Damage to the adult mammalian central nervous system （CNS） often results in persistent neurological deficits with limited recovery of functions. The past decade has seen in- creasing research efforts in neural regen...Damage to the adult mammalian central nervous system （CNS） often results in persistent neurological deficits with limited recovery of functions. The past decade has seen in- creasing research efforts in neural regeneration research with the ultimate goal of achieving functional recovery. Many studies have focused on prevention of further neural damage and restoration of functional connections that are com- promised after iniurY or pathological damage.展开更多
In recent years,organoid technology,i.e.,in vitro three-dimensional(3D)tissue culture,has attracted increasing attention in biomedical engineering.Organoids are cell complexes induced by differentiation of stem cells ...In recent years,organoid technology,i.e.,in vitro three-dimensional(3D)tissue culture,has attracted increasing attention in biomedical engineering.Organoids are cell complexes induced by differentiation of stem cells or organ-progenitor cells in vitro using 3D culture technology.They can replicate the key structural and functional characteristics of the target organs in vivo.With the opening up of this new field of health engineering,there is a need for engineering-system approaches to the production,control,and quantitative analysis of organoids and their microenvironment.Traditional organoid technology has limitations,including lack of physical and chemical microenvironment control,high heterogeneity,complex manual operation,imperfect nutritional supply system,and lack of feasible online analytical technology for the organoids.The introduction of microfluidic chip technology into organoids has overcome many of these limitations and greatly expanded the scope of applications.Engineering organoid microfluidic system has become an interdisciplinary field in biomedical and health engineering.In this review,we summarize the development and culture system of organoids,discuss how microfluidic technology has been used to solve the main technical challenges in organoid research and development,and point out new opportunities and prospects for applications of organoid microfluidic system in drug development and screening,food safety,precision medicine,and other biomedical and health engineering fields.展开更多
To adapt to a complex and variable environment,self-adaptive camouflage technology is becoming more and more important in all kinds of military applications by overcoming the weakness of the static camouflage.In natur...To adapt to a complex and variable environment,self-adaptive camouflage technology is becoming more and more important in all kinds of military applications by overcoming the weakness of the static camouflage.In nature,the chameleon can achieve self-adaptive camouflage by changing its skin color in real time with the change of the background color.To imitate the chameleon skin,a camouflaged film controlled by a color-changing microfluidic system is proposed in this paper.The film with microfluidic channels fabricated by soft materials can achieve dynamic cloaking and camouflage by circulating color liquids through channels inside the film.By sensing and collecting environmental color change information,the control signal of the microfluidic system can be adjusted in real time to imitate chameleon skin.The microstructure of the film and the working principle of the microfluidic color-changing system are introduced.The mechanism to generate the control signal by information processing of background colors is illustrated.“Canny”double-threshold edge detection algorithm and color similarity are used to analyze and evaluate the camouflage.The tested results show that camouflaged images have a relatively high compatibility with environmental backgrounds and the dynamic cloaking eff ect can be achieved.展开更多
Exosomes are now raising focus as a prospective biomarker for cancer diagnostics and prognosis owing to its unique bio-origin and composition.Exosomes take part in cellular communication and receptor mediation and tra...Exosomes are now raising focus as a prospective biomarker for cancer diagnostics and prognosis owing to its unique bio-origin and composition.Exosomes take part in cellular communication and receptor mediation and transfer their cargos(e.g.,proteins,m RNA and DNA).Quantitative analysis of tumor-related nucleic acid mutations can be a potential method to cancer diagnosis and prognosis in early stages.Here we present an integrated microfluidic system for exosome on-chip isolation and lung cancer RNA analysis through droplet digital PCR(dd PCR).Gradient dilution experiments show great linearity over a large concentration range with R^(2)=0.9998.Utilizing the system,four cell lines and two mutation targets were parallelly detected for mutation analysis.The experiments demonstrated mutation heterogeneity and the results were agree with cell researches.These results proved our integrated microfluidic system as a promising means for early cancer diagnosis and prognosis in the era of liquid biopsy.展开更多
A microfluidic system was developed for the synthesis of trigonal selenium（t-Se） nanowires, which was composed of a glass microchip coupled with a poly（methyl methacrylate）（PMMA） microchip. In the glass microchi...A microfluidic system was developed for the synthesis of trigonal selenium（t-Se） nanowires, which was composed of a glass microchip coupled with a poly（methyl methacrylate）（PMMA） microchip. In the glass microchip, amorphous selenium（a-Se） colloid was prepared by reducing selenious acid with an excess amount of hydrazine at a temperature of 100 ℃. In the coupled PMMA microchip, a-Se was transformed into more stable t-Se seeds via sonication at room temperature. The residence time of the reactants in both microchips was optimized by varying the dimension and length of the microchannel each. The t-Se nanowires were formed by anisotropic growth of selenium crystallite during sonication and aging under the assistance of β-cyclodextrin（β-CD）. Various stages of the nanowires＇ growth were investigated. The as-synthesized products were characterized by powder X-Ray diffraction（XRD）, Raman spectroscopy, scanning electron microscopy（SEM）, transmission electron microscopy（TEM） and selected-area electron diffraction（SAED）.展开更多
