A novel integrated microfluidic chip for on-demand electrostatic droplet charging and sorting

On-demand droplet sorting is extensively applied for the efficient manipulation and genome-wide analysis of individual cells.However,state-of-the-art microfluidic chips for droplet sorting still suffer from low sorting speeds,sample loss,and labor-intensive preparation procedures.Here,we demonstrate the development of a novel microfluidic chip that integrates droplet generation,on-demand electrostatic droplet charging,and high-throughput sorting.The charging electrode is a copper wire buried above the nozzle of the microchannel,and the deflecting electrode is the phosphate buffered saline in the microchannel,which greatly simplifies the structure and fabrication process of the chip.Moreover,this chip is capable of high-frequency droplet generation and sorting,with a frequency of 11.757 kHz in the drop state.The chip completes the selective charging process via electrostatic induction during droplet generation.On-demand charged microdroplets can arbitrarilymove to specific exit channels in a three-dimensional(3D)-deflected electric field,which can be controlled according to user requirements,and the flux of droplet deflection is thereby significantly enhanced.Furthermore,a lossless modification strategy is presented to improve the accuracy of droplet deflection or harvest rate from 97.49% to 99.38% by monitoring the frequency of droplet generation in real time and feeding it back to the charging signal.This chip has great potential for quantitative processing and analysis of single cells for elucidating cell-to-cell variations.

Microfluidic-oriented synthesis of enriched iridium nanodots/carbon architecture for robust electrocatalytic nitrogen fixation

Electrocatalytic nitrogen reduction reaction(NRR)is considered as a promising candidate to achieve ammonia synthesis because of clean electric energy,moderate reaction condition,safe operating process and harmless by-products.However,the chemical inertness of nitrogen and poor activated capacity on catalyst surface usually produce low ammonia yield and faradic efficiency.Herein,the microfluidic technology is proposed to efficiently fabricate enriched iridium nanodots/carbon architecture.Owing to in-situ co-precipitation reaction and microfluidic manipulation,the iridium nanodots/carbon nanomaterials possess small average size,uniform dispersion,high conductivity and abundant active sites,producing good proton activation and rapid electrons transmission and moderate adsorption/desorption capacity.As a result,the as-prepared iridium nanodots/carbon nanomaterials realize large ammonia yield of 28.73 μg h^(-1) cm^(-2) and faradic efficiency of 9.14%in KOH solution.Moreover,the high ammonia yield of 11.21 μg h^(-1) cm^(-2) and faradic efficiency of 24.30%are also achieved in H_(2)SO_(4) solution.The microfluidic method provides a reference for large-scale fabrication of nano-sized catalyst materials,which may accelerate the progress of electrocatalytic NRR in industrialization field.

Bio-Inspired Screwed Conduits from the Microfluidic Rope-Coiling Effect for Microvessels and Bronchioles

Tubular microfibers have recently attracted extensive interest for applications in tissue engineering.However,the fabrication of tubular fibers with intricate hierarchical structures remains a major challenge.Here,we present a novel one-step microfluidic spinning method to generate bio-inspired screwed conduits(BSCs).Based on the microfluidic rope-coiling effect,a viscous hydrogel precursor is first curved into a helix stream in the channel,and then consecutively packed as a hollow structured stream and gelated into a screwed conduit(SC)via ionic and covalent crosslinking.By taking advantage of the excellent fluid-controlling ability of microfluidics,various tubes with diverse structures are fabricated via simple control over fluid velocities and multiple microfluidic device designs.The perfusability and permeability results,as well as the encapsulation and culture of human umbilical vein endothelial cells(HUVECs),human pulmonary alveolar epithelial cells(HPAs),and myogenic cells(C2C12),demonstrate that these SCs have good perfusability and permeability and the ability to induce the formation of functional biostructures.These features support the uniqueness and potential applications of these BSCs as biomimetic blood vessels and bronchiole tissues in combination with tissue microstructures,with likely application possibilities in biomedical engineering.

