Design Of Microfluidic Chip Research Articles

Quantitative investigation of a 3D bubble trapper in a high shear stress microfluidic chip using computational fluid dynamics and L*A*B* color space

Microfluidic chips often face challenges related to the formation and accumulation of air bubbles, which can hinder their performance. This study investigated a bubble trapping mechanism integrated into microfluidic chip to address this issue. Microfluidic chip design includes a high shear stress section of fluid flow that can generate up to 2.7 Pa and two strategically placed bubble traps. Commercially available magnets are used for fabrication, effectively reducing production costs. The trapping efficiency is assessed through video recordings with a phone camera and analysis of captured air volumes by injecting dye at flow rates of 50, 100, and 150 µL/min. This assessment uses L*A*B* color space with analysis of the perceptual color difference ∆E and computational fluid dynamics (CFD) simulations. The results demonstrate successful application of the bubble trap mechanism for lab-on-chip bubble detection, effectively preventing bubbles from entering microchannels and mitigating potential damage. Furthermore, the correlation between the L*A*B* color space and volume fraction from CFD simulations allows accurate assessment of trap performance. Therefore, this observation leads to the hypothesis that ∆E could be used to estimate the air volume inside the bubble trap. Future research will validate the bubble trap performance in cell cultures and develop efficient methods for long-term air bubble removal.Graphical abstract

Hybrid Microfluidic Chip Design with Two‐Photon Polymerized Protein‐Based Hydrogel Microstructures for Single Cell Experiments

Hybrid Microfluidic Chip Design with Two‐Photon Polymerized Protein‐Based Hydrogel Microstructures for Single Cell Experiments

Guide to microfluidic systems and the preparation of emulsions

AbstractMicrofluidic technology, as an effective method for precise manipulation of microfluid volumes, has demonstrated significant potential in the preparation of emulsions. This guideline introduces key components of a microfluidic operating system, including the design of microfluidic chips (such as T‐junction, flow‐focusing, and co‐flowing structures), fluid driving systems, control systems, and observation and detection systems, explaining how they collaborate to accurately control the droplet generation process. In terms of specific steps for emulsion preparation, the guideline details the workflow utilizing microfluidic technology to fabricate both single‐layer O/W and W/O emulsions, as well as complex multi‐layer emulsions, emphasizing critical considerations during experimentation. Through in‐depth understanding and judicious application of microfluidic technology, there is a promise to advance emulsion preparation techniques across various domains, including drug delivery, food technology, biotechnology, and materials science.

Microfluidic Constant Composition Expansion for Black Oils and Retrograde Gas Condensates

Summary Building a robust pressure/volume/temperature (PVT) model critically relies on accurate phase behavior data, traditionally obtained using PVT cells. While the PVT cell can provide accurate data, it requires a large volume of downhole or recombined samples, which are usually expensive to collect or time-consuming to create. A novel microfluidic chip design and method are presented in this work to rapidly measure saturation pressure, relative volume, and liquid volume percentages of black oils and retrograde gas condensates (RGCs). The chip was initially charged with the single-phase sample at a given temperature, and the saturation pressure, relative volume, and liquid volume percentages were quantified at prescribed pressure steps. The waiting time at each pressure step was adjusted to ensure that the equilibrium condition is achieved. The measurements were conducted for various oil and RGC samples with a wide range of API gravity. The high-resolution optical access along with an in-house-developed automated image analysis algorithm was used to detect the saturation pressures and quantify the phase volumes. The saturation pressures, relative volumes, and liquid volume percentages measured by microfluidics were compared with those obtained from conventional constant composition expansion (CCE) method, showing a strong agreement between the data (i.e., within less than 5% deviation). The microfluidic platform developed in this work can be an alternative approach to some of the conventional PVT tests with an order of magnitude higher laboratory throughput but similar accuracy. This makes PVT data accessible by reducing cost and sample size, and potentially moves the energy industry to a data-on-demand model. With a much smaller physical size inherent to microfluidic devices, this platform can be deployed to operation sites, alleviating the logistical challenges associated with sample handling and shipment that the industry currently struggles with.

