Microfluidic valve and method of making same

• US 10,710,069 B2
• Filed: 06/27/2014
• Issued: 07/14/2020
• Est. Priority Date: 11/14/2006
• Status: Active Grant

• Current Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Original Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Inventors: Handique, Kalyan, Parunak, Gene, Haley, Cecelia
• Primary Examiner(s): Ramdhanie, Bobby
• Assistant Examiner(s): Anderson, Denise R.
• Application Number:
  US14/318,160
• Publication Number:
  US 20150064702A1
• Time in Patent Office: 2,209 Days
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2200/142 Preventing evaporation
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/14 Means for pressure control
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1844 using fans
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0677 phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 2400/0694 vents used to stop and induce flow, backpressure valves
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502723 characterised by venting arrangements
• 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: B81C 1/00087 Holes
• CPC Class Codes: C12Q 1/6806 Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/686 : Polymerase chain reaction [PCR]
• CPC Class Codes: F16K 2099/008 : Multi-layer fabrications
• CPC Class Codes: F16K 2099/0084 : Chemistry or biology, e.g. "lab-on-a-chip" technology
• CPC Class Codes: F16K 99/0001 : Microvalves microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006

Abstract

The present technology provides for a microfluidic substrate configured to carry out PCR on a number of polynucleotide-containing samples in parallel. The substrate can be a single-layer substrate in a microfluidic cartridge. Also provided are a method of making a microfluidic cartridge comprising such a substrate. Still further disclosed are a microfluidic valve suitable for use in isolating a PCR chamber in a microfluidic substrate, and a method of making such a valve.

Claims

1. A method of making a microfluidic valve in a microfluidic device comprising a reactor and a window disposed relative to the reactor to allow detection of fluorescence from the reactor, the method of making comprising:

directing a dispensing head over an inlet hole in a microfluidic substrate of the microfluidic device;

propelling a quantity of thermally responsive substance as a succession of fluid dots from the dispensing head into the inlet hole; and

maintaining a temperature of the microfluidic substrate so that the thermally responsive substance flows by capillary action from the inlet hole into a microfluidic loading channel in communication with the inlet hole, the microfluidic loading channel comprising a first end and a second end, the second end of the microfluidic loading channel intersecting a microfluidic flow channel at a T-junction such that the flow of thermally responsive substance stops when the thermally responsive substance reaches the microfluidic flow channel without entering the microfluidic flow channel to form the microfluidic valve.

2. The method of claim 1, wherein the T-junction intersection between the microfluidic loading channel and the microfluidic flow channel comprises a higher cross section than the microfluidic loading channel.

3. The method of claim 1, wherein capillary forces in the T-junction intersection between the microfluidic loading channel and the microfluidic flow channel are lower than in the microfluidic loading channel.

4. The method of claim 1, wherein the quantity of thermally responsive substance dispensed by the dispensing head varies between a minimum and a maximum shot size.

5. The method of claim 4, wherein the volume of the microfluidic loading channel does not exceed the maximum shot size.

6. The method of claim 4, wherein the quantity is 75±

15 nl.

7. The method of claim 1, wherein the propelling utilizes heated air.

8. The method of claim 1, wherein the propelling utilizes compressed air.

9. The method of claim 1, wherein the thermally responsive substance is wax.

10. The method of claim 1, wherein the dispensing head is heated.

11. The method claim 1, further comprising maintaining a temperature of the thermally responsive substance in the dispensing head so that the thermally responsive substance is dispensed in molten form into the inlet hole.

12. The method of claim 1, wherein the directing is automatically controlled.

13. A microfluidic valve made by the method of claim 1, wherein the microfluidic loading channel and the microfluidic flow channel form a ninety degree angle at the T-junction.

14. A microfluidic substrate comprising one or more microfluidic valves made by the method of claim 1, wherein the T-junction has a dimension to reduce capillary forces at the T-junction.

15. A method of making a microfluidic valve, the method of comprising:

directing a dispensing head over an inlet hole in a microfluidic substrate;

propelling a quantity of fluid thermally responsive substance from the dispensing head into the inlet hole;

flowing by capillary action the thermally responsive substance from the inlet hole into a microfluidic loading channel in communication with the inlet hole, the microfluidic loading channel comprising a first end and a second end, the second end of the microfluidic loading channel intersecting a microfluidic flow channel; and

stopping the flow of thermally responsive substance when the thermally responsive substance reaches the microfluidic flow channel without entering the microfluidic flow channel to form the microfluidic valve.

16. The method of claim 15, wherein the second end of the microfluidic loading channel intersects the microfluidic flow channel at a T-junction.

17. The method of claim 16, wherein the T-junction intersection between the microfluidic loading channel and the microfluidic flow channel comprises a higher cross section than the microfluidic loading channel.

18. A method comprising:

directing a first dispensing head over a first inlet hole in a microfluidic substrate;

propelling a quantity of fluid thermally responsive substance from the first dispensing head into the first inlet hole;

flowing by capillary action the thermally responsive substance from the first inlet hole into a microfluidic loading channel in communication with the first inlet hole, the microfluidic loading channel comprising a first end and a second end, the second end of the microfluidic loading channel intersecting a microfluidic flow channel;

stopping the flow of thermally responsive substance when the thermally responsive substance reaches the microfluidic flow channel without entering the microfluidic flow channel, wherein

the microfluidic substrate comprises a second inlet hole figured to receive a sample dispensed with a second dispensing head.

19. The method of claim 18, wherein the microfluidic substrate further comprises a plurality of sample lanes configured to receive a plurality of samples, and wherein inlets of the respective plurality of sample lanes are spaced apart from one another to permit simultaneous loading from a multiple-pipette head dispenser.