Functional microfluidics:theory,microfabrication,and applications

Microfluidic devices are composed of microchannels with a diameter ranging from ten to a few hundred micrometers.Thus,quite a small(10-9–10-18l)amount of liquid can be manipulated by such a precise system.In the past three decades,significant progress in materials science,microfabrication,and various applications has boosted the development of promising functional microfluidic devices.In this review,the recent progress on novel microfluidic devices with various functions and applications is presented.First,the theory and numerical methods for studying the performance of microfluidic devices are briefly introduced.Then,materials and fabrication methods of functional microfluidic devices are summarized.Next,the recent significant advances in applications of microfluidic devices are highlighted,including heat sinks,clean water production,chemical reactions,sensors,biomedicine,capillaric circuits,wearable electronic devices,and microrobotics.Finally,perspectives on the challenges and future developments of functional microfluidic devices are presented.This review aims to inspire researchers from various fields engineering,materials,chemistry,mathematics,physics,and more—to collaborate and drive forward the development and applications of functional microfluidic devices,specifically for achieving carbon neutrality.

Biomimetic Erythrocyte-Like Particles from Microfluidic Electrospray for Tissue Engineering

Microparticles have demonstrated value for regenerative medicine.Attempts in this field tend to focus on the development of intelligent multifunctional microparticles for tissue regeneration.Here,inspired by erythrocytes-associated self-repairing process in damaged tissue,we present novel biomimetic erythrocyte-like microparticles(ELMPs).These ELMPs,which are composed of extracellular matrix-like hybrid hydrogels and the functional additives of black phosphorus,hemoglobin,and growth factors(GFs),are generated by using a microfluidic electrospray.As the resultant ELMPs have the capacity for oxygen delivery and near-infrared-responsive release of both GFs and oxygen,they would have excellent biocompatibility and multifunctional performance when serving as microscaffolds for cell adhesion,stimulating angiogenesis,and adjusting the release profile of cargoes.Based on these features,we demonstrate that the ELMPs can stably overlap to fill a wound and realize controllable cargo release to achieve the desired curative effect of tissue regeneration.Thus,we consider our biomimetic ELMPs with discoid morphology and cargo-delivery capacity to be ideal for tissue engineering.

Simulation and fabrication of in vitro microfluidic microelectrode array chip for patterned culture and electrophysiological detection of neurons

To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip was designed based on the specific structure of neurons and the requirements for detection and modulation.Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels.By employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated successfully.Primary hippocampal neurons were cultured on the chip,forming a well-defined neural network.Spontaneous electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array.This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.

Femtosecond laser-induced nanoparticle implantation into flexible substrate for sensitive and reusable microfluidics SERS detection

Surface-enhanced Raman spectroscopy(SERS)microfluidic system,which enables rapid detection of chemical and biological analytes,offers an effective platform to monitor various food contaminants and disease diagnoses.The efficacy of SERS microfluidic systems is greatly dependent on the sensitivity and reusability of SERS detection substrates to ensure repeated use for prolonged periods.This study proposed a novel process of femtosecond laser nanoparticle array(NPA)implantation to achieve homogeneous forward transfer of gold NPA on a flexible polymer film and accurately integrated it within microfluidic chips for SERS detection.The implanted Au-NPA strips show a remarkable electromagnetic field enhancement with the factor of 9×108 during SERS detection of malachite green(MG)solution,achieving a detection limit lower than 10 ppt,far better than most laser-prepared SERS substrates.Furthermore,Au-NPA strips show excellent reusability after several physical and chemical cleaning,because of the robust embedment of laser-implanted NPA in flexible substrates.To demonstrate the performance of Au-NPA,a SERS microfluidic system is built to monitor the online oxidation reaction between MG/NaClO reactants,which helps infer the reaction path.The proposed method of nanoparticle implantation is more effective than the direct laser structuring technique.It provides better performance for SERS detection,robustness of detection,and substrate flexibility and has a wider range of applications for microfluidic systems without any negative impact.

