Thin reaction chambers for containing and handling liquid microvolumes

• US 5,922,604 A
• Filed: 06/05/1997
• Issued: 07/13/1999
• Est. Priority Date: 06/05/1997
• Status: Expired due to Fees

• Current Assignee: Gene Tec Corporation
• Original Assignee: Gene Tec Corporation
• Inventors: Harrington, William, Stapleton, Marilyn
• Primary Examiner(s): ALEXANDER, LYLE
• Application Number:
  US08/869,491
• Time in Patent Office: 768 Days
• Field of Search: 422/99, 422/102-104, 422/58, 422/61, 422/100, 422/101, 435/286.1, 435/286.5, 435/288.5, 436/45-47
• US Class Current: 436/46
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2200/142 Preventing evaporation
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0822 Slides
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502723 characterised by venting arrangements
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/508 rigid containers not provided for above
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: G02B 21/34 Microscope slides, e.g. mounting specimens on microscope slides
• CPC Class Codes: Y10T 436/112499 with sample on test slide

Abstract

The invention is an apparatus and a process for containing and handling liquids in a thin capillary space. Two opposing walls positioned at a first and a second distance apart define a thin space having at least two different heights and two different regions of capillary liquid attraction. Enclosing the thin space with side walls defines a reaction chamber. A liquid receiving area, entry and exit ports and features projecting from, or encircling, at least one wall allow coatings on the internal surface of either of the two opposing walls to react with multiple microvolumes of reagents and wash treatments in series. Liquids flow into, or are withdrawn from, the thin space in a way in which bubbles are not introduced into the thin space. Bubbles that may arise in the thin space move along a sloped feature out of the thin space into an annular enclosure. The liquids are withdrawn after reacting with the coatings, either to empty the chamber and recover the liquid volume, or to wash the coatings with treatment liquids and introduce new treatment liquids. The ability to control liquid movement in spaces thin enough to exhibit capillarity is useful for analyzing biological specimens cost-effectively with less reagent volume and more information per specimen and without sacrificing convenience in liquid handling or surface reaction space.

Claims

1. An apparatus for handling liquids in a thin capillary space, comprising

(a) two opposing walls forming a thin capillary space;

(b) at least one feature projecting from a wall into the thin capillary space to create regions of capillarity stronger than other regions;

(c) a liquid receiving area in fluid communication with the thin capillary space; and

wherein the liquids from the liquid receiving area fill the thin capillary space in a predictable manner under the control of differential capillarities.

2. The apparatus according to claim 1, wherein the projecting feature forms a channel between the two opposing walls, in which channel there is a strong capillary liquid attraction;

wherein said channel directs the flow of liquids from said liquid receiving area into the thin space.

3. The apparatus according to claim 1, wherein one or more projecting features comprises a base and an apex, said projecting features defining differential capillarites between said the two opposing walls;

and wherein liquids flow into and preferentially fill the region of thin capillary space between the two opposing walls.

4. The apparatus according to claim 3, further comprising an annular enclosure surrounding and in fluid communication with the thin capillary space;

said annular enclosure having a weaker liquid attraction than the thin capillary space;

whereupon bubbles arising in a liquid residing in said thin capillary space move into said annular enclosure.

5. The apparatus according to claim 1, further comprising a fibrous matrix feature projecting from at least one of said two opposing walls and forming interfacing capillary channels between the two opposing walls, said capillary channels having a strong capillary attraction;

wherein said interfacing capillary channels draw liquid from the liquid receiving area into said apparatus and direct the flow of liquids into said thin space.

6. The apparatus according to claim 1, further comprising materials for the purpose of reacting and analyzing components of biological specimens which are selected from the group consisting of liquids which are biological specimens, liquids which contain biological specimens and solid biological specimens.

7. An apparatus for holding liquids in a thin capillary space, comprising a wall forming a thin space with respect to the plane of another wall positioned opposite said apparatus;

wherein said wall of the apparatus has features creating differential capillarities in the thin space when said wall of apparatus is positioned opposite another wall;

wherein liquids in the the thin capillary space flow in a predictable manner under the control of said differential capillarities.

8. The apparatus according to claim 7, further comprising a feature projecting from said wall into the thin space, said feature forming a channel between said wall of apparatus and another wall positioned opposite it;

in which channel there is a strong capillary liquid attraction;

wherein said channel directs the flow of liquids from said liquid receiving area into the thin space.

9. The apparatus according to claim 7, further comprising a sloped feature having a base and an apex and projecting from the surface of said wall, said sloped feature gradually increasing in height from the base towards the apex, said sloped feature defining a thin capillary space when positioned opposite another wall;

wherein said thin capillary space has regions between the apex and the base of said sloped feature, said regions progressively decreasing in height from the base of the sloped feature toward the apex; and

wherein liquids flow into and fill in preference the region of the thin capillary space near the apex of said sloped feature and then fill progressively regions towards the base of the sloped feature.

