Optical projection imaging system and method for automatically detecting cells with molecular marker compartmentalization associated with malignancy and disease
First Claim
1. A method for the detection of cells with molecular marker compartmentalization associated with malignancy and/or disease including a cancer, the method comprising the steps of:
- a) obtaining a cell sample having a plurality of cells and suspending the plurality of cells in a solution;
b) if required, fixing the plurality of cells of the cell sample;
c) labeling at least one molecular marker in the plurality of cells with tagged molecular probes or stains;
d) illuminating at least one cell of the plurality of cells with at least one point source of light;
e) obtaining at least two different projection images through the at least one cell with a digital array detector;
f) compensating the at least two projection images for variations in illumination;
g) analyzing the at least two projection images to detect at least one labeled molecular marker having densitometric and location features;
h) analyzing the location of the at least one molecular marker within the at least one cell;
i) measuring compartmentalization of the at least one labeled molecular marker by using the densitometric and location features; and
j) analyzing compartmentalization of the at least one labeled molecular marker with at least one classifier for the detection of malignancy and/or disease associated molecular marker-compartmentalization.
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Accused Products
Abstract
A system and method for rapidly detecting cells associated with malignancy and disease using molecular marker compartmentalization includes an optical tomography (OT) or a flow optical tomography (FOT) instrument capable of producing various optical projection images (or shadowgrams) containing accurate density information from a cell or cells labeled with tagged molecular probes or stains, a computer and software to analyze and reconstruct the projection images into a multi-dimensional data set, and automated feature collection and object classifiers. The system and method are particularly useful in the early detection of cancers such as lung cancer using cells from sputum or cheek scrapings and cervical/ovarian cancer using a cervical scraping, and the system can be used to detect rare cells in specimens including blood.
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Citations
32 Claims
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1. A method for the detection of cells with molecular marker compartmentalization associated with malignancy and/or disease including a cancer, the method comprising the steps of:
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a) obtaining a cell sample having a plurality of cells and suspending the plurality of cells in a solution;
b) if required, fixing the plurality of cells of the cell sample;
c) labeling at least one molecular marker in the plurality of cells with tagged molecular probes or stains;
d) illuminating at least one cell of the plurality of cells with at least one point source of light;
e) obtaining at least two different projection images through the at least one cell with a digital array detector;
f) compensating the at least two projection images for variations in illumination;
g) analyzing the at least two projection images to detect at least one labeled molecular marker having densitometric and location features;
h) analyzing the location of the at least one molecular marker within the at least one cell;
i) measuring compartmentalization of the at least one labeled molecular marker by using the densitometric and location features; and
j) analyzing compartmentalization of the at least one labeled molecular marker with at least one classifier for the detection of malignancy and/or disease associated molecular marker-compartmentalization. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)
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19. A method for the detection of cells with molecular marker compartmentalization associated with malignancy and disease including a cancer, the method comprising the steps of:
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a) obtaining a cell sample having a plurality of cells and suspending the plurality of cells in a solution;
b) if required, fixing the plurality of cells of the cell sample;
c) labeling at least one molecular marker in the plurality of cells with tagged molecular probes or stains;
d) illuminating at least one cell of the plurality of cells with at least one point source of light;
e) obtaining at least one projection image through the at least one cell with a digital array detector;
f) compensating the at least one projection image for variations in illumination;
g) analyzing the at least one projection image to detect at least one labeled molecular marker;
h) analyzing the location of the at least one molecular marker in two-dimensional (2D) space within the at least one cell;
i) measuring compartmentalization of the at least one labeled molecular marker by using the densitometric and location features; and
j) analyzing compartmentalization of the at least one labeled molecular marker with at least one classifier for the detection of malignancy and/or disease associated molecular marker-compartmentalization. - View Dependent Claims (20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32)
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Specification