Microchannel Network Research Articles

Bioconjugated liquid-like solid enhances characterization of solid tumor - chimeric antigen receptor T cell interactions

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable success as an immunotherapy for hematological malignancies, and its potential for treating solid tumors is an active area of research. However, limited trafficking and mobility of T cells within the tumor microenvironment (TME) present challenges for CAR T cell therapy in solid tumors. To gain a better understanding of CAR T cell function in solid tumors, we subjected CD70-specific CAR T cells to a challenge by evaluating their immune trafficking and infiltration through a confined 3D microchannel network in a bio-conjugated liquid-like solid (LLS) medium. Our results demonstrated successful CAR T cell migration and anti-tumor activity against CD70-expressing glioblastoma and osteosarcoma tumors. Through comprehensive analysis of cytokines and chemokines, combined with in situ imaging, we elucidated that immune recruitment occurred via chemotaxis, and the effector-to-target ratio plays an important role in overall antitumor function. Furthermore, through single-cell collection and transcriptomic profiling, we identified differential gene expression among the immune subpopulations. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach. Statement of significanceThe use of specialized immune cells named CAR T cells to combat cancers has demonstrated remarkable success against blood cancers. However, this success is not replicated in solid tumors, such as brain or bone cancers, mainly due to the physical barriers of these solid tumors. Currently, preclinical technologies do not allow for reliable evaluation of tumor-immune cell interactions. To better study these specialized CAR T cells, we have developed an innovative in vitro three-dimensional model that promises to dissect the interactions between tumors and CAR T cells at the single-cell level. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach.

P07.06.A PATIENT-DERIVED GLIOBLASTOMA MINIATURE AND CANCER STEM CELL SUICIDE-INDUCING NANO-AWAKENER BASED ON IT

Abstract BACKGROUND Patient-specific anti-tumor therapies can evolve by vitalizing the mother tissue-like cancer niche, cellular profile, genetic signature, and drug responsiveness. This evolution elucidated a key mechanism along with the development of the cancer therapy. The present study aimed to meet these clinical demands by approaching the direct culture of GBM patient tissues with a 1 mm post-punching diameter in a 3D microchannel network chip (“GBM miniature”). MATERIAL AND METHODS Hence, we directly cultured of GBM patient tissue (1 mm diameter) in a microchannel network chip (GBM miniature) to preserve mother tissue-like characteristic signatures and microenvironment. When chemoradiation therapy were administered within 1 day, the responsiveness of the tissue in the chip mirroring the clinical outcomes. The characteristics of migrating cells from GBM miniature were analyzed, and peptides that target these migrating CSCs were searched for. And, by attaching this CSC peptide to the nanovesicle, the therapeutic effect was confirmed in GBM miniature. RESULTS Upon testing within 1 day, the tissue chip reflected patient drug responsiveness as seen in the clinic. As the tissue chip culture was continued, the intact GBM signature was getting lost, and the outward migration of stem cells from the tissue origin increased, indicating a leaving-home effect on the family dismantle. Nanovesicle production using GBM stem cells enabled self-chasing of the cells that escaped the temozolomide effect owing to quiescence. The anti-PTPRZ1 peptide display and temozolomide loading to nanovesicles awaked stem cells from the quiescent stage to death. CONCLUSION This research proposes a GBM patient avatar platform and mechanism-learned nanotherapy for translation.

Study on Flow and Heat Transfer Characteristics and Anti-Clogging Performance of Tree-Like Branching Microchannels

In this paper, a tree-like branching microchannel with bifurcating interconnections is designed for gas turbine blade cooling. A theoretical analysis, experimental study, and numerical simulation of the heat transfer and hydrodynamic characteristics of the tree-like branching microchannel is performed, and the influence of the total number of branching levels m on the anti-clogging performance is also studied. The results indicate that the total heat transfer ratio and pressure drop ratio are closely related to the structur ne parameters. The comprehensive thermal performance increase with an increase in the ratio of Lb/L0 and fractal dimension D. Nu/Nus, f/fs, and η are increased as m increases from 3 to 5. Furthermore, the tree-like microchannel network exhibits robustness for cooling gas turbine blades. A greater total number of branching levels and a higher Re number are advantageous for enhancing the anti-clogging performance of the tree-like branching microchannel.

