A flexible glucose biosensor modified by reduced-swelling and conductive zwitterionic hydrogel enzyme membrane.

This paper reports a flexible glucose biosensor which is modified by a reduced-swelling and conductive zwitterionic hydrogel enzyme membrane that contains two forms of chemical cross-links. One chemical cross-linking is induced by thermal initiators and forms the basal network of the hydrogel. Another cross-linking is achieved by the coordination interactions between the multivalent metal ion Al3+ and anionic group -COO- of zwitterionic poly-carboxy betaine (pCBMA), which significantly increase the cross-linking density of the zwitterionic hydrogel, improving the reduced-swelling property and reducing the pore size. The better reduced-swelling property and reduced diameters of pores within the zwitterionic hydrogel make less glucose oxidase (GOx) leakage, thus significantly improving the enzyme membrane's service life. By introducing the Al3+ and Cl-, the conductivity of the zwitterionic hydrogel is enhanced approximately 10.4-fold. According to the enhanced conductivity, the reduced-swelling property, and the high GOx loading capacity of the zwitterionic hydrogel, the sensitivity of the biosensor with GOx/pCBMA-Al3+ is significantly improved by 5 times and has a long service life. Finally, the proposed GOx/pCBMA-Al3+ biosensor was applied in non-invasive blood glucose detection on the human body, verifying the capability in practice.

Extended-depth-of-field imaging with an ultra-thin folded lens.

Optical systems with extended depth of field (EDOF) are crucial for observation and measurement applications, where achieving compactness and a substantial depth of field (DOF) presents a considerable challenge with conventional optical elements. In this paper, we propose an innovative solution for the miniaturization of EDOF imaging systems by introducing an ultra-thin annular folded lens (AFL). To validate the practical feasibility of the theory, we design an annular four-folded lens with an effective focal length of 80.91 mm and a total thickness of only 8.50 mm. Simulation results show that the proposed folded lens has a DOF of 380.55 m. We further developed an AFL-based test system exhibiting a resolution of 0.11 mrad across a wide wavelength range of 486-656 nm. Additionally, we present experimental results from a miniature compact prototype, which further highlights the promising potential of folded lenses for long-range EDOF imaging.

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.

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.

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.

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.

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 hydrogel-based glucose affinity microsensor.

We present a hydrogel-based affinity microsensor for continuous glucose measurements. The microsensor is based on microelectromechanical systems (MEMS) technology, and incorporates a synthetic hydrogel that is attached to the device surface via in situ polymerization. Glucose molecules that diffuses into and out of the device binds reversibly with boronic acid groups in the hydrogel via affinity binding, and causes changes in the dielectric properties of the hydrogel, which can be measured using a MEMS capacitive transducer to determine the glucose concentration. The use of the in situ polymerized hydrogel eliminates mechanical moving parts found in other types of affinity microsensors, as well as mechanical barriers such as semipermeable membranes that are otherwise required to hold the glucose-sensitive material. This facilitates the miniaturization and robust operation of the microsensor, and can potentially improve the tolerance of the device, when implanted subcutaneously, to biofouling. Experimental results demonstrate that in a glucose concentration range of 0-500 mg/dL and with a resolution of 0.35 mg/dL or better, the microsensor exhibits a repeatable and reversible response, and can potentially be useful for continuous glucose monitoring in diabetes care.

A method for measuring the volume of transdermally extracted interstitial fluid by a three-electrode skin resistance sensor.

It is difficult to accurately measure the volume of transdermally extracted interstitial fluid (ISF), which is important for improving blood glucose prediction accuracy. Skin resistance, which is a good indicator of skin permeability, can be used to determine the volume of extracted ISF. However, it is a challenge to realize in vivo longitudinal skin resistance measurements of microareas. In this study, a three-electrode sensor was presented for measuring single-point skin resistance in vivo, and a method for determining the volume of transdermally extracted ISF using this sensor was proposed. Skin resistance was measured under static and dynamic conditions. The correlation between the skin resistance and the permeation rate of transdermally extracted ISF was proven. The volume of transdermally extracted ISF was determined using skin resistance. Factors affecting the volume prediction accuracy of transdermally extracted ISF were discussed. This method is expected to improve the accuracy of blood glucose prediction, and is of great significance for the clinical application of minimally invasive blood glucose measurement.

