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.

Exploring viscosity influence mechanisms on coating removal: Insights from single cavitation bubble behaviours in low-frequency ultrasonic settings.

The role of acoustic cavitation in various surface cleaning disciplines is important. However, the physical mechanisms underlying acoustic cavitation-induced surface cleansing are poorly understood. This is due to the combination of microscopic and ultrashort timescales associated with the dynamics of acoustic cavitation bubbles. Here, we have precisely controlled single-bubble cavitation in both space and time. Ultrasonic excitation leads to the cavitation of generated single bubbles. A synchronous ultrafast photomicrographic system simultaneously records the dynamics of single acoustic cavitation bubbles (SACBs) and the cleaning process of the nearby surface in liquids with varying viscosities. Finally, we analysed the correlation between bubble dynamics and surface cleaning situations. The differences in the typical dynamic characteristics of the bubbles during collapse in liquids with varying viscosities reveal two main mechanisms underlying surface cleaning by acoustic cavitation, which are respective the Laplace pressure during the bubble's movement and liquid jets during bubble collapse. Our study provides a better physical understanding of the ultrasonic cleaning process based on acoustic cavitation, and will help to optimize and facilitate the applications of surface cleaning, especially for the cleaning of substrates with tightly attached dirt.

Mechanistic study of ultrasound and microbubble enhanced cancer therapy in a 3D vascularized microfluidic cancer model.

Accumulating evidence has shown that ultrasound exposure combined with microbubbles can enhance cancer therapy. However, the underlying mechanisms at the tissue level have not been fully understood yet. The conventional cell culture in vitro lacks complex structure and interaction, while animal studies cannot provide micron-scale dynamic information. To bridge the gap, we designed and assembled a 3D vascularized microfluidic cancer model, particularly suitable for ultrasound and microbubble involved mechanistic studies. Using this model, we first studied SonoVue microbubble traveling dynamics in 3D tissue structure, then resolved SonoVue microbubble cavitation dynamics in tissue mimicking agarose gels at a frame rate of 0.675 M fps, and finally explored the impacts of ultrasound and microbubbles on cancer cell spheroids. Our results demonstrate that microbubble penetration in agarose gel was enhanced by increasing microbubble concentration, flow rate and decreasing viscosity of the gel, and little affected by mild acoustic radiation force. SonoVue microbubble exhibited larger expansion amplitudes in 2 %(w/v) agarose gels than in water, which can be explained theoretically by the relaxation of the cavitation medium. The immediate impacts of ultrasound and SonoVue microbubbles to cancer cell spheroids in the 3D tissue model included improved cancer cell spheroid penetration in micron-scale and sparse direct permanent cancer cell damage. Our study provides new insights of the mechanisms for ultrasound and microbubble enhanced cancer therapy at the tissue level.

A dual-mode fiber-shaped flexible capacitive strain sensor fabricated by direct ink writing technology for wearable and implantable health monitoring applications.

Flexible fiber-shaped strain sensors show tremendous potential in wearable health monitoring and human‒machine interactions due to their compatibility with everyday clothing. However, the conductive and sensitive materials generated by traditional manufacturing methods to fabricate fiber-shaped strain sensors, including sequential coating and solution extrusion, exhibit limited stretchability, resulting in a limited stretch range and potential interface delamination. To address this issue, we fabricate a fiber-shaped flexible capacitive strain sensor (FSFCSS) by direct ink writing technology. Through this technology, we print parallel helical Ag electrodes on the surface of TPU tube fibers and encapsulate them with a high dielectric material BTO@Ecoflex, endowing FSFCSS with excellent dual-mode sensing performance. The FSFCSS can sense dual-model strain, namely, axial tensile strain and radial expansion strain. For axial tensile strain sensing, FSFCSS exhibits a wide detection range of 178%, a significant sensitivity of 0.924, a low detection limit of 0.6%, a low hysteresis coefficient of 1.44%, and outstanding mechanical stability. For radial expansion strain sensing, FSFCSS demonstrates a sensitivity of 0.00086 mmHg-1 and exhibits excellent responsiveness to static and dynamic expansion strain. Furthermore, FSFCSS was combined with a portable data acquisition circuit board for the acquisition of physiological signals and human‒machine interaction in a wearable wireless sensing system. To measure blood pressure and heart rate, FSFCSS was combined with a printed RF coil in series to fabricate a wireless hemodynamic sensor. This work enables simultaneous application in wearable and implantable health monitoring, thereby advancing the development of smart textiles.

