Immune cholangitis related to anti-programmed cell death and programmed cell death ligand agents for the treatment of intrahepatic cholangiocarcinoma.

Anti-programmed cell death (anti-PD1) and anti-programmed cell death ligand (anti-PDL1) agents represent a burgeoning field of immunotherapy with an expanding array of indications. In this report, we present the observation of a patient with intrahepatic cholangiocarcinoma exhibiting features of immune-related cholangitis.

Metrics of Anterior Sclera in Normal Chinese Adults: Anterior Segment Imaging Using the Swept-Source Optical Coherence Tomography.

PURPOSE: To measure the corneoscleral limbus and anterior sclera parameters of normal Chinese adults by swept-source optical coherence tomography (OCT). MATERIALS AND METHODS: In this cross-sectional study, a total of 56 Chinese subjects with ametropia were evaluated in the Eye Hospital of Wenzhou Medical University from September 2020 to December 2020, including 26 (46.4%) men, with an average age of 24.7±1.8 years old. The OCT SS-1000 (CASIA, Tomey, Tokyo, Japan) was used to measure the sagittal height, corneoscleral junction (CSJ) angle, and scleral angle. RESULTS: The chord was across the corneal center and the line connecting the center of the cornea and the center of the chord was perpendicular to the chord. The mean sagittal height at chord lengths of 10.0, 12.3, and 15.0 mm were 1,756±72, 2,658±110, and 3,676±155 µm, respectively. The absolute values of the differences between horizontal and vertical meridians at three chord lengths were 54±40, 70±67, and 117±95 µm, respectively. One-way analysis of variance showed that the differences of CSJ angles at 12.3-mm chord and scleral angles at 15.0-mm chord in the four segments were statistically significant ( F values were 32.01 and 13.37, respectively, both P <0.001). The CSJ angles from low to high were 176.53±2.14° (nasal), 178.66±1.84° (inferior), 179.13±1.20° (temporal), and 179.31±1.68° (superior), and 87.5% of the nasal angles were less than 179°. The scleral angles from high to low were 38.35±2.47° (temporal), 38.26±3.37° (superior), 35.37±3.10° (nasal), and 35.30±4.71° (inferior). CONCLUSIONS: The morphology of corneoscleral limbus and anterior sclera is asymmetrical in normal Chinese adults. The nasal side of the corneoscleral limbus has the largest angle, and the superior and temporal sides of the scleral angle are larger.

Double-Glued Multi-Focal Bionic Compound Eye Camera.

Compound eye cameras are a vital component of bionics. Compound eye lenses are currently used in light field cameras, monitoring imaging, medical endoscopes, and other fields. However, the resolution of the compound eye lens is still low at the moment, which has an impact on the application scene. Photolithography and negative pressure molding were used to create a double-glued multi-focal bionic compound eye camera in this study. The compound eye camera has 83 microlenses, with ommatidium diameters ranging from 400 µm to 660 µm, and a 92.3 degree field-of-view angle. The double-gluing structure significantly improves the optical performance of the compound eye lens, and the spatial resolution of the ommatidium is 57.00 lp mm-1. Additionally, the measurement of speed is investigated. This double-glue compound eye camera has numerous potential applications in the military, machine vision, and other fields.

Multistage microfluidic cell sorting method and chip based on size and stiffness.

High performance sorting of circulating tumor cells (CTCs) from peripheral blood is key to liquid biopsies. Size-based deterministic lateral displacement (DLD) technique is widely used in cell sorting. But conventional microcolumns have poor fluid regulation ability, which limits the sorting performance of DLD. When the size difference between CTCs and leukocytes is small (e.g., less than 3 µm), not only DLD, many size-based separation techniques fail due to low specificity. CTCs have been confirmed to be softer than leukocytes, which could serve as a basis for sorting. In this study, we presented a multistage microfluidic CTCs sorting method, first sorting CTCs using a size-based two-array DLD chip, then purifying CTCs mixed by leukocytes using a stiffness-based cone channel chip, and finally identifying cell types using Raman techniques. The entire CTCs sorting and analysis process was label free, highly pure, high-throughput and efficient. The two-array DLD chip employed a droplet-shaped microcolumn (DMC) developed by optimization design rather than empirical design. Attributed to the excellent fluid regulation capability of DMC, the CTCs sorter system developed by parallelizing four DMC two-array DLD chips was able to process a sample of 2.5 mL per minute with a recovery efficiency of 96.30 ± 2.10% and a purity of 98.25 ± 2.48%. To isolate CTCs mixed dimensionally by leukocytes, a cone channel sorting method and chip were developed based on solid and hydrodynamic coupled analysis. The cone channel chip allowed CTCs to pass through the channel and entrap leukocytes, improving the purity of CTCs mixed by leukocytes by 1.8-fold.

