Cleat serves as the primary flow pathway for coalbed methane(CBM)and water.However,few studies consider the impact of local contact on two-phase flow within cleats.A visual generalized model of endogenous cleats was c...Cleat serves as the primary flow pathway for coalbed methane(CBM)and water.However,few studies consider the impact of local contact on two-phase flow within cleats.A visual generalized model of endogenous cleats was constructed based on microfluidics.A microscopic and mesoscopic observation technique was proposed to simultaneously capture gas-liquid interface morphology of pores and throat and the two-phase flow characteristics in entire cleat system.The local contact characteristics of cleats reduced absolute permeability,which resulted in a sharp increase in the starting pressure.The reduced gas flow capacity narrowed the co-infiltration area and decreased water saturation at the isotonic point in a hydrophilic environment.The increased local contact area of cleats weakened gas phase flow capacity and narrowed the co-infiltration area.Jumping events occurred in methane-water flow due to altered porosity caused by local contact in cleats.The distribution of residual phases changed the jumping direction on the micro-scale as well as the dominant channel on the mesoscale.Besides,jumping events caused additional energy dissipation,which was ignored in traditional two-phase flow models.This might contribute to the overestimation of relative permeability.The work provides new methods and insights for investigating unsaturated flow in complex porous media.展开更多
Drug research and development(R&D)plays a crucial role in supporting public health.However,the traditional drug-discovery paradigm is hindered by significant drawbacks,including high costs,lengthy development time...Drug research and development(R&D)plays a crucial role in supporting public health.However,the traditional drug-discovery paradigm is hindered by significant drawbacks,including high costs,lengthy development timelines,high failure rates,and limited output of new drugs.Recent advances in micro/nanotechnology,along with progress in computer science,have positioned microfluidics and artificial intelligence(AI)as promising transformative tools for drug development.Microfluidics offers miniaturized,multiplexed,and versatile platforms for high-dimensional data acquisition,while AI enables the rapid processing of complex,large-scale microfluidic data;together,they are accelerating a paradigm shift in the drug-discovery process.This paper first outlines the mainstream microfluidic strategies and AI models used in drug R&D.It then summarizes and discusses real-world applications of the integrated use of these technologies across various stages of drug discovery,including early drug discovery,drug screening,drug evaluation,drug manufacturing,and drug delivery systems.Finally,the paper examines the main limitations of microfluidics and AI in drug R&D and offers an outlook on the future convergence of these technologies.展开更多
Soft rot is a destructive disease that inflicts significant losses on agricultural production and the economy post-harvest.Biocontrol strategies based on antagonistic microorganisms have a broad application prospect t...Soft rot is a destructive disease that inflicts significant losses on agricultural production and the economy post-harvest.Biocontrol strategies based on antagonistic microorganisms have a broad application prospect to fight against plant pathogens.This study utilized fluorescence-activated droplet sorting(FADS)technology as an alternative to traditional plate culture methods to isolate microorganisms with antagonistic activity against the soft rot pathogen Erwinia carotovora Ecc15.Initially,the culture performance of the FADS platform was evaluated by analyzing bacterial diversity in droplet culture samples and agar plate culture samples,our data showed that droplet culture exhibited higher species richness and diversity than plate culture,and more than 95%of the operational taxonomic units(OTUs)in the droplet samples belonged to the rare biosphere.Additionally,we developed a green fluorescent protein(GFP)-Ecc15-based FADS screening system,which achieved an enrichment ratio of up to 148.Using this system,we successfully screened 32 antagonistic bacteria from rhizosphere soil sample of healthy konjac plants,and some may be novel microbial resources,including the genera Lelliottia,Buttiauxella and Leclercia.Notably,strain D-62 exhibited the strongest antibacterial ability against Ecc15,with an inhibition zone diameter of(20.86±1.56)mm.In vivo experiments conducted on the corms of Amorphophallus konjac demonstrated that strain D-62 could effectively reduce the infection ability of Ecc15 to the corms,indicating that strain D-62 has the potential to be developed as a biocontrol agent.Our findings suggested that the FADS screening system showed a screening efficiency approximately 3×10^(3)times higher than plate screening system,while significantly reducing costs of infrastructure,labor and consumables,it provides theoretical guidance for the screening of other plant pathogen biocontrol bacteria.展开更多
Due to the rapid development and potential applications of iron(Ⅲ)-alginate(Fe-Alg)microgels in biomedical as well as environmental engineering,this study explores the preparation and characterization of spherical Fe...Due to the rapid development and potential applications of iron(Ⅲ)-alginate(Fe-Alg)microgels in biomedical as well as environmental engineering,this study explores the preparation and characterization of spherical Fe-Alg microgels using droplet microfluidics combined with an external ionic crosslinking method.This study focused on the role of Fe^(3+)and examined its effects on the physical/chemical properties of microgels under different ionic conditions and reduced or oxidized states.The pH-dependent release behavior of Fe^(3+)from these microgels demonstrates their potential biomedical and environmental applications.Furthermore,the microgels can exhibit magnetism simply by utilizing in situ oxidation,which can be further used for targeted drug delivery and magnetic separation technologies.展开更多