To improve the performance of real-time recombinase polymerase amplification(RPA),a microfluidic system with active mixing is developed to optimize the reaction dynamics.Instead of adopting a single typical reaction c...To improve the performance of real-time recombinase polymerase amplification(RPA),a microfluidic system with active mixing is developed to optimize the reaction dynamics.Instead of adopting a single typical reaction chamber,a specific reactor including a relatively large chamber in center with two adjacent zig-zag channels at two sides is integrated into the microfluidic chip.Active mixing is achieved by driving the viscous reagent between the chamber and the channel back and forth periodically with an outside compact peristaltic pump.To avoid reagent evapora-tion,one end of the reactor is sealed with paraffin oil.A hand-held companion device is developed to facilitate real-time RPA amplification within 20 min.The whole area of the reactor is heated with a resistance heater to provide uniform reaction temperature.To achieve real-time monitoring,a compact fluorescence detection module is integrated into the hand-held device.A smartphone with custom application software is adopted to control the hand-held device and display the real-time fluorescence curves.The performances of two cases with and without active on-chip mixing are compared between each other by detecting African swine fever viruses.It has been demonstrated that,with active on-chip mixing,the amplification efficiency and detection sensitivity can be signifi-cantly improved.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
Combining deep-learning image inpainting algorithms with the microfluidic technology,the paper proposes a method to achieve dynamic stealth and camouflage by using a microfluidic vision camouflage system simulating th...Combining deep-learning image inpainting algorithms with the microfluidic technology,the paper proposes a method to achieve dynamic stealth and camouflage by using a microfluidic vision camouflage system simulating the chameleon skin.The basic principle is to perceive color changes in the external environment and collect ambient image information,and then utilize the image inpainting algorithm to adjust the control signals of the microfluidic system in real time.The detailed working principle of the microfluidic vision camouflage system is presented,and the mechanism of generating control signals for the system through deep-learning image inpainting algorithms and image-processing techniques is elucidated.The camouflage effect of the chameleon skin is analyzed and evaluated using color similarity.Results indicate that the camouflaged images are consistent with the background environment,thereby improving the target’s stealth and maneuvering characteristics.The camouflage technology developed in the paper based on the microfluidic vision camouflage system can be applied to several situations,such as military camouflage uniforms,robot skins,and weapon equipment.展开更多
Previously we had developed a microfluidic system that can be easily fabricated by bending a stainless-steel tube into large circular loops.In this study,a fast and continuous preparation method for superfine TiO_(2) ...Previously we had developed a microfluidic system that can be easily fabricated by bending a stainless-steel tube into large circular loops.In this study,a fast and continuous preparation method for superfine TiO_(2) nanoparticles(TiO_(2)-NPs)was developed for the aforementioned microfluidic system.The proposed method can yield anatase TiO_(2) in 3.5 min,in contrast to the traditional hydrothermal reaction method,which requires hours or even days.Different reaction conditions,such as reaction temperature(120-200℃),urea concentration(20-100 g/L),and tube length(5-20 m)were investigated.X-ray diffraction and Brunauer-Emmett-Teller analysis indicate that the as-prepared TiO_(2)-NPs have crystalline sizes of 4.1-5.8 nm and specific surface areas of 250.7-330.7 m^(2)/g.Transmission electron microscopy images show that these TiO_(2)-NPs have an even diameter of approximately 5 nm.Moreover,because of their small crystalline sizes and large specific surface areas,most of these as-prepared TiO_(2)-NPs exhibit considerably better absorption and photocatalytic performance with methylene blue than commercial P5 TiO_(2) does.展开更多
The outbreak of virus-induced infectious diseases poses a global public-health challenge.Nucleic acid amplification testing(NAAT)enables early detection of pandemic viruses and plays a vital role in preventing onward ...The outbreak of virus-induced infectious diseases poses a global public-health challenge.Nucleic acid amplification testing(NAAT)enables early detection of pandemic viruses and plays a vital role in preventing onward transmission.However,the requirement of skilled operators,expensive instrumentation,and biosafety laboratories has hindered the use of NAAT for screening and diagnosis of suspected patients.Here we report development of a fully automated centrifugal microfluidic system with sample-in-answer-out capability for sensitive,specific,and rapid viral nucleic acid testing.The release of nucleic acids and the subsequent reverse transcription loop-mediated isothermal amplification(RT-LAMP)were integrated into the reaction units of a microfluidic disc.The whole processing steps such as injection of reagents,fluid actuation by rotation,heating and temperature control,and detection of fluorescence signals were carried out automatically by a customized instrument.We validate the centrifugal microfluidic system using oropharyngeal swab samples spiked with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)armored RNA particles.The estimated limit of detection for armored RNA particles is 2 copies per reaction,the throughput is 21 reactions per disc,and the assay sample-to-answer time is approximately 70 min.This enclosed and automated microfluidic system efficiently avoids viral contamination of aerosol,and can be readily adapted for virus detection outside the diagnostic laboratory.展开更多
Endothelial cells arranged on the vessel lumen are constantly stimulated by blood flow,blood pressure and pressureinduced cyclic stretch.These stimuli are sensed through mechanical sensory structures and converted int...Endothelial cells arranged on the vessel lumen are constantly stimulated by blood flow,blood pressure and pressureinduced cyclic stretch.These stimuli are sensed through mechanical sensory structures and converted into a series of functional responses through mechanotransduction pathways.The process will eventually affect vascular health.Therefore,there has been an urgent need to establish in vitro endothelial biomechanics and mechanobiology of models,which reproduce three-dimensional structure vascular system.In recent years,the rapid development in microfluidic technology makes it possible to replicate the key structural and functionally biomechanical characteristics of vessels.Here,we summarized the progress of microfluidic chips used for the investigation of endothelial biomechanics and mechanobiology of the vascular system.Firstly,we elucidated the contribution of shear stress and circumferential stress,to vascular physiology.Then,we reviewed some applications using microfluidic technology in angiogenesis and vasculogenesis,endothelial permeability and mechanotransduction,as well as the blood-brain barrier under these physical forces.Finally,we discussed the future obstacles in terms of the development and application of microfluidic vascular chips.展开更多
