POLYMERASE CHAIN REACTION SYSTEMS

• US 20120244604A1
• Filed: 03/23/2011
• Published: 09/27/2012
• Est. Priority Date: 05/21/2010
• Status: Active Grant

• Current Assignee: Alexander Govyadinov, David P. Markel, Erik D. Torniainen, Pavel Kornilovich
• Original Assignee: Hewlett-Packard Development Company, L.P. (HP Inc.)
• Inventors: Kornilovich, Pavel, Torniainen, Erik D., Govyadinov, Alexander, Markel, David P.
• Granted Patent: US 9,963,739 B2
• Time in Patent Office: Days
• US Class Current: 435/286.1
• 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 2300/0681 Filter
• 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 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 7/525 with physical movement of samples between temperature zones
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]

Abstract

In one embodiment, a polymerase chain reaction (PCR) system includes a mixture chamber, a denature chamber, an annealing chamber, an extension chamber, and a product chamber, that are fluidically coupled to one another through a plurality of microfluidic channels. An inertial pump is associated with each microfluidic channel, and each inertial pump includes a fluid actuator integrated asymmetrically within its associated microfluidic channel. The fluid actuators are capable of selective activation to circulate fluid between the chambers in a controlled cycle.

Claims

1. A polymerase chain reaction (PCR) system comprising:

a mixture chamber, a denature chamber, an annealing chamber, an extension chamber, and a product chamber, the chambers fluidically coupled to one another through a plurality of microfluidic channels; and

an inertial pump associated with each microfluidic channel, each inertial pump including a fluid actuator integrated asymmetrically within the associated microfluidic channel; and

wherein the fluid actuators are capable of selective activation to circulate a fluidic PCR mixture through the chambers for a controlled number of cycles.

2. A PCR system as in claim 1, wherein the inertial pumps comprise bidirectional inertial pumps, and the bidirectional inertial pumps comprise a single fluid actuator controllable to generate compressive and tensile fluid displacements of varying durations.

3. A PCR system as in claim 1, wherein the inertial pumps are selected from the group consisting of bidirectional pumps and unidirectional pumps.

4. A PCR system as in claim 1, further comprising:

a controller; and

instruction modules executable by the controller to control fluid flow directions, fluid flow rates, chamber temperatures, and the number of cycles the PCR mixture circulates through the chambers through selective and controlled activation of the fluid actuators.

5. A PCR system as in claim 1, wherein controlled activation of the fluid actuators comprises controlling compressive and tensile fluid displacement durations of the fluid actuators.

6. A PCR system as in claim 1, further comprising a microchip on which the chambers, the microfluidic channels and the inertial pumps are fabricated.

7. A PCR system as in claim 1, wherein chambers comprise:

temperature sensors to sense the temperatures of the chambers; and

resistive heaters to maintain the temperatures in the chambers within controlled temperature ranges according to sensed temperatures from the temperature sensors.

8. A PCR system as in claim 7, further comprising:

a controller; and

a temperature control module executable on the controller to monitor the temperature sensor and activate the resistive heater such that each chamber is maintained within a controlled temperature range.

9. A PCR system as in claim 1, wherein the chambers comprise a linear PCR architecture with the denature chamber coupled to the mixture chamber and the annealing chamber, and the extension chamber coupled to the annealing chamber and the product chamber.

10. A PCR system as in claim 9, comprising a plurality of the linear PCR architectures on a microchip capable of parallel PCR processing.

11. A PCR system as in claim 1, wherein the chambers comprise a circular PCR architecture with the denature chamber coupled to the mixture, annealing and extension chambers, and the extension chamber coupled to the annealing and reaction chambers.

12. A PCR system as in claim 11, comprising a plurality of the circular PCR architectures on a microchip capable of parallel PCR processing.

13. A polymerase chain reaction (PCR) system comprising:

a single premixture chamber to provide PCR solution;

a plurality of sample chambers to provide sample DNA fragments;

a temperature cycling area;

a plurality of mixing chambers each fluidically coupled through microfluidic channels to the single premixture chamber, the temperature cycling area, and to a distinct one of the plurality of sample chambers; and

inertial pumps, each having a fluid actuator integrated asymmetrically within a microfluidic channel and capable of selective and controlled activation to move PCR solution and sample DNA fragments into the mixing chambers, and to move PCR mixture from the mixing chambers through the temperature cycling area in a controlled cycle.

14. A PCR system as in claim 13, wherein the temperature cycling area comprises:

a denature area;

an annealing area; and

an extension area.

15. A PCR system as in claim 13, further comprising a product area to receive reaction products from the temperature cycling area.

16. A PCR system as in claim 13, wherein an inertial pump is located between each mixing chamber and the premixture chamber, between each mixing chamber and a distinct sample chamber, and between each mixing chamber and the temperature cycling area.

17. A PCR system as in claim 13, wherein inertial pumps between each mixing chamber and the temperature cycling area are bidirectional pumps.

18. A PCR system as in claim 13, further comprising:

a microchip on which the chambers, the microfluidic channels, the temperature cycling area, and the inertial pumps are fabricated; and

a controller to control the direction of fluidic flow through the microfluidic channels through selective and controlled activation of the fluid actuators.

19. A PCR system as in claim 18, wherein controlled activation of the fluid actuators comprises controlling durations of compressive and tensile fluid displacements generated by the fluid actuators.

20. A PCR system as in claim 13, further comprising:

machine executable instruction modules; and

a controller to control by execution of the executable instruction modules, fluid flow rates and directions, temperatures in the temperature cycling area, and a number of cycles the PCR mixture is to be moved through the temperature cycling area.

21. A polymerase chain reaction (PCR) system as in claim 13, wherein the single premixture chamber is a plurality of premixture chambers and the plurality of sample chambers is a single sample chamber, and wherein each of the plurality of mixing chambers is fluidically coupled through microfluidic channels to the single sample chamber, the PCR temperature cycling area, and to a distinct one of the premixture chambers.

22. A polymerase chain reaction (PCR) system comprising:

a grid of intersecting microfluidic channels having mixing chambers at each intersection;

premixture chambers individually coupled to microfluidic channels at a first side of the grid;

sample chambers individually coupled to microfluidic channels at a second side of the grid;

a cleaning agent reservoir coupled to the grid through secondary microfluidic channels that intersect the grid at cleaning junctions; and

inertial pumps having fluid actuators integrated asymmetrically within microfluidic channels to pump PCR solutions from the premixture chambers into the mixing chambers, sample DNA fragments from the sample chambers into the mixing chambers, PCR mixture from the mixing chambers through a PCR temperature cycling area, and cleaning solution from the cleaning agent reservoir through the grid of intersecting microfluidic channels.