Methods and compositions for detecting rare cells from a biological sample

A method for isolating a target cell from a biological sample containing other types of cells, said method comprising:

• a) enriching the sample by selectively removing at least one non-target cell type without removing the target cell;
• b) debulking the sample by reducing the sample volume without removing the target cell;
• and
• c) subjecting the enriched sample comprising the target cell to a downstream process that identifies, characterizes, or utilizes the target cell population
• wherein the target cell is an epithelial cell, a mesenchymal cell, a tumor cell, an infected cell, a mutated cell, a damaged cell, a stem cell, or a fetal cell.

A method for detecting a non-hematopoietic cancer cell in a blood sample, comprising the steps of:

• a) removing the majority of the hematopoietic cells from the sample using depletion methods without removing the cancer cells if any are present, to provide an enriched sample;
• and
• b) assessing the presence or activity level of telomerase in the enriched sample, or detecting the presence or expression level in the enriched sample of a nucleic acid that encodes telomerase;
• wherein the presence or amount of telomerase activity or telomerase nucleic acid or telomerase expression is used to determine a probability that the blood sample contained at least one cancer cell.