Engineering and Evaluating Vascularized Organotypic Spheroids On-Chip.

Organotypic spheroids are evolving as a mainstream in vitro modeling platform, but it is crucial to integrate vascular tissue and perfusion for maintaining their longevity, stability, and physiological relevance. Current vascularization methods remain underdeveloped, and several protocols are poorly reproducible and are limited to use by a few select groups who have designed these methods. To achieve standardization, we offer a step-by-step guide to vascularize organotypic spheroids in case studies of pancreatic islets and cancer spheroids. Our systematic approach spans microfluidic chip design, spheroid fabrication, and vascularization techniques (vasculogenesis and angiogenesis) while describing critical tissue engineering methods. We also include additional insights and operating guidelines within our protocols that characterize and quantitate these models with molecular assays as well as our integrated computational algorithms of mass transport through formed capillary vessels. These protocols contribute to establishing reproducibility, standardization, and enhanced adoption by other contemporary organ-chip researchers, who want to engineer vascularized organoid-based microphysiological platforms. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Design and fabrication of microfluidic chips for vascularized spheroids Basic Protocol 2: Organotypic spheroid fabrication Basic Protocol 3: Vascularized spheroids on-chip Basic Protocol 4: Functionality assays Support Protocol 1: Cell Culture Support Protocol 2: Immunocytochemistry.

The design and fabrication of thermoplastic microfluidic chips with integrated micropillars for particle separation

Microfluidic technology utilizing the deterministic lateral displacement (DLD) method holds significant promise for efficiently separating micro-particles and biological cells. Despite the notable high throughput advantages associated with DLD chips, their widespread application is impeded by the substantial manufacturing costs of tens of thousands of micropillars. This study aims to explore the feasibility of employing the injection molding method for the mass production of DLD microfluidic chips. A multistage DLD chip with varied critical diameters was designed to isolate white blood cells from the human whole blood. The separation effectiveness was verified with the polydimethylsiloxane chip fabricated by standard soft lithography. Subsequently, nickel mold inserts were electroformed to fabricate thermoplastic DLD chips via the injection molding. The replication quality of micropillars under different molding parameters was studied. The capability of injection-molded chips to effectively achieve particle separation was validated. Results showed that thermoplastic chips with good replication quality were obtained, providing a scale-up production strategy for fabricating polymer-based microfluidic chips for disposable separation applications.

Custom microfluidic chip design enables cost-effective three-dimensional spatiotemporal transcriptomics with a wide field of view.

Spatial transcriptomic techniques offer unprecedented insights into the molecular organization of complex tissues. However, integrating cost-effectiveness, high throughput, a wide field of view and compatibility with three-dimensional (3D) volumes has been challenging. Here we introduce microfluidics-assisted grid chips for spatial transcriptome sequencing (MAGIC-seq), a new method that combines carbodiimide chemistry, spatial combinatorial indexing and innovative microfluidics design. This technique allows sensitive and reproducible profiling of diverse tissue types, achieving an eightfold increase in throughput, minimal cost and reduced batch effects. MAGIC-seq breaks conventional microfluidics limits by enhancing barcoding efficiency and enables analysis of whole postnatal mouse sections, providing comprehensive cellular structure elucidation at near single-cell resolution, uncovering transcriptional variations and dynamic trajectories of mouse organogenesis. Our 3D transcriptomic atlas of the developing mouse brain, consisting of 93 sections, reveals the molecular and cellular landscape, serving as a valuable resource for neuroscience and developmental biology. Overall, MAGIC-seq is a high-throughput, cost-effective, large field of view and versatile method for spatial transcriptomic studies.

