Reconstruction Filters Improving the Spatial Resolution and Signal-to-Noise Ratio of Surface Plasmon Resonance Microscopy.

Benefitting from high sensitivity, real-time, and label-free imaging, surface plasmon resonance microscopy (SPRM) has become a powerful tool for dynamic detection of nanoparticles. However, the evanescent propagation of surface plasmon polaritons (SPPs) induces interference between scattered and launched SPPs, which deteriorates the spatial resolution and signal-to-noise ratio (SNR). Due to the simplicity and fast processing, image reconstruction based on deconvolution has shown the feasibility of improving the spatial resolution of SPRM imaging. Retrieving the particle scattering from SPRM interference imaging by filters is crucial for reconstruction. In this work, we illustrate the effect of filters extracting SPP scattering of nanoparticles with different sizes and shapes for reconstruction. The results indicate that the optimum filters are determined by the material of nanoparticles instead of particle sizes. The reconstruction of single Au and PS nanospheres as well as Ag nanowires with optimum filters is achieved. The reconstructed spatial resolution is improved to 254 nm, and the SNR is increased by 8.1 times. Our research improves the quality of SPRM imaging and provides a reliable method for fast detection of particles with diverse sizes and shapes.

Directional surface plasmon polariton scattering using single magnetic nanoparticles.

Directional surface plasmon polaritons (SPPs) are expected to promote the energy efficiency of plasmonic devices, via limiting the energy in a given spatial domain. The directional scattering of dielectric nanoparticles induced by the interference between electric and magnetic responses presents a potential candidate for directional SPPs. Magnetic nanoparticles can introduce permeability as an extra manipulation, whose directional scattered SPPs have not been investigated yet. In this work, we demonstrated the directional scattered SPPs by using single magnetic nanoparticles via simulation and experiment. By increasing the permeability and particle size, the high-order TEM modes are excited inside the particle and induce more forward directional SPPs. It indicated that the particle size manifests larger tuning range compared with the permeability. Experimentally, the maximum forward-to-backward (F-to-B) SPP scattering intensity ratio of 118.52:1 is visualized by using a single 1 µm Fe3O4 magnetic nanoparticle. The directional scattered SPPs of magnetic nanoparticles are hopeful to improve the efficiency of plasmonic devices and pave the way for plasmonic circuits on-chip.

Curved and Annular Diaphragm Coupled Piezoelectric Micromachined Ultrasonic Transducers for High Transmit Biomedical Applications.

In this paper, we present a novel three-dimensional (3D) coupled configuration of piezoelectric micromachined ultrasound transducers (pMUTs) by combing a curved and an annular diaphragm for transmit performance optimization in biomedical applications. An analytical equivalent circuit model (EQC) is developed with varied excitation methods to incorporate the acoustic-structure coupling of the curved and annular diaphragm-coupled pMUTs (CAC-pMUTs). The model-derived results align well with the reference simulated by the finite element method (FEM). Using this EQC model, we optimize the key design parameters of the CAC-pMUTs in order to improve the output sound pressure, including the width of the annular membrane, the thickness of the passive layer, and the phase difference of the driving voltage. In the anti-phase mode, the designed CAC-pMUTs demonstrate a transmit efficiency 285 times higher than that of single annular pMUTs. This substantial improvement underscores the potential of CAC-pMUTs for large array applications.

Cardiac Multi-Frequency Vibration Signal Sensor Module and Feature Extraction Method Based on Vibration Modeling.

Cardiovascular diseases pose a long-term risk to human health. This study focuses on the rich-spectrum mechanical vibrations generated during cardiac activity. By combining Fourier series theory, we propose a multi-frequency vibration model for the heart, decomposing cardiac vibration into frequency bands and establishing a systematic interpretation for detecting multi-frequency cardiac vibrations. Based on this, we develop a small multi-frequency vibration sensor module based on flexible polyvinylidene fluoride (PVDF) films, which is capable of synchronously collecting ultra-low-frequency seismocardiography (ULF-SCG), seismocardiography (SCG), and phonocardiography (PCG) signals with high sensitivity. Comparative experiments validate the sensor's performance and we further develop an algorithm framework for feature extraction based on 1D-CNN models, achieving continuous recognition of multiple vibration features. Testing shows that the recognition coefficient of determination (R2), mean absolute error (MAE), and root mean square error (RMSE) of the 8 features are 0.95, 2.18 ms, and 4.89 ms, respectively, with an average prediction speed of 60.18 us/point, meeting the re-quirements for online monitoring while ensuring accuracy in extracting multiple feature points. Finally, integrating the vibration model, sensor, and feature extraction algorithm, we propose a dynamic monitoring system for multi-frequency cardiac vibration, which can be applied to portable monitoring devices for daily dynamic cardiac monitoring, providing a new approach for the early diagnosis and prevention of cardiovascular diseases.