Energetic materials,characterized by their capacity to store and release substantial energy,hold pivotal significance in some fields,particularly in defense applications.Microfluidics,with its ability to manipulate fl...Energetic materials,characterized by their capacity to store and release substantial energy,hold pivotal significance in some fields,particularly in defense applications.Microfluidics,with its ability to manipulate fluids and facilitate droplet formation at the microscale,enables precise control of chemical reactions.Recent scholarly endeavors have increasingly harnessed microfluidic reactors in the realm of energetic materials,yielding morphologically controllable particles with enhanced uniformity and explosive efficacy.However,crucial insights into microfluidic-based methodologies are dispersed across various publications,necessitating a systematic compilation.Accordingly,this review addresses this gap by concentrating on the synthesis of energetic materials through microfluidics.Specifically,the methods based on micro-mixing and droplets in the previous papers are summarized and the strategies to control the critical parameters within chemical reactions are discussed in detail.Then,the comparison in terms of advantages and disadvantages is attempted.As demonstrated in the last section regarding perspectives,challenges such as clogging,dead zones,and suboptimal production yields are non-ignoble in the promising fields and they might be addressed by integrating sound,optics,or electrical energy to meet heightened requirements.This comprehensive overview aims to consolidate and analyze the diverse array of microfluidic approaches in energetic material synthesis,offering valuable insights for future research directions.展开更多
Radionuclide imaging is divided into positron emission tomography and single photon emission tomography and is widely used in clinical practice for diagnosis and treatment,as well as in clinical research for the devel...Radionuclide imaging is divided into positron emission tomography and single photon emission tomography and is widely used in clinical practice for diagnosis and treatment,as well as in clinical research for the development and evaluation of new therapies.Although it is a visually intuitive form of three-dimensional functional imaging,this modality requires the injection of radiopharmaceuticals labeled with positron-or gamma-emitting isotopes into patients to assess and quantify anabolism,gene expression,and other processes.For this reason,radiopharmaceuticals must undergo rigorous quality control(QC)to ensure product purity,efficacy,and safety.Traditional QC of pharmaceuticals is manual,requiring specially trained personnel,a range of expensive analytical and chemical equipment and laboratory space,the consumption of many samples,and usually a long time.Compared with ordinary pharmaceuticals,radiopharmaceuticals have the following unique characteristics:radioactivity,short lifetime,low synthesis yield,and high cost.Therefore,analytical methods and instrumentation must be exclusively developed for the QC of radiopharmaceuticals to avoid large losses owing to radioactive decay or handling.Microfluidics integrates microchannels or microchambers into several square centimeters of a microscale chip through micro-nanofabrication,allowing a precise manipulation of the fluid in microtubules,where various traditional physical,chemical,or biological experiments occur.Microfluidics is gaining attention in the field of analytical testing owing to significantly reduced consumption of samples and reagents,reduced analysis time,increased detection sensitivity,increased multiplexing,and reduced instrument size.Features such as micro size,micro volume,high sensitivity,and on-line testing have led to increasing interest in microfluidics.This review covers the development of integrated microfluidic QC devices that can automatically process,test,analyze,and calculate completed test metrics online.展开更多
Nano-TATB was developed in microchannels by physical method and chemical method,respectively.The effects of total flow rate,number of microreactor plates,solvent/non-solvent ratio and temperature on the particle size ...Nano-TATB was developed in microchannels by physical method and chemical method,respectively.The effects of total flow rate,number of microreactor plates,solvent/non-solvent ratio and temperature on the particle size of TATB in the physical method were studied.Prepared TATB were characterized by Nano Sizer,Scanning Electron Microscopy,Specific surface aperture analyzer,X-ray diffraction,Fourier transform infrared spectroscopy and Differential Scanning Calorimetry.The results show that the TATB obtained by physical method and chemical method are spherical,with average particle size of 130.66 nm and 108.51 nm,respectively.Specific surface areas of TATB obtained by physical and chemical methods are 21.37 m^(2)/g and 21.91 m^(2)/g,respectively.Compared with the specific surface area of micro-TATB(0.0808 m^(2)/g),the specific surface area of nano-TATB is significantly increased.DSC test results show that the smaller the particle size of TATB,the lower the thermal decomposition temperature.In addition,by simulating the mixing state of fluid in microchannels and combining with the classical nucleation theory,the mechanism of preparing nano-TATB by microchannels was proposed.展开更多
Lightweight and mechanically strong natural silk fibers have been extensively investigated over the past decades.Inspired by this research,many artificial spinning techniques(wet spinning,dry spinning,electrospinning,...Lightweight and mechanically strong natural silk fibers have been extensively investigated over the past decades.Inspired by this research,many artificial spinning techniques(wet spinning,dry spinning,electrospinning,etc.)have been developed to fabricate robust protein fibers.As the traditional spinning methods provide poor control over the as-spun fibers,microfluidics has been integrated with these techniques to allow the fabrication of biological fibers in a well-designed manner,with simplicity and cost efficiency.The mechanical behavior of the developed fibers can be precisely modulated by controlling the type iop and size of microfluidic channel,flow rate,and shear force.This technique has been successfully used to manufacture a broad range of protein fibers,and can accelerate the production and application of protein fibers in various fields.This review outlines recent progress in the design and fabrication of protein-based fibers based on microfluidics.We first briefly discuss the natural spider silk-spinning process and the microfluidics spinning process.Next,the fabrication and mechanical properties of regenerated protein fibers via microfluidics are discussed,followed by a discussion of recombinant protein fibers.Other sourced protein fibers are also reviewed in detail.Finally,a brief outlook on the development of microfluidic technology for producing protein fibers is presented.展开更多
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 ear...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.展开更多
