Sample preparation apparatus

• US 20100050749A1
• Filed: 10/28/2008
• Published: 03/04/2010
• Est. Priority Date: 08/28/2008
• Status: Active Grant

• Current Assignee: MicroFluidic Systems, Inc.
• Original Assignee: Microfluidic Systems Limited
• Inventors: Yuan, Bob
• Granted Patent: US 8,133,451 B2
• Time in Patent Office: Days
• US Class Current: 73/61.550
• CPC Class Codes: B01L 2200/04 Exchange or ejection of cartridges, containers or reservoirs
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0681 Filter
• 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 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way 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: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: G01N 30/96 using ion-exchange G01N30/02, G01N30/90 take precedence
• CPC Class Codes: G01N 35/08 using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A capture and purification apparatus is configured as a stand-alone apparatus or as part of a larger system. The capture and purification apparatus can be configured as a microfluidic cartridge that includes microfluidic circuitry and individually controlled valves. The microfluidic cartridge can be configured to function independently, or can be configured to be coupled to a separate instrument that provides the actuation to perform the capture and purification process. The capture and purification apparatus is configured as a volume-driven system that applies single-direction valves, a single fluid driving device, and fluid lines to control and discretely direct fluid flow within a full-loaded fluidic system. Such control enables various fluid sample processing techniques to be performed including, but not limited to, lysis, thermal cycling, and/or target analyte capture and purification, for example using a combination of ion-exchange chromatography and size-exclusion chromatography (SEC).

Claims

1. An apparatus to process an input fluid sample including one or more targeted analytes, the apparatus comprising:

a. a master fluid driver configured to be actuated in discrete increments;

b. a plurality of individually actuated fluid valves configured to regulate fluid flow, wherein each fluid valve is configured to be actuated no more than once;

c. a plurality of slave fluid drivers coupled to the master fluid driver, wherein actuation of the master fluid driver selectively actuates the plurality of slave fluid drivers according to a number of increments the master slave fluid driver is incremented and according to a number of fluid valves that are actuated; and

d. fluid lines coupled to the master fluid driver, the plurality of fluid valves, and the plurality of slave fluid drivers,

wherein the apparatus is fully loaded with a plurality of processing fluids and the fluid sample, further wherein the selective actuation of the plurality of slave fluid drivers functions to selectively displace the one or more targeted analytes between a plurality of processing areas and to selectively provide one or more of the plurality of processing fluids to the processing areas.

2. The apparatus of claim 1 further comprising a control module coupled to the master fluid driver and the plurality of fluid valves, wherein the control module is configured to provide control signals to independently actuate the master fluid driver and each of the plurality of fluid valves.

3. The apparatus of claim 1 wherein actuation of the master fluid driver forces fluid flow within the apparatus.

4. The apparatus of claim 1 wherein a position of each processing fluid and the one or more target analytes within the apparatus is defined according to a fluid front of each processing fluid and the fluid sample, and the position of each fluid front is determined according to a cumulative amount of actuation increments performed by the master fluid driver.

5. The apparatus of claim 1 wherein each valve is configured to actuate from a closed position to an open position.

6. The apparatus of claim 1 further comprises a plurality of waste vessels coupled to the fluid lines, wherein the plurality of waste vessels are configured to store all waste generated while processing the fluid sample, further wherein the apparatus is disposable.

7. The apparatus of claim 6 wherein each waste vessel includes a plunger and a plunger stop, the plunger configured to be displaced by incoming waste and the plunger stop positioned to regulate a maximum amount of waste to be added to the waste vessel.

8. The apparatus of claim 1 wherein each slave fluid driver includes a plunger and a plunger stop, the plunger configured to displace a specific processing fluid stored in the slave fluid driver and the plunger stop positioned to regulate a maximum fluid displaced by the plunger.

9. The apparatus of claim 1 wherein each of the processing areas comprises one of the group consisting of a lysing chamber, an ion-exchange chromatography column, a size-exclusion chromatography column, and a thermal cycling chamber.

10. The apparatus of claim 9 further comprising a sonication horn coupled to the lysing chamber.

11. The apparatus of claim 9 further comprising a thermo-electric cooler coupled to the thermal cycling chamber.

12. The apparatus of claim 1 wherein the master fluid driver includes a stepper motor and each discrete increment of the master fluid driver is a step of the stepper motor.