Immunoassays are useful for many bioassays. Many new techniques and materials are introduced into the immunoassay to improve the efficiency. This paper reviews recent progress in the application of microfluidic system...Immunoassays are useful for many bioassays. Many new techniques and materials are introduced into the immunoassay to improve the efficiency. This paper reviews recent progress in the application of microfluidic systems and gold nanoparticles in immunoassay. The micro/nano technologies and materials can offer good sensitivity, fast detection, cost-effectiveness and easy signal readout. In particular, the miniaturization of microfluidics and colorimetric assays based on gold nanoparticles have dramatically improved the efficiency of immunoassays.展开更多
Microfluidic solvent extraction （micro SX） of gadolinium was conducted using a mono- and diester mixture （MDEHPA） as the cationic extractant. A microfluidic Y-Y channel was fabricated using CO2- laser technique in...Microfluidic solvent extraction （micro SX） of gadolinium was conducted using a mono- and diester mixture （MDEHPA） as the cationic extractant. A microfluidic Y-Y channel was fabricated using CO2- laser technique in a glass microchip used as the extraction system. Compared with batch extraction, extraction kinetic is found fast, and extraction equilibrium is attained within 15 s. Stoichiometry of the extracted complex is found to be Gd（NOs）3-3MDEHPA using log-log plot method. Additionally, the operating parameters and overall volumetric mass transfer coefficient （kLα） were investigated to determine the mass transfer performance. Optimal condition of microextraction for gadolinium using response surface methodology was determined （feed solutions 31 mg/L adjusted to pH value 2.5, extractant concentration 2.9 vol% and extraction time 13.5 s）. In optimal condition, gadolinium extraction yield is obtained 95.5%. Findings of this study approve simplicity, portability, effectiveness, swiftness, and environmental friendliness microfluidic solvent extraction process and reveal that micro SX is useful in the field of extraction strategic metals present at low concentrations, which are otherwise not technically amenable or economically feasible to extract using current traditional methods.展开更多
Bacteria producingβ-lactamases have become a major issue in the global public health field.To restrain the development of drug resistance and reduce the abuse of antibiotics,it is very important to rapidly identify b...Bacteria producingβ-lactamases have become a major issue in the global public health field.To restrain the development of drug resistance and reduce the abuse of antibiotics,it is very important to rapidly identify bacteria producingβ-lactamases and put forward a reasonable treatment plan.Here,an integrated microfluidic chip-mass spectrometry system was proposed for rapid screening ofβ-lactamaseproducing bacteria and optimization ofβ-lactamase inhibitor dosing concentration.The concentration gradient generator followed by an array of bacterial culture chambers,as well as micro-solid-phase extraction columns was designed for sample pretreatment before mass analysis.By using the combination system,the process of the hydrolysis of antibiotics byβ-lactamase-producing bacteria could be analyzed.To validate the feasibility,four antibiotics and two antibiotic inhibitors were investigated using three strains including negative control,SHV-1 and TEM-1 strains.SHV-1 and TEM-1 strains were successfully distinguished as theβ-lactamase producing strains.And the acquired optimal concentrations ofβ-lactamase inhibitors were in accordance with the results by that obtained from the traditional microdilution broth method.The total analysis time only needed around 2 h,which was faster than conventional methods that require a few days.The technique presented herein provides an easy and rapid protocol forβ-lactamase resistance related studies,which is important for the inhibition of antimicrobial resistance development and the reduction of antibiotics abuse.展开更多
Microfluidic chip and giant magnetoimpedance(GMI)-related technology has developed quickly over the past decades in the field of biological detection.In this work,we designed and fabricated a GMI-based microfluidic sy...Microfluidic chip and giant magnetoimpedance(GMI)-related technology has developed quickly over the past decades in the field of biological detection.In this work,we designed and fabricated a GMI-based microfluidic system for screening of multiplex gastric cancer biomarkers.The microfluidic chip and GMI sensor were prepared by micro-electromechanical systems(MEMS)technology.This system can analyse 8 gastric cancer protein biomarkers simultaneously in less than 25 mins and offer more stable detection signal than conventional enzymological or fluorescent methods.The microfluidic chip was then tested in 150 clinical specimens and compared with enzyme-linked immunosorbent assay(ELISA)method.The results indicated no significant difference and excellent agreement.In short,the prototype of GMI-based microfluidic system has been developed successfully and showed promising potentials for parallel screening of cancer biomarkers.展开更多
Objective:To investigate the anti-invasion efficacy of the ethanol extract of Oldenlandia diffusa Will.(EEOD) on a three-dimensional(3D) human malignant glioma(MG) cell invasion and perfusion model based on microfluid...Objective:To investigate the anti-invasion efficacy of the ethanol extract of Oldenlandia diffusa Will.(EEOD) on a three-dimensional(3D) human malignant glioma(MG) cell invasion and perfusion model based on microfluidic chip culture and the possible mechanism of action of Oldenlandia diffusa Will.(OD).Methods:The comprehensive pharmacodynamic analysis method in this study was based on microfluidic chip 3D cell perfusion culture technology,and the action mechanism of Chinese medicine(CM) on human MG cells was investigated through network pharmacology analysis.First,the components of EEOD were analyzed by ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS).Then,cell viability and apoptosis were assessed to determine the optimum concentration of EEOD for invasion experiments,and two-dimensional(2D) migration and invasion abilities of U87 and U251 MG cells were evaluated using scratch wound and Transwell assays.The possible mechanism underlying the effects of EEOD on glioma was analyzed through a network pharmacology approach.Results:Thirty-five compounds of EEOD were detected by UPLC-Q-TOF/MS.EEOD suppressed the viability of MG cells,promoted their apoptosis,and inhibited their migratory and invasive potentials(all P<0.05).Network pharmacology analysis showed that OD inhibited the invasion of MG cells by directly regulating MAPK and Wnt pathways through MAPK,EGFR,MYC,GSK3B,and other targets.The anti-invasion effect of OD was also found to be related to the indirect regulation of microtubule cytoskeleton organization.Conclusion:EEOD could inhibit the invasion of human MG cells,and the anti-invasion mechanism of OD might be regulating MAPK and Wnt signaling pathways and microtubule cytoskeleton organization.展开更多
