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

• US 20070026416A1
• Filed: 12/29/2005
• Published: 02/01/2007
• Est. Priority Date: 07/29/2005
• Status: Abandoned Application

• Current Assignee: CELLective Dx Corporation
• Original Assignee: CELLective Dx Corporation
• Inventors: Fuchs, Martin
• Application Number:
  US11/323,961
• Publication Number:
  US 20070026416A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• 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 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• 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 15/12 by observing changes in resistance or impedance across apertures when traversed by individual particles, e.g. by using the Coulter principle
• 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 33/57492 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 processing a cellular sample, said device comprising a channel comprising a first array of obstacles that form a network of gaps, wherein said obstacles are configured to cause one or more first cells to preferentially make contact with said obstacles, and wherein at least some of said obstacles comprise one or more binding moieties that selectively bind said first cells.

2. The device of claim 1, wherein said first cells comprise 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.

3. The device of claim 2, wherein said first cells comprise epithelial cells or cancer cells.

4. The device of claim 1, wherein said cellular sample comprises blood, sweat, tears, ear flow, sputum, lymph, bone marrow suspension, urine, saliva, semen, vaginal flow, cerebrospinal fluid, brain fluid, ascites, milk, secretions of the respiratory, intestinal or genitourinary tract, amniotic fluid, or a water sample.

5. The device of claim 1, wherein said array of obstacles is a two-dimensional array.

6. The device of claim 1, wherein said array of obstacles comprises a plurality of rows, each successive row being offset by less than half of the period of the previous row.

7. The device of claim 1, wherein said array of obstacles comprises a staggered two-dimensional array of obstacles.

8. The device of claim 7, said device further comprising a second staggered two-dimensional array of obstacles that form a network of gaps, wherein said first array and said second array are oriented in different directions.

9. The device of claim 1, said device further comprising a second array of obstacles that form a network of gaps, wherein said first array is situated upstream of said second array, and wherein said second array has a higher density than said first array.

10. The device of claim 9, said device further comprising one or more additional arrays of obstacles that form a network of gaps, wherein each additional array has an equal or higher density than any array upstream of said additional array.

11. The device of claim 1, wherein said gaps are at least 40 microns.

12. The device of claim 1, wherein said binding moieties specifically bind a cell surface cancer marker.

13. The device of claim 12, wherein said cell surface cancer marker is selected from Table 1.

14. The device of claim 12, 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).

15. The device of claim 1, wherein said binding moieties comprise a polypeptide.

16. The device of claim 15, wherein said polypeptide comprises an antibody.

17. The device of claim 16, wherein said antibody specifically binds 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.

18. The device of claim 1, wherein said device comprises an inlet for delivery of said cellular sample.

19. The device of claim 18, wherein said device is configured for delivery of a second fluid medium through said inlet, said fluid medium comprising a buffer, a lysis reagent, a nucleic acid amplification reagent, an osmolarity regulating reagent, a labeling reagent, a preservative, or a fixing reagent.

20. The device of claim 1, wherein said device further comprises a programmable heating unit.

23. The device of claim 1, wherein fluid flows through said gaps such that said fluid is divided unequally into a major flux and a minor flux.

21. A method of detecting cancer cells in a cellular sample, said method comprising the steps of:

a) introducing said cellular sample into a device comprising a channel comprising a first array of obstacles that form a network of gaps, wherein said obstacles are configured to cause one or more first cells to preferentially make contact with said obstacles, and wherein at least some of said obstacles comprise one or more binding moieties that selectively bind said first cells; and

b) detecting the presence or absence of cancer cells in said device.

22. A method for diagnosing whether a subject has cancer, said method comprising the steps of:

a) introducing a cellular sample from said subject comprising one or more cancer cells into a device comprising a channel comprising a first array of obstacles that form a network of gaps, wherein said obstacles are configured to cause one or more first cells to preferentially make contact with said obstacles, and wherein at least some of said obstacles comprise one or more binding moieties that selectively bind said first cells;

b) detecting the presence or absence of said cancer cells in said device; and

c) diagnosing the presence or absence of cancer in said subject based on the results of step b).