The real-time screening of biomolecules and single cells in biochips is extremely important for disease prediction and diagnosis,cellular analysis,and life science research.Barcode biochip technology,which is integrat...The real-time screening of biomolecules and single cells in biochips is extremely important for disease prediction and diagnosis,cellular analysis,and life science research.Barcode biochip technology,which is integrated with microfluidics,typically comprises barcode array,sample loading,and reaction unit array chips.Here,we present a review of microfluidics barcode biochip analytical approaches for the high-throughput screening of biomolecules and single cells,including protein biomarkers,microRNA(miRNA),circulating tumor DNA(ctDNA),single-cell secreted proteins,single-cell exosomes,and cell interactions.We begin with an overview of current high-throughput detection and analysis approaches.Following this,we outline recent improvements in microfluidic devices for biomolecule and single-cell detection,highlighting the benefits and limitations of these devices.This paper focuses on the research and development of microfluidic barcode biochips,covering their self-assembly substrate materials and their specific applications with biomolecules and single cells.Looking forward,we explore the prospects and challenges of this technology,with the aim of contributing toward the use of microfluidic barcode detection biochips in medical diagnostics and therapies,and their large-scale commercialization.展开更多
In the past two decades,the biological and medical fields have seen great advances in the development of biosensors and bioehips capable of characterizing and quantifying biomolecules.This lecture is meant to discuss ...In the past two decades,the biological and medical fields have seen great advances in the development of biosensors and bioehips capable of characterizing and quantifying biomolecules.This lecture is meant to discuss the development and applications of advanced electroanalysis,biophotonics,nanotechnology,MEMS- based biosensors and biochips for biomedical diagnostics and physical performances of athlete.展开更多
A novel maskless technique, self-driving micro-fluid porous type printing （SMPTP）, was reported to in situ synthesize oligonucleotide arrays on glass slide, which has the merits of low cost, high quality and simple ...A novel maskless technique, self-driving micro-fluid porous type printing （SMPTP）, was reported to in situ synthesize oligonucleotide arrays on glass slide, which has the merits of low cost, high quality and simple craft. In SMPTP for fabricating gene- chips, porous fiber tubes with a number of nanometric or micron channels functioned as ＂active letters＂ and were assembled in designed patterns, which are identical to the distribution of monomers in each layer of the array, and four patterns were needed for each layer. By means of capillarity, the synthesis solution was automatically taken into porous tubes assembled in a printing plate and reached the surface. An oligonucleotide array of 160 features with four different 15-mer probes was in situ synthesized using this technique. The four specific oligonucleotide probes, including the matched and the mismatched by the fluorescent target sequence, gave obviously different hybridization fluorescent signals.展开更多
In this article ,we chiefly discuss optical part and photoelectrical part, and analyze the result data to make out the relationship between pinhole and special resolution and the influence of PMT on the result data.
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
A device,that is used for biomedical operation or safety-critical applications like point-of-care health asssment,massive parallel DNA analysis,automated drug discovery,air-quality monitoring and food-safety testing,m...A device,that is used for biomedical operation or safety-critical applications like point-of-care health asssment,massive parallel DNA analysis,automated drug discovery,air-quality monitoring and food-safety testing,must have the attributes like relia bility,dependability and correctness.As the biochips are used for these purposes;therefore,these devices must be fault free all the time.Naturally before usi ng these chips,they must be well tested.We are proposing a novel technique that can detect mutiple fults,locate the fault positions within the biochip,as well as calculate the traversal time if the biochip is fault free.The proposed technique also highlights a new idea how to select the appropriate base node or pseudo source(start electrode).The main idea of the proposed technique is to form multiple loops with the neighboring electrode arrays and then test each loop by traversing test droplet to check whether there is any fault.If a fault is detected then the propoed technique also locates it by backtracking the test droplet.In case,no fault is detected,the biochip is fault free then the proposed technique also calculates the time to traverse the chip.The result suggests that the proposed technique is eficient and shows significant improvement to ca lculate fault-free biochip traversal time over existing method.展开更多
