Tracking the movement of droplets in digital microfluidics is essential to improve its control stability and obtain dynamic information for its applications such as point-of-care testing,environment monitoring and che...Tracking the movement of droplets in digital microfluidics is essential to improve its control stability and obtain dynamic information for its applications such as point-of-care testing,environment monitoring and chemical synthesis.Herein,an intelligent,accurate and fast droplet tracking method based on machine vision is developed for applications of digital microfluidics.To continuously recognize the transparent droplets in real-time and avoid the interferes from background patterns or inhomogeneous illumination,we introduced the correlation filter tracker,enabling online learning of the multi-features of the droplets in Fourier domain.Results show the proposed droplet tracking method could accurately locate the droplets.We also demonstrated the capacity of the proposed method for estimation of the droplet velocity as faster as 20 mm/s,and its application in online monitoring the Griess reaction for both colorimetric assay of nitrite and study of reaction kinetics.展开更多
Nucleic acid amplification tests(NAAT)have long been used in laboratory facilities and recently revolutionized the field of molecular diagnostics in point-of-care testing.Digital microfluidics(DMF)has emerged as a pro...Nucleic acid amplification tests(NAAT)have long been used in laboratory facilities and recently revolutionized the field of molecular diagnostics in point-of-care testing.Digital microfluidics(DMF)has emerged as a promising tool to complete the entire NAAT workflow in a miniaturized format with minimum human intervention.Based on electric fields to manipulate independent reaction droplets,the compact DMF system could perform multiple processes simultaneously and automatically in a programmable fashion.This combination is beginning to establish powerful sample-to-answer platforms in remote or resource-limited settings.Herein,we provide a comprehensive overview of the state-of-the-art DMF technology for point-of-care NAAT.This review focused on key principles of DMF platforms and the latest trends in system integration for automated processes of nucleic acid extraction,amplification,and detection.Also,this article discusses current challenges,including control systems,scalability and throughput,as well as future prospects of DMF-based NAAT strategy for the next generation of point-of-care diagnostics.展开更多
Single-cell analysis is crucial for deciphering cellular heterogeneity and understanding complex biological systems.However,most existing single-cell sample manipulation(SCSM)systems suffer from various drawbacks such...Single-cell analysis is crucial for deciphering cellular heterogeneity and understanding complex biological systems.However,most existing single-cell sample manipulation(SCSM)systems suffer from various drawbacks such as high cost,low throughput,and heavy reliance on human interventions.Currently,large language models(LLMs)have been used in robotic platforms,but a limited number of studies have reported the application of LLMs in the field of lab-ona-chip automation.Consequently,we have developed an active-matrix digital microfluidic(AM-DMF)platform that realizes fully automated biological procedures for intelligent SCSM.By combining this with a fully programmable labon-a-chip system,we present a breakthrough for SCSM by combining LLMs and object detection technologies.With the proposed platform,the single-cell sample generation rate and identification precision reach up to 25%and 98%,respectively,which are much higher than the existing platforms in terms of SCSM efficiency and performance.Furthermore,a three-class detection method considering droplet edges is implemented to realize the automatic identification of cells and oil bubbles.This method achieves a 1.0%improvement in cell recognition accuracy according to the AP_(75)^(test)metric,while efficiently distinguishing obscured cells at droplet edges,where approximately 20%of all droplets contain cells at their edges.More importantly,as the first attempt,a ubiquitous tool for automatic SCSM workflow generation is developed based on the LLMs,thus advancing the development and progression of the field of single-cell analysis in the life sciences.展开更多
Outbreaks of both influenza virus and the novel coronavirus SARS-CoV-2 are serious threats to human health and life. It is very important to establish a rapid, accurate test with large-scale detection potential to pre...Outbreaks of both influenza virus and the novel coronavirus SARS-CoV-2 are serious threats to human health and life. It is very important to establish a rapid, accurate test with large-scale detection potential to prevent the further spread of the epidemic. An optimized RPA-Cas12a-based platform combined with digital microfluidics(DMF), the RCD platform, was established to achieve the automated, rapid detection of influenza viruses and SARS-CoV-2. The probe in the RPA-Cas12a system was optimized to produce maximal fluorescence to increase the amplification signal. The reaction droplets in the platform were all at the microliter level and the detection could be accomplished within 30 min due to the effective mixing of droplets by digital microfluidic technology. The whole process from amplification to recognition is completed in the chip, which reduces the risk of aerosol contamination. One chip can contain multiple detection reaction areas, offering the potential for customized detection.The RCD platform demonstrated a high level of sensitivity, specificity(no false positives or negatives), speed(≤30 min),automation and multiplexing. We also used the RCD platform to detect nucleic acids from influenza patients and COVID-19 patients. The results were consistent with the findings of q PCR. The RCD platform is a one-step, rapid, highly sensitive and specific method with the advantages of digital microfluidic technology, which circumvents the shortcomings of manual operation. The development of the RCD platform provides potential for the isothermal automatic detection of nucleic acids during epidemics.展开更多
