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.

Nano-scale Reinforcements and Properties of Al-Si-Cu Alloy Processed by High-Pressure Torsion

To improve the comprehensive mechanical properties of Al-Si-Cu alloy,it was treated by a high-pressure torsion process,and the effect of the deformation degree on the microstructure and properties of the Al-Si-Cu alloy was studied.The results show that the reinforcements(β-Si andθ-CuAl_(2)phases)of the Al-Si-Cu alloy are dispersed in theα-Al matrix phase with finer phase size after the treatment.The processed samples exhibit grain sizes in the submicron or even nanometer range,which effectively improves the mechanical properties of the material.The hardness and strength of the deformed alloy are both significantly raised to 268 HV and 390.04 MPa by 10 turns HPT process,and the fracture morphology shows that the material gradually transits from brittle to plastic before and after deformation.The elements interdiffusion at the interface between the phases has also been effectively enhanced.In addition,it is found that the severe plastic deformation at room temperature induces a ternary eutectic reaction,resulting in the formation of ternary Al+Si+CuAl_(2)eutectic.

Experimental and Finite Element Analysis of Corroded High-Pressure Pipeline Repaired by Laminated Composite

Repairs of corroded high-pressure pipelines are essential for fluids transportation under high pressure.One of the methods used in their repairs is the use of layered composites.The composite used must have the necessary strength.Therefore,the experiments and analytical solutions presented in this paper are performed according to the relevant standards and codes,including ASME PCC-2,ASME B31.8S,ASME B31.4,ISO 24817 and ASME B31.G.In addition,the experimental tests are replicated numerically using the finite element method.Setting the strain gauges at different distances from the defect location,can reduce the nonlinear effects,deformation,and fluctuations due to the high pressure.The direct relationship between the depth of an axial defect and the stress concentration is observed at the inner side edges of the defect.Composite reparation reduces the non-linearities related to the sharp variation of the geometry and a more reliable numerical simulation could be performed.

Green microfluidics in microchemical engineering for carbon neutrality

The concept of“carbon neutrality”poses a huge challenge for chemical engineering and brings great opportunities for boosting the development of novel technologies to realize carbon offsetting and reduce carbon emissions.Developing high-efficient,low-cost,energy-efficient and eco-friendly microfluidicbased microchemical engineering is of great significance.Such kind of“green microfluidics”can reduce carbon emissions from the source of raw materials and facilitate controllable and intensified microchemical engineering processes,which represents the new power for the transformation and upgrading of chemical engineering industry.Here,a brief review of green microfluidics for achieving carbon neutral microchemical engineering is presented,with specific discussions about the characteristics and feasibility of applying green microfluidics in realizing carbon neutrality.Development of green microfluidic systems are categorized and reviewed,including the construction of microfluidic devices by bio-based substrate materials and by low carbon fabrication methods,and the use of more biocompatible and nondestructive fluidic systems such as aqueous two-phase systems(ATPSs).Moreover,low carbon applications benefit from green microfluidics are summarized,ranging from separation and purification of biomolecules,high-throughput screening of chemicals and drugs,rapid and cost-effective detections,to synthesis of fine chemicals and novel materials.Finally,challenges and perspectives for further advancing green microfluidics in microchemical engineering for carbon neutrality are proposed and discussed.

Thermal and ignition properties of hexanitrostilbene(HNS) microspheres prepared by droplet microfluidics

HNS-IV(Hexanitrostilbene-IV) is the main charge of the exploding foil initiators(EFI), and the microstructure of the HNS will directly affect its density, flowability, sensitivity, and stability. HNS microspheres were prepared using droplet microfluidics, and the particle size, morphology, specific surface area, thermal performance, and ignition threshold of the HNS microspheres were characterized and tested. The results shown that the prepared HNS microspheres have high sphericity, with an average particle size of 20.52 μm(coefficient of variation less than 0.2), and a specific surface area of 21.62 m^(2)/g(6.87 m^(2)/g higher than the raw material). Without changing the crystal structure and thermal stability of HNS-IV, this method significantly enhances the sensitivity of HNS-IV to short pulses and reduces the ignition threshold of the slapper detonator to below 1000 V. This will contribute to the miniaturization and low cost of EFI.