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...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.展开更多
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....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.展开更多
Advances in microbiology rely on innovations in technology. Droplet microfluidics, as a versatile and powerful technique that allows high-throughput generation and manipulation of subnanoliter volume droplets, has bec...Advances in microbiology rely on innovations in technology. Droplet microfluidics, as a versatile and powerful technique that allows high-throughput generation and manipulation of subnanoliter volume droplets, has become an indispensable tool shifting experimental paradigms in microbiology. Droplet microfluidics has opened new avenues to various microbiological research, from resolving single-cell heterogeneity to investigating spatiotemporal dynamics of microbial communities, from precise quantitation of microbiota to systematic decipherment of microbial interactions, and from isolating rare and uncultured microbes to improving genetic engineered strains. In this review, we present recent advances of droplet microfluidics in various fields of microbiology: i) microbial cultivation, ii) microorganism detection and characterization, iii) antibiotic susceptibility testing, iv) microbial interactions, v) microbial biotechnology.We also provide our perspectives on the challenges and future directions for droplet microfluidic-based microbiology research.展开更多
Additive manufacturing plays a vital role in the food,mechanical,pharmaceutical,and medical fields.Within these fields,medical additive manufacturing has led to especially obvious improvements in medical instruments,p...Additive manufacturing plays a vital role in the food,mechanical,pharmaceutical,and medical fields.Within these fields,medical additive manufacturing has led to especially obvious improvements in medical instruments,prostheses,implants,and so forth,based on the advantages of cost-effectiveness,customizability,and quick manufacturing.With the features of precise structural control,high throughput,and good component manipulation,microfluidic techniques present distinctive benefits in medical additive manufacturing and have been applied in the areas of drug discovery,tissue engineering,and organs on chips.Thus,a comprehensive review of microfluidic techniques for medical additive manufacturing is useful for scientists with various backgrounds.Herein,we review recent progress in the development of microfluidic techniques for medical additive manufacturing.We evaluate the distinctive benefits associated with microfluidic technologies for medical additive manufacturing with respect to the fabrication of droplet/fiber templates with different structures.Extensive applications of microfluidic techniques for medical additive manufacturing are emphasized,such as cell guidance,three-dimensional(3D)cell culture,tissue assembly,and cell-based therapy.Finally,we present challenges in and future perspectives on the development of microfluidics for medical additive manufacturing.展开更多
Tumor heterogeneity plays a critical role in the determination of appropriate anticancer therapy.As cir-culating tumor cells(CTCs)contain all tumor-related information,the genetic changes on CTCs could help us choose ...Tumor heterogeneity plays a critical role in the determination of appropriate anticancer therapy.As cir-culating tumor cells(CTCs)contain all tumor-related information,the genetic changes on CTCs could help us choose the appropriate treatments for different patients.Single-base mutations are very common in tumor genetic changes which may result in drug resistance.Here,we introduce a single-cell mutation de-tection platform based on droplet microfluidics.This platform integrates cell capsulation,cell lysis,poly-merase chain reaction(PCR)and the observation process.The droplets’generation speed is over 6000 per minute and more than 600 cells could be encapsulated in one second.To verify the performance of our platform in practical use,we performed the mutation analysis of 4 kinds of cells with our platform and noted that the genetic status of each single cell was clearly discriminated.Moreover,these results agreed with those from direct sequencing.Compared with other forms of single-cell mutation detection techniques,our platform has high throughput,short experimental time and less experimental operations.展开更多
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 emiss...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.展开更多
Traditional diagnostic strategies for infectious disease detection require benchtop instruments that are inappropriate for point-of-care testing(POCT). Emerging microfluidics, a highly miniaturized, automatic, and int...Traditional diagnostic strategies for infectious disease detection require benchtop instruments that are inappropriate for point-of-care testing(POCT). Emerging microfluidics, a highly miniaturized, automatic, and integrated technology,are a potential substitute for traditional methods in performing rapid, low-cost, accurate, and on-site diagnoses.Molecular diagnostics are widely used in microfluidic devices as the most effective approaches for pathogen detection.This review summarizes the latest advances in microfluidics-based molecular diagnostics for infectious diseases from academic perspectives and industrial outlooks. First, we introduce the typical on-chip nucleic acid processes,including sample preprocessing, amplification, and signal read-out. Then, four categories of microfluidic platforms are compared with respect to features, merits, and demerits. We further discuss application of the digital assay in absolute nucleic acid quantification. Both the classic and recent microfluidics-based commercial molecular diagnostic devices are summarized as proof of the current market status. Finally, we propose future directions for microfluidics-based infectious disease diagnosis.展开更多
As a marine bacterial pathogen, Photobacterium damselae subsp. damselae(PDD) is distributed in seawater worldwide. It can infect different animals as well as humans, even cause deaths. The highly conserved regions of ...As a marine bacterial pathogen, Photobacterium damselae subsp. damselae(PDD) is distributed in seawater worldwide. It can infect different animals as well as humans, even cause deaths. The highly conserved regions of PDD mcp gene on chromosome and dly gene on plasmid were selected as the target fragments to design the specific primers. Recombinant plasmid standard was prepared based on the primers. With GENECHECKER UF-150 qRT-PCR instrument as the platform, a fluorescence-based quantitative real-time PCR(qRT-PCR) method was established for the detection of PDD. This method can specifically detect PDD and distinguish the highly virulent strains. Additionally, the test results can be qualitatively judged by visualization, while the quantitative detection can be achieved through the standard curve calculation. The minimum limit of detection was 1.0×101 copies μL-1, and the detection time was less than 20 min. In summary, this new method has outstanding advantages, such as strong specificity, high sensitivity, and low site requirements. It is a rapid on-site detection technology for highly virulent PDD strains.展开更多