Digital microfluidics （DMF） is a versatile microfluidics technology that has significant application potential in the areas of automation and miniaturization. In DME discrete droplets containing samples and reagents...Digital microfluidics （DMF） is a versatile microfluidics technology that has significant application potential in the areas of automation and miniaturization. In DME discrete droplets containing samples and reagents are controlled to implement a series of operations via electrowetting-on-dielectric. This process works by apply- ing electrical potentials to an array of electrodes coated with a hydrophobic dielectric layer. Unlike microchannels, DMF facilitates precise control over multiple reaction processes without using complex pump, microvalve, and tubing networks. DMF also presents other distinct features, such as portability, less sample consumption, shorter chemical reaction time, flexibility, and easier combination with other technology types. Due to its unique advantages, DMF has been applied to a broad range of fields （e.g., chemistry, biology, medicine, and environment）. This study reviews the basic principles of droplet actuation, configuration design, and fabrication of the DMF device, as well as discusses the latest progress in DMF from the biochemistry perspective.展开更多
Digital microfluidics technology offers a platform for developing diagnostic applications with the advantages of portability,sample and reagent volume reduction,faster analysis,increased automation,low power consumpti...Digital microfluidics technology offers a platform for developing diagnostic applications with the advantages of portability,sample and reagent volume reduction,faster analysis,increased automation,low power consumption,compatibility with mass manufacturing and high throughput.In addition to diagnostics,digital microfluidics is finding use in nucleic acid analysis,peptide and protein analysis,cell analysis,drug analysis and delivery and immunization analysis.In this review,we describe these applications,their implementation,and associated design issues.As other review in the digital microfluidics technology,there have been and will be unexpected developments as DMF matures,but we predict that the future is bright for this promising technology at the last section.展开更多
Single-cell joint analysis of methylome and transcriptome reveals how the methylation regulates the transcriptional activity.However,traditional bench-top protocols for single-cell DNA methylation and RNA transcriptio...Single-cell joint analysis of methylome and transcriptome reveals how the methylation regulates the transcriptional activity.However,traditional bench-top protocols for single-cell DNA methylation and RNA transcription co-detection are laborintensive,cost-ineffective and contaminant-prone.Herein,we establish the DMF-sc MT-seq,a highly-efficient and cost-effective method to simultaneously analyze single-cell DNA methylation and transcriptional activity based on digital microfluidics.DMFsc MT-seq automates the workflow of single-cell isolation,cellular hypotonic lysis,nucleic acid separation and methylome/transcriptome library construction in a contactless and addressable way.The system ensures high accuracy(R>0.85),high gene detection ability(14,697 genes per cell at 4 million sequencing depth),and high CpG coverage(677,198 CpG sites per cell at 1million sequencing depth).By using DMF-sc MT-seq,the relationship of DNA methylation and RNA transcription under different genomic contexts is resolved.We further apply DMF-sc MT-seq to study the dynamics of transcription regulation with methylation-inhibiting anti-tumor Decitabine,and identify the methylated promoter/gene body driven genes in response to Decitabine treatment.DMF-sc MT-seq facilitates the construction of the correlation of DNA methylation and transcriptional activity at the single-cell level in a flexible,sensitive and accurate way,which is anticipated to be a powerful tool in studying single-cell biological systems.展开更多
Over the past two decades,digital microfluidic biochips have been in much demand for safety-critical and biomedical applications and increasingly important in point-of-care analysis,drug discovery,and immunoassays,amo...Over the past two decades,digital microfluidic biochips have been in much demand for safety-critical and biomedical applications and increasingly important in point-of-care analysis,drug discovery,and immunoassays,among other areas.However,for complex bioassays,finding routes for the transportation of droplets in an electrowetting-on-dielectric digital biochip while maintaining their discreteness is a challenging task.In this study,we propose a deep reinforcement learning-based droplet routing technique for digital microfluidic biochips.The technique is implemented on a distributed architecture to optimize the possible paths for predefined source–target pairs of droplets.The actors of the technique calculate the possible routes of the source–target pairs and store the experience in a replay buffer,and the learner fetches the experiences and updates the routing paths.The proposed algorithm was applied to benchmark suitesⅠand Ⅲ as two different test benches,and it achieved significant improvements over state-of-the-art techniques.展开更多