An optimized MOPSA algorithm for highly accurate deterministic lateral displacement microfluidic sorting chip design

Abstract Deterministic lateral displacement (DLD) sorting is a passive sorting technology. Due to the advantages of small volume and high accuracy, the DLD devices have been used in many applications. The critical diameter (Dc) value of the DLD device depends on the geometric structure of the internal post array. However, the existing empirical formula cannot match all types of post-arrays. Achieving the desired Dc value typically involves multiple iterative processes, leading to increased labor and time costs. In this paper, we propose an optimized trajectory prediction algorithm based on the original MOPSA, which considers the impact of fluidic pressure on particle trajectories. The method is to stretch the 2D physical field space into 3D, the particle expands from a 2D circle into a 3D ball on the pressure analysis. The net pressure on the particle is calculated, and the displacement of the particle is predicted by combining Newton’s second law and the displacement formula. A DLD device with Dc=10.6 μm was designed using this optimized algorithm and fabricated. It is verified by separation of 10 μm and 11 μm polystyrene particles. The test results were consistent with the simulation results. Compared with the empirical formula and the original MOPSA, this optimized algorithm can improve the prediction accuracy of particle trajectories in DLD devices.

Machine Learning-Driven Prediction of DLD Chip Throughput

Abstract The microfluidic chip technology, capable of manipulating fluids at the micrometer-scale, is increasingly being applied in the fields of cell biology, molecular biology, chemistry, and life sciences. The densely integrated microfluidic chip devices enable high-throughput parallel experiments and integration of various operational units. However, the development of densely integrated microfluidic chips also comes with high demands on driving equipment. Due to manufacturing processes and inherent design limitations, the driving capability of the equipment is restricted. To address potential challenges faced by microfluidic chips in the development towards integrated biological microsystems and to maximize their high-throughput performance, improvements are required not only in selecting appropriate driving equipment but also in design aspects. This study focuses on the DLD chip and delves into the complexity of microfluidic chip design. By combining Bézier curves to characterize arbitrarily shaped micropillars and conducting finite element analysis to compute the pressure field of DLD chips, we explore methods utilizing random forest, XGBoost, LightGBM, and ANN machine learning algorithms to predict the impedance of DLD chips. Our objective is to guide engineers in designing chips with smaller impedance (lower pressure drop) and larger throughput more quickly and efficiently during the design phase. Ultimately, through evaluating the predictive capabilities of the four models on new data, we select the ANN algorithm model to predict the pressure drop under different designs of DLD chips. This offers possibilities for enhancing the efficiency and integration of microfluidic technology in biomedical applications.

Detachable acoustofluidic droplet-sorter

BackgroundCell sorting is crucial in isolating specific cell populations. It enables detailed analysis of their functions and characteristics and plays a vital role in disease diagnosis, drug discovery, and regenerative medicine. Fluorescence-activated cell sorting (FACS) is considered the gold standard for high-speed single-cell sorting. However, its high cost, complex instrumentation, and lack of portability are significant limitations. Additionally, the high pressure and electric fields used in FACS can harm cell integrity. In this work, an acoustofluidic device was developed in combination with surface acoustic wave (SAW) and droplet microfluidics to isolate single-cell droplets with high purity while maintaining high cell viability. ResultHuman embryonic kidney cells, transfected with fluorescent reporter plasmids, were used to demonstrate the targeted droplet sorting containing single cells. The acoustofluidic sorter achieved a recovery rate of 81 % and an accuracy rate higher than 97 %. The device maintained a cell viability rate of 95 % and demonstrated repeatability over 20 consecutive trials without compromising efficiency, thus underscoring its reliability. Thermal image analysis revealed that the temperature of the interdigital transducer (IDT) during SAW operation remained within the permissible range for maintaining cell viability. SignificanceThe findings highlighted the sensitivity and effectiveness of the developed acoustofluidic device as a tool for single-cell sorting. The detachable microfluidic chip design enables the reusability of the expensive IDT, making it cost-effective and reducing the risk of cross-contamination between different biological samples. The results underscore its capability to accurately isolate individual cells on the basis of specific criteria, showcasing its potential to advance research and clinical applications requiring precise cell sorting methodologies.

