MICROFLUIDIC REACTOR SYSTEM

• US 20120177543A1
• Filed: 01/09/2012
• Published: 07/12/2012
• Est. Priority Date: 11/30/2005
• Status: Active Grant

• Current Assignee: Revvity Health Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Micronics Inc. (Sony Group Corp.)
• Inventors: Battrell, C. Frederick, Clemmens, John, Sprague, Isaac
• Granted Patent: US 9,056,291 B2
• Time in Patent Office: Days
• US Class Current: 422/187
• CPC Class Codes: B01F 31/65 the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
• CPC Class Codes: B01F 31/651 Mixing by successively aspirating a part of the mixture in a conduit, e.g. a piston, and reinjecting it through the same conduit into the receptacle
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: F04B 43/043 Micropumps
• CPC Class Codes: F04B 43/06 Pumps having fluid drive
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing

Abstract

A compact device for operatively coupling a solid planar substrate, for example a glass slide, to a microfluidic circuit and performing a reaction or reactions on organic matter bound to the face of the planar substrate. Typical reactions include binding, staining and/or labeling reactions. In use, a sealed reaction chamber is formed, the chamber enclosing the organic matter and at least a part of the solid substrate. Headspace in the sealed chamber between the solid substrate is generally of microfluidic dimensions, and diaphragm pump members are used to inject, exchange and/or mix the fluids in the chamber.

Claims

1. An apparatus for sealingly enclosing a first aspect of a substrate member in a reaction chamber, the apparatus comprising:

a) a baseplate member having a first surface, wherein said first surface comprises a platform medially disposed thereon, said platform having a top surface dimensioned for contactingly receiving the first aspect of the substrate member in juxtaposition with said top surface thereof, and outside edges and outside lateral wall surfaces therearound, wherein said top surface is interrupted by a recess defined by interior walls having a height ranging from 5 to 100 micrometers, a recessed slab connecting the bottom edges of the interior walls, and a boundary ledge connecting the top edges of the interior walls and the outside edges of the platform, said ledge for supporting the first aspect of the substrate member thereon, whereby a reaction chamber with headspace volume is formed between the recessed slab and the first aspect of the substrate member when sealed to said flat ledge;

b) a gasket member fitted to the outside edges of said platform, and

c) a first bellows pump and a second bellows pump, said first bellows pump having a first fluidic connection to said reaction chamber and said second bellows pump having a second fluidic connection to said reaction chamber, at least one of said first and second bellows pumps having one or more fluidic connections to one or more reagent reservoirs or vents disposed outside the reaction chamber.

2. The apparatus of claim 1, wherein said bellows pumps are pneumatically driven and have a positive stroke and a negative suction stroke.

3. The apparatus of claim 1, wherein a reciprocating flow between said first fluidic connection and said second fluidic connection to said reaction chamber is driven by repetitively actuating said first and second bellows pumps by applying a positive pressure pulse to each said bellows pumps in alternation.

4. The apparatus of claim 3, wherein a reciprocating flow between said first fluidic connection and said second fluidic connection to said reaction chamber is driven by actuating said first and second bellows pumps by applying a positive pressure pulse to said first bellows pump and a suction pressure pulse to said second bellows pump, and then reversing the pressure of the pulses applied to each bellows pump.

5. The apparatus of claim 1, wherein said bellows pumps are magnetically driven and have a positive pump stroke and a negative pump stroke, and further wherein a reciprocating flow between said first fluidic connection and said second fluidic connection to said reaction chamber is enabled by inverting the polarity of a first pump stroke of said first bellows pump and a second pump stroke of said second bellows pump in alternation.

6. The apparatus of claim 1, comprising a plurality of pairs of bellows pumps, each bellows pump of said pair having a fluidic connection to said reaction chamber, wherein said pairs are disposed to drive fluid flow across and through said reaction chamber.

7. The apparatus of claim 1, wherein the apparatus comprises an observation window for accessing a viewing area on the substrate member.

8. The apparatus of claim 7, wherein the observation window for accessing a viewing area on the substrate member is formed in said gasket.

9. The apparatus of claim 7, wherein said observation window is proportioned for enabling a bar code label to be applied to the substrate member outside of the viewing area.

10. The apparatus of claim 1, wherein an observation window for accessing a viewing area on the substrate member is formed in said baseplate and extends through said raised platform.

11. The apparatus of claim 1, further comprising a waste outlet in fluid communication with at least one of said bellows pumps.

12. The apparatus of claim 1, wherein the substrate member is a glass slide having a first face on which organic matter is bound.

13. The apparatus of claim 1, wherein the first bellows pump and second bellows pump are disposed proximate to the platform.

