Contactless manipulation of samples,particularly the ability to dynamically handle multiple fragile specimens while maintaining their integrity and viability,is crucial for various applications in biology,medicine,eng...Contactless manipulation of samples,particularly the ability to dynamically handle multiple fragile specimens while maintaining their integrity and viability,is crucial for various applications in biology,medicine,engineering,and physics.While hydrodynamic tweezers have emerged as a promising approach for gentle,label-free manipulation of a wide range of sample types and sizes,they typically have limited flexibility in terms of dynamic control,making it challenging to realize high-resolution and programmable manipulation of multiple samples.Here,we introduce the Streaming-based Tweezers for Routing,Engineering,And Manipulation of multiparticles(STREAM)with sub-wavelength resolution.The platform employs an array of piezoelectric plates arranged in a space-reciprocal pattern to generate acoustic streaming,creating localized trapping points.The mechanism of particle trapping and the improvement of routing resolution via multiunit activation were investigated.Subsequently,a convolutional neural network(CNN)with arbitrary voltage combination as the input and predicted trapping position as the output was integrated into the system.The CNN calibration is vital to the system as it enhances the platform’s performance,enabling precise control of the trapping positions beyond traditional physical unit size limitations.We demonstrated the STREAM platform’s capabilities through single particle routing with sub-wavelength precision,simultaneous manipulation of multiple particles,and on-demand assembly of samples.The STREAM platform opens new possibilities for applications requiring precise and dynamic control of particles and samples,with the potential to advance fields including biology,chemistry,and materials science.展开更多
Separating plasma from whole blood is an important sample processing technique required for fundamental biomedical research,medical diagnostics,and therapeutic applications.Traditional protocols for plasma isolation r...Separating plasma from whole blood is an important sample processing technique required for fundamental biomedical research,medical diagnostics,and therapeutic applications.Traditional protocols for plasma isolation require multiple centrifugation steps or multiunit microfluidic processing to sequentially remove large red blood cells(RBCs)and white blood cells(WBCs),followed by the removal of small platelets.Here,we present an acoustofluidic platform capable of efficiently removing RBCs,WBCs,and platelets from whole blood in a single step.By leveraging differences in the acoustic impedances of fluids,our device generates significantly greater forces on suspended particles than conventional microfluidic approaches,enabling the removal of both large blood cells and smaller platelets in a single unit.As a result,undiluted human whole blood can be processed by our device to remove both blood cells and platelets(>90%)at low voltages(25 Vpp).The ability to successfully remove blood cells and platelets from plasma without altering the properties of the proteins and antibodies present creates numerous potential applications for our platform in biomedical research,as well as plasma-based diagnostics and therapeutics.Furthermore,the microfluidic nature of our device offers advantages such as portability,cost efficiency,and the ability to process small-volume samples.展开更多
Large-field nanoscale fluorescence imaging is invaluable for many applications,such as imaging subcellular structures,visualizing protein interactions,and high-resolution tissue imaging.Unfortunately,conventional fluo...Large-field nanoscale fluorescence imaging is invaluable for many applications,such as imaging subcellular structures,visualizing protein interactions,and high-resolution tissue imaging.Unfortunately,conventional fluorescence microscopy requires a trade-off between resolution and field of view due to the nature of the optics used to form the image.To overcome this barrier,we developed an acoustofluidic scanning fluorescence nanoscope that simultaneously achieves superior resolution,a large field of view,and strong fluorescent signals.The acoustofluidic scanning fluorescence nanoscope utilizes the superresolution capabilities of microspheres that are controlled by a programmable acoustofluidic device for rapid fluorescence enhancement and imaging.The acoustofluidic scanning fluorescence nanoscope resolves structures that cannot be resolved with conventional fluorescence microscopes with the same objective lens and enhances the fluorescent signal by a factor of~5 without altering the field of view of the image.The improved resolution realized with enhanced fluorescent signals and the large field of view achieved via acoustofluidic scanning fluorescence nanoscopy provides a powerful tool for versatile nanoscale fluorescence imaging for researchers in the fields of medicine,biology,biophysics,and biomedical engineering.展开更多
Laboratory automation technologies have revolutionized biomedical research.However,the availability of automation solutions at the single-cell level remains scarce,primarily owing to the inherent challenges of handlin...Laboratory automation technologies have revolutionized biomedical research.However,the availability of automation solutions at the single-cell level remains scarce,primarily owing to the inherent challenges of handling cells with such small dimensions in a precise,biocompatible manner.Here,we present a single-cell-level laboratory automation solution that configures various experiments onto standardized,microscale test-tube matrices via our precise ultrasonic liquid sample ejection technology,known as PULSE.PULSE enables the transformation of titer plates into microdroplet arrays by printing nanodrops and single cells acoustically in a programmable,scalable,and biocompatible manner.Unlike pipetting robots,PULSE enables researchers to conduct biological experiments using single cells as anchoring points(e.g.,1 cell vs.1000 cells per“tube”),achieving higher resolution and potentially more relevant data for modeling and downstream analyses.We demonstrate the ability of PULSE to perform biofabrication,precision gating,and deterministic array barcoding via preallocated droplet-addressable primers.Single cells can be gently printed at a speed range of 5–20 cell⋅s−1 with an accuracy of 90.5–97.7%,which can then adhere to the substrate and grow for up to 72 h while preserving cell integrity.In the deterministic barcoding experiment,95.6%barcoding accuracy and 2.7%barcode hopping were observed by comparing the phenotypic data with known genotypic data from two types of single cells.Our PULSE platform allows for precise and dynamic analyses by automating experiments at the single-cell level,offering researchers a powerful tool in biomedical research.展开更多
基金support from the National Institutes of Health(R01GM141055 and R01GM145960)the National Science Foundation(CMMI-2104295).