Dynamic Characteristics of λ-DNA Molecules Translocating through Tapered Microfluidic Channel System Driven by Electric Field Force

The dynamic characteristics of single DNA molecules translocating within micro/nano-channels are fundamental for a wide range of applications such as stretching, separating, mapping, and even sequencing of DNA molecules. In this study, a type of tapered microchannel chip with uniform height for all configurations was fabricated, with the major tapered structure having a length of 13 μm and a width that tapers from 5 μm to 20 μm. The dynamic characteristics such as the trajectories and velocities of λ-DNA molecules translocating from different positions driven by an external DC electric field force were systematically investigated by single-molecule fluorescence imaging technology. Some dynamic characteristics of DNA molecules translocation were found. Considering simply the effects of electrophoretic force and electro-osmotic force on the DNA molecules, the dynamic characteristics of DNA molecules are well understood. For example, the velocity of the DNA molecule is inversely proportional to the diameter of the tapered channel and the turning phenomena of the trajectory of the DNA molecules translocating through microchannels. This study is helpful and proposes new ideas for the design and development of microfluidic chips for the quantitative manipulation of DNA molecules.

The Edifice of Vasculature-On-Chips: A Focused Review on the Key Elements and Assembly of Angiogenesis Models.

The conception of vascularized organ-on-a-chip models provides researchers with the ability to supply controlled biological and physical cues that simulate the in vivo dynamic microphysiological environment of native blood vessels. The intention of this niche research area is to improve our understanding of the role of the vasculature in health or disease progression in vitro by allowing researchers to monitor angiogenic responses and cell-cell or cell-matrix interactions in real time. This review offers a comprehensive overview of the essential elements, including cells, biomaterials, microenvironmental factors, microfluidic chip design, and standard validation procedures that currently govern angiogenesis-on-a-chip assemblies. In addition, we emphasize the importance of incorporating a microvasculature component into organ-on-chip devices in critical biomedical research areas, such as tissue engineering, drug discovery, and disease modeling. Ultimately, advances in this area of research could provide innovative solutions and a personalized approach to ongoing medical challenges.

Carbon nanotubes integrated photonic barcodes in Herringbone Microfluidics for Multiplex Biomarker Quantification

Early monitoring of cardiovascular disease (CVD) is crucial for its treatment and prognosis. Hence, highly specific and sensitive detection method is urgently needed. In this study, we propose a novel herringbone microfluid chip with aptamer functionalized core-shell photonic crystal (PhC) barcode integration for high throughput multiplex CVD detection. Based on the PhC derived from co-assembled carboxylated single-wall carbon nanotubes and silicon dioxide nanoparticles, we obtain core-shell PhC barcodes by hydrogel replicating and partially etching. These core-shell PhC barcodes not only retain the original structural colors coding element, but also fully expose a large number of carboxyl elements in the ore for the probe immobilization. We further combine the functionalized barcodes with herringbone groove microfluidic chip to elucidate its acceptability in testing clinical sample. It is demonstrated that the special design of microfluidic chip can significantly enhance fluid vortex resistance and contact frequency, improving the sample capture efficiency and detection sensitivity. These features indicate that our core-shell PhC barcodes-integrated herringbone microfluidic system possesses great potential for multiplex biomarker detection in clinical application.