This article is a concise overview about the developing microfluidic systems named surface-tension-confined droplet microfluidics （STORMs）. Different from traditional complexed droplet microfluidics which generated ...This article is a concise overview about the developing microfluidic systems named surface-tension-confined droplet microfluidics （STORMs）. Different from traditional complexed droplet microfluidics which generated and confined the droplets by three-dimensional （3D） poly（dimethylsiloxane）-based microchannels, STORM systems provide two- dimensional （2D） platforms for control of droplets. STORM devices utilize surface energy, with methods such as surface chemical modification and mechanical processing, to control the movement of fluid droplets. Various STORM devices have been readily prepared, with distinct advantages over conventional droplet microfluidics, which generated and confined the droplets by 3D poly（dimethylsiloxane）-based microchannels, such as significant reduction of energy consumption neces- sary for device operation, facile or even direct introduction of droplets onto patterned surface without external driving force such as a micropump, thus increased frequency or efficiency of droplets generation of specific STORM device, among others. Thus, STORM devices can be excellent alternatives for majority areas in droplet microfluidics and irreplaceable choices in certain fields by contrast. In this review, fabrication methods or strategies, manipulation methods or mechanisms, and main applications of STORM devices are introduced.展开更多
With the advantages of better mimicking the specificity of natural tissues,three-dimensional(3D)cell culture plays a major role in drug development,toxicity testing,and tissue engineering.However,existing scaffolds or...With the advantages of better mimicking the specificity of natural tissues,three-dimensional(3D)cell culture plays a major role in drug development,toxicity testing,and tissue engineering.However,existing scaffolds or microcarriers for 3D cell culture are often limited in size and show suboptimal performance in simulating the vascular complexes of living organisms.Therefore,we present a novel hierarchically inverse opal porous scaffold made via a simple microfluidic approach for promoting 3D cell co-culture techniques.The designed scaffold is constructed using a combined concept involving an emulsion droplet template and inert polymer polymerization.This work demonstrates that the resultant scaffolds ensure a sufficient supply of nutrients during cell culture,so as to achieve large-volume cell culture.In addition,by serially planting different cells in the scaffold,a 3D co-culture system of endothelial-cellencapsulated hepatocytes can be developed for constructing certain functional tissues.It is also demonstrated that the use of the proposed scaffold for a co-culture system helps hepatocytes to maintain specific in vivo functions.These hierarchically inverse opal scaffolds lay the foundation for 3D cell culture and even the construction of biomimetic tissues.展开更多
Droplet-based microfluidics enables the generation of uniform microdroplets at picoliter or nanoliter scale with high frequency(∼kHz)under precise control.The droplets can function as bioreactors for versatile chemic...Droplet-based microfluidics enables the generation of uniform microdroplets at picoliter or nanoliter scale with high frequency(∼kHz)under precise control.The droplets can function as bioreactors for versatile chemical/biological study and analysis.Taking advantage of the discrete compartment with a confined volume,(1)isolation and manipulation of a single cell,(2)improvement of in-droplet effective concen-trations,(3)elimination of heterogeneous population effects,(4)diminution of contamination risks can be achieved,making it a powerful tool for rapid,sensitive,and high-throughput detection and analysis of bacteria,even for rare or unculturable strains in conventional methods.This mini-review will focus on the generation and manipulation of micro-droplets and bacteria detection and analysis carried out by droplet-based microfluidics.Finally,applications with high potential of droplet-based bacteria analysis are briefly introduced.Due to the advantages of rapid,sensitive,high throughput,and compatibility with rare and unculturable bacteria in conventional methods,droplet-based microfluidics has tremendous potential of providing novel solutions for biological medicine,microbiological engineering,environmental ecology,etc.展开更多
基金the financial support from the National Natural Science Foundation of China (No.42102127)the Postdoctoral Research Foundation of China (No.2024 M751860)。
文摘Cleat serves as the primary flow pathway for coalbed methane(CBM)and water.However,few studies consider the impact of local contact on two-phase flow within cleats.A visual generalized model of endogenous cleats was constructed based on microfluidics.A microscopic and mesoscopic observation technique was proposed to simultaneously capture gas-liquid interface morphology of pores and throat and the two-phase flow characteristics in entire cleat system.The local contact characteristics of cleats reduced absolute permeability,which resulted in a sharp increase in the starting pressure.The reduced gas flow capacity narrowed the co-infiltration area and decreased water saturation at the isotonic point in a hydrophilic environment.The increased local contact area of cleats weakened gas phase flow capacity and narrowed the co-infiltration area.Jumping events occurred in methane-water flow due to altered porosity caused by local contact in cleats.The distribution of residual phases changed the jumping direction on the micro-scale as well as the dominant channel on the mesoscale.Besides,jumping events caused additional energy dissipation,which was ignored in traditional two-phase flow models.This might contribute to the overestimation of relative permeability.The work provides new methods and insights for investigating unsaturated flow in complex porous media.