Recent progress in aptamer-based microfluidics for the detection of circulating tumor cells and extracellular vesicles

Liquid biopsy is a technology that exhibits potential to detect cancer early,monitor therapies,and predict cancer prognosis due to its unique characteristics,including noninvasive sampling and real-time analysis.Circulating tumor cells(CTCs)and extracellular vesicles(EVs)are two important components of circulating targets,carrying substantial disease-related molecular information and playing a key role in liquid biopsy.Aptamers are single-stranded oligonucleotides with superior affinity and specificity,and they can bind to targets by folding into unique tertiary structures.Aptamer-based microfluidic platforms offer new ways to enhance the purity and capture efficiency of CTCs and EVs by combining the advantages of microfluidic chips as isolation platforms and aptamers as recognition tools.In this review,we first briefly introduce some new strategies for aptamer discovery based on traditional and aptamer-based microfluidic approaches.Then,we subsequently summarize the progress of aptamer-based microfluidics for CTC and EV detection.Finally,we offer an outlook on the future directional challenges of aptamer-based microfluidics for circulating targets in clinical applications.

Junction matters in hydraulic circuit bio-design of microfluidics

Microfluidic channels are at micrometer scales;thus,their fluid flows are laminar,resulting in the linear dependence of pressure drop on flow rate in the length of the channel.The ratio of the pressure drop to flow rate,referred to as resistance,depends on channel size and dynamic viscosity.Usually,a microfluidic chip is analogous to an electric circuit in design,but the design is adjusted to optimize channel size.However,whereas voltage loss is negligible at the nodes of an electric circuit,hydraulic pressure drops at the nodes of microfluidic chips by a magnitude are comparable to the pressure drops in the straight channels.Here,we prove by experiment that one must fully consider the pressure drops at nodes so as to accurately design a precise microfluidic chip.In the process,we numerically calculated the pressure drops at hydraulic nodes and list their resistances in the range of flows as concerned.We resorted to machine learning to fit the calculated results for complex junctions.Finally,we obtained a library of node resistances for common junctions and used them to design three established chips that work for single-cell analysis and for precision allocation of solutes(in gradient and averaging concentration microfluidic networks).Endothelial cells were stimulated by generating concentrations of adriamycin hydrochloride from the last two microfluidic networks,and we analyzed the response of endothelial cells.The results indicate that consideration of junction resistances in design calculation brings experimental results closer to the design values than usual.This approach may therefore contribute to providing a platform for the precise design of organ chips.

A new transition metal diphosphideα-MoP_(2) synthesized by a high-temperature and high-pressure technique

Monoclinicα-MoP_(2),with the OsGe2-type structure(space group C2/m,Z=4)and lattice parameters a=8.7248(11)Å,b=3.2322(4)Å,c=7.4724(9)Å,andβ=119.263°,was synthesized under a pressure of 4~GPa at a temperature between 1100℃and 1200℃.The structure ofα-MoP_(2) and its relationship to other transition metal diphosphides are discussed.Surprisingly,the ambient pressure phase orthorhombicβ-MoP_(2)(space group Cmc21)is denser in structure thanα-MoP_(2).Room-temperature high-pressure x-ray diffraction studies exclude the possibility of phase transition fromβ-MoP_(2) to α-MoP_(2),suggesting thatα-MoP_(2) is a stable phase at ambient conditions;this is also supported by the total energy and phonon calculations.

An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening

Background:Tumor cell heterogeneity mediated drug resistance has been recognized as the stumbling block of cancer treatment.Elucidating the cytotoxicity of anticancer drugs at single-cell level in a high-throughput way is thus of great value for developing precision therapy.However,current techniques suffer from limitations in dynamically characterizing the responses of thousands of single cells or cell clones presented to multiple drug conditions.Methods:We developed a new microfluidics-based“SMART”platform that is Simple to operate,able to generate a Massive single-cell array and Multiplex drug concentrations,capable of keeping cells Alive,Retainable and Trackable in the microchambers.These features are achieved by integrating a Microfluidic chamber Array(4320 units)and a sixConcentration gradient generator(MAC),which enables highly efficient analysis of leukemia drug effects on single cells and cell clones in a high-throughput way.Results:A simple procedure produces 6 on-chip drug gradients to treat more than 3000 single cells or single-cell derived clones and thus allows an efficient and precise analysis of cell heterogeneity.The statistic results reveal that Imatinib(Ima)and Resveratrol(Res)combination treatment on single cells or clones is much more efficient than Ima or Res single drug treatment,indicated by the markedly reduced half maximal inhibitory concentration(IC50).Additionally,single-cell derived clones demonstrate a higher IC_(50) in each drug treatment compared to single cells.Moreover,primary cells isolated from two leukemia patients are also found with apparent heterogeneity upon drug treatment on MAC.Conclusions:This microfluidics-based“SMART”platform allows high-throughput single-cell capture and culture,dynamic drug-gradient treatment and cell response monitoring,which represents a new approach to efficiently investigate anticancer drug effects and should benefit drug discovery for leukemia and other cancers.

