Apparatus for sorting cells and cell alignment substrate of the same

• US 20030209059A1
• Filed: 03/28/2003
• Published: 11/13/2003
• Est. Priority Date: 03/29/2002
• Status: Active Grant

• Current Assignee: Aisin Seiki Co., Ltd. (Aisin Corp.)
• Original Assignee: Aisin Seiki Co., Ltd. (Aisin Corp.)
• Inventors: Kawano, Takashi, Yamada, Takahiro
• Granted Patent: US 6,994,218 B2
• Time in Patent Office: Days
• US Class Current: 73/53.01
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0663 Whole sensors
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• 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: B01L 3/502776 specially adapted for focusing or laminating flows
• CPC Class Codes: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: G01N 15/149 specially adapted for sorting particles, e.g. by their size or optical properties

Abstract

An apparatus for sorting cells includes a cell alignment portion applying a process to a cell-suspending fluid with a great number of cells and arraying the tells with a spacing between each cell, a cell information detecting portion detecting information on the cells, a cell sorting portion for sorting the cells based upon the information detected by the cell information detecting portion, a first passage of the cell alignment portion so as to let the cell-suspending fluid flow, and a second passage of the cell alignment portion, intersecting with the first passage so as to communicate therewith, letting a splitting fluid flow so as to split the flow of the cell-suspending fluid in the first passage and forming a great number of small cell-containing liquid drops.

Claims

1. An apparatus for sorting cells, comprising:

a cell alignment portion applying a process to a cell-suspending fluid in which a great number of cells are suspended and arraying the cells with a spacing between each cell;

a cell information detecting portion applying a detecting process to the cells arrayed by the cell alignment portion and detecting information on the cells;

a cell sorting portion for sorting the cells based upon the information detected by the cell information detecting portion;

a first passage included in the cell alignment portion so as to let the cell-suspending fluid flow; and

a second passage included in the cell alignment portion, intersecting with the first passage so as to communicate with the first passage, letting a splitting fluid flow so as to split the flow of the cell-suspending fluid in the first passage, and forming a great number of small cell-containing liquid drops.

2. An apparatus for sorting cells according to claim 1, wherein the cell alignment portion comprises a common base having the first passage and the second passage.

3. An apparatus for sorting cells according to claim 1, further comprising:

a detecting position provided at the cell alignment portion, the detecting position being a position at which the cell contained in the cell-containing liquid drop arrayed by the cell alignment portion is applied with the detecting process by the cell information detecting portion; and

a guiding portion for guiding the cell-containing liquid drop flowing in the second passage to the detecting position.

4. An apparatus for sorting cells according to claim 1, further comprising:

a cell outlet port defined at a downstream portion of the second passage; and

a gas jet portion for applying gas to the cell-containing liquid drop and for dropping the cell-containing liquid drop reached the cell outlet port out of the cell outlet port by a pressure of the gas applied to the cell-containing liquid drop.

5. An apparatus for sorting cells according to claim 3, further comprising:

a cell outlet port defined at a downstream portion of the second passage; and

a gas jet portion for applying gas to the cell-containing liquid drop and for dropping the cell-containing liquid drop reached the cell outlet port out of the cell outlet port by a pressure of the gas applied to the cell-containing liquid drop.

6. An apparatus for sorting cells according to claim 4, further comprising:

a fluid source for adding a fluid to the cell-containing liquid drop when the cell-containing liquid drop is dropped out of the cell outlet port of the second passage or prior to the dropping operation, wherein a liquid portion of the cell-containing liquid drop is increased in weight.

7. An apparatus for sorting cells according to claim 5, further comprising:

a fluid source for adding a fluid to the cell-containing liquid drop when the cell-containing liquid drop is dropped out of the cell outlet port of the second passage or prior to the dropping operation, wherein a liquid portion of the cell-containing liquid drop is increased in weight.

8. An apparatus for sorting cells according to claim 1, wherein the cell alignment portion includes a surrounding wall portion along a cross section intersecting with a fluid flow direction in the first passage so as to surround the first passage, and the other surrounding wall portion along a cross section intersecting with a fluid flow direction in the second passage so as to surround the second passage.