基金s supported by the National Natural Science Foundation of China(82425104)the National Key Research and Development Program of China(2022YFC3400501).
文摘Drug research and development(R&D)plays a crucial role in supporting public health.However,the traditional drug-discovery paradigm is hindered by significant drawbacks,including high costs,lengthy development timelines,high failure rates,and limited output of new drugs.Recent advances in micro/nanotechnology,along with progress in computer science,have positioned microfluidics and artificial intelligence(AI)as promising transformative tools for drug development.Microfluidics offers miniaturized,multiplexed,and versatile platforms for high-dimensional data acquisition,while AI enables the rapid processing of complex,large-scale microfluidic data;together,they are accelerating a paradigm shift in the drug-discovery process.This paper first outlines the mainstream microfluidic strategies and AI models used in drug R&D.It then summarizes and discusses real-world applications of the integrated use of these technologies across various stages of drug discovery,including early drug discovery,drug screening,drug evaluation,drug manufacturing,and drug delivery systems.Finally,the paper examines the main limitations of microfluidics and AI in drug R&D and offers an outlook on the future convergence of these technologies.
基金supported by the Guizhou Province High-level Innovative Talent Project(Qiankehe Platform Talent-GCC[2022]027-1)the National Key Research and Development Program of China(2019YFA0904800).
文摘Soft rot is a destructive disease that inflicts significant losses on agricultural production and the economy post-harvest.Biocontrol strategies based on antagonistic microorganisms have a broad application prospect to fight against plant pathogens.This study utilized fluorescence-activated droplet sorting(FADS)technology as an alternative to traditional plate culture methods to isolate microorganisms with antagonistic activity against the soft rot pathogen Erwinia carotovora Ecc15.Initially,the culture performance of the FADS platform was evaluated by analyzing bacterial diversity in droplet culture samples and agar plate culture samples,our data showed that droplet culture exhibited higher species richness and diversity than plate culture,and more than 95%of the operational taxonomic units(OTUs)in the droplet samples belonged to the rare biosphere.Additionally,we developed a green fluorescent protein(GFP)-Ecc15-based FADS screening system,which achieved an enrichment ratio of up to 148.Using this system,we successfully screened 32 antagonistic bacteria from rhizosphere soil sample of healthy konjac plants,and some may be novel microbial resources,including the genera Lelliottia,Buttiauxella and Leclercia.Notably,strain D-62 exhibited the strongest antibacterial ability against Ecc15,with an inhibition zone diameter of(20.86±1.56)mm.In vivo experiments conducted on the corms of Amorphophallus konjac demonstrated that strain D-62 could effectively reduce the infection ability of Ecc15 to the corms,indicating that strain D-62 has the potential to be developed as a biocontrol agent.Our findings suggested that the FADS screening system showed a screening efficiency approximately 3×10^(3)times higher than plate screening system,while significantly reducing costs of infrastructure,labor and consumables,it provides theoretical guidance for the screening of other plant pathogen biocontrol bacteria.
基金financially supported by the Fundamental Research Funds for the Central Universities(No.KVJBMC23001536)Guangdong Provincial Key Laboratory of Technique and Equipment for Macromolecular Advanced Manufacturing(No.20240518)+2 种基金the State Key Laboratory of Molecular Engineering of Polymers(Fudan University)(No.K2024-15)the Central Universities support from Beijing Jiaotong University(No.KVYJS24011536)the National Natural Science Foundation of China(No.62175012).
文摘Due to the rapid development and potential applications of iron(Ⅲ)-alginate(Fe-Alg)microgels in biomedical as well as environmental engineering,this study explores the preparation and characterization of spherical Fe-Alg microgels using droplet microfluidics combined with an external ionic crosslinking method.This study focused on the role of Fe^(3+)and examined its effects on the physical/chemical properties of microgels under different ionic conditions and reduced or oxidized states.The pH-dependent release behavior of Fe^(3+)from these microgels demonstrates their potential biomedical and environmental applications.Furthermore,the microgels can exhibit magnetism simply by utilizing in situ oxidation,which can be further used for targeted drug delivery and magnetic separation technologies.
