Microchannel Network Research Articles

Fabrication of endothelialized capillary-like microchannel networks using sacrificial thermoresponsive microfibers.

In the body, capillary beds fulfill the metabolic needs of cells by acting as the sites of diffusive transport for vital gasses and nutrients. In artificial tissues, replicating the scale and complexity of these capillary vessels has proved challenging, especially in a three-dimensional context. In order to better develop thick artificial tissues, it will be necessary to recreate both the form and function of capillaries. Here we demonstrate a top-down method of patterning hydrogels using sacrificial templates formed from thermoresponsive microfibers whose size and architecture approach those of natural capillaries. Within the resulting microchannels, we cultured endothelial monolayers that remain viable for over three weeks and exhibited functional barrier properties. Additionally, we cultured endothelialized microchannels within hydrogels containing fibroblasts and characterized the viability of the co-cultures to demonstrate this approach's potential to when applied to cell-laden hydrogels. This method represents a step forward in the evolution of artificial tissues and a path towards producing viable capillary-scale microvasculature for engineered organs.

Production of complex microchanneled parts of ZrB2-MoSi2 ultra-high temperature ceramics by freeze casting and pressureless spark plasma sintering

A novel approach for manufacturing complex parts of ultra-high-temperature ceramics (UHTCs) is proposed, combining freeze casting with pressureless spark plasma sintering (SPS). With the aid of MoSi2 sintering additive (15 vol% or more), this combination enables the production of fully dense ZrB2-based UHTC parts at 1900 °C. Producing complex-shaped samples including an intricate network of internal microchannels seems feasible, by using additive manufacturing techniques in the production of templates for the external silicone mould and the internal microchannel network to be used during the freeze casting process. Although defects are prone to occur either during freeze drying, due to thermal stresses arising from the expansion mismatch between the internal resin template and the ceramic preform, or during the resin burn-out or SPS cycles, the resulting samples exhibited a fully dense microstructure and similar hardness (17 ± 1 GPa) as the bulk material. Thus, the proposed approach shows promise in the production of arbitrarily complex-shaped UHTC parts that may find application in numerous industrial sectors including aerospace, aviation, and energy generation and storage.

Microfluidics-A novel technique for high-quality sperm selection for greater ART outcomes.

Microfluidics represent a quality sperm selection technique. Human couples fail to conceive and this is so in a significant population of animals worldwide. Defects in male counterpart lead to failure of conception so are outcomes of assisted reproduction affected by quality of sperm. Microfluidics, deals with minute volumes (μL) of liquids run in small-scale microchannel networks in the form of laminar flow streamlines. Microfluidic sperm selection designs have been developed in chip formats, mimicking invivo situations. Here sperms are selected and analyzed based on motility and sperm behavioral properties. Compared to conventional sperm selection methods, this selection method enables to produce high-quality motile sperm cells possessing non-damaged or least damaged DNA, achieve greater success of insemination in bovines, and achieve enhanced pregnancy rates and live births in assisted reproduction-in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Besides, the concentration of sperm available to oocyte can be controlled by regulating the flow rate in microfluidic chips. The challenges in this technology are commercialization of chips, development of fully functional species-specific microfluidic tools, limited number of studies available in literature, and need of thorough understanding in reproductive physiology of domestic animals. In conclusion, incorporation of microfluidic system in assisted reproduction for sperm selection may promise a great success in IVF and ICSI outcomes. Future prospectives are to make this technology more superior and need to modify chip designs which is cost effective and species specific and ready for commercialization. Comprehensive studies in animal species are needed to be carried out for wider application of microfluidic sperm selection in invitro procedures.

Systematic design of tree-like branching network microchannel heat sinks for enhanced heat transfer with nanofluids

Branched or tree-shaped networks of microchannels are often preferred heatsink designs for microelectronic cooling due to their ability to offer a substantially large surface area-to-volume ratio. Designing an optimized tree-shaped heatsink in terms of hydrothermal performance poses challenges due to the intricate geometry and small-scale fluid–structure interactions involved, making prototyping challenging. We propose a systematically designed microchannel network heat exchanger inspired by tree branching patterns, aiming for ease in rapid prototyping and improved flow distributions offering enhanced thermal performance. Starting from a simpler geometrical consideration, we systematically improve the design by introducing a pin fin at the junction for improved flow distribution and then by imparting a converging angle in the channel for enhanced thermal performance. Additionally, we conduct an entropy generation analysis to examine the thermal performance of various nanofluid concentrations within the proposed device and witness significant thermal performance improvement that can benefit the thermal management of microelectronic components and other cooling applications.