A Surface Electromyography (sEMG) System Applied for Grip Force Monitoring.

Muscles play an indispensable role in human life. Surface electromyography (sEMG), as a non-invasive method, is crucial for monitoring muscle status. It is characterized by its real-time, portable nature and is extensively utilized in sports and rehabilitation sciences. This study proposed a wireless acquisition system based on multi-channel sEMG for objective monitoring of grip force. The system consists of an sEMG acquisition module containing four-channel discrete terminals and a host computer receiver module, using Bluetooth wireless transmission. The system is portable, wearable, low-cost, and easy to operate. Leveraging the system, an experiment for grip force prediction was designed, employing the bald eagle search (BES) algorithm to enhance the Random Forest (RF) algorithm. This approach established a grip force prediction model based on dual-channel sEMG signals. As tested, the performance of acquisition terminal proceeded as follows: the gain was up to 1125 times, and the common mode rejection ratio (CMRR) remained high in the sEMG signal band range (96.94 dB (100 Hz), 84.12 dB (500 Hz)), while the performance of the grip force prediction algorithm had an R2 of 0.9215, an MAE of 1.0637, and an MSE of 1.7479. The proposed system demonstrates excellent performance in real-time signal acquisition and grip force prediction, proving to be an effective muscle status monitoring tool for rehabilitation, training, disease condition surveillance and scientific fitness applications.

Real-time measurement of the trans-epithelial electrical resistance in an organ-on-a-chip during cell proliferation.

The trans-epithelial electrical resistance (TEER) is widely used to quantitatively evaluate cellular barrier function at the organ level in vitro. The measurement of the TEER in organ-on-chips (organ chips) plays a significant role in medical and pharmacological research. However, due to the limitation of the electrical equivalent model for organ chips, the existing TEER measurements usually neglect the changes of the TEER during cell proliferation, resulting in the low accuracy of the measurements. Here, we proposed a new whole-region model of the TEER and developed a real-time TEER measurement system that contains an organ chip with a plate electrode. A whole region circuit model considering the impedance of the non-cell covered region was also established, which enables TEER measurements to be independent of the changes in the cell covered region. The impedance of the non-cell covered region is here attributed to the resistance of the porous membrane. By combining the real-time measurement system and the whole region model, subtle changes in cellular activity during the proliferation stage were measured continuously every 6 minutes and a more sensitive TEER response was obtained. Furthermore, the TEER measurement accuracy was also verified by the real-time measurement of the TEER with stimulation using the permeability enhancer ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA). The obtained results indicated that the new proposed whole region model and the real-time measurement system have higher accuracy and greater sensitivity than the traditional model.

A parylene-mediated plasmonic-photonic hybrid fiber-optic sensor and its instrumentation for miniaturized and self-referenced biosensing.

With the development of advanced nanofabrication techniques over the past decades, different nanostructure-based plasmonic fiber-optic sensors have been developed and have presented a low limit of detection for various biomolecules. However, owing to both the dependence on complex equipment and the trade-off between the fabrication cost and sensing performance, nanostructured plasmonic fiber-optic sensors are rarely used outside laboratories. To facilitate wider application of the plasmonic fiber-optic sensors, a parylene-mediated hybrid plasmonic-photonic cavity-based sensor was developed. Compared with a similar plasmonic sensor which only works in the plasmonic mode, the proposed hybrid sensor shows a higher reproducibility (CV < 2.5%) due to its resistance to fabrication variations. Meanwhile, a self-referenced detection mechanism and a novel miniaturized system were developed to adapt to the hybrid resonance sensor. The entire system only has a weight of 263 g, and a size of 12 cm × 10 cm × 8 cm, and is especially suitable for outdoor applications in a handheld manner. In experiments, a high refractive index sensitivity of 3.148 RIU-1 and real-time biomolecule monitoring at nanomolar concentrations were achieved by the proposed system, further confirming the potential of the miniaturized system as a candidate for point-of-care health diagnostics outside laboratories.

