Paper-based microchips have different advantages,such as better biocompatibility,simple production,and easy handling,making them promising candidates for clinical diagnosis and other fields.This study describes ametho...Paper-based microchips have different advantages,such as better biocompatibility,simple production,and easy handling,making them promising candidates for clinical diagnosis and other fields.This study describes amethod developed to fabricate modular three-dimensional(3D)paper-based microfluidic chips based on projection-based 3D printing(PBP)technology.A series of two-dimensional(2D)paper-based microfluidic modules was designed and fabricated.After evaluating the effect of exposure time on the accuracy of the flow channel,the resolution of this channel was experimentally analyzed.Furthermore,several 3D paper-based microfluidic chips were assembled based on the 2D ones using different methods,with good channel connectivity.Scaffold-based 2D and hydrogel-based 3D cell culture systems based on 3D paper-based microfluidic chips were verified to be feasible.Furthermore,by combining extrusion 3D bioprinting technology and the proposed 3D paper-based microfluidic chips,multiorgan microfluidic chips were established by directly printing 3D hydrogel structures on 3D paperbased microfluidic chips,confirming that the prepared modular 3D paper-based microfluidic chip is potentially applicable in various biomedical applications.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
Nickel(II)as one of the primary categories of heavy metals can lead to serious health problems if achieving the critical levels in the water.Thus,it is vital to propose a stable,reliable,and economical approach for de...Nickel(II)as one of the primary categories of heavy metals can lead to serious health problems if achieving the critical levels in the water.Thus,it is vital to propose a stable,reliable,and economical approach for detecting Ni ions.The microfluidic paper-based analytical devices(µPADs)are potential candidates for the detection of water quality parameters including pH,heavy ions,nitrite and so on.However,it suffers from a huge error caused by the environment and artificial mistakes.In this study,we proposed an improved technique route to increase the stability and reliability of microfluidic paper-based analytical devices.The main technique points include a stable light source,a matched camera,improved reliability of the devices,and effective calculated methods.Finally,we established 15 standard curves that could be used to detect nickel ions and obtained uniform colorimetric results with reliability and repeatability.With those improvements,the relative errors for the five types of real water samples from the Zhongshan industrial parks were reduced to 0.26%,14.78%,24.20%,50.29%and 3.53%,respectively.These results were conducive to exploring this technique for the detection of nickel ions in wastewater from the Zhongshan industrial parks.The results demonstrated that the above technique route is promising for the detection of other heavy metal ions in industrial effluent.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
The first example of the microfluidic chips(MFCs) consisting of centimeter-level 3D channels with highdensity and large-volume fabricated by femtosecond laser micromachining were utilized to develop a time-saving, eco...The first example of the microfluidic chips(MFCs) consisting of centimeter-level 3D channels with highdensity and large-volume fabricated by femtosecond laser micromachining were utilized to develop a time-saving, economical and hazardless flow synthesis process, and its advantages have been proved by in situ formation of aryldiazonium salts and subsequent borylation with bis(pinacolato)diboron. There are several important advantages in our 3D MFC-based flow synthesis technology, including the following:(1) the reaction temperature was altered from ice bath to room temperature;(2) the residence time was reduced by 10 times;(3) the yield was greatly improved, that is, several arylboronates were successfully obtained with higher yield compared to traditional batch process. Therefore, it can be envisioned that a novel, simplified flow synthetic protocol will be developed toward green organic synthesis via MFCs.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
To solve the problems of long experiment period and difficult measurement in core imbibition experiments,fracture-matrix microfluidic chips of different sizes,boundary conditions and wettability regulated by surface p...To solve the problems of long experiment period and difficult measurement in core imbibition experiments,fracture-matrix microfluidic chips of different sizes,boundary conditions and wettability regulated by surface property modification were designed to research the imbibition mechanisms of oil-water,oil-surfactant solution and oil-WinsorⅢtype surfactant solution.In the oil-water,and oil-wettability modification system imbibition process,oil was replaced from the matrix through Haines jump,the capillary back pressure was the main resistance blocking the flow of oil,the reduction of interfacial tension caused the weakening of Haines jump,reduction of oil discharge rate,and increase of oil recovery.The imbibition of oil-water or oil-surfactant solution with low interfacial tension was a counter-current imbibition process dominated by capillary force,in which all boundaries had similar contribution to imbibition,and the recovery data obtained from this experiment fit well with the classic imbibition scaling equation.The imbibition of oil and Winsor III type surfactant solution was a co-current imbibition process dominated by gravity under super-low interfacial tension,and is essentially the formation and re-balance of neutral microemulsion.The imbibition dynamics obtained from this experiment fit well with the modified imbibition scaling equation.展开更多