The diameter of the excitation beam was decreased greatly by integrating the fiber on the microfluidic chip as light propagation medium.The coupling efficiency of the fiber was improved with optical fiber collimation ...The diameter of the excitation beam was decreased greatly by integrating the fiber on the microfluidic chip as light propagation medium.The coupling efficiency of the fiber was improved with optical fiber collimation device coupling beam. The chip was placed in the darkroom to avoid the interference of the external light.The cost of the instrument was decreased with a high brightness blue LED as excitation source;the performance of the system was valuated by the determination of FITC fluorescein with a minimum detectable concentration of 2.2×10^(-8) mol/L,the Signal-to-Noise Ratio (SNR) S/N=5.The correlation coefficient of the detection system within the range of 1.8×10^(-7) mol/L～4×10^(-5)mol/L was 0.9972.展开更多
Thrombosis remains a major global health concern mainly characterized by high rates of morbidity and mortality.Animal models serve as an indispensable tool to understand the underlying pathogenesis of thrombosis and a...Thrombosis remains a major global health concern mainly characterized by high rates of morbidity and mortality.Animal models serve as an indispensable tool to understand the underlying pathogenesis of thrombosis and assess the efficacy of novel antithrombotic drugs.Currently,zebrafish has emerged as a valuable model organism for thrombosis research.However,the traditional method of studying zebrafish thrombosis requires a laborious and time-consuming procedure,including anesthesia and manual immobilization of zebrafish.In this study,based on hydrodynamic force,a lateral-immobilization zebrafish microfluidic chip(LIZMC)was designed to evaluate the cardiovascular system of multiple larvae within a single microscope field of view.Specifically,coupling with microscope imaging,real-time monitoring of the peripheral blood circulation in the tail of phenylhydrazine(PHZ)-induced zebrafish thrombosis was enabled.Furthermore,the reliability of LIZMC for in vivo evaluation of antithrombotic agents in zebrafish was verified using aspirin.Collectively,this novel LIZMC-based system can be used for in vivo zebrafish thrombosis studies and rapid screening of antithrombotic agents.展开更多
Recent developments in the utilization of microfluidic chips(MFCs) have shown their potential utility in multiphase organic synthesis by enabling efficient organic reactions in flow chemistry. However, MFCs technology...Recent developments in the utilization of microfluidic chips(MFCs) have shown their potential utility in multiphase organic synthesis by enabling efficient organic reactions in flow chemistry. However, MFCs technology has been wandering in the laboratory of small dose synthetic routes, which is limited to the level of "tiny" fluid flux. To address this issue, we herein report the first case of the chips with highthroughput 3D channels produced by femtosecond laser being used to create a time-saving, cost-effective and risk-free approach suitable for large-scale flow synthesis. Several multiphase reactions have been successfully prepared on demand in our designed flow synthesis system containing 3D MFCs: 1) benzyl alcohol was converted to benzaldehyde in 3 min with a yield of 97.50% by liquid-liquid two-phase transfer catalytic oxidation;2) organozinc reagents and α-cyano carbonyl carbon compounds were synthesized by solid-liquid two-phase metal insertion reaction in 7 min, and the yield was up to 100%;3) benzoic acid was synthesized by gas-liquid two-phase carboxylation reaction in 2.8 s with a yield of 96%. Significant gains in production rate result from the effective scaling of flow reactors from microliters per hour in MFCs to intermediate milliliters per minute without affecting mass transport performance. Meanwhile,our 3D MFCs show excellent mass and heat transfer efficiency in large-scale industrial units, breaking through the bottleneck in this field. As a result, it is possible to imagine the creation of a new, streamlined flow synthetic technique via MFCs for green multiphase organic synthesis.展开更多
Optically induced electroporation(OIE)is a promising microfluidic-based approach for the electroporation of cell membranes.However,previously proposed microfluidic cell-electroporation devices required tedious sample ...Optically induced electroporation(OIE)is a promising microfluidic-based approach for the electroporation of cell membranes.However,previously proposed microfluidic cell-electroporation devices required tedious sample pre-treatment steps,specifically,periodic media exchange.To enable the use of this OIE process in a practical protocol,we developed a new design for a microfluidic device that can perform continuous OIE;i.e.,it is capable of automatically replacing the culture medium with electroporation buffers.Integrating medium exchanges on-chip with OIE minimises critical issues such as cell loss and damage,both of which are common in traditional,centrifuge-based approaches.Most importantly,our new system is suitable for handling small or rare cell populations.Two medium exchange modules,including a micropost array railing structure and a deterministic lateral displacement structure,were first adopted and optimised for medium exchange and then integrated with the OIE module.The efficacy of these integrated microfluidic systems was demonstrated by transfecting an enhanced green fluorescent protein(EGFP)plasmid into human embryonic kidney 293T cells,with an efficiency of 8.3%.This result is the highest efficiency reported for any existing OIE-based microfluidic system.In addition,successful co-transfections of three distinct plasmids(EGFP,DsRed and ECFP)into cells were successfully achieved.Hence,we demonstrated that this system is capable of automatically performing multiple gene transfections into mammalian cells.展开更多
基金supported by grants from NIH National Institute of Mental Health MH085267National Institute of Neurological Disorders and Stroke NS060017
文摘Damage to the adult mammalian central nervous system （CNS） often results in persistent neurological deficits with limited recovery of functions. The past decade has seen in- creasing research efforts in neural regeneration research with the ultimate goal of achieving functional recovery. Many studies have focused on prevention of further neural damage and restoration of functional connections that are com- promised after iniurY or pathological damage.
