEG, EMG, EOG, etc.) by supporting simultaneous connectivity of multiple worn devices over the 802.11n WiFi protocol. Each channel achieves 28dB of gain over 70Hz bandwidth with a noise level of 0.92 μ Vpp and CMRR of 110.8 dB. In-ear and forehead EEG measurements taken from subjects captured modulation of alpha brain activity, EOG characteristic eye movements, and EMG from jaw muscles. The small footprint, performance, and flexibility of the weDAQ lay the foundation for online brain computer interface (BCI) experiments and smart, multimodal biosignal monitoring.

A Versatile In-Ear Biosensing System for Continuous Brain and Health Monitoring

Amplifiers in biomedical sensing systems play a crucial role in elucidating often weak biosignals such as those originating from the brain in electroencephalograms (EEG) but can suffer from flicker (1/f) and thermal noise. Correlated double-sampling (CDS) is a method that can be used to reduce low frequency noise. Conventionally implemented as an analog reset of the amplifier between samples of interest, the CDS operation adds kT/C sampling noise which may exceed the low-frequency noise being removed, especially if the reset is not allowed adequate time to settle. Analog CDS therefore, puts a limitation on the sampling frequency of such sensing systems, making them less ideal for the fast, high-bandwidth acquisition required for applications such as neural interfaces. Digital CDS is presented here as a technique which relies on intermittent sampling of an internal reference voltage taken during brief disconnections from the sensor between real samples for a noise correction performed digitally post-acquisition. This work demonstrates the implementation of digital CDS on a neural interface system-on-chip (NISoC) and details the optimization of a windowed weighting correction algorithm to achieve a 71% improvement in noise performance. In-Ear EEG and EOG recordings were performed with and without CDS for comparison.

Min Yul Lee

Papers

Epidermal Microfluidic Electrochemical Detection System: Enhanced Sweat Sampling and Metabolite Detection

A Versatile In-Ear Biosensing System for Continuous Brain and Health Monitoring

Neural Recording Analog Front-End Noise Reduction with Digital Correlated Double Sampling