Diabetes mellitus is a global health problem resulting from islet dysfunction or insulin resistance.The mechanisms of islet dysfunction are still under investigation.Islet hormone secretion is the main function of isl...Diabetes mellitus is a global health problem resulting from islet dysfunction or insulin resistance.The mechanisms of islet dysfunction are still under investigation.Islet hormone secretion is the main function of islets,and serves an important role in the homeostasis of blood glucose.Elucidating the detailed mechanism of islet hormone secretome distortion can provide clues for the treatment of diabetes.Therefore,it is crucial to develop accurate,real-time,laborsaving,high-throughput,automated,and cost-effective techniques for the sensing of islet secretome.Microfluidic chips,an elegant platform that combines biology,engineering,computer science,and biomaterials,have attracted tremendous interest from scientists in the field of diabetes worldwide.These tiny devices are miniatures of traditional experimental systems with more advantages of timesaving,reagent-minimization,automation,high-throughput,and online detection.These features of microfluidic chips meet the demands of islet secretome analysis and a variety of chips have been designed in the past 20 years.In this review,we present a brief introduction of microfluidic chips,and three microfluidic chipsbased islet hormone sensing techniques.We focus mainly on the theory of these techniques,and provide detailed examples based on these theories with the hope of providing some insights into the design of future chips or whole detection systems.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
A pressure force control system for hot embossing of microfluidic chips is designed with a moment motor and a ball bearing lead screw. Based on the numeric PID technique, the algorithm of pulsant integral accelerated ...A pressure force control system for hot embossing of microfluidic chips is designed with a moment motor and a ball bearing lead screw. Based on the numeric PID technique, the algorithm of pulsant integral accelerated PID control is presented and the negative effects of nonlinearity from friction, clearance and saturation are eliminated. In order to improve the quick-resixmse characteristic, independent thread technique is adopted. The method of pressure force control based on pulsant integral accelerated PID control and independent thread technique is applied with satisfactory control performance.展开更多
Zinc and its compounds, alloys and composites play an important role in the modern day world and find application in almost every aspect that can improve the quality of our lives. This ranges from supplements and phar...Zinc and its compounds, alloys and composites play an important role in the modern day world and find application in almost every aspect that can improve the quality of our lives. This ranges from supplements and pharmaceuticals that are meant to improve our health and wellbeing to additives meant to guard or reduce corrosion in metals. However, over the past several years, a new area of technology has been garnering a great deal of attention and has made use of zinc and its compounds. This is with reference to paper-based microfluidic technology that offers several advantages and that keeps expanding in the amount of applications it covers. In this paper, a review is offered for the applications that have used zinc or zinc compounds in paper-based microfluidic devices.展开更多
The development of pharmaceutical analytical methods represents one of the most significant aspects of drug development. Recent advances in microfabrication and microfluidics could provide new approaches for drug anal...The development of pharmaceutical analytical methods represents one of the most significant aspects of drug development. Recent advances in microfabrication and microfluidics could provide new approaches for drug analysis, including drug screening, active testing and the study of metabolism. Microfluidic chip technologies, such as lab-on-a-chip technology, three-dimensional (3D) cell culture, organs-on-chip and droplet techniques, have all been developed rapidly. Microfluidic chips coupled with various kinds of detection techniques are suitable for the high-throughput screening, detection and mechanistic study of drugs. This review highlights the latest (2010–2018) microfluidic technology for drug analysis and discusses the potential future development in this field.展开更多
In this work,a multi-functional analysis platform by coupling a microfluidic chip to a mass spectrometry(MS) detector was described.We constructed a three-dimensional tumor-endothelial co-culture model for simulating ...In this work,a multi-functional analysis platform by coupling a microfluidic chip to a mass spectrometry(MS) detector was described.We constructed a three-dimensional tumor-endothelial co-culture model for simulating drug resistance during tumor treatment.On this specially designed integrated platform,the first step was to prepare heterogeneous cell-encapsulated alginate microcapsules for threedimensional co-culture,and the second step was to achieve on-line perfusion culture and continuous drug stimulation on chip.It facilitates cell proliferation analysis and the collection of metabolism medium.After micro solid phase extraction column(SPE) pretreatment,subsequent mass spectrometry could detect drug metabolism.The high activity of two kinds of cells(A549 and HUVEC) shows the biocompatibility of the platform.Paclitaxel was used as a model drug,the distinctions of drug absorption between the mono-culture group and co-culture group were clearly observed by electrospray ionization quadrupole time-of-flight mass spectrometry(ESI-Q-TOF MS).Therefore,the integrated platform has shown promise as a high throughput,low cost for cell metabolism research and drug screening processes.展开更多
