Glymphatic flow has been proposed to clear brain waste while we sleep.Cerebrospinal fluid moves from periarterial to perivenous spaces through the parenchyma,with subsequent cerebrospinal fluid drainage to dural lymph...Glymphatic flow has been proposed to clear brain waste while we sleep.Cerebrospinal fluid moves from periarterial to perivenous spaces through the parenchyma,with subsequent cerebrospinal fluid drainage to dural lymphatics.Glymphatic disruption is associated with neurological conditions such as Alzheimer’s disease and traumatic brain injury.Therefore,investigating its structure and function may improve understanding of pathophysiology.The recent controversy on whether glymphatic flow increases or decreases during sleep demonstrates that the glymphatic hypothesis remains contentious.However,discrepancies between different studies could be due to limitations of the specific techniques used and confounding factors.Here,we review the methods used to study glymphatic function and provide a toolkit from which researchers can choose.We conclude that tracer analysis has been useful,ex vivo techniques are unreliable,and in vivo imaging is still limited.Finally,we explore the potential for future methods and highlight the need for in vitro models,such as microfluidic devices,which may address technique limitations and enable progression of the field.展开更多
With the continuous advancement of bionanomaterial technology,the design and fabrication strategies of biomimetic nanocarriers have undergone significant strategic transformations and innovations.This article systemat...With the continuous advancement of bionanomaterial technology,the design and fabrication strategies of biomimetic nanocarriers have undergone significant strategic transformations and innovations.This article systematically reviews the evolution from single-cell membrane nanovesicles to hybrid cell membrane nanovesicles integrating multiple cell membranes,culminating in cell membrane hybrid lipid nanoparticles(CM-LNPs)combining natural cell membranes or membrane proteins with engineered synthetic phospholipids.This technological progression enables the synergistic retention of multicellular biological functions and the incorporation of advantageous synthetic material properties,such as enhanced engineering flexibility and surface modifiability.Additionally,the article discusses the advantages and limitations of traditional extrusion and ultrasonication methods in the preparation of cell membrane nanovesicles,highlights the benefits and development prospects of novel microfluidic techniques in the preparation of CM-LNPs,and explores the future application prospects and challenges of CM-LNPs in the biomedical field.展开更多
Encapsulation of water-soluble cargoes in millimeter-sized capsules has enabled major advances in various fields,including pharmaceuticals,food,cosmetics,packaging,and materials.However,because of the lack of fabricat...Encapsulation of water-soluble cargoes in millimeter-sized capsules has enabled major advances in various fields,including pharmaceuticals,food,cosmetics,packaging,and materials.However,because of the lack of fabrication precision,low cargo retention,suboptimal mechanical properties,and difficulty in preventing water evaporation,this technique is more challenging than microencapsulation techniques.In this study,we developed a surfactant-free and organic solvent-free water-in-oil in-air emulsification approach for synthesizing double-layered“milli-capsules”for the precise encapsulation,enhanced retention,and force-triggered burst release of water-soluble bioactive cargoes.In particular,we synthesized milli-capsules with a first shell of poly(ethylene glycol dimethacrylate)for the efficient encapsulation of bioactive cargoes and a second shell of beeswax to prolong the retention of the entrapped bioactive compounds.Unlike traditional milli-capsules,which exhibit poor shape uniformity and mechanical stability,we introduced metallic ions to stabilize the interfacial tension and employed constant rotation to balance the gravity,buoyancy,inertial,and viscous forces imposed on the droplets,resulting in uniform and rigid milli-capsules with narrow rupture forces.Furthermore,additional hydrophobic beeswax coating prevented water volatilization and substantially prolonged the shelf life of the encapsulated compounds from a few days to a few months while maintaining their bioactivities.The proposed milli-capsule system addresses the challenge of precise fabrication of large carriers for water-soluble cargoes,representing a significant step toward the long-term storage and controlled release of bioactive cargoes for various industrial applications.展开更多
The capillary pressure curve provides fundamental insights into the dynamics of fluid-fluid displacement and phase distributions.Capillary scaling is crucial for extrapolating capillary pressure-saturation data from l...The capillary pressure curve provides fundamental insights into the dynamics of fluid-fluid displacement and phase distributions.Capillary scaling is crucial for extrapolating capillary pressure-saturation data from laboratory tests to field applications.However,the classic scaling method fails to capture the effect of wettability as the pore surface approaches neutral wetting.Here,inspired by the role of pore-filling events in controlling fluid-fluid displacement,we perform a theoretical analysis of the burst events occurring during drainage processes.We find that the median threshold capillary pressure,which corresponds to the occurrence of burst events for the median pore throat,is closely correlated with the capillary pressure curve across various contact angles.Using this concept,we propose a new scaling method for capillary pressure curves under various wetting conditions.We conduct microfluidic experiments and pore-network modeling across different contact angles,porosities,and disorders to evaluate the new scaling methods,indicating that the new scaling method performs better than the Leverett J-function as the contact angle approaches 90°.We further perform geometry analysis on the critical radius of curvature for burst events in an ideal tetrahedral arrangement and extend the new scaling method to 3D(three-dimensional)porous media.Model evaluation shows that the 3D version of the scaling method also performs well but requires fewer parameters compared to the Leverett J-function.Our work enhances the prediction and interpretation of experimental data for capillary pressure curves under various wet conditions,and more importantly,establishes a methodology that relates Darcy-scale flow behavior to pore-scale fluid displacements.展开更多
Droplet-based microfluidics is a transformative technology with applications across diverse scientific and industrial domains.However,predicting the droplet size generated by individual microchannels before experiment...Droplet-based microfluidics is a transformative technology with applications across diverse scientific and industrial domains.However,predicting the droplet size generated by individual microchannels before experiments or simulations remains a significant challenge.In this study,we focus on a double T-junction microfluidic geometry and employ a hybrid modeling approach that combines machine learning with metaheuristic optimization to address this issue.Specifically,particle swarm optimization(PSO)is used to optimize the hyperparameters of a decision tree(DT)model,and its performance is compared with that of a DT optimized through grid search(GS).The hybrid models are developed to estimate the droplet diameter based on four parameters:the main width,side width,thickness,and flow rate ratio.The dataset of more than 300 cases,generated by a three-dimensional numerical model of the double T-junction,is used for training and testing.Multiple evaluation metrics confirm the predictive accuracy of the models.The results demonstrate that the proposed DT-PSO model achieves higher accuracy,with a coefficient of determination of 0.902 on the test data,while simultaneously reducing prediction time.This methodology holds the potential to minimize design iterations and accelerate the integration of microfluidic technology into the biological sciences.展开更多
