Apparatus and method for label-free analysis of rare cells from bodily fluids
AssigneeThe Regents of the University of California
InventorsDino Di Carlo, Derek Go, Mahdokht Masaeli, Elodie Sollier
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Abstract
A system and method for the label-free analysis of cells includes a purification device configured to receive a heterogeneous population of cells, the purification device temporarily trapping therein a subpopulation of cells from the heterogeneous population of cells and a cell analysis device positioned downstream of the purification device and configured to measure one or more cellular parameters including cell count, measured cell size, and/or cell morphology. In an alternative embodiment, the subpopulation of cells is analyzed while they are trapped within the purification device.
Claims17
A system for the label-free analysis of cells comprising:
- an adjustable flow rate pumping device coupled to a fluid sample containing a heterogeneous population of label-free cells;
- a purification device configured to receive the heterogeneous population of label-free cells, the purification device comprising an inlet coupled to the pumping device and further coupled to a plurality of microfluidic channels, each microfluidic channel having along a length thereof a plurality of expansion regions, and an outlet located downstream of the plurality of expansion regions, wherein vortices are generated in the expansion regions and temporarily trap therein a subpopulation of cells from the heterogeneous population of label-free cells in response to flow of the fluid sample within the microfluidic channels at a first flow rate from the adjustable flow rate pumping device and wherein the subpopulation of cells are released from the plurality of expansion regions and flow into the outlet at a second, reduced flow rate from the adjustable flow rate pumping device;
- and
- a high-speed camera imaging system positioned at an imaging region in the outlet and configured to acquire video images of the subpopulation of cells moving through the imaging region and comprising one or more processors executing image processing software configured to extract and process image frames in the video images and further configured to perform at least one assessment on the cells of the subpopulation comprising:
- count cells, measure cell size, and/or measure cell morphology.
A method for the label-free analysis of cells comprising:
- flowing a heterogeneous population of label-free cells within a microfluidic device at a first flow rate, the microfluidic device comprising an inlet coupled to a pumping device and further coupled to a plurality of microfluidic channels, each microfluidic channel having along a length thereof a plurality of expansion regions;
- trapping within vortices created in the plurality of expansion regions a subpopulation of cells from the heterogeneous population of label-free cells in response to flow of the fluid sample within the microfluidic channels;
- reducing the flow rate through the microfluidic device to release the trapped subpopulation of cells from the plurality of expansion regions into an outlet;
- and
- capturing video images of the moving subpopulation of cells in the outlet with a high-speed camera;
- subjecting the captured video images to image processing to isolate individual cells of the subpopulation;
- automatically performing at least one of counting the trapped subpopulation of cells, measuring size of the trapped subpopulation of cells, and measuring morphology of the trapped subpopulation of cells.
A method of characterizing the health of a subject from a fluid sample comprising:
- flowing the fluid sample containing a heterogeneous population of label-free cells within a microfluidic device at a first flow rate, the microfluidic device comprising an outlet, an inlet coupled to a pumping device and further fluidically coupled to a plurality of microfluidic channels, each microfluidic channel having along a length thereof a plurality of expansion regions;
- trapping within vortices created in the plurality of expansion regions a subpopulation of cells from the heterogeneous population of label-free cells in response to flow of the fluid sample within the microfluidic channels at the first flow rate;
- reducing the flow rate through the microfluidic device to release the trapped subpopulation of cells from the plurality of expansion regions;
- capturing video images of the moving subpopulation of cells in the outlet with a high-speed camera;
- subjecting the captured video images to image processing to isolate and count individual cells of the subpopulation;
- and
- generating a characterization of the health of the subject based at least in part on the count of the subpopulation of cells, wherein the health of the subject is characterized as unhealthy when the count exceeds a threshold value.
Dependencies are inferred from the claim text.