Abstract: Immunomagnetic-based cell separation techniques, developed over the last decade, have shown to be extremely efficient at obtaining highly purified cell populations from a mixture of heterogeneous cells. Commercially available immunomagnetic cell separation devices are valuable tools that enrich cell suspensions by targeting the desired cells with a suitable monoclonal antibody conjugated to magnetic particles. However, one of the main drawbacks of these devices is their limited capacity to remove undesired cells that express low numbers of surface receptors. The development of flow-through devices such as the Quadrupole Magnetic Cell Sorter (QMS) has led to further application of immunomagnetic cell separation techniques in the clinical field. QMS has already proved efficient in selecting hematopoietic stem cells, T-helper, T-cytotoxic cells and cancer cells. The use of QMS offers the following advantage: the possibility of predicting outcomes of the sorted fractions, the capability of continuous operation, and the flexibility of changing operational conditions according to the magnetophoretic mobility of the labeled cell population to obtain the desired results. QMS can operate in positive selection (when cells of interest are labeled) or negative selection (when cells of interest are not targeted). Our investigation focuses on the challenges presented in negative selection. Presently, studies involving rare cell detection (cancer cells circulating in blood), T-cell depletion, and allogeneic T-cell depletion studies are being performed to evaluate the operational suitability of the device in the medical arena. Studies conducted on T-cell depletion and allogeneic T-cell depletion indicate that the sorting efficacy using QMS outperforms past methods. These studies are vital in order to develop a device that can expand the donor pool for cells needed for therapies, such as bone marrow transplants or stem cells transplant. Our results lead us to believe that the goal to obtain cell grafts free or with very low number of both T- or allogeneic T-cells is possible. The impact of those results is vast, as our research has demonstrated cell depletion levels below those detected by flow cytometry. We are confident that the Quadrupole Magnetic Cell Sorter has many future applications including use in cell selection for bone marrow or cell therapy treatment. Additionally, QMS may become one of the first FDA-approved devices for cell selection before cell therapy.