In recent years,microfluidic technology has emerged as a powerful and innovative tool,attracting significant attention for its ability to provide real-time visualization of CO_(2)flow,mass transfer,and reaction proces...In recent years,microfluidic technology has emerged as a powerful and innovative tool,attracting significant attention for its ability to provide real-time visualization of CO_(2)flow,mass transfer,and reaction processes in porous media.This review examines the application of microfluidic technology in CO_(2)sequestration in saline aquifers,emphasizing the advantages of saline aquifer for geological sequestration,including safety,high storage capacity,stability,and cost-effectiveness.The materials used for microfluidic chips and the design of microchannels are systematically reviewed,offering forward-looking recommendations for chip selection and microchannel characterization in future research on CO_(2)sequestration in saline aquifer.Based on a detailed analysis of advancements in microfluidic technology,this review highlights key findings related to CO_(2)trapping mechanisms,salt precipitation,and CO_(2)-water-rock chemical interactions within saline aquifers.Although microfluidic technology shows great promise in these areas,this review identifies limitations in current studies and outlines future research directions,aiming to promote further innovation and broader application of microfluidic technology in the field of CO_(2)sequestration in saline aquifer.展开更多
Multi-organ-on-a-chip(MOOC)technology represents a pivotal direction in the organ-on-a-chip field,seeking to emulate the complex interactions of multiple human organs in vitro through microfluidic systems.This technol...Multi-organ-on-a-chip(MOOC)technology represents a pivotal direction in the organ-on-a-chip field,seeking to emulate the complex interactions of multiple human organs in vitro through microfluidic systems.This technology overcomes the limitations of traditional single-organ models,providing a novel platform for investigating complex disease mechanisms and evaluating drug efficacy and toxicity.Although it demonstrates broad application prospects,its development still faces critical bottlenecks,including inadequate physiological coupling between organs,short functional maintenance durations,and limited real-time monitoring capabilities.Contemporary research is advancing along three key directions,including functional coupling,sensor integration,and full-process automation systems,to propel the technology toward enhanced levels of physiological relevance and predictive accuracy.展开更多
Liposomes serve as critical carriers for drugs and vaccines,with their biological effects influenced by their size.The microfluidic method,renowned for its precise control,reproducibility,and scalability,has been wide...Liposomes serve as critical carriers for drugs and vaccines,with their biological effects influenced by their size.The microfluidic method,renowned for its precise control,reproducibility,and scalability,has been widely employed for liposome preparation.Although some studies have explored factors affecting liposomal size in microfluidic processes,most focus on small-sized liposomes,predominantly through experimental data analysis.However,the production of larger liposomes,which are equally significant,remains underexplored.In this work,we thoroughly investigate multiple variables influencing liposome size during microfluidic preparation and develop a machine learning(ML)model capable of accurately predicting liposomal size.Experimental validation was conducted using a staggered herringbone micromixer(SHM)chip.Our findings reveal that most investigated variables significantly influence liposomal size,often interrelating in complex ways.We evaluated the predictive performance of several widely-used ML algorithms,including ensemble methods,through cross-validation(CV)for both lipo-some size and polydispersity index(PDI).A standalone dataset was experimentally validated to assess the accuracy of the ML predictions,with results indicating that ensemble algorithms provided the most reliable predictions.Specifically,gradient boosting was selected for size prediction,while random forest was employed for PDI prediction.We successfully produced uniform large(600 nm)and small(100 nm)liposomes using the optimised experimental conditions derived from the ML models.In conclusion,this study presents a robust methodology that enables precise control over liposome size distribution,of-fering valuable insights for medicinal research applications.展开更多
Surface engineering plays a crucial role in improving the performance of high energy materials,and polydopamine(PDA)is widely used in the field of energetic materials for surface modification and functionalization.In ...Surface engineering plays a crucial role in improving the performance of high energy materials,and polydopamine(PDA)is widely used in the field of energetic materials for surface modification and functionalization.In order to obtain high-quality HMX@PDA-based PBX explosives with high sphericity and a narrow particle size distribution,composite microspheres were prepared using co-axial droplet microfluidic technology.The formation mechanism,thermal behavior,mechanical sensitivity,electrostatic spark sensitivity,compressive strength,and combustion performance of the microspheres were investigated.The results show that PDA can effectively enhance the interfacial interaction between the explosive particles and the binder under the synergistic effect of chemical bonds and the physical"mechanical interlocking"structure.Interface reinforcement causes the thermal decomposition temperature of the sample microspheres to move to a higher temperature,with the sensitivity to impact,friction,and electrostatic sparks(for S-1)increasing by 12.5%,31.3%,and 81.5%respectively,and the compressive strength also increased by 30.7%,effectively enhancing the safety performance of the microspheres.Therefore,this study provides an effective and universal strategy for preparing high-quality functional explosives,and also provides some reference for the safe use of energetic materials in practical applications.展开更多
Point-of-care testing(POCT)refers to a category of diagnostic tests that are performed at or near to the site of the patients(also called bedside testing)and is capable of obtaining accurate results in a short time by...Point-of-care testing(POCT)refers to a category of diagnostic tests that are performed at or near to the site of the patients(also called bedside testing)and is capable of obtaining accurate results in a short time by using portable diagnostic devices,avoiding sending samples to the medical laboratories.It has been extensively explored for diagnosing and monitoring patients’diseases and health conditions with the assistance of development in biochemistry and microfluidics.Microfluidic paper-based analytical devices(μPADs)have gained dramatic popularity in POCT because of their simplicity,user-friendly,fast and accurate result reading and low cost.SeveralμPADs have been successfully commercialized and received excellent feedback during the past several decades.This review briefly discusses the main types ofμPADs,preparation methods and their detection principles,followed by a few representative examples.The future perspectives of the development inμPADs are also provided.展开更多