14. The apparatus of claim 1, wherein the platform is raised.

15. The apparatus of claim 1, wherein said gasket member is formed of an elastomer, a vinyl rubber, or a silicone.

16. The apparatus of claim 1, wherein said gasket member comprises a stretchable web member for coveringly and sealingly enclosing the substrate member on top of the boundary ledge and a peripheral skirt member for sealingly engaging said outside edges and outside lateral wall surfaces therearound.

17. The apparatus of claim 1, wherein a cutout is formed on a lateral aspect of the gasket member, said cutout for sealedly enclosing the first aspect of the substrate member inside the reaction chamber and a projecting segment of the substrate member outside the reaction chamber.

18. The apparatus of claim 17, wherein said cutout is adapted for receiving a substrate member or glass slide having an electrical junction mounted on the projecting segment of the substrate member or glass slide, said electrical junction connecting to a circuit within said reaction chamber.

19. An apparatus for enclosing a substrate member in a sealed reaction chamber, which comprises

a) a slide minicassette having a housing body with internal tray, gasketed peripheral rails, and end-mounted clamping members for sealingly receiving a mated substrate member and thereby forming a sealed reaction chamber, further wherein said tray is provided with a first fluidic connection adaptor and a second fluidic connection adaptor, said adaptors for establishing a fluidic channel between said sealed reaction chamber and a fluidic circuit in a baseplate module having a docking bay into which said slide minicassette reversibly inserts;

b) said baseplate module having a first surface, wherein said first surface comprises said docking bay medially disposed thereon, said docking bay having a recessed surface dimensioned for receiving the slide minicassette, wherein said docking bay is provided with a first fluidic connection channel with sealing member and a second fluidic connection channel with sealing member, said first and second channels for forming a fluidic path through said sealed reaction chamber when sealedly engaged with said first and second adaptors of said slide minicassette; and

,

c) a first bellows pump and a second bellows pump, said first bellows pump having a first fluidic connection to said reaction chamber and said second bellows pump having a second fluidic connection to said reaction chamber, at least one of said first and second bellows pumps having one or more fluidic connections to one or more reagent reservoirs or vents disposed outside the reaction chamber.

20. The apparatus of claim 19, wherein said slide minicassette is configured to dock exchangeably to a plurality of identical baseplate modules.

21. The apparatus of claim 19, wherein said reagent reservoir or plurality of reservoirs are interchangeable, having an adaptor for removably engaging the baseplate and fluidic circuitry therein.

22. The apparatus of claim 21, wherein said reagent reservoirs are packaged as a kit, each reagent reservoir having a fluid sealed therein.

23. The apparatus of claim 21, wherein said adaptor is a threaded nipple for engaging a female receptacle in the baseplate, the female receptacle for forming a sealable fluidic connection to said fluidic circuitry.

24. The apparatus of claim 19, wherein said bellows pumps are pneumatically driven and have a positive stroke and a suction stroke.

25. The apparatus of claim 24, wherein a reciprocating flow between said first fluidic connection and said second fluidic connection to said reaction chamber is driven by actuating said first and second bellows pumps by applying one positive pressure pulse to each said bellows pumps in alternation.

26. The apparatus of claim 24, wherein a reciprocating flow between said first fluidic connection and said second fluidic connection to said reaction chamber is driven by actuating said first and second bellows pumps by applying a positive pressure pulse to said first bellows pump and a suction pressure pulse to said second bellows pump, and then reversing the polarity of the pulses.

27. The apparatus of claim 19, wherein said bellows pumps are electromagnetically driven and have a positive pump stroke and a negative pump stroke, and further wherein a reciprocating flow between said first fluidic connection and said second fluidic connection to said reaction chamber is enabled by inverting the polarity of a first pump stroke of said first bellows pump and a second pump stroke of said second bellows pump in alternation.

28. The apparatus of claim 19, comprising a plurality of pairs of bellows pumps, each bellows pump of said pair having a fluidic connection to said reaction chamber, wherein said pairs are disposed to drive fluid flow across and through said reaction chamber.

29. The apparatus of claim 19, wherein said baseplate module and slide minicassette are configured to be operated in a vertical orientation, a horizontal orientation, or an inverted orientation.

30. The apparatus of claim 19, wherein said baseplate module and slide minicassette are configured to interface with an automated apparatus for performing multiple substrate member-based reactions in parallel.

31. The apparatus of claim 19, wherein the substrate member is a glass slide having a first face on which organic matter is bound.

32. The apparatus of claim 19, wherein the first and second bellows pumps are disposed proximate to the docking bay.

33. The apparatus of claim 19, further comprising a waste outlet fluidically connected to at least one of said bellows pumps.