基金This work was supported by the Key Areas Research Development Projects of Guangdong Province(No.2019B020210001)the Tsinghua-U Tokyo Collaborative Research Fund(No.20193080052)the Key Areas Research Development Projects of Hebei Province(No.20375502D).
文摘In recent years,organoid technology,i.e.,in vitro three-dimensional(3D)tissue culture,has attracted increasing attention in biomedical engineering.Organoids are cell complexes induced by differentiation of stem cells or organ-progenitor cells in vitro using 3D culture technology.They can replicate the key structural and functional characteristics of the target organs in vivo.With the opening up of this new field of health engineering,there is a need for engineering-system approaches to the production,control,and quantitative analysis of organoids and their microenvironment.Traditional organoid technology has limitations,including lack of physical and chemical microenvironment control,high heterogeneity,complex manual operation,imperfect nutritional supply system,and lack of feasible online analytical technology for the organoids.The introduction of microfluidic chip technology into organoids has overcome many of these limitations and greatly expanded the scope of applications.Engineering organoid microfluidic system has become an interdisciplinary field in biomedical and health engineering.In this review,we summarize the development and culture system of organoids,discuss how microfluidic technology has been used to solve the main technical challenges in organoid research and development,and point out new opportunities and prospects for applications of organoid microfluidic system in drug development and screening,food safety,precision medicine,and other biomedical and health engineering fields.
基金the National Natural Science Foundation of China for the support(No.51175101)on this paper.
文摘To adapt to a complex and variable environment,self-adaptive camouflage technology is becoming more and more important in all kinds of military applications by overcoming the weakness of the static camouflage.In nature,the chameleon can achieve self-adaptive camouflage by changing its skin color in real time with the change of the background color.To imitate the chameleon skin,a camouflaged film controlled by a color-changing microfluidic system is proposed in this paper.The film with microfluidic channels fabricated by soft materials can achieve dynamic cloaking and camouflage by circulating color liquids through channels inside the film.By sensing and collecting environmental color change information,the control signal of the microfluidic system can be adjusted in real time to imitate chameleon skin.The microstructure of the film and the working principle of the microfluidic color-changing system are introduced.The mechanism to generate the control signal by information processing of background colors is illustrated.“Canny”double-threshold edge detection algorithm and color similarity are used to analyze and evaluate the camouflage.The tested results show that camouflaged images have a relatively high compatibility with environmental backgrounds and the dynamic cloaking eff ect can be achieved.
基金National Natural Science Foundation of China(Nos.61971410,and 62001458)Shanghai Sailing Program(No.20YF1457100)。
文摘Exosomes are now raising focus as a prospective biomarker for cancer diagnostics and prognosis owing to its unique bio-origin and composition.Exosomes take part in cellular communication and receptor mediation and transfer their cargos(e.g.,proteins,m RNA and DNA).Quantitative analysis of tumor-related nucleic acid mutations can be a potential method to cancer diagnosis and prognosis in early stages.Here we present an integrated microfluidic system for exosome on-chip isolation and lung cancer RNA analysis through droplet digital PCR(dd PCR).Gradient dilution experiments show great linearity over a large concentration range with R^(2)=0.9998.Utilizing the system,four cell lines and two mutation targets were parallelly detected for mutation analysis.The experiments demonstrated mutation heterogeneity and the results were agree with cell researches.These results proved our integrated microfluidic system as a promising means for early cancer diagnosis and prognosis in the era of liquid biopsy.
基金Supported by the Natural Science Foundation of Zhejiang Province,China(No.Z407029)the Hangzhou Qianjiang Scholar Foundation,China(No.HZ2010-41)
文摘A microfluidic system was developed for the synthesis of trigonal selenium（t-Se） nanowires, which was composed of a glass microchip coupled with a poly（methyl methacrylate）（PMMA） microchip. In the glass microchip, amorphous selenium（a-Se） colloid was prepared by reducing selenious acid with an excess amount of hydrazine at a temperature of 100 ℃. In the coupled PMMA microchip, a-Se was transformed into more stable t-Se seeds via sonication at room temperature. The residence time of the reactants in both microchips was optimized by varying the dimension and length of the microchannel each. The t-Se nanowires were formed by anisotropic growth of selenium crystallite during sonication and aging under the assistance of β-cyclodextrin（β-CD）. Various stages of the nanowires＇ growth were investigated. The as-synthesized products were characterized by powder X-Ray diffraction（XRD）, Raman spectroscopy, scanning electron microscopy（SEM）, transmission electron microscopy（TEM） and selected-area electron diffraction（SAED）.
基金supported by the National Natural Science Foundation of China(Nos.81871505,61971026)the Fundamental Research Fund for the Central Universities(No.XK1802-4)+1 种基金the National Science and Technology Major Project(No.2018ZX10732101-001-009)the Research Fund to the Top Scientific and Technological Innovation Team from Beijing University of Chemical Technology(No.buctylkjcx06).
文摘To improve the performance of real-time recombinase polymerase amplification(RPA),a microfluidic system with active mixing is developed to optimize the reaction dynamics.Instead of adopting a single typical reaction chamber,a specific reactor including a relatively large chamber in center with two adjacent zig-zag channels at two sides is integrated into the microfluidic chip.Active mixing is achieved by driving the viscous reagent between the chamber and the channel back and forth periodically with an outside compact peristaltic pump.To avoid reagent evapora-tion,one end of the reactor is sealed with paraffin oil.A hand-held companion device is developed to facilitate real-time RPA amplification within 20 min.The whole area of the reactor is heated with a resistance heater to provide uniform reaction temperature.To achieve real-time monitoring,a compact fluorescence detection module is integrated into the hand-held device.A smartphone with custom application software is adopted to control the hand-held device and display the real-time fluorescence curves.The performances of two cases with and without active on-chip mixing are compared between each other by detecting African swine fever viruses.It has been demonstrated that,with active on-chip mixing,the amplification efficiency and detection sensitivity can be signifi-cantly improved.