Continuous Electrophoretic Separation of Charged Dyes in Liquid Foam

A novel electrophoretic separation technique is presented, where continuous electrophoretic separation is demonstrated using free flowing liquid foams. Continuous foam electrophoresis combines the principle of capillary electrophoresis and interactions between analytes and the electrical double layer, with the ability of Free Flow Electrophoresis to continuously separate and recover analytes automatically. A liquid foam is used to provide a network of deformable micro and nano channels with a high surface area, presenting a novel platform for electrophoresis, where interfacial phenomena could be exploited to modify analyte migration. The main purpose of this paper is to present a proof-of-concept study and provide fundamental understanding of a complex foam system in continuous separation mode, i.e., flowing liquid foam under an external electric field with electrophoresis and chemical reactions at the electrodes continuously changing the system. Liquid foam is generated using a mixture of anionic and non-ionic surfactants and pumped through a microfluidic separation chamber between two electrodes. The effectiveness of the device is demonstrated using a dye mixture containing a neutral dye and an anionic dye. At the outlet, the foam is separated and collected into five fractions which are individually probed for the concentration of the two dyes used. The anionic dye was concentrated up to 1.75 (±0.05) times the initial concentration in a select outlet, while the neutral dye concentration remained unchanged in all outlets, demonstrating the potential for electrophoretic foam separations.

Capillary-Scale Hydrogel Microchannel Networks by Wire Templating.

Microvascular networks are essential for the efficient transport of nutrients, waste products, and drugs throughout the body. Wire-templating is an accessible method for generating laboratory models of these blood vessel networks, but it has difficulty fabricating microchannels with diameters of ten microns and narrower, a requirement for modeling human capillaries. This study describes a suite of surface modification techniques to selectively control the interactions amongst wires, hydrogels, and world-to-chip interfaces. This wire templating method enables the fabrication of perfusable hydrogel-based rounded cross-section capillary-scale networks whose diameters controllably narrow at bifurcations down to 6.1±0.3 microns in diameter. Due to its low cost, accessibility, and compatibility with a wide range of common hydrogels of tunable stiffnesses such as collagen, this technique may increase the fidelity of experimental models of capillary networks for the study of human health and disease.

Innervation of Sensing Microchannels for Three‐Dimensional Stimuli Perception

AbstractStimuli perception enables animals and robots to interact with unknown environments safely and predictably. For the sensing of soft robotics and wearable devices, although electronic skins have already been widely accepted and studied, their planar geometries are not applicable for multi‐direction volume sensing. Herein, the innervation of sensing microchannel networks into elastic matrices to mimic the exteroception and proprioception of the human bodies is employed. Soft actuators with interlaced actuating and sensing microchannels resembling the distribution of muscle fiber and proprioceptors are fabricated and the internal stimuli perception of deformation configurations (bending, elongating, and bending directions) and magnitudes (bending angle and elongation) of the soft actuators are demonstrated. It is also demonstrated that a soft cubic sensor containing 3D microchannels (diameter: 400 µm) is capable of identifying 3D external stimuli, including force types (pressing, squeezing, shearing, and twisting) and real‐time directions by measuring the resistance variation, and its application in the virtual reality field is exhibited.

