357d Quantification of Non-Specific Binding of Magnetic Nanoparticles: Implication for Detection and Magnetic Cell Separation

Jeffrey Chalmers1, Ying Xiong2, Mei Shao3, Xiaodong Tong2, Sherif Farag4, and Maciej Zborowski5. (1) Chemical and Biomolecular Engineering, Ohio State University, 140 W. 19th Avenue, Columbus, OH 43210, (2) Chemical and Biomolecular Engineering, The Ohio State Unversity, 140 W 19th Ave, Columbus, OH 43210, (3) The Ohio State University, 140 w19th Ave, Columbus, OH 43210, (4) Bone Marrow and Stem Cell Transplantation, Indiana University School of Medicine, 635 Barnhill Drive, Room 224G, Indianapolis, IN 46202, (5) Department of Biomedical Engineering, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH

The maturity of magnetic cell separation technology, as indicated by both the commercial success of a number of companies, and high number of citations indicating its use, also places increasing demands on magnetic cell separation performance. While a number of factors can cause sub-optimal performance, one of the major challenges can be non-specific binding of magnetic nano or micro particles to non-targeted cells. Depending on the type of separation, this non-specific binding can have a negative effect on the final purity, the recovery of the targeted cell, or both. In this work, we quantitatively demonstrate that non-specific binding of magnetic nanoparticles can impart a magnetization in cells such that they thee cells can be retained in a MACS separation column in such a way to significantly impact the purity of the final product. We also demonstrate that the nonspecific binding can negatively impact the recovery of desired cells. While highly variable, cells without specifically or non-specifically bound MACS beads can be retained in a MACS column, compromising the performance of the separation. How, this phenomenon is not easily reproducible. We also demonstrate experimentally, and through theoretical arguments that the number of MACS magnetic particles needed to impart a magnetization that can cause non-targeted cells to be retained in the column to be on the order of 500 to 1000 nanoparticles. This number was demonstrated experimentally with an instrument, cell tracking velocity, CTV, and it is demonstrated that the sensitivity of the CTV instruments for Fe atoms is several order of magnitude more sensitive than ICP-MS.