[Research on glucose measuring technique by surface plasmon resonance based on thiol coupling].

In the glucose measuring technique by surface plasmon resonance, D-galactose/D-glucose binding protein (GGBP) that can specifically adsorb glucose was introduced, and high-precision specific detection of glucose concentration was realized. In the present paper, the GGBP protein was bound on the surface of SPR sensor through thiol coupling method. GGBP binding experiment was carried out on SPR sensor and then glucose concentration experiment was conducted with this sensor. The results indicated that the SPR sensor had good linearity, stability and repeatability in the range of 0.1-10 mg x dL(-1). SPR sensor bound with GGBP would have great potential and vast development prospects.

[Study on detection methods of interstitial fluid glucose concentration based on infrared attenuated total reflection].

Measuring the glucose concentrations in the interstitial fluid is currently the main method to achieve the continuous blood glucose monitoring. The MIR-ATR(Mid-infrared, Attenuated Total Reflection)Spectroscopy has prominent advantage on the analysis of small biological molecule for composition information like the glucose, but it is still an unresolved problem that how to detect the subcutaneous glucose concentration by using the MIR-ATR Spectroscopy. In the present paper, we carry out the experiment based on MIR-ATR for the detection of subcutaneous glucose information on both the natural state and the penetration state based on the theoryanalysis of MIR penetration depth. Firstly, collect spectral data of the subcutaneous glucose concentration of human finger on the natural state were collected as the light shined the skin directly, and it was discussed whether the MIR can penetrate the skin to get the information of subcutaneous glucose. On this basis, collect spectral data of the subcutaneous glucose concentration of human finger at the penetration state were collected when the Interstitial fluid is permeated to the surface layer by using low-frequency ultrasound and vacuum, then it analyzed that whether it can detect the glucose-specific information or not. As the two-dimensional correlation spectroscopy has high resolution and good versatility, it is widely used to analyze the inter-molecular reaction and judge the absorption peaks information in many fields including the MIR spectroscopy field, so we choose the Two-dimensional correlation spectroscopy to analyze the information of subcutaneous glucose concentration at the natural state and the penetration state. The experiment result shows that the MIR-ATR spectroscopy can't be applied in the detection of subcutaneous glucose concentrationdirectly, and it is a promising direction to make the Interstitial fluid permeated to the surface layer by the physical methods or chemical methods.

Deep-learning enabled smart insole system aiming for multifunctional foot-healthcare applications.

Real-time foot pressure monitoring using wearable smart systems, with comprehensive foot health monitoring and analysis, can enhance quality of life and prevent foot-related diseases. However, traditional smart insole solutions that rely on basic data analysis methods of manual feature extraction are limited to real-time plantar pressure mapping and gait analysis, failing to meet the diverse needs of users for comprehensive foot healthcare. To address this, we propose a deep learning-enabled smart insole system comprising a plantar pressure sensing insole, portable circuit board, deep learning and data analysis blocks, and software interface. The capacitive sensing insole can map both static and dynamic plantar pressure with a wide range over 500 kPa and excellent sensitivity. Statistical tools are used to analyze long-term foot pressure usage data, providing indicators for early prevention of foot diseases and key data labels for deep learning algorithms to uncover insights into the relationship between plantar pressure patterns and foot issues. Additionally, a segmentation method assisted deep learning model is implemented for exercise-fatigue recognition as a proof of concept, achieving a high classification accuracy of 95%. The system also demonstrates various foot healthcare applications, including daily activity statistics, exercise injury avoidance, and diabetic foot ulcer prevention.

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.

A MEMS Dielectric Affinity Glucose Biosensor.