Hierarchical hydrogel microarrays fabricated based on a microfluidic printing platform for high-throughput screening of stem cell lineage specification.

2D cell cultures are suitable for rapid exploration of the factors in the extracellular matrix affecting the development of cells. The technology of the micrometre-sized hydrogel array provides a feasible, miniaturized, and high-throughput strategy for the process. However, current microarray devices lack a handy and parallelized methodology in sample treatment, which makes the process of high-throughput cell screening (HTCS) expensive and inefficient. Here, based on the functionalization of micro-nano structures and the fluid control capability of microfluidic chips, we build a microfluidic spotting-screening platform (MSSP). The MSSP can print 20000 microdroplet spots within 5 min, coupled with a simple strategy for parallel addition of compound libraries. Compared with open microdroplet arrays, the MSSP can control the evaporation rate of nanoliter droplets, providing a stable fabrication platform for hydrogel-microarray-based materials. As a proof-of-concept demonstration, the MSSP successfully controlled the adhesion, adipogenic, and osteogenic differentiation behavior of mesenchymal stem cells by rationally designing the substrate stiffness, adhesion area, and cell density. We anticipate that the MSSP may provide an accessible and promising tool for hydrogel-based HTCS. STATEMENT OF SIGNIFICANCE: High-throughput screening of cells is a common approach to improve the efficiency of biological experiments, and one challenge of the existing technologies is to achieve rapid and precise cell screening with a low-cost and simple strategy. Through the integration of the microfluidic and micro-nanostructure technologies, we fabricated a microfluidic spotting-screening platforms. Benefiting from the flexible control of the fluids, the device can print 20000 microdroplet spots within 5 min, coupled with a simple procedure for parallel addition of compound libraries. High-throughput screening of stem cell lineage specification has also been achieved by the platform, which provides a high-throughput, high-content information extraction strategy for cell-biomaterial interaction research.

A Meniscus Multifocusing Compound Eye Camera Based on Negative Pressure Forming Technology.

To meet the challenge of preparing a high-resolution compound eye, this paper proposes a multi-focal-length meniscus compound eye based on MEMS negative pressure molding technology. The aperture is increased, a large field of view angle of 101.14° is obtained, and the ommatidia radius of each stage is gradually increased from 250 µm to 440 µm. A meniscus structure is used to improve the imaging quality of the marginal compound eye so that its resolution can reach 36.00 lp/mm. The prepared microlenses have a uniform shape and a smooth surface, and both panoramic image stitching and moving object tracking are achieved. This technology has great potential for application in many fields, including automatic driving, machine vision, and medical endoscopy.

Micro two-dimensional slit-array for super resolution beyond pixel Nyquist limits in grating spectrometers.

This paper presents a new micro 2-D slit-array device for spectral resolution enhancement in grating spectrometers. The 2-D slit-array is encoded in Hadamard matrix and the device is fabricated based on the micro-electromechanical system (MEMS) technology. By just using this 2-D slit-array to replace the single slit in the conventional grating spectrometer, real-time super spectral resolution detection beyond the pixel Nyquist limit, which is determined by the size of the detector pixel, can be realized. Furthermore, no other configuration of the spectrometer is changed, no movable parts are used, and the spectral range and instrument size remain almost unchanged while the resolution is improved. A series of experimental verifications for the feasibility of this design are included in this work.

Cell-sorting centrifugal microfluidic chip with a flow rectifier.