基金financially supported by Science and Technology on Applied Physical Chemistry Laboratory,China(Grant No.61426022220303)supported by the Young Scientists Fund of the National Natural Science Foundation of China(Grant No.52305617)。
文摘Energetic materials,characterized by their capacity to store and release substantial energy,hold pivotal significance in some fields,particularly in defense applications.Microfluidics,with its ability to manipulate fluids and facilitate droplet formation at the microscale,enables precise control of chemical reactions.Recent scholarly endeavors have increasingly harnessed microfluidic reactors in the realm of energetic materials,yielding morphologically controllable particles with enhanced uniformity and explosive efficacy.However,crucial insights into microfluidic-based methodologies are dispersed across various publications,necessitating a systematic compilation.Accordingly,this review addresses this gap by concentrating on the synthesis of energetic materials through microfluidics.Specifically,the methods based on micro-mixing and droplets in the previous papers are summarized and the strategies to control the critical parameters within chemical reactions are discussed in detail.Then,the comparison in terms of advantages and disadvantages is attempted.As demonstrated in the last section regarding perspectives,challenges such as clogging,dead zones,and suboptimal production yields are non-ignoble in the promising fields and they might be addressed by integrating sound,optics,or electrical energy to meet heightened requirements.This comprehensive overview aims to consolidate and analyze the diverse array of microfluidic approaches in energetic material synthesis,offering valuable insights for future research directions.
基金supported by National Natural Science Foundation of China(Grants 32027802 and 22178307)National Key Research and Development Program of China(Grant 2021YFA1101700)the Science Technology Department of Zhejiang Province(Grant 2024C03100).
文摘Radionuclide imaging is divided into positron emission tomography and single photon emission tomography and is widely used in clinical practice for diagnosis and treatment,as well as in clinical research for the development and evaluation of new therapies.Although it is a visually intuitive form of three-dimensional functional imaging,this modality requires the injection of radiopharmaceuticals labeled with positron-or gamma-emitting isotopes into patients to assess and quantify anabolism,gene expression,and other processes.For this reason,radiopharmaceuticals must undergo rigorous quality control(QC)to ensure product purity,efficacy,and safety.Traditional QC of pharmaceuticals is manual,requiring specially trained personnel,a range of expensive analytical and chemical equipment and laboratory space,the consumption of many samples,and usually a long time.Compared with ordinary pharmaceuticals,radiopharmaceuticals have the following unique characteristics:radioactivity,short lifetime,low synthesis yield,and high cost.Therefore,analytical methods and instrumentation must be exclusively developed for the QC of radiopharmaceuticals to avoid large losses owing to radioactive decay or handling.Microfluidics integrates microchannels or microchambers into several square centimeters of a microscale chip through micro-nanofabrication,allowing a precise manipulation of the fluid in microtubules,where various traditional physical,chemical,or biological experiments occur.Microfluidics is gaining attention in the field of analytical testing owing to significantly reduced consumption of samples and reagents,reduced analysis time,increased detection sensitivity,increased multiplexing,and reduced instrument size.Features such as micro size,micro volume,high sensitivity,and on-line testing have led to increasing interest in microfluidics.This review covers the development of integrated microfluidic QC devices that can automatically process,test,analyze,and calculate completed test metrics online.
基金National Natural Science Foundation of China(No.21875109)to provide fund for conducting experiments.
文摘Nano-TATB was developed in microchannels by physical method and chemical method,respectively.The effects of total flow rate,number of microreactor plates,solvent/non-solvent ratio and temperature on the particle size of TATB in the physical method were studied.Prepared TATB were characterized by Nano Sizer,Scanning Electron Microscopy,Specific surface aperture analyzer,X-ray diffraction,Fourier transform infrared spectroscopy and Differential Scanning Calorimetry.The results show that the TATB obtained by physical method and chemical method are spherical,with average particle size of 130.66 nm and 108.51 nm,respectively.Specific surface areas of TATB obtained by physical and chemical methods are 21.37 m^(2)/g and 21.91 m^(2)/g,respectively.Compared with the specific surface area of micro-TATB(0.0808 m^(2)/g),the specific surface area of nano-TATB is significantly increased.DSC test results show that the smaller the particle size of TATB,the lower the thermal decomposition temperature.In addition,by simulating the mixing state of fluid in microchannels and combining with the classical nucleation theory,the mechanism of preparing nano-TATB by microchannels was proposed.
文摘Lightweight and mechanically strong natural silk fibers have been extensively investigated over the past decades.Inspired by this research,many artificial spinning techniques(wet spinning,dry spinning,electrospinning,etc.)have been developed to fabricate robust protein fibers.As the traditional spinning methods provide poor control over the as-spun fibers,microfluidics has been integrated with these techniques to allow the fabrication of biological fibers in a well-designed manner,with simplicity and cost efficiency.The mechanical behavior of the developed fibers can be precisely modulated by controlling the type iop and size of microfluidic channel,flow rate,and shear force.This technique has been successfully used to manufacture a broad range of protein fibers,and can accelerate the production and application of protein fibers in various fields.This review outlines recent progress in the design and fabrication of protein-based fibers based on microfluidics.We first briefly discuss the natural spider silk-spinning process and the microfluidics spinning process.Next,the fabrication and mechanical properties of regenerated protein fibers via microfluidics are discussed,followed by a discussion of recombinant protein fibers.Other sourced protein fibers are also reviewed in detail.Finally,a brief outlook on the development of microfluidic technology for producing protein fibers is presented.
基金supported by National Key Basic Research Program of China (Grant No.2017FYA0205300 and No.2015 CB931802)National Natural Scientific Foundation of China (No. 81571835)
文摘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.
基金financially supported by a foundation item from the China People’s Liberation Army General Armaments Department。
文摘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.