High-throughput microfluidic production of carbon capture microcapsules:fundamentals,applications,and perspectives

In the last three decades,carbon dioxide(CO_(2)) emissions have shown a significant increase from various sources.To address this pressing issue,the importance of reducing CO_(2) emissions has grown,leading to increased attention toward carbon capture,utilization,and storage strategies.Among these strategies,monodisperse microcapsules,produced by using droplet microfluidics,have emerged as promising tools for carbon capture,offering a potential solution to mitigate CO_(2) emissions.However,the limited yield of microcapsules due to the inherent low flow rate in droplet microfluidics remains a challenge.In this comprehensive review,the high-throughput production of carbon capture microcapsules using droplet microfluidics is focused on.Specifically,the detailed insights into microfluidic chip fabrication technologies,the microfluidic generation of emulsion droplets,along with the associated hydrodynamic considerations,and the generation of carbon capture microcapsules through droplet microfluidics are provided.This review highlights the substantial potential of droplet microfluidics as a promising technique for large-scale carbon capture microcapsule production,which could play a significant role in achieving carbon neutralization and emission reduction goals.

Micro-nano-fabrication of green functional materials by multiphase microfluidics for environmental and energy applications

Multiphase microfluidic has emerged as a powerful platform to produce novel materials with tailor-designed functionalities,as microfluidic fabrication provides precise controls over the size,component,and structure of resultant materials.Recently,functional materials with well-defined micro-/nanostructures fabricated by microfluidics find important applications as environmental and energy materials.This review first illustrated in detail how different structures or shapes of droplet and jet templates are formed by typical configurations of microfluidic channel networks and multiphase flow systems.Subsequently,recent progresses on several representative energy and environmental applications,such as water purification,water collecting and energy storage,were overviewed.Finally,it is envisioned that integrating microfluidics and other novel materials will play increasing important role in contributing environmental remediation and energy storage in near future.

Microfluidic thermotaxic selection of highlymotile sperm and in vitro fertilization

The selection of the most motile and functionally competent sperm is an essential basis for in vitro fertilization(IVF)and normal embryonic development.Widely adopted clinical approaches for sperm sample processing intensely rely on centrifugation and wash steps that may induce mechanical damage and oxidative stress to sperm.Although a few microfluidic sperm sorting devices may avoid these adverse effects by exploiting intrinsic guidance mechanisms of sperm swimming,none of these approaches have been fully validated by clinical-grade assessment criteria.In this study,a microfluidic sperm sorting device that enables the selection of highly motile and functional sperm via their intrinsic thermotaxis is presented.Bioinspired by the temperature microenvironment in the fallopian tube during natural sperm selection,a microfluidic device with controllable temperature gradients along the sperm separation channel was designed and fabricated.This study investigated the optimal temperature conditions for human sperm selection and fully characterized thermotaxis-selected sperm with 45 human sperm samples.Results indicated that a temperature range of 35–36.5℃along the separation channel significantly improves human sperm motility rate((85.25±6.28)%vs.(60.72±1.37)%;P=0.0484),increases normal sperm morphology rate((16.42±1.43)%vs.(12.55±0.88)%;P<0.0001),and reduces DNA fragmentation((7.44±0.79)%vs.(10.36±0.72)%;P=0.0485)compared to the nonthermotaxis group.Sperm thermotaxis is species-specific,and selected mouse sperm displayed the highest motility in response to a temperature range of 36–37.5℃ along the separation channel.Furthermore,IVF experiments indicated that the selected sperm permitted an increased fertilization rate and improved embryonic development from zygote to blastocyst.This microfluidic thermotaxic selection approach will be translated into clinical practice to improve the IVF success rate for patients with oligozoospermia and asthenozoospermia.

Rapid fabrication of modular 3D paper-basedmicrofluidic chips using projection-based 3D printing

Paper-based microchips have different advantages,such as better biocompatibility,simple production,and easy handling,making them promising candidates for clinical diagnosis and other fields.This study describes amethod developed to fabricate modular three-dimensional(3D)paper-based microfluidic chips based on projection-based 3D printing(PBP)technology.A series of two-dimensional(2D)paper-based microfluidic modules was designed and fabricated.After evaluating the effect of exposure time on the accuracy of the flow channel,the resolution of this channel was experimentally analyzed.Furthermore,several 3D paper-based microfluidic chips were assembled based on the 2D ones using different methods,with good channel connectivity.Scaffold-based 2D and hydrogel-based 3D cell culture systems based on 3D paper-based microfluidic chips were verified to be feasible.Furthermore,by combining extrusion 3D bioprinting technology and the proposed 3D paper-based microfluidic chips,multiorgan microfluidic chips were established by directly printing 3D hydrogel structures on 3D paperbased microfluidic chips,confirming that the prepared modular 3D paper-based microfluidic chip is potentially applicable in various biomedical applications.