Self-healing injectable hydrogels incorporating hyaluronic acid and phytic acid: Rheological insights and implications for regenerative medicine

Eying the increasing impact of hyaluronic acid (HA) and its multifaceted applications, this study employs a non-toxic, one-pot strategy to develop injectable, self-healing hydrogels for biomedical applications. Phytic acid (PA), a plant-derived organic acid with high biocompatibility and numerous hydroxyl groups, can act as a cross-linking agent to form hydrogen-bonded networks with the HA chains. The study examined the optimal mass ratio of HA to PA to achieve superior hydrogel performance. Fourier transform infrared spectroscopy, rheological studies, and thermal analysis confirmed the successful formation of the hydrogels, which exhibited injectability, rapid self-healing, malleability, and elasticity. The investigation of different compositions revealed a sensitive influence of PA on the self-assembly phenomena of HA during flow. SEM cross-section images of the freeze-dried gels revealed a porous surface in the form of an interconnected network of microchannels. In addition, the hydrogel exhibits good tissue adhesion properties and promotes cell proliferation in biocompatibility tests on human gingival fibroblasts. The significance of this study lies in the ability of the proposed materials to be injected, to conform to the complex 3D structure of host tissues as well as their ability to recover after damage, indicating significant potential as scaffolds for wound healing.

Universal Correlation for Droplet Fragmentation in a Microfluidic T-Junction.

Despite extensive research on droplet dynamics at microfluidic T-junction, for different droplet lengths and Capillary numbers, there remains limited understanding of their dynamics at different viscosity ratio. In this study, we adopt a modeling framework in a three-dimensional (3D) configuration to numerically investigate the droplet dynamics as it passes through a symmetric T-junction with varying Capillary numbers, droplet lengths, and viscosity ratios. We present a 3D regime map for the first time to demarcate the droplet breakup and no breakup regimes. Herein, we propose a simple surface equation accounting for the critical Capillary number for breakup, in terms of viscosity ratio and dimensionless droplet length. The proposed universal relationship aligns well with experimental and computational findings from the existing literature. Furthermore, we reveal a new droplet breakup characteristic at high viscosity ratio and high Capillary number where the droplet spreads almost twice its initial value before splitting. Overall, this research provides comprehensive understanding of droplet dynamics at the T-junction and has significant implications for several related applications, including the large-scale synthesis of microdroplets using microchannel networks.

Theoretical study on sequential splitting of droplets flowing through fractal tree-shaped microchannel networks

A theoretical model for describing the sequential splitting of droplets flowing through the fractal tree-shaped microchannel network with arbitrary branch level is developed to explore the mechanisms underlying the hydraulic imbalance on the high-throughput droplets production. Accordingly, detailed droplet splitting characteristics are presented, including the droplet velocities in branches, droplet distribution coefficient, and monodispersity of droplets production. It is found that the uniformity of droplet mainly depends on two key dimensionless parameters, namely Λ1 and Λ2, where Λ1 is determined by the initial working condition involving the initial lengths and viscosity of the continuous and discrete phases, the width of the 0th level channel, and the initial capillary number, and Λ2 is concerned with the outlet pressure pout, [2n-1] and the pressure drops of the continuous and discrete phases at the 0th level channel. The monodispersity of droplets goes down with the decreasing Λ1 and the increasing Λ2. Based on the Λ1 and Λ2, the optimal design strategies contributing to enhancing the droplet generation uniformity are recommended, including increasing Ca, enlarging the length of continuous phase flow at the main channel, and increasing the lengths of each level channels. Furthermore, the tree-shaped microchannel networks with higher branch level (n) have stronger ability to resist asymmetric disturbances. In particular, in our work, the width fractal dimension Δ = 2 is adopted as a proper key structure parameter, so as to ensure sequential breakup of droplet at each T-junction under symmetric condition.

A Photonic Immunosensor Detection Method for Viable and Non-Viable E. coli in Water Samples.

