Provided are methods and compositions for isolating and detecting rare cells from a biological sample containing other types of cells, particularly including debulking that uses a microfabricated filter for filtering samples. The enriched rare cells can be used in a downstream process such as identification, characterization or growth in culture, or in other ways. Also included is a method of determining tumor aggressiveness or the number or proportion of cancer cells in the enriched sample by detecting telomerase activity, nucleic acid or expression after enrichment of rare cells. Also provided is an efficient, rapid method to specifically remove red and white blood cells from a biological sample containing at least one of the cell types, leading to enrichment of rare target cells including circulating tumor (CTC), stromal, mesenchymal, endothelial, fetal, stem, or non-hematopoietic cells et cetera from a blood sample.