Microfluidic preparation of surfactant-free ultrafine DAAF with tunable particle size for insensitive initiator explosives

High purity and ultrafine DAAF(u-DAAF)is an emerging insensitive charge in initiators.Although there are many ways to obtain u-DAAF,developing a preparation method with stable operation,accurate control,good quality consistency,equipment miniaturization,and minimum manpower is an inevitable requirement to adapt to the current social technology development trend.Here reported is the microfluidic preparation of u-DAAF with tunable particle size by a passive swirling microreactor.Under the guidance of recrystallization growth kinetics and mixing behavior of fluids in the swirling microreactor,the key parameters(liquid flow rate,explosive concentration and crystallization temperature)were screened and optimized through screening experiments.Under the condition that no surfactant is added and only experimental parameters are controlled,the particle size of recrystallized DAAF can be adjusted from 98 nm to 785 nm,and the corresponding specific surface area is 8.45 m^(2)·g^(-1)to 1.33 m^(2)·g^(-1).In addition,the preparation method has good batch stability,high yield(90.8%-92.6%)and high purity(99.0%-99.4%),indicating a high practical application potential.Electric explosion derived flyer initiation tests demonstrate that the u-DAAF shows an initiation sensitivity much lower than that of the raw DAAF,and comparable to that of the refined DAAF by conventional spraying crystallization method.This study provides an efficient method to fabricate u-DAAF with narrow particle size distribution and high reproducibility as well as a theoretical reference for fabrication of other ultrafine explosives.

Application of microfluidic chip technology in pharmaceutical analysis:A review

The development of pharmaceutical analytical methods represents one of the most significant aspects of drug development. Recent advances in microfabrication and microfluidics could provide new approaches for drug analysis, including drug screening, active testing and the study of metabolism. Microfluidic chip technologies, such as lab-on-a-chip technology, three-dimensional (3D) cell culture, organs-on-chip and droplet techniques, have all been developed rapidly. Microfluidic chips coupled with various kinds of detection techniques are suitable for the high-throughput screening, detection and mechanistic study of drugs. This review highlights the latest (2010–2018) microfluidic technology for drug analysis and discusses the potential future development in this field.

Advances in isolation and detection of circulating tumor cells based on microfluidics

Circulating tumor cells(CTCs) are the cancer cells that circulate in the peripheral blood after escaping from the original or metastatic tumors. CTCs could be used as non-invasive source of clinical information in early diagnosis of cancer and evaluation of cancer development. In recent years, CTC research has become a hotspot field wherein many novel CTC detection technologies based on microfluidics have been developed. Great advances have been made that exhibit obvious technical advantages, but cannot yet satisfy the current clinical requirements. In this study, we review the main advances in isolation and detection methods of CTC based on microfluidics research over several years, propose five technical indicators for evaluating these methods, and explore the application prospects. We also discuss the concepts, issues, approaches, advantages, limitations, and challenges with an aim of stimulating a broader interest in developing microfluidics-based CTC detection technology.

Advances in tumor-endothelial cells co-culture and interaction on microfluidics

The metastasis in which the cancer cells degrade the extracellular matrix （ECM） and invade to the sur- rounding and far tissues of the body is the leading cause of mortality in cancer patients, With a lot of advancement in the field, yet the biological cause of metastasis are poorly understood, The microfluidic system provides advanced technology to reconstruct a variety of in vivo-like environment for studying the interactions between tumor ceils （TCs） and endothelial ceils （ECs）. This review gives a brief account of both two-dimensional models and three-dimensional microfluidic systems for the analysis of TCs-ECs co- culture as well as their applications to anti-cancer drug screening, Furthermore, the advanced methods for analyzing cell-to-cell interactions at single-cell level were also discussed,

Microfluidic temperature sensor based on temperature-dependent dielectric property of liquid

We propose a low-cost compact microfluidic temperature sensor by virtue of the temperature-dependent permittivity of liquid.The sensor is composed of a coplanar waveguide(CPW)transmission line loaded with three resonators and a microfluidic plate with three channels.The resonant frequency of each resonator relies on the temperature-dependent dielectric property of liquid in corresponding channel,which therefore can be used to extract the temperature.The proposed sensor features a compact size and low cost since it requires only micro fluid volume instead of additional electronic components to produce significant frequency shift with changing temperature.Moreover,it exhibits decent accuracy and stability in a temperature sensing range from 30℃ to 95℃.A theoretical analysis of the sensor is provided,followed by the detailed characterization method,and a prototype is designed,manufactured,and measured to verify the theoretical analysis.