Centrifugal microfluidic chips offer rapid, highly integrable and simultaneous multi-channel microfluidic control without relying on external pressure pumps and pipelines. Current centrifugal microfluidic chips mainly separate particles of differing density based on the sedimentation method. However, in some biological cells, the volume difference is more notable than the density difference. In particular, cancer cells are generally larger than normal cells. The instability of particle velocity caused by the non-steady flow of the fluid in the centrifugal microfluidic chip leads to low separation purity of particles of different sizes. Thus, we propose herein a centrifugal microfluidic chip with a flow rectifier that transforms the centrifugal non-steady flow into locally steady flow with continuous flow. This chip resolves the problems caused by particle sedimentation in the sample chamber and non-steady flow and greatly improves the recovery ratio and separation purity of target particles. Therefore, it can be used to separate particles of differing size. The experimental results show that the chip can separate an equal-volume mixture of 25 µm and 12 µm polystyrene particles diluted 50 times with a ratio of 1 : 6 and obtain a recovery ratio and separation purity better than 95% for the 25 µm particles. In addition, rare tumour cells are separated from high-concentration white blood cells (ratio 1 : 25) with a recovery ratio of 90.4% ± 2.4% and separation purity of 83.0% ± 3.8%. In conclusion, this chip is promising for sorting of various biological cells and has significant potential for use in biomedical and clinical applications.

Design and Integration of the Single-Lens Curved Multi-Focusing Compound Eye Camera.

Compared with a traditional optical system, the single-lens curved compound eye imaging system has superior optical performance, such as a large field of view (FOV), small size, and high portability. However, defocus and low resolution hinder the further development of single-lens curved compound eye imaging systems. In this study, the design of a nonuniform curved compound eye with multiple focal lengths was used to solve the defocus problem. A two-step gas-assisted process, which was combined with photolithography, soft photolithography, and ultraviolet curing, was proposed for fabricating the ommatidia with a large numerical aperture precisely. Ommatidia with high resolution were fabricated and arranged in five rings. Based on the imaging experimental results, it was demonstrated that the high-resolution and small-volume single-lens curved compound eye imaging system has significant advantages in large-field imaging and rapid recognition.

Complex network dynamics of the topological structure in a geochemical field from the Nanling area in South China.

The topological classification of geochemical elements is widely used as a reference for regional prospecting prediction. In this study, we analyze the topological correlation structures of 39 representative geochemical elements from the Nanling area of South China by implementing the complex networks theory. The topological correlation structures of geochemical elements have a high clustering coefficient (0.8120-0.8880), but the magnitude of the shortest path (1.2950-2.3600) is small. In combination with the analysis of complex networks characteristics, we report that the topological correlation structures of the geochemical elements in this area have small-world characteristics, which reveals the self-organized criticality. As shown in the topological network, two random elements have some level of associations, which present a specific community feature. Our preliminary result shows that with changing the control parameter (k) of "coarse-graining", the topological correlation structures undergo two critical phase transitions. As the control parameter (k) reaches 0.44, the entire element system evolves into two parts. When the control parameter (k) reaches 0.63, the system forms three "communities". It is worth noting that the three "communities" are basically consistent with the Goldschmidt's geochemical classification of the elements, which are lithophile, siderophile, and chalcophile groups, respectively. In these "communities", we also found that a small level of component units is nested.

Identification of loci and candidate gene GmSPX-RING1 responsible for phosphorus efficiency in soybean via genome-wide association analysis.

BACKGROUND: Phosphorus (P) is an essential element in maintaining high biomass and yield in crops. Soybean [Glycine max (L.) Merr.] requires a large amount of P during growth and development. Improvement of P efficiency and identification of P efficiency genes are important strategies for increasing soybean yield. RESULTS: Genome-wide association analysis (GWAS) with NJAU 355 K SoySNP array was performed to identify single nucleotide polymorphisms (SNPs) significantly associated with three shoot P efficiency-related traits of a natural population of 211 cultivated soybeans and relative values of these traits under normal P (+P) condition and P deficiency (-P) condition. A total of 155 SNPs were identified significantly associated with P efficiency-related traits. SNPs that were significantly associated with shoot dry weight formed a SNP cluster on chromosome 11, while SNPs that were significantly associated with shoot P concentration formed a SNP cluster on chromosome 10. Thirteen haplotypes were identified based on 12 SNPs, and Hap9 was considered as the optimal haplotype. Four SNPs (AX-93636685, AX-93636692, AX-93932863, and AX-93932874) located on chromosome 10 were identified to be significantly associated with shoot P concentration under +P condition in two hydroponic experiments. Among these four SNPs, two of them (AX-93636685 and AX-93932874) were also significantly associated with the relative values of shoot P concentration under two P conditions. One SNP AX-93932874 was detected within 5'-untranslated region of Glyma.10 g018800, which contained SPX and RING domains and was named as GmSPX-RING1. Furthermore, the function research of GmSPX-RING1 was carried out in soybean hairy root transformation. Compared with their respective controls, P concentration in GmSPX-RING1 overexpressing transgenic hairy roots was significantly reduced by 32.75% under +P condition; In contrast, P concentration in RNA interference of GmSPX-RING1 transgenic hairy roots was increased by 38.90 and 14.51% under +P and -P conditions, respectively. CONCLUSIONS: This study shows that the candidate gene GmSPX-RING1 affects soybean phosphorus efficiency by negatively regulating soybean phosphorus concentration in soybean hairy roots. The SNPs and candidate genes identified should be potential for improvement of P efficiency in future soybean breeding programs.