Accurate single-cell capture is a crucial step for single cell biological and chemical analysis. Conventional single-cell capturing often confront operational complexity, limited efficiency, cell damage, large scale b...Accurate single-cell capture is a crucial step for single cell biological and chemical analysis. Conventional single-cell capturing often confront operational complexity, limited efficiency, cell damage, large scale but low accuracy, incompetence in the acquirement of nano-upgraded single-cell liquid. Flow cytometry has been widely used in large-scale single-cell detection, while precise single-cell isolation relies on both a precision operating platform and a microscope, which is not only extremely inefficient, but also not conducive to couple with modern analytical instruments. Herein, we develop a modular single-cell pipette(m SCP) microfluidic chip with high efficiency and strong applicability for accurate direct capture of single viable cell from cell suspensions into nanoliter droplets(30-1000 n L). The m SCP is used as a sampling platform for the detection of Cd Te quantum dots in single cells with electrothermal atomic absorption spectrometry(ETAAS) for the first time. It also ensures precise single-cell sampling and detection by inductively coupled plasma mass spectrometry(ICP-MS).展开更多
Background:Early diagnosis and classification of infections increase the cure rate while decreasing complications,which is significant for severe infections,especially for war surgery.However,traditional methods rely ...Background:Early diagnosis and classification of infections increase the cure rate while decreasing complications,which is significant for severe infections,especially for war surgery.However,traditional methods rely on laborious operations and bulky devices.On the other hand,point-of-care(POC)methods suffer from limited robustness and accuracy.Therefore,it is of urgent demand to develop POC devices for rapid and accurate diagnosis of infections to fulfill on-site militarized requirements.Methods:We developed a wave-shaped microfluidic chip(WMC)assisted multiplexed detection platform(WMC-MDP).WMC-MDP reduces detection time and improves repeatability through premixing of the samples and reaction of the reagents.We further combined the detection platform with the streptavidin–biotin(SA-B)amplified system to enhance the sensitivity while using chemiluminescence(CL)intensity as signal readout.We realized simultaneous detection of C-reactive protein(CRP),procalcitonin(PCT),and interleukin-6(IL-6)on the detection platform and evaluated the sensitivity,linear range,selectivity,and repeatability.Finally,we finished detecting 15 samples from volunteers and compared the results with commercial ELISA kits.Results:Detection of CRP,PCT,and IL-6 exhibited good linear relationships between CL intensities and concentrations in the range of 1.25–40μg/ml,0.4–12.8 ng/ml,and 50–1600 pg/ml,respectively.The limit of detection of CRP,PCT,and IL-6 were 0.54μg/ml,0.11 ng/ml,and 16.25 pg/ml,respectively.WMC-MDP is capable of good adequate selectivity and repeatability.The whole detection procedure takes only 22 min that meets the requirements of a POC device.Results of 15 samples from volunteers were consistent with the results detected by commercial ELISA kits.Conclusions:WMC-MDP allows simultaneous,rapid,and sensitive detection of CRP,PCT,and IL-6 with satisfactory selectivity and repeatability,requiring minimal manipulation.However,WMC-MDP takes advantage of being a microfluidic device showing the coefficients of variation less than 10%enabling WMC-MDP to be a type of point-of-care testing(POCT).Therefore,WMC-MDP provides a promising alternative to POCT of multiple biomarkers.We believe the practical application of WMC-MDP in militarized fields will revolutionize infection diagnosis for soldiers.展开更多
EGFR mutations companion diagnostics have been proved to be crucial for the efficacy of tyrosine kinase inhibitor targeted cancer therapies. To uncover multiple mutations occurred in minority of EGFR-mutated cells,whi...EGFR mutations companion diagnostics have been proved to be crucial for the efficacy of tyrosine kinase inhibitor targeted cancer therapies. To uncover multiple mutations occurred in minority of EGFR-mutated cells,which may be covered by the noises from majority of unmutated cells, is currently becoming an urgent clinical requirement. Here we present the validation of a microfluidic-chip-based method for detecting EGFR multimutations at single-cell level. By trapping and immunofluorescently imaging single cells in specifically designed silicon microwells, the EGFR-expressed cellswere easily identified. By in situ lysing single cells, the cell lysates of EGFR-expressed cells were retrieved without cross-contamination. Benefited from excluding the noise from cells without EGFR expression, the simple and cost-effective Sanger's sequencing, but not the expensive deep sequencing of the whole cell population, was used to discover multi-mutations. We verified the new method with precisely discovering three most important EGFR drugrelated mutations from a sample in which EGFR-mutated cells only account for a small percentage of whole cell population. The microfluidic chip is capable of discovering not only the existence of specific EGFR multi-mutations,but also other valuable single-cell-level information: on which specific cells the mutations occurred, or whether different mutations coexist on the same cells. This microfluidic chip constitutes a promising method to promote simple and cost-effective Sanger's sequencing to be a routine test before performing targeted cancer therapy.展开更多
