A wearable microfluidic system for efficient sweat collection and real-time detection.

Sweat is an important biofluid with rich physiological information that can evaluate human health condition. Wearable sweat sensors have received widespread attention in recent years due to the benefits of non-invasive, continuous, and real-time monitoring. Currently, an efficient device integrating sweat collection and detection is still needed. Here, a wearable sweat microfluidic system was fabricated for real-time collection and analysis of sweat. The fabricated microfluidic system consisted of four layers, including a skin adhesive layer, a microfluidic layer, an electrode layer, and a capping layer. The sweat collection rate was around 0.79 µL/min, which demonstrated efficient sweat sampling, storage, and refreshing capabilities. Simultaneous detection of multiple sweat biomarkers was achieved with a screen-printed sweat sensing array, which could realize high-precision detection of Na+, K+, and glucose. Moreover, the sensing array also showed good repeatability and stability, with a relative standard deviation of sensitivity of less than 5%. Additionally, human testing was conducted to demonstrate that this microfluidic system can continuously monitor Na+, K+, and glucose in subjects' sweat during exercise, which showed high potential for non-invasive human health monitoring.

Editorial for the Special Issue on Physics in Micro/Nano Devices: From Fundamental to Application.

With the continuous miniaturization of micro/nano devices, it is of great importance to study the physics of these devices, both for fundamental and practical research [...].

An inkjet-printed bendable antenna for wearable electronics.

104Flexible antennas, which can conform to the skin and transfer signals to terminals, are particularly useful for wearable electronics. Bending, which frequently occurs to flexible devices, significantly affects the performance of flexible antennas. Inkjet printing has been used as an additive manufacturing technology for fabricating flexible antenna in recent years. However, there is little research on the bending performance of inkjet printing antenna in both simulation and experiment. This paper proposes a bendable coplanar waveguide antenna with a small size of 30 × 30 × 0.05 mm3 by combining the advantages of fractal antenna and serpentine antenna, which realizes the ultra-wideband feature and avoids the problems of large dielectric layer thickness (greater than 1 mm) and large volume of traditional microstrip antenna at the same time. The structure of the antenna was optimized by simulation using the Ansys high-frequency structure simulator, and the antenna was fabricated on a flexible polyimide substrate by inkjet printing. The experimental characterization results show that the central frequency of the antenna is 2.5 GHz, the return loss is -32 dB, and the absolute bandwidth is 850 MHz, which is consistent with the simulation results. The results demonstrate that the antenna has anti-interference capability and can meet the ultra-wideband characteristics. When the traverse and longitudinal bending radius are greater than 30 mm and skin proximity greater than 1 mm, the resonance frequency offsets are mostly within 360 MHz, and return losses of the bendable antenna are within the -14 dB compared with the no bending condition. The results exhibit that the proposed inkjet-printed flexible antenna is bendable and promising for wearable applications.

Effect of interstitial fluid pH on transdermal glucose extraction by reverse iontophoresis.

Reverse iontophoresis (RI) is a promising technology in the field of continuous glucose monitoring (CGM), offering significant advantages such as finger-stick-free operation, wearability, and non-invasiveness. In the glucose extraction process based on RI, the pH of the interstitial fluid (ISF) is a critical factor that needs further investigation, as it directly influences the accuracy of transdermal glucose monitoring. In this study, a theoretical analysis was conducted to investigate the mechanism by which pH affects the glucose extraction flux. Modeling and numerical simulations performed at different pH conditions indicated that the zeta potential was significantly impacted by the pH, thereby altering the direction and flux of the glucose iontophoretic extraction. A screen-printed glucose biosensor integrated with RI extraction electrodes was developed for ISF extraction and glucose monitoring. The accuracy and stability of the ISF extraction and glucose detection device were demonstrated with extraction experiments using different subdermal glucose concentrations ranging from 0 to 20 mM. The extraction results for different ISF pH values exhibited that at 5 mM and 10 mM subcutaneous glucose, the extracted glucose concentration was increased by 0.08212 mM and 0.14639 mM for every 1 pH unit increase, respectively. Furthermore, the normalized results for 5 mM and 10 mM glucose demonstrated a linear correlation, indicating considerable potential for incorporating a pH correction factor in the blood glucose prediction model used to calibrate glucose monitoring.

Electrically Inspired Flexible Electrochemical Film Power Supply for Long-Term Epidermal Sensors.