Detection and enumeration of coliform bacteria using traditional methods and current molecular techniques against E. coli usually involve long processes with less sensitivity and specificity to distinguish between viable and non-viable bacteria for microbiological water analysis. This approach involves developing and validating an immunosensor comprising ring resonators functionalized with specific antibodies surrounded by a network of microchannels as an alternative method for detecting and indirectly enumerating Escherichia coli in samples of water for consumption. Different ELISA assays were conducted to characterize monoclonal and polyclonal antibodies selected as detection probes for specific B-galactosidase enzymes and membrane LPS antigens of E. coli. An immobilization control study was performed on silicon nitride surfaces used in the immunosensor, immobilized with the selected antibodies from the ELISA assays. The specificity of this method was confirmed by detecting as few as 10 CFU/mL of E. coli from viable and non-viable target bacteria after applying various disinfection methods to water samples intended for human consumption. The 100% detection rate and a 100 CFU/mL Limit of Quantification of the proposed method were validated through a comprehensive assessment of the immunosensor-coupled microfluidic system, involving at least 50 replicates with a concentration range of 10 to 106 CFU/mL of the target bacteria and 50 real samples contaminated with and without disinfection treatment. The correlation coefficient of around one calculated for each calibration curve obtained from the results demonstrated sensitive and rapid detection capabilities suitable for application in water resources intended for human consumption within the food industry. The biosensor was shown to provide results in less than 4 h, allowing for rapid identification of microbial contamination crucial for ensuring water monitoring related to food safety or environmental diagnosis and allowing for timely interventions to mitigate contamination risks. Indeed, the achieved setup facilitates the in situ execution of laboratory processes, allowing for the detection of both viable and non-viable bacteria, and it implies future developments of simultaneous detection of pathogens in the same contaminated sample.

Electroosmotic Flow in Fractal Tree‐Like Convergent Microchannel Network

AbstractElectroosmotic flow (EOF) in a fractal tree‐like microfluidic network has wide applications. To reduce the fluid resistance of EOF in the network, this paper numerically studies the influences of the branch convergence α, the level convergence κ, the length ratio λ, the branching number N, the maximum branching level M, and the channel height H of a fractal tree‐like convergent microchannel network (FTCMCN) on the EOF flowrate and analyzes the optimal structure of FTCMCN to maximize the EOF transport efficiency. The present paper finds the optimal structure of FTCMCN and its dependence on the various geometric and structural parameters. This work is beneficial to the optimization design of the FTCMCN to achieve the highest EOF transport efficiency.

High-Density Microporous Drainage-Integrating Sheath Flow Generator for Streamlining Microfluidic Cell Sorting Systems.

Tremendous efforts have been made to develop practical and efficient microfluidic cell and particle sorting systems; however, there are technological limitations in terms of system complexity and low operability. Here, we propose a sheath flow generator that can dramatically simplify operational procedures and enhance the usability of microfluidic cell sorters. The device utilizes an embedded polydimethylsiloxane (PDMS) sponge with interconnected micropores, which is in direct contact with microchannels and seamlessly integrated into the microfluidic platform. The high-density micropores on the sponge surface facilitated fluid drainage, and the drained fluid was used as the sheath flow for downstream cell sorting processes. To fabricate the integrated device, a new process for sponge-embedded substrates was developed through the accumulation, incorporation, and dissolution of PMMA microparticles as sacrificial porogens. The effects of the microchannel geometry and flow velocity on the sheath flow generation were investigated. Furthermore, an asymmetric lattice-shaped microchannel network for cell/particle sorting was connected to the sheath flow generator in series, and the sorting performances of model particles, blood cells, and spiked tumor cells were investigated. The sheath flow generation technique developed in this study is expected to streamline conventional microfluidic cell-sorting systems as it dramatically improves versatility and operability.

Porous array of BaLi4 alloy microchannels enforced carbon cloth for a stable Li composite anode

Integrating metallic lithium (Li) with a three-dimensional (3D) host is a popular strategy for long-life Li composite anodes, where the structure and physicochemical nature of the framework are critical for the electrochemical performance. Herein, Li-rich dual-phase barium (Ba)-based alloy composed of BaLi4 intermetallic compounds and Li metal phases is thermally incorporated into commercial carbon cloth sheets to develop Li-Ba alloy composite (LBAC) anodes featuring a porous array of BaLi4 microchannels as the built-in 3D skeleton. Doping of metallic Ba can greatly lower the surface tension of liquid Li and improve the wettability of the molten Li-Ba alloy toward the carbon cloth substrate. Moreover, LBAC benefits from the superior lithiophilicity and the porous architecture of BaLi4 skeleton nested in a conductive carbon fiber matrix, leading to stable cycling performance by confining Li stripping/plating in microchannels network of BaLi4 alloy framework and dissipating high current densities. As a result, the LBAC symmetrical cells can run stably for 1,000 h under 1 mA cm-2 and 1 mA h cm-2, and the capacity retention can retain 93.3% after 300 cycles in the full cell with areal capacity of 2.45 mA h cm-2. This work offers a smart designing strategy of 3D Li alloy composite anodes by introducing porous and lithiophilic alloy scaffold as sub-framework of the carbon hosting anode, promising the prospect of Li metal batteries for future applications.

