Hybrid Printing of Fully Integrated Microfluidic Devices for Biosensing.

The advent of 3D printing has facilitated the rapid fabrication of microfluidic devices that are accessible and cost-effective. However, it remains a challenge to fabricate sophisticated microfluidic devices with integrated structural and functional components due to limited material options of existing printing methods and their stringent requirement on feedstock material properties. Here, a multi-materials multi-scale hybrid printing method that enables seamless integration of a broad range of structural and functional materials into complex devices is reported. A fully printed and assembly-free microfluidic biosensor with embedded fluidic channels and functionalized electrodes at sub-100 µm spatial resolution for the amperometric sensing of lactate in sweat is demonstrated. The sensors present a sensitive response with a limit of detection of 442 nm and a linear dynamic range of 1-10 mm, which are performance characteristics relevant to physiological levels of lactate in sweat. The versatile hybrid printing method offers a new pathway toward facile fabrication of next-generation integrated devices for broad applications in point-of-care health monitoring and sensing.

A "Two-Part" Resonance Circuit Based Detachable Sweat Patch for Noninvasive Biochemical and Biophysical Sensing.

Wearable electronics play important roles in noninvasive, continuous, and personalized monitoring of multiple biosignals generated by the body. To unleash their full potential for next-generation human centered bio-integrated electronics, the wireless sensing capability is a desirable feature. However, state-of-the-art wireless sensing technologies exploit rigid and bulky electronic modules for power supply, signal generation, and data transmission. This study reports a battery-free device technology based on a "two-part" resonance circuit model with modularized, physically separated, and detachable functional units for magnetic coupling and biosensing. The resulting platform combines advantages of electronics and microfluidics with low cost, minimized form factors, and improved performance stability. Demonstration of a detachable sweat patch capable of simultaneous recording of cortisol concentration, pH value, and temperature highlights the potential of the "two-part" circuit for advanced, transformative biosensing. The resulting wireless sensors provide a new engineering solution to monitoring biosignals through intimate and seamless integration with skin surfaces.

Hydrovoltaic Nanogenerators for Self-Powered Sweat Electrolyte Analysis.

Human sweat comprises various electrolytes that are health status indicators. Conventional potentiometric electrolyte sensors require an electrical power source, which is expensive, bulky, and requires a complex architecture. Herein, this work demonstrates an electric nanogenerator fabricated using silicon nanowire (SiNW) arrays comprising modified carbon nanoparticles. The SiNW arrays platform is demonstrated as an effective self-powered sensor for sweat electrolyte analysis. It has been shown that an evaporation-induced water flow in nanochannels can yield an open-circuit voltage (Voc ) of 0.45 V and a short-circuit current of 10.2 µA at room temperature as a result of overlapped electric double layers. The electrolyte in the water flow results in a Voc decrease due to the charge shielding effect. The Voc is inversely proportional to the electrolyte concentration. The fabricated hydrovoltaic device shows the capability for sensing electrolytes in human sweat, which is useful in evaluating the hydration status of volunteers following intense physical exercise. The device depicts a novel response mechanism compared to conventional electrochemical sensors. Furthermore, the hydrovoltaic device shows a maximum output power of 1.42 µW, and as such has been successfully shown to drive various electronic devices including light-emitting diodes, a calculator, and an electronic timer.

Flexible and printable integrated biosensors for monitoring sweat and skin condition.

Wearable and flexible sensors are playing increasing roles in health monitoring (like physiological electrical signals and components of biofluids). Therein, sweat as a carrier of informative biomarkers would attract great attention for health status identification. However, most wearable biosensors have a short lifetime with complex fabrication processes and expensive costs, which would largely limit the application scene to some extent. Here, we developed a state-of-the-art flexible and integrated sensor patch with screen-printing technology for in-situ and real-time monitoring of electrolyte balance and skin state. The screen-printed sensor patch was easily fabricated, highly reproducible, disposable and relatively stable, which was extremely for sweat sensors with low cost. The state of art sensors on the patch of Na+, pH, skin impedance and temperature all showed excellent performance with high linearity (coefficient of determinations (R2) are 0.998, 0.994, 0.998 and 0.997, respectively). Besides, the detection ranges of Na+ and pH sensors are wide enough for sweat analysis of 10-100 mM and 2-8, respectively. The proposed device provides a new strategy for real-time sweat analysis, preventing dehydration and skin state monitoring during exercise.

Super-Hydrophilic Zwitterionic Polymer Surface Modification Facilitates Liquid Transportation of Microfluidic Sweat Sensors.

The transportation of sweat in an epidermal sweat sensor is critical for the monitoring of biochemical compositions of human sweat. However, it is still a challenge to engineer microfluidic devices with super-wetting channels for such epidermal sweat sensors. Herein, a zwitterionic poly (2-methacryloyloxyethyl phosphorylcholine) (PMPC) modified microfluidic device with super-wetting and good liquid transport ability via an azo coupling reaction of PMPC onto the surface of polydimethylsiloxane microfluidic devices is reported. The obtained PMPC-modified microfluidic device can be integrated with flexible electrochemical sensor to measure the ion compositions of human sweat in real-time. The super-hydrophilic zwitterionic polymer surface modification can greatly facilitate the transportation of body fluids in microfluidic sensors for the detection of various biomarkers. Such microfluidic sensors have great potential for next-generation personalized healthcare.

Advanced Wearable Microfluidic Sensors for Healthcare Monitoring.