文摘Contactless manipulation of samples,particularly the ability to dynamically handle multiple fragile specimens while maintaining their integrity and viability,is crucial for various applications in biology,medicine,engineering,and physics.While hydrodynamic tweezers have emerged as a promising approach for gentle,label-free manipulation of a wide range of sample types and sizes,they typically have limited flexibility in terms of dynamic control,making it challenging to realize high-resolution and programmable manipulation of multiple samples.Here,we introduce the Streaming-based Tweezers for Routing,Engineering,And Manipulation of multiparticles(STREAM)with sub-wavelength resolution.The platform employs an array of piezoelectric plates arranged in a space-reciprocal pattern to generate acoustic streaming,creating localized trapping points.The mechanism of particle trapping and the improvement of routing resolution via multiunit activation were investigated.Subsequently,a convolutional neural network(CNN)with arbitrary voltage combination as the input and predicted trapping position as the output was integrated into the system.The CNN calibration is vital to the system as it enhances the platform’s performance,enabling precise control of the trapping positions beyond traditional physical unit size limitations.We demonstrated the STREAM platform’s capabilities through single particle routing with sub-wavelength precision,simultaneous manipulation of multiple particles,and on-demand assembly of samples.The STREAM platform opens new possibilities for applications requiring precise and dynamic control of particles and samples,with the potential to advance fields including biology,chemistry,and materials science.
基金support from the National Institutes of Health(R01GM132603,R01GM141055,R44HL140800,and R21HD102790)Z.M.acknowledges the financial support from the China Scholarship CouncilE.C.was funded by the Hartwell Foundation.
文摘Separating plasma from whole blood is an important sample processing technique required for fundamental biomedical research,medical diagnostics,and therapeutic applications.Traditional protocols for plasma isolation require multiple centrifugation steps or multiunit microfluidic processing to sequentially remove large red blood cells(RBCs)and white blood cells(WBCs),followed by the removal of small platelets.Here,we present an acoustofluidic platform capable of efficiently removing RBCs,WBCs,and platelets from whole blood in a single step.By leveraging differences in the acoustic impedances of fluids,our device generates significantly greater forces on suspended particles than conventional microfluidic approaches,enabling the removal of both large blood cells and smaller platelets in a single unit.As a result,undiluted human whole blood can be processed by our device to remove both blood cells and platelets(>90%)at low voltages(25 Vpp).The ability to successfully remove blood cells and platelets from plasma without altering the properties of the proteins and antibodies present creates numerous potential applications for our platform in biomedical research,as well as plasma-based diagnostics and therapeutics.Furthermore,the microfluidic nature of our device offers advantages such as portability,cost efficiency,and the ability to process small-volume samples.
基金support from the National Institutes of Health(R01GM143439,R01HD103727,UH3TR002978,and U18TR003778)the National Science Foundation(CMMI-2104295)a National Science Foundation Graduate Research Fellowship under Grant no.2139754.
文摘Large-field nanoscale fluorescence imaging is invaluable for many applications,such as imaging subcellular structures,visualizing protein interactions,and high-resolution tissue imaging.Unfortunately,conventional fluorescence microscopy requires a trade-off between resolution and field of view due to the nature of the optics used to form the image.To overcome this barrier,we developed an acoustofluidic scanning fluorescence nanoscope that simultaneously achieves superior resolution,a large field of view,and strong fluorescent signals.The acoustofluidic scanning fluorescence nanoscope utilizes the superresolution capabilities of microspheres that are controlled by a programmable acoustofluidic device for rapid fluorescence enhancement and imaging.The acoustofluidic scanning fluorescence nanoscope resolves structures that cannot be resolved with conventional fluorescence microscopes with the same objective lens and enhances the fluorescent signal by a factor of~5 without altering the field of view of the image.The improved resolution realized with enhanced fluorescent signals and the large field of view achieved via acoustofluidic scanning fluorescence nanoscopy provides a powerful tool for versatile nanoscale fluorescence imaging for researchers in the fields of medicine,biology,biophysics,and biomedical engineering.
基金support from the National Institutes of Health(Grant numbers:R01HD103727,UH3TR002978,R01GM141055,R44OD024963,R44HL140800,and R44AG063643).
文摘Laboratory automation technologies have revolutionized biomedical research.However,the availability of automation solutions at the single-cell level remains scarce,primarily owing to the inherent challenges of handling cells with such small dimensions in a precise,biocompatible manner.Here,we present a single-cell-level laboratory automation solution that configures various experiments onto standardized,microscale test-tube matrices via our precise ultrasonic liquid sample ejection technology,known as PULSE.PULSE enables the transformation of titer plates into microdroplet arrays by printing nanodrops and single cells acoustically in a programmable,scalable,and biocompatible manner.Unlike pipetting robots,PULSE enables researchers to conduct biological experiments using single cells as anchoring points(e.g.,1 cell vs.1000 cells per“tube”),achieving higher resolution and potentially more relevant data for modeling and downstream analyses.We demonstrate the ability of PULSE to perform biofabrication,precision gating,and deterministic array barcoding via preallocated droplet-addressable primers.Single cells can be gently printed at a speed range of 5–20 cell⋅s−1 with an accuracy of 90.5–97.7%,which can then adhere to the substrate and grow for up to 72 h while preserving cell integrity.In the deterministic barcoding experiment,95.6%barcoding accuracy and 2.7%barcode hopping were observed by comparing the phenotypic data with known genotypic data from two types of single cells.Our PULSE platform allows for precise and dynamic analyses by automating experiments at the single-cell level,offering researchers a powerful tool in biomedical research.