Pollution-Free and Highly Sensitive Lactate Detection in Cell Culture Based on a Microfluidic Chip

Cell metabolite detection is important for cell analysis. As a cellular metabolite, lactate and its detection play an important role in disease diagnosis, drug screening and clinical therapeutics. This paper reports a microfluidic chip integrated with a backflow prevention channel for cell culture and lactate detection. It can effectively realize the upstream and downstream separation of the culture chamber and the detection zone, and prevent the pollution of cells caused by the potential backflow of reagent and buffer solutions. Due to such a separation, it is possible to analyze the lactate concentration in the flow process without contamination of cells. With the information of residence time distribution of the microchannel networks and the detected time signal in the detection chamber, it is possible to calculate the lactate concentration as a function of time using the de-convolution method. We have further demonstrated the suitability of this detection method by measuring lactate production in human umbilical vein endothelial cells (HUVEC). The microfluidic chip presented here shows good stability in metabolite quick detection and can work continuously for more than a few days. It sheds new insights into pollution-free and high-sensitivity cell metabolism detection, showing broad application prospects in cell analysis, drug screening and disease diagnosis.

Perfusable Biohybrid Designs for Bioprinted Skeletal Muscle Tissue.

Engineered, centimeter-scale skeletal muscle tissue (SMT) can mimic muscle pathophysiology to study development, disease, regeneration, drug response, and motion. Macroscale SMT requires perfusable channels to guarantee cell survival, and support elements to enable mechanical cell stimulation and uniaxial myofiber formation. Here, stable biohybrid designs of centimeter-scale SMT are realized via extrusion-based bioprinting of an optimized polymeric blend based on gelatin methacryloyl and sodium alginate, which can be accurately coprinted with other inks. A perfusable microchannel network is designed to functionally integrate with perfusable anchors for insertion into a maturation culture template. The results demonstrate that i) coprinted synthetic structures display highly coherent interfaces with the living tissue, ii) perfusable designs preserve cells from hypoxia all over the scaffold volume, iii) constructs can undergo passive mechanical tension during matrix remodeling, and iv) the constructs can be used to study the distribution of drugs. Extrusion-based multimaterial bioprinting with the inks and design realizes in vitro matured biohybrid SMT for biomedical applications.

Bioconjugation of COL1 protein on liquid-like solid surfaces to study tumor invasion dynamics.

Tumor invasion is likely driven by the product of intrinsic and extrinsic stresses, reduced intercellular adhesion, and reciprocal interactions between the cancer cells and the extracellular matrix (ECM). The ECM is a dynamic material system that is continuously evolving with the tumor microenvironment. Although it is widely reported that cancer cells degrade the ECM to create paths for migration using membrane-bound and soluble enzymes, other nonenzymatic mechanisms of invasion are less studied and not clearly understood. To explore tumor invasion that is independent of enzymatic degradation, we have created an open three-dimensional (3D) microchannel network using a novel bioconjugated liquid-like solid (LLS) medium to mimic both the tortuosity and the permeability of a loose capillary-like network. The LLS is made from an ensemble of soft granular microgels, which provides an accessible platform to investigate the 3D invasion of glioblastoma (GBM) tumor spheroids using in situ scanning confocal microscopy. The surface conjugation of the LLS microgels with type 1 collagen (COL1-LLS) enables cell adhesion and migration. In this model, invasive fronts of the GBM microtumor protruded into the proximal interstitial space and may have locally reorganized the surrounding COL1-LLS. Characterization of the invasive paths revealed a super-diffusive behavior of these fronts. Numerical simulations suggest that the interstitial space guided tumor invasion by restricting available paths, and this physical restriction is responsible for the super-diffusive behavior. This study also presents evidence that cancer cells utilize anchorage-dependent migration to explore their surroundings, and geometrical cues guide 3D tumor invasion along the accessible paths independent of proteolytic ability.

