Detecting rare cells within blood has numerous applications in disease diagnostics.Existing rare cell detection techniques are typically hindered by their high cost and low throughput.Here,we present a computational c...Detecting rare cells within blood has numerous applications in disease diagnostics.Existing rare cell detection techniques are typically hindered by their high cost and low throughput.Here,we present a computational cytometer based on magnetically modulated lensless speckle imaging,which introduces oscillatory motion to the magneticbead-conjugated rare cells of interest through a periodic magnetic force and uses lensless time-resolved holographic speckle imaging to rapidly detect the target cells in three dimensions(3D).In addition to using cell-specific antibodies to magnetically label target cells,detection specificity is further enhanced through a deep-learning-based classifier that is based on a densely connected pseudo-3D convolutional neural network(P3D CNN),which automatically detects rare cells of interest based on their spatio-temporal features under a controlled magnetic force.To demonstrate the performance of this technique,we built a high-throughput,compact and cost-effective prototype for detecting MCF7 cancer cells spiked in whole blood samples.Through serial dilution experiments,we quantified the limit of detection(LoD)as 10 cells per millilitre of whole blood,which could be further improved through multiplexing parallel imaging channels within the same instrument.This compact,cost-effective and high-throughput computational cytometer can potentially be used for rare cell detection and quantification in bodily fluids for a variety of biomedical applications.展开更多
基金the support of the KocGroup,NSF Engineering Research Center(ERC,PATHS-UP)the Army Research Office(ARO+7 种基金W911NF-13-1-0419 and W911NF-13-1-0197)the ARO Life Sciences Division,the National Science Foundation(NSF)CBET Division Biophotonics Programthe NSF INSPIRE Award,NSF Partnerships for Innovation:Building Innovation Capacity(PFI:BIC)Programthe National Institutes of Health(NIH,R21EB023115)the Howard Hughes Medical Institute(HHMI)the Vodafone Americas Foundationthe Mary Kay Foundationthe Steven&Alexandra Cohen Foundation.
文摘Detecting rare cells within blood has numerous applications in disease diagnostics.Existing rare cell detection techniques are typically hindered by their high cost and low throughput.Here,we present a computational cytometer based on magnetically modulated lensless speckle imaging,which introduces oscillatory motion to the magneticbead-conjugated rare cells of interest through a periodic magnetic force and uses lensless time-resolved holographic speckle imaging to rapidly detect the target cells in three dimensions(3D).In addition to using cell-specific antibodies to magnetically label target cells,detection specificity is further enhanced through a deep-learning-based classifier that is based on a densely connected pseudo-3D convolutional neural network(P3D CNN),which automatically detects rare cells of interest based on their spatio-temporal features under a controlled magnetic force.To demonstrate the performance of this technique,we built a high-throughput,compact and cost-effective prototype for detecting MCF7 cancer cells spiked in whole blood samples.Through serial dilution experiments,we quantified the limit of detection(LoD)as 10 cells per millilitre of whole blood,which could be further improved through multiplexing parallel imaging channels within the same instrument.This compact,cost-effective and high-throughput computational cytometer can potentially be used for rare cell detection and quantification in bodily fluids for a variety of biomedical applications.
