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.

Advances in wireless technologies, low-power electronics, the internet of things, and in the domain of connected health are driving innovations in wearable medical devices at a tremendous pace. Wearable sensor systems composed of flexible and stretchable materials have the potential to better interface to the human skin, whereas silicon-based electronics are extremely efficient in sensor data processing and transmission. Therefore, flexible and stretchable sensors combined with low-power silicon-based electronics are a viable and efficient approach for medical monitoring. Flexible medical devices designed for monitoring human vital signs, such as body temperature, heart rate, respiration rate, blood pressure, pulse oxygenation, and blood glucose have applications in both fitness monitoring and medical diagnostics. As a review of the latest development in flexible and wearable human vitals sensors, the essential components required for vitals sensors are outlined and discussed here, including the reported sensor systems, sensing mechanisms, sensor fabrication, power, and data processing requirements.

Monitoring of Vital Signs with Flexible and Wearable Medical Devices

Non-invasive wearable electrochemical sensors: a review

Thin-film electronics intimately laminated onto the skin imperceptibly equip the human body with electronic components for health-monitoring and information technologies. When electronic devices are worn, the mechanical flexibility and/or stretchability of thin-film devices helps to minimize the stress and discomfort associated with wear because of their conformability and softness. For industrial applications, it is important to fabricate wearable devices using processing methods that maximize throughput and minimize cost. We demonstrate ultraflexible and conformable three-color, highly efficient polymer light-emitting diodes (PLEDs) and organic photodetectors (OPDs) to realize optoelectronic skins (oe-skins) that introduce multiple electronic functionalities such as sensing and displays on the surface of human skin. The total thickness of the devices, including the substrate and encapsulation layer, is only 3 μm, which is one order of magnitude thinner than the epidermal layer of human skin. By integrating green and red PLEDs with OPDs, we fabricate an ultraflexible reflective pulse oximeter. The device unobtrusively measures the oxygen concentration of blood when laminated on a finger. On-skin seven-segment digital displays and color indicators can visualize data directly on the body.

Ultraflexible organic photonic skin

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.

This paper presents a noninvasive wireless sensor platform for continuous health monitoring. The sensor system integrates a loop antenna, wireless sensor interface chip, and glucose sensor on a polymer substrate. The IC consists of power management, readout circuitry, wireless communication interface, LED driver, and energy storage capacitors in a 0.36-mm2 CMOS chip with no external components. The sensitivity of our glucose sensor is 0.18 μA·mm-2·mM-1. The system is wirelessly powered and achieves a measured glucose range of 0.05-1 mM with a sensitivity of 400 Hz/mM while consuming 3 μW from a regulated 1.2-V supply.

A 3- $\mu\hbox{W}$ CMOS Glucose Sensor for Wireless Contact-Lens Tear Glucose Monitoring

We present the design, construction and in vivo rabbit testing of a wirelessly powered contact lens display. The display consists of an antenna, a 500 × 500 µm2 silicon power harvesting and radio integrated circuit, metal interconnects, insulation layers and a 750 × 750 µm2 transparent sapphire chip containing a custom-designed micro-light emitting diode with peak emission at 475 nm, all integrated onto a contact lens. The display can be powered wirelessly from ~1 m in free space and ~2 cm in vivo on a rabbit. The display was tested on live, anesthetized rabbits with no observed adverse effect. In order to extend display capabilities, design and fabrication of micro-Fresnel lenses on a contact lens are presented to move toward a multipixel display that can be worn in the form of a contact lens. Contact lenses with integrated micro-Fresnel lenses were also tested on live rabbits and showed no adverse effect.

https://iopscience.iop.org/article/10.1088/0960-1317/21/12/125014/pdf

A single-pixel wireless contact lens display

A contact lens having an integrated glucose sensor is provided. The contact lens includes an electrochemical sensor configured to measure the level of glucose in the tear fluid of the eye of the user wearing the contact lens. The electrochemical sensor is powered by radiation off-lens, through an RF antenna or a photovoltaic device mounted on the periphery of the contact lens. The power provided to the contact lens also enables transmission of data from the electrochemical sensor, for example by backscatter communications or optically by an LED mounted to the lens.

Wireless powered contact lens with glucose sensor

We present an integrated functional contact lens, composed of a differential glucose sensor module, metal interconnects, sensor read-out circuit, antenna and telecommunication circuit, to monitor tear glucose levels wirelessly, continuously and non-invasively. The electrochemical differential sensor module is based on immobilization of activated and de-activated glucose oxidase. We characterized the sensor on a model polymer eye and determined that it showed good repeatability, molecular interference rejection and linearity in the range of 0–2 mM glucose, covering normal tear glucose concentrations (0.1–0.6 mM). We also report the temperature, ageing and protein-fouling sensitivity of the sensor. We report the design and implementation of a low-power (3 µW) sensor read-out and telecommunication circuit to deliver wireless power and transmit data for the sensor module. Using this small chip (0.36 mm2), we produced an integrated contact lens with sensors and demonstrated wireless operation of the system and glucose read-out over the distance of several centimeters.

https://iopscience.iop.org/article/10.1088/0960-1317/22/7/075007/pdf

A contact lens with integrated telecommunication circuit and sensors for wireless and continuous tear glucose monitoring

By utilizing a differential tunable active inductor for the LC-tank, a wide tuning-range CMOS voltage-controlled oscillator (VCO) is presented. In the proposed circuit topology, the coarse frequency tuning is achieved by the tunable active inductor, while the fine tuning is controlled by the varactor. Using a 0.18-mum CMOS process, a prototype VCO is implemented for demonstration. The fabricated circuit provides an output frequency from 500 MHz to 3.0 GHz, resulting in a tuning range of 143% at radio frequencies. The measured phase noise is from -101 to -118 dBc/Hz at a 1-MHz offset within the entire frequency range. Due to the absence of the spiral inductors, the fully integrated VCO occupies an active area of 150times300 mum2

Yu-Te Liao

Papers

A 3- $\mu\hbox{W}$ CMOS Glucose Sensor for Wireless Contact-Lens Tear Glucose Monitoring

A single-pixel wireless contact lens display

Wireless powered contact lens with glucose sensor

A contact lens with integrated telecommunication circuit and sensors for wireless and continuous tear glucose monitoring

A Wide Tuning-Range CMOS VCO With a Differential Tunable Active Inductor