Artificial Vasa‐Vasorum Serves as an On‐Site Regenerative Promoter of Cell‐Free Vascular Grafting

AbstractThe control paradigm of small vessel pathophysiology has changed to focus on the vascular out‐wall rather than the lumen‐intimal factors. As an emerging controller of the external wall, the microvasculature (“vasa vasorum”) provides interactional routes between the in‐and out‐sides of the vascular wall. Despite numerous approaches to developing small‐diameter vascular grafts, engineering artificial vasa vasorum (AVV) has not been projected as a multi‐functional solution to address long‐standing issues such as thrombotic and immune controls for wall regeneration. Here, the AVV is engineered using a microchannel network hydrogel after a multi‐study validation of implantation functions and then used to wrap the external wall of the cell‐free vessel post‐decellularization while preserving its mechanical properties. Upon inter‐positional and bypass grafting to rabbit arteries, the AVV graft facilitates the recruitment of vascular cells into the cell‐free wall by promoting invasion of angiogenic and vasculogenic cells through the microchannel‐mediated M2 polarization of macrophages. This function results in the efficient restoration of smooth muscle cells, and the revitalized vascular elasticity helps to maintain long‐term patency. The AVV, therefore, serves as an effective catalyst for vascular wall regeneration, offering a solution to clinically successful small‐diameter vascular grafting.

Enhancing the Thermal Performance of Shape Memory Polymers: Designing a Minichannel Structure.

This research proposes a numerical approach to improve the thermal performance of shape memory polymers (SMPs) while their mechanical properties remain intact. Sixteen different 3D minichannel structures were numerically designed to investigate the impact of embedded water flow in microchannel networks on the thermal response and shape recovery of SMPs. This work employs two approaches, each with different physics: approach A focuses on solid mechanics analysis and, accordingly, thermal analysis in solids without considering the fluid. approach B tackles solid and fluid mechanics analysis and thermal analysis in both solid and fluid subdomains, which inherently calls for fluid-structure coupling in a uniform procedure. Finally, the results of these two approaches are compared to predict the SMP's thermal and mechanical behavior. The structural designs are then analyzed in terms of their shape recovery speed, recovery ratio, and recovery parameters. The results indicate that isotropic structures thermally outperform their anisotropic counterparts, exhibiting improved thermal characteristics and faster shape recovery. Additionally, it was observed that polymeric structures with a low volume fraction of embedded branches thermally perform efficiently. The findings of this study predict that the geometrical angle between the main branch and sub-branches of SMP favorably impacts the enhancement of thermal characteristics of the structure, accelerating its shape recovery. Approach B accelerates the shape recovery rate in SMPs due to fluid flow and uniform heat transfer within the structures.

SUBCHONDRAL MICROCHANNEL NETWORK CHANGES IN EARLY OSTEOARTHRITIS

Articular cartilage (AC) and subchondral bone (SB) are intimately intertwined, forming a complex unit called the AC-SB interface. Our recent studies have shown that cartilage and bone marrow are connected by a three-dimensional network of microchannels (i.e. cartilage-bone marrow microchannel connector; CMMC), which differ microarchitecturally in number, size and morphology depending on the maturation stage of the bone and the region of the joint. However, the pathological significance of CMMC is largely unknown. Here, we quantitatively assessed how CMMC microarchitecture relates to cartilage condition and regional differences in early idiopathic osteoarthritis (OA).Two groups of cadaveric female human femoral heads (intact cartilage vs early cartilage lesions) were identified and biopsy-based high-resolution micro-CT imaging was used. Subchondral bone (SB) thickness, CMMC number, maximum and minimum CMMC size, and CMMC morphology were quantified and compared between the two groups. The effect of joint region and cartilage condition on each dependent variable was examined.The number and morphology of CMMCs were influenced by the region of the joint, but not by the cartilage condition. On the other hand, the minimum and maximum CMMC size was modified by both joint location and cartilage condition. The smallest CMMCs were consistently found in the load bearing region (LBR) of the joint. Compared to healthy subjects, the size of the microchannels was increased in early OA, most notably in the non-load bearing region (NLBR) and the peripheral rim (PR) of the femoral head. In addition, subchondral bone thinning was observed in early OA as a localized event associated with areas of partial chondral defect.Our data suggest an enlargement of the SB microchannel network and a collective structural deterioration of the SB in early idiopathic OA.

