Method and apparatus for computer controlled rare cell, including fetal cell, based diagnosis

An automated diagnostic method for detecting abnormalities associated with a rare cell, found in a cell sample applied to a microscope slide at a concentration no greater than one cell in 10,000 cells, using an computerized automated microscopy system operatively configured to automatically search a microscope slide, to detect signals from said slide, and to process said signals, said method comprising the steps of:

• treating said cell sample with a selective identification label of said rare cell to label said rare cell with a signal detectable by said automated microscopy system;
• treating said cell sample with a diagnostic label selective to a diagnostic condition that may be detected in said rare cell, said diagnostic label producing a signal which is detectable by said automated microscopy system;
• affixing a portion of said cell sample containing said rare cell(s) as a monolayer on a microscope slide such that the monolayer comprises no greater than one cell in 10,000 cells;
• detecting by said automated microscopy system a signal indicative of said identification label associated with said rare cell and from said signal detected automatically determining the position of said rare cell(s) on said slide;
• detecting by said automated microscopy system a signal indicative of said diagnostic label associated with the position of said rare cell(s);
• automatically providing a putative diagnosis based on detection of said diagnostic label being associated with one or more detected rare cell(s).

A diagnostic method for detecting an abnormality associated with a rare cell, comprising:

• providing a computerized microscope;
• forming on a substrate a monolayer of an unenriched sample including the rare cell;
• using the computerized microscope to search the substrate for a first signal indicative of the rare cell;
• using the computerized microscope to detect a second signal indicative of the rare cell;
• and
• using the microscope to provide a diagnosis of the abnormality of the rare cell based on the second signal.

A diagnostic method for detecting an abnormality associated with a rare cell using a computerized microscope, comprising:

• forming on a substrate a monolayer of an unenriched sample including the rare cell;
• searching the substrate for a first signal indicative of the rare cell;
• positioning the microscope relative to the first signal to detect a second signal indicative of the rare cell;
• and
• providing a diagnosis of the abnormality of the rare cell based on the second signal.

A method of obtaining from a sample of cells a signal having diagnostic significance relative to a rare cell in the sample of cells, comprising the steps of:

• obtaining a monolayer of the sample of cells fixed on a substrate, wherein one or more rare cell(s) of interest is present in the monolayer sample at no greater than one in every 10,000 cells;
• contacting the rare cell(s) of interest with an agent to generate a diagnostic signal associated with one or more components of each of said rare cell of interest, the diagnostic signal having diagnostic significance;
• automatically determining the position of one or more said rare cell(s) of interest on said slide using a computerized microscopic vision system;
• automatically determining whether a diagnostic signal is associated with the determined position of each of said rare cells of interest using said computerized microscopic vision system.

A method of obtaining from a sample of unenriched maternal blood containing a naturally present concentration of fetal cells, a signal having diagnostic significance relative to the fetal cells, the method comprising:

• preparing a smear of the sample of unenriched maternal blood on a substrate;
• observing the smear using a computerized microscopic vision system operatively configured to read said substrate and to obtain a first signal indicative of the presence of a fetal cell;
• contacting the fetal cell with an agent to generate a second signal, the second signal having the diagnostic significance;
• observing the fetal cell using the computerized microscopic vision system to obtain the second signal;
• and
• counting occurrences of the second signal in a plurality of fetal cells eliciting said first signal.