Carbon nanoparticles-based hydrogel nanocomposite induces bone repair in vivo.

The main objective of the current study is to fabricate a 3D scaffold using alginate hydrogel implemented with carbon nanoparticles (CNPs) as the filler. The SEM imaging revealed that the scaffold possesses a porous internal structure with interconnected pores. The swelling value of the scaffolds (more than 400%) provides a wet niche for bone cell proliferation and migration. The in vitro evaluations showed that the scaffolds were hemocompatible (with hemolysis induction lower than 5%) and cytocompatible (inducing significant proliferative effect (cell viability of 121 ± 4%, p < 0.05) for AlG/CNPs 10%). The in vivo studies showed that the implantation of the fabricated 3D nanocomposite scaffolds induced a bone-forming effect and mediated bone formation into the induced bone defect. In conclusion, these results implied that the fabricated NFC-integrated 3D scaffold exhibited promising characteristics beneficial for bone regeneration and can be applied as the bone tissue engineering scaffold.

Effects of nanoparticle sizes, shapes, and permittivity on plasmonic imaging.

Plasmonic imaging has exhibited superiority in label-free and fast detection to single nanoparticles due to its high sensitivity and high temporal resolution, which plays an important role in environmental monitoring and biomedical research. As containing plenty of information associated with particle features, plasmonic imaging has been used for identifying the particle sizes, shapes, and permittivity. Yet, the effects of the nanoparticle features on plasmonic imaging are not investigated, which hinders the in-depth understanding to plasmonic imaging and its applications in particle identification. In this work, we analyzed five types of nanoparticles, including polystyrene (PS), Au, silicon nanospheres as well as PS and Ag nanowires. We illustrated the effects of nanoparticle sizes, shapes, and permittivity on spatial resolution, imaging contrast, and interference fringes. We found that nanoparticle sizes and permittivity influenced the imaging contrast. Via introducing size parameter relevant to interference fringes, the connection between particle shape and reduction rate of size parameter is built, and the effects of particle shapes on the interference patterns are revealed. Our research provides a basis for improving the plasmonic imaging and presents guidance for applications on particle identification in nano-detection, biosensor, and environmental monitoring.

Locally excited surface plasmon resonance for refractive index sensing with high sensitivity and high resolution.

An angle-interrogated surface plasmon resonance (SPR) sensor based on a prism-coupled configuration has been extensively applied in biomedicine, environment monitoring, and food safety. Yet, the low sensitivity and low spatial resolution impede its further development. In this Letter, we investigated objective-coupled locally excited SPR for refractive index (RI) sensing with high sensitivity and high resolution. Through theoretical analysis, the SPR angle was retrieved from back focal plane imaging, which was highly correlated to the RI of the surrounding medium. Experimentally, a RI sensitivity of 77.41° refractive index unit (RIU)-1 was achieved with a detection range of 0.068 RIU when using glucose solutions for the demonstration. Furthermore, we acquired the spatial resolution of the configuration being 290 nm, and the RI measurement to a polydimethylsiloxane droplet with high spatial resolution was implemented. As a result, compared with the classical prism-coupled configuration, the locally excited SPR provides a method to achieve RI sensing with high sensitivity and high resolution.

Convex-Meniscus-Assisted Self-Assembly at the Air/Water Interface to Prepare a Wafer-Scale Colloidal Monolayer Without Overlap.

Self-assembly at the air/water interface (AWI) has proven to be an efficient strategy for fabricating two-dimensional (2D) colloidal monolayers, which was widely used as the template for nanosphere lithography in nanophononics, optofluidics, and solar cell studies. However, the monolayers fabricated at the AWI usually suffer from a small domain area and quasi-double layer structure caused by submerged particles. To overcome this, we proposed an improved protocol to prepare 2D colloidal monolayers free of overlapping nanospheres at the AWI. Utilizing the stable suspension infusion to the water surface, a convex meniscus, whose height is related to viscous force, was formed adjoining the three-phase boundary. As a result of the resistance of the convex meniscus, the polystyrene nanospheres in the initial suspension directly self-assembled into a preliminary monolayer, which proved effective in preventing nanospheres' sinking and increasing the colloidal crystal domain size. An optimal parameter for transferring the monolayer was also developed based on the numerical simulation results. Finally, a wafer-scale monolayer, covered with less than one nanosphere per 100 µm × 100 µm area, was achieved on the desired substrate with an average domain size attaining centimeter scale. The high-quality 2D colloidal crystal may further promote the application of nanosphere lithography, especially in the fields that require a defect-free template.