Progress of Microfluidics for Biology and Medicine

Microfluidics has been considered as a potential technology to miniaturize the conventional equipments and technologies. It offers advantages in terms of small volume, low cost, short reaction time and highthroughput. The applications in biology and medicine research and related areas are almost the most extensive and profound. With the appropriate scale that matches the scales of cells, microfluidics is well positioned to contribute significantly to cell biology. Cell culture, fusion and apoptosis were successfully performed in microfluidics. Microfluidics provides unique opportunities for rare circulating tumor cells isolation and detection from the blood of patients, which furthers the discovery of cancer stem cell biomarkers and expands the understanding of the biology of metastasis. Nucleic acid amplification in microfluidics has extended to single-molecule, high-throughput and integration treatment in one chip. DNA computer which is based on the computational model of DNA biochemical reaction will come into practice from concept in the future. In addition, microfluidics offers a versatile platform for protein-protein interactions, protein crystallization and high-throughput screening. Although microfluidics is still in its infancy, its great potential has already been demonstrated and will provide novel solutions to the high-throughput applications.

Electroosmotic oscillatory flow of micropolar fluid in microchannels:application to dynamics of blood flow in microfluidic devices

The electroosmotic flow of a micropolar fluid in a microchannel bounded by two parallel porous plates undergoing periodic vibration is studied. The equations for conservation of linear and angular momentums and Gauss＇s law of charge distribution are solved within the framework of the Debye-Hückel approximation. The fluid velocity and microrotation are assumed to depend linearly on the Reynolds number. The study shows that the amplitude of microrotation is highly sensitive to the changes in the magnitude of the suction velocity and the width of the microchannel. An increase in the micropolar parameter gives rise to a decrease in the amplitude of microrotation. Numerical estimates reveal that the microrotation of the suspended microelements in blood also plays an important role in controlling the electro-osmotically actuated flow dynamics in microbio-fluidic devices.

EXPERIMENTAL STUDY ON THE HOT EMBOSSING POLYMER MICROFLUIDIC CHIP

Experiments are used to study the fabrication of polymer microfluidic chip with hot embossing method. The pattern fidelity with respect to the process parameters is analyzed. Experiment results show that the relationship between the imprint temperature and the microchannel width is approximately exponential. However, the depth of micro channel isn＇t sensitive to the imprint temperature. When the imprint pressure is larger than 1 MPa and the imprint time is longer than 2 min, the increasing of imprint pressure and holding time has little impact on the microchannel width. So over long holding time is not needed in hot embossing. Based on the experiment analysis, a series of optimization process parameters is obtained and a fine microfluidic chip is fabricated. The electrophoresis separation experiment are used to verify the microfluidic chip performance after bonding. The results show that 100bp-ladder DNA sample can be separated in less than 5 min successfully.

Microfluidic three-dimensional cell culture of stem cells for high-throughput analysis

Although the recent advances in stem cell engineering have gained a great deal of attention due to their high potential in clinical research,the applicability of stem cells for preclinical screening in the drug discovery process is still challenging due to difficulties in controlling the stem cell microenvironment and the limited availability of high-throughput systems.Recently,researchers have been actively developing and evaluating three-dimensional(3D)cell culture-based platforms using microfluidic technologies,such as organ-on-a-chip and organoid-on-a-chip platforms,and they have achieved promising breakthroughs in stem cell engineering.In this review,we start with a comprehensive discussion on the importance of microfluidic 3D cell culture techniques in stem cell research and their technical strategies in the field of drug discovery.In a subsequent section,we discuss microfluidic 3D cell culture techniques for high-throughput analysis for use in stem cell research.In addition,some potential and practical applications of organ-on-a-chip or organoid-on-a-chip platforms using stem cells as drug screening and disease models are highlighted.