Search Results (14)

A robust and elegant approach, based on the Two-Zone Moment Analysis (TZMA) method, is proposed to assess the contributions of the mobile and stationary zones, $H_{Cm}$ and $H_{Cs}$, to the C term $H_C$ in the van Deemter equation for plate height. The TZMA method yields two formulations for $H_{Cm}$ and $H_{Cs}$, both fully equivalent in terms of $H_C$, yet offering different decompositions of the contributions from the mobile and stationary zones. The first formulation proposes an expression for the term $H_{Cs}$ that has strong similarities, but also significant differences, from the well-known and widely used one proposed by Giddings. While it addresses the inherent limitation of Giddings’ approach—namely, the complete decoupling of transport phenomena in the moving and stationary zones—it introduces the drawback of a non-unique decomposition of $H_C$. Despite this, it proves highly valuable in highlighting the limitations and flaws of Giddings’ method. In contrast, the second formulation not only properly accounts for the interaction between the moving and stationary zones, but provides a unique and consistent decomposition of $H_C$ into its components. Three different geometries are investigated in detail: the 2D triangular array of cylinders (pillar array columns), the 2D array of rectangular pillars (radially elongated pillar array columns) and the 3D face-centered cubic array of spheres. It is shown that Giddings’ approach significantly underestimates the $H_{Cs}$ term, especially for porous-shell particles. Its accuracy is limited, being reliable only when intra-particle diffusivity ($D_s$) and the zone retention factor ($k^{″}$) are very low, or when axially invariant systems are considered. Full article

With the aim of determining the damage characteristics and a reasonable positional arrangement of the surrounding rock in a bottom-pumping roadway influenced by mining in a high-gas mine, the boundary equation for the plastic zone of the surrounding rock in a circular roadway under an unequal compressive stress field was adopted to analyze the relationship between the distribution characteristics of the plastic zone of the bottom-pumping roadway and the stability of the rock surrounding the bottom-pumping roadway under different bidirectional stress ratios. This was carried out in the bottom-pumping roadway of the working face of Licun coal mine 3301 as the engineering background, where the nature of the coal seams mined is bituminous coal, and the absolute gas outflow is 0.5 m³/min⁻¹. A numerical simulation was used to analyze the distribution characteristics of the surrounding rock stress and the bidirectional stress ratio, as well as the deformation and damage characteristics of the surrounding rock at different positions in the bottom-pumping roadway. A numerical simulation was applied to analyze the distribution characteristics of the surrounding rock stress and the two-way stress ratio, as well as the deformation and damage characteristics of the rock surrounding the bottom-pumping roadway when the bottom-pumping roadway was arranged in different locations. The results show that, with an increase in the bidirectional stress ratio, the plastic zone of the perimeter rock in the bottom-pumping roadway shows nonuniform “butterfly” distribution characteristics, which seriously affects the stability of the rock on the perimeter of the roadway; the stress on the bottom plate of the working face after excavation can be divided into four areas according to the size of the bidirectional stress ratio and the stress loading and unloading states. In addition, the size of the perimeter rock deformation can be sorted into four areas according to the damage range of the perimeter of the rock plastic zone in the bottom-pumping roadway. The size of the deformation in the surrounding rock can be sorted as follows: unpressurized high-stress ratio > unpressurized stress ratio stable area > pressurized low-stress ratio area > original rock stress ratio area. Accordingly, we found that the reasonable location of the bottom-pumping roadway is arranged at the 15 m position outside the hollow area below the coal pillar, along the limestone upper medium-grained sandstone layer along the bottom. The study’s results were applied to the field. The industrial experiments on the site show that the deformation of the surrounding rock is reasonable when the bottom-pumping roadway is dug along the limestone roof and arranged 15 m outside the fault of the mining hollow area below the coal pillar. Full article

