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Chemotherapeutic drugs such as paclitaxel and vinblastine interact with microtubules and thus induce complex cell states of mitosis arrest at the G2/M phase followed by apoptosis dependent on drug exposure time and concentration. Microfluidic impedance cytometry (MIC), as a label-free and high-throughput technology for single-cell analysis, has been applied for viability assay of cancer cells post drug exposure at fixed time and dosage, yet verification of this technique for varied tumor cell states after anticancer drug treatment remains a challenge. Here we present a novel MIC device and for the first time perform impedance cytometry on carcinoma cells exhibiting progressive states of G2/M arrest followed by apoptosis related to drug concentration and exposure time, after treatments with paclitaxel and vinblastine, respectively. Our results from impedance cytometry reveal increased amplitude and negative phase shift at low frequency as well as higher opacity for HeLa cells under G2/M mitotic arrest compared to untreated cells. The cells under apoptosis, on the other hand, exhibit opposite changes in these electrical parameters. Therefore, the impedance features differentiate the HeLa cells under progressive states post anticancer drug treatment. We also demonstrate that vinblastine poses a more potent drug effect than paclitaxel especially at low concentrations. Our device is fabricated using a unique sacrificial layer-free soft lithography process as compared to the existing MIC device, which gives rise to readily aligned parallel microelectrodes made of silver-PDMS embedded in PDMS channel sidewalls with one molding step. Our results uncover the potential of the MIC device, with a fairly simple and low-cost fabrication process, for cellular state screening in anticancer drug therapy. [ABSTRACT FROM AUTHOR]

This paper proposes using a fractional-order digital loop integrator to improve the robust stability of Sigma-Delta modulator, thus extending the integer-order Sigma-Delta modulator to a non-integer-order (fractional-order) one in the Sigma-Delta ADC design field. The proposed fractional-order Sigma-Delta modulator has reasonable noise characteristics, dynamic range, and bandwidth; moreover the signal-to-noise ratio (SNR) is improved remarkably. In particular, a 2nd-order digital loop integrator and a digital PIλDμ controller are combined to work as the fractional-order digital loop integrator, which is realized using FPGA; this will reduce the ASIC analog circuit layout design and chip testing difficulties. The parameters of the proposed fractional-order Sigma-Delta modulator are tuned by using swarm intelligent algorithm, which offers opportunity to simplify the process of tuning parameters and further improve the noise performance. Simulation results are given and they demonstrate the efficiency of the proposed fractional-order Sigma-Delta modulator. [ABSTRACT FROM AUTHOR]

[Display omitted] • The SPR and fluorescence dual-mode detection system were applied. • The whole cell and membrane region of a single cell were analyzed simultaneously. • The temporal and spatial correspondences were established. • Effectiveness of multiple drugs on A549 cells was tested. The investigation of the interactions between cells and drugs forms a crucial aspect of biological and clinical medical studies. Generally, single-cell or local-cellular studies require a microscopic imaging system with high magnifications, which suffers from low detection throughputs and poor time responses. The study presented in this paper combined SPR and fluorescence to achieve cell localization, real-time monitoring of cell images and quantitative analysis of drugs. In order to obtain more comprehensive, accurate and real-time data, a dual-mode system based on surface plasmon resonance (SPR) and fluorescence was constructed based on a 4× magnification lens. This enables simultaneous studies of an entire cell and a specific region of the cell membrane. An adaptive adjustment algorithm was established for distorted SPR images, achieving temporal and spatial matching of the dual-mode detection. The combination of SPR and fluorescence not only achieved micro-detection but also complemented the qualitative or quantitative limitations of SPR or fluorescence method alone. In system characterization, the response signal of SPR was noticed to increase with the increasing concentration of EGF in stimulated cells. It indicated that this platform could be employed for quantitative detection of the cell membrane region. Upon addition of EGF, a peak in the SPR curve was observed, and the cells in the corresponding SPR image turned whiter. This indicated that the platform can simultaneously monitor the SPR response signal and image changes. The response time of fluorescence in EGF testing was several seconds earlier than SPR, revealing that signal transduction first occurred in the whole cell and then propagated to the cell membrane region. The inhibitory ability of Gefitinib on cells was verified in a fast and real-time manner within 20 min. The results indicated that the detection limit of this method was 20 IU/mL for EGF and 10 µg/mL for Gefitinib. In conclusion, this study demonstrates the advantages of SPR and fluorescence dual-mode techniques in the analysis of cell-drug interactions, as well as their strong potential in drug screening. [ABSTRACT FROM AUTHOR]