creening of foodborne pathogens is important to prevent contaminated foods from their supply chains.n this study, a portable detection device was developed for rapid, sensitive and simple detection of viable almonella...creening of foodborne pathogens is important to prevent contaminated foods from their supply chains.n this study, a portable detection device was developed for rapid, sensitive and simple detection of viable almonella using a finger-actuated microfluidic chip and an improved recombinase aided amplification (RAA) assay. Improved propidium monoazide(PMAxx) was combined with RAA to enable this device to distinguish viable bacteria from dead ones. The modification of PMAxx into dead bacteria, the magnetic xtraction of nucleic acids from viable bacteria and the RAA detection of extracted nucleic acids were performed using the microfluidic chip on its supporting device by finger press-release operations. The fluorescent signal resulting from RAA amplification of the nucleic acids was collected using a USB camera nd analyzed using a self-developed smartphone App to quantitatively determine the bacterial concenration. This device could detect Salmonella typhimurium in spiked chicken meats from 1.3 × 10^(2) CFU/m L o 1.3 × 10^(7) CFU/m L in 2 h with a lower detection limit of 130 CFU/m L, and has shown its potential for on-site detection of foodborne pathogens.展开更多
Experiments are used to study the fabrication of polymer microfluidic chip with hot embossing method.The pattern fidelity with respect to the process parameters is analyzed.Experiment results show that the relationshi...Experiments are used to study the fabrication of polymer microfluidic chip with hot embossing method.The pattern fidelity with respect to the process parameters is analyzed.Experiment results show that the relationship between the imprint temperature and the microchannel width is approximately exponential.However,the depth of micro channel isn't sensitive to the imprint temperature.When the imprint pressure is larger than 1 MPa and the imprint time is longer than 2 min,the increasing of imprint pressure and holding time has little impact on the microchannel width.So over long holding time is not needed in hot embossing.Based on the experiment analysis,a series of optimization process parameters is obtained and a fine microfluidic chip is fabricated.The electrophoresis separation experiment are used to verify the microfluidic chip performance after bonding.The results show that 100bp-ladder DNA sample can be separated in less than 5 min successfully.展开更多
The rise of antibiotic resistance as one of the most serious global public health threats has necessitated the timely clinical diagnosis and precise treatment of deadly bacterial infections.To identify which types and...The rise of antibiotic resistance as one of the most serious global public health threats has necessitated the timely clinical diagnosis and precise treatment of deadly bacterial infections.To identify which types and doses of antibiotics remain effective for fighting against multi-drug-resistant pathogens,the development of rapid and accurate antibiotic-susceptibility testing(AST)is of primary importance.Conventional methods for AST in well-plate formats with disk diffusion or broth dilution are both labor-intensive and operationally tedious.The microfluidic chip provides a versatile tool for evaluating bacterial AST and resistant behaviors.In this paper,we develop an operationally simple,3D-printed microfluidic chip for AST which automatically deploys antibiotic concentration gradients and fluorescence intensity-based reporting to ideally reduce the report time for AST to within 5 h.By harnessing a commercially available,digital light processing(DLP)3D printing method that offers a rapid,high-precision microfluidic chip-manufacturing capability,we design and realize the accurate generation of on-chip antibiotic concentration gradients based on flow resistance and diffusion mechanisms.We further demonstrate the employment of the microfluidic chip for the AST of E.coli to representative clinical antibiotics of three classes:ampicillin,chloramphenicol,and kanamycin.The determined minimum inhibitory concentration values are comparable to those reported by conventional well-plate methods.Our proposed method demonstrates a promising approach for realizing robust,convenient,and automatable AST of clinical bacterial pathogens.展开更多
基金sponsored by the National Natural Science Foundation of China(No.52235007,YH)the Science Fund for Creative Research Groups of the National Natural Science Foundation of China(No.T2121004,YH)+3 种基金the NationalNatural Science Foundation of China(No.52305300,MJX)the Fellowship of China Postdoctoral Science Foundation(No.2022M722826,MJX)the National Natural Science Foundation of China(No.82203602,JW)the Zhejiang Provincial Natural Science Foundation of China(No.LQ22H160020,JW)。
