Fluidics device allowing fluid flow between a plurality of wells

• US 9,573,128 B1
• Filed: 09/03/2013
• Issued: 02/21/2017
• Est. Priority Date: 09/06/2012
• Status: Active Grant

• Current Assignee: SciKon Innovation, Inc.
• Original Assignee: SciKon Innovation, Inc.
• Inventors: McClelland, Randall
• Primary Examiner(s): Hobbs, Michael
• Application Number:
  US14/016,913
• Time in Patent Office: 1,267 Days
• Field of Search: 435/309.1
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0457 passive flow or gravitation
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: C12M 23/12 Well or multiwell plates C12M25/04 takes precedence
• CPC Class Codes: C12M 25/04 in combination with well or multiwell plates, i.e. culture inserts
• CPC Class Codes: C12M 41/00 Means for regulation, monitoring, measurement or control, e.g. flow regulation controlling or regulating chemical, physical or physicochemical processes B01J19/0006; heating or cooling apparatus for laboratory use B01L7/00; electro optical investigation of individual particles, flow cytometers G01N15/14; automatic analysis G01N35/00; controlling or regulating in general G06N

Abstract

Disclosed are fluidics devices and assemblies allowing for fluid flow between a plurality of wells. The fluidics devices and assemblies that are provided mimic in vivo tissue environments by allowing for initially segregated tissue cultures that can then be linked through fluid flow to measure integrated tissue response. The devices and assemblies provide a pumpless system using surface tension, gravity, and channel geometries. By linking human tissue functional systems to better simulate in vivo feedback and response signals between the tissues, the need for testing in animals can be minimized.

Claims

1. A fluidics device comprising:

a unitarily constructed tray configured to rest on a substantially flat surface including;

a dosing well positioned upstream from a plurality of wells aligned in a row for containing a respective host fluid,

wherein each of the plurality of wells defines a cavity having a bottom surface, a wall surface extending from the bottom surface and an open side defined by a circumference of the wall surface,

wherein, when the tray rests on the flat surface, each of the open sides is in a step-down position relative to the open side of each adjacent upstream well and the wall surface is substantially perpendicular to the flat surface; and

one or more channels extending between the open side of adjacent upstream wells and the open side of the adjacent downstream wells to define a channel fluid flow path there between.

2. The fluidics device of claim 1, further comprising a wick downstream from at least a portion of the plurality of wells and in fluid contact with the channel fluid flow path for regulating fluid flow through the plurality of wells.

3. The fluidics device of claim 2, wherein the device and/or the wick comprises one of a polymer, a synthetic polymer, a biodegradable polymer, a plastic, a biodegradable plastic, a thermoplastic, a polystyrene, a polyethylene, a polypropylene, a polyvinyl chloride, a polytetrafluoroethylene, a silicone, a glass, a PYREX, a borosilicate, and combinations thereof.

4. The fluidics device of claim 2, wherein the wick regulates fluid flow through the plurality of wells at a rate ranging from 0.0007 ml/min to 30 ml/min.

5. The fluidics device of claim 1, further comprising a collection well downstream from the plurality of wells to collect the respective host fluid after having flowed through the plurality of wells.

6. The fluidics device of claim 5, further comprising a wick contained in the collection well and the wick in fluid contact with the channel fluid flow path for regulating fluid flow through the plurality of wells.

7. The fluidics device of claim 6, wherein the wick is carried by a shoulder or by one or more posts defined by the collection well such that the wick does not contact a bottom surface of the collection well.

8. The fluidics device of claim 7, wherein the wick defines a gap such that only a portion of an edge of the wick is in fluid contact with the channel fluid flow path.

9. The fluidics device of claim 1, further comprising a dosing well channel extending from a bottom of the dosing well to the channel fluid flow path such that the dosing fluid flows to the respective host fluid of the adjacent downstream well through the dosing well channel and along the channel fluid flow path.

10. The fluidics device of claim 9, further comprising a dosing well channel cover configured to enclose the dosing well channel.

11. The fluidics device of claim 10, wherein the dosing well channel cover comprises one of a polymer, a synthetic polymer, a biodegradable polymer, a plastic, a biodegradable plastic, a thermoplastic, a polystyrene, a polyethylene, a polypropylene, a polyvinyl chloride, a polytetrafluoroethylene, a silicone, a glass, a PYREX, a borosilicate, and combinations thereof.

12. The fluidics device of claim 1, wherein a side of the dosing well defines an angle of greater than 90°

extending from a bottom of the dosing well up to the channel fluid flow path of the adjacent well.

13. The fluidics device of claim 5, wherein the collection well has a floor defining a divot, wherein the floor is angled such that the divot is defined at a lower portion of the floor.

14. The fluidics device of claim 5, further comprising a collection well channel extending from the channel fluid flow path to a bottom of the collection well such that the respective host fluid of the adjacent upstream well flows along the channel fluid flow path and through the collection well channel into the collection well.

15. The fluidics device of claim 1, wherein the one or more channels has a width ranging from 10 to 3500 microns and a depth of 10 to 1500 microns.