Mechanisms underlying the influence of skin properties on a single cavitation bubble in low-frequency sonophoresis.

As a safe and effective method for systemic transdermal drug delivery (TDD), sonophoresis has drawn much attention from researchers. Despite numerous studies confirming cavitation as the main reason for sonophoresis, the effect skin has on cavitation bubble dynamics remains elusive due to the difficulty of experimental challenges. For a start, we reveal how single cavitation bubble (SCB) dynamics are affected by skin properties, including elasticity, hydrophilicity and texture. We use polydimethylsiloxane (PDMS) to simulate human skin and record the temporary evolution of SCBs with synchronous ultrafast photography. The influences of skin properties on SCBs are concluded: 1) SCBs collapse later near walls with better elasticities and generate microjets with higher speed; 2) SCBs collapse later near hydrophilic walls with slower microjets; and 3) the existence of a texture structure on walls also delays the time of bubble collapse near them and slows the velocities of microjets (v) during collapses.

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 Wettability on the Collision Behavior of Acoustically Excited Droplets.

Acoustic droplet ejection (ADE) is a noncontact technique for micro-liquid handling (usually nanoliters or picoliters) that is not restricted by nozzles and enables high-throughput liquid dispensing without sacrificing precision. It is widely regarded as the most advanced solution for liquid handling in large-scale drug screening. Stable coalescence of the acoustically excited droplets on the target substrate is a fundamental requirement during the application of the ADE system. However, it is challenging to investigate the collision behavior of nanoliter droplets flying upward during the ADE. In particular, the dependence of the droplet's collision behavior on substrate wettability and droplet velocity has yet to be thoroughly analyzed. In this paper, the kinetic processes of binary droplet collisions were investigated experimentally for different wettability substrate surfaces. Four states occur as the droplet collision velocity increases: coalescence after minor deformation, complete rebound, coalescence during rebound, and direct coalescence. For the hydrophilic substrate, there are wider ranges of Weber number (We) and Reynolds number (Re) in the complete rebound state. And with the decrease of the substrate wettability, the critical Weber and Reynolds numbers for the coalescence during rebound and the direct coalescence decrease. It is further revealed that the hydrophilic substrate is susceptible to droplet rebound because the sessile droplet has a larger radius of curvature and the viscous energy dissipation is greater. Besides, the prediction model of the maximum spreading diameter was established by modifying the droplet morphology in the complete rebound state. It is found that, under the same Weber and Reynolds numbers, droplet collisions on the hydrophilic substrate achieve a smaller maximum spreading coefficient and greater viscous energy dissipation, so the hydrophilic substrate is prone to droplet bounce.

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.

Cell mechanical responses to subcellular perturbations generated by ultrasound and targeted microbubbles.

The inherently dynamic and anisotropic microenvironment of cells imposes not only global and slow physical stimulations on cells but also acute and local perturbations. However, cell mechanical responses to transient subcellular physical signals remain unclear. In this study, acoustically activated targeted microbubbles were used to exert mechanical perturbations to single cells. The cellular contractile force was sensed by elastic micropillar arrays, while the pillar deformations were imaged using brightfield high-speed video microscopy at a frame rate of 1k frames per second for the first 10s and then confocal fluorescence microscopy. Cell mechanical responses are accompanied by cell membrane integrity changes. Both processes are determined by the perturbation strength generated by microbubble volumetric oscillations. The instantaneous cellular traction force relaxation exhibits two distinct patterns, correlated with two cell fates (survival or permanent damage). The mathematical modeling unveils that force-induced actomyosin disassembly leads to gradual traction force relaxation in the first few seconds. The perturbation may also influence the far end subcellular regions from the microbubbles and may propagate into connected cells with attenuations and delays. This study carefully characterizes the cell mechanical responses to local perturbations induced by ultrasound and microbubbles, advancing our understanding of the fundamentals of cell mechano-sensing, -responsiveness, and -transduction. STATEMENT OF SIGNIFICANCE: Subcellular physical perturbations commonly exist but haven't been fully explored yet. The subcellular perturbation generated by ultrasound and targeted microbubbles covers a wide range of strength, from mild, intermediate to intense, providing a broad biomedical relevance. With µm2 spatial sensing ability and up to 1ms temporal resolution, we present spatiotemporal details of the instantaneous cellular contractile force changes followed by attenuated and delayed global responses. The correlation between the cell mechanical responses and cell fates highlights the important role of the instantaneous mechanical responses in the entire cellular reactive processes. Supported by mathematical modeling, our work provides new insights into the dynamics and mechanisms of cell mechanics.