Molecular dynamics characteristics have important significance in studying the interaction between biomolecules, such as drug screening, environmental monitoring and evaluation of virus infectivity. In this work, a simulation method based on step function is proposed to study the molecular binding and dissociation processes, which is further coupled with surface plasmon wave evanescent field. A complete simulation model is established from biomolecular reaction to surface plasmon resonance (SPR) optical detection, which is consistent with the experimental process. Furthermore, experimental verification studies were carried out on human serum albumin (HSA), a marker of the urinary protein disease. The effects of microchannel size, liquid flow rate, molecular concentration, complex samples and other conditions on the molecular dynamics binding characteristics were studied under the conditions of antibody fixation and antigen–antibody binding reaction. Optimized parameters are obtained such as microchannel size and liquid flow rate, which can save reaction reagents reduce the experimental process and improve the experimental detection accuracy. Therefore, the established simulation and experimental methods include a complete process from biological information to optical information, which is expected to be a powerful tool for molecular interaction analysis in the future. [ABSTRACT FROM AUTHOR]

Dielectrophoresis has been widely applied in microfluidic cell separation, and it enables label-free and size-independent cell sorting based on their dielectric fingerprints which is prerequisite for downstream biomedical analysis. The linear flow velocity and cross-sectional area are the two key factors proportional to the flow rate and thus directly related to the sample processing throughput. Aiming at higher flow rate, the state-of-art techniques mostly focus on the cross-sectional area, either by using wide chamber with angled electrode digits or 3D volumetric electrodes with expanded channel depth. On the other hand, the velocity is always carefully limited because cells have very squeezed time to interact with the DEP force that drives them to migrate, and the flow drag induced by high velocity potentially poses adverse effect against the DEP-driven cell migration. In this paper, we present DEP-activated cell sorting at high-velocity being 1–2 orders of magnitude higher than the existing DEP separators, which is enabled by easily-fabricated two-layer 3D sidewall electrodes extending along the entire flow channel. Such electrodes project DEP force fully decoupled from the flow drag, and acting on cells continuously, allowing sufficient time for cell migration. The two-layer design leads to cell migration across a shorter distance between the upper and lower layers, with a unique bridge adaptor evolved at the downstream for the collection of the cells vertically separated. The DEP device achieves separation of live and dead yeast cells at high velocity up to 78.3 mm/s, more than a full order of magnitude higher compared to any reported DEP platforms. This velocity corresponds to a competitive flow rate of 3.1 mL/h given the fairly small cross-sectional area, where the averaged collection rate is over 95 %. For the separation between the live and dead Hela cells, our device enables a high velocity up to 50.5 mm/s with an averaged collection rate of ∼85 %. A high throughput of 1.79 × 1 0^(5) cells/min for the live and dead Hela cell separation has been achieved with 89.7 % collection for live cells and a velocity of 30.3 mm/s. • A unique design of two-layer electrodes extending along the entire channel. • Rapid cell lateral migration enabled by continuously exerted strong DEP force. • Fully decoupled DEP force and flow drag force, eliminating their interference. • DEP-driven cell migration from the lower to upper layer across a short distance. • High velocity up to78.3 mm/s achieved for DEP-activated cell separation [ABSTRACT FROM AUTHOR]

The finite-difference (FD) scheme is extensively applied in seismic modelling, imaging and inversion due to its advantages of large-scale parallel computing and programming. However, numerical dispersion caused by using a difference operator in substitution for the differential operator is non-negligible, which reduces the accuracy of the modelling and can lead to some misinterpretations. In addition, the computing resources required by the FD scheme is highly demanding when dealing with large models, which limits its applicability. In this paper, a new optimised FD scheme is proposed, which is based on an improved particle swarm optimisation (PSO) algorithm. We improve the conventional PSO algorithm by introducing strategies related to local learning and global learning, which contribute to accelerating the convergence rate and effectively avoiding getting trapped in local extrema. Then, the improved PSO algorithm is used to improve the conventional FD scheme. Dispersion analysis and numerical modelling demonstrate that the low-order optimised FD scheme can achieve higher accuracy than a high-order conventional operator. Compared with the conventional FD scheme and a FD scheme based on the Remez exchange algorithm, the optimised FD scheme based on the improved PSO algorithm can more efficiently suppress numerical dispersion and increase computational efficiency. [ABSTRACT FROM AUTHOR]