Microfuidic systems have been widely utilized in high-throughput biology analysis,but thedificulties in iquid manipulation and cell cultivation limit its application.This work has developed a new digital microfluidic(...Microfuidic systems have been widely utilized in high-throughput biology analysis,but thedificulties in iquid manipulation and cell cultivation limit its application.This work has developed a new digital microfluidic(DMF)system for on-demand droplet control.By adopting anextending-depth-of-field(EDoF)phase modulator to the optical system,the entire depth of themicrofluidic channel can be covered in one image without any refocusing process,ensuring that 95%of the particles in the droplet are captured within three shots together with shaking pro-cesses.With this system,suspension droplets are generated and droplets containing only oneyeast cll can be recognized,then each single cell is cultured in the array of the chip.Byobservingtheir growth in cell numbers and the green fluorescence protein(GFP)production via fluorescence imaging,the single cell with the highest production can be identified.The results haveproved the heterogeneity of yeast cells,and showed that the combined system can be applied forrapid single-cell sorting,cultivation,and analysis.展开更多
In this paper, an electrohydrodynamic approach is used to model and study dynamics of evaporating microdroplets in digital microfluidic systems. A numerical eleetrohydrodynamic approach is used to calculate the drivin...In this paper, an electrohydrodynamic approach is used to model and study dynamics of evaporating microdroplets in digital microfluidic systems. A numerical eleetrohydrodynamic approach is used to calculate the driving force and shear force （due to the walls）. Effects of contact line pinning is considered by adding a three-phase contact line force, and also considering dynamic contact angle which modifies the mierodroplet boundary conditions. Since air is used as the filler fluid, the drag force is neglected. Although energy equation is not solved （constant temperature assumption）, effects of the evaporation is considered from two aspects： It is shown that an additional force is needed to balance the dynamic equation of the mierodroplet motion. Also, at each time step the microdroplet interface has to be deformed due to the change in the microdroplet radius. Important findings of the proposed model includes the transient velocity and displacement of the microdroplet as well as the driving and opposing forces acting on the microdroplet as functions of time. It is shown that mass loss due to evaporation tends to accelerate the droplet; whereas the competitive effect of the reduced driving force decelerates the droplet at the end of motion. The modeling results indicate that evaporation plays a crucial role in microdroplet motion by changing the force balance and the microdroplet boundary condition.展开更多
Heavy metal pollution in water environments poses a great threat to public health and to the ecological environment due to its high toxicity and non-degradability.However,many existing detection methods require labora...Heavy metal pollution in water environments poses a great threat to public health and to the ecological environment due to its high toxicity and non-degradability.However,many existing detection methods require laboratory-based bulky instruments and time-consuming manual operations.Although some on-site systems exist,they are difficult to deploy on a large scale owing to their large size and high cost.Here,we report a sensing node featuring low power consumption and low cost,achieved by integrating microsensor,microfluidic,and electronic modules into a compact size for automatic and scalable heavy metal pollution monitoring.Digital microfluidic and electrochemical sensing modules are integrated on a chip,thereby combining the procedures of sample pretreatment,electrochemical sensing,and waste removal for automatic and continuous monitoring.The feasibility of the platform is demonstrated by Pb2+detection in tap water.With a 3500 mAh battery,the compact sensing node could work for several years in principle.There is scope for further improvements to the system in terms of wider functionality and reductions in size,power consumption,and cost.The sensing node presented here is a strong candidate for distributed monitoring of water quality as an Internet-of-Things application.展开更多