13. The apparatus of claim 12 wherein each of the fluid valves is independently actuated according to a specific cumulative number of increments.

14. The apparatus of claim 1 further comprising one or more sensors positioned in each of the slave fluid drivers, wherein each sensor is configured to detect a position of a plunger in the slave fluid driver.

15. The apparatus of claim 14 each of the fluid valves is independently actuated according to the detected positions of the plungers.

16. The apparatus of claim 1 wherein each of the fluid valves includes a solenoid configured to actuate the fluid valve.

17. The apparatus of claim 1 further comprises a fluid sample input port coupled to one of the processing areas.

18. An apparatus to process an input fluid sample including one or more targeted analytes, the apparatus comprising:

a. an actuation instrument comprising;

i. a drive motor configured to provide discrete increments of actuation; and

ii. a plurality of valve actuation mechanisms;

b. a cartridge coupled to the actuation instrument, the cartridge comprising;

i. a driving syringe coupled to the drive motor;

ii. a plurality of reagent syringes, wherein a fluid input port of each reagent syringe is commonly coupled to the driving syringe, further wherein each reagent syringe is configured to displace a reagent fluid in response to an actuation of the driving syringe, each reagent fluid is used to process the one of more target analytes;

iii. a plurality of processing vessels, each processing vessel configured to process the one or more target analytes;

iv. microfluidic circuitry including a plurality of valves and fluid lines configured to couple the driving syringe, the plurality of reagent syringes, and the plurality of processing vessels, wherein each valve is coupled to one valve actuation mechanism and each valve is configured to actuate no more than once, further wherein a position of the one or more target analytes within the cartridge is determined according to a cumulative amount of actuation increments of the drive motor; and

c. a control module coupled to the drive motor and the plurality of valve actuation mechanisms, wherein the control module is configured to provide control signals to independently actuate the drive motor and each of the plurality of valve actuation mechanisms.

19. The apparatus of claim 18 wherein the cartridge is fully loaded with fluid prior to an initial actuation of the drive motor.

20. The apparatus of claim 19 wherein actuation of the drive motor forces fluid flow within the cartridge.

21. The apparatus of claim 20 wherein a position of each reagent fluid within the cartridge is defined according to a fluid front of each reagent fluid, and the position of each fluid front is determined according to the cumulative amount of actuation increments performed by the drive motor.

22. The apparatus of claim 18 wherein each valve is configured to actuate from a closed position to an open position.

23. The apparatus of claim 18 wherein the cartridge further comprises a plurality of waste vessels coupled to the microfluidic circuitry, wherein the plurality of waste vessels are configured to store all waste generated while processing the fluid sample, further wherein the cartridge is disposable.

24. The apparatus of claim 23 wherein each waste vessel includes a plunger and a plunger stop, the plunger configured to be displaced by incoming waste and the plunger stop positioned to regulate a maximum amount of waste to be added to the waste vessel.

25. The apparatus of claim 18 wherein each reagent syringe includes a plunger and a plunger stop, the plunger configured to displace the reagent fluid and the plunger stop positioned to regulate a maximum fluid displaced by the plunger.

26. The apparatus of claim 18 wherein each of the processing vessels comprises one of the group consisting of a lysing chamber, an ion-exchange chromatography column, a size-exclusion chromatography column, and a thermal cycling chamber.

27. The apparatus of claim 26 wherein the actuation instrument further comprises a sonication horn coupled to the lysing chamber.

28. The apparatus of claim 26 wherein the actuation instrument further comprises a thermo-electric cooler coupled to the thermal cycling chamber.

29. The apparatus of claim 18 wherein the drive motor comprises a stepper motor and the cumulative amount of actuation increments is a cumulative number of steps of the drive motor.

30. The apparatus of claim 29 wherein the control module is configured to independently actuate each of the valve mechanisms according to a specific cumulative amount of actuation increments.

31. The apparatus of claim 18 further comprising one or more sensors positioned in each of the reagent syringes, wherein each sensor is configured to detect a position of the plunger in the reagent syringe.

32. The apparatus of claim 31 wherein the control module is configured to independently actuate each of the valve mechanisms according to the detected positions of the plungers.

33. The apparatus of claim 18 wherein each of the valve actuation mechanisms comprises a solenoid.

34. The apparatus of claim 18 wherein the cartridge further comprises a fluid sample input port coupled to one of the processing vessels.