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 National Natural Science Foundation of China for the support(No.51175101)on this paper.
文摘Combining deep-learning image inpainting algorithms with the microfluidic technology,the paper proposes a method to achieve dynamic stealth and camouflage by using a microfluidic vision camouflage system simulating the chameleon skin.The basic principle is to perceive color changes in the external environment and collect ambient image information,and then utilize the image inpainting algorithm to adjust the control signals of the microfluidic system in real time.The detailed working principle of the microfluidic vision camouflage system is presented,and the mechanism of generating control signals for the system through deep-learning image inpainting algorithms and image-processing techniques is elucidated.The camouflage effect of the chameleon skin is analyzed and evaluated using color similarity.Results indicate that the camouflaged images are consistent with the background environment,thereby improving the target’s stealth and maneuvering characteristics.The camouflage technology developed in the paper based on the microfluidic vision camouflage system can be applied to several situations,such as military camouflage uniforms,robot skins,and weapon equipment.
基金This work was financially supported by the National Natural Science Foundation of China(grant Nos.21878169 and 21991102)the National Key Research and Development Program of China(grant No.2019YFA0905100)the Tsinghua University Initiative Scientific Research Program(grant No.2018Z05JZY010).
文摘Previously we had developed a microfluidic system that can be easily fabricated by bending a stainless-steel tube into large circular loops.In this study,a fast and continuous preparation method for superfine TiO_(2) nanoparticles(TiO_(2)-NPs)was developed for the aforementioned microfluidic system.The proposed method can yield anatase TiO_(2) in 3.5 min,in contrast to the traditional hydrothermal reaction method,which requires hours or even days.Different reaction conditions,such as reaction temperature(120-200℃),urea concentration(20-100 g/L),and tube length(5-20 m)were investigated.X-ray diffraction and Brunauer-Emmett-Teller analysis indicate that the as-prepared TiO_(2)-NPs have crystalline sizes of 4.1-5.8 nm and specific surface areas of 250.7-330.7 m^(2)/g.Transmission electron microscopy images show that these TiO_(2)-NPs have an even diameter of approximately 5 nm.Moreover,because of their small crystalline sizes and large specific surface areas,most of these as-prepared TiO_(2)-NPs exhibit considerably better absorption and photocatalytic performance with methylene blue than commercial P5 TiO_(2) does.
基金supported by the National Natural Science Foundation of China(91959101,21904028)Chinese Academy of Sciences(YJKYYQ20180055,YJKYYQ20190068,ZDBS-LY-SLH025)the Strategic Priority Research Program of Chinese Academy of Sciences(XDB36000000)。
文摘The outbreak of virus-induced infectious diseases poses a global public-health challenge.Nucleic acid amplification testing(NAAT)enables early detection of pandemic viruses and plays a vital role in preventing onward transmission.However,the requirement of skilled operators,expensive instrumentation,and biosafety laboratories has hindered the use of NAAT for screening and diagnosis of suspected patients.Here we report development of a fully automated centrifugal microfluidic system with sample-in-answer-out capability for sensitive,specific,and rapid viral nucleic acid testing.The release of nucleic acids and the subsequent reverse transcription loop-mediated isothermal amplification(RT-LAMP)were integrated into the reaction units of a microfluidic disc.The whole processing steps such as injection of reagents,fluid actuation by rotation,heating and temperature control,and detection of fluorescence signals were carried out automatically by a customized instrument.We validate the centrifugal microfluidic system using oropharyngeal swab samples spiked with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)armored RNA particles.The estimated limit of detection for armored RNA particles is 2 copies per reaction,the throughput is 21 reactions per disc,and the assay sample-to-answer time is approximately 70 min.This enclosed and automated microfluidic system efficiently avoids viral contamination of aerosol,and can be readily adapted for virus detection outside the diagnostic laboratory.
基金supported by the National Natural Science Research Foundation of China(61533016,11827803,31971244,31570947,11772036,11421202 and U20A20390)the National Key Research and Development Program of China(2016YFC1102202 and 2016YFC1101101)Beijing Natural Science Foundation(4194079)and the 111 Project(B13003).
文摘Endothelial cells arranged on the vessel lumen are constantly stimulated by blood flow,blood pressure and pressureinduced cyclic stretch.These stimuli are sensed through mechanical sensory structures and converted into a series of functional responses through mechanotransduction pathways.The process will eventually affect vascular health.Therefore,there has been an urgent need to establish in vitro endothelial biomechanics and mechanobiology of models,which reproduce three-dimensional structure vascular system.In recent years,the rapid development in microfluidic technology makes it possible to replicate the key structural and functionally biomechanical characteristics of vessels.Here,we summarized the progress of microfluidic chips used for the investigation of endothelial biomechanics and mechanobiology of the vascular system.Firstly,we elucidated the contribution of shear stress and circumferential stress,to vascular physiology.Then,we reviewed some applications using microfluidic technology in angiogenesis and vasculogenesis,endothelial permeability and mechanotransduction,as well as the blood-brain barrier under these physical forces.Finally,we discussed the future obstacles in terms of the development and application of microfluidic vascular chips.