Digital microfluidic(DMF)technology is widely used in bioanalysis and chemical reactions due to its accuracy and flexibility in manipulating droplets.However,most DMF systems usually rely on complex electrode fabricat...Digital microfluidic(DMF)technology is widely used in bioanalysis and chemical reactions due to its accuracy and flexibility in manipulating droplets.However,most DMF systems usually rely on complex electrode fabrication and high driving voltages.Sensor integration in DMF systems is also quite rare.In this study,a programmable magnetic digital microfluidic(PMDMF)platform integrated with electrochemical detection system was proposed.It enables non-contact,flexible droplet manipulation without complex processes and high voltages,meeting the requirements of automated electrochemical detection.The platform includes a magnetic control system,a microfluidic chip,and an electrochemical detection system.The magnetic control system consists of a microcoil array circuit board,a N52 permanent magnet,and an Arduino control module.N52 magnets generate localized magnetic fields to drive droplet movement,while the Arduino module enables programmable control for precise manipulation.The maximum average velocity of the droplet is about 3.9 cm/s.The microfluidic chip was fabricated using 3D printing and the superhydrophobic surface of chip was fabricated by spray coating.The electrochemical detection system consists of the MoS_(2)@CeO_(2)/PVA working electrode,Ag/AgCl reference electrode,and carbon counter electrode.To evaluate the practical value of the integrated platform,glucose in sweat was automatically and accurately detected.The proposed platform has a wide linear detection range(0.01–0.25 mM),a lower LOD(6.5μM),a superior sensitivity(7833.54μA·mM^(−1)·cm^(−2)),and excellent recovery rate(88.1-113.5%).It has an extensive potential for future application in the fields of medical diagnostics and point-of-care testing.展开更多
Theadvancementofdigital microfluidics technology has been pivotal in academic research andengineering applications.However,the prevailing limitation is that traditional voltage sources generate an excess of Joule heat...Theadvancementofdigital microfluidics technology has been pivotal in academic research andengineering applications.However,the prevailing limitation is that traditional voltage sources generate an excess of Joule heat,adversely impacting droplet operation.Moreover,the power supply equipment required by digital microfluidics limits its applications.Here,we propose a self-powered microdroplet manipulation(SMDM)via triboelectric nanogenerator(TENG),which presents a capability for spliting and mixing different kinds of droplets.Fundamentally,SMDM is based on the electroosmotic flow principle,thereby enabling droplet spliting in the range of from 2 to 630μL.Notably,for droplet spliting in the range of from 5 to 60μL,the TENG only requires a power output ranging from 2.704 to 6.084 mW.In addition,SMDM demonstrates proficiency in droplet mixing,which achieves complete mixing of 10μL droplets in 60 s and 30μL droplets in a mere 53 s.Therefore,leveraging the strengths of the TENG,a self-powered microdroplet manipulated system is designed for digital microfluidics.It carries significant advantages over the traditional voltage source,including self-powered,low-Joule heat,increased safety and enhanced portability.This research provides a new solution for portable applications of digital microfluidics.展开更多
This review article examines digital microfluidic systems that manipulate droplets through surface anisotropy.These systems are categorized as surface tension driven or contact line driven.Surface tension driven syste...This review article examines digital microfluidic systems that manipulate droplets through surface anisotropy.These systems are categorized as surface tension driven or contact line driven.Surface tension driven systems include electrowetting on dielectric,Marangoni flow on microheater arrays,and chemical gradient surfaces,whereas contact line driven systems include anisotropic ratchet conveyors,nanostructured Parylene ratchets,and tilted pillar arrays.This article describes the operating principles and outlines the fabrication procedures for each system.We also present new equations that unify several previous models of contact line driven systems.The strengths and weaknesses of each system are compared,with a focus on their ability to perform the generation,switching,fusion,and fission of droplets.Finally,we discuss current and potential future applications of these systems.展开更多
基金the financial support from the National Natural Science Foundation of China(Nos.31701698,81972017)Shanghai Key Laboratory of Forensic Medicine,Academy of Forensic Science(No.KF1910)Shanghai Shenkang Hospital Development Center to promote clinical skills and clinical innovation ability in municipal hospitals of the Three-year Action Plan Project(No.SHDC2020CR3006A).
文摘Tracking the movement of droplets in digital microfluidics is essential to improve its control stability and obtain dynamic information for its applications such as point-of-care testing,environment monitoring and chemical synthesis.Herein,an intelligent,accurate and fast droplet tracking method based on machine vision is developed for applications of digital microfluidics.To continuously recognize the transparent droplets in real-time and avoid the interferes from background patterns or inhomogeneous illumination,we introduced the correlation filter tracker,enabling online learning of the multi-features of the droplets in Fourier domain.Results show the proposed droplet tracking method could accurately locate the droplets.We also demonstrated the capacity of the proposed method for estimation of the droplet velocity as faster as 20 mm/s,and its application in online monitoring the Griess reaction for both colorimetric assay of nitrite and study of reaction kinetics.
基金support from The Ivan Bowen Family Foundation and the Department of Physiology and Biomedical Engineering at Mayo Clinic,Rochester MN.