Objective Cerebral palsy(CP)is a prevalent neurodevelopmental disorder acquired during the perinatal period,with periventricular white matter injury(PWMI)serving as its primary pathological hallmark.PWMI is characteri...Objective Cerebral palsy(CP)is a prevalent neurodevelopmental disorder acquired during the perinatal period,with periventricular white matter injury(PWMI)serving as its primary pathological hallmark.PWMI is characterized by the loss of oligodendrocytes(OLs)and the disintegration of myelin sheaths,leading to impaired neural connectivity and motor dysfunction.Neural stem cells(NSCs)represent a promising regenerative source for replenishing lost OLs;however,conventional twodimensional(2D)in vitro culture systems lack the three-dimensional(3D)physiological microenvironment.Microfluidic chip technology has emerged as a powerful tool to overcome this limitation by enabling precise spatial and temporal control over 3D microenvironmental conditions,including the establishment of stable concentration gradients of bioactive molecules.Catalpol,an iridoid glycoside derived from traditional medicinal plants,exhibits dual antioxidant and anti-apoptotic properties.Despite its therapeutic potential,the capacity of catalpol to drive NSC differentiation toward OLs under biomimetic 3D conditions,as well as the underlying molecular mechanisms,remains poorly understood.This study aims to develop a microfluidic-based 3D biomimetic platform to systematically investigate the concentration-dependent effects of catalpol on promoting NSCs-to-OLs differentiation and to elucidate the role of the caveolin-1(Cav-1)signaling pathway in this process.Methods We developed a novel multiplexed microfluidic device featuring parallel microchannels with integrated gradient generators capable of establishing and maintaining precise linear concentration gradients(0-3 g/L catalpol)across 3D NSCs cultures.This platform facilitated the continuous perfusion culture of NSC-derived 3D spheroids,mimicking the dynamic in vivo microenvironment.Real-time cell viability was assessed using Calcein-AM/propidium iodide(PI)dual staining,with fluorescence imaging quantifying live/dead cell ratios.Oligodendrocyte differentiation was evaluated through quantitative reverse transcription polymerase chain reaction(qRT-PCR)for MBP and SOX10 gene expression,complemented by immunofluorescence staining to visualize corresponding protein changes.To dissect the molecular mechanism,the Cav-1-specific pharmacological inhibitor methyl‑β‑cyclodextrin(MCD)was employed to perturb the pathway,and its effects on differentiation markers were analyzed.Results Catalpol demonstrated excellent biocompatibility,with cell viability exceeding 96%across the entire tested concentration range(0-3 g/L),confirming its non-cytotoxic nature.At the optimal concentration of 0-3 g/L,catalpol significantly upregulated both MBP and SOX10 expression(P<0.05,P<0.01),indicating robust promotion of oligodendroglial differentiation.Intriguingly,Cav-1 mRNA expression was progressively downregulated during NSC differentiation into OLs.Further inhibition of Cav-1 with MCD further enhanced this effect,leading to a statistically significant increase in OL-specific gene expression(P<0.05,P<0.01),suggesting Cav-1 acts as a negative regulator of OLs differentiation.Conclusion This study established an integrated microfluidic gradient chip-3D NSC spheroid culture system,which combines the advantages of precise chemical gradient control with physiologically relevant 3D cell culture.The findings demonstrate that 3 g/L catalpol effectively suppresses Cav-1 signaling to drive NSC differentiation into functional OLs.This work not only provides novel insights into the Cav-1-dependent mechanisms of myelination but also delivers a scalable technological platform for future research on remyelination therapies,with potential applications in cerebral palsy and other white matter disorders.The platform’s modular design permits adaptation for screening other neurogenic compounds or investigating additional signaling pathways involved in OLs maturation.展开更多
Bubble breakup at T-junction microchannels is the basis for the numbering-up of gas−liquid two-phase flow in parallelized microchannels. This article presents the bubble breakup in viscous liquids at a microfluidic T-...Bubble breakup at T-junction microchannels is the basis for the numbering-up of gas−liquid two-phase flow in parallelized microchannels. This article presents the bubble breakup in viscous liquids at a microfluidic T-junction. Nitrogen is used as the gas phase, and glycerol-water mixtures with different mass concentration of glycerol as the liquid phase. The evolution of the gas−liquid interface during bubble breakup at the microfluidic T-junction is explored. The thinning of the bubble neck includes the squeezing stage and the rapid pinch-off stage. In the squeezing stage, the power law relation is found between the minimum width of the bubble neck and the time, and the values of exponents α1 and α2 are influenced by the viscous force. The values of pre-factors m_(1) and m_(2) are negatively correlated with the capillary number. In the rapid pinch-off stage, the thinning of the bubble neck is predominated by the surface tension, and the minimum width of the bubble neck can be scaled with the remaining time as power-law. The propagation of the bubble tip can be characterized by the power law between the movement distance and the time, with decreasing exponent as increased liquid viscosity.展开更多
The vascular network is integral to the developmental and metabolic processes of various tissues and functions as a systemic circulatory system that also interconnects organs throughout the body.In this study,we descr...The vascular network is integral to the developmental and metabolic processes of various tissues and functions as a systemic circulatory system that also interconnects organs throughout the body.In this study,we describe a multilayered microfluidic organ-on-a-chip platform designed for reproducing various three-dimensional(3D)vascularized microtissue models for biological applications.This platform utilizes a porous membrane as a physical barrier and leverages capillary action for hydrogel self-filling.Its high flow resistance mitigates the risk of gel bursting into the medium channels and facilitates the delivery of substances to generate a wide range of interstitial flow and biochemical factor concentration gradients.This study demonstrated that this platform can be used to accurately replicate 3D microenvironments for vasculogenesis,angiogenesis,and vascularized tumor modeling.We also investigated the critical role of multiple microenvironmental regulations in vascular formation on a chip.Moreover,we reproduced the process of tumor angiogenesis,including primary solid tumor features and the inhibitory effects of antitumor drugs on tumor growth and tumor vasculature before and after angiogenesis.Hence,our multilayered microfluidic platform is valuable for exploring multiple vascular mechanisms and constructing specific microtissues that closely mimic in vivo physiological conditions,providing new strategies for cancer research.Furthermore,the multilayered configuration improves design flexibility and scalability,providing the potential for a multi-organ interconnected platform for high-throughput drug screening.展开更多
Professor LIN Jin-Ming is a distinguished scholar in the Department of Chemistry,Tsinghua University.He was selected into the Chinese Academy of Sciences"Hundred Talents Program"in 2001,and received the Outs...Professor LIN Jin-Ming is a distinguished scholar in the Department of Chemistry,Tsinghua University.He was selected into the Chinese Academy of Sciences"Hundred Talents Program"in 2001,and received the Outstanding Young Scholars Fund from the National Science Foundation in the same year.He is a fellow of the Chinese Chemical Society and a fellow of the Royal Society of Chemistry.Prof.LIN has received about 30 academic awards for his contributions in microfluidics,chemiluminescence and separation science.He is the author or co-author of more than 500 original research papers published in international journals,45 review papers,and 8 books,and holds 50 invention patents.His current research focuses on cell culture and analysis on microfluidics with mass spectrometry and chemiluminescence.展开更多