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.

Mechanobiology Platform Realized Using Photomechanical Mxene Nanocomposites: Bilayer Photoactuator Design and In Vitro Mechanical Forces Stimulation.

Mechanotransduction is the process by which cells convert external forces and physical constraints into biochemical signals that control several aspects of cellular behavior. A number of approaches have been proposed to investigate the mechanisms of mechanotransduction; however, it remains a great challenge to develop a platform for dynamic multivariate mechanical stimulation of single cells and small colonies of cells. In this study, we combined polydimethylsiloxane (PDMS) and PDMS/Mxene nanoplatelets (MNPs) to construct a soft bilayer nanocomposite for extracellular mechanical stimulation. Fast backlash actuation of the bilayer as a result of near-infrared irradiation caused mechanical force stimulation of cells in a controllable manner. The excellent controllability of the light intensity and frequency allowed backlash bending acceleration and frequency to be manipulated. As gastric gland carcinoma cell line MKN-45 was the research subject, mechanical force loading conditions could trigger apoptosis of the cells in a stimulation duration time-dependent manner. Cell apoptotic rates were positively related to the duration time. In the case of 6 min mechanical force loading, apoptotic cell percentage rose to 34.46% from 5.5% of the control. This approach helps apply extracellular mechanical forces, even with predesigned loading cycles, and provides a solution to study cell mechanotransduction in complex force conditions. It is also a promising therapeutic technique for combining physical therapy and biomechanics.

Modular Microfluidics: Current Status and Future Prospects.

This review mainly studies the development status, limitations, and future directions of modular microfluidic systems. Microfluidic technology is an important tool platform for scientific research and plays an important role in various fields. With the continuous development of microfluidic applications, conventional monolithic microfluidic chips show more and more limitations. A modular microfluidic system is a system composed of interconnected, independent modular microfluidic chips, which are easy to use, highly customizable, and on-site deployable. In this paper, the current forms of modular microfluidic systems are classified and studied. The popular fabrication techniques for modular blocks, the major application scenarios of modular microfluidics, and the limitations of modular techniques are also discussed. Lastly, this review provides prospects for the future direction of modular microfluidic technologies.

A Fiber-Based SPR Aptasensor for the In Vitro Detection of Inflammation Biomarkers.

It is widely accepted that the abnormal concentrations of different inflammation biomarkers can be used for the early diagnosis of cardiovascular disease (CVD). Currently, many reported strategies, which require extra report tags or bulky detection equipment, are not portable enough for onsite inflammation biomarker detection. In this work, a fiber-based surface plasmon resonance (SPR) biosensor decorated with DNA aptamers, which were specific to two typical inflammation biomarkers, C-reactive protein (CRP) and cardiac troponin I (cTn-I), was developed. By optimizing the surface concentration of the DNA aptamer, the proposed sensor could achieve a limit of detection (LOD) of 1.7 nM (0.204 µg/mL) and 2.5 nM (57.5 ng/mL) to CRP and cTn-I, respectively. Additionally, this biosensor could also be used to detect other biomarkers by immobilizing corresponding specific DNA aptamers. Integrated with a miniaturized spectral analysis device, the proposed sensor could be applied for constructing a portable instrument to provide the point of care testing (POCT) for CVD patients.

Influence of Surface Tension on Dynamic Characteristics of Single Bubble in Free-Field Exposed to Ultrasound.

The motion of bubbles in an ultrasonic field is a fundamental physical mechanism in most applications of acoustic cavitation. In these applications, surface-active solutes, which could lower the surface tension of the liquid, are always utilized to improve efficiency by reducing the cavitation threshold. This paper examines the influence of liquids' surface tension on single micro-bubbles motion in an ultrasonic field. A novel experimental system based on high-speed photography has been designed to investigate the temporary evolution of a single bubble in the free-field exposed to a 20.43 kHz ultrasound in liquids with different surface tensions. In addition, the R-P equations in the liquid with different surface tension are solved. It is found that the influences of the surface tension on the bubble dynamics are obvious, which reflect on the changes in the maximum size and speed of the bubble margin during bubble oscillating, as well as the weaker stability of the bubble in the liquid with low surface tension, especially for the oscillating bubble with higher speed. These effects of the surface tension on the bubble dynamics can explain the mechanism of surfactants for promoting acoustic cavitation in numerous application fields.