This paper, for the first time, reports an electrically inspired flexible electrochemical film power supply for long-term epidermal sensors. This device can periodically provide electrical power for several hours after a short-time electrical activation. The electrical activation makes acetylcholine, which is infused into the subcutaneous tissue by iontophoresis. The interstitial fluid (ISF) with glucose molecules is then permeated autonomously for several hours. At this period, the device can provide electrical power. The electrical power is generated from the catalyzing reaction between the glucose oxidase immobilized on the anode and the permeated glucose molecules. After the ISF permeation stops, we give a short-time electrical activation to provide electrical power for several hours again. The power supply is flexible, which makes it adaptively conform to skin. The episodic short-time electrical activation can be enabled by an integrated small film lithium-ion battery. This method extends the service life of a lithium-ion battery 10-fold and suggests the application of small lithium-ion batteries for long-term epidermal sensors.

Flexible organic field-effect transistors-based biosensors: progress and perspectives.

Organic field-effect transistors (OFETs) have been proposed beyond three decades while becoming a research hotspot again in recent years because of the fast development of flexible electronics. Many novel flexible OFETs-based devices have been reported in these years. Among these devices, flexible OFETs-based sensors made great strides because of the extraordinary sensing capability of FET. Most of these flexible OFETs-based sensors were designed for biological applications due to the advantages of flexibility, reduced complexity, and lightweight. This paper reviews the materials, fabrications, and applications of flexible OFETs-based biosensors. Besides, the challenges and opportunities of the flexible OFETs-based biosensors are also discussed.

Reverse iontophoresis with the development of flexible electronics: A review.

Skin-centric diagnosis techniques, such as epidermal physiological parameter monitoring, have developed rapidly in recent years. The analysis of interstitial fluid (ISF), a body liquid with abundant physiological information, is a promising method to obtain health status because ISF is easily assessed by implanted or percutaneous measurements. Reverse iontophoresis extracts ISF by applying an electric field onto the skin, and it is a promising method to noninvasively obtain ISF, which, in turn, enables noninvasive epidermal physiological parameter monitoring. However, the development of reverse iontophoresis was relatively slow around the 2010s due to the rigidity and low biocompatibility of the applied devices. With the rapid development of flexible electronic technology in recent years, new progress has been made in the field of reverse iontophoresis, especially in the field of blood glucose monitoring and drug monitoring. This review summarizes the recent advances and discusses the challenges and opportunities of reverse iontophoresis.

A thermal activated and differential self-calibrated flexible epidermal biomicrofluidic device for wearable accurate blood glucose monitoring.

This paper reports a flexible electronics-based epidermal biomicrofluidics technique for clinical continuous blood glucose monitoring, overcoming the drawback of the present wearables, unreliable measurements. A thermal activation method is proposed to improve the efficiency of transdermal interstitial fluid (ISF) extraction, enabling extraction with a low current density to notably reduce skin irritation. An Na+ sensor and a correction model are proposed to eliminate the effect of individual differences, which leads to fluctuations in the amount of ISF extraction. An electrochemical sensor with a 3D nanostructured working electrode surface is designed to enable precise in situ glucose measurement. A differential structure is proposed to eliminate the effect of passive perspiration, which leads to inaccurate blood glucose prediction. Fabrications of the epidermal biomicrofluidic device including formation of flexible electrodes, nanomaterial modification, and enzyme immobilization are fully realized by inkjet printing to enable facile manufacturing with low cost, which benefits practical production.

Step emulsification in microfluidic droplet generation: mechanisms and structures.

The droplet-based microfluidic techniques have been applied widely in functional material synthesis and biomedical information measurements, wherein step emulsification as an integrated system combines the advantages of homogeneity and throughput in monodisperse droplet formation. This paper reviews the mechanisms and classical structures of step emulsification. In terms of droplet formation mechanisms, we describe the droplet size and detachment regimes related to the microchannel geometry. Distinguished by droplet formation, microfluidic step emulsification driven by interfacial tension and centrifugal step emulsification related to buoyancy are introduced respectively, including their improved structures for enhancing the droplet homogeneity and throughput. Finally, the perspectives about the developments of step emulsification in mechanisms, fabrications, and applications are discussed.

Experimental investigation on the effects of the standoff distance and the initial radius on the dynamics of a single bubble near a rigid wall in an ultrasonic field.

Bubble behaviors near a boundary in an ultrasonic field are the fundamental forms of acoustic cavitation and of substantial importance in various applications, such as industry cleaning, chemical engineering and food processing. The effects of two important factors that strongly affect the dynamics of a single acoustic cavitation bubble, namely, the initial bubble radius and the standoff distance, were investigated in this work. The temporal evolution of the bubble was recorded using high speed microphotography. Meanwhile, the time of bubble collapse and the characteristics of the liquid jets were analyzed. The results demonstrate that the intensity of the acoustic cavitation, which is characterized by the time of bubble collapse and the liquid jet speed, reaches the optimum level under suitable values of the initial bubble radius and the normalized standoff distance. As the initial bubble radius and the normalized standoff distance increase or decrease from the optimal values, the time of the bubble collapse increases, and the first liquid jet's speed decreases substantially, whereas the speeds of the second and third liquid jets exhibit no substantial changes. These results on bubble dynamics in an ultrasonic field are important for identifying or correcting the mechanisms of acoustic cavitation and for facilitating its optimization and application.