On-demand droplet manipulation plays a critical role in microfluidics,bio/chemical detection and microreactions.Acoustic droplet manipulation has emerged as a promising technique due to its non-contact nature,biocompa...On-demand droplet manipulation plays a critical role in microfluidics,bio/chemical detection and microreactions.Acoustic droplet manipulation has emerged as a promising technique due to its non-contact nature,biocompatibility and precision,circumventing the complexities associated with other methods requiring surface or droplet pretreatment.Despite their promise,existing methods for acoustic droplet manipulation often involve complex hardware setups and difficulty for controlling individual droplet amidst multiple ones.Here we fabricate simple yet effective acoustic tweezers for in-surface and out-of-surface droplet manipulation.It is found that droplets can be transported on the superhydrophobic surfaces when the acoustic radiation force surpasses the friction force.Using a two-axis acoustic tweezer,droplets can be maneuvered along arbitrarily programmed paths on the surfaces.By introducing multiple labyrinthine structures on the superhydrophobic surface,individual droplet manipulation is realized by constraining the unselected droplets in the labyrinthine structures.In addition,a three-axis acoustic tweezer is developed for manipulating droplets in three-dimensional space.Potential applications of the acoustic tweezers for micro-reaction,bio-assay and chemical analysis are also demonstrated.展开更多
As prepubertal boys do not yet produce spermatozoa,they cannot rely on sperm cryopreservation for fertility preservation before gonadotoxic therapy,such as high-dose alkylating agents or radiotherapy in the case of ch...As prepubertal boys do not yet produce spermatozoa,they cannot rely on sperm cryopreservation for fertility preservation before gonadotoxic therapy,such as high-dose alkylating agents or radiotherapy in the case of childhood cancers.According to the current guidelines,cryopreservation of testicular biopsies containing spermatogonial stem cells(SSCs)may be proposed to high-risk patients for potential later therapeutic use to fulfill the patients’wish for a biological child.One promising technique for human in vitro spermatogenesis and in vitro propagation of human SSCs is microfluidic(MF)culture,in which cells or tissues are subjected to a continuous flow of medium.This provides exact control over such parameters as nutrient content and gradients,as well as the removal of waste metabolites.While MF has been shown to maintain tissues and cell populations of organs for longer than conventional in vitro culture techniques,it has not been widely used for testicular in vitro culture.MF could advance human testicular in vitro culture and is also applicable to reprotoxicity studies.This review summarizes the findings and achievements of testis-on-chip(ToC)setups to date and discusses the benefits and limitations of these for spermatogenesis in vitro and toxicity assessment.展开更多
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
Chemical synthesis is essential in industries such as petrochemicals, fine chemicals, and pharmaceuticals, driving economic and social development. The increasing demand for new molecules and materials calls for novel...Chemical synthesis is essential in industries such as petrochemicals, fine chemicals, and pharmaceuticals, driving economic and social development. The increasing demand for new molecules and materials calls for novel chemical reactions;however, manual experimental screening is time-consuming. Artificial intelligence (AI) offers a promising solution by leveraging large-scale experimental data to model chemical reactions, although challenges such as the lack of standardization and predictability in chemical synthesis hinder AI applications. Additionally, the multi-scale nature of chemical reactions, along with complex multiphase processes, further complicates the task. Recent advances in microchemical systems, particularly continuous flow methods using microreactors, provide precise control over reaction conditions, enhancing reproducibility and enabling high-throughput experimentation. These systems minimize transport-related inconsistencies and facilitate scalable industrial applications. This review systematically explores recent developments in intelligent synthesis based on microchemical systems, focusing on reaction system design, synthesis robots, closed-loop optimization, and high-throughput experimentation, while identifying key areas for future research.展开更多
The rapid development of microfluidic technology has led to the evolution of microdroplets from simple emulsion structures to complex multilayered and multicompartmental configurations.These advancements have endowed ...The rapid development of microfluidic technology has led to the evolution of microdroplets from simple emulsion structures to complex multilayered and multicompartmental configurations.These advancements have endowed microdroplets with the capability to contain multiple compartments that remain isolated from one another,enabling them to carry different molecules of interest.Consequently,researchers can now investigate intricate spatially confined chemical reactions and signal transduction pathways within subcellular organelles.Moreover,modern microdroplets often possess excellent optical transparency,allowing fluorescently labelled,multi-layered,and compartmental droplets to provide detailed insights through real-time,in situ,and dynamic fluorescence imaging.Hence,this review systematically summarizes current methodologies for preparing multicomponent microdroplets and their applications,particularly focusing on fluorescent microdroplets.Additionally,it discusses existing critical challenges and outlines future research directions.By offering a comprehensive overview of the preparation methods and applications of fluorescent microdroplets,this review aims to stimulate the interest of researchers and foster their utilization in more complex and biomimetic environments.展开更多
Bacillus thuringiensis,a safe bacterium widely used in agriculture for the biocontrol of pests,has great potential for protein production.The linear plasmid expression system,bacterial orthogonal DNA replication syste...Bacillus thuringiensis,a safe bacterium widely used in agriculture for the biocontrol of pests,has great potential for protein production.The linear plasmid expression system,bacterial orthogonal DNA replication system constructed based on B.thuringiensis prophage GIL16,can achieve stable and high levels of gene expression in the absence of external selection pressure,facilitating development of B.thuringiensis chassis cells.However,the regulatory elements of gene expression and protein secretion suitable for the B.thuringiensis expression system are still lacking.Therefore,the development and optimization of different genetic tools are required.We constructed a promoter library containing 107 different-strength promoters(covering persistently high/intermediate/low level)by transcriptomic analysis of the cell at different growth stages and a signal peptide library(59 signal peptides from Bacillus subtilis and four endogenous signal peptides from B.thuringiensis)to enrich the genetic toolbox using alpha-lactalbumin(α-LA)as the characterization product.Then,a high-throughput microfluidic screening platform based on BacORep and self-assembled split fluorescent protein was developed to further optimize expression elements,resulting in an improved α-LA-producing B.thuringiensis.Finally,the maximum copy number of linear plasmids was 9.3 times higher than that of the original.The titer of α-LA reached 107.7 mg/L in a 3 L bioreactor,which was comparable to the highest yield reported in Komagataella phaffii.We substantially expanded the synthetic biology toolbox for linear plasmid expression systems and provided a strategy for creating efficient prokaryotic expression system.展开更多
基金supported by the European Union Horizon 2020 Research and Innovation Programme(Marie Skłodowska-Curie grant agreement No 847419)supported by the Biotechnology and Biological Sciences Research Council via a Discovery Fellowship(BB/W00934X/1)+6 种基金the Aston University RKE Pump Priming Programmefunded by UKRI’s Research England as part of their Expanding Excellence in England(E3)fundsupported by a UKRI Frontier Research Grant EP/Y023684/1(following assessment as an ERC Advanced grant,FORTIFY,ERC-2022-ADG-101096882 under the UK Government Guarantee scheme)acknowledged a Biotechnology and Biological Sciences Research Council Pioneer Award(BB/Y512874/1)MMS was supported by a Medical Research Council Career Development Award(MR/W027119/1)acknowledged support from the BHF Centre of Research Excellence,University of Oxford(grant code:RE/24/130024)a Biotechnology and Biological Sciences Research Council Pioneer Award(BB/Y512874/1).
