CELL SEPARATION USING MICROCHANNEL HAVING PATTERNED POSTS

• US 20090136982A1
• Filed: 01/05/2006
• Published: 05/28/2009
• Est. Priority Date: 01/18/2005
• Status: Abandoned Application

• Current Assignee: Biocept, Inc.
• Original Assignee: Biocept, Inc.
• Inventors: Tang, Zhongliang, Bhatt, Ram S., Tsinberg, Pavel
• Application Number:
  US11/814,276
• Publication Number:
  US 20090136982A1
• Time in Patent Office: Days
• US Class Current: 435/29
• CPC Class Codes: B01F 25/51 in which the mixture is circulated through a set of tubes, e.g. with gradual introduction of a component into the circulating flow
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/088 Channel loops
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• 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: G01N 1/34 Purifying; Cleaning processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003
• CPC Class Codes: G01N 1/40 Concentrating samples
• CPC Class Codes: G01N 1/405 by adsorption or absorption
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing

Abstract

A micro now device (11, 71) for separating or isolating cells from a bodily fluid or other liquid sample uses a flow path where straight-line flow is interrupted by a pattern of transverse posts (23, 81). The posts are spaced across the width of an expanded collection chamber region (17, 75) in the flow path, extending between the upper and lower surfaces thereof: they have rectilinear surfaces, being curved in cross-sections, e.g. circular or tear-drop shaped, and are randomly arranged so as to disrupt streamlined flow. The device is oriented so that its lower surface is aligned at about 45° to the horizontal. Sequestering agents, such as Abs, which are attached to surfaces of the collection region via a hydrophilic coating, preferably a permeable hydrogel containing isocyanate moieties, are highly effective in capturing cells or other targeted biomolecules while the remainder of the liquid sample exits horizontally.

Claims

1. A microflow apparatus comprising:

a body having a randomized flow path which comprises an inlet means, an outlet means, and a microchannel arrangement extending between said inlet and outlet means,

wherein said microchannel arrangement includes a plurality of transverse separator posts being integral with a base surface of said microchannel and projecting therefrom, wherein said posts are arranged in a pattern capable of providing said randomized flow path, and wherein said inlet means comprises an inlet passageway that is aligned at an angle of between about 30°

to about 60°

to said base surface.

2. The apparatus of claim 1, wherein said posts are from about 70 μ

M to about 130 μ

M in diameter.

3. The apparatus of claim 1, wherein the minimum distance between two said posts is from about 50 μ

M to about 70 μ

M.

4. The apparatus of claim 1, wherein said outlet means comprises an outlet passageway, and wherein said inlet passageway and said outlet passageway are angularly aligned at 90°

to each other.

5. The apparatus of claim 1, wherein said outlet means comprises an outlet passageway which is horizontal.

6. The apparatus of claim 1, wherein said outlet means is connected to a pump.

7. The apparatus of claim 1, wherein said microchannel is sealed with a plate affixed to the free ends of said posts, wherein the plate contains a flow regulation means.

16. A method of capturing a target molecule in a sample comprising causing a body of liquid containing said sample to flow through said microchannel of the apparatus of claim 1, wherein the surface of said microchannel is coated with a sequestering agent capable of binding to the target molecule.

17. The method of claim 16, wherein the body of liquid containing said sample flows through said microchannel at a speed of about 0.2 mm to about 1 mm per second.

18. The method of claim 16, wherein the body of liquid is mixed prior to flowing through said microchannel arrangement.

8. A microflow apparatus comprising:

a body having a randomized flow path which comprises an inlet means, an outlet means, and a microchannel arrangement extending between said inlet and outlet means,

wherein said microchannel arrangement includes a plurality of transverse separator posts being integral with a base surface of said microchannel and projecting therefrom, wherein said posts are arranged in a pattern capable of providing said randomized flow path, and wherein the body has a flat surface and the microchannel arrangement is located in a cavity of the body below the flat surface.

9. The apparatus of claim 8, wherein said posts are from about 70 μ

M to about 130 μ

M in diameter.

10. The apparatus of claim 8, wherein the minimum distance between two said posts is from about 50 μ

M to about 70 μ

M.

11. The apparatus of claim 8, wherein said inlet means comprises an inlet passageway that is aligned at an angle of between about 30°

to about 60°

to said base surface.

12. The apparatus of claim 8, wherein said inlet means and said outlet means comprise an inlet passageway and an outlet passageway, respectively, and wherein said inlet passageway and said outlet passageway are angularly aligned at 90°

to each other.

13. The apparatus of claim 8, wherein said outlet means comprises an outlet passageway which is horizontal.

14. The apparatus of claim 8, wherein said outlet means is connected to a pump.

15. The apparatus of claim 8, wherein said microchannel is sealed with a plate affixed to the free ends of said posts, wherein the plate contains a flow regulation means.

19. A method of capturing a target molecule in a sample comprising causing a body of liquid containing said sample to flow through said microchannel of the apparatus of claim 8, wherein the surface of said microchannel is coated with a sequestering agent capable of binding to the target molecule.

20. The method of claim 19, wherein the body of liquid containing said sample flows through said microchannel at a speed of about 0.2 mm to about 1 mm per second.

21. The method of claim 19, wherein the body of liquid is mixed prior to flowing through said microchannel arrangement.