Three-dimensional (3D) culture platforms have been adopted in a high-throughput screening (HTS) system to mimic in vivo physiological microenvironments. The automated dispenser has been established commercially to enable spotting or distributing non-viscous or viscous biomaterials onto microplates. However, there are still challenges to the precise and accurate dispensation of cells embedded in hydrogels such as Alginate- and Matrigel-extracellular matrices. We developed and improved an automated contact-free dispensing machine, the ASFA SPOTTER (V5 and V6), which is compatible with 96- and 384-pillar/well plates and 330- and 532-micropillar/well chips for the support of 3D spheroid/organoid models using bioprinting techniques. This enables the distribution of non-viscous and viscous biosamples, including chemical drugs and cancer cells, for large-scale drug screening at high speed and small volumes (20 to 4000 nanoliters) with no damage to cells. The ASFA SPOTTER (V5 and V6) utilizes a contact-free method that minimizes cross-contamination for the dispensation of encapsulated tissue cells with highly viscous scaffolds (over 70%). In particular, the SPOTTER V6 does not require a washing process and offers the advantage of almost no dead volume (defined as additional required sample volume, including a pre-shot and flushing shot for dispensing). It can be successfully applied for the achievement of an organoid culture in automation, with rapid and easy operation, as well as miniaturization for high-throughput screening. In this study, we report the advantages of the ASFA SPOTTER, which distributes standard-sized cell spots with hydrogels onto a 384-pillar/well plate with a fast dispensing speed, small-scale volume, accuracy, and precision. Full article

The deformation control of roadways surrounded by rock in the fully mechanized amplification sections of extra-thick coal seams is problematic. To analyze the failure and failure characteristics of a support frame, as well as the deformation and failure processes of the surrounding rock, through theoretical analysis and industrial tests, the deformation and support conditions of a return airway of a fully mechanized caving face in an extra-thick coal seam in the Yangchangwan Coal Mine, in the Ningdong mining, area were examined. Combined with limit equilibrium theory and roadway section size, the width of the coal pillar of the return air roadway at the 130,205 working face was calculated to be 6 m. The layout scheme and implementation parameters of roof blasting pressure relief, coal pillar grouting modification, and bolt (cable) support were designed. Based on the analysis, a “Coal pillar optimization–roof cutting destressing–routing modification–rock bolting” system for surrounding rock control in synergy with the fully enlarged section mining roadway in the extra-thick coal seam was proposed, and the deformation of the surrounding rock was monitored, along with the stress of the support body and the grouting effect on the site. Field experiments show that after the implementation of the surrounding rock control in synergy with the roadway, the maximum subsidence of the top plate was 55 mm, the maximum bottom heave of the bottom plate was 55 mm, the maximum values of the upper and lower side drums were 30 mm and 70 mm, respectively, and the breaking rate of the bolt (cable) and the deformation of the surrounding rock of the roadway was reduced by more than 90% and 70%, respectively. The effective performance of the coal pillar grouting was observed as well. Field practice of the roadway surrounding rock control in the synergy method indicated that rock deformation was effectively controlled, and the successful application of this technology was able to provide reliable technical and theoretical support for the Ningdong mining area and mines with similar conditions. Full article

Recently, there has been renewed interest in cell therapy, which plays a key role in the clinical research of genetic diseases, advanced blood disease, and other diseases. It shows considerable clinical application value and is known as “the new pillar of future medicine”. Automatic cell culture and operation technology is the key to ensuring scale, standardization, and stability between batches of therapeutic cells. The pH of the cell culture medium is vital for cell growth. Most cells are suitable for growth at pH 7.2~7.4. A pH of cell culture medium lower than 6.8 or higher than 7.6 is harmful to cells, and cells will degenerate or even die. At present, the monitoring method of cell culture medium pH of automatic cell culture equipment is mainly a visual observation method, which can not accurately or quickly reflect changes in the cell culture medium. To address the issue of monitoring of cell culture fluid pH for automated cell culture equipment and the inability to employ invasive sensors to measure pH during well plate culture, a pH monitoring method for orifice plate culture medium algorithm based on HSV (hue, saturation, value) model is proposed by studying the changes of cell culture medium in the process of cell culture. The research presented here reveals the laws of cell culture fluid pH change and its color moment, and the intelligent monitoring of cell culture fluid pH was successfully achieved. The problem of non-destructive monitoring of the pH of cell culture fluids in well plates is also addressed. Full article