文摘Paper-based microchips have different advantages,such as better biocompatibility,simple production,and easy handling,making them promising candidates for clinical diagnosis and other fields.This study describes amethod developed to fabricate modular three-dimensional(3D)paper-based microfluidic chips based on projection-based 3D printing(PBP)technology.A series of two-dimensional(2D)paper-based microfluidic modules was designed and fabricated.After evaluating the effect of exposure time on the accuracy of the flow channel,the resolution of this channel was experimentally analyzed.Furthermore,several 3D paper-based microfluidic chips were assembled based on the 2D ones using different methods,with good channel connectivity.Scaffold-based 2D and hydrogel-based 3D cell culture systems based on 3D paper-based microfluidic chips were verified to be feasible.Furthermore,by combining extrusion 3D bioprinting technology and the proposed 3D paper-based microfluidic chips,multiorgan microfluidic chips were established by directly printing 3D hydrogel structures on 3D paperbased microfluidic chips,confirming that the prepared modular 3D paper-based microfluidic chip is potentially applicable in various biomedical applications.
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funded by the Beijing Natural Science Foundation[Grant No.Z210006]the National Natural Science Foundation of China[Grant No.62275061].
文摘Nickel(II)as one of the primary categories of heavy metals can lead to serious health problems if achieving the critical levels in the water.Thus,it is vital to propose a stable,reliable,and economical approach for detecting Ni ions.The microfluidic paper-based analytical devices(µPADs)are potential candidates for the detection of water quality parameters including pH,heavy ions,nitrite and so on.However,it suffers from a huge error caused by the environment and artificial mistakes.In this study,we proposed an improved technique route to increase the stability and reliability of microfluidic paper-based analytical devices.The main technique points include a stable light source,a matched camera,improved reliability of the devices,and effective calculated methods.Finally,we established 15 standard curves that could be used to detect nickel ions and obtained uniform colorimetric results with reliability and repeatability.With those improvements,the relative errors for the five types of real water samples from the Zhongshan industrial parks were reduced to 0.26%,14.78%,24.20%,50.29%and 3.53%,respectively.These results were conducive to exploring this technique for the detection of nickel ions in wastewater from the Zhongshan industrial parks.The results demonstrated that the above technique route is promising for the detection of other heavy metal ions in industrial effluent.
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supported by the Shanghai Municipal Science and Technology Major Project (“Beyond Limits manufacture”)。
文摘The first example of the microfluidic chips(MFCs) consisting of centimeter-level 3D channels with highdensity and large-volume fabricated by femtosecond laser micromachining were utilized to develop a time-saving, economical and hazardless flow synthesis process, and its advantages have been proved by in situ formation of aryldiazonium salts and subsequent borylation with bis(pinacolato)diboron. There are several important advantages in our 3D MFC-based flow synthesis technology, including the following:(1) the reaction temperature was altered from ice bath to room temperature;(2) the residence time was reduced by 10 times;(3) the yield was greatly improved, that is, several arylboronates were successfully obtained with higher yield compared to traditional batch process. Therefore, it can be envisioned that a novel, simplified flow synthetic protocol will be developed toward green organic synthesis via MFCs.
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 China National Science and Technology Major Project(2017ZX05009-005-003)the Strategic Consulting Project of Chinese Academy of Engineering(2018-XZ-09)the Science Foundation of China University of Petroleum,Beijing(No.2462019QNXZ04)。
文摘To solve the problems of long experiment period and difficult measurement in core imbibition experiments,fracture-matrix microfluidic chips of different sizes,boundary conditions and wettability regulated by surface property modification were designed to research the imbibition mechanisms of oil-water,oil-surfactant solution and oil-WinsorⅢtype surfactant solution.In the oil-water,and oil-wettability modification system imbibition process,oil was replaced from the matrix through Haines jump,the capillary back pressure was the main resistance blocking the flow of oil,the reduction of interfacial tension caused the weakening of Haines jump,reduction of oil discharge rate,and increase of oil recovery.The imbibition of oil-water or oil-surfactant solution with low interfacial tension was a counter-current imbibition process dominated by capillary force,in which all boundaries had similar contribution to imbibition,and the recovery data obtained from this experiment fit well with the classic imbibition scaling equation.The imbibition of oil and Winsor III type surfactant solution was a co-current imbibition process dominated by gravity under super-low interfacial tension,and is essentially the formation and re-balance of neutral microemulsion.The imbibition dynamics obtained from this experiment fit well with the modified imbibition scaling equation.
