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Imaging Flow Cytometry Enabled by a Spatial-Frequency Filter

通过空间频率滤波器实现成像流式细胞术

基本信息

批准号：
9139362
负责人：
Sung Hwan Cho
金额：
$ 21.4万
依托单位：
NANOCELLECT BIOMEDICAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-15 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9139362
关键词：
Address Algorithms Architecture Area Back Benchmarking Big Data Biochemical Biological Assay Biological Process Biomedical Research Cell Cycle Cell Separation Cell Size Cell membrane Cell surface Cells Characteristics Clinical Code Collection Communities Complex Detection Devices Disease Flow Cytometry Fluorescence Fluorescence-Activated Cell Sorting Frequencies Image Image Cytometry Imaging Techniques Imaging technology Label Location Marketing Masks Methods Microfluidics Microscopy Mission Mus Nuclear Nuclear Protein Optics Performance Phagocytosis Phase Ploidies Process Property Proteins Publishing Research Research Personnel Resources Shapes Side Signal Transduction Sorting - Cell Movement Staining method Stains Stream System Technology Time Tube Zymosan base cell motility cellular imaging clinical application cost design detector fluorescence imaging fluorescence microscope innovation instrument light scattering macrophage microscopic imaging optic flow cytometer particle photomultiplier precision medicine programs public health relevance rapid growth sensor tool

项目摘要

DESCRIPTION (provided by applicant): Fluorescence-activated-cell-sorting (FACS) or flow cytometry enables clinicians and researchers to quantitatively characterize the physical (cell size, shape, and granularity) and biochemical (DNA content, cell cycle distribution, cell surface markers, and viability) properties of cells, however FACS devices do not produce an image of the cell. Increasing sophistication of research assays now rely on the collection of cells based on their phenotypical and spatial characteristics; with the capabilities offered only by microscopic imaging cytometers having severe limits in throughput and lacking cell isolation. We propose an innovative, low cost design to combine the merits of FACS and microscopic imaging cytometry without the limits of each, offering the biomedical research and clinical community a unique tool to address the needs for current and emerging applications. The key innovation is based on a significant extension of the spatial-coding algorithms our team demonstrated in the past years. In the proposed design, we create a special filter with a matrix of periodic slits in front of each PMT detector. The resulting PMT signal is composed of the multiplexed cell signals modulated by the filter, which can subsequently be deconvolved to produce fluorescence and scatter generated from different areas of the cell: the image. In this Phase I program, we will integrate imaging technology into our existing WOLF Cell Sorter to produce the very first imaging cytometer with cell sorting capabilities. Since we use conventional, non-pixelated detectors (e.g. PMTs) found in conventional flow cytometers, this technology is compatible with existing flow cytometer architectures allowing for wide use. Equipped with cell imaging capabilities, researchers can track many important biological processes by analyzing not only the intensity but the localization of certain proteins within cytosolic, nuclear, or cell membrane domains and subdomains. With the rapidly developing capabilities of handling "big data", images of millions of single cells in a flow cytometer provide vast resources for research and disease analysis, and rapid growth has been predicted in the market of such high-content imaging cytometer cell sorters for emerging applications such as precision medicine. We believe the proposed design is a major breakthrough that can potentially revolutionize the field of flow cytometry, and its impact and ramifications on both fundamental biomedical research and clinical applications can be tremendous.