High aspect ratio (HAR) through-silicon vias (TSVs) are in urgent need to achieve smaller keep-out zones (KOZs) and higher integration density for the miniaturization of high-performance three-dimensional (3D) integration of integrated circuits (IC), micro-electro-mechanical systems (MEMS), and other devices. In this study, HAR TSVs with a diameter of 11 μm and an aspect ratio of 10:1 are successfully fabricated in a low-cost process flow. Conformal polyimide (PI) liners are deposited using a vacuum-assisted spin coating technique, and the effects of spin coating time and speed on the deposition results are discussed. Then, continuous Cu seed layers are fabricated by sequential sputtering and ultrasound-assisted electroless plating. Additionally, void-free and seamless Cu conductors are formed by electroplating. Moreover, a semi-additive method is used to fabricate the redistribution layers (RDLs) on the insulating layers of photosensitive PI (PSPI). Notably, a plasma bombardment process is introduced to remove residual PSPI in the contact windows between RDLs and central pillars. Results show that the resistance of a single TSV from a daisy chain of 144 TSVs with density of 2000/mm² is about 28 mΩ. Additionally, the S-parameters of a single TSV are obtained using L-2L de-embedding technology, and the experimental and simulated results agree well. The proposed low-cost fabrication technologies and the related electrical characterization of PI-TSVs are significant for the application of HAR TSVs in modern heterogeneous integration systems. Full article

It is well known that layered double hydroxides (LDHs) are two-dimensional (2D) layered compounds. However, we modified these 2D layered compounds to become one-dimensional (1D) nanostructures destined for high-performance supercapacitors applications. In this direction, silicon was inserted inside the nanolayers of Co-LDHs producing nanofibers of Si/Co LDHs through the intercalation of cyanate anions as pillars for building nanolayered structures. Additionally, nanoparticles were observed by controlling the preparation conditions and the silicon percentage. Scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and thermal analyses have been used to characterize the nanolayered structures of Si/Co LDHs. The electrochemical characterization was performed by cyclic voltammetry and galvanic charge–discharge technique in 2M KOH electrolyte solution using three-electrode cell system. The calculated specific capacitance results indicated that the change of morphology from nanoparticles or plates to nanofibers had a positive effect for improving the performance of specific capacitance of Si/Co LDHs. The specific capacitance enhanced to be 621.5 F g⁻¹ in the case of the nanofiber of Si/Co LDHs. Similarly, the excellent cyclic stability (84.5%) was observed for the nanofiber. These results were explained through the attribute of the nanofibrous morphology and synergistic effects between the electric double layer capacitive character of the silicon and the pseudo capacitance nature of the cobalt. The high capacitance of ternary Si/Co/cyanate LDHs nanocomposites was suggested to be used as active electrode materials for high-performance supercapacitors applications. Full article

Proton beam therapy (PBT) is a critical treatment modality for head and neck squamous cell carcinoma (HNSCC). However, not much is known about drug combinations that may improve the efficacy of PBT. This study aimed to test the feasibility of a three-dimensional (3D) tumor-spheroid-based high-throughput screening platform that could assess cellular sensitivity against PBT. Spheroids of two HNSCC cell lines—Fadu and Cal27—cultured with a mixture of Matrigel were arrayed on a 384-pillar/well plate, followed by exposure to graded doses of protons or targeted drugs including olaparib at various concentrations. Calcein staining of HNSCC spheroids revealed a dose-dependent decrease in cell viability for proton irradiation or multiple targeted drugs, and provided quantitative data that discriminated the sensitivity between the two HNSCC cell lines. The combined effect of protons and olaparib was assessed by calculating the combination index from the survival rates of 4 × 4 matrices, showing that Cal27 spheroids had greater synergy with olaparib than Fadu spheroids. In contrast, adavosertib did not synergize with protons in both spheroids. Taken together, we demonstrated that the 3D pillar/well array platform was a useful tool that provided rapid, quantitative data for evaluating sensitivity to PBT and drug combinations. Our results further supported that administration of the combination of PBT and olaparib may be an effective treatment strategy for HNSCC patients. Full article