Rolling Stone Gathers Moss: Rolling Microneedles Generate Meta Microfluidic Microneedles (MMM)

AbstractMicrofluidic chips play crucial roles while lack satisfactory controllability and comprehensive functionality. Inspired by biological systems, this study proposes a method utilizing rolling microneedles (RMNs) to generate muti‐structured templates, realizing photonic crystal membrane (PC) based meta microfluidic microneedle chip (MMM) for efficient wound management. This approach offers advantages in terms of speed and cost‐effectiveness, achieving dual‐sided permeation and patterned design by directly RMNs at desired locations, serving as both template tools for microneedle fabrication. The integration of RMNs with a PC membrane results in the design of 3D multilayer microfluidic channels, effectively addressing issues related to spontaneous fluid flow. As fluid reaches the PC membrane, it generates distinctive structural colors and exhibits fluorescence enhancement, enabling the monitoring of inflammatory factors in mouse wounds and facilitating efficient wound management. In summary, this preparation method involving RMNs paves the way for the design and fluid control of microfluidic chips. This bioinspired patch holds significant potential not only for wound management but also for areas such as clinical drug delivery and point‐of‐care testing (POCT).

Unraveling the complex infiltration and repairing behaviors in defect coatings

Organic coatings are commonly used to protect the metals or alloys from corrosion. However, defects such as scratches or natural aging of the coating can induce unexpected diffusion paths for the corrosive media, so the wettability of repairing liquids and the selection of suitable repairing liquids are crucial. In this study, we systematically investigated the capillary impregnation phenomenon by using liquids with various surface tensions and glass capillaries with different surface energies. We utilized this regularity to instruct the defects repairing process. By using an ultra-depth field microscope, scanning electron microscope, and electrochemical analysis, two kinds of repairing liquids, high surface tension liquid (HSTL) and low surface tension liquid (LSTL), were investigated for repairing man-made defects of coatings. Our results showed that the substrate and the surface energy of the liquids significantly influence the infiltration of the repair liquid. By effectively leveraging the relationship between the repair liquid and the substrate, the repair agent can not only establish a uniform and dense repairing layer but also notably enhance the corrosion resistance of the defective coating. This study provides valuable insights into the repairing of coating defects, as well as liquids transportation, microfluidic chip design, and surface modification of microporous materials.

A microparticle manipulation method facilitated via microfluidic chip based on swirling flow topology design and its application in sorting

Microfluidics technology is trustworthy for microparticle operation as it doesn't involve destructive contact. Our research endeavors have encompassed microparticles manipulation by generating swirling flow region (SFR). Now we try to utilize swirl and flow topology to promote microfluidic chip design because serial operation is still not well enabled. Herein, a new model is proposed for a 6-microchannel microfluidic chip, which has realized active control of microparticles. The chip is capable of trapping, transferring, and enriching microparticles, and is applied for microparticles sorting. Simulation is performed to substantiate the viability of generating SFRs, and experiments are conducted on 3D-printed chips to validate the envisioned functions of the proposed microfluidic chip. Encouragingly, our experiments yield convincing outcomes, wherein microparticles are successfully trapped, transferred, and enriched in separated SFRs. With the help of a self-developed vision algorithm, the size sorting of microparticles is facilitated. Significantly, the manipulation of different microparticles can be achieved by tuning the microchannel velocities and tailoring the flow topology. This work presents a pioneering flow field structure and provides a feasible scheme for sorting microparticles, which is a noteworthy advance in swirl-based microfluidic chip applications. It is a potential mean for bio-/chemical analysis and fluidic-directed assembly of multiple microparticles.

One-step flow synthesis of size-controlled polymer nanogels in a fluorocarbon microfluidic chip.

