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Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.

Real-time monitoring of human health can be significantly improved by designing novel electronic skin (E-skin) platforms that mimic the characteristics and sensitivity of human skin. A high-quality E-skin platform that can simultaneously monitor multiple physiological and metabolic biomarkers without introducing skin discomfort or irritation is an unmet medical need. Conventional E-skins are either monofunctional or made from elastomeric films that do not include key synergistic features of natural skin, such as multi-sensing, breathability, and thermal management capabilities in a single patch. Herein, a biocompatible and biodegradable E-skin patch based on flexible gelatin methacryloyl aerogel (FGA) for non-invasive and continuous monitoring of multiple biomarkers of interest is engineered and demonstrated. Taking advantage of cryogenic temperature treatment and slow polymerization, FGA is fabricated with a highly interconnected porous structure that displays good flexibility, passive-cooling capabilities, and ultra-lightweight properties that make it comfortable to wear for long periods of time. It also provides numerous permeable capillary channels for thermal-moisture transfer, ensuring its excellent breathability. Therefore, the engineered FGA-based E-skin can simultaneously monitor body temperature, hydration, and biopotentials via electrophysiological sensors and detect glucose, lactate, and alcohol levels via electrochemical sensors. This work offers a previously unexplored materials strategy for next-generation E-skin platforms with superior practicality.

Wearable piezoresistive sensors are being developed as electronic skins (E-skin) for broad applications in human physiological monitoring and soft robotics. Tactile sensors with sufficient sensitivities, durability, and large dynamic ranges are required to replicate this critical component of the somatosensory system. Multiple micro/nanostructures, materials, and sensing modalities have been reported to address this need. However, a trade-off arises between device performance and device complexity. Inspired by the microstructure of the spinosum at the dermo epidermal junction in skin, a low-cost, scalable, and high-performance piezoresistive sensor is developed with high sensitivity (0.144 kPa-1 ), extensive sensing range ( 0.1-15 kPa), fast response time (less than 150 ms), and excellent long-term stability (over 1000 cycles). Furthermore, the piezoresistive functionality of the device is realized via a flexible transparent electrode (FTE) using a highly stable reduced graphene oxide self-wrapped copper nanowire network. The developed nanowire-based spinosum microstructured FTEs are amenable to wearable electronics applications.

Gelatin methacryloyl (GelMA) is a widely used hydrogel with skin-derived gelatin acting as the main constituent. However, GelMA has not been used in the development of wearable biosensors, which are emerging devices that enable personalized healthcare monitoring. This work highlights the potential of GelMA for wearable biosensing applications by demonstrating a fully solution-processable and transparent capacitive tactile sensor with microstructured GelMA as the core dielectric layer. A robust chemical bonding and a reliable encapsulation approach are introduced to overcome detachment and water-evaporation issues in hydrogel biosensors. The resultant GelMA tactile sensor shows a high-pressure sensitivity of 0.19 kPa-1 and one order of magnitude lower limit of detection (0.1 Pa) compared to previous hydrogel pressure sensors owing to its excellent mechanical and electrical properties (dielectric constant). Furthermore, it shows durability up to 3000 test cycles because of tough chemical bonding, and long-term stability of 3 days due to the inclusion of an encapsulation layer, which prevents water evaporation (80% water content). Successful monitoring of various human physiological and motion signals demonstrates the potential of these GelMA tactile sensors for wearable biosensing applications.

Animal models and traditional cell cultures are essential tools for drug development. However, these platforms can show striking discrepancies in efficacy and side effects when compared to human trials. These differences can lengthen the drug development process and even lead to drug withdrawal from the market. The establishment of preclinical drug screening platforms that have higher relevancy to physiological conditions is desirable to facilitate drug development. Here, a heart-on-a-chip platform, incorporating microgrooves and electrical pulse stimulations to recapitulate the well-aligned structure and synchronous beating of cardiomyocytes (CMs) for drug screening, is reported. Each chip is made with facile lithographic and laser-cutting processes that can be easily scaled up to high-throughput format. The maturation and phenotypic changes of CMs cultured on the heart-on-a-chip is validated and it can be treated with various drugs to evaluate cardiotoxicity and cardioprotective efficacy. The heart-on-a-chip can provide a high-throughput drug screening platform in preclinical drug development.

