Abstract: The present invention relates to compositions and methods for separating cells. The present invention utilizes a combination of techniques to deplete non-nucleated and nucleated cells in a biological sample. The use of this invention assists in reducing the complexity of a biological sample such as peripheral blood, and help in the diagnosis and prognosis of many conditions. The invention includes solutions and methods to selectively deplete red and white blood cells from a blood sample. The preferred sample is blood, effusion, or aspirate samples containing one or more cell types that can be enriched from such a sample. The present invention provides methods for identifying target cells, nucleic acids or chromosome quantification.