Devices and methods for enrichment and alteration of circulating tumor cells and other particles

Abstract

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.

What is claimed is: 
     
         1 . A device for cell enrichment comprising:
 a) a receptacle;   b) a lid detachably attached to said receptacle, said lid comprising a functionalized lid surface, wherein said functionalized lid surface comprises one or more capture moieties that selectively capture a first cell from a cellular sample, and wherein said lid is configured to fit within said receptacle; and   c) a sample mobilizer coupled to either said receptacle or said lid.   
     
     
         2 . The device of  claim 1 , wherein said functionalized lid surface has a cross section that is square, rectangular, or circular. 
     
     
         3 . The device of  claim 1 , wherein said lid comprises glass, silicon, or plastic. 
     
     
         4 . The device of  claim 1 , wherein said receptacle comprises glass, silicon, or plastic. 
     
     
         5 . The device of  claim 1 , wherein said functionalized lid surface comprises a microstructure. 
     
     
         6 . The device of  claim 5 , wherein said microstructure comprises a micro-obstacle, a micro-corrugation, a micro-groove, or a micro-fin. 
     
     
         7 . The device of  claim 1 , wherein said capture moieties comprise one or more antibodies that specifically bind said first cell. 
     
     
         8 . The device of  claim 7 , wherein said antibodies comprise an array. 
     
     
         9 . The device of  claim 7 , wherein said antibodies specifically bind leukocytes or epithelial cells. 
     
     
         10 . The device of  claim 7 , wherein said antibodies specifically bind a cell surface cancer marker. 
     
     
         11 . The device of  claim 10 , wherein said cell surface cancer marker is selected from Table 1. 
     
     
         12 . The device of  claim 10 , wherein said cell surface cancer marker is selected from the group consisting of EpCAM, E-Cadherin, Mucin-1, Cytokeratin 8, EGFR, and leukocyte associated receptor (LAR). 
     
     
         13 . The device of  claim 1 , wherein said receptacle comprises a functionalized receptacle surface comprising one or more capture moieties that selectively capture a second cell from said cellular sample. 
     
     
         14 . The device of  claim 13 , wherein said functionalized receptacle surface comprises a microstructure. 
     
     
         15 . The device of  claim 14 , wherein said microstructure comprises a micro-obstacle, a micro-corrugation, a micro-groove, or a micro-fin. 
     
     
         16 . The device of  claim 15 , wherein said capture moieties that selectively capture a second cell comprise one or more antibodies that specifically bind said second cell. 
     
     
         17 . The device of  claim 16 , wherein said antibodies specifically bind leukocytes or epithelial cells. 
     
     
         18 . The device of  claim 16 , wherein said antibodies specifically bind a cell surface cancer marker of said second cell. 
     
     
         19 . The device of  claim 18 , wherein said cell surface cancer marker is selected from Table 1. 
     
     
         20 . The device of  claim 18 , wherein said cell surface cancer marker is selected from the group consisting of EpCAM, E-Cadherin, Mucin-1, Cytokeratin 8, EGFR, and leukocyte associated receptor (LAR). 
     
     
         21 . The device of  claim 1 , wherein said lid fits in said receptacle at a nonorthogonal angle with respect to a wall of said receptacle. 
     
     
         22 . The device of  claim 1 , wherein said sample mobilizer comprises a mechanical rocker. 
     
     
         23 . The device of  claim 1 , wherein said sample mobilizer is adapted to provide centrifugal force to said receptacle and said lid. 
     
     
         24 . The device of  claim 23 , wherein said centrifugal force drives cell rolling along said lid surface. 
     
     
         25 . The device of  claim 23 , wherein said sample mobilizer comprises an axle that rotates said receptacle. 
     
     
         26 . The device of  claim 25 , wherein said centrifugal force is capable of driving said lid into a nonorthogonal angle with respect to said axle. 
     
     
         27 . The device of  claim 1 , wherein said sample mobilizer comprises a first chamber fluidically coupled to a second chamber, wherein each said chamber has a surface in contact with the internal space of said receptacle, and wherein fluid movement between said chambers results in a change in shape of each chamber. 
     
     
         28 . The device of  claim 1 , wherein said receptacle can hold at least 10 mL of fluid. 
     
     
         29 . The device of  claim 1 , wherein said receptacle can hold at least 50 mL of fluid. 
     
     
         30 . A method for enriching one or more first cells from a cellular sample, said method comprising the steps of:
 a) placing said cellular sample in a device comprising:
 i) a receptacle; 
 ii) a lid detachably attached to said receptacle, said lid comprising at least one functionalized lid surface, wherein said functionalized lid surface comprises one or more capture moieties that selectively capture said first cells from said cellular sample, and wherein said lid is configured to fit within said receptacle; and 
 iii) a sample mobilizer coupled to either said receptacle or said lid; 
   b) covering said cellular sample with said lid;   c) mobilizing said sample using said sample mobilizer; and   d) removing said lid from said receptacle.   
     
     
         31 . The method of  claim 30 , wherein said first cell is a cancer cell or an epithelial cell. 
     
     
         32 . The method of  claim 30 , wherein step c) comprises applying a centrifugal force to said receptacle. 
     
     
         33 . The method of  claim 32 , wherein said receptacle is subjected to an average relative centrifugal field of between 1,000 g and 10,000 g. 
     
     
         34 . The method of  claim 30 , wherein step c) comprises applying:
 i) a4 first force; and   ii) a second force opposite to said first force.   
     
     
         35 . The method of  claim 34 , wherein said first force and said second force are applied repeatedly and in alternation. 
     
     
         36 . The method of  claim 35 , further comprising waiting for an interval of time between applications of said forces.