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.

Recent progress in electronic skin or e-skin research is broadly reviewed, focusing on technologies needed in three main applications: skin-attachable electronics, robotics, and prosthetics. First, since e-skin will be exposed to prolonged stresses of various kinds and needs to be conformally adhered to irregularly shaped surfaces, materials with intrinsic stretchability and self-healing properties are of great importance. Second, tactile sensing capability such as the detection of pressure, strain, slip, force vector, and temperature are important for health monitoring in skin attachable devices, and to enable object manipulation and detection of surrounding environment for robotics and prosthetics. For skin attachable devices, chemical and electrophysiological sensing and wireless signal communication are of high significance to fully gauge the state of health of users and to ensure user comfort. For robotics and prosthetics, large-area integration on 3D surfaces in a facile and scalable manner is critical. Furthermore, new signal processing strategies using neuromorphic devices are needed to efficiently process tactile information in a parallel and low power manner. For prosthetics, neural interfacing electrodes are of high importance. These topics are discussed, focusing on progress, current challenges, and future prospects.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.201904765

Electronic Skin: Recent Progress and Future Prospects for Skin‐Attachable Devices for Health Monitoring, Robotics, and Prosthetics

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

Wearable sweat sensors have the potential to provide continuous measurements of useful biomarkers. However, current sensors cannot accurately detect low analyte concentrations, lack multimodal sensing or are difficult to fabricate at large scale. We report an entirely laser-engraved sensor for simultaneous sweat sampling, chemical sensing and vital-sign monitoring. We demonstrate continuous detection of temperature, respiration rate and low concentrations of uric acid and tyrosine, analytes associated with diseases such as gout and metabolic disorders. We test the performance of the device in both physically trained and untrained subjects under exercise and after a protein-rich diet. We also evaluate its utility for gout monitoring in patients and healthy controls through a purine-rich meal challenge. Levels of uric acid in sweat were higher in patients with gout than in healthy individuals, and a similar trend was observed in serum.

A laser-engraved wearable sensor for sensitive detection of uric acid and tyrosine in sweat.

Recent advances in soft materials and system integration technologies have provided a unique opportunity to design various types of wearable flexible hybrid electronics (WFHE) for advanced human healthcare and human-machine interfaces. The hybrid integration of soft and biocompatible materials with miniaturized wireless wearable systems is undoubtedly an attractive prospect in the sense that the successful device performance requires high degrees of mechanical flexibility, sensing capability, and user-friendly simplicity. Here, the most up-to-date materials, sensors, and system-packaging technologies to develop advanced WFHE are provided. Details of mechanical, electrical, physicochemical, and biocompatible properties are discussed with integrated sensor applications in healthcare, energy, and environment. In addition, limitations of the current materials are discussed, as well as key challenges and the future direction of WFHE. Collectively, an all-inclusive review of the newly developed WFHE along with a summary of imperative requirements of material properties, sensor capabilities, electronics performance, and skin integrations is provided.

Advanced Soft Materials, Sensor Integrations, and Applications of Wearable Flexible Hybrid Electronics in Healthcare, Energy, and Environment.

The disclosed invention provides a sweat sensing device and method capable of collecting a sweat sample, concentrating the sample with respect to a target analyte, and measuring the target analyte in the concentrated sample. The invention is also capable of determining the change in molarity of the sweat sample with respect to the target analyte, as the sample is concentrated by the device.

Devices capable of sample concentration for extended sensing of sweat analytes

To explore how the one-host tick Dermacentor albipictus survives off-host, we determined water balance characteristics of eggs and larvae. In contrast to eggs, larvae lost water fast, absorbed water vapour and died from a low amount of water loss. Placing mated females under near water-saturated conditions yielded larvae that absorbed and survived only at high relative humidities. We observed larvae forming clusters. Water loss rate of larvae decreased as group size increased. In response to day length, larvae lost water slower under long day than short day conditions. Larvae could switch quickly between fast water loss rate (short day) and slow water loss rate (long day) within a day, independent of the photoperiodic experience of the egg or mother. Long day exposure had no effect on water relations, incubation and survival of eggs. We conclude that eggs are modified for water conservation. Larvae survive by having a water balance maternal effect; i.e. capacity for water vapour absorption in the ...

Water balance attributes for off-host survival in larvae of the winter tick (Dermacentor albipictus; Acari: Ixodidae) from wild moose

Non-invasive wearable biosensors provide real-time, continuous, and actionable health information However, difficulties detecting diluted biomarkers in excreted biofluids limit practical applications Most biomarkers of interest are transported paracellularly into excreted biofluids from biomarker-rich blood and interstitial fluid during normal modulation of cellular tight junctions Calcium chelators are reversible tight junction modulators that have been shown to increase absorption across the intestinal epithelium However, calcium chelators have not yet been shown to improve the extraction of biomarkers Here we show that for glucose, a paracellularly transported biomarker, the flux into sweat can be increased by >10x using citrate, a calcium chelator, in combination with electroosmosis Our results demonstrate a method of increasing glucose flux through the sweat gland epithelium, thereby increasing the concentration in sweat Future work should examine if this method enhances flux for other paracellularly transported biomarkers to make it possible to detect more biomarkers with currently available biosensors

/pdf/enhancing-glucose-flux-into-sweat-by-increasing-paracellular-4yvh8gzf2j.pdf

Enhancing glucose flux into sweat by increasing paracellular permeability of the sweat gland.

A device (100) for sensing biofluid placed on skin (12) with at least one pre-existing pathway (14) includes a first analyte-specific sensor (120) for sensing a first analyte in the biofluid and a volume-reduced pathway between skin (12) and the first analyte-specific sensor (120) configured to allow an advective flow of the biofluid from the at least one pre-existing pathway (14) toward the first analyte-specific sensor (120). The first analyte-specific sensor (120) does not consume the first analyte. The device (100) further includes an iontophoresis electrode (150) and a counter electrode (152) for bringing the first analyte into the at least one pre-existing pathway. The biofluid may be more than 50% interstitial fluid or more than 50% sweat. The device (100) may also include at least one of a wicking collector (136), a wicking coupler (130), or a wicking pump (138).

Reduced sample volume for sensing of analytes generated by reverse iontophoresis

To determine whether pollen is a significant food source for Balaustium cf. murorum (tentative identification), behavioural responses to pollen feeding were examined in short-range Petri plate bioassays. Evans blue dye was used as a tracer to stain pollen after being incorporated into the gut. The results show that all active stages (larva, deutonymph and adult) ingested whole pollen from viburnum shrub (Viburnum) and daffodil (Narcissus) cultivars. All active stages fed on all types of pollen tested: tulip (Tulipa), daffodil (Narcissus), pear (Pyrus), maple (Acer), viburnum (Viburnum) and crabapple (Malus) cultivars except for tulip in the adult and tulip, pear and crabapple in the deutonymph. A higher percentage of larvae fed on pollen-covered surfaces and cleared pollen at a faster rate than other life stages in the bioassays. Clearance of viburnum and daffodil pollen by larvae and deutonymphs was particularly rapid, but this shifted to maple and crabapple pollen in the adult. In pheromone bioassays, p...

Andrew J. Jajack

Papers

Devices capable of sample concentration for extended sensing of sweat analytes

Water balance attributes for off-host survival in larvae of the winter tick (Dermacentor albipictus; Acari: Ixodidae) from wild moose

Enhancing glucose flux into sweat by increasing paracellular permeability of the sweat gland.

Reduced sample volume for sensing of analytes generated by reverse iontophoresis

Pollen feeding in Balaustium murorum (Acari: Erythraeidae): visualization and behaviour