BOTTOMHOLE FORMATION ZONE RESTORATION MECHANISMS AND METHODS

The importance of the choice of well exploitation methods is analyzed. Mechanical methods applicable in carbonate reservoirs are discussed. To maintain the efficiency of field development, it is important to maintain the productivity of wells at the planned level throughout the entire production period by increasing their productivity. Productivity increase, skin effect reduction is achieved with the help of acid treatment, the main principle of which is rock dissolution to form a man-made network of microchannels in the bottomhole formation zone, which allows maintaining the recovery rate at the planned level for a long period of time. Forecasting the flow rate of wells in fields with reserves of high-viscosity oil is one of the most difficult tasks in the development of oil fields. Acid treatments quality increasing through new working agent’s usage and improving the technology analysis is performed. Acidizing a reservoir is inherently dual in nature in terms of the desired effect: while in some conditions it has a positive effect, in other conditions it may not be applicable at all.

Development of Microfluidic Impedance Flow Cytometry Enabling the Quantification of Intrinsic Single-Cell Bio-Dielectric Parameters Based on Constrictional Microchannel, Numerical Simulation, and Neural Network

This study presents a microfluidic impedance flow cytometry enabling the quantification of intrinsic single-cell bio-dielectric parameters (e.g., cell radius of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${R}_{\text {c}}$ </tex-math></inline-formula> , relative membrane permittivity of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\varepsilon _{\text {mem}}$ </tex-math></inline-formula> , and cytoplasmic conductivity of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\sigma _{\text {cyto}}$ </tex-math></inline-formula> ) based on constrictional microchannel, numerical simulation, and neural network. Numerical simulation of a traveling cell within constrictional microchannel was conducted to locate relationship between intrinsic bio-dielectric parameters of single cells with corresponding impedance profiles, functioning as “reference” cells for the feedforward neural network, producing fitting accuracies of 1.00 ± 0.00 of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${R}_{\text {c}}$ </tex-math></inline-formula> , 1.00 ± 0.00 of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\varepsilon _{\text {mem}}$ </tex-math></inline-formula> , and 1.00 ± 0.01 of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\sigma _{\text {cyto}}$ </tex-math></inline-formula> . Then, the fitted analytical equation based on numerical simulation and neural network was further used to translate measured impedance profiles into intrinsic bio-dielectric parameters of single cells, where <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${R}_{\text {c}}$ </tex-math></inline-formula> , <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\varepsilon _{\text {mem}}$ </tex-math></inline-formula> , and <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\sigma _{\text {cyto}}$ </tex-math></inline-formula> were quantified as 7.6 ± <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$0.8 \mu \text{m}$ </tex-math></inline-formula> , 16.73 ± 2.97, and 1.38 ± 0.34 S/m of K562 cells ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${n}_{\text {cell}}=1284$ </tex-math></inline-formula> ), 6.4 ± <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$0.8 \mu \text{m}$ </tex-math></inline-formula> , 17.47 ± 5.09, and 1.46 ± 0.47 S/m of Jurkat cells ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${n}_{\text {cell}}=2116$ </tex-math></inline-formula> ), 5.9 ± <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$0.7 \mu \text{m}$ </tex-math></inline-formula> , 17.40 ± 3.14, and 1.96 ± 0.81 S/m of HL-60 cells ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${n}_{\text {cell}}=3543$ </tex-math></inline-formula> ), respectively. Compared to phenomenal electrical signals (i.e., real and imaginary parts at specific frequency) detected by conventional electrical flow cytometry, which were prone to environmental variations, this microfluidic platform enabled the quantification of intrinsic bio-dielectric parameters of single cells and thus provides an effective tool in the field of flow cytometry.

Investigation on the heat dissipation of high heat flux chip array by fractal microchannel networks