10. The apparatus according to claim 9, further comprising an annular enclosure surrounding and in fluid communication with said thin capillary space defined by said sloped feature when apparatus is positioned opposite another wall;

wherein said annular enclosure has cross-sectional distances providing a weaker capillary liquid attraction than the adjoining region of thin capillary space;

wherein liquids flow into and preferentially fill the regions of the thin capillary space and then progressively fill said annular enclosure; and

wherein bubbles arising in liquid residing in said thin capillary space defined by said sloped feature move into the annular enclosure.

11. The apparatus according to claim 7, further comprising a matrix feature on said wall of apparatus forming interfacing capillary channels in fluid communication with the liquid receiving area and the thin space between the wall of the apparatus and the plane of an opposing wall, said capillary channels having a strong capillary attraction;

wherein said interfacing capillary channels draw liquid from the liquid receiving area into said apparatus and direct the flow of liquids into the thin space when the apparatus is positioned opposite another wall.

12. The apparatus according to claim 7, further comprising materials which are selected from the group consisting of, but not limited to, microprobe arrays for the purpose of reacting and analyzing components of biological specimens.

13. A process for handling liquids in a thin space for analyzing a sample, comprising:

(a) providing a thin space between two opposing walls, said two opposing walls having features made by a method selected from a group consisting of, but not limited to, molding and micromachining and forming a thin space having regions of stronger capillary liquid attraction between the two opposing walls than other regions;

(b) providing a liquid receiving area in fluid communication with said thin space between said two opposing walls;

(c) dispensing a liquid drop to said liquid receiving area;

wherein the liquid drop fills the regions of weaker and stronger capillary liquid attractions predictably.

14. The process according to claim 13, further comprising:

(a) providing one or more coatings on a surface of the apparatus, said coatings selected from a group consisting of, but not limited to, a microprobe array;

(b) adding and reacting liquids with one or more said coatings;

wherein the surface having one or more said coatings is preferentially covered with said liquids.

15. The process according to claim 13, further comprising:

(a) enclosing said thin space with side walls so that a thin chamber is formed;

(b) providing an entry port and an exit port in fluid communication with said thin space;

(c) providing a channel from the entry port into the thin space, said channel having a stronger capillary liquid attraction than the region of the space where the two opposing walls are the first distance apart;

wherein capillary attraction draws liquids into the channel prior to filling the region of the space where the two opposing walls are the first distance apart.

16. The process according to claim 13, wherein the height of the thin space between said two opposing walls gradually increases from the first distance to the second distance;

wherein the region of the space at the first distance has the strongest capillary liquid attraction between the two opposing walls and capillary liquid attraction decreases towards the region of the space at the second distance, further comprising providing an annular space surrounding and in fluid communication with the thin space, said annular space having a cross-sectional height and width so that the annular space provides a weaker capillary attraction than the thin space;

wherein the stronger capillary liquid attraction draws liquids from the liquid receiving area into and fills the thin space without bubbles first and in preference to said annular space.

17. The process according to claim 15, wherein a liquid is residing in the channel and in the thin space, further comprising:

(a) providing a liquid removing device;

(b) making liquid communication between the liquid removing device and the liquid residing in the channel through the entry port;

wherein the liquid removing device withdraws liquid from the channel first and the liquid flows out of the thin space between the two opposing walls through the channel until the thin space is empty.

18. The process according to claim 15, wherein a liquid removing device is provided, further comprising:

(a) providing one or more coatings on the surface of at least one of the two opposing walls;

(b) providing a first liquid in the thin space between two opposing walls in liquid communication with said one or more coatings;

(c) adding a second liquid in the liquid receiving area;

(d) withdrawing the first liquid from the thin space between the two opposing walls with the liquid removing device through the exit port;

(e) repeating steps (c) and (d) until the first liquid reacting with one or more coatings on said surface is effectively replaced by the second liquid;

wherein the second liquid in the liquid receiving area enters the region of the thin space between two opposing walls and becomes mixed with and progressively dilutes the first liquid in the thin space with each repeated addition of the second liquid;

until the liquid in liquid communication with said one or more coatings is effectively changed.

19. The process according to claim 15;

further comprising;

(a) filling said thin chamber with a first liquid;

(b) closing entry and exit ports with sealing means; and

(c) increasing the temperature of the liquid residing in said thin chamber;

wherein air bubbles evacuate from said liquid residing in the thin space between two opposing walls having a stronger capillary attraction in preference to said thin space having a weaker capillary attraction.

20. The process according to claim 18, wherein gravitational drip replaces providing a liquid removing device, further comprising providing an exit port where a first liquid remains in the thin space by capillary attraction until liquid in the liquid receiving area 18 forms a pressure head causing liquid in the thin space to form a hanging drop from the exit port 30, overcome surface tension and fall as a drop;

wherein liquids dripping toward a gravitational attraction replaces withdrawing liquid with a liquid removing device in (d).