Microsphere mediated exosome isolation and ultra-sensitive detection on a dielectrophoresis integrated microfluidic device.

Tumor-derived exosomes have been recognized as potential biomarkers for cancer diagnosis because they are actively involved in cancer progression and metastasis. However, progress in practical exosome analysis is still slow due to the limitation in exosome isolation and detection. The development of microfluidic devices has provided a promising analytical platform compared with traditional methods. In this study, we develop an exosome isolation and detection method based on a microfluidic device (ExoDEP-chip), which realized microsphere mediated dielectrophoretic isolation and immunoaffinity detection. Exosomes were firstly isolated by binding to antibodies pre-immobilized on the polystyrene (PS) microsphere surface and were further detected using fluorescently labeled antibodies by fluorescence microscopy. Single microspheres were then trapped into single microwells under the DEP force in the ExoDEP-chip. A wide range from 1.4 × 103 to 1.4 × 108 exosomes per mL with a detection limit of 193 exosomes per mL was obtained. Through monitoring five proteins (CD81, CEA, EpCAM, CD147, and AFP) of exosomes from three different cell lines (A549, HEK293, and HepG2), a significant difference in marker expression levels was observed in different cell lines. Therefore, this method has good prospects in exosome-based tumor marker detection and cancer diagnosis.

Model-Based Analysis of Muscle Strength and EMG-Force Relation with respect to Different Patterns of Motor Unit Loss.

This study presents a model-based sensitivity analysis of the strength of voluntary muscle contraction with respect to different patterns of motor unit loss. A motor unit pool model was implemented including simulation of a motor neuron pool, muscle force, and surface electromyogram (EMG) signals. Three different patterns of motor unit loss were simulated, including (1) motor unit loss restricted to the largest ones, (2) motor unit loss restricted to the smallest ones, and (3) motor unit loss without size restriction. The model outputs including muscle force amplitude, variability, and the resultant EMG-force relation were quantified under two different motor neuron firing strategies. It was found that motor unit loss restricted to the largest ones had the most dominant impact on muscle strength and significantly changed the EMG-force relation, while loss restricted to the smallest motor units had a pronounced effect on force variability. These findings provide valuable insight toward our understanding of the neurophysiological mechanisms underlying experimental observations of muscle strength, force control, and EMG-force relation in both normal and pathological conditions.

Muscle Fiber Diameter and Density Alterations after Stroke Examined by Single-Fiber EMG.

This study presents single-fiber electromyography (EMG) analysis for assessment of paretic muscle changes after stroke. Single-fiber action potentials (SFAPs) were recorded from the first dorsal interosseous (FDI) muscle bilaterally in 12 individuals with hemiparetic stroke. The SFAP parameters, including the negative peak duration and the peak-peak amplitude, were measured and further used to estimate muscle fiber diameter through a model based on the quadratic function. The SFAP parameters, fiber density, and muscle fiber diameter derived from the model were compared between the paretic and contralateral muscles. The results show that SFAPs recorded from the paretic muscle had significantly smaller negative peak duration than that from the contralateral muscle. As a result, the derived muscle fiber diameter of the paretic muscle was significantly smaller than that of the contralateral muscle. The fiber density of the paretic muscle was significantly higher than that of the contralateral muscle. These results provide further evidence of remodeled motor units after stroke and suggest that paretic muscle weakness can be due to both complex central and peripheral neuromuscular alterations.

Microfluidic devices for neutrophil chemotaxis studies.

Neutrophil chemotaxis plays a vital role in human immune system. Compared with traditional cell migration assays, the emergence of microfluidics provides a new research platform of cell chemotaxis study due to the advantages of visualization, precise control of chemical gradient, and small consumption of reagents. A series of microfluidic devices have been fabricated to study the behavior of neutrophils exposed on controlled, stable, and complex profiles of chemical concentration gradients. In addition, microfluidic technology offers a promising way to integrate the other functions, such as cell culture, separation and analysis into a single chip. Therefore, an overview of recent developments in microfluidic-based neutrophil chemotaxis studies is presented. Meanwhile, the strength and drawbacks of these devices are compared.

Detecting the morphology of single graphene sheets by dual channel sampling plasmonic imaging.