基金supported by the National Natural Science Foundation of China (90813032, 20890020 & 21025520)the Ministry of Science and Technology (2009CB930000 & 2011CB933201)+2 种基金the Ministry of Health (2008ZX10001-010)Chinese Academy of Sciences (KJCX2-YW-M15)the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry
文摘Immunoassays are useful for many bioassays. Many new techniques and materials are introduced into the immunoassay to improve the efficiency. This paper reviews recent progress in the application of microfluidic systems and gold nanoparticles in immunoassay. The micro/nano technologies and materials can offer good sensitivity, fast detection, cost-effectiveness and easy signal readout. In particular, the miniaturization of microfluidics and colorimetric assays based on gold nanoparticles have dramatically improved the efficiency of immunoassays.
基金Project supported by Department of Chemical,Petroleum and Gas Engineering,Iran University of Science&Technology(IUST)
文摘Microfluidic solvent extraction （micro SX） of gadolinium was conducted using a mono- and diester mixture （MDEHPA） as the cationic extractant. A microfluidic Y-Y channel was fabricated using CO2- laser technique in a glass microchip used as the extraction system. Compared with batch extraction, extraction kinetic is found fast, and extraction equilibrium is attained within 15 s. Stoichiometry of the extracted complex is found to be Gd（NOs）3-3MDEHPA using log-log plot method. Additionally, the operating parameters and overall volumetric mass transfer coefficient （kLα） were investigated to determine the mass transfer performance. Optimal condition of microextraction for gadolinium using response surface methodology was determined （feed solutions 31 mg/L adjusted to pH value 2.5, extractant concentration 2.9 vol% and extraction time 13.5 s）. In optimal condition, gadolinium extraction yield is obtained 95.5%. Findings of this study approve simplicity, portability, effectiveness, swiftness, and environmental friendliness microfluidic solvent extraction process and reveal that micro SX is useful in the field of extraction strategic metals present at low concentrations, which are otherwise not technically amenable or economically feasible to extract using current traditional methods.
基金supported by Research and Development Program in Key Areas of Guangdong Province,China(No.2019B020209009)Natural Science Foundation of Guangdong Province,China(Nos.2020A1515010660 and 2022A1515011437)Shenzhen Fundamental Research and Discipline Layout project(No.JCYJ20180508152244835)。
文摘Bacteria producingβ-lactamases have become a major issue in the global public health field.To restrain the development of drug resistance and reduce the abuse of antibiotics,it is very important to rapidly identify bacteria producingβ-lactamases and put forward a reasonable treatment plan.Here,an integrated microfluidic chip-mass spectrometry system was proposed for rapid screening ofβ-lactamaseproducing bacteria and optimization ofβ-lactamase inhibitor dosing concentration.The concentration gradient generator followed by an array of bacterial culture chambers,as well as micro-solid-phase extraction columns was designed for sample pretreatment before mass analysis.By using the combination system,the process of the hydrolysis of antibiotics byβ-lactamase-producing bacteria could be analyzed.To validate the feasibility,four antibiotics and two antibiotic inhibitors were investigated using three strains including negative control,SHV-1 and TEM-1 strains.SHV-1 and TEM-1 strains were successfully distinguished as theβ-lactamase producing strains.And the acquired optimal concentrations ofβ-lactamase inhibitors were in accordance with the results by that obtained from the traditional microdilution broth method.The total analysis time only needed around 2 h,which was faster than conventional methods that require a few days.The technique presented herein provides an easy and rapid protocol forβ-lactamase resistance related studies,which is important for the inhibition of antimicrobial resistance development and the reduction of antibiotics abuse.
基金supported by project SKLPBS1403,14QNP117 and AWS15J006,and the National Key Basic Research Program(973 Project)(No.2015CB931802)National Natural Scientific Fund(No.81225010,81327002,and 31100717)+1 种基金863 Project of China(2014AA020700)Shanghai Science and Technology Fund(No.13NM1401500 and 15DZ2252000).
文摘Microfluidic chip and giant magnetoimpedance(GMI)-related technology has developed quickly over the past decades in the field of biological detection.In this work,we designed and fabricated a GMI-based microfluidic system for screening of multiplex gastric cancer biomarkers.The microfluidic chip and GMI sensor were prepared by micro-electromechanical systems(MEMS)technology.This system can analyse 8 gastric cancer protein biomarkers simultaneously in less than 25 mins and offer more stable detection signal than conventional enzymological or fluorescent methods.The microfluidic chip was then tested in 150 clinical specimens and compared with enzyme-linked immunosorbent assay(ELISA)method.The results indicated no significant difference and excellent agreement.In short,the prototype of GMI-based microfluidic system has been developed successfully and showed promising potentials for parallel screening of cancer biomarkers.
基金Supported by the National TCM Characteristic Technology Inheritance Talent Training Program (No. J20194828003).
文摘Objective:To investigate the anti-invasion efficacy of the ethanol extract of Oldenlandia diffusa Will.(EEOD) on a three-dimensional(3D) human malignant glioma(MG) cell invasion and perfusion model based on microfluidic chip culture and the possible mechanism of action of Oldenlandia diffusa Will.(OD).Methods:The comprehensive pharmacodynamic analysis method in this study was based on microfluidic chip 3D cell perfusion culture technology,and the action mechanism of Chinese medicine(CM) on human MG cells was investigated through network pharmacology analysis.First,the components of EEOD were analyzed by ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS).Then,cell viability and apoptosis were assessed to determine the optimum concentration of EEOD for invasion experiments,and two-dimensional(2D) migration and invasion abilities of U87 and U251 MG cells were evaluated using scratch wound and Transwell assays.The possible mechanism underlying the effects of EEOD on glioma was analyzed through a network pharmacology approach.Results:Thirty-five compounds of EEOD were detected by UPLC-Q-TOF/MS.EEOD suppressed the viability of MG cells,promoted their apoptosis,and inhibited their migratory and invasive potentials(all P<0.05).Network pharmacology analysis showed that OD inhibited the invasion of MG cells by directly regulating MAPK and Wnt pathways through MAPK,EGFR,MYC,GSK3B,and other targets.The anti-invasion effect of OD was also found to be related to the indirect regulation of microtubule cytoskeleton organization.Conclusion:EEOD could inhibit the invasion of human MG cells,and the anti-invasion mechanism of OD might be regulating MAPK and Wnt signaling pathways and microtubule cytoskeleton organization.