With the development of integrated circuits, high power, and high integration chip array devices are facing the requirements of high heat flux and temperature uniformity. The micro-channel heat sink can meet the heat dissipation requirements of chip array devices with high heat flux, and the flow channel with fractal structure can achieve high temperature uniformity of chip array. In this study, the H-shaped fractal micro-channel structure was proposed to cooling the 4?4 chip (1 ? 1 mm) array. The interior fillet structure was introduced to optimize T-shaped and L-shaped corner structures in the fractal channel. The simulation results show that the overall pressure drop of micro-channel heat sink with is reduced 18.7%, and the maximum temperature difference of 4?4 chip array is less than 1.2? at 1000 W/cm2. The micro-channel heat sink with interior fillet structure interior fillet structure was fabricated and assembled, and the hydro-thermal performance was characterized by thermal test chip at different flow rates and heat fluxes. The experimental results show that the standard deviation of temperature of 4?4 chip array is less than 3.5? at 1000 W/cm2 and 480 ml per minute. The error between experimental and simulation data is within ?1.5%, which proves the reasonability of CFD modelling and simulation. Furthermore, the results demonstrate that by introducing interior fillet structure into the T-shaped and L-shaped structures could reduce pumping power and improve temperature uniformity of chip array, which can be applied to improve the performance of the chip array devices with high heat flux.

Generation of Dynamic Concentration Profile Using A Microfluidic Device Integrating Pneumatic Microvalves.

Generating and maintaining the concentration dilutions of diffusible molecules in microchannels is critical for high-throughput chemical and biological analysis. Conventional serial network microfluidic technologies can generate high orders of arbitrary concentrations by a predefined microchannel network. However, a previous design requires a large occupancy area and is unable to dynamically generate different profiles in the same chip, limiting its applications. This study developed a microfluidic device enabling dynamic variations of both the concentration in the same channel and the concentration distribution in multiple channels by adjusting the flow resistance using programmable pneumatic microvalves. The key component (the pneumatic microvalve) allowed dynamic adjustment of the concentration profile but occupied a tiny space. Additionally, a Matlab program was developed to calculate the flow rates and flow resistance of various sections of the device, which provided theoretical guidance for dimension design. In silico investigations were conducted to evaluate the microvalve deformation with widths from 100 to 300 µm and membrane thicknesses of 20 and 30 µm under the activation pressures between 0 and 2000 mbar. The flow resistance of the deformed valve was studied both numerically and experimentally and an empirical model for valve flow resistance with the form of was proposed. Afterward, the fluid flow in the valve region was characterized using Micro PIV to further demonstrate the adjustment mechanism of the flow resistance. Then, the herringbone structures were employed for fast mixing to allow both quick variation of concentration and minor space usage of the channel network. Finally, an empirical formula-supported computational program was developed to provide the activation pressures required for the specific concentration profile. Both linear ( = −0.2k + 1) and nonlinear = concentration distribution in four channels were varied using the same device by adjusting microvalves. The device demonstrated the capability to control the concentration profile dynamically in a small space, offering superior application potentials in analytical chemistry, drug screening, and cell biology research.

Changes of the subchondral bone microchannel network in early osteoarthritis

We have identified a 3D network of subchondral microchannels that connects the deep zone of cartilage to the bone marrow (i.e., cartilage-bone marrow microchannel connectors; CMMC). However, the pathological significance of CMMC is largely unknown. Here, we quantitatively evaluated how the CMMC microarchitecture is related to cartilage condition, as well as regional differences in early idiopathic osteoarthritis (OA). Two groups of cadaveric female human femoral heads (intact cartilage vs early cartilage lesions) were identified, and a biopsy-based high-resolution micro-CT imaging was employed. Subchondral bone (SB) thickness, CMMC number, maximum and minimum CMMC size, and the CMMC morphology were quantified and compared between the two groups. The effect of joint's region and cartilage condition was examined on each dependent variable. The CMMC number and morphology were affected by region of the joint, but not by cartilage condition. On the other hand, the minimum and maximum CMMC size was changed by both the location on the joint, as well as the cartilage condition. The smallest CMMC were consistently detected at the load-bearing region (LBR) of the joint. Compared to non-pathological subjects, the size of the microchannels was enlarged in early OA, most noticeably at the non-load-bearing region (NLBR) and the peripheral rim (PR) of the femoral head. Furthermore, subchondral bone thinning was observed in early OA as a localized occurrence linked with areas of partial chondral defect. Our data point to an enlargement of the SB microchannel network, and a collective structural deterioration of SB in early idiopathic OA.