The development of wearable biosensors for continuous noninvasive monitoring of target biomarkers is limited to assays of a single sampled biofluid. An example of simultaneous noninvasive sampling and analysis of two different biofluids using a single wearable epidermal platform is demonstrated here. The concept is successfully realized through sweat stimulation (via transdermal pilocarpine delivery) at an anode, alongside extraction of interstitial fluid (ISF) at a cathode. The system thus allows on-demand, controlled sampling of the two epidermal biofluids at the same time, at two physically separate locations (on the same flexible platform) containing different electrochemical biosensors for monitoring the corresponding biomarkers. Such a dual biofluid sampling and analysis concept is implemented using a cost-effective screen-printing technique with body-compliant temporary tattoo materials and conformal wireless readout circuits to enable real-time measurement of biomarkers in the sampled epidermal biofluids. The performance of the developed wearable device is demonstrated by measuring sweat-alcohol and ISF-glucose in human subjects consuming food and alcoholic drinks. The different compositions of sweat and ISF with good correlations of their chemical constituents to their blood levels make the developed platform extremely attractive for enhancing the power and scope of next-generation noninvasive epidermal biosensing systems.

The use of conducting polymers such as poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) for the development of soft organic bioelectronic devices, such as organic electrochemical transistors (OECTs), is rapidly increasing. However, directly manipulating conducting polymer thin films on soft substrates remains challenging, which hinders the development of conformable organic bioelectronic devices. A facile transfer‐printing of conducting polymer thin films from conventional rigid substrates to flexible substrates offers an alternative solution. In this work, it is reported that PEDOT:PSS thin films on glass substrates, once mixed with surfactants, can be delaminated with hydrogels and thereafter be transferred to soft substrates without any further treatments. The proposed method allows easy, fast, and reliable transferring of patterned PEDOT:PSS thin films from glass substrates onto various soft substrates, facilitating their application in soft organic bioelectronics. By taking advantage of this method, skin‐attachable tattoo‐OECTs are demonstrated, relevant for conformable, imperceptible, and wearable organic biosensing. [ABSTRACT FROM AUTHOR]

Microphysiological systems, also known as organ‐on‐a‐chip platforms, show promise for the development of new testing methods that can be more accurate than both conventional two‐dimensional (2D) cultures and costly animal studies. The development of more intricate microphysiological systems can help to better mimic the human physiology and highlight the systemic effects of different drugs and materials. Nanomaterials are among a technologically important class of materials used for diagnostic, therapeutic, and monitoring purposes; all of which can be tested using new organ‐on‐a‐chip systems. In addition, the toxicity of nanomaterials which have entered the body from ambient air or diet can have deleterious effects on various body systems. This in turn can be studied in newly developed microphysiological systems. While organ‐on‐a‐chip models can be useful, they cannot pick up secondary and systemic toxicity. Thus, the utilization of multiorgan‐on‐a‐chip systems for advancing nanotechnology will largely be reflected in the future of drug development, toxicology studies, and precision medicine. Various aspects of related studies, current challenges, and future perspectives are discussed in this paper. [ABSTRACT FROM AUTHOR]

The contact lens (CL) industry has made great strides in improving CL-wearing experiences. However, a large amount of CL wearers continue to experience ocular dryness, known as contact lens-induced dry eye (CLIDE), stemming from the reduction in tear volume, tear film instability, increased tear osmolarity followed by inflammation and resulting in ocular discomfort and visual disturbances. In this article, to address tear film thinning between the CL and the ocular surface, the concept of using a CL with microchannels to deliver the tears from the pre-lens tear film (PrLTF) to the post-lens ocular surface using in vitro eye-blink motion is investigated. This study reports an eye-blink mimicking system with microfluidic poly(2-hydroxyethyl methacrylate) (poly(HEMA)) hydrogel with integrated microchannels to demonstrate eye-blink assisted flow through microchannels. This in vitro experimental study provides a proof-of-concept result that tear transport from PrLTF to post-lens tear film can be enhanced by an artificial eyelid motion in a pressure range of 0.1-5 kPa (similar to human eyelid pressure) through poly(HEMA) microchannels. Simulation is conducted to support the hypothesis. This work demonstrates the feasibility of developing microfluidic CLs with the potential to help prevent or minimize CLIDE and discomfort by the enhanced transport of pre-lens tears to the post-lens ocular surface., (© 2022 Wiley-VCH GmbH.)

Wearable and implantable pressure sensors are in great demand for personalized health monitoring. Pressure sensors with low operation voltage and low power-consumption are desired for energy-saving devices. Organic iontronic devices, such as organic electrochemical transistors (OECTs), have demonstrated great potential for low power-consumption bioelectronic sensing applications. The ability to conduct both electrons and ions, in addition to their low-operation voltage has enabled the widespread use of OECTs in different biosensing fields. However, despite these merits, OECTs have not been demonstrated for pressure sensing applications. This is because most OECTs are gated with aqueous electrolyte, which fails to respond to external pressure. Here, a low power-consumption iontronic pressure sensor is presented based on an OECT, in which an ionic hydrogel is used as a solid gating medium. The resultant iontronic device operated at voltages less than 1 V, with a power-consumption between ~ 10 1 -10 3 μ W, while maintaining a tunable sensitivity between 1 ~ 10 kPa -1 . This work places OECTs on the frontline for developing low power-consumption iontronic pressure sensors and for biosensing applications.