A Rubik's microfluidic cube.

A Rubik's cube as a reconfigurable microfluidic system is presented in this work. Composed of physically interlocking microfluidic blocks, the microfluidic cube enables the on-site design and configuration of custom microfluidics by twisting the faces of the cube. The reconfiguration of the microfluidics could be done by solving an ordinary Rubik's cube with the help of Rubik's cube algorithms and computer programs. An O-ring-aided strategy is used to enable self-sealing and the automatic alignment of the microfluidic cube blocks. Owing to the interlocking mechanics of cube blocks, the proposed microfluidic cube exhibits good reconfigurability and robustness in versatile applications and proves to be a promising candidate for the rapid deployment of microfluidic systems in resource-limited settings.

Inkjet Pattern-Guided Liquid Templates on Superhydrophobic Substrates for Rapid Prototyping of Microfluidic Devices.

This paper presents a novel method of rapidly customizing microfluidic systems using a consumer-grade inkjet printer and a commercially available superhydrophobic spray. By casting polydimethylsiloxane (PDMS) on liquid templates that are defined by inkjet-printed hydrophilic patterns on superhydrophobically-coated PDMS substrates, microfluidic devices can be directly fabricated. Utilizing the interfacial properties of the superhydrophobic coating and the template liquid, the fabrication of microfluidics could be done with minimum effort and expertise, and unlike previously reported works, no mask and bonding process is necessary. As a proof of concept, we created different microfluidic devices for various applications, like gradient generation and pneumatic control of fluid. Appealing in its simplicity and rapidness, the newly proposed technique could provide an easy-to-use microfluidic platform for front-line researchers with different backgrounds to quickly customize microfluidic devices.

Effect of low-frequency ultrasonic field at different power on the dynamics of a single bubble near a rigid wall.

Various bubble dynamics near the boundary in an acoustic field play a significantly important role in destructive erosion which has been associated with applications in industry cleaning, chemical engineering and biomedicine. But the effect mechanism of the high pressure on the boundary induce by single acoustic cavitation bubble has not been fully elucidated, which is vital for further application. The objective of this paper is to investigate the behaviors of a gas bubble near a rigid wall in a low frequency ultrasonic field. The temporal evolution of the bubble was recorded by means of synchronous high-speed recordings. Meanwhile, the time of bubble collapse, velocity of the bubble margin and the characteristics of the liquid jet were analyzed. In addition, the bubble dynamics were simulated based on potential flow theory coupled with the boundary integral method (BIM). Results are presented for a single bubble generated near the rigid wall with the normalized standoff distance γ = 1.85 under a wide range of ultrasonic power. The results show that the dynamics of the bubble can be divided into four phases: oscillation, movement, collapse and rebound. And when the applied ultrasonic power increases, the time of bubble collapse has a clear trend to decrease and the maximum velocity of the bubble margin increases apparently. Furthermore, the bubble behaviors after its first collapse, such as the number and the velocity of the effective jets, also vary evidently as the increase of the ultrasonic power. These results about bubble dynamics in ultrasonic field may be significant to determine or correct the main mechanisms of acoustic cavitation.

Sticker Microfluidics: A Method for Fabrication of Customized Monolithic Microfluidics.

This paper proposes a novel strategy and an all-in-one toolbox that allows instrument-free customization of integrated microfluidic systems. Unlike the modular design of combining multiple microfluidic chips in the previous literature, this work, for the first time, proposes a "template sticker" method, in which sacrificial templates for microfluidic components are batch-produced in the form of standardized stickers and packaged into a toolbox. To create a customized monolithic microfluidic system, the end users only need to select and combine various template stickers following formulated steps. The fabricated microfluidic devices have well-defined microscale features, while the fabrication process is inexpensive and time-saving. Various functional microfluidic devices were fabricated and tested using this toolbox. The capability to create microchannels on curved surfaces is also demonstrated. As a proof of concept, we developed with the proposed toolbox a colorimetric testing platform for the detection of nitrite ions. The sticker toolbox, as the first self-contained portable platform for microfluidic fabrication, allows prompt customization of monolithic devices, enabling deployment of microfluidics with both ideal performance and customizability.

Flattened fiber-optic ATR sensor enhanced by silver nanoparticles for glucose measurement.