基金financial support from the National Science Foundation of China under Grant number 20299030,60427001 and 60501020.
文摘The diameter of the excitation beam was decreased greatly by integrating the fiber on the microfluidic chip as light propagation medium.The coupling efficiency of the fiber was improved with optical fiber collimation device coupling beam. The chip was placed in the darkroom to avoid the interference of the external light.The cost of the instrument was decreased with a high brightness blue LED as excitation source;the performance of the system was valuated by the determination of FITC fluorescein with a minimum detectable concentration of 2.2×10^(-8) mol/L,the Signal-to-Noise Ratio (SNR) S/N=5.The correlation coefficient of the detection system within the range of 1.8×10^(-7) mol/L～4×10^(-5)mol/L was 0.9972.
基金supported in part by the National Natural Science Foundation of China(Nos.81825020 and 82150208)the Shanghai Science and Technology Commission Biomedical Science and Technology Support Special Project(Nos.21S11907900 and 20S11901000)+3 种基金the Fundamental Research Funds for the Central Universitiesthe Shanghai“Beyond Limits Manufacturing”Projectsponsored by National Program for Special Supports of Eminent ProfessionalsNational Program for Support of Top-notch Young Professionals。
文摘Thrombosis remains a major global health concern mainly characterized by high rates of morbidity and mortality.Animal models serve as an indispensable tool to understand the underlying pathogenesis of thrombosis and assess the efficacy of novel antithrombotic drugs.Currently,zebrafish has emerged as a valuable model organism for thrombosis research.However,the traditional method of studying zebrafish thrombosis requires a laborious and time-consuming procedure,including anesthesia and manual immobilization of zebrafish.In this study,based on hydrodynamic force,a lateral-immobilization zebrafish microfluidic chip(LIZMC)was designed to evaluate the cardiovascular system of multiple larvae within a single microscope field of view.Specifically,coupling with microscope imaging,real-time monitoring of the peripheral blood circulation in the tail of phenylhydrazine(PHZ)-induced zebrafish thrombosis was enabled.Furthermore,the reliability of LIZMC for in vivo evaluation of antithrombotic agents in zebrafish was verified using aspirin.Collectively,this novel LIZMC-based system can be used for in vivo zebrafish thrombosis studies and rapid screening of antithrombotic agents.
基金supported by the Shanghai Municipal Science and Technology Major Project (“Beyond Limits manufacture”)。
文摘Recent developments in the utilization of microfluidic chips(MFCs) have shown their potential utility in multiphase organic synthesis by enabling efficient organic reactions in flow chemistry. However, MFCs technology has been wandering in the laboratory of small dose synthetic routes, which is limited to the level of "tiny" fluid flux. To address this issue, we herein report the first case of the chips with highthroughput 3D channels produced by femtosecond laser being used to create a time-saving, cost-effective and risk-free approach suitable for large-scale flow synthesis. Several multiphase reactions have been successfully prepared on demand in our designed flow synthesis system containing 3D MFCs: 1) benzyl alcohol was converted to benzaldehyde in 3 min with a yield of 97.50% by liquid-liquid two-phase transfer catalytic oxidation;2) organozinc reagents and α-cyano carbonyl carbon compounds were synthesized by solid-liquid two-phase metal insertion reaction in 7 min, and the yield was up to 100%;3) benzoic acid was synthesized by gas-liquid two-phase carboxylation reaction in 2.8 s with a yield of 96%. Significant gains in production rate result from the effective scaling of flow reactors from microliters per hour in MFCs to intermediate milliliters per minute without affecting mass transport performance. Meanwhile,our 3D MFCs show excellent mass and heat transfer efficiency in large-scale industrial units, breaking through the bottleneck in this field. As a result, it is possible to imagine the creation of a new, streamlined flow synthetic technique via MFCs for green multiphase organic synthesis.
基金The authors gratefully acknowledge the financial support provided to this study by“the National Science Council in Taiwan(NSC102-2218-E-007-001)”.
文摘Optically induced electroporation(OIE)is a promising microfluidic-based approach for the electroporation of cell membranes.However,previously proposed microfluidic cell-electroporation devices required tedious sample pre-treatment steps,specifically,periodic media exchange.To enable the use of this OIE process in a practical protocol,we developed a new design for a microfluidic device that can perform continuous OIE;i.e.,it is capable of automatically replacing the culture medium with electroporation buffers.Integrating medium exchanges on-chip with OIE minimises critical issues such as cell loss and damage,both of which are common in traditional,centrifuge-based approaches.Most importantly,our new system is suitable for handling small or rare cell populations.Two medium exchange modules,including a micropost array railing structure and a deterministic lateral displacement structure,were first adopted and optimised for medium exchange and then integrated with the OIE module.The efficacy of these integrated microfluidic systems was demonstrated by transfecting an enhanced green fluorescent protein(EGFP)plasmid into human embryonic kidney 293T cells,with an efficiency of 8.3%.This result is the highest efficiency reported for any existing OIE-based microfluidic system.In addition,successful co-transfections of three distinct plasmids(EGFP,DsRed and ECFP)into cells were successfully achieved.Hence,we demonstrated that this system is capable of automatically performing multiple gene transfections into mammalian cells.
