Devices and methods for enrichment and alteration of circulating tumor cells and other particles
The invention features devices and methods for detecting, enriching, and analyzing circulating tumor cells and other particles. The invention further features methods of diagnosing a condition, e.g., cancer, in a subject by analyzing a cellular sample from the subject.
1 . A device for processing a cellular sample, said device comprising:
a) a channel comprising a structure that directs one or more first cells in a first direction to produce a first output sample enriched in said first cells and one or more second cells in a second direction to produce a second output sample enriched in said second cells, wherein said device is configured either:
i) to direct cells having a hydrodynamic size greater than 12 microns in said first direction, and cells having a hydrodynamic size less than or equal to 12 microns in said second direction; or
ii) to direct cells having a hydrodynamic size greater than or equal to 6 microns and less than or equal to 12 microns in said first direction, and cells having a hydrodynamic size less than 6 microns or cells having a hydrodynamic size greater than 12 microns in said second direction; and
b) a detection module for analyzing said first output sample or said second output sample, wherein said detection module is fluidically coupled to said channel.
2 . The device of claim 1 , wherein said device is configured to direct cells having a hydrodynamic size greater than or equal to 6 microns and less than or equal to 12 microns in said first direction, and cells having a hydrodynamic size less than 6 microns or cells having a hydrodynamic size greater than 12 microns in said second direction.
3 . The device of claim 1 , wherein said device is configured to direct cells having a hydrodynamic size greater than or equal to 8 microns and less than or equal to 10 microns in said first direction, and cells having a hydrodynamic size less than 8 microns or cells having a hydrodynamic size greater than 10 microns in said second direction.
4 . The device of claim 1 , wherein said detection module is adapted to identify a marker associated with cancer in said first cells.
5 . The device of claim 1 , wherein said detection module comprises an antibody that specifically binds said first cells.
6 . The device of claim 5 , wherein said antibody specifically binds one or more markers selected from Table 1.
7 . The device of claim 1 , wherein said detection module is configured to detect one or more epithelial cells, cancer cells, bone marrow cells, fetal cells, progenitor cells, stem cells, foam cells, mesenchymal cells, immune system cells, endothelial cells, endometrial cells, connective tissue cells, trophoblasts, bacteria, fungi, or pathogens.
8 . The device of claim 1 , wherein said detection module comprises a microscope, a cell counter, a magnet, a biocavity laser, a mass spectrometer, a PCR device, an RT-PCR device, a matrix, a microarray, or a hyperspectral imaging system.
9 . A device for processing a cellular sample, said device comprising:
a) a channel comprising a structure that directs one or more cancer cells in a first direction to produce a first output sample enriched in said cancer cells and one or more second cells in a second direction to produce a second output sample enriched in said second cells; and
b) a capture module for capturing said cancer cells or said second cells, wherein said capture module is fluidically coupled to said channel, and wherein said capture module comprises one or more binding moieties that selectively bind said cancer cells or said second cells.
10 . The device of claim 9 , wherein said structure comprises an array of obstacles that form a network of gaps.
11 . The device of claim 9 , wherein said one or more binding moieties specifically bind one or more epithelial cells, cancer cells, bone marrow cells, fetal cells, progenitor cells, stem cells, foam cells, mesenchymal cells, immune system cells, endothelial cells, endometrial cells, connective tissue cells, trophoblasts, bacteria, fungi, or pathogens.
12 . The device of claim 10 , wherein said obstacles comprise said binding moieties.
13 . The device of claim 9 , wherein said device is configured to direct cells having a hydrodynamic size greater than 12 microns in said first direction.
14 . The device of claim 9 , wherein said device is configured to direct cells having a hydrodynamic size greater than 14 microns in said first direction.
15 . The device of claim 9 , wherein said device is configured to direct cells having a hydrodynamic size greater than 16 microns in said first direction.
16 . The device of claim 9 , further comprising a cell counting module fluidically coupled to said capture module.
17 . The device of claim 9 , wherein said one or more binding moieties comprise a polypeptide.
18 . The device of claim 17 , wherein said polypeptide comprises an antibody or fragment thereof.
19 . The device of claim 18 , wherein said antibody or fragment thereof is monoclonal.
20 . The device of claim 19 , wherein said monoclonal antibody or fragment thereof binds to EpCAM.
21 . A device for processing a cellular sample, said device comprising a channel comprising a structure that directs one or more first cells in a first direction to produce a first output sample enriched in said first cells and one or more second cells in a second direction to produce a second output sample enriched in said second cells, wherein said structure comprises an array of obstacles that form a network of gaps, and wherein at least some of said obstacles comprise monoclonal anti-EpCAM antibodies or fragments thereof that selectively bind said first cells or said second cells.
22 . A device for processing a cellular sample, said device comprising:
a) an enrichment module that is capable of enriching cells in said cellular sample based on size; and
b) a cell counting module for determining the number of cells enriched by said enrichment module, wherein said cell counting module is fluidically coupled to said enrichment module.
23 . The device of claim 22 , wherein said enrichment module comprises a channel comprising a structure that directs one or more first cells in a first direction to produce a first output sample enriched in said first cells and one or more second cells in a second direction to produce a second output sample enriched in said second cells.
24 . The device of claim 23 , wherein said device is configured to direct cells having a hydrodynamic size greater than 12 microns in said first direction, and cells having a hydrodynamic size less than or equal to 12 microns in said second direction.
25 . The device of claim 23 , wherein said device is configured to direct cells having a hydrodynamic size greater than or equal to 6 microns and less than or equal to 12 microns in said first direction, and cells having a hydrodynamic size less than 6 microns or cells having a hydrodynamic size greater than 12 microns in said second direction.
26 . The device of claim 23 , wherein said first cells comprise cancer cells.
27 . The device of claim 23 , wherein said structure comprises an array of obstacles that form a network of gaps.
28 . The device of claim 22 , wherein said cell counting module utilizes impedance, optics, or capacitance to determine said number of cells in said first output sample or said second output sample.
29 . The device of claim 9 , 21 , or 22 , wherein said device further comprises a detector adapted to visualize said first output sample or said second output sample, said detector fluidically coupled to said capture module.
30 . The device of claim 1 , wherein said channel comprises an array of obstacles forming a network of gaps, and wherein fluid flows through said gaps such that said fluid is divided unequally into a major flux and a minor flux.