Wearable flexible sensors based on integrated microfluidic networks with multiplex analysis capability are emerging as a new paradigm to assess human health status and show great potential in application fields such as clinical medicine and athletic monitoring. Well-designed microfluidic sensors can be attached to the skin surface to acquire various pieces of physiological information with high precision, such as sweat loss, information regarding metabolites, and electrolyte balance. Herein, the recent progress of wearable microfluidic sensors for applications in healthcare monitoring is summarized, including analysis principles and microfabrication methods. Finally, the challenges and opportunities for wearable microfluidic sensors in practical applications are discussed.

Flexible molecularly imprinted electrochemical sensor for cortisol monitoring in sweat.

A selective cortisol sensor based on molecularly imprinted poly(glycidylmethacrylate-co ethylene glycol dimethacrylate) (poly(GMA-co-EGDMA)) has been demonstrated for detection of cortisol in human sweat. The non-enzymatic biomimetric flexible sweat sensor was fabricated inexpensively by layer by layer (LbL) assembly. The sensor layers comprised a stretchable polydimethylsiloxane (PDMS) base with carbon nanotubes-cellulose nanocrystals (CNC/CNT) conductive nanoporous nanofilms. The imprinted (MIP) poly(GMA-co-EGDMA) deposited on the CNC/CNT was the cortisol biomimetric receptor. Rapid in analyte response (3 min), the cortisol MIP sensor demonstrated excellent performance. The sensor has a limit of detection (LOD) of 2.0 ng/mL ± 0.4 ng/mL, dynamic range of 10-66 ng/mL, and a sensor reproducibility of 2.6% relative standard deviation (RSD). The MIP sensor also had high cortisol specificity and was inherently blind to selected interfering species including glucose, epinephrine, ß-estradiol, and methoxyprogestrone. The MIP was four orders of magnitude more sensitive than its non-imprinted (NIP) counterpart. The MIP sensor remains stable over time, responding proportionately to doses of cortisol in human sweat. Graphical abstract.

Integrated mental stress smartwatch based on sweat cortisol and HRV sensors.

Mental stress, a human's common emotion that is difficult to recognize and describe, can give rise to serious psychological disorders. Skin and sweat are easily accessible sources of biomarkers and bio-signals that contain information about mental stress. It is challenging for current wearable devices to monitor psychological stress in real-time with a non-invasive manner. Therefore, we have developed a smartwatch integrated with a sweat cortisol sensor and a heart rate variation (HRV) sensor. This smartwatch can simultaneously record the cortisol levels in sweat and HRV index in real time over a long period. The cortisol sensors based on organic electrochemical transistor (OECT) are fabricated by utilizing the Prussian-blue (PB) doped molecular imprinting polymer (MIP) modified gate electrode. The sensor signal current will decrease following the combination of sweat cortisol, due to the blocking of the PBMIP conductive path, demonstrating good sensitivity, selectivity, and stability. The HRV sensor is manufactured by a photoplethysmography method. We have integrated the two sensors into a wearable smartwatch that can match well with the mobile phone APP and the upper computer software. Through the use of this smartwatch, we have observed a negative correlation between cortisol levels in sweat and the HRV index in short-term stressful environments. Our research presents a great progress in real-time and non-invasive monitoring human's stress levels, which promotes not only the stress management, but also better psychological research.

Skin-Attachable Ink-Dispenser-Printed Paper Fluidic Sensor Patch for Colorimetric Sweat Analysis.

In situ analysis of sweat biomarkers potentially provides noninvasive lifestyle monitoring and early diagnosis. Quantitative detection of sweat rate is crucial for thermoregulation and preventing heat injuries. Here, a skin-attachable paper fluidic patch is reported for in situ colorimetric sensing of multiple sweat markers (pH, glucose, lactate, and uric acid) with concurrent sweat rate tracking. Two sets of fluidic patterns-multiplexed detection zones and a longitudinal sweat rate channel-are directly printed by an automated ink dispenser from a specially developed ceramic-based ink. The ceramic ink thermal-cures into an impervious barrier, confining sweat within the channels. The ceramic-ink-printed boundary achieves higher pattern resolution, prevents fluid leakage, attains pattern thermal stability, and resistant to organic solvents. The cellulose matrix of the detection zones is modified with nanoparticles to improve the color homogeneity and sweat sensor sensitivity. The sweat rate channel is made moisture sensitive by incorporating a metal-salt-based dye. The change in saturation/color of the detection zones and/or channels upon sweat addition can be visually detected or quantified by a smartphone camera. A cost-effective way is provided to fabricate paper fluidic sensor patches, successfully demonstrating on-body multiplexed evaluation of sweat analytes. Such skin wearables offer on-site analysis, meaningful to an increasingly health-conscious population.

Adaptively resettable microfluidic patch for sweat rate and electrolytes detection.

Skin-interfaced microfluidic patch has become a reliable device for sweat collection and analysis. However, the intractable problems of emptying the microchannel for reuse, and the channel's volumetric capacity limited by the size of the patch, directly hinder the practical application of sweat sensors. Herein, we report an adaptively resettable microfluidic sweat patch (Art-Sweat patch) capable of continuously monitoring both sweat rate (0.2-4.0 µL min-1) and total ionic charge concentration (10-200 mmol L-1). We develop a platform with a vertical and horizontal microchannel combined strategy, enabling repeatedly filling sweat and emptying the microchannel for autonomously resetting and detecting. The variation in the emptied volume is designed to be adaptively identified by the sensor, resulting in enhanced stability and an enlarged volumetric capacity of over 300 µL. By integrating with self-designed wireless transmission modules, the proposed Art-Sweat patch shows product-level wearability and high performance in monitoring variations in regional sweat rate and concentration for hydration status assessment.