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

• US 20070026469A1
• Filed: 12/29/2005
• Published: 02/01/2007
• Est. Priority Date: 07/29/2005
• Status: Active Grant

• Current Assignee: Gpb Scientific, LLC
• Original Assignee: Gpb Scientific, LLC
• Inventors: Fuchs, Martin, Huang, Yi-Shuian, Wang, Ying-Xin, Krueger, Neil
• Granted Patent: US 8,921,102 B2
• Time in Patent Office: Days
• US Class Current: 435/7.230
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: G01N 2333/705 Assays involving receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: G01N 2333/70589 CD45
• CPC Class Codes: G01N 2333/71 for growth factors; for growth regulators
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/56966 Animal cells
• CPC Class Codes: G01N 33/57484 involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
• CPC Class Codes: G01N 33/57492 involving compounds localized on the membrane of tumor or cancer cells

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.

Claims

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) a 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.