Spheroid, a 3D aggregate of tumor cells in a spherical shape, has overcome the limitations of conventional 3D cell models to accurately mimic the in-vivo environment of a human body. The spheroids are cultured with other primary cells and embedded in collagen drops using hang drop plates and low-attachment well plates to construct a spheroid–hydrogel model that better mimics the cell–cell and cell–extracellular matrix (ECM) interactions. However, the conventional methods of culturing and embedding spheroids into ECM have several shortcomings. The procedure of transferring a single spheroid at a time by manual pipetting results in well-to-well variation and even loss or damage of the spheroid. Based on the previously introduced droplet contact-based spheroid transfer technique, we present a poly(dimethylsiloxane) and resin-based drop array chip and a pillar array chip with alignment stoppers, which enhances the alignment between the chips for uniform placement of spheroids. This method allows the facile and stable transfer of the spheroid array and even eliminates the need for a stereomicroscope while handling the cell models. The novel platform demonstrates a homogeneous and time-efficient construction and diverse analysis of an array of fibroblast-associated glioblastoma multiforme spheroids that are embedded in collagen. Full article

High-throughput, pillar-strip-based assays have been proposed as a drug-safety screening tool for developmental toxicity. In the assay described here, muscle cell culture and differentiation were allowed to occur at the end of a pillar strip (eight pillars) compatible with commercially available 96-well plates. Previous approaches to characterize cellular differentiation with immunostaining required a burdensome number of washing steps; these multiple washes also resulted in a high proportion of cellular loss resulting in poor yield. To overcome these limitations, the approach described here utilizes cell growth by easily moving the pillars for washing and immunostaining without significant loss of cells. Thus, the present pillar-strip approach is deemed suitable for monitoring high-throughput myogenic differentiation. Using this experimental high-throughput approach, eight drugs (including two well-known myogenic inhibitory drugs) were tested at six doses in triplicate, which allows for the generation of dose–response curves of nuclei and myotubes in a 96-well platform. As a result of comparing these F-actin (an actin-cytoskeleton protein), nucleus, and myotube data, two proposed differentiation indices—curve-area-based differentiation index (CA-DI) and maximum-point-based differentiation index (MP-DI) were generated. Both indices successfully allowed for screening of high-myogenic inhibitory drugs, and the maximum-point-based differentiation index (MP-DI) experimentally demonstrated sensitivity for quantifying drugs that inhibited myogenic differentiation. Full article

A common method of three-dimensional (3D) cell cultures is embedding single cells in Matrigel. Separated cells in Matrigel migrate or grow to form spheroids but lack cell-to-cell interaction, which causes difficulty or delay in forming mature spheroids. To address this issue, we proposed a 3D aggregated spheroid model (ASM) to create large single spheroids by aggregating cells in Matrigel attached to the surface of 96-pillar plates. Before gelling the Matrigel, we placed the pillar inserts into blank wells where gravity allowed the cells to gather at the curved end. In a drug screening assay, the ASM with Hepatocellular carcinoma (HCC) cell lines showed higher drug resistance compared to both a conventional spheroid model (CSM) and a two-dimensional (2D) cell culture model. With protein expression, cytokine activation, and penetration analysis, the ASM showed higher expression of cancer markers associated with proliferation (p-AKT, p-Erk), tight junction formation (Fibronectin, ZO-1, Occludin), and epithelial cell identity (E-cadherin) in HCC cells. Furthermore, cytokine factors were increased, which were associated with immune cell recruitment/activation (MIF-3α), extracellular matrix regulation (TIMP-2), cancer interaction (IL-8, TGF-β2), and angiogenesis regulation (VEGF-A). Compared to CSM, the ASM also showed limited drug penetration in doxorubicin, which appears in tissues in vivo. Thus, the proposed ASM better recapitulated the tumor microenvironment and can provide for more instructive data during in vitro drug screening assays of tumor cells and improved prediction of efficacious drugs in HCC patients. Full article