基金Supported by the Project of Suzhou Hospital of Anhui Medical University,No.2020A1Natural Science Project of North Anhui Health Vocational College,No.WZK201907.
文摘Diabetes mellitus is a global health problem resulting from islet dysfunction or insulin resistance.The mechanisms of islet dysfunction are still under investigation.Islet hormone secretion is the main function of islets,and serves an important role in the homeostasis of blood glucose.Elucidating the detailed mechanism of islet hormone secretome distortion can provide clues for the treatment of diabetes.Therefore,it is crucial to develop accurate,real-time,laborsaving,high-throughput,automated,and cost-effective techniques for the sensing of islet secretome.Microfluidic chips,an elegant platform that combines biology,engineering,computer science,and biomaterials,have attracted tremendous interest from scientists in the field of diabetes worldwide.These tiny devices are miniatures of traditional experimental systems with more advantages of timesaving,reagent-minimization,automation,high-throughput,and online detection.These features of microfluidic chips meet the demands of islet secretome analysis and a variety of chips have been designed in the past 20 years.In this review,we present a brief introduction of microfluidic chips,and three microfluidic chipsbased islet hormone sensing techniques.We focus mainly on the theory of these techniques,and provide detailed examples based on these theories with the hope of providing some insights into the design of future chips or whole detection systems.
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This project is supported by National Hi-tech Research and Development Program of China (863 Program, No. 2004AA404260).
文摘A pressure force control system for hot embossing of microfluidic chips is designed with a moment motor and a ball bearing lead screw. Based on the numeric PID technique, the algorithm of pulsant integral accelerated PID control is presented and the negative effects of nonlinearity from friction, clearance and saturation are eliminated. In order to improve the quick-resixmse characteristic, independent thread technique is adopted. The method of pressure force control based on pulsant integral accelerated PID control and independent thread technique is applied with satisfactory control performance.
文摘Zinc and its compounds, alloys and composites play an important role in the modern day world and find application in almost every aspect that can improve the quality of our lives. This ranges from supplements and pharmaceuticals that are meant to improve our health and wellbeing to additives meant to guard or reduce corrosion in metals. However, over the past several years, a new area of technology has been garnering a great deal of attention and has made use of zinc and its compounds. This is with reference to paper-based microfluidic technology that offers several advantages and that keeps expanding in the amount of applications it covers. In this paper, a review is offered for the applications that have used zinc or zinc compounds in paper-based microfluidic devices.
基金financial support from the National Natural Science Foundation of China(No.81673398)
文摘The development of pharmaceutical analytical methods represents one of the most significant aspects of drug development. Recent advances in microfabrication and microfluidics could provide new approaches for drug analysis, including drug screening, active testing and the study of metabolism. Microfluidic chip technologies, such as lab-on-a-chip technology, three-dimensional (3D) cell culture, organs-on-chip and droplet techniques, have all been developed rapidly. Microfluidic chips coupled with various kinds of detection techniques are suitable for the high-throughput screening, detection and mechanistic study of drugs. This review highlights the latest (2010–2018) microfluidic technology for drug analysis and discusses the potential future development in this field.
基金supported by the National Natural Science Foundation of China(Nos.21727814,21435002 and 21621003)。
文摘In this work,a multi-functional analysis platform by coupling a microfluidic chip to a mass spectrometry(MS) detector was described.We constructed a three-dimensional tumor-endothelial co-culture model for simulating drug resistance during tumor treatment.On this specially designed integrated platform,the first step was to prepare heterogeneous cell-encapsulated alginate microcapsules for threedimensional co-culture,and the second step was to achieve on-line perfusion culture and continuous drug stimulation on chip.It facilitates cell proliferation analysis and the collection of metabolism medium.After micro solid phase extraction column(SPE) pretreatment,subsequent mass spectrometry could detect drug metabolism.The high activity of two kinds of cells(A549 and HUVEC) shows the biocompatibility of the platform.Paclitaxel was used as a model drug,the distinctions of drug absorption between the mono-culture group and co-culture group were clearly observed by electrospray ionization quadrupole time-of-flight mass spectrometry(ESI-Q-TOF MS).Therefore,the integrated platform has shown promise as a high throughput,low cost for cell metabolism research and drug screening processes.