文摘Nucleic acid amplification tests(NAAT)have long been used in laboratory facilities and recently revolutionized the field of molecular diagnostics in point-of-care testing.Digital microfluidics(DMF)has emerged as a promising tool to complete the entire NAAT workflow in a miniaturized format with minimum human intervention.Based on electric fields to manipulate independent reaction droplets,the compact DMF system could perform multiple processes simultaneously and automatically in a programmable fashion.This combination is beginning to establish powerful sample-to-answer platforms in remote or resource-limited settings.Herein,we provide a comprehensive overview of the state-of-the-art DMF technology for point-of-care NAAT.This review focused on key principles of DMF platforms and the latest trends in system integration for automated processes of nucleic acid extraction,amplification,and detection.Also,this article discusses current challenges,including control systems,scalability and throughput,as well as future prospects of DMF-based NAAT strategy for the next generation of point-of-care diagnostics.
基金the National Key R&D Program of China(2023YFF0721500)The National Natural Science Foundation of China(Nos.62374102,82172077,22201298,and 62027825)+3 种基金The Innovation and Entrepreneurship Team of Jiangsu Province(JSSCTD202145)The Science and Technology Innovation Project of Foshan,Guangdong Province,China(No.1920001000047)The Science and Technology Development Project of Jilin Province(No.20210204110YY and 20250204092YY)The Suzhou Basic Research Project(SSD2023013).
文摘Single-cell analysis is crucial for deciphering cellular heterogeneity and understanding complex biological systems.However,most existing single-cell sample manipulation(SCSM)systems suffer from various drawbacks such as high cost,low throughput,and heavy reliance on human interventions.Currently,large language models(LLMs)have been used in robotic platforms,but a limited number of studies have reported the application of LLMs in the field of lab-ona-chip automation.Consequently,we have developed an active-matrix digital microfluidic(AM-DMF)platform that realizes fully automated biological procedures for intelligent SCSM.By combining this with a fully programmable labon-a-chip system,we present a breakthrough for SCSM by combining LLMs and object detection technologies.With the proposed platform,the single-cell sample generation rate and identification precision reach up to 25%and 98%,respectively,which are much higher than the existing platforms in terms of SCSM efficiency and performance.Furthermore,a three-class detection method considering droplet edges is implemented to realize the automatic identification of cells and oil bubbles.This method achieves a 1.0%improvement in cell recognition accuracy according to the AP_(75)^(test)metric,while efficiently distinguishing obscured cells at droplet edges,where approximately 20%of all droplets contain cells at their edges.More importantly,as the first attempt,a ubiquitous tool for automatic SCSM workflow generation is developed based on the LLMs,thus advancing the development and progression of the field of single-cell analysis in the life sciences.
基金supported by the Science and Technology Program of Fujian Province (2018Y4013 to B.-A.L.)the Science and Technology Project of Xiamen Science and Technology Bureau (3502Z20193023 to B.-A.L.)+4 种基金the Health-Education Joint Research Project of Fujian Province (2019-WJ-34 to B.-A.L. and Z.-M.Z)the COVID-19 Emergency Research Project of Xiamen Science and Technology Bureau (3502Z2020YJ21 to Bio Detect (Xiamen) Biotechnology Co., Ltd.)the COVID-19 Emergency Research Project of Xiamen University (X2106103 to B.-A.L.)the National Natural Science Foundation of China (U1705284, 81972458, and 81772958 to B.-A.L.)Project 111 sponsored by the State Bureau of Foreign Experts and Ministry of Education (B06016)。
文摘Outbreaks of both influenza virus and the novel coronavirus SARS-CoV-2 are serious threats to human health and life. It is very important to establish a rapid, accurate test with large-scale detection potential to prevent the further spread of the epidemic. An optimized RPA-Cas12a-based platform combined with digital microfluidics(DMF), the RCD platform, was established to achieve the automated, rapid detection of influenza viruses and SARS-CoV-2. The probe in the RPA-Cas12a system was optimized to produce maximal fluorescence to increase the amplification signal. The reaction droplets in the platform were all at the microliter level and the detection could be accomplished within 30 min due to the effective mixing of droplets by digital microfluidic technology. The whole process from amplification to recognition is completed in the chip, which reduces the risk of aerosol contamination. One chip can contain multiple detection reaction areas, offering the potential for customized detection.The RCD platform demonstrated a high level of sensitivity, specificity(no false positives or negatives), speed(≤30 min),automation and multiplexing. We also used the RCD platform to detect nucleic acids from influenza patients and COVID-19 patients. The results were consistent with the findings of q PCR. The RCD platform is a one-step, rapid, highly sensitive and specific method with the advantages of digital microfluidic technology, which circumvents the shortcomings of manual operation. The development of the RCD platform provides potential for the isothermal automatic detection of nucleic acids during epidemics.
