Optimal Halbach Configuration for Flow-through Immunomagnetic CTC Enrichment

Due to the low frequency of circulating tumor cells (CTC), the standard CellSearch method of enumeration and isolation using a single tube of blood is insufficient to measure treatment effects consistently, or to steer personalized therapy. Using diagnostic leukapheresis this sample size can be increased; however, this also calls for a suitable new method to process larger sample inputs. In order to achieve this, we have optimized the immunomagnetic enrichment process using a flow-through magnetophoretic system. An overview of the major forces involved in magnetophoretic separation is provided and the model used for optimizing the magnetic configuration in flow through immunomagnetic enrichment is presented. The optimal Halbach array element size was calculated and both optimal and non-optimal arrays were built and tested using anti-EpCAM ferrofluid in combination with cell lines of varying EpCAM antigen expression. Experimentally measured distributions of the magnetic moment of the cell lines used for comparison were combined with predicted recoveries and fit to the experimental data. Resulting predictions agree with measured data within measurement uncertainty. The presented method can be used not only to optimize magnetophoretic separation using a variety of flow configurations but could also be adapted to optimize other (static) magnetic separation techniques.

Automated summary

This study optimized the immunomagnetic enrichment process using a flow-through magnetophoretic system to increase sample size for more accurate treatment effects measurement and personalized therapy guidance. Experimental data confirmed the effectiveness of optimizing magnetophoretic separation methods in combination with cell lines of varying EpCAM antigen expression.