文摘Glymphatic flow has been proposed to clear brain waste while we sleep.Cerebrospinal fluid moves from periarterial to perivenous spaces through the parenchyma,with subsequent cerebrospinal fluid drainage to dural lymphatics.Glymphatic disruption is associated with neurological conditions such as Alzheimer’s disease and traumatic brain injury.Therefore,investigating its structure and function may improve understanding of pathophysiology.The recent controversy on whether glymphatic flow increases or decreases during sleep demonstrates that the glymphatic hypothesis remains contentious.However,discrepancies between different studies could be due to limitations of the specific techniques used and confounding factors.Here,we review the methods used to study glymphatic function and provide a toolkit from which researchers can choose.We conclude that tracer analysis has been useful,ex vivo techniques are unreliable,and in vivo imaging is still limited.Finally,we explore the potential for future methods and highlight the need for in vitro models,such as microfluidic devices,which may address technique limitations and enable progression of the field.
基金financially supported by the National Natural Science Foundation of China(32371475)。
文摘With the continuous advancement of bionanomaterial technology,the design and fabrication strategies of biomimetic nanocarriers have undergone significant strategic transformations and innovations.This article systematically reviews the evolution from single-cell membrane nanovesicles to hybrid cell membrane nanovesicles integrating multiple cell membranes,culminating in cell membrane hybrid lipid nanoparticles(CM-LNPs)combining natural cell membranes or membrane proteins with engineered synthetic phospholipids.This technological progression enables the synergistic retention of multicellular biological functions and the incorporation of advantageous synthetic material properties,such as enhanced engineering flexibility and surface modifiability.Additionally,the article discusses the advantages and limitations of traditional extrusion and ultrasonication methods in the preparation of cell membrane nanovesicles,highlights the benefits and development prospects of novel microfluidic techniques in the preparation of CM-LNPs,and explores the future application prospects and challenges of CM-LNPs in the biomedical field.
基金supported by the National Natural Science Foundation of China(Nos.52273102,31870957,and 52302344)the Fundamental Research Funds for the Central Universities(Nos.DUT24YG155,DUT20YG103,and DUT22LAB601)Liaoning Provincial Science and Technology Plan Joint Plan(No.2023JH2/101700341)。
文摘Encapsulation of water-soluble cargoes in millimeter-sized capsules has enabled major advances in various fields,including pharmaceuticals,food,cosmetics,packaging,and materials.However,because of the lack of fabrication precision,low cargo retention,suboptimal mechanical properties,and difficulty in preventing water evaporation,this technique is more challenging than microencapsulation techniques.In this study,we developed a surfactant-free and organic solvent-free water-in-oil in-air emulsification approach for synthesizing double-layered“milli-capsules”for the precise encapsulation,enhanced retention,and force-triggered burst release of water-soluble bioactive cargoes.In particular,we synthesized milli-capsules with a first shell of poly(ethylene glycol dimethacrylate)for the efficient encapsulation of bioactive cargoes and a second shell of beeswax to prolong the retention of the entrapped bioactive compounds.Unlike traditional milli-capsules,which exhibit poor shape uniformity and mechanical stability,we introduced metallic ions to stabilize the interfacial tension and employed constant rotation to balance the gravity,buoyancy,inertial,and viscous forces imposed on the droplets,resulting in uniform and rigid milli-capsules with narrow rupture forces.Furthermore,additional hydrophobic beeswax coating prevented water volatilization and substantially prolonged the shelf life of the encapsulated compounds from a few days to a few months while maintaining their bioactivities.The proposed milli-capsule system addresses the challenge of precise fabrication of large carriers for water-soluble cargoes,representing a significant step toward the long-term storage and controlled release of bioactive cargoes for various industrial applications.
基金supported by the National Natural Science Foundation of China(Grant Nos.52379107 and 52309141).
文摘The capillary pressure curve provides fundamental insights into the dynamics of fluid-fluid displacement and phase distributions.Capillary scaling is crucial for extrapolating capillary pressure-saturation data from laboratory tests to field applications.However,the classic scaling method fails to capture the effect of wettability as the pore surface approaches neutral wetting.Here,inspired by the role of pore-filling events in controlling fluid-fluid displacement,we perform a theoretical analysis of the burst events occurring during drainage processes.We find that the median threshold capillary pressure,which corresponds to the occurrence of burst events for the median pore throat,is closely correlated with the capillary pressure curve across various contact angles.Using this concept,we propose a new scaling method for capillary pressure curves under various wetting conditions.We conduct microfluidic experiments and pore-network modeling across different contact angles,porosities,and disorders to evaluate the new scaling methods,indicating that the new scaling method performs better than the Leverett J-function as the contact angle approaches 90°.We further perform geometry analysis on the critical radius of curvature for burst events in an ideal tetrahedral arrangement and extend the new scaling method to 3D(three-dimensional)porous media.Model evaluation shows that the 3D version of the scaling method also performs well but requires fewer parameters compared to the Leverett J-function.Our work enhances the prediction and interpretation of experimental data for capillary pressure curves under various wet conditions,and more importantly,establishes a methodology that relates Darcy-scale flow behavior to pore-scale fluid displacements.
文摘Droplet-based microfluidics is a transformative technology with applications across diverse scientific and industrial domains.However,predicting the droplet size generated by individual microchannels before experiments or simulations remains a significant challenge.In this study,we focus on a double T-junction microfluidic geometry and employ a hybrid modeling approach that combines machine learning with metaheuristic optimization to address this issue.Specifically,particle swarm optimization(PSO)is used to optimize the hyperparameters of a decision tree(DT)model,and its performance is compared with that of a DT optimized through grid search(GS).The hybrid models are developed to estimate the droplet diameter based on four parameters:the main width,side width,thickness,and flow rate ratio.The dataset of more than 300 cases,generated by a three-dimensional numerical model of the double T-junction,is used for training and testing.Multiple evaluation metrics confirm the predictive accuracy of the models.The results demonstrate that the proposed DT-PSO model achieves higher accuracy,with a coefficient of determination of 0.902 on the test data,while simultaneously reducing prediction time.This methodology holds the potential to minimize design iterations and accelerate the integration of microfluidic technology into the biological sciences.