文摘Digital microfluidics （DMF） is a versatile microfluidics technology that has significant application potential in the areas of automation and miniaturization. In DME discrete droplets containing samples and reagents are controlled to implement a series of operations via electrowetting-on-dielectric. This process works by apply- ing electrical potentials to an array of electrodes coated with a hydrophobic dielectric layer. Unlike microchannels, DMF facilitates precise control over multiple reaction processes without using complex pump, microvalve, and tubing networks. DMF also presents other distinct features, such as portability, less sample consumption, shorter chemical reaction time, flexibility, and easier combination with other technology types. Due to its unique advantages, DMF has been applied to a broad range of fields （e.g., chemistry, biology, medicine, and environment）. This study reviews the basic principles of droplet actuation, configuration design, and fabrication of the DMF device, as well as discusses the latest progress in DMF from the biochemistry perspective.
基金supported by the National Natural Science Foundation of China(NO.60927001,60971045)the National Key Program for Developing Basic Research(2010CB933903,2007CB936104)+1 种基金the Chinese 863 High Tech Project(NO.2007AA022007)China National Science and Technology Major Projects(2009ZX10004-311).
文摘Digital microfluidics technology offers a platform for developing diagnostic applications with the advantages of portability,sample and reagent volume reduction,faster analysis,increased automation,low power consumption,compatibility with mass manufacturing and high throughput.In addition to diagnostics,digital microfluidics is finding use in nucleic acid analysis,peptide and protein analysis,cell analysis,drug analysis and delivery and immunization analysis.In this review,we describe these applications,their implementation,and associated design issues.As other review in the digital microfluidics technology,there have been and will be unexpected developments as DMF matures,but we predict that the future is bright for this promising technology at the last section.
基金supported by the National Natural Science Foundation of China(21927806,22204132,22104080)the National Key R&D Program of China(2019YFA0905800)+1 种基金the Innovative Research Team of High-Level Local Universities in Shanghai,and the Fundamental Research Funds for the Central Universities(2072021000,20720210005)the Natural Science Foundation of Fujian Province(2022J011360)。
文摘Single-cell joint analysis of methylome and transcriptome reveals how the methylation regulates the transcriptional activity.However,traditional bench-top protocols for single-cell DNA methylation and RNA transcription co-detection are laborintensive,cost-ineffective and contaminant-prone.Herein,we establish the DMF-sc MT-seq,a highly-efficient and cost-effective method to simultaneously analyze single-cell DNA methylation and transcriptional activity based on digital microfluidics.DMFsc MT-seq automates the workflow of single-cell isolation,cellular hypotonic lysis,nucleic acid separation and methylome/transcriptome library construction in a contactless and addressable way.The system ensures high accuracy(R>0.85),high gene detection ability(14,697 genes per cell at 4 million sequencing depth),and high CpG coverage(677,198 CpG sites per cell at 1million sequencing depth).By using DMF-sc MT-seq,the relationship of DNA methylation and RNA transcription under different genomic contexts is resolved.We further apply DMF-sc MT-seq to study the dynamics of transcription regulation with methylation-inhibiting anti-tumor Decitabine,and identify the methylated promoter/gene body driven genes in response to Decitabine treatment.DMF-sc MT-seq facilitates the construction of the correlation of DNA methylation and transcriptional activity at the single-cell level in a flexible,sensitive and accurate way,which is anticipated to be a powerful tool in studying single-cell biological systems.
文摘Over the past two decades,digital microfluidic biochips have been in much demand for safety-critical and biomedical applications and increasingly important in point-of-care analysis,drug discovery,and immunoassays,among other areas.However,for complex bioassays,finding routes for the transportation of droplets in an electrowetting-on-dielectric digital biochip while maintaining their discreteness is a challenging task.In this study,we propose a deep reinforcement learning-based droplet routing technique for digital microfluidic biochips.The technique is implemented on a distributed architecture to optimize the possible paths for predefined source–target pairs of droplets.The actors of the technique calculate the possible routes of the source–target pairs and store the experience in a replay buffer,and the learner fetches the experiences and updates the routing paths.The proposed algorithm was applied to benchmark suitesⅠand Ⅲ as two different test benches,and it achieved significant improvements over state-of-the-art techniques.