Biochip is essentially a bio-microarray device that can perform hundreds or thousands of simultaneous biochemical reactions.[1, 2] It offers the researchers a new way for large-scale genomic, proteomic and functional ...Biochip is essentially a bio-microarray device that can perform hundreds or thousands of simultaneous biochemical reactions.[1, 2] It offers the researchers a new way for large-scale genomic, proteomic and functional genomic analyses. The biochips also enable people to quickly screen large numbers of biological analyses for many different purposes, from disease diagnosis to detection of bioterrorism chemical agents.[3]展开更多
A multifunctional integrated microfluidic biochip device was engineered to estimate the activity-toxicity and composition principle of medicine in a cell model in vitro. This biochip could be used for disease cells an...A multifunctional integrated microfluidic biochip device was engineered to estimate the activity-toxicity and composition principle of medicine in a cell model in vitro. This biochip could be used for disease cells and healthy cells in two modules of "Yin-Yang" on the same chip for detecting the medicine efficacytoxicity simultaneously, as well as adjust different gradient ratios of concentration through the Christmas tree structure in both "Yin-Yang" modules autonomously for detecting the best compatibility of medicine in maximum efficacy and minimal toxicity. In the applicability experiment, the best concentration of three chemical compounds including dinatin, diosmetin and cisplatin, were detected using the biochip and traditional 96-cell plate. Biochip assays showed perfect positive correlation compared with the results of traditional 96-cell plate, in addition presented advantages as less detection time and much lower price than the traditional 96-cell plate, which indicated the biochip is both convenient and feasible.Thus, the novel microfluidic chip-based multifunctional integrated system congregated the virtues of high throughput, rapid, sensitive, specific, cost-effective, and similar to the physical environment of the human body, which was especially suitable for the medicine efficacy-toxicity and compatibility evaluation.展开更多
Porous silicon （PSi） prepared from Pt metal-assisted chemical etching （MACE） was demonstrated to possess higher hydrosi- lylation efficiency （-57%） than anodized PSi （-11%） by surface reaction with co-undeceny...Porous silicon （PSi） prepared from Pt metal-assisted chemical etching （MACE） was demonstrated to possess higher hydrosi- lylation efficiency （-57%） than anodized PSi （-11%） by surface reaction with co-undecenyl alcohol （UO）. Deconvolution of the SiHx （x = 1-3） stretching bands revealed the abundance of SiH2 species on MaCE PSi was 53%, -10% higher than on ano- dized samples, while both of Sill1 and Sill3 were -5% lower correspondently on MaCE PSi than on anodized samples. The surface SiHx abundances were suggested to account for the higher hydrosilylation efficiency on MaCE PSi. Optimization of Pt-assisted chemical etching parameters suggested a 7-15 nm thick Pt-coating and an etching time of 3-10 min for biochip ap- plications. Scanning electron microscopy images revealed that an isotropic top meso-porous layer was beneficial for hydrosi- lylation and long-term durability under ambient conditions. To end, an example of histidine-tagged protein immobilization and microarray was illustrated. Combining the materials＇ property, surface chemistry, and micro-fabrication technology together, we envision that silicon based biochip applications have a prosperous future.展开更多
Laboratory on a chip technology has attracted wide interest in recent years, where the sample preparation, bio chemical reaction, separation, detection and analysis are performed in a small biochip of the size o...Laboratory on a chip technology has attracted wide interest in recent years, where the sample preparation, bio chemical reaction, separation, detection and analysis are performed in a small biochip of the size of a fingernail. To obtain a high detection sensitivity of 1 fluors/μm 2 (one fluorescence molecule per square micrometer) in biochip scanning systems, the scanning objective lens is required to have a high numerical aperture (>0.5), very small focal spot (<5 μm), and long back focal length (>3 mm). This study presents the design of optimum combined lenses including scanning objective and fluorescence focal lenses. The scanning objective had a high numerical aperture (NA) of 0.72, a very small focal spot of 1.67 μm, a long back focal length of 3.2 mm, and a high resolving power of 760 lines/mm. The fluorescence focal lenses had an NA of 0.3, a fluorescence focal spot of 16 μm, a long back focal length of 16.7 mm and a resolving power of 590 lines/mm. The phase aberrations of the combined lenses, including the aspherical aberration and the chromatic aberration corresponding to wavelengths of 532, 570, 635, and 670 nm, were well corrected. The encircled energy diagram of the lenses was within the diffraction limit. The study also included the focal spot diagram, the optical path difference diagram, the transverse ray fan plot, and the modulation transfer function. A confocal biochip scanning system with designed combined lenses was developed and some experiments were conducted on a multi channel biochip.展开更多