On modelling coolant penetration into the microchannels at the tool-workpiece interface

A network of microchannels is formed at the interface between the cutting tool and the workpiece during machining due to their rough surface structures. The penetration of coolant into these microchannels has a great effect on the machined surface quality by changing the frictional behaviour and heat transfer characteristics of the interfaces. Most of the present studies focus on the macroscopic coolant delivery process but the mechanism of the microscopic penetration phenomena in the channels at the interface remains unclear. Thus, this study proposes a multi-scale and multi-phase comprehensive theoretical model by combining the machining process, coolant flowing in microchannels and lubrication process, to analyse the coolant transportation in the microchannels and investigate its lubrication effects and the friction mechanisms at the interface between the tool and the workpiece. Then, an orthogonal turning testing of Inconel 718 is designed to verify the proposed model. The cooling and lubrication effect of coolant in the microchannels on the reduction of tool wear, contact length, cutting force and temperature has been demonstrated. And the improvement of chip fragment and microstructure has also been revealed.

Fabrication and Testing of Multi-Hierarchical Porous Scaffolds Designed for Bone Regeneration via Additive Manufacturing Processes.

Bone implants or replacements are very scarce due to the low donor availability and the high rate of body rejection. For this reason, tissue engineering strategies have been developed as alternative solutions to this problem. This research sought to create a cellular scaffold with an intricate and complex network of interconnected pores and microchannels using salt leaching and additive manufacturing (3D printing) methods that mimic the hierarchical internal structure of the bone. A biocompatible hydrogel film (based on poly-ethylene glycol) was used to cover the surface of different polymeric scaffolds. This thin film was then exposed to various stimuli to spontaneously form wrinkled micropatterns, with the aim of increasing the contact area and the material’s biocompatibility. The main innovation of this study was to include these wrinkled micropatterns on the surface of the scaffold by taking advantage of thin polymer film surface instabilities. On the other hand, salt and nano-hydroxyapatite (nHA) particles were included in the polymeric matrix to create a modified filament for 3D printing. The printed part was leached to eliminate porogen particles, leaving homogenously distributed pores on the structure. The pores have a mean size of 26.4 ± 9.9 μm, resulting in a global scaffold porosity of ~42% (including pores and microchannels). The presence of nHA particles, which display a homogeneous distribution according to the FE-SEM and EDX results, have a slight influence on the mechanical resistance of the material, but incredibly, despite being a bioactive compound for bone cells, did not show a significant increase in cell viability on the scaffold surface. However, the synergistic effect between the presence of the hydrogel and the pores on the material does produce an increase in cell viability compared to the control sample and the bare PCL material.

Tissue Niche Miniature of Glioblastoma Patient Treated with Nano-Awakeners to Induce Suicide of Cancer Stem Cells.

Patient-specific cancer therapies can evolve by vitalizing the mother tissue-like cancer niche, cellular profile, genetic signature, and drug responsiveness. This evolution has enabled the elucidation of a key mechanism along with development of the mechanism-driven therapy. After surgical treatment, glioblastoma (GBM) patients require prompt therapy within 14 days in a patient-specific manner. Hence, this study approaches direct culture of GBM patient tissue (1mm diameter) in a microchannel network chip. Cancer vasculature-mimetic perfusion can support the preservation of the mother tissue-like characteristic signatures and microenvironment. When temozolomide and radiation are administered within 1 day, the responsiveness of the tissue in the chip reflected the clinical outcomes, thereby overcoming the time-consuming process of cell and organoid culture. When the tissue chip culture is continued, the intact GBM signature gets lost, and the outward migration of stem cells from the tissue origin increases, indicating a leaving-home effect on the family dismantle. Nanovesicle production using GBM stem cells enables self-chasing of the cells that escape the temozolomide effect owing to quiescence. The anti-PTPRZ1 peptide display and temozolomide loading to nanovesicles awakes cancer stem cells from the quiescent stage to death. This study suggests a GBM clinic-driven avatar platform and mechanism-learned nanotherapy for translation.