基金supported by the National Key R&D Program of China(2021YFF0502900)the National Natural Science Foundation of China(62175034,62175036)+7 种基金the Anhui Province KeyR&D Project(202003a07020020)the ShanghaiNatural Science Foundation(grant No.20ZR1405100)the Science and Technology Research Program ofShanghai(grant No.19DZ2282100)the Shanghaikey discipline construction plan(2020-2022)(grantNo.GWV-10.1-XK01)the Shanghai EngineeringTechnology Research Center of Hair Medicine(19DZ2250500)the Medical Engineering Fund of Fudan University(yg2021-022)the Pioneering Project of Academy for Engineering and Technology,the Fudan University(gy2018-001,gy2018-002)the Yantai Returned Scholars'Pioneering Park.
文摘Microfuidic systems have been widely utilized in high-throughput biology analysis,but thedificulties in iquid manipulation and cell cultivation limit its application.This work has developed a new digital microfluidic(DMF)system for on-demand droplet control.By adopting anextending-depth-of-field(EDoF)phase modulator to the optical system,the entire depth of themicrofluidic channel can be covered in one image without any refocusing process,ensuring that 95%of the particles in the droplet are captured within three shots together with shaking pro-cesses.With this system,suspension droplets are generated and droplets containing only oneyeast cll can be recognized,then each single cell is cultured in the array of the chip.Byobservingtheir growth in cell numbers and the green fluorescence protein(GFP)production via fluorescence imaging,the single cell with the highest production can be identified.The results haveproved the heterogeneity of yeast cells,and showed that the combined system can be applied forrapid single-cell sorting,cultivation,and analysis.
文摘In this paper, an electrohydrodynamic approach is used to model and study dynamics of evaporating microdroplets in digital microfluidic systems. A numerical eleetrohydrodynamic approach is used to calculate the driving force and shear force （due to the walls）. Effects of contact line pinning is considered by adding a three-phase contact line force, and also considering dynamic contact angle which modifies the mierodroplet boundary conditions. Since air is used as the filler fluid, the drag force is neglected. Although energy equation is not solved （constant temperature assumption）, effects of the evaporation is considered from two aspects： It is shown that an additional force is needed to balance the dynamic equation of the mierodroplet motion. Also, at each time step the microdroplet interface has to be deformed due to the change in the microdroplet radius. Important findings of the proposed model includes the transient velocity and displacement of the microdroplet as well as the driving and opposing forces acting on the microdroplet as functions of time. It is shown that mass loss due to evaporation tends to accelerate the droplet; whereas the competitive effect of the reduced driving force decelerates the droplet at the end of motion. The modeling results indicate that evaporation plays a crucial role in microdroplet motion by changing the force balance and the microdroplet boundary condition.
基金supported by the National Natural Science Foundation of China(Nos.51375341,61901295,and 62001322)the Nanchang Institute for Microtechnology of Tianjin University.
文摘Heavy metal pollution in water environments poses a great threat to public health and to the ecological environment due to its high toxicity and non-degradability.However,many existing detection methods require laboratory-based bulky instruments and time-consuming manual operations.Although some on-site systems exist,they are difficult to deploy on a large scale owing to their large size and high cost.Here,we report a sensing node featuring low power consumption and low cost,achieved by integrating microsensor,microfluidic,and electronic modules into a compact size for automatic and scalable heavy metal pollution monitoring.Digital microfluidic and electrochemical sensing modules are integrated on a chip,thereby combining the procedures of sample pretreatment,electrochemical sensing,and waste removal for automatic and continuous monitoring.The feasibility of the platform is demonstrated by Pb2+detection in tap water.With a 3500 mAh battery,the compact sensing node could work for several years in principle.There is scope for further improvements to the system in terms of wider functionality and reductions in size,power consumption,and cost.The sensing node presented here is a strong candidate for distributed monitoring of water quality as an Internet-of-Things application.
基金supported by grants from the National Key Research and Development Program of China(No.2023YFB3208200)the equipment research and development projects of the Chinese Academy of Sciences(PTYQ2024YZ0010)+3 种基金the Science and Technology Commission of Shanghai Municipality Project(XTCX-KJ-2024-038)National Natural Science Foundation of China(62401555)Shanghai Science and Technology Development Funds(23J21900100)supported by the Postdoctoral Fellowship Program of CPSF under Grant Number GZC20232838.