基金financial support of the National Natural Science Foundation of China (Nos. 21727811,21922402)the Fundamental Research Funds for the Central Universities (Nos. N2005003, N2105017)+1 种基金the Liaoning Revitalization Talents Program (No. XLYC1802016)Scientific Research Funding Project of the Education Department of Liaoning (No. LJKZ0007)。
文摘Accurate single-cell capture is a crucial step for single cell biological and chemical analysis. Conventional single-cell capturing often confront operational complexity, limited efficiency, cell damage, large scale but low accuracy, incompetence in the acquirement of nano-upgraded single-cell liquid. Flow cytometry has been widely used in large-scale single-cell detection, while precise single-cell isolation relies on both a precision operating platform and a microscope, which is not only extremely inefficient, but also not conducive to couple with modern analytical instruments. Herein, we develop a modular single-cell pipette(m SCP) microfluidic chip with high efficiency and strong applicability for accurate direct capture of single viable cell from cell suspensions into nanoliter droplets(30-1000 n L). The m SCP is used as a sampling platform for the detection of Cd Te quantum dots in single cells with electrothermal atomic absorption spectrometry(ETAAS) for the first time. It also ensures precise single-cell sampling and detection by inductively coupled plasma mass spectrometry(ICP-MS).
基金the National Natural Science Foundation of China(81902167,52075138)the Natural Science Foundation of Jiangsu Province(BK20190872).
文摘Background:Early diagnosis and classification of infections increase the cure rate while decreasing complications,which is significant for severe infections,especially for war surgery.However,traditional methods rely on laborious operations and bulky devices.On the other hand,point-of-care(POC)methods suffer from limited robustness and accuracy.Therefore,it is of urgent demand to develop POC devices for rapid and accurate diagnosis of infections to fulfill on-site militarized requirements.Methods:We developed a wave-shaped microfluidic chip(WMC)assisted multiplexed detection platform(WMC-MDP).WMC-MDP reduces detection time and improves repeatability through premixing of the samples and reaction of the reagents.We further combined the detection platform with the streptavidin–biotin(SA-B)amplified system to enhance the sensitivity while using chemiluminescence(CL)intensity as signal readout.We realized simultaneous detection of C-reactive protein(CRP),procalcitonin(PCT),and interleukin-6(IL-6)on the detection platform and evaluated the sensitivity,linear range,selectivity,and repeatability.Finally,we finished detecting 15 samples from volunteers and compared the results with commercial ELISA kits.Results:Detection of CRP,PCT,and IL-6 exhibited good linear relationships between CL intensities and concentrations in the range of 1.25–40μg/ml,0.4–12.8 ng/ml,and 50–1600 pg/ml,respectively.The limit of detection of CRP,PCT,and IL-6 were 0.54μg/ml,0.11 ng/ml,and 16.25 pg/ml,respectively.WMC-MDP is capable of good adequate selectivity and repeatability.The whole detection procedure takes only 22 min that meets the requirements of a POC device.Results of 15 samples from volunteers were consistent with the results detected by commercial ELISA kits.Conclusions:WMC-MDP allows simultaneous,rapid,and sensitive detection of CRP,PCT,and IL-6 with satisfactory selectivity and repeatability,requiring minimal manipulation.However,WMC-MDP takes advantage of being a microfluidic device showing the coefficients of variation less than 10%enabling WMC-MDP to be a type of point-of-care testing(POCT).Therefore,WMC-MDP provides a promising alternative to POCT of multiple biomarkers.We believe the practical application of WMC-MDP in militarized fields will revolutionize infection diagnosis for soldiers.