基金Ministry of Science and Technology of China(No.2010CB933901)Science and Technology Innovation fund of SJTU-University of Michigan
文摘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.
基金supported by National Natural Science Foundation of China (Nos. 82173774, 31925037, 22104041)the Fundamental Research Funds for the Central Universities (Nos 2662021DKQD001, 2662021JC001)the Cheeloo Scholar Program of Shandong University (to W. Liu)。
文摘Advances in microbiology rely on innovations in technology. Droplet microfluidics, as a versatile and powerful technique that allows high-throughput generation and manipulation of subnanoliter volume droplets, has become an indispensable tool shifting experimental paradigms in microbiology. Droplet microfluidics has opened new avenues to various microbiological research, from resolving single-cell heterogeneity to investigating spatiotemporal dynamics of microbial communities, from precise quantitation of microbiota to systematic decipherment of microbial interactions, and from isolating rare and uncultured microbes to improving genetic engineered strains. In this review, we present recent advances of droplet microfluidics in various fields of microbiology: i) microbial cultivation, ii) microorganism detection and characterization, iii) antibiotic susceptibility testing, iv) microbial interactions, v) microbial biotechnology.We also provide our perspectives on the challenges and future directions for droplet microfluidic-based microbiology research.
基金This work was supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(22002061,52073060,and 61927805)+1 种基金the Natural Science Foundation of Jiangsu(BE2018707)the Jiangsu Agricultural Science and Technology Innovation Fund(CX(20)3051).
文摘Additive manufacturing plays a vital role in the food,mechanical,pharmaceutical,and medical fields.Within these fields,medical additive manufacturing has led to especially obvious improvements in medical instruments,prostheses,implants,and so forth,based on the advantages of cost-effectiveness,customizability,and quick manufacturing.With the features of precise structural control,high throughput,and good component manipulation,microfluidic techniques present distinctive benefits in medical additive manufacturing and have been applied in the areas of drug discovery,tissue engineering,and organs on chips.Thus,a comprehensive review of microfluidic techniques for medical additive manufacturing is useful for scientists with various backgrounds.Herein,we review recent progress in the development of microfluidic techniques for medical additive manufacturing.We evaluate the distinctive benefits associated with microfluidic technologies for medical additive manufacturing with respect to the fabrication of droplet/fiber templates with different structures.Extensive applications of microfluidic techniques for medical additive manufacturing are emphasized,such as cell guidance,three-dimensional(3D)cell culture,tissue assembly,and cell-based therapy.Finally,we present challenges in and future perspectives on the development of microfluidics for medical additive manufacturing.
基金supported by the National Key Research and Development Program of China(No.2017YFA0205300)National Natural Science Foundation of China(Nos.61971410,61701171,61801464,61801465 and 62001458)+1 种基金Shanghai Sailing Program(No.20YF1457100),Shanghai Engineer&Technology Research Center of Internet of Things for Respiratory Medicine(No.20DZ2254400)the Science and Technology Commission of Shanghai Munic-ipality(No.19511104200).
文摘Tumor heterogeneity plays a critical role in the determination of appropriate anticancer therapy.As cir-culating tumor cells(CTCs)contain all tumor-related information,the genetic changes on CTCs could help us choose the appropriate treatments for different patients.Single-base mutations are very common in tumor genetic changes which may result in drug resistance.Here,we introduce a single-cell mutation de-tection platform based on droplet microfluidics.This platform integrates cell capsulation,cell lysis,poly-merase chain reaction(PCR)and the observation process.The droplets’generation speed is over 6000 per minute and more than 600 cells could be encapsulated in one second.To verify the performance of our platform in practical use,we performed the mutation analysis of 4 kinds of cells with our platform and noted that the genetic status of each single cell was clearly discriminated.Moreover,these results agreed with those from direct sequencing.Compared with other forms of single-cell mutation detection techniques,our platform has high throughput,short experimental time and less experimental operations.
基金the supports of the National Science Foundation of China (22008130, 22025801)the China Postdoctoral Science Foundation (2020M682124)+1 种基金the Qingdao Postdoctoral Researchers Applied Research Project Foundation (RZ2000001426)the Scientific Research Foundation for Youth Scholars from Qingdao University (DC1900014265) for this work
文摘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.
基金supported by the Nationa l Key Research and Development Program of China (2021YFA1101500)the National Natural Science Foundation of China (22074047)+1 种基金the Hubei Provincial Natural Science Foundation of China (2020CFB578)the Fundamental Research Funds for Central Universities,HUST (2020kfy XJJS034)。
文摘Traditional diagnostic strategies for infectious disease detection require benchtop instruments that are inappropriate for point-of-care testing(POCT). Emerging microfluidics, a highly miniaturized, automatic, and integrated technology,are a potential substitute for traditional methods in performing rapid, low-cost, accurate, and on-site diagnoses.Molecular diagnostics are widely used in microfluidic devices as the most effective approaches for pathogen detection.This review summarizes the latest advances in microfluidics-based molecular diagnostics for infectious diseases from academic perspectives and industrial outlooks. First, we introduce the typical on-chip nucleic acid processes,including sample preprocessing, amplification, and signal read-out. Then, four categories of microfluidic platforms are compared with respect to features, merits, and demerits. We further discuss application of the digital assay in absolute nucleic acid quantification. Both the classic and recent microfluidics-based commercial molecular diagnostic devices are summarized as proof of the current market status. Finally, we propose future directions for microfluidics-based infectious disease diagnosis.