基金supported by the National Natural Science Foundation of China(Grant Nos.U23A20671 and 12302344)the Creative Groups of Natural Science Foundation of Hubei Province,China(Grant No.2021CFA030).
文摘In recent years,microfluidic technology has emerged as a powerful and innovative tool,attracting significant attention for its ability to provide real-time visualization of CO_(2)flow,mass transfer,and reaction processes in porous media.This review examines the application of microfluidic technology in CO_(2)sequestration in saline aquifers,emphasizing the advantages of saline aquifer for geological sequestration,including safety,high storage capacity,stability,and cost-effectiveness.The materials used for microfluidic chips and the design of microchannels are systematically reviewed,offering forward-looking recommendations for chip selection and microchannel characterization in future research on CO_(2)sequestration in saline aquifer.Based on a detailed analysis of advancements in microfluidic technology,this review highlights key findings related to CO_(2)trapping mechanisms,salt precipitation,and CO_(2)-water-rock chemical interactions within saline aquifers.Although microfluidic technology shows great promise in these areas,this review identifies limitations in current studies and outlines future research directions,aiming to promote further innovation and broader application of microfluidic technology in the field of CO_(2)sequestration in saline aquifer.
基金supported by the Shenzhen Medical Research Fund(Grant No.A2303049)Guangdong Basic and Applied Basic Research(Grant No.2023A1515010647)+1 种基金National Natural Science Foundation of China(Grant No.22004135)Shenzhen Science and Technology Program(Grant No.RCBS20210706092409020,GXWD20201231165807008,20200824162253002).
文摘Multi-organ-on-a-chip(MOOC)technology represents a pivotal direction in the organ-on-a-chip field,seeking to emulate the complex interactions of multiple human organs in vitro through microfluidic systems.This technology overcomes the limitations of traditional single-organ models,providing a novel platform for investigating complex disease mechanisms and evaluating drug efficacy and toxicity.Although it demonstrates broad application prospects,its development still faces critical bottlenecks,including inadequate physiological coupling between organs,short functional maintenance durations,and limited real-time monitoring capabilities.Contemporary research is advancing along three key directions,including functional coupling,sensor integration,and full-process automation systems,to propel the technology toward enhanced levels of physiological relevance and predictive accuracy.
基金supported by the National Key Research and Development Plan of the Ministry of Science and Technology,China(Grant No.:2022YFE0125300)the National Natural Science Foundation of China(Grant No:81690262)+2 种基金the National Science and Technology Major Project,China(Grant No.:2017ZX09201004-021)the Open Project of National facility for Translational Medicine(Shanghai),China(Grant No.:TMSK-2021-104)Shanghai Jiao Tong University STAR Grant,China(Grant Nos.:YG2022ZD024 and YG2022QN111).
文摘Liposomes serve as critical carriers for drugs and vaccines,with their biological effects influenced by their size.The microfluidic method,renowned for its precise control,reproducibility,and scalability,has been widely employed for liposome preparation.Although some studies have explored factors affecting liposomal size in microfluidic processes,most focus on small-sized liposomes,predominantly through experimental data analysis.However,the production of larger liposomes,which are equally significant,remains underexplored.In this work,we thoroughly investigate multiple variables influencing liposome size during microfluidic preparation and develop a machine learning(ML)model capable of accurately predicting liposomal size.Experimental validation was conducted using a staggered herringbone micromixer(SHM)chip.Our findings reveal that most investigated variables significantly influence liposomal size,often interrelating in complex ways.We evaluated the predictive performance of several widely-used ML algorithms,including ensemble methods,through cross-validation(CV)for both lipo-some size and polydispersity index(PDI).A standalone dataset was experimentally validated to assess the accuracy of the ML predictions,with results indicating that ensemble algorithms provided the most reliable predictions.Specifically,gradient boosting was selected for size prediction,while random forest was employed for PDI prediction.We successfully produced uniform large(600 nm)and small(100 nm)liposomes using the optimised experimental conditions derived from the ML models.In conclusion,this study presents a robust methodology that enables precise control over liposome size distribution,of-fering valuable insights for medicinal research applications.
基金supported by the National Natural Science Foundation of China(Grant No.22005275).
文摘Surface engineering plays a crucial role in improving the performance of high energy materials,and polydopamine(PDA)is widely used in the field of energetic materials for surface modification and functionalization.In order to obtain high-quality HMX@PDA-based PBX explosives with high sphericity and a narrow particle size distribution,composite microspheres were prepared using co-axial droplet microfluidic technology.The formation mechanism,thermal behavior,mechanical sensitivity,electrostatic spark sensitivity,compressive strength,and combustion performance of the microspheres were investigated.The results show that PDA can effectively enhance the interfacial interaction between the explosive particles and the binder under the synergistic effect of chemical bonds and the physical"mechanical interlocking"structure.Interface reinforcement causes the thermal decomposition temperature of the sample microspheres to move to a higher temperature,with the sensitivity to impact,friction,and electrostatic sparks(for S-1)increasing by 12.5%,31.3%,and 81.5%respectively,and the compressive strength also increased by 30.7%,effectively enhancing the safety performance of the microspheres.Therefore,this study provides an effective and universal strategy for preparing high-quality functional explosives,and also provides some reference for the safe use of energetic materials in practical applications.
文摘Point-of-care testing(POCT)refers to a category of diagnostic tests that are performed at or near to the site of the patients(also called bedside testing)and is capable of obtaining accurate results in a short time by using portable diagnostic devices,avoiding sending samples to the medical laboratories.It has been extensively explored for diagnosing and monitoring patients’diseases and health conditions with the assistance of development in biochemistry and microfluidics.Microfluidic paper-based analytical devices(μPADs)have gained dramatic popularity in POCT because of their simplicity,user-friendly,fast and accurate result reading and low cost.SeveralμPADs have been successfully commercialized and received excellent feedback during the past several decades.This review briefly discusses the main types ofμPADs,preparation methods and their detection principles,followed by a few representative examples.The future perspectives of the development inμPADs are also provided.
