William G. Lowrie Department of Chemical and Biomolecular Engineering Director, Analytical Cytometry Shared Resource, The OSU Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
Department of Biomedical Engineering Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Biotechnol Bioeng. 2018 May;115(5):1288-1300. doi: 10.1002/bit.26550. Epub 2018 Feb 9.
Magnetic separation of cells has been, and continues to be, widely used in a variety of applications, ranging from healthcare diagnostics to detection of food contamination. Typically, these technologies require cells labeled with antibody magnetic particle conjugate and a high magnetic energy gradient created in the flow containing the labeled cells (i.e., a column packed with magnetically inducible material), or dense packing of magnetic particles next to the flow cell. Such designs, while creating high magnetic energy gradients, are not amenable to easy, highly detailed, mathematic characterization. Our laboratories have been characterizing and developing analysis and separation technology that can be used on intrinsically magnetic cells or spores which are typically orders of magnitude weaker than typically immunomagnetically labeled cells. One such separation system is magnetic deposition microscopy (MDM) which not only separates cells, but deposits them in specific locations on slides for further microscopic analysis. In this study, the MDM system has been further characterized, using finite element and computational fluid mechanics software, and separation performance predicted, using a model which combines: 1) the distribution of the intrinsic magnetophoretic mobility of the cells (spores); 2) the fluid flow within the separation device; and 3) accurate maps of the values of the magnetic field (max 2.27 T), and magnetic energy gradient (max of 4.41 T /mm) within the system. Guided by this model, experimental studies indicated that greater than 95% of the intrinsically magnetic Bacillus spores can be separated with the MDM system. Further, this model allows analysis of cell trajectories which can assist in the design of higher throughput systems.
细胞的磁分离已经并将继续广泛应用于各种应用，从医疗保健诊断到食品污染检测。通常，这些技术需要用抗体磁珠偶联物标记细胞，并在含有标记细胞的流中创建高磁场能量梯度（即，填充有可诱导磁性材料的柱子），或在流道旁边密集排列磁性颗粒。虽然这种设计可以产生高磁场能量梯度，但它不适用于易于进行、高度详细的数学描述。我们的实验室一直在对可以用于固有磁性细胞或孢子的分析和分离技术进行特性描述和开发，这些细胞或孢子的磁性通常比通常免疫磁标记的细胞弱几个数量级。一种这样的分离系统是磁沉积显微镜（MDM），它不仅可以分离细胞，还可以将其沉积在载玻片上的特定位置，以便进一步进行显微镜分析。在这项研究中，使用有限元法和计算流体力学软件进一步对 MDM 系统进行了特性描述，并使用结合以下三个方面的模型来预测分离性能：1）细胞（孢子）固有磁泳动率的分布；2）分离装置内的流体流动；3）系统内磁场（最大值为 2.27 T）和磁场能量梯度（最大值为 4.41 T/mm）的精确图谱。该模型指导实验研究表明，超过 95%的固有磁性芽孢杆菌孢子可以用 MDM 系统进行分离。此外，该模型还可以分析细胞轨迹，这有助于设计更高通量的系统。
