(300c) Cell Capture Behavior in C.E.E™ Microfluidic Rare Cell Capture and Enrichment System

Rare cell extraction and enrichment has long been recognized as a valuable tool for diagnostic medicine. Biocept had identified the emerging technology of microfluidics and bioMEMS to be well suited for diagnostic applications, for which we've developed the Cell Enrichment and Extraction (CEE?) technology platform. CEE? enriches rare cells from large biological volumes by combining antibody-functionalized surfaces with a microfluidics channel. Cells flowing through the CEE system are captured along a randomized array of functionalized posts, and subsequent processing makes medical diagnosis from rare cells possible. The characteristics of cell capture under different physical conditions were explored experimentally, using JEG-3 choriocarcinoma and K562 erythroleukemia cells as models of specific capture. Capture efficiencies were recorded for channels at various flow rates, antibody concentrations, and angles to the horizontal plane. Cell locations were also noted in terms of capture on the posts or the channel floor, as well as their distance along the channel. We observed higher capture efficiency at greater run angles and flow rates under the conditions investigated. More cells were captured on posts vs. channel floor at higher flow rates.

Cell capture in the CEE? system is only possible when the target cells make physiochemical contact with the capturing surfaces. However, this aspect of an actual capturing system is often complex and not always practical to optimize empirically. Thus, numerical simulations of cell suspensions in interaction with this complex microfluidic device were employed to investigate the problem. The current standard treatment of particulate flow by commercial CFD software using Discrete Phase Modeling (DPM) treats all particles as point masses. This approach is not suitable for modeling enrichment of rare cells due to the relatively large volumes of the cells compared to the fluidic system of interest. The Macroscopic Particle Model (MPM) currently under development by Fluent, Inc., relates physical and numerical parameters to collision frequencies and patterns observed in experimental systems. Many of MPM's parameters are explored according to their effects on the accuracy and overall similarity of the simulations to observed systems.