Mixing Performance of a Planar Asymmetric Contraction-and-Expansion Micromixer.

Micromixers are one of the critical components in microfluidic devices. They significantly affect the efficiency and sensitivity of microfluidics-based lab-on-a-chip systems. This study introduces an efficient micromixer with a simple geometrical feature that enables easy incorporation in a microchannel network without compromising the original design of microfluidic devices. The study proposes a newly designed planar passive micromixer, termed a planar asymmetric contraction-and-expansion (P-ACE) micromixer, with asymmetric vertical obstacle structures. Numerical simulation and experimental investigation revealed that the optimally designed P-ACE micromixer exhibited a high mixing efficiency of 80% or more within a microchannel length of 10 mm over a wide range of Reynolds numbers (0.13 ≤ Re ≤ 13), eventually attaining approximately 90% mixing efficiency within a 20 mm microchannel length. The highly asymmetric geometric features of the P-ACE micromixers enhance mixing because of their synergistic effects. The flow velocities and directions of the two fluids change differently while alternately crossing the longitudinal centerline of the microchannel, with the obstacle structures asymmetrically arranged on both sidewalls of the rectangular microchannel. This flow behavior increases the interfacial contact area between the two fluids, thus promoting effective mixing in the P-ACE micromixer. Further, the pressure drops in the P-ACE micromixers were experimentally investigated and compared with those in a serpentine micromixer with a perfectly symmetric mixing unit.

Terahertz transmission characteristics of xanthan gum colloids in a microfluidic chip

Terahertz time-domain spectroscopy (THz-TDS) technology has great application prospects for the detection of biological macromolecules, whereas microfluidic technology uses micro-channel networks to manipulate liquids, which can reduce the influence of hydrogen bonds in liquids on THz waves. The combination of these two technologies makes the detection of THz waves in aqueous solutions of biomolecules more accurate and efficient. In this study, microfluidic technology and THz-TDS technology were applied to study the THz transmission characteristics of xanthan gum, providing three feasible methods for the detection of xanthan gum colloids.

A novel approach for pore-scale study of fines migration mechanism in porous media

The migration of fine particles in oil reservoir rock is the most important cause of formation damage and permeability impairment. The mechanism of this phenomenon includes fines detachment, mobilization, agglomeration, and re-attachment, which lead to throat clogging and/or blocking. Therefore, accurate modeling of this complex mechanism requires a model with high solver efficiency.In this work, based on the physical features of fines migration in pore throat, the conventional DPM model of ANSYS FLUENT software was initially modified by UDF code. Then, predetermined scenarios of suspension injection into a two dimensional (2D) microchannel were simulated for predicting pressure drop as a function of injected pore volume using the modified DPM model. Next, based on these simulation results, a proxy model using the artificial neural network (ANN) was developed for computational cost reduction of fines migration modeling in the microchannel (pore throat). Secondly, a dual pore scale numerical model by combination of proxy model and pore network modeling approach was developed to predict pressure drop as well as permeability impairment in a network of microchannels (porous media). Moreover, for rapid computation of pressure drop in the network model, a meta-heuristic method of rain optimization algorithm (ROA) has been used. Finally, for model validation, a series of laboratory tests including suspension injections into the glass micromodels were conducted.A comparison of simulation results using both proxy model and dual pore scale model with experimental data shows a good agreement and according to the obtained results, a decrease in the particles mean size, and Reynolds number as well as increase in particles concentration lead to increase in pressure drop and permeability reduction. On the other hand, use of a proxy model based on artificial neural network and a meta-heuristic method of rain optimization algorithm lead to significant computational cost reduction, while the accuracy of fines migration modeling is high enough. Hence, using our modeling approach for fines migration study in porous media as an accurate and fast computational tool can help for a better understanding of this phenomenon, which is very important in the petroleum industry.