We will be concerned with the mathematical modeling, numerical simulation, and shape optimization of micro fluidic biochips that are used for various biomedical applications. A particular feature is that the fluid flo...We will be concerned with the mathematical modeling, numerical simulation, and shape optimization of micro fluidic biochips that are used for various biomedical applications. A particular feature is that the fluid flow in the fluidic network on top of the biochips is in- duced by surface acoustic waves generated by interdigital transducers. We are thus faced with a multiphysics problem that will be modeled by coupling the equations of piezoelectricity with the compressible Navier-Stokes equations. Moreover, the fluid flow exhibits a multiscale character that will be taken care of by a homogenization approach. We will discuss and analyze the mathematical models and deal with their numerical solution by space-time discretizations featuring appropriate finite element approximations with respect to hierarchies of simplicial triangulations of the underlying computational domains. Simulation results will be given for the propagation of the surface acoustic waves on top of the piezoelectric substrate and for the induced fluid flow in the microchannels of the fluidic network. The performance of the operational behavior of the biochips can be significantly improved by shape optimization. In particular, for such purposes we present a multilevel interior point method relying on a predictor-corrector strategy with an adaptive choice of the continuation steplength along the barrier path. As a specific example, we will consider the shape optimization of pressure driven capillary barriers between microchannels and reservoirs.展开更多
This nanoprinting process allows researchers to 3D print more material on a biochip than ever before,making it easier to study biomedical issues.Making biochips,a key technology in studying disease,just got a little e...This nanoprinting process allows researchers to 3D print more material on a biochip than ever before,making it easier to study biomedical issues.Making biochips,a key technology in studying disease,just got a little easier.This new nanoprinting process?uses gold-plated pyramids,an LED light,and photochemical reactions to print more organic material on the surface of one single biochip than ever before.The technique uses an array of polymer pyramids that are covered in gold and mounted onto an atomic force mi-展开更多
Biochip as a new research field has enjoyed its rapid development in the past 10 years. Using microfabrication technology, thousands or hundred thousands of biological molecules can be assembled on a centimeter square...Biochip as a new research field has enjoyed its rapid development in the past 10 years. Using microfabrication technology, thousands or hundred thousands of biological molecules can be assembled on a centimeter square microchip. Those chip-based devices can be used to analyze mutations, antigens, cells, etc. Compared with the traditional analytical instruments, chip-based micro total analytical systems have many advantages, such as reduced size, lower consumption of both reagents and energy contamination-free, etc. Biochip technology is believed to revolutionize the future research in life sciences, disease diagnosis, drug discovery forensic sciences and outer space exploitation in the coming展开更多
基金supported by the National Key Research and Development Plan of China(2023YFB3210400)the Natural Science Innovation Group Foundation of China(T2321004)+3 种基金the National Natural Science Foundation of China(62174101)Shandong University Integrated Research and Cultivation Project(2022JC001)Key Research and Development Plan of Shandong Province(Major Science and Technology Innovation Project2022CXGC020501).
文摘The real-time screening of biomolecules and single cells in biochips is extremely important for disease prediction and diagnosis,cellular analysis,and life science research.Barcode biochip technology,which is integrated with microfluidics,typically comprises barcode array,sample loading,and reaction unit array chips.Here,we present a review of microfluidics barcode biochip analytical approaches for the high-throughput screening of biomolecules and single cells,including protein biomarkers,microRNA(miRNA),circulating tumor DNA(ctDNA),single-cell secreted proteins,single-cell exosomes,and cell interactions.We begin with an overview of current high-throughput detection and analysis approaches.Following this,we outline recent improvements in microfluidic devices for biomolecule and single-cell detection,highlighting the benefits and limitations of these devices.This paper focuses on the research and development of microfluidic barcode biochips,covering their self-assembly substrate materials and their specific applications with biomolecules and single cells.Looking forward,we explore the prospects and challenges of this technology,with the aim of contributing toward the use of microfluidic barcode detection biochips in medical diagnostics and therapies,and their large-scale commercialization.
文摘In the past two decades,the biological and medical fields have seen great advances in the development of biosensors and bioehips capable of characterizing and quantifying biomolecules.This lecture is meant to discuss the development and applications of advanced electroanalysis,biophotonics,nanotechnology,MEMS- based biosensors and biochips for biomedical diagnostics and physical performances of athlete.