Continuous glucose monitoring (CGM) sensors based on affinity detection are desirable for long-term and stable glucose management. However, most affinity sensors contain mechanical moving structures and complex design in sensor actuation and signal readout, limiting their reliability in subcutaneously implantable glucose detection. We have previously demonstrated a proof-of-concept dielectric glucose sensor that measured pre-mixed glucose-sensitive polymer solutions at various glucose concentrations. This sensor features simplicity in sensor design, and possesses high specificity and accuracy in glucose detection. However, lack of glucose diffusion passage, this device is unable to fulfill real-time in-vivo monitoring. As a major improvement to this device, we present in this paper a fully implantable MEMS dielectric affinity glucose biosensor that contains a perforated electrode embedded in a suspended diaphragm. This capacitive-based sensor contains no moving parts, and enables glucose diffusion and real-time monitoring. The experimental results indicate that this sensor can detect glucose solutions at physiological concentrations and possesses good reversibility and reliability. This sensor has a time constant to glucose concentration change at approximately 3 min, which is comparable to commercial systems. The sensor has potential applications in fully implantable CGM that require excellent long-term stability and reliability.

A MEMS differential viscometric sensor for affinity glucose detection in continuous glucose monitoring.

Micromachined viscometric affinity glucose sensors have been previously demonstrated using vibrational cantilever and diaphragm. These devices featured a single glucose detection module that determines glucose concentrations through viscosity changes of glucose-sensitive polymer solutions. However, fluctuations in temperature and other environmental parameters might potentially affect the stability and reliability of these devices, creating complexity in their applications in subcutaneously implanted continuous glucose monitoring (CGM). To address these issues, we present a MEMS differential sensor that can effectively reject environmental disturbances while allowing accurate glucose detection. The sensor consists of two magnetically driven vibrating diaphragms situated inside microchambers filled with a boronic-acid based glucose-sensing solution and a reference solution insensitive to glucose. Glucose concentrations can be accurately determined by characteristics of the diaphragm vibration through differential capacitive detection. Our in-vitro and preliminary in-vivo experimental data demonstrate the potential of this sensor for highly stable subcutaneous CGM applications.

[Application of mid-infrared wavelength tunable laser in glucose determination].

The authors proposed a method of control and stabilization for laser emission wavelengths and power, and presented the mid-infrared wavelength tunable laser with broad emission spectrum band of 9.19-9.77 microm, half wave width of 4 cm(-1), spectral resolution of 2.7 x 10(4) and max power of 800 mW with fluctuation < 0.8% in the present paper. The tunable laser was employed as the light source in combination with ATR sensor for glucose measurement in PBS solution. In our experiments, absorbance at the five laser emission wavelengths, including 1 081, 1 076, 1 051, 1 041 and 1 037 cm(-1) in the 9R and 9P band of the laser emission spectrum, all correlates well with the glucose concentration (R2 > 0.99, SD < 0.0004, P < 0.000 1). Especially, the sensitivity of this laser spectroscopy system is about 4 times as high as that of traditional FTIR spectrometer.

[Effect of borate polymer layers on measurement of glucose concentration by SPR].

A new borate polymer PAA-ran-PAAPBA that can specifically adsorb glucose was introduced in the glucose measurement based on surface plasmon resonance, and the high-precision specific detection of glucose concentration was realized. Six layers and twelve layers of borate polymer were respectively bound onto the SPR sensors through the layer-by-layer self-assembly binding method, and the effect of different layers of borate polymer on the glucose surface plasmon resonance measurement was studied. The experiment was conducted in the concentration range of 1-10 mg x dL(-1) (interval delta = 1 mg x dL(-1)), 10-100 mg x dL(-1) (interval delta = 10 mg x dL(-1)), and 100-1 000 mg x dL(-1) (interval delta = 100 mg x dL(-1)), experiment data was fitted by quadric curve and the fitting degree of refractive index difference deltaRU and glucose concentration was obtained. Results showed that the 12-layer-polymer sensor was better than the 6-layer-polymer sensor in the first two smaller ranges, and the measuring result was not significantly affected by layers in the third range, indicating that for the small concentrations increasing polymer layer can dramatically improve the measurement.

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.

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.