Obtaining a continuous relationship between input and output is essential during sensor characteristic determination. However, it is a little challenging for complicated input data, for example, image data. In this article, a sensor characteristic determining method using deep learning Compact yet Efficient Cascade Context-based Estimation (C3E) network, which can establish the continuous relationship between the input and the output, was proposed. A UV sensing system based on this C3E method was presented. The sensor after algorithm optimization has a sensitivity of $1~\mu \text{W}$ /cm2. The limit of detection is $9~\mu \text{W}$ /cm2. The network test time is close to 3 s, and the error rate is 5%, which is very suitable to transplant to the embedded platform and provides solutions for compact instruments. [ABSTRACT FROM AUTHOR]

Dielectrophoresis (DEP) is a powerful technique for label-free cell separation in microfluidics. Easily-fabricated DEP separators with low cost and short turnaround time are in extremely high demand in practical applications, especially clinical usage where disposable devices are needed. DEP separators exploiting microelectrodes made of conducting polydimethylsiloxane (PDMS) composites enable the construction of advantageous 3D volumetric electrodes with a simple soft-lithography process. Yet, existing devices incorporating microelectrodes in conducting PDMS generally have their fluidic sidewalls constructed using a different material, and consequently require extra lithography of a sacrificial layer on the semi-finished master for molding the electrode and fluidic sidewalls in separate steps. Here we demonstrate a novel microfluidic DEP separator with a 3D electrode and fluidic structure entirely integrated within silver-PDMS composites. We develop a further simplified one-step molding process with lower cost using a readily-available and reusable SU8 master, eliminating the need for the additional lithography step in existing techniques. The uniquely designed two-layer electrode exhibits a spatially non-uniform electric field that enables cell migration in the vertical direction. The electrode upper layer then offers a harbor-like region for the trapping of the target cells that have drifted upwards, which shelters them from being dragged away by the main flow streams in the lower layer, and thus allows higher operation flow rate. We also optimize the upper layer thickness as a critical dimension for protecting the trapped cells from high drag and show easy widening of our device by elongation of the digits. We demonstrate that the elongated digits involving more parallel flow paths maintain a high capture efficiency of 95.4% for live cells with 85.6% purity in the separation of live/dead HeLa cells. We also investigate the device feasibility in a viability assay for cells post anti-cancer drug treatment. [ABSTRACT FROM AUTHOR]

Polymerase chain reaction (PCR) is an extremely important tool for molecular diagnosis, as it can specifically amplify nucleic acid templates for sensitive detection. As another division of PCR, free convective PCR was invented in 2001, which can be performed in a capillary tube pseudo-isothermally within a significantly short time. Convective PCR thermal cycling is implemented by inducing thermal convection inside the capillary tube, which stratifies the reaction into spatially separate and stable melting, annealing, and extension zones created by the temperature gradient. Convective PCR is a promising tool that can be used for nucleic acid diagnosis as a point-of-care test (POCT) due to the significantly simplified heating strategy, reduced cost, and shortened detection time without sacrificing sensitivity and accuracy. Here, we review the history of free convective PCR from its invention to development and its commercial applications. Image 1 • Systematically review convective PCR (CPCR) from its invention to development and even commercial applications. • Different CPCR with different implementation formats were discussed. • Key characteristics of CPCR reactor such as material, fabrication, and thermal control were compared. • Different detection methods and formats of CPCR were compared. • CPCR system integration and commercial applications were discussed. [ABSTRACT FROM AUTHOR]

We report the velocity measurement of microscopic particles flowing at ultrahigh speed with optofluidic time-stretch microscopy at high throughput. This is a study of using optical time-stretch microcopy as a tool for particle velocimetry, where we developed a custom algorithm to process the images acquired from the optofluidic platform for the velocity calculation of individual particles. We experimentally determined the actual flow velocities for polystyrene microspheres with different sizes and traveling through the microchannel at a throughput of ∼10 000 particles/s. We also examined microfluidic channels with different aspect ratios (depth-to-width) for particle velocimetry. The result indicates a measurable flow velocity up to 2.51 m/s. Our method provides a promising tool for label-free and high-throughput particle velocimetry at high velocity magnitudes. [ABSTRACT FROM AUTHOR]