Synthetic polymer nanoparticles (NPs) with biomimetic properties are ideally suited for different biomedical applications such as drug delivery and direct therapy. However, bulk synthetic approaches can suffer from poor reproducibility and scalability when precise size control or multi-step procedures are required. Herein, we report an integrated microfluidic chip for the synthesis of polymer NPs. The chip could sequentially perform homopolymer synthesis and subsequent crosslinking into NPs without intermediate purification. This was made possible by fabrication of the chip with a fluorinated elastomer and incorporation of two microfluidic mixers. The first was a long channel with passive mixing features for the aqueous RAFT synthesis of stimuli-responsive polymers in ambient conditions. The polymers were then directly fed into a hydrodynamic flow focusing (HFF) junction that rapidly mixed them with a crosslinker solution to produce NPs. Compared to microfluidic systems made of PDMS or glass, our chip had better compatibility and facile fabrication. The polymers were synthesized with high monomer conversion and the NP size was found to be influenced by the flow rate ratio between the crosslinker solution and polymer solution. This allowed for the size to be predictably controlled by careful adjustment of the fluid flow rates. The size of the NPs and their stimuli-responses were studied using DLS and SEM imaging. This microfluidic chip design can potentially streamline and provide some automation for the bottom-up synthesis of polymer NPs while offering on-demand size control.

From ex ovo to in vitro: xenotransplantation and vascularization of mouse embryonic kidneys in a microfluidic chip.

Organoids are emerging as a powerful tool to investigate complex biological structures in vitro. Vascularization of organoids is crucial to recapitulate the morphology and function of the represented human organ, especially in the case of the kidney, whose primary function of blood filtration is closely associated with blood circulation. Current in vitro microfluidic approaches have only provided initial vascularization of kidney organoids, whereas in vivo transplantation to animal models is problematic due to ethical problems, with the exception of xenotransplantation onto a chicken chorioallantoic membrane (CAM). Although CAM can serve as a good environment for vascularization, it can only be used for a fixed length of time, limited by development of the embryo. Here, we propose a novel lab on a chip design that allows organoids of different origin to be cultured and vascularized on a CAM, as well as to be transferred to in vitro conditions when required. Mouse embryonic kidneys cultured on the CAM showed enhanced vascularization by intrinsic endothelial cells, and made connections with the chicken vasculature, as evidenced by blood flowing through them. After the chips were transferred to in vitro conditions, the vasculature inside the organoids was successfully maintained. To our knowledge, this is the first demonstration of the combination of in vivo and in vitro approaches applied to microfluidic chip design.

Molecular Separation by Using Active and Passive Microfluidic chip Designs: A Comprehensive Review (Adv. Mater. Interfaces 2/2024)

Molecular Separation by Using Active and Passive Microfluidic chip Designs: A Comprehensive Review (Adv. Mater. Interfaces 2/2024)

Development of a microfluidic device to enrich and detect zearalenone in food using quantum dot-embedded molecularly imprinted polymers.

Mycotoxins are secondary metabolites of certain moulds, prevalent in 60-80% of food crops and many processed products but challenging to eliminate. Consuming mycotoxin-contaminated food and feed can lead to various adverse effects on humans and livestock. Therefore, testing mycotoxin residue levels is critical to ensure food safety. Gold standard analytical methods rely on liquid chromatography coupled with optical detectors or mass spectrometers, which are high-cost with limited capacity. This study reported the successful development of a microfluidic "lab-on-a-chip" device to enrich and detect zearalenone in food samples based on the fluorescence quenching effect of quantum dots and selective affinity of molecularly imprinted polymers (MIPs). The dummy template and functional polymer were synthesized and characterized, and the detailed microfluidic chip design and optimization of the flow conditions in the enrichment module were discussed. The device achieved an enrichment factor of 9.6 (±0.5) in 10 min to quantify zearalenone spiked in food with high recoveries (91-105%) at 1-10 mg kg-1, covering the concerned residue levels in the regulations. Each sample-to-answer test took only 20 min, involving 3 min of manual operation and no advanced equipment. This microfluidic device was mostly reusable, with a replaceable detection module compatible with fluorescence measurement using a handheld fluorometer. To our best knowledge, the reported device was the first application of an MIP-based microfluidic sensor for detecting mycotoxin in real food samples, providing a novel, rapid, portable, and cost-effective tool for monitoring mycotoxin contamination for food safety and security.