Innovative Microsystems: Novel Nanostructures to Capture Circulating Breast Cancer Cells; Annual rept. 23 Apr 2007-22 Apr 2008

摘要

The goal of this project is to develop a microsystem for sorting metastatic breast cancer cells from a heterogeneous suspension of cells circulating in the blood stream. Conceptually, the technique requires the transformation of a distinguishing biochemical characteristic of the target cells, such as up-regulated cadherin phenotype, into a mechanical or electrical that makes it possible to selectively manipulate the cells on the microscale. The project includes developments of a model system of cells to evaluate cadherin-mediated cell sorting and an integrated bio-functional microfluidic system to capture target cells from heterogeneous suspensions of cells. We have succeeded in the transfection of MDA-MB-231 cells with an N-cadherin expression vector deriving a homogeneous population. An anti-N-cad functionalized surface has been shown to capture N-cad expressing prostate cancer cells (PC3N) with high degree of selectivity. An assay to characterize and a technique to control the amount of immobilized anti-N-cad antibodies on surfaces have been developed to maximize the cell capture efficiency. Microchannels with anti-N-cad functionalized surfaces have been fabricated. Under flow conditions, the capture rate is poor; however, after 15min of incubation time, the capture rate is high. Once captured, the cell/surface adhesion bond is strong enough to sustain high flow-induced shears stress.