Fabrication and Characterization of Curved Compound Eyes Based on Multifocal Microlenses.

Curved compound eyes have generated great interest owing to the wide field of view but the application of devices is hindered for the lack of proper detectors. One-lens curved compound eyes with multi-focal microlenses provide a solution for wide field imaging integrated in a commercial photo-detector. However, it is still a challenge for manufacturing this kind of compound eye. In this paper, a rapid and accurate method is proposed by a combination of photolithography, hot embossing, soft photolithography, and gas-assisted deformation techniques. Microlens arrays with different focal lengths were firstly obtained on a polymer, and then the planar structure was converted to the curved surface. A total of 581 compound eyes with diameters ranging from 152.8 µm to 240.9 µm were successfully obtained on one curved surface within a few hours, and the field of view of the compound eyes exceeded 108°. To verify the characteristics of the fabricated compound eyes, morphology deviation was measured by a probe profile and a scanning electron microscope. The optical performance and imaging capability were also tested and analyzed. As a result, the ommatidia made up of microlenses showed not only high accuracy in morphology, but also imaging uniformity on a focal plane. This flexible massive fabrication of compound eyes indicates great potential for miniaturized imaging systems.

High-sensitivity microliter blood pressure sensors based on patterned micro-nanostructure arrays.

Herein we present a micro-nanostructure integrated liquid pressure sensor, which features an ultra-high sensitivity of 16.71 mbar-1, a low-pressure regime of 2 mbar, a trace sample volume of less than 1.3 µL and a visible display element. The measurable pressure ranges of the sensors include not only from micro-scale fluids to bulk liquids but also from hydraulic pressures to blood pressures, opening a window for liquid pressure sensing in lab-on-chip platforms, point-of-care diagnostics, and even robotics.

Pressure-controlled microfluidic sub-picoliter ultramicro-volume syringes based on integrated micro-nanostructure arrays.

Ultramicro-volume syringes were fabricated by integrating micro-nanostructure arrays in microchannels for quantitatively dispensing sub-picoliter volumes of liquids. Using this system, liquids were dispensed in volume increments as low as 0.5 pL with 96% accuracy. Specifically, the controllable synthesis of nanocrystals was achieved using a lab-on-chip platform that was integrated with the syringes.

Ultrasensitive label-free optical microfiber coupler biosensor for detection of cardiac troponin I based on interference turning point effect.

Sensitive detection of cardiac biomarkers is critical for clinical diagnostics of myocardial infarction (MI) while such detection is quite challenging due to the ultra-low concentration of cardiac biomarkers. In this work, a label-free immunosensor based on optical microfiber coupler (OMC) has been developed for the ultrasensitive detection of cardiac troponin I (cTnI), a selective and highly sensitive biomarker of acute myocardial infarction (AMI). CTnI monoclonal antibodies were immobilized on the surface of the fiber through polyelectrolyte layer using layer-by-layer deposition technique. For refractive index sensing characterization, an ultra-high sensitivity of 91777.9 nm/RIU was achieved when the OMC works around the dispersion turning point, which is the highest experimental demonstration in the field of fiber-optic evanescent biosensors. For biosensing, the immunosensor with good specificity showed a linear wavelength shift in the range of 2-10 fg/mL and an ultra-low detection limit of 2 fg/mL. Such immunosensors have huge application potential for the detection of cardiac biomarkers of myocardial infarction due to simple detection scheme, quick response time, ease of handling and miniaturation.

Colloidal lithography-based fabrication of highly-ordered nanofluidic channels with an ultra-high surface-to-volume ratio.