基金supported by the National HighTech R&D Program of China(No.2015AA020408)National Natural Science Foundation of China(No.61204118,81500900 and21503054)+1 种基金Beijing Municipal Science and Technology Project(No.Z171100002017013)Key Research Program of the Chinese Academy of Sciences,Grant NO.KFZD-SW-210
文摘EGFR mutations companion diagnostics have been proved to be crucial for the efficacy of tyrosine kinase inhibitor targeted cancer therapies. To uncover multiple mutations occurred in minority of EGFR-mutated cells,which may be covered by the noises from majority of unmutated cells, is currently becoming an urgent clinical requirement. Here we present the validation of a microfluidic-chip-based method for detecting EGFR multimutations at single-cell level. By trapping and immunofluorescently imaging single cells in specifically designed silicon microwells, the EGFR-expressed cellswere easily identified. By in situ lysing single cells, the cell lysates of EGFR-expressed cells were retrieved without cross-contamination. Benefited from excluding the noise from cells without EGFR expression, the simple and cost-effective Sanger's sequencing, but not the expensive deep sequencing of the whole cell population, was used to discover multi-mutations. We verified the new method with precisely discovering three most important EGFR drugrelated mutations from a sample in which EGFR-mutated cells only account for a small percentage of whole cell population. The microfluidic chip is capable of discovering not only the existence of specific EGFR multi-mutations,but also other valuable single-cell-level information: on which specific cells the mutations occurred, or whether different mutations coexist on the same cells. This microfluidic chip constitutes a promising method to promote simple and cost-effective Sanger's sequencing to be a routine test before performing targeted cancer therapy.
基金funded by National Natural Science Foundation of China (No. 32071899)Walmart Foundation (No. UA2020– 154)。
文摘creening of foodborne pathogens is important to prevent contaminated foods from their supply chains.n this study, a portable detection device was developed for rapid, sensitive and simple detection of viable almonella using a finger-actuated microfluidic chip and an improved recombinase aided amplification (RAA) assay. Improved propidium monoazide(PMAxx) was combined with RAA to enable this device to distinguish viable bacteria from dead ones. The modification of PMAxx into dead bacteria, the magnetic xtraction of nucleic acids from viable bacteria and the RAA detection of extracted nucleic acids were performed using the microfluidic chip on its supporting device by finger press-release operations. The fluorescent signal resulting from RAA amplification of the nucleic acids was collected using a USB camera nd analyzed using a self-developed smartphone App to quantitatively determine the bacterial concenration. This device could detect Salmonella typhimurium in spiked chicken meats from 1.3 × 10^(2) CFU/m L o 1.3 × 10^(7) CFU/m L in 2 h with a lower detection limit of 130 CFU/m L, and has shown its potential for on-site detection of foodborne pathogens.
基金National Hi-tech Research Development Program of China(863 Program,No.2002AA421150)Research Foundation of Doctorial Project of Ministry of Education,China(No.20030335091)
文摘Experiments are used to study the fabrication of polymer microfluidic chip with hot embossing method.The pattern fidelity with respect to the process parameters is analyzed.Experiment results show that the relationship between the imprint temperature and the microchannel width is approximately exponential.However,the depth of micro channel isn't sensitive to the imprint temperature.When the imprint pressure is larger than 1 MPa and the imprint time is longer than 2 min,the increasing of imprint pressure and holding time has little impact on the microchannel width.So over long holding time is not needed in hot embossing.Based on the experiment analysis,a series of optimization process parameters is obtained and a fine microfluidic chip is fabricated.The electrophoresis separation experiment are used to verify the microfluidic chip performance after bonding.The results show that 100bp-ladder DNA sample can be separated in less than 5 min successfully.
基金the National Natural Science Foundation of China(No.51908467)and by institutional funds from the Westlake University。
文摘The rise of antibiotic resistance as one of the most serious global public health threats has necessitated the timely clinical diagnosis and precise treatment of deadly bacterial infections.To identify which types and doses of antibiotics remain effective for fighting against multi-drug-resistant pathogens,the development of rapid and accurate antibiotic-susceptibility testing(AST)is of primary importance.Conventional methods for AST in well-plate formats with disk diffusion or broth dilution are both labor-intensive and operationally tedious.The microfluidic chip provides a versatile tool for evaluating bacterial AST and resistant behaviors.In this paper,we develop an operationally simple,3D-printed microfluidic chip for AST which automatically deploys antibiotic concentration gradients and fluorescence intensity-based reporting to ideally reduce the report time for AST to within 5 h.By harnessing a commercially available,digital light processing(DLP)3D printing method that offers a rapid,high-precision microfluidic chip-manufacturing capability,we design and realize the accurate generation of on-chip antibiotic concentration gradients based on flow resistance and diffusion mechanisms.We further demonstrate the employment of the microfluidic chip for the AST of E.coli to representative clinical antibiotics of three classes:ampicillin,chloramphenicol,and kanamycin.The determined minimum inhibitory concentration values are comparable to those reported by conventional well-plate methods.Our proposed method demonstrates a promising approach for realizing robust,convenient,and automatable AST of clinical bacterial pathogens.