基金supported by grants from the Liaoning Province Excellent Talent Program Project(XLYC1902031)Dalian Science and Technology Talent Innovation Plan Grant(2022RG18)Basic Research Project of the Department of Education of Liaoning Province(LJKQZ20222395)。
文摘Objective Cerebral palsy(CP)is a prevalent neurodevelopmental disorder acquired during the perinatal period,with periventricular white matter injury(PWMI)serving as its primary pathological hallmark.PWMI is characterized by the loss of oligodendrocytes(OLs)and the disintegration of myelin sheaths,leading to impaired neural connectivity and motor dysfunction.Neural stem cells(NSCs)represent a promising regenerative source for replenishing lost OLs;however,conventional twodimensional(2D)in vitro culture systems lack the three-dimensional(3D)physiological microenvironment.Microfluidic chip technology has emerged as a powerful tool to overcome this limitation by enabling precise spatial and temporal control over 3D microenvironmental conditions,including the establishment of stable concentration gradients of bioactive molecules.Catalpol,an iridoid glycoside derived from traditional medicinal plants,exhibits dual antioxidant and anti-apoptotic properties.Despite its therapeutic potential,the capacity of catalpol to drive NSC differentiation toward OLs under biomimetic 3D conditions,as well as the underlying molecular mechanisms,remains poorly understood.This study aims to develop a microfluidic-based 3D biomimetic platform to systematically investigate the concentration-dependent effects of catalpol on promoting NSCs-to-OLs differentiation and to elucidate the role of the caveolin-1(Cav-1)signaling pathway in this process.Methods We developed a novel multiplexed microfluidic device featuring parallel microchannels with integrated gradient generators capable of establishing and maintaining precise linear concentration gradients(0-3 g/L catalpol)across 3D NSCs cultures.This platform facilitated the continuous perfusion culture of NSC-derived 3D spheroids,mimicking the dynamic in vivo microenvironment.Real-time cell viability was assessed using Calcein-AM/propidium iodide(PI)dual staining,with fluorescence imaging quantifying live/dead cell ratios.Oligodendrocyte differentiation was evaluated through quantitative reverse transcription polymerase chain reaction(qRT-PCR)for MBP and SOX10 gene expression,complemented by immunofluorescence staining to visualize corresponding protein changes.To dissect the molecular mechanism,the Cav-1-specific pharmacological inhibitor methyl‑β‑cyclodextrin(MCD)was employed to perturb the pathway,and its effects on differentiation markers were analyzed.Results Catalpol demonstrated excellent biocompatibility,with cell viability exceeding 96%across the entire tested concentration range(0-3 g/L),confirming its non-cytotoxic nature.At the optimal concentration of 0-3 g/L,catalpol significantly upregulated both MBP and SOX10 expression(P<0.05,P<0.01),indicating robust promotion of oligodendroglial differentiation.Intriguingly,Cav-1 mRNA expression was progressively downregulated during NSC differentiation into OLs.Further inhibition of Cav-1 with MCD further enhanced this effect,leading to a statistically significant increase in OL-specific gene expression(P<0.05,P<0.01),suggesting Cav-1 acts as a negative regulator of OLs differentiation.Conclusion This study established an integrated microfluidic gradient chip-3D NSC spheroid culture system,which combines the advantages of precise chemical gradient control with physiologically relevant 3D cell culture.The findings demonstrate that 3 g/L catalpol effectively suppresses Cav-1 signaling to drive NSC differentiation into functional OLs.This work not only provides novel insights into the Cav-1-dependent mechanisms of myelination but also delivers a scalable technological platform for future research on remyelination therapies,with potential applications in cerebral palsy and other white matter disorders.The platform’s modular design permits adaptation for screening other neurogenic compounds or investigating additional signaling pathways involved in OLs maturation.
基金supports for this project from State Key Laboratory of Chemical Safety(SKLCS–2024001)are gratefully acknowledged。
文摘Bubble breakup at T-junction microchannels is the basis for the numbering-up of gas−liquid two-phase flow in parallelized microchannels. This article presents the bubble breakup in viscous liquids at a microfluidic T-junction. Nitrogen is used as the gas phase, and glycerol-water mixtures with different mass concentration of glycerol as the liquid phase. The evolution of the gas−liquid interface during bubble breakup at the microfluidic T-junction is explored. The thinning of the bubble neck includes the squeezing stage and the rapid pinch-off stage. In the squeezing stage, the power law relation is found between the minimum width of the bubble neck and the time, and the values of exponents α1 and α2 are influenced by the viscous force. The values of pre-factors m_(1) and m_(2) are negatively correlated with the capillary number. In the rapid pinch-off stage, the thinning of the bubble neck is predominated by the surface tension, and the minimum width of the bubble neck can be scaled with the remaining time as power-law. The propagation of the bubble tip can be characterized by the power law between the movement distance and the time, with decreasing exponent as increased liquid viscosity.
基金supported by grants from the Interdisciplinary Program of Shanghai Jiao Tong University(No.YG2023LC04)the National Natural Science Foundation of China(Nos.32471473,62231025,and 82171011)+1 种基金the Research Program of Shanghai Science and Technology Committee(Nos.24141900900 and 25JC3201100)Chongqing Natural Science Foundation(No.CSTB2022NSCQ-MSX0767)
文摘The vascular network is integral to the developmental and metabolic processes of various tissues and functions as a systemic circulatory system that also interconnects organs throughout the body.In this study,we describe a multilayered microfluidic organ-on-a-chip platform designed for reproducing various three-dimensional(3D)vascularized microtissue models for biological applications.This platform utilizes a porous membrane as a physical barrier and leverages capillary action for hydrogel self-filling.Its high flow resistance mitigates the risk of gel bursting into the medium channels and facilitates the delivery of substances to generate a wide range of interstitial flow and biochemical factor concentration gradients.This study demonstrated that this platform can be used to accurately replicate 3D microenvironments for vasculogenesis,angiogenesis,and vascularized tumor modeling.We also investigated the critical role of multiple microenvironmental regulations in vascular formation on a chip.Moreover,we reproduced the process of tumor angiogenesis,including primary solid tumor features and the inhibitory effects of antitumor drugs on tumor growth and tumor vasculature before and after angiogenesis.Hence,our multilayered microfluidic platform is valuable for exploring multiple vascular mechanisms and constructing specific microtissues that closely mimic in vivo physiological conditions,providing new strategies for cancer research.Furthermore,the multilayered configuration improves design flexibility and scalability,providing the potential for a multi-organ interconnected platform for high-throughput drug screening.
文摘Professor LIN Jin-Ming is a distinguished scholar in the Department of Chemistry,Tsinghua University.He was selected into the Chinese Academy of Sciences"Hundred Talents Program"in 2001,and received the Outstanding Young Scholars Fund from the National Science Foundation in the same year.He is a fellow of the Chinese Chemical Society and a fellow of the Royal Society of Chemistry.Prof.LIN has received about 30 academic awards for his contributions in microfluidics,chemiluminescence and separation science.He is the author or co-author of more than 500 original research papers published in international journals,45 review papers,and 8 books,and holds 50 invention patents.His current research focuses on cell culture and analysis on microfluidics with mass spectrometry and chemiluminescence.