16. The fluidics device of claim 1, wherein the one or more channels defines a triangular-shape extending between each of the adjacent wells and generally converging at each adjacent downstream well.

17. The fluidics device of claim 16, further comprising 2, 3, or 4 microchannels contiguous with the triangular-shape channel, and each of the microchannels having a width ranging from 200 to 750 microns and a depth of 10 to 1500 microns.

18. The fluidics device of claim 1, further comprising a channel cover configured for engagement on top of the one or more channels extending between the adjacent wells to enclose the channel.

19. The fluidics device of claim 18, wherein the channel cover comprises one of a polymer, a synthetic polymer, a biodegradable polymer, a plastic, a biodegradable plastic, a thermoplastic, a polystyrene, a polyethylene, a polypropylene, a polyvinyl chloride, a polytetrafluoroethylene, a silicone, a glass, a PYREX, a borosilicate, and combinations thereof.

20. The fluidics device of claim 1, comprising 12 wells in a respective row and a total of 8 rows.

21. The fluidics device of claim 1, wherein the plurality of wells contain a respective cell culture such that an effect on the cells of coming into contact with the dosing fluid can be measured.

22. The fluidics device of claim 21, wherein the respective cell culture is a stem cell culture or a progenitor cell culture.

23. The fluidics device of claim 1, wherein a surface of one or more of the plurality of wells is modified with one or both of a chemical layer and a protein layer to support a cell culture.

24. The fluidics device of claim 23, wherein the protein layer comprises one of collagen I, collagen II, collagen III, laminin, fibronection, and combinations thereof.

25. The fluidics device of claim 1, wherein the cavity of each of the downstream wells defines a substantially same volume and the bottom surface of each of the downstream wells defines a substantially same thickness.

26. The fluidics device of claim 1, wherein a dosing fluid deposited into the dosing well flows to the respective host fluid of the adjacent downstream well along the channel fluid flow path there between, and the respective host fluid subsequently flows to each adjacent downstream well along the channel fluid flow path there between.

27. An assembly for allowing fluid flow between a plurality of wells comprising:

a first fluidics device comprising;

a dosing well positioned upstream from a plurality of wells aligned in a row for containing a respective host fluid,

wherein each of the plurality of wells defines a cavity having a bottom surface a wall surface extending from the bottom surface and an open side defined by a circumference of the wall surface,

wherein each of the open sides is in a step-down position relative to the open side of each adjacent upstream well; and

one or more channels extending between the open side of adjacent upstream wells and the open side of the adjacent downstream wells to define a channel fluid flow path there between; and

a reservoir tray configured for nesting engagement on top of the first fluidics device, the reservoir tray comprising;

at least one chamber for containing a respective chamber fluid; and

a reservoir aperture defined in a floor of the at least one chamber and configured such that the reservoir aperture is positioned above the dosing well of the first fluidics device when in nesting engagement with the first fluidics device, wherein the floor of the at least one chamber is angled and the reservoir aperture is defined at a lower portion of the floor of the at least one chamber such that the chamber fluid flows through the reservoir aperture into the dosing well of the first fluidics device when the reservoir tray and the first fluidics device are nestably engaged.

28. The assembly of claim 27, further comprising a cover tray configured for nesting engagement on top of the reservoir tray or the first fluidics device.

29. The assembly of claim 27, wherein the first fluidics device comprises:

a collection well downstream from the plurality of wells to collect the respective host fluid after its having flowed through the plurality of wells, wherein the collection well defines a collection aperture; and

a second reservoir tray comprising at least one chamber for containing a respective chamber fluid and configured for nesting engagement underneath the first fluidics device such that fluid from the collection well of the first fluidics device flows through the collection aperture into the chamber of the second reservoir tray when the second reservoir tray and the first fluidics device are nestably engaged.

30. The assembly of claim 27, further comprising a second fluidics device configured for nesting engagement underneath the first fluidics device, wherein the first fluidics device comprises a collection well downstream from the plurality of wells to collect the respective host fluid after its having flowed through the plurality of wells, and wherein the collection well defines a collection aperture such that fluid from the collection well flows through the collection aperture into the dosing well of the second fluidics device when the first and second fluidics devices are nestably engaged.

31. The assembly of claim 30, further comprising one or more additional fluidics devices configured for nesting engagement underneath the second fluidics device, wherein the one or more additional fluidics devices each comprise an additional collection well downstream from a respective plurality of wells to collect the respective host fluid after its having flowed through the respective plurality of wells, and the additional collection well of each of the one or more additional fluidics device defines an additional aperture such that fluid from the additional collection well flows through the additional aperture into the dosing well of another one of the one or more additional fluidics device positioned underneath when the one or more additional fluidics devices are nestably engaged with the second fluidics device.

32. The fluidics device of claim 27, wherein the cavity of each of the downstream wells defines a substantially same volume and the bottom surface of each of the downstream wells defines a substantially same thickness.

33. The assembly of claim 27, wherein a dosing fluid deposited into the dosing well flows to the respective host fluid of the adjacent downstream well along the channel fluid flow path there between, and the respective host fluid subsequently flows to each adjacent downstream well along the channel fluid flow path there between.