Microfluidic isolation of tumor cells or other rare cells from whole blood or other liquids
Microdevices are disclosed to efficiently, accurately, and rapidly isolate and enumerate rare cells, such as circulating tumor cells, from liquids such as whole blood. The system employs multiple parallel meandering channels having a width on the order of 1-2 cell diameters. The microdevices can be produced at low-cost, may readily be automated, and in many instances may be used without pre-processing of the sample. They may be used to isolate and enumerate rare cells, including for example the detection and diagnosis of cancers, cancer staging, or evaluating the effectiveness of a therapeutic intervention, or detecting pathogenic bacteria. The device may optionally be used to nondestructively capture and later to release target cells.
1. A microfluidic device for capturing or isolating circulating tumor cells from a liquid, the microfluidic device comprising:
a substrate comprising a common fluid input and a common fluid output, a plurality of parallel channels configured to capture or isolate circulating tumor cells and fluidically connected to the common fluid input and the common fluid output, wherein the circulating tumor cells have a mean diameter, and wherein:
a. a cross-section of each of said plurality of parallel channels has a height and width taken in direction perpendicular to a length of the channels, and the length extends longitudinally from the common fluid input to the common fluid output;
b. the width of each of said plurality of parallel channels is at least about the mean diameter of the circulating tumor cells, and is not greater than about twice the mean diameter of the circulating tumor cells;
c. the height of each of said plurality of parallel channels is at least about three times the width of each respective channel;
d. at least part of the surface within each of said plurality of parallel channels is covalently linked to one or more capture elements; wherein said capture elements comprise antibodies or aptamers that selectively bind molecules on the membranes of the circulating tumor cells; and
e. each of said plurality of parallel channels has a sinusoidal or quasi-sinusoidal shape.
2. The microfluidic device of claim 1 , wherein said capture elements comprise monoclonal antibodies.