DETECTION OF CIRCULATING TUMOR CELLS USING IMAGING FLOW CYTOMETRY
First Claim
1. A method for detecting cancer or a precancerous condition from images collected from a population of cells present in a bodily fluid, comprising the steps of:
- (a) providing a first population of abnormal cells and a second population of normal cells, the abnormal cells comprising at least one type of cells selected from the group consisting of cancer cells and cancer precursor cells;
(b) imaging the first population of cells in flow to collect first image data, and imaging the second population of cells in flow to collect second image data, such that the first and second image data for each cell in the respective populations of cells includes a plurality of simultaneously collected images, the plurality of simultaneously collected images for each cell comprising at least one of the following two types of images;
(i) multispectral images; and
(ii) multimodal images;
(c) analyzing the first and second image data to identify at least one cell characteristic that can be measured using the first and second image data and that enables the abnormal cells to be distinguished from the normal cells;
(d) collecting a bodily fluid comprising a third population of cells;
(e) imaging the third population of cells in flow to collect third image data, such that the third image data for each cell includes a plurality of simultaneously collected images, the plurality of simultaneously collected images comprising at least one of the following two types of images;
(i) multispectral images; and
(ii) multimodal images; and
(f) analyzing the third image data to determine if any abnormal cells are present in the third population, by determining if the at least one cell characteristic that enables the abnormal cells to be distinguished from the normal cells is present in the third image data, the presence of abnormal cells indicating the presence of cancer or a precancerous condition.
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Abstract
Photometric and morphometric features derived from multi-mode imaged. An imaging system simultaneously acquires a plurality of images for each cell passing through the field of view of the imaging system. Acquiring a plurality of different images (i.e., bright field, dark field, and fluorescent images) facilitates the determination of different morphological and morphometric parameters. Simultaneously acquiring the plurality of images enables relatively large populations of cells to be rapidly imaged, so that relatively small numbers of cancer cells in a large population of cells can be detected. Initially, known cancer cells are imaged to enable a marker to be identified. Then, a sample that may include cancer cells is imaged to determine if the marker is present.
204 Citations
20 Claims
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1. A method for detecting cancer or a precancerous condition from images collected from a population of cells present in a bodily fluid, comprising the steps of:
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(a) providing a first population of abnormal cells and a second population of normal cells, the abnormal cells comprising at least one type of cells selected from the group consisting of cancer cells and cancer precursor cells; (b) imaging the first population of cells in flow to collect first image data, and imaging the second population of cells in flow to collect second image data, such that the first and second image data for each cell in the respective populations of cells includes a plurality of simultaneously collected images, the plurality of simultaneously collected images for each cell comprising at least one of the following two types of images; (i) multispectral images; and (ii) multimodal images; (c) analyzing the first and second image data to identify at least one cell characteristic that can be measured using the first and second image data and that enables the abnormal cells to be distinguished from the normal cells; (d) collecting a bodily fluid comprising a third population of cells; (e) imaging the third population of cells in flow to collect third image data, such that the third image data for each cell includes a plurality of simultaneously collected images, the plurality of simultaneously collected images comprising at least one of the following two types of images; (i) multispectral images; and (ii) multimodal images; and (f) analyzing the third image data to determine if any abnormal cells are present in the third population, by determining if the at least one cell characteristic that enables the abnormal cells to be distinguished from the normal cells is present in the third image data, the presence of abnormal cells indicating the presence of cancer or a precancerous condition. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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14. An imaging system configured to acquire and analyze image data collected from a population of cells, to enable a cancerous or precancerous condition to be detected, comprising:
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(a) an image acquisition subsystem configured to simultaneously acquire a plurality of images of individual cells from the population of cells, while there is relative movement between the image acquisition subsystem and an individual cell, the plurality of images comprising at least two types of images selected from the group consisting of; (i) a bright field image; (ii) a dark field image; and (iii) a fluorescent image; (b) a database including at least one cell characteristic indicative of an abnormal condition, where the abnormal condition comprises at least one condition selected from the group consisting of a cancerous condition, and a precancerous condition, and where the at least one cell characteristic can be measured using the plurality of images acquired by the image acquisition subsystem; and (c) a processor configured to analyze the plurality of images of individual cells to determine if the at least one cell characteristic is present in the population of cells. - View Dependent Claims (15, 16, 17, 18, 19)
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20. An imaging system configured to acquire and analyze image data collected from a population of cells, where the image data include a plurality of images of individual cells that are acquired simultaneously, to enable a cancerous or precancerous condition to be detected, comprising:
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(a) a collection lens disposed so that light traveling from an individual cell passes through the collection lens and travels along a collection path; (b) a spectral separation element disposed in the collection path so as to spectrally separate light that has passed through the collection lens, thereby producing spectrally separated light; (c) an imaging lens disposed to focus the spectrally separated light, producing focused spectrally separated light; (d) a detector disposed to receive the focused spectrally separated light, such that the focused spectrally separated light incident on the detector simultaneously comprises a plurality of images of the individual cell, the plurality of images comprising the image data, the plurality of images being dispersed across the detector such that the plurality of images do not overlap, and the plurality of images being dispersed in a direction orthogonal to a direction of motion of the plurality of images across the detector when there is relative movement between the individual cell and the imaging system; and (e) a processor configured to analyze the image data for the plurality of images collected for individual cells in the population of cells, to determine if the image data indicate that any individual cell in the population of cells exhibits the cancerous or precancerous condition.
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Specification