Innovative Microsystems: Novel Nanostructures to Capture Circulating Breast Cancer Cells
Annual rept. 23 Apr 2008-22 Apr 2009
ARIZONA UNIV TUCSON
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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 cellsurface adhesion bond is strong enough to sustain high flow-induced shears stress.
- Medicine and Medical Research