Ideal urine screening should realize the detection of a variety of different urine proteins, corresponding to the diagnosis of different diseases. However, there is a lack of effective instruments to realize the simultaneous screening of albumin and light chain protein. In this paper, a specialized multiplexed urine protein detection instrument based on SPR technology was developed for quantitative detection of human serum albumin (HSA), beta-2-microglobulin (B2M), kappa light chain and lambda light chain protein. A modified BSA sensor membrane was developed to realize one-step direct detection of the analyte. The sensitivity, repeatability and specificity of the SPR instrument were analyzed and tested, and the standard curves of four proteins were calculated. Comparing the results between healthy people and nephrotic patients by our instrument, it was found that there was a significant difference in the two groups for HSA and B2M detection (p < 0.01), indicating that HSA and B2M are suitable markers for nephropathy diagnosis. Furthermore, the performance of our instrument was compared with commercialized platforms and got lower experimental concentrations than the immunoturbidimetry method in kappa and lambda detection. It will promote early screening of kidney and tumour diseases simultaneously by applying our SPR sensor in the future. • A specialized multiplexed urine protein detection instrument. • The lowest concentrations of four urinary proteins all met the requirements of clinical sample detection. • The regeneration times of the SPR chip surface is more than 50. • Better detection limit than immunoturbidimetry method. • Early diagnosis and screening of clinical samples for renal and tumor diseases. [ABSTRACT FROM AUTHOR]

Most prism-based surface plasmon resonance (SPR) experiments use matching fluid with a similar refractive index to mount the chip on the optical prism. The fluidity of the matching fluid easily affects the transmission of the optical signal. In this paper, an integrated SPR sensor chip comprises a three-layer structure of flow layer, metal layer and refractive index matching layer is demonstrated to address the problems related to consistency and uniformity. The Young's modulus, array spacing, shape and other parameters of the matching film were calculated and optimized. The chip can self-adhere to the optical prism, and effectively avoids the generation of air bubbles. The refractive index detection sensitivity of the integrated SPR sensor chip was 3.4359 × 10−6 RIU (refractive index unit), and the chip stabilization time has been effectively shortened. The integrated SPR sensor chip was also used to detect kappa light chain protein and human serum albumin (HSA) in urine samples. The detection limit of kappa light chain protein was 0.06 μg/mL compared with 18.5 μg/mL by conventional immunoturbidimetry. The integrated SPR sensor chip based on refractive index matching film array has great potential in biomedical detection and other fields, including point-of-care testing (POCT). [Display omitted] • Integrated surface plasmon resonance chip based on refractive index matching film array. • SPR chip self-adsorbed on optical prism by matching film. • SPR chip stabilization time has been effectively shortened. • Sensing sensitivity and biochemical performance of the integrated SPR chip is within a diagnostically-useful range. [ABSTRACT FROM AUTHOR]

The wearable sensors based on image processing possess distinct advantages such as being power-free and without complex wire connections, which are of low cost and easy to manufacture. In this paper, a wearable UV sensor made from photochromic material and PDMS was proposed to be employed in real-time UV monitoring and daily solar protection. The convolutional neural network image processing method was introduced and developed for quantifying UV intensity, and it was shown to decrease the impact of ambient light significantly. The limit of detection of the sensor was about 9 μW/cm2 and the recognition rate of the network exceeded 90% under different ambient light conditions. The CNN test was complete within 3 s. Finally, regarding applied scenarios, a UV intensity recognition APP based on a mobile convolutional neural network was designed, which displayed the real-time UV intensity by simple photting. [Display omitted] • AA wearable UV sensor which is made from photochromic material and PDMS was proposed. • The limit of detection of the sensor was about 9 μW/cm2 and the recognition rate of the network is above 90%. • The CNN test could be finished within 3 s. • A UV intensity recognition APP based on a mobile convolutional neural network. [ABSTRACT FROM AUTHOR]

