Crystal forming devices and systems and methods for using the same

• US 20050201901A1
• Filed: 01/25/2005
• Published: 09/15/2005
• Est. Priority Date: 01/25/2004
• Status: Active Grant

• Current Assignee: Standard Biotools Incorporated
• Original Assignee: Fluidigm Corporation
• Inventors: Unger, Marc, Pieprzyk, Martin, Chou, Hou-Pu, Lam, Phillip, Grossman, Robert, Kimball, Jake
• Granted Patent: US 8,105,553 B2
• Time in Patent Office: Days
• US Class Current: 422/100
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/14 Means for pressure control
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 3/0293 for liquids
• CPC Class Codes: B01L 3/06 Crystallising dishes
• 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 3/50273 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: B01L 3/5635 connecting two containers face to face, e.g. comprising a filter
• CPC Class Codes: B01L 3/565 Seals in general F16L
• CPC Class Codes: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C30B 29/58 Macromolecular compounds
• CPC Class Codes: C30B 7/00 Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions from molten solvents C30B9/00; by normal or gradient freezing C30B11/00; under a protective fluid C30B27/00
• CPC Class Codes: Y10T 436/11 Automated chemical analysis

Abstract

The present invention provides for microfluidic devices and methods for their use. The invention further provides for apparatus and systems for using the microfluidic devices, analyze reactions carried out in the microfluidic devices, and systems to generate, store, organize, and analyze data generated from using the microfluidic devices. The invention further provides methods of using and making microfluidic systems and devices which, in some embodiments, are useful for crystal formation. In one embodiment, an apparatus includes a platen having a platen face with one or more fluid ports therein. The fluid ports spatially correspond to one or more wells on a surface of the microfluidic device. A platform for holding the microfluidic device relative to the platen is included, and a platen actuator for urging the platen against the microfluidic device so that at least one of the fluid ports of the platen is urged against one of the wells to form a pressure chamber comprising the well and the port, so that when pressurized fluid is introduced or removed into or from the pressure chamber through one of the ports, fluid pressure is changed therein.

Claims

1. An apparatus for operating a microfluidic device, comprising:

a platen having a platen face with one or more fluid ports therein, the fluid ports spatially corresponding to one or more inlets on a surface of the microfluidic device,

a platform for holding the microfluidic device relative to the platen,

a platen actuator for urging the platen against the microfluidic device so that at least one of the fluid ports of the platen is urged against one of the inlets to form a pressure chamber comprising the inlet and the port, so that when pressurized fluid is introduced or removed into or from the pressure chamber through one of the ports, fluid pressure is changed therein.

2. The apparatus as in claim 1 wherein the platen actuator comprises a robotic platen actuator.

3. The apparatus as in claim 2 wherein the platen actuator is under electronic control by a controller.

4. The apparatus as in claim 3 wherein the controller is a computer or under computer control.

5. The apparatus as in claim 4 wherein the computer is following a program.

6. The apparatus as in claim 5 wherein the program was customized by a user of the apparatus.

7. The apparatus as in claim 1 wherein the microfluidic device comprises:

first and second chambers in fluid communication with each other through a channel; and

a valve disposed along the channel which when opened or closed controls fluid communication between the first and second chambers;

wherein the valve is under the control of an automated valve actuating device when the microfluidic device is coupled to the platen.

8. The apparatus as in claim 7 wherein the automated valve actuating device is further under computer control.

9. The apparatus as in claim 7 wherein the valve is opened and closed using the automated valve actuating device.

10. The apparatus as in claim 7 wherein the valve comprises a deflectable membrane.

11. The apparatus as in claim 1 wherein the platen actuator is adapted for delivering a pressurized fluid to the at least one fluid pressure port using a pressure between about one (1) psi and about thirty-five (35) psi.

12. A microfluidic system, comprising:

a receiving station, the receiving station adapted to receive a microfluidic device having a plurality of chambers, the microfluidic device coupled to a carrier, with at least some of the plurality of chambers coupled to a plurality of inlets in the carrier;

an interface plate adapted to engage at least one of the inlets in the carrier;

a fluid source coupled to the interface plate and adapted to provide pressurized fluid to at least one of the inlets in the carrier; and

a controller coupled to the fluid source and to the interface plate for directing fluid from the fluid source to the carrier.

13. The system as in claim 12 wherein the microfluidic device further comprises a plurality of valve lines, and wherein the fluid is directed into at least some of the valve lines by the controller.

14. The system as in claim 13 wherein the controller is further adapted to open and close at least some of the valve lines.

15. The system as in claim 12 wherein the carrier further comprises a plurality of wells, and wherein at least some of the wells are coupled to corresponding inlets of the plurality of inlets, the corresponding inlets being adapted to receive a fluid for analysis in the microfluidic device.

16. The system as in claim 15 wherein the controller is adapted to apply a pressure through the interface plate to at least some of the plurality of wells in order to drive the fluid therein into at least some of the plurality of chambers.

17. The system as in claim 12 wherein the interface plate comprises two or more separate interface plates each adapted to engage at least one inlet in the carrier.

18. The system as in claim 12 wherein the carrier comprises an accumulator chamber having an accumulator port, and wherein the interface plate comprises a port that is in fluid communication with the accumulator chamber.

19. The system as in claim 18 wherein the accumulator chamber further comprises a valve for controlling fluid movement into the accumulator chamber through the accumulator port, the valve being in fluid communication with the accumulator port.

20. The system as in claim 19, wherein the valve permits fluid flow into the accumulator chamber through the accumulator port while restricting fluid flow out of the accumulator chamber through the accumulator port.

21. The system as in claim 20 wherein the valve permits fluid flow out of the accumulator when the valve is actuated.

22. The system as in claim 21, wherein the valve is actuated mechanically.

23. The system as in claim 21, wherein the valve is a check valve.

24. The system as in claim 19 wherein the interface plate comprises a valve actuator which is adapted to engage the valve when the interface plate and carrier are coupled.

25. The system as in claim 18 wherein the accumulator chamber further comprises a liquid.

26. The system as in claim 18 wherein the accumulator chamber further comprises a gas.

27. The system as in claim 18 wherein the accumulator further comprises a gas and a liquid.

28. The system as in claim 26 wherein the gas is pressurized relative to a gas pressure outside of the accumulator chamber.

29. The system as in claim 12 wherein the interface plate further comprises a sealing gasket.

30. The system as in claim 18 wherein the accumulator is adapted to maintain a pressure above a desired pressure level in order to a maintain a valve in the microfluidic device in a closed state.

31. The system as in claim 30 wherein the closed valve lasts for at least two (2) days.

32. A method for conducting a step in a protein crystallization condition screening, the method comprising:

providing a microfluidic device; and

performing one of the steps from the group consisting of;

robotically filling a well in said microfluidic device with a reagent,

robotically moving said microfluidic device from a robotic liquid dispensing station to a different location,

robotically placing said microfluidic device into the system of claim 12,

removing said microfluidic device from the system of claim 12,

robotically placing the microfluidic device into an optical inspection station,

optically interrogating the microfluidic device using an automated imaging system,

wherein robotically means movement of the microfluidic device caused by a mechanical device under control of a computer or electronic controller.