基金supported by the National Key Research and Development Program of China (No. 2019YFD0900104)the Key Projects of Science and Technology In-novation of Shandong Province (No. 2018YFJH0703)。
文摘As a marine bacterial pathogen, Photobacterium damselae subsp. damselae(PDD) is distributed in seawater worldwide. It can infect different animals as well as humans, even cause deaths. The highly conserved regions of PDD mcp gene on chromosome and dly gene on plasmid were selected as the target fragments to design the specific primers. Recombinant plasmid standard was prepared based on the primers. With GENECHECKER UF-150 qRT-PCR instrument as the platform, a fluorescence-based quantitative real-time PCR(qRT-PCR) method was established for the detection of PDD. This method can specifically detect PDD and distinguish the highly virulent strains. Additionally, the test results can be qualitatively judged by visualization, while the quantitative detection can be achieved through the standard curve calculation. The minimum limit of detection was 1.0×101 copies μL-1, and the detection time was less than 20 min. In summary, this new method has outstanding advantages, such as strong specificity, high sensitivity, and low site requirements. It is a rapid on-site detection technology for highly virulent PDD strains.
基金Project supported by the Shanghai Pujiang Program(Grant No.16PJ1403200)the Research Grant(Grant No.16DZ2260601)from Science and Technology Commission of Shanghai Municipality
文摘This article is a concise overview about the developing microfluidic systems named surface-tension-confined droplet microfluidics （STORMs）. Different from traditional complexed droplet microfluidics which generated and confined the droplets by three-dimensional （3D） poly（dimethylsiloxane）-based microchannels, STORM systems provide two- dimensional （2D） platforms for control of droplets. STORM devices utilize surface energy, with methods such as surface chemical modification and mechanical processing, to control the movement of fluid droplets. Various STORM devices have been readily prepared, with distinct advantages over conventional droplet microfluidics, which generated and confined the droplets by 3D poly（dimethylsiloxane）-based microchannels, such as significant reduction of energy consumption neces- sary for device operation, facile or even direct introduction of droplets onto patterned surface without external driving force such as a micropump, thus increased frequency or efficiency of droplets generation of specific STORM device, among others. Thus, STORM devices can be excellent alternatives for majority areas in droplet microfluidics and irreplaceable choices in certain fields by contrast. In this review, fabrication methods or strategies, manipulation methods or mechanisms, and main applications of STORM devices are introduced.
基金the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(52073060,32101159,and 61927805)+1 种基金the Shenzhen Fundamental Research Program(JCYJ20190813152616459)the Wenzhou Institute,University of Chinese Academy of Sciences(WIUCAS)’startup fund(WIUCASQD2019007).
文摘With the advantages of better mimicking the specificity of natural tissues,three-dimensional(3D)cell culture plays a major role in drug development,toxicity testing,and tissue engineering.However,existing scaffolds or microcarriers for 3D cell culture are often limited in size and show suboptimal performance in simulating the vascular complexes of living organisms.Therefore,we present a novel hierarchically inverse opal porous scaffold made via a simple microfluidic approach for promoting 3D cell co-culture techniques.The designed scaffold is constructed using a combined concept involving an emulsion droplet template and inert polymer polymerization.This work demonstrates that the resultant scaffolds ensure a sufficient supply of nutrients during cell culture,so as to achieve large-volume cell culture.In addition,by serially planting different cells in the scaffold,a 3D co-culture system of endothelial-cellencapsulated hepatocytes can be developed for constructing certain functional tissues.It is also demonstrated that the use of the proposed scaffold for a co-culture system helps hepatocytes to maintain specific in vivo functions.These hierarchically inverse opal scaffolds lay the foundation for 3D cell culture and even the construction of biomimetic tissues.
基金supported by National Natural Science Foundation of China (No. 22104117)“the Fundamental Research Funds for the Central Universities” (No. JC2110)+1 种基金Wuhu and Xidian University special fund for industry-university-research cooperation (No. XWYCXY-012020012)Open Fund of Zhijiang Lab (No. 2021MC0AB02)
文摘Droplet-based microfluidics enables the generation of uniform microdroplets at picoliter or nanoliter scale with high frequency(∼kHz)under precise control.The droplets can function as bioreactors for versatile chemical/biological study and analysis.Taking advantage of the discrete compartment with a confined volume,(1)isolation and manipulation of a single cell,(2)improvement of in-droplet effective concen-trations,(3)elimination of heterogeneous population effects,(4)diminution of contamination risks can be achieved,making it a powerful tool for rapid,sensitive,and high-throughput detection and analysis of bacteria,even for rare or unculturable strains in conventional methods.This mini-review will focus on the generation and manipulation of micro-droplets and bacteria detection and analysis carried out by droplet-based microfluidics.Finally,applications with high potential of droplet-based bacteria analysis are briefly introduced.Due to the advantages of rapid,sensitive,high throughput,and compatibility with rare and unculturable bacteria in conventional methods,droplet-based microfluidics has tremendous potential of providing novel solutions for biological medicine,microbiological engineering,environmental ecology,etc.