DNA-Based Biosensors for the Biochemical Analysis: A Review.

In recent years, DNA-based biosensors have shown great potential as the candidate of the next generation biomedical detection device due to their robust chemical properties and customizable biosensing functions. Compared with the conventional biosensors, the DNA-based biosensors have advantages such as wider detection targets, more durable lifetime, and lower production cost. Additionally, the ingenious DNA structures can control the signal conduction near the biosensor surface, which could significantly improve the performance of biosensors. In order to show a big picture of the DNA biosensor's advantages, this article reviews the background knowledge and recent advances of DNA-based biosensors, including the functional DNA strands-based biosensors, DNA hybridization-based biosensors, and DNA templated biosensors. Then, the challenges and future directions of DNA-based biosensors are discussed and proposed.

Controllable Droplet Ejection of Multiple Reagents through Focused Acoustic Beams.

Acoustic droplet ejection (ADE) technology has revolutionized fluid handling with its contactless and fast fluid transfer. For precise droplet ejection and stable droplet coalescence at the target substrates for further detection, the input power of the ADE system needs to be adjusted. Currently, the existing power control method depends on scanning the source fluid wells one by one, which cannot afford precise and highly efficient droplet velocity adjustment, and the complicated operation caused by the repeated power evaluation processes for thousands of fluid transfers will waste much time. We propose a new method, which realizes the controllable ejection of multiple reagents by analyzing the effect of the product of kinematic viscosity and surface tension of the reagents on the droplet initial velocity. The experimental results obtained by ejecting dimethyl sulfoxide coincide well with the predicted results, and the relative error in the droplet initial velocity is mostly less than 8%. On the basis of the input power prediction method proposed in this paper, the ADE system is successfully constructed for continuous dispensing of polystyrene microspheres as cell surrogates, which provided an advanced liquid handling solution for research in biochemistry and other fields.

Effects of surface tension on the dynamics of a single micro bubble near a rigid wall in an ultrasonic field.

Acoustic cavitation is a very important hydrodynamic phenomenon, and is often implicated in a myriad of industrial, medical, and daily living applications. In these applications, the effect mechanism of liquid surface tension on improving the efficiency of acoustic cavitation is a crucial concern for researchers. In this study, the effects of liquid surface tension on the dynamics of an ultrasonic driven bubble near a rigid wall, which could be the main mechanism of efficiency improvement in the applications of acoustic cavitation, were investigated at the microscale level. A synchronous high-speed microscopic imaging method was used to clearly record the temporary evolution of single acoustic cavitation bubble in the liquids with different surface tension. Meanwhile, the bubble dynamic characteristics, such as the position and time of bubble collapse, the size and stability of the bubbles, the speed of bubble boundaries and the micro-jets, were analyzed and compared. In the case of the single bubbles near a rigid wall, it was found that low surface tension reduces the stability of the bubbles in the liquid medium. Meanwhile, the bubbles collapse earlier and farther from the rigid wall in the liquids with lower surface tension. In addition, the surface tension has no significant influence on the speed of the first micro-jet, but it can substantially increase the speed of second and the third micro-jets after the first collapse of the bubble. These effects of liquid surface tension on the bubble dynamics can explain the mechanism of surfactants in numerous fields of acoustic cavitation for facilitating its optimization and application.

A review on acoustic droplet ejection technology and system.

The pace of change in chemical and biological research enabled by improved detection systems demands fundamental liquid handling and sample preparation changes. The acoustic droplet ejection (ADE)-based liquid handling method has the advantages of improving precision and data reproducibility, reducing costs, hands-on time, and eliminating waste. ADE gradually replaced traditional aspiration-and-dispense liquid-handling robots in applications such as synthetic biology, genotyping, personalized medicine, and next-generation sequencing. This review emphatically introduces the setup of the ADE system and the critical technologies of each part, including acoustic droplet generation, optimized design of the source fluid wells, droplet coalescence, and power control. The advantages and disadvantages of these technologies are discussed, and the future development of acoustic droplet ejection technology is also predicted.