文摘Digital microfluidic(DMF)technology is widely used in bioanalysis and chemical reactions due to its accuracy and flexibility in manipulating droplets.However,most DMF systems usually rely on complex electrode fabrication and high driving voltages.Sensor integration in DMF systems is also quite rare.In this study,a programmable magnetic digital microfluidic(PMDMF)platform integrated with electrochemical detection system was proposed.It enables non-contact,flexible droplet manipulation without complex processes and high voltages,meeting the requirements of automated electrochemical detection.The platform includes a magnetic control system,a microfluidic chip,and an electrochemical detection system.The magnetic control system consists of a microcoil array circuit board,a N52 permanent magnet,and an Arduino control module.N52 magnets generate localized magnetic fields to drive droplet movement,while the Arduino module enables programmable control for precise manipulation.The maximum average velocity of the droplet is about 3.9 cm/s.The microfluidic chip was fabricated using 3D printing and the superhydrophobic surface of chip was fabricated by spray coating.The electrochemical detection system consists of the MoS_(2)@CeO_(2)/PVA working electrode,Ag/AgCl reference electrode,and carbon counter electrode.To evaluate the practical value of the integrated platform,glucose in sweat was automatically and accurately detected.The proposed platform has a wide linear detection range(0.01–0.25 mM),a lower LOD(6.5μM),a superior sensitivity(7833.54μA·mM^(−1)·cm^(−2)),and excellent recovery rate(88.1-113.5%).It has an extensive potential for future application in the fields of medical diagnostics and point-of-care testing.
基金The authors are grateful for the support from the National Natural Science Foundation of China(No.52405052)the Open Foundation of the State Key Laboratory of Fluid Power and Mechatronic Systems(No.GZKF-202305)+1 种基金the Postdoctoral Fellowship Program(Grade B)of China Postdoctoral Science Foundation(No.GZB20230731)the National Key R&D Project from Minister of Science and Technology(No.2021YFA1201601).
文摘Theadvancementofdigital microfluidics technology has been pivotal in academic research andengineering applications.However,the prevailing limitation is that traditional voltage sources generate an excess of Joule heat,adversely impacting droplet operation.Moreover,the power supply equipment required by digital microfluidics limits its applications.Here,we propose a self-powered microdroplet manipulation(SMDM)via triboelectric nanogenerator(TENG),which presents a capability for spliting and mixing different kinds of droplets.Fundamentally,SMDM is based on the electroosmotic flow principle,thereby enabling droplet spliting in the range of from 2 to 630μL.Notably,for droplet spliting in the range of from 5 to 60μL,the TENG only requires a power output ranging from 2.704 to 6.084 mW.In addition,SMDM demonstrates proficiency in droplet mixing,which achieves complete mixing of 10μL droplets in 60 s and 30μL droplets in a mere 53 s.Therefore,leveraging the strengths of the TENG,a self-powered microdroplet manipulated system is designed for digital microfluidics.It carries significant advantages over the traditional voltage source,including self-powered,low-Joule heat,increased safety and enhanced portability.This research provides a new solution for portable applications of digital microfluidics.
基金This work was supported by National Science Foundation grant ECCS-1308025 Droplet Ratchets:Low Cost Digital Microfluidics.HRH would like to acknowledge the National Defense Science and Engineering Graduate Fellowship(NDSEG)for their support of this workFabrication of ARCs was performed at the Washington Nanofabrication Facility(WNF),a National Nanotechnology Coordinated Infrastructure(NNCI)site at the University of Washington,which is supported in part by the National Science Foundation(awards 1542101,1337840 and 0335765),the Washington Research Foundation,the M.J.Murdock Charitable Trust,Altatech,ClassOne Technology,GCE Market,Google and SPTS.
文摘This review article examines digital microfluidic systems that manipulate droplets through surface anisotropy.These systems are categorized as surface tension driven or contact line driven.Surface tension driven systems include electrowetting on dielectric,Marangoni flow on microheater arrays,and chemical gradient surfaces,whereas contact line driven systems include anisotropic ratchet conveyors,nanostructured Parylene ratchets,and tilted pillar arrays.This article describes the operating principles and outlines the fabrication procedures for each system.We also present new equations that unify several previous models of contact line driven systems.The strengths and weaknesses of each system are compared,with a focus on their ability to perform the generation,switching,fusion,and fission of droplets.Finally,we discuss current and potential future applications of these systems.