This article shows a new strategy for the fabrication of nanofluidics based on nanoscale gaps in nanopillar arrays. Silicon nanopillar arrays are prepared in a designed position by combining conventional photolithography with colloidal lithography. The nanogaps between the pillars are used as nanochannels for the connection of two polydimethylsiloxane-based microchannels in microfluidics. The gap between neighbouring nanopillars can be accurately controlled by changing the size of initial colloidal spheres and by an etching process, which further determines the dimensions of the nanochannels. At a low ionic strength, the surface charge-governed ion transportation shows that the nanochannels possess the same electrokinetic properties as typical nanofluidics. Benefiting from the advantage of photolithography, large-area nanochannel arrays can be prepared in a parallel manner. Due to the perm-selectivity of the nanochannels, the nanofluidic chips can be used to preconcentrate low concentration samples. The large-area ordered nanostructures preserve their high-throughput property and large surface-to-volume ratio, which shows their great potential in the development of nanofluidics and their applications, such as in the separation of small molecules, energy conversion, etc.

Signal-to-noise ratio enhancement of a Hadamard transform spectrometer using a two-dimensional slit-array.

The encoding and decoding principle of the Hadamard transform spectrometer with a 2D slit-array mask is described in this paper. Based on the Hadamard transform theory, the signal-to-noise ratio (SNR) enhancement of a 2D slit-array Hadamard transform spectrometer is deduced and verified experimentally. Affected by the optical system of the spectrometer, there are differences between the experimental results and theoretical calculations. At the end of this paper, we discuss the influence of the spectrometer's optical system on the SNR enhancement based on the spatial frequency analysis.

Autonomous Control of Fluids in a Wide Surface Tension Range in Microfluidics.

In this paper, we report the preparation of anisotropic wetting surfaces that could control various wetting behaviors of liquids in a wide surface tension range (from water to oil), which could be employed as a platform for controlling the flow of liquids in microfluidics (MFs). The anisotropic wetting surfaces are chemistry-asymmetric "Janus" silicon cylinder arrays, which are fabricated via selecting and regulating the functional groups on the surface of each cylinder unit. Liquids (in a wide surface tension range) wet in a unidirectional manner along the direction that was modified by the group with large surface energy. Through introducing the Janus structure into a T-shaped pattern and integrating it with an identical T-shaped poly(dimethylsiloxane) microchannel, the as-prepared chips can be utilized to perform as a surface tension admeasuring apparatus or a one-way valve for liquids in a wide surface tension range, even oil. Furthermore, because of the excellent ability in controlling the flowing behavior of liquids in a wide surface tension range in an open system or a microchannel, the anisotropic wetting surfaces are potential candidates to be applied both in open MFs and conventional MFs, which would broaden the application fields of MFs.

Thermal-Responsive Anisotropic Wetting Microstructures for Manipulation of Fluids in Microfluidics.

We show morphology-patterned stripes modified by thermal-responsive polymer for smartly guiding flow motion of fluid in chips. With a two-step modification process, we fabricated PNIPAAm-modified Si stripes on silicon slides, which were employed as substrates for fluid manipulation in microchannels. When the system temperature switches between above and below the lower critical solution temperature (LCST) of PNIPAAm, the wettability of the substrates also switches between strong anisotropy and weak anisotropy, which resulted in anisotropic (even unidirectional) flow and isotropic flow behavior of liquid in microchannels. The thermal-responsive flow motion of fluid in the chip is influenced by the applied pressure, the thickness of PNIPAAm, and dimension of the microchannels. Moreover, we measured the feasible applied pressure scopes under different structure factors. Because of the excellent reversibility and quick switching speed, the chip could be used as a thermal-responsive microvalve. Through tuning the system temperature and adding the assistant gas, we realized successive "valve" function. We believe that the practical and simple chip could be widely utilized in medical detection, immunodetection, protein analysis, and cell cultures.

Band gap in tubular pillar phononic crystal plate.

In this paper, a phononic crystal (PC) plate with tubular pillars is presented and investigated. The band structures and mode displacement profiles are calculated by using finite element method. The result shows that a complete band gap opens when the ratio of the pillar height to the plate thickness is about 1.6. However, for classic cylinder pillar structures, a band gap opens when the ratio is equal or greater than 3. A tubular pillar design with a void room in it enhances acoustic multiple scattering and gives rise to the opening of the band gap. In order to verify it, a PC structure with double tubular pillars different in size (one within the other) is introduced and a more than 2times band gap enlargement is observed. Furthermore, the coupling between the resonant mode and the plate mode around the band gap is characterized, as well as the effect of the geometrical parameters on the band gap. The behavior of such structure could be utilized to design a pillar PC with stronger structural stability and to enlarge band gaps.