Bio-inspired surfaces with superamphiphobic properties are well known as effective candidates for antifouling technology. However, the limitation of large-area mastering, patterning and pattern collapsing upon physical contact are the bottleneck for practical utilization in marine and medical applications. In this study, a roll-to-plate nanoimprint lithography (R2P NIL) process using Morphotonics’ automated Portis NIL600 tool was used to replicate high aspect ratio (5.0) micro-structures via reusable intermediate flexible stamps that were fabricated from silicon master molds. Two types of Morphotonics’ in-house UV-curable resins were used to replicate a micro-pillar (PIL) and circular rings with eight stripe supporters (C-RESS) micro-structure onto polycarbonate (PC) and polyethylene terephthalate (PET) foil substrates. The pattern quality and surface wettability was compared to a conventional polydimethylsiloxane (PDMS) soft lithography process. It was found that the heights of the R2P NIL replicated PIL and C-RESS patterns deviated less than 6% and 5% from the pattern design, respectively. Moreover, the surface wettability of the imprinted PIL and C-RESS patterns was found to be superhydro- and oleophobic and hydro- and oleophobic, respectively, with good robustness for the C-RESS micro-structure. Therefore, the R2P NIL process is expected to be a promising method to fabricate robust C-RESS micro-structures for large-scale anti-biofouling application. Full article

We report on the challenges in a hybrid sub-micrometer fabrication process while using three dimensional femtosecond direct laser writing and electroplating. With this hybrid subtractive and additive fabrication process, it is possible to generate metallic polarization elements with sub-wavelength dimensions of less than 400 nm in the cladding area. We show approaches for improving the adhesion of freestanding photoresist pillars as well as of the metallic cladding area, and we also demonstrate the avoidance of an inhibition layer and sticking of the freestanding pillars. Three-dimensional direct laser writing in a positive tone photoresist is used as a subtractive process to fabricate free-standing non-metallic photoresist pillars with an area of about 850 nm × 1400 nm, a height of 3000 nm, and a distance between the pillars of less than 400 nm. In a subsequent additive fabrication process, these channels are filled with gold by electrochemical deposition up to a final height of 2200 nm. Finally, the polarization elements are characterized by measuring the degree of polarization in order to show their behavior as quarter- and half-wave plates. Full article

With the aim of selecting particular frequencies of interest and rejecting others, the waveguiding and filtering properties of a two-dimensional phononic crystal slab are investigated in the context of a filtering application. To this end, we designed and manufactured a metallic device that consists of a square lattice of cylindrical pillars mounted on the top of a plate by using 3D printing technology. We respectively explored the theoretical and experimental characteristics of the device by using finite element method, a Micro System Analyzer (MSA) and a scanning laser Doppler vibrometer. The proposed device shows a complete band gap for Lamb wave around 0.3 MHz with a relative band-width of $30\%$ . Tailorable waveguides are realized inside this phononic crystal by inserting several space gaps to achieve a demultiplexing effect through the splitting of an acoustic signal towards three different bandpass frequency channels. The demultiplexing performance has been experimentally demonstrated by achieving rejection levels up to 60 dB. The proposed phononic platform can have a significant impact in signal processing as well as droplet manipulation for biological applications. Full article