Numerical Simulation Analysis of the Transformer Fire Extinguishing Process with a High-Pressure Water Mist System under Different Conditions

To thoroughly study the extinguishing effect of a high-pressure water mist fire extinguishing system when a transformer fire occurs,a 3D experimental model of a transformer is established in this work by employing Fire Dynamics Simulator(FDS)software.More specifically,by setting different parameters,the process of the highpressure water mist fire extinguishing system with the presence of both diverse ambient temperatures and water mist sprinkler laying conditions is simulated.In addition,the fire extinguishing effect of the employed high-pressure water mist system with the implementation of different strategies is systematically analyzed.The extracted results show that a fire source farther away fromthe centerline leads to a lower local temperature distribution.In addition,as the ambient temperature increases,the temperature above the fire source decreases,while the temperature and the concentrationof theupperflue gas layer bothdecrease.Interestingly,after thehigh-pressurewatermist sprinkler begins to operate,both the temperature distribution above the fire source and the concentration of the flue gas decrease,which indicates that the high-pressure water mist system plays the role of cooling and dust removal.By comparing various sprinkler laying methods,it is found that the lower sprinkler height has a better effect on the temperature above the fire source,the temperature of the upper flue gas layer,and the concentration of the flue gas.Moreover,when the sprinkler is spread over thewhole transformer,the cooling effect on both the temperature above the fire source and the temperature of the upper flue gas layer is good,whereas the change in the concentration of the flue gas above the fire source is not obvious compared to the case where the sprinkler is not fully spread.

High-pressure new phases of V–N compounds

The high-pressure diagram of V–N compounds is enriched by proposed seven new stable high-pressure phases.The P-1-VN_4with the armchair N-rich structure may be quenched to ambient conditions.The formed N–N covalent bond plays an important role for the structural stability of N-chain.The charge transfer results in a V–N ionic bond interaction,which further improves the stability of N-chain structure.The P-1-VN_4,P4mnc-VN_8,and Immm-VN_(10)with the outstanding detonation properties have potential application in explosive field.

The discovery of TiO_(2)-Ⅱ,the α-PbO_(2)-structured high-pressure polymorph of rutile,in the Suizhou L6 chondrite

We report the discovery of TiO_(2)-Ⅱ in the unmelted rock of the shocked Suizhou L6 chondrite.Natural TiO_(2)-Ⅱ was previously found in ultrahigh-pressure metamorphic and mantle-derived rocks,terrestrial impact structures,and tektite.Our microscopic,Raman spectroscopic,electron microprobe and transmission electron microscopic investigations have revealed:(1) All observed TiO_(2)-Ⅱ grains are related with ilmenite and pyrophanite;(2) TiO_(2)-Ⅱ occurs as needle-and leaf-shaped inclusions in llmenite and patch-,tape-shaped body in pyrophanite;(3)The composition of TiO_(2)-Ⅱ is identical with that of its precursor rutile;(4) The Raman spectrum of TiO_(2)-Ⅱ is in good agreement with that of natural and synthesized α-PbO_(2)-type TiO_(2);(5) TiO_(2)-Ⅱ occurs mainly in the form of well-ordered nano-domains and small mis-orientation among the domains can be observed.(6) All electron diffraction reflections from TiO_(2)-Ⅱ can be indexed to α-PbO_(2)structure in space group Pbcn with lattice parameters of a=4.481 ?,b=5.578 A and c=4.921 A;(7) The exsolution inclusions of rutile from host ilmenite are mostly connected with an alternation process along the lamellar twinning plane of ilmenite induced by shockinduced high pressure and high temperature;(8) The P-T regime of 20-25 GPa and 1000 ℃ estimated for the Suizhou unmelted rock is suitable for phase transition of rutile into TiO_(2)-Ⅱ phase.

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.

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.

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.

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.

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,