High-throughput 3D microfluidic chip for generation of concentration gradients and mixture combinations.

Concentration gradient generation and mixed combinations of multiple solutions are of great value in the field of biomedical research. However, existing concentration gradient generators for single or two-drug solutions cannot simultaneously achieve multiple concentration gradient formations and mixed solution combinations. Furthermore, the whole system was huge, and required expensive auxiliary equipment, which may lead to complex operations. To address this problem, we devised a novel 3D microchannel network design, which is capable of creating all the desired mixture combinations and concentration gradients of given small amounts of the input solutions. As a proof of concept, the device we presented was verified by both colorimetric and fluorescence detection methods to test the efficiency. This can enable the implementation of one to three solutions with no driving pump and facilitate unique multiple types of more concentration gradients and mixture combinations in a single operation. We envision that this will be a promising candidate for the development of simplified methods for screening of the appropriate concentration and combination, such as various drug screening applications.

Biomimetic microchannel network with functional endothelium formed by sacrificial electrospun fibers inside 3D gelatin methacryloyl (GelMA) hydrogel models

Biomimetic microchannel network with functional endothelium formed by sacrificial electrospun fibers inside 3D gelatin methacryloyl (GelMA) hydrogel models

Generation of Multiple Concentration Gradients Using a Two-Dimensional Pyramid Array.

Concentration heterogeneity of diffusible reactants is a prevalent phenomenon in biochemical processes, requiring the generation of concentration gradients for the relevant experiments. In this study, we present a high-density pyramid array microfluidic network for the effective and precise generation of multiple concentration gradients. The complex gradient distribution in the 2D array can be adaptively adjusted by modulating the reactant velocities and concentrations at the inlets. In addition, the unique design of each reaction chamber and mixing block in the array ensures uniform concentrations within each chamber during dynamic changes, enabling large-scale reactions with low reactant volumes. Through detailed numerical simulation of mass transport within the complex microchannel networks, the proposed method allows researchers to determine the desired number of reaction chambers within a given concentration range based on experimental requirements and to quickly obtain the operating conditions with the help of machine learning-based prediction. The effectiveness in generating a multiple concentration gradient environment was further demonstrated by concentration-dependent calcium carbonate crystallization experiments. This device provides a highly efficient mixing and adaptable concentration platform that is well suited for high-throughput and multiplexed reactions.

Microzone Melting Method of Porous Reactor Fabrication with Structure-Controlled Microchannel Networks for High Yield In Situ DNA Synthesis

Microzone Melting Method of Porous Reactor Fabrication with Structure-Controlled Microchannel Networks for High Yield In Situ DNA Synthesis

MODL-33. PATIENT-DERIVED GLIOBLASTOMA MINIATURE AND CANCER STEM CELL SUICIDE-INDUCING NANO-AWAKENER BASED ON IT

Abstract 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”). 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. 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. This research proposes a GBM patient avatar platform and mechanism-learned nanotherapy for translation.

Programmable and Pixelated Solute Concentration Fields Controlled by Three-Dimensionally Networked Microfluidic Source/Sink Arrays.

Membrane-integrated microfluidic platforms have played a pivotal role in understanding natural phenomena coupled with solute concentration gradients at the micro- and nanoscale, enabling on-chip microscopy in well-defined planar concentration fields. However, the standardized two-dimensional fabrication schemes in microfluidics have impeded the realization of more complex and diverse chemical environmental conditions due to the limited possible arrangements of source/sink conditions in a fluidic domain. In this study, we present a microfluidic platform with a three-dimensional microchannel network design, where discretized membranes can be integrated and individually controlled in a two-dimensional array format at any location within the entire quasi-two-dimensional solute concentration field. We elucidate the principles of the device to implement operations of the pixel-like sources/sinks and dynamically programmable control of various long-lasting solute concentration fields. Furthermore, we demonstrate the application of the generated solute concentration fields in manipulating the transport of micrometer or submicrometer particles with a high degree of freedom, surpassing conventionally available solute concentration fields. This work provides an experimental tool for investigating complex systems under high-order chemical environmental conditions, thereby facilitating the extensive development of higher-performance micro- and nanotechnologies.