PCR has been widely used in different fields including molecular biology, pathogen detection, medical diagnosis, food detection and etc. However, the difficulty of promoting PCR in on-site point-of-care testing reflects on challenges relative to its speed, convenience, complexity, and even cost. With the emerging state-of-art of microfluidics, rapid PCR can be achieved with more flexible ways in micro-reactors. PCR plays a critical role in the detection of SARS-CoV-2. Under this special background of COVID-19 pandemic, this review focuses on the latest rapid microfluidic PCR. Rapid PCR is concluded in two main features, including the reactor (type, size, material) and the implementation of thermal cycling. Especially, the compromise between speed and sensitivity with microfluidic PCR is explored based on the system ratio of (thermal cycling time)/(reactor size). Representative applications about the detection of pathogens and SARS-CoV-2 viruses based on rapid PCR or other isothermal amplification are discussed as well. • Reviewing rapid PCR from both the reactor (type, size and material) and the implementation of thermal cycling. • Key characteristics of different implementations of thermal cycling (space- and time-domain based) were analyzed. • Convection PCR, as a special rapid nucleic acid amplification method, was discussed and compared with other rapid PCR. • To show the compromise between speed and sensitivity, the system ratio (thermal cycling time)/(reactor size) was defined. • Witnessing the global COVID-19 pandemic, emphasizing the key contribution of rapid PCR or isothermal amplification. [ABSTRACT FROM AUTHOR]

• Ideally straight electrode-tracks made of silver-PDMS (AgPDMS) that assisted smooth sliding of cells under pDEP affinity were developed for continuous-flow DEP-activated cell sorting. • The electrode-tracks were scalable by mirroring to form V-shaped tracks that enabled bidirectional cell sliding and involve elevated number of flow paths for further enhanced throughput. • Greatly enhanced throughput with comparably high efficiencies for DEP-activated cell sorting were achieved as compared to the existing devices incorporating conducting-PDMS electrodes, with further simplified replica molding process. Dielectrophoresis (DEP) as a label-free cell separation approach in microdevices has been extensively investigated for a variety of applications. 3D microelectrodes made of conducting-PDMS inherit the merit of volumetric electrodes for generating influential DEP force throughout the entire channel depth and meanwhile, exploit low-cost fabrication process by soft lithography. However, the configuration of conducting-PDMS electrodes is limited to being embedded in sidewall of flow chamber, which leads to rather low flow rate and difficulties in extension of the flow rate. We previously reported a more effective configuration with 3D interdigitated electrodes made of silicon that assist cell sliding along solid tracks, yet such device requires expensive silicon dry etching and, moreover, the track appears to be patterned with non-straight and wavy outline, which not only hinders the flow rate but also allows cell sliding to occur only along its downstream side. Here we demonstrate low-cost silver-PDMS electrode-track featuring ideally straight outline that induces rather uniform drag to drive smooth cell sliding. Such design achieves live and dead cell separation at flow rate twice as that of silicon tracks with cell loading concentration 10 times higher. It also fully utilizes the track to enable cell sliding on both of the up- and down-stream sides. Notably, we also demonstrate that this track is expandable to be V-shape for more advanced bidirectional cell sliding, which is showcased here by tumor cells separation from lymphocytes at 1.2 mL/h. Such results greatly enhance the throughput as compared to the state-of-art conducting-PDMS based cell separator. [ABSTRACT FROM AUTHOR]

Electronic skin (e‐skin) integrating pressure sensors and strain sensors has shown great potential applications in smart robotics and healthcare monitoring for their flexibility and wearability. However, making the sensor low cost and highly durable for industrialization and commercialization is still a problem to be addressed. An embedded 3D printing technology is developed based on novel thermosetting printing ink which is prepared using the Ecoflex and carbon nanoparticles. The properties of the printing ink including printability and electrical conductivity are first studied and then optimized. By using this technology, a glove‐shaped e‐skin integrating both strain sensors and pressure sensors is fabricated, and the properties of the sensors are studied. Both types of sensors have excellent stability and reliability which are verified by multiple long‐term measurements (10 000 testing cycles). Specifically, the sensors possess a great shock resistance and high durability which are significant for application in real life. Furthermore, some applications for human activity monitoring and personal healthcare are demonstrated, including complex gesture recognition using 15 strain sensors, hardness sensing using pressure sensors coupled with strain sensors, and arterial pulse measurement using pressure sensors, which are promising for smart robotic sensing and wearable biomedical devices. [ABSTRACT FROM AUTHOR]