文摘A novel maskless technique, self-driving micro-fluid porous type printing （SMPTP）, was reported to in situ synthesize oligonucleotide arrays on glass slide, which has the merits of low cost, high quality and simple craft. In SMPTP for fabricating gene- chips, porous fiber tubes with a number of nanometric or micron channels functioned as ＂active letters＂ and were assembled in designed patterns, which are identical to the distribution of monomers in each layer of the array, and four patterns were needed for each layer. By means of capillarity, the synthesis solution was automatically taken into porous tubes assembled in a printing plate and reached the surface. An oligonucleotide array of 160 features with four different 15-mer probes was in situ synthesized using this technique. The four specific oligonucleotide probes, including the matched and the mismatched by the fluorescent target sequence, gave obviously different hybridization fluorescent signals.
文摘In this article ,we chiefly discuss optical part and photoelectrical part, and analyze the result data to make out the relationship between pinhole and special resolution and the influence of PMT on the result data.
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.
文摘A device,that is used for biomedical operation or safety-critical applications like point-of-care health asssment,massive parallel DNA analysis,automated drug discovery,air-quality monitoring and food-safety testing,must have the attributes like relia bility,dependability and correctness.As the biochips are used for these purposes;therefore,these devices must be fault free all the time.Naturally before usi ng these chips,they must be well tested.We are proposing a novel technique that can detect mutiple fults,locate the fault positions within the biochip,as well as calculate the traversal time if the biochip is fault free.The proposed technique also highlights a new idea how to select the appropriate base node or pseudo source(start electrode).The main idea of the proposed technique is to form multiple loops with the neighboring electrode arrays and then test each loop by traversing test droplet to check whether there is any fault.If a fault is detected then the propoed technique also locates it by backtracking the test droplet.In case,no fault is detected,the biochip is fault free then the proposed technique also calculates the time to traverse the chip.The result suggests that the proposed technique is eficient and shows significant improvement to ca lculate fault-free biochip traversal time over existing method.
文摘Biochip is essentially a bio-microarray device that can perform hundreds or thousands of simultaneous biochemical reactions.[1, 2] It offers the researchers a new way for large-scale genomic, proteomic and functional genomic analyses. The biochips also enable people to quickly screen large numbers of biological analyses for many different purposes, from disease diagnosis to detection of bioterrorism chemical agents.[3]
文摘A multifunctional integrated microfluidic biochip device was engineered to estimate the activity-toxicity and composition principle of medicine in a cell model in vitro. This biochip could be used for disease cells and healthy cells in two modules of "Yin-Yang" on the same chip for detecting the medicine efficacytoxicity simultaneously, as well as adjust different gradient ratios of concentration through the Christmas tree structure in both "Yin-Yang" modules autonomously for detecting the best compatibility of medicine in maximum efficacy and minimal toxicity. In the applicability experiment, the best concentration of three chemical compounds including dinatin, diosmetin and cisplatin, were detected using the biochip and traditional 96-cell plate. Biochip assays showed perfect positive correlation compared with the results of traditional 96-cell plate, in addition presented advantages as less detection time and much lower price than the traditional 96-cell plate, which indicated the biochip is both convenient and feasible.Thus, the novel microfluidic chip-based multifunctional integrated system congregated the virtues of high throughput, rapid, sensitive, specific, cost-effective, and similar to the physical environment of the human body, which was especially suitable for the medicine efficacy-toxicity and compatibility evaluation.
基金the financial support of the National Basic Research Program of China(2013CB922101)the National Natural Science Foundation of China(20827001,91027019,21021062)
文摘Porous silicon （PSi） prepared from Pt metal-assisted chemical etching （MACE） was demonstrated to possess higher hydrosi- lylation efficiency （-57%） than anodized PSi （-11%） by surface reaction with co-undecenyl alcohol （UO）. Deconvolution of the SiHx （x = 1-3） stretching bands revealed the abundance of SiH2 species on MaCE PSi was 53%, -10% higher than on ano- dized samples, while both of Sill1 and Sill3 were -5% lower correspondently on MaCE PSi than on anodized samples. The surface SiHx abundances were suggested to account for the higher hydrosilylation efficiency on MaCE PSi. Optimization of Pt-assisted chemical etching parameters suggested a 7-15 nm thick Pt-coating and an etching time of 3-10 min for biochip ap- plications. Scanning electron microscopy images revealed that an isotropic top meso-porous layer was beneficial for hydrosi- lylation and long-term durability under ambient conditions. To end, an example of histidine-tagged protein immobilization and microarray was illustrated. Combining the materials＇ property, surface chemistry, and micro-fabrication technology together, we envision that silicon based biochip applications have a prosperous future.