Due to their excellent physical and chemical properties, graphene sheets are widely used in industry, which makes detection important to guarantee their performance. Atomic force microscopy, scanning electron microscopy, and Raman spectroscopy are the most common detection methods, which is either time-consuming or easily destructive. In this work, we presented a fast and nondestructive method to detect single graphene sheets by using plasmonic imaging. Dual channel sampling plasmonic imaging combining the image processing algorithm is used to improve the deterioration from propagation length of surface plasmon polaritons and reconstruct the complete morphology of single graphene sheets. The fast and nondestructive detection method paves the way to applications of graphene, and can be extended to the detections of two-dimensional materials, single biological molecule, viruses, and nanomaterials.

Detecting a single nanoparticle by imaging the localized enhancement and interference of surface plasmon polaritons: erratum.

In this erratum, the function ${\lambda _{{\rm SPP}}}$λSPP in the third page of Opt. Lett.44, 5707 (2019)OPLEDP0146-959210.1364/OL.44.005707 has been corrected.

Wafer-level fabrication of 3D nanoparticles assembled nanopillars and click chemistry modification for sensitive SERS detection of trace carbonyl compounds.

In this work, we develop a new method for fabricating wafer-level gold nanoparticles covered silicon nanopillars (SNPs) combined with surface chemical modification to detect trace level carbonyl compounds based on surface-enhanced Raman scattering (SERS) technique. The SNPs are fabricated with an etching process using nano masks synthesized in oxygen-plasma bombardment of photoresist, and further deposited with gold nanoparticles on the surface, thus forming a 3D 'particles on pillars' nanostructure for sensitive SERS detection. The enhancement factor (EF) of the devices for R6G detection can achieve 1.56 × 106 times compared with a flat Si substrate. We also developed an oximation click chemistry reaction procedure by chemically modifying the nanostructures with aminooxy dodecane thiol (ADT) self-assemble modification. The chip is further integrated with a polydimethylsiloxane (PDMS) microfluidic chamber, which allows fast and convenient detection of trace carbonyl compounds in liquid samples. The SERS detection capability was demonstrated by the dropwise addition of fluorescent carbonyl compounds before and after elution. Furthermore, the device was proved with high surface consistency(<70%) for repeated measurement, which has the potential for ppb(parts per billion) level concentration of carbonyl compounds detection.

Detecting a single nanoparticle by imaging the localized enhancement and interference of surface plasmon polaritons.

Label-free single-nanoparticle detection is crucial for the fast detection of nanoparticles and viruses in environmental monitoring and biological sciences. In this Letter, benefiting from the leakage radiation that transforms the near-field surface plasmon polariton (SPP) distribution along the interface to the far field, we demonstrated the plasmonic imaging of single polystyrene nanoparticles with a particle size down to 39 nm. The imaging is composed of the localized enhancement and interference of SPPs. The localized enhancement is the result of the accumulation of charges around the nanoparticle, and it is connected to the size and refractive index of nanoparticles. The interference is induced by the coupling between the incident SPPs and the scattered SPPs, verified by extracting the interference fringe periodicity to be half of the SPP wavelength. Our study provides an in-depth physical understanding of plasmonic imaging of single nanoparticles, which paves the way for a fast identification of nanomaterials.

Crossing constriction channel-based microfluidic cytometry capable of electrically phenotyping large populations of single cells.

This paper presents a crossing constriction channel-based microfluidic system for high-throughput characterization of specific membrane capacitance (Csm) and cytoplasm conductivity (σcy) of single cells. In operations, cells in suspension were forced through the major constriction channel and instead of invading the side constriction channel, they effectively sealed the side constriction channel, which led to variations in impedance data. Based on an equivalent circuit model, these raw impedance data were translated into Csm and σcy. As a demonstration, the developed microfluidic system quantified Csm (3.01 ± 0.92 µF cm-2) and σcy (0.36 ± 0.08 S m-1) of 100 000 A549 cells, which could generate reliable results by properly controlling cell positions during their traveling in the crossing constriction channels. Furthermore, the developed microfluidic impedance cytometry was used to distinguish paired low- and high-metastatic carcinoma cell types of SACC-83 (ncell = ∼100 000) and SACC-LM cells (ncell = ∼100 000), distinguishing significant differences in both Csm (3.16 ± 0.90 vs. 2.79 ± 0.67 µF cm-2) and σcy (0.36 ± 0.06 vs.0.41 ± 0.08 S m-1). As high-throughput microfluidic impedance cytometry, this technique may add a new marker-free dimension to flow cytometry in single-cell analysis.