9. An apparatus for sorting cells according to claim 8, wherein the cell alignment portion includes a substrate portion and a cover portion, the substrate portion possesses the first passage and the second passage, and the cover portion is in contact with the substrate portion so as to cover the first passage and the second passage.

10. An apparatus for sorting cells according to claim 1, wherein at least either the first passage or the second passage is applied with a process so as to be-lyophobic relative to the cell-suspending fluid or the splitting fluid.

11. An apparatus for sorting cells according to claim 3, wherein the guiding portion includes a passage width narrowing means for narrowing a width of the second passage.

12. An apparatus for sorting cells according to claim 11, wherein the passage width narrowing means is an inclined surface of the second passage.

13. An apparatus for sorting cells according to claim 12, wherein the inclined surface is provided at one side of the second passage, and the one side is defined at an opposite side of the intersecting point with the first passage relative to a longitudinal direction of the second passage.

14. An apparatus for sorting cells according to claim 12, wherein the inclined surface is provided at both sides of the second passage, one of the sides is defined at an opposite side of the intersecting point with the first passage relative to a longitudinal direction of the second passage, and the other one of the sides is defined at the same side of the intersecting point with the first passage relative to the longitudinal direction of the second passage.

15. An apparatus for sorting cells according to claim 12, wherein the second passage includes an upstream communicating passage and a downstream communicating passage, the narrowing means is defined between the upstream communicating passage and the downstream communicating passage, and a diameter of the downstream communicating passage is substantially equal to or slightly less than a diameter of the cell-containing liquid drop.

16. An apparatus for sorting cells according to claim 6, wherein a cell outlet port possesses a diameter being greater than a diameter of the cell-containing liquid drop.

17. An apparatus for sorting cells according to claim 1, wherein the first passage intersects with the second passage at a T-shaped angle and communicates with the second passage.

18. An apparatus for sorting cells according to claim 1, wherein the second passage intersects with the first passage having a tip end at an intersecting side, the tip end possesses a slope in a downstream direction of the second passage.

19. An apparatus for sorting cells according to claim 1, wherein the second passage intersects with the first passage having a tip end at an intersecting side, and the tip end possesses a slope in an upstream direction of the second passage.

20. An apparatus for sorting cells according to claim 1, further comprising:

a collecting passage branched from an end portion of the second passage;

a waste fluid passage branched from the end portion of the second passage, wherein the collecting passage, the waste fluid passage, and the second passage forms a Y-shaped structure;

a cell outlet port connected to the collecting passage;

a waste fluid drain port connected to the waste fluid passage;

a first guiding means disposed at an upstream portion of the branch portion of the collecting passage and the waste fluid passage so as to guide the cell-containing liquid drop to either the collecting passage or the waste fluid passage;

a second guiding means disposed at the waste fluid passage so as to guide the cell-containing liquid drop to the waste fluid drain port; and

a third guiding means disposed at the collecting passage so as to guide the cell-containing liquid drop to the cell outlet port.

21. An apparatus for sorting cells according to claim 20, wherein the first guiding means is an electrode for electrically charging the cell-containing liquid drop, the second guiding means is an electrode for applying voltage to the cell-containing liquid drop electrically charged by the first guiding means when the cell information detecting portion detects that the cell is not a target cell, the third guiding means is an electrode for applying voltage to the cell-containing liquid drop electrically charged by the first guiding means where the cell information detecting portion detects that the cell is the target cell.

22. An apparatus, for sorting cells according to claim 21, further comprising:

a gas jet portion for applying gas to the cell-containing liquid drop in the cell outlet port and for dropping the cell-containing liquid drop in the cell outlet port out of the cell outlet port by a pressure of the gas applied to the cell-containing liquid drop.

23. A cell alignment substrate for arraying cells with a spacing between each cell by letting a cell-suspending fluid, in which the cells are suspended, flow comprising:

a first passage letting the cell-suspending fluid flow; and

a second passage intersecting with the first passage so as to communicate with the first passage, letting a splitting fluid flow for splitting the flow of the cell-suspending fluid in the first passage and forming a great under of small cell-containing liquid drops.