基金supported by National Natural Science Foundation of China(Nos.12072381,22072185,21805315)Guangdong Basic and Applied Basic Research Foundation(No.2024A1515011812)Science and Technology Innovation Project of Guangzhou(No.202102020263).
文摘On-demand droplet manipulation plays a critical role in microfluidics,bio/chemical detection and microreactions.Acoustic droplet manipulation has emerged as a promising technique due to its non-contact nature,biocompatibility and precision,circumventing the complexities associated with other methods requiring surface or droplet pretreatment.Despite their promise,existing methods for acoustic droplet manipulation often involve complex hardware setups and difficulty for controlling individual droplet amidst multiple ones.Here we fabricate simple yet effective acoustic tweezers for in-surface and out-of-surface droplet manipulation.It is found that droplets can be transported on the superhydrophobic surfaces when the acoustic radiation force surpasses the friction force.Using a two-axis acoustic tweezer,droplets can be maneuvered along arbitrarily programmed paths on the surfaces.By introducing multiple labyrinthine structures on the superhydrophobic surface,individual droplet manipulation is realized by constraining the unselected droplets in the labyrinthine structures.In addition,a three-axis acoustic tweezer is developed for manipulating droplets in three-dimensional space.Potential applications of the acoustic tweezers for micro-reaction,bio-assay and chemical analysis are also demonstrated.
文摘As prepubertal boys do not yet produce spermatozoa,they cannot rely on sperm cryopreservation for fertility preservation before gonadotoxic therapy,such as high-dose alkylating agents or radiotherapy in the case of childhood cancers.According to the current guidelines,cryopreservation of testicular biopsies containing spermatogonial stem cells(SSCs)may be proposed to high-risk patients for potential later therapeutic use to fulfill the patients’wish for a biological child.One promising technique for human in vitro spermatogenesis and in vitro propagation of human SSCs is microfluidic(MF)culture,in which cells or tissues are subjected to a continuous flow of medium.This provides exact control over such parameters as nutrient content and gradients,as well as the removal of waste metabolites.While MF has been shown to maintain tissues and cell populations of organs for longer than conventional in vitro culture techniques,it has not been widely used for testicular in vitro culture.MF could advance human testicular in vitro culture and is also applicable to reprotoxicity studies.This review summarizes the findings and achievements of testis-on-chip(ToC)setups to date and discusses the benefits and limitations of these for spermatogenesis in vitro and toxicity assessment.
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supported by the National Natural Science Foundation of China(22378227)Shijiazhuang Science and Technology Bureau(231790163A).
文摘Chemical synthesis is essential in industries such as petrochemicals, fine chemicals, and pharmaceuticals, driving economic and social development. The increasing demand for new molecules and materials calls for novel chemical reactions;however, manual experimental screening is time-consuming. Artificial intelligence (AI) offers a promising solution by leveraging large-scale experimental data to model chemical reactions, although challenges such as the lack of standardization and predictability in chemical synthesis hinder AI applications. Additionally, the multi-scale nature of chemical reactions, along with complex multiphase processes, further complicates the task. Recent advances in microchemical systems, particularly continuous flow methods using microreactors, provide precise control over reaction conditions, enhancing reproducibility and enabling high-throughput experimentation. These systems minimize transport-related inconsistencies and facilitate scalable industrial applications. This review systematically explores recent developments in intelligent synthesis based on microchemical systems, focusing on reaction system design, synthesis robots, closed-loop optimization, and high-throughput experimentation, while identifying key areas for future research.
基金the National Nature Science Foundation of China(No.22107028)Natural Science Foundation of Chongqing(No.CSTB2023NSCQ-MSX0335)。
文摘The rapid development of microfluidic technology has led to the evolution of microdroplets from simple emulsion structures to complex multilayered and multicompartmental configurations.These advancements have endowed microdroplets with the capability to contain multiple compartments that remain isolated from one another,enabling them to carry different molecules of interest.Consequently,researchers can now investigate intricate spatially confined chemical reactions and signal transduction pathways within subcellular organelles.Moreover,modern microdroplets often possess excellent optical transparency,allowing fluorescently labelled,multi-layered,and compartmental droplets to provide detailed insights through real-time,in situ,and dynamic fluorescence imaging.Hence,this review systematically summarizes current methodologies for preparing multicomponent microdroplets and their applications,particularly focusing on fluorescent microdroplets.Additionally,it discusses existing critical challenges and outlines future research directions.By offering a comprehensive overview of the preparation methods and applications of fluorescent microdroplets,this review aims to stimulate the interest of researchers and foster their utilization in more complex and biomimetic environments.
基金financially supported by the National Science Fund for Excellent Young Scholars(32222069)National Natural Science Foundation of China(32172349)+1 种基金Foundation for Innovative Research Groups of the National Natural Science Foundation of China(32021005)National Key Research and Development Program of China(2020YFA0908300).
文摘Bacillus thuringiensis,a safe bacterium widely used in agriculture for the biocontrol of pests,has great potential for protein production.The linear plasmid expression system,bacterial orthogonal DNA replication system constructed based on B.thuringiensis prophage GIL16,can achieve stable and high levels of gene expression in the absence of external selection pressure,facilitating development of B.thuringiensis chassis cells.However,the regulatory elements of gene expression and protein secretion suitable for the B.thuringiensis expression system are still lacking.Therefore,the development and optimization of different genetic tools are required.We constructed a promoter library containing 107 different-strength promoters(covering persistently high/intermediate/low level)by transcriptomic analysis of the cell at different growth stages and a signal peptide library(59 signal peptides from Bacillus subtilis and four endogenous signal peptides from B.thuringiensis)to enrich the genetic toolbox using alpha-lactalbumin(α-LA)as the characterization product.Then,a high-throughput microfluidic screening platform based on BacORep and self-assembled split fluorescent protein was developed to further optimize expression elements,resulting in an improved α-LA-producing B.thuringiensis.Finally,the maximum copy number of linear plasmids was 9.3 times higher than that of the original.The titer of α-LA reached 107.7 mg/L in a 3 L bioreactor,which was comparable to the highest yield reported in Komagataella phaffii.We substantially expanded the synthetic biology toolbox for linear plasmid expression systems and provided a strategy for creating efficient prokaryotic expression system.
