A Bio-MEMS Device for Separation of Breast Cancer Cells from Peripheral Whole Blood.

Juan Feng, Louisiana State University

The goal of this study was to develop a microfluidics prototype of high sensitivity that could detect breast tumor cells from circulating blood. The researchers exploited the fact that breast cancer cells (cell line MCF-7) overexpress EpCAM (Epithelial Cell Adhesion Molecule) on their surfaces. By immobilizing anti-EpCAM in the microfluidics channel and passing the blood through the microchannel at an optimal rate, MCF-7 cells could be trapped via antigen-antibody interaction.

The device essentially consists of a PMMA channel in which the contact surface is amine-functionalized to allow for the cross-linking of anti-EpCAM. A suspension of blood cells and MCF-7 in cell culture media was passed through the microchannel via syringe pump. This suspension is representative of human blood, especially since the only epithelial cells that are ever present in human blood are tumor cells. Using flow models and empirical determination, parameters such as flow velocity, channel diameter, and concentration of anti-EpCAM immobilization were optimized. The channel is able to detect one MCF-7 cell in 10^7 normal blood cells. This detection was measured via fluorescence marker that was activated when the EpCAM-anti-EpCAM event occured. The next generation device of this microfluidics channel is anticipated by the researchers to be a part of a lab-on-a-chip device, wherein the blood sample can be introduced and analyzed on a microchip, returning a result immediately.

In this way, many objectives of the ideal breast cancer diagnostic tool are being addressed. This research addresses the specificity and selectivity needed in a breast cancer diagnostic tool, since the antigen-antibody binding is a rare interaction of high affinity, and the channel is able to detect the tumor cells at a very low concentration. This is important because cancer is inherently metastatic. Low concentrations of tumor cells are circulating through the bloodstream at early stages of tumor development. This makes it possible to detect breast cancer even before conventional techniques are able to. The lab-on-a-chip idea has appeal as well. The use of relatively inexpensive materials, coupled with miniaturization, allows the monetary cost of breast cancer detection to be dramatically reduced. As a result, the frequency of testing can be increased and early detection enabled.

The PMMA microchannel construct. Note: The radius of the channel ranges from 20-50 μm.

Inside the PMMA microchannel. The white spots are the immobilized anti-EpCAM