This paper proposes a novel fiber attenuated total reflection (ATR) sensor with silver nanoparticles (AgNPs) on the flattened structure based on mid-infrared spectroscopy for detecting low concentration of glucose with high precision. The flattened structure was designed to add the effective optical path length to improve the sensitivity. AgNPs were then deposited on the surface of the flattened area of the fiber via chemical silver mirror reaction for further improving the sensitivity by enhancing the infrared absorption. Combining the AgNPs modified flattened fiber ATR sensor with a CO2 laser showed a strong mid-infrared glucose absorption, with an enhancement factor of 4.30. The glucose concentration could be obtained by a five-variable partial least-squares model with a root-mean-square error of 4.42 mg/dL, which satisfies clinical requirements. Moreover, the fiber-based technique provides a pretty good method to fabricate miniaturized ATR sensors that are suitable to be integrated into a microfluidic chip for continuous glucose monitoring with high sensitivity.

A flexible enzyme-electrode sensor with cylindrical working electrode modified with a 3D nanostructure for implantable continuous glucose monitoring.

A novel cylindrical flexible enzyme-electrode sensor was fabricated with a bigger working electrode (WE) surface than the traditional pin-like one for implantable continuous glucose monitoring. On the WE surface, a 3D nanostructure consisting of graphene and platinum nanoparticles was constructed to enhance the sensitivity; in conjunction with the bigger WE, this nanostructure enabled hypoglycemia detection, which is still a big challenge in clinics. The cylindrical sensor was fabricated by rotated inkjet printing which enabled direct patterning of microstructures on a curved surface, thus overcoming the restriction of the traditional planar micromachining by photolithography. Specifically, the cylindrical substrate (polyetheretherketone, PEEK) was modified by (3-aminopropyl) trimethoxysilane and (3-mercaptopropyl) trimethoxysilane to facilitate surface wettability, which discourages the coalescence of adjacent droplets, and to facilitate the adhesion of metals to PEEK in order to construct robust electrodes. A synchronous heating method was used to evaporate the solvent of the droplets quickly to prevent them from running along the cylindrical surface, which affects the formation of the printed electrode significantly. In vitro experimental results showed that the proposed sensor was able to detect the glucose concentration ranging from 0 to 570 mg dL-1 which demonstrated its capability for physiological glucose detection. In vivo experiments were conducted with rats, and the measurement results recorded using the implanted cylindrical sensor showed great compliance to those recorded using a commercial glucometer which exhibited the viability of the proposed sensor for implantable continuous glucose monitoring, even under the hypoglycemic conditions.

From functional structure to packaging: full-printing fabrication of a microfluidic chip.

This paper presents a concept of a full-printing methodology aiming at convenient and fast fabrication of microfluidic devices. For the first time, we achieved a microfluidic biochemical sensor with all functional structures fabricated by inkjet printing, including electrodes, immobilized enzymes, microfluidic components and packaging. With the cost-effective and rapid process, this method provides the possibility of quick model validation of a novel lab-on-chip system. In this study, a three-electrode electrochemical system was integrated successfully with glucose oxidase immobilization gel and sealed in an ice channel, forming a disposable microfluidic sensor for glucose detection. This fully-printed chip was characterized and showed good sensitivity and a linear section at a low-level concentration of glucose (0-10 mM). With the aid of automatic equipment, the fully-printed sensor can be massively produced with low cost.

A continuous glucose monitoring device by graphene modified electrochemical sensor in microfluidic system.

This paper presents a continuous glucose monitoring microsystem consisting of a three-electrode electrochemical sensor integrated into a microfluidic chip. The microfluidic chip, which was used to transdermally extract and collect subcutaneous interstitial fluid, was fabricated from five polydimethylsiloxane layers using micromolding techniques. The electrochemical sensor was integrated into the chip for continuous detection of glucose. Specifically, a single-layer graphene and gold nanoparticles (AuNPs) were decorated onto the working electrode (WE) of the sensor to construct a composite nanostructured surface and improve the resolution of the glucose measurements. Graphene was transferred onto the WE surface to improve the electroactive nature of the electrode to enable measurements of low levels of glucose. The AuNPs were directly electrodeposited onto the graphene layer to improve the electron transfer rate from the activity center of the enzyme to the electrode to enhance the sensitivity of the sensor. Glucose oxidase (GOx) was immobilized onto the composite nanostructured surface to specifically detect glucose. The factors required for AuNPs deposition and GOx immobilization were also investigated, and the optimized parameters were obtained. The experimental results displayed that the proposed sensor could precisely measure glucose in the linear range from 0 to 162 mg/dl with a detection limit of 1.44 mg/dl (S/N = 3). The proposed sensor exhibited the potential to detect hypoglycemia which is still a major challenge for continuous glucose monitoring in clinics. Unlike implantable glucose sensors, the wearable device enabled external continuous monitoring of glucose without interference from foreign body reaction and bioelectricity.