基金Supported by the National High-Tech DevelopmentProgram of China(No.863 -10 3 -13 0 -5 0 2 )the"973"National Science Foundation of China (No.G19990 1160 3 )+1 种基金the National Natural ScienceFoundation of China (No. 3 0 0 0 0 0 40 ) the NaturalScie
文摘Laboratory on a chip technology has attracted wide interest in recent years, where the sample preparation, bio chemical reaction, separation, detection and analysis are performed in a small biochip of the size of a fingernail. To obtain a high detection sensitivity of 1 fluors/μm 2 (one fluorescence molecule per square micrometer) in biochip scanning systems, the scanning objective lens is required to have a high numerical aperture (>0.5), very small focal spot (<5 μm), and long back focal length (>3 mm). This study presents the design of optimum combined lenses including scanning objective and fluorescence focal lenses. The scanning objective had a high numerical aperture (NA) of 0.72, a very small focal spot of 1.67 μm, a long back focal length of 3.2 mm, and a high resolving power of 760 lines/mm. The fluorescence focal lenses had an NA of 0.3, a fluorescence focal spot of 16 μm, a long back focal length of 16.7 mm and a resolving power of 590 lines/mm. The phase aberrations of the combined lenses, including the aspherical aberration and the chromatic aberration corresponding to wavelengths of 532, 570, 635, and 670 nm, were well corrected. The encircled energy diagram of the lenses was within the diffraction limit. The study also included the focal spot diagram, the optical path difference diagram, the transverse ray fan plot, and the modulation transfer function. A confocal biochip scanning system with designed combined lenses was developed and some experiments were conducted on a multi channel biochip.
基金support by the NSF under Grants No. DMS-0511611, DMS-0707602, DMS-0810156, DMS-0811153by the German National Science Foundation DFG within the Priority Program SPP 1253
文摘We will be concerned with the mathematical modeling, numerical simulation, and shape optimization of micro fluidic biochips that are used for various biomedical applications. A particular feature is that the fluid flow in the fluidic network on top of the biochips is in- duced by surface acoustic waves generated by interdigital transducers. We are thus faced with a multiphysics problem that will be modeled by coupling the equations of piezoelectricity with the compressible Navier-Stokes equations. Moreover, the fluid flow exhibits a multiscale character that will be taken care of by a homogenization approach. We will discuss and analyze the mathematical models and deal with their numerical solution by space-time discretizations featuring appropriate finite element approximations with respect to hierarchies of simplicial triangulations of the underlying computational domains. Simulation results will be given for the propagation of the surface acoustic waves on top of the piezoelectric substrate and for the induced fluid flow in the microchannels of the fluidic network. The performance of the operational behavior of the biochips can be significantly improved by shape optimization. In particular, for such purposes we present a multilevel interior point method relying on a predictor-corrector strategy with an adaptive choice of the continuation steplength along the barrier path. As a specific example, we will consider the shape optimization of pressure driven capillary barriers between microchannels and reservoirs.
文摘This nanoprinting process allows researchers to 3D print more material on a biochip than ever before,making it easier to study biomedical issues.Making biochips,a key technology in studying disease,just got a little easier.This new nanoprinting process?uses gold-plated pyramids,an LED light,and photochemical reactions to print more organic material on the surface of one single biochip than ever before.The technique uses an array of polymer pyramids that are covered in gold and mounted onto an atomic force mi-
文摘Biochip as a new research field has enjoyed its rapid development in the past 10 years. Using microfabrication technology, thousands or hundred thousands of biological molecules can be assembled on a centimeter square microchip. Those chip-based devices can be used to analyze mutations, antigens, cells, etc. Compared with the traditional analytical instruments, chip-based micro total analytical systems have many advantages, such as reduced size, lower consumption of both reagents and energy contamination-free, etc. Biochip technology is believed to revolutionize the future research in life sciences, disease diagnosis, drug discovery forensic sciences and outer space exploitation in the coming
