Methods and systems for control of general purpose microfluidic devices

• US 10,571,935 B2
• Filed: 11/21/2014
• Issued: 02/25/2020
• Est. Priority Date: 03/28/2001
• Status: Expired due to Term

• Current Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Original Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Inventors: Handique, Kalyan, Ganesan, Karthik, Brahmasandra, Sundaresh N.
• Primary Examiner(s): Warden, Jill A
• Application Number:
  US14/550,657
• Publication Number:
  US 20150142186A1
• Time in Patent Office: 1,922 Days
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01F 33/3033 using heat to mix or move the fluids
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00831 Glass
• CPC Class Codes: B01J 2219/00833 Plastic
• CPC Class Codes: B01J 2219/00835 Comprising catalytically active material
• CPC Class Codes: B01J 2219/00837 comprising coatings other than catalytically active coatings
• CPC Class Codes: B01J 2219/0086 Dimensions of the flow channels
• CPC Class Codes: B01J 2219/00862 Dimensions of the reaction cavity itself
• CPC Class Codes: B01J 2219/00873 Heat exchange
• CPC Class Codes: B01J 2219/00889 Mixing micromixers B01F33/30
• CPC Class Codes: B01J 2219/00891 Feeding or evacuation
• CPC Class Codes: B01J 2219/00936 UV-radiations
• CPC Class Codes: B01J 2219/00943 Visible light, e.g. sunlight
• CPC Class Codes: B01J 2219/00945 Infrared light
• CPC Class Codes: B01J 2219/00961 Temperature
• CPC Class Codes: B01J 2219/0097 Optical sensors
• CPC Class Codes: B01J 2219/00986 Microprocessor
• CPC Class Codes: B01L 2200/0605 : Metering of fluids
• CPC Class Codes: B01L 2200/0673 : Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/147 : Employing temperature sensors
• CPC Class Codes: B01L 2300/0816 : Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/0442 : thermal energy, e.g. vaporisation, bubble jet
• 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 3/502784 : specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• 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 1/4077 : by other techniques involving separation of suspended solids
• CPC Class Codes: G01N 35/00584 : Control arrangements for automatic analysers
• CPC Class Codes: G05B 15/02 : electric
• CPC Class Codes: G05B 19/43 : fluidic
• CPC Class Codes: G05B 2219/34198 : Electric and fluidic modules integrated on one substrate
• CPC Class Codes: G05D 7/0617 : specially adapted for fluid materials
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis

Abstract

The present invention provides control methods, control systems, and control software for microfluidic devices that operate by moving discrete micro-droplets through a sequence of determined configurations. Such microfluidic devices are preferably constructed in a hierarchical and modular fashion which is reflected in the preferred structure of the provided methods and systems. In particular, the methods are structured into low-level device component control functions, middle-level actuator control functions, and high-level micro-droplet control functions. Advantageously, a microfluidic device may thereby be instructed to perform an intended reaction or analysis by invoking micro-droplet control function that perform intuitive tasks like measuring, mixing, heating, and so forth. The systems are preferably programmable and capable of accommodating microfluidic devices controlled by low voltages and constructed in standardized configurations. Advantageously, a single control system can thereby control numerous different reactions in numerous different microfluidic devices simply by loading different easily understood micro-droplet programs.

Claims

1. A digital controller configured for a microfluidic processor comprising at least one passage capable of confining at least one micro-droplet responsive to applied control signals, the controller comprising:

first computer readable medium storing a pre-selected group of micro-droplet processing requests, wherein each request specifies the creation or transformation of at least one micro-droplet confined in the microfluidic processor, and

one or more microprocessors and a second computer readable medium having stored thereon computer executable instructions that, upon execution, cause the one or more microprocessors to at least;

(i) receive sense signals from the microfluidic processor, and (ii) select a micro-droplet processing request from a plurality of micro-droplet processing requests in response to the received signals, wherein each request specifies the creation or transformation of at least one micro-droplet confined in the microfluidic processor, and

accept the selected processing request, and generate control signals that, when applied to the microfluidic processor, cause that microfluidic processor to perform the micro-droplet creation or transformation specified by the processing request.

2. The controller of claim 1 wherein the micro-droplet processing request further specifies the moving of at least one micro-droplet from a first position to a selected one of a plurality of possible next positions, and wherein the computer executable instructions, upon execution, cause the one or more microprocessors to select the next position to move to from the plurality of next positions in response to at least one received sense signal.

3. The controller of claim 1 wherein at least one micro-droplet processing request is associated with a plurality of possible next processing requests, and wherein the computer executable instructions, upon execution, cause the one or more microprocessors to select the particular next processing request from the plurality of next requests in response to at least one received sense signal.

4. The controller of claim 1 wherein at least one received sense signal is responsive to a characteristic of at least one micro-droplet when confined in the microfluidic processor.

5. The controller of claim 4 wherein the characteristic comprises the position of the micro-droplet.

6. The controller of claim 4 wherein the characteristic comprises the composition of the micro-droplet.

7. The controller of claim 1 wherein at least one received sense signal is responsive to a temperature in the microfluidic processor.

8. The controller of claim 1, wherein the computer executable instructions, upon execution, cause the one or more microprocessors to receive sense signals indicative of a result of performing at least one selected micro-droplet processing request.

9. The controller of claim 1, wherein the at least one micro-droplet has a length approximately from 50 μ

m to 10 mm.

10. The controller of claim 1, wherein the first computer readable medium stores a plurality of predetermined processes each accompanied by a stored processing program.

11. The controller of claim 1, wherein at least one stored micro-droplet processing request includes encoded instructions for the controllable switching of a micro-droplet among a plurality of next positions.

12. The controller of claim 1, wherein at least one stored micro-droplet processing request includes encoded instructions for the formation of a micro-droplet having a composition suitable for a pre-selected chemical process or chemical reaction.

13. The controller of claim 1, wherein at least one stored micro-droplet processing request includes encoded instructions for the performance of a pre-selected chemical process in a suitable micro-droplet.

14. The controller of claim 1, wherein the computer executable instructions, upon execution, cause the one or more microprocessors to select a next micro-droplet processing request from the stored pre-selected group of micro-droplet processing requests until no next processing requests remain to be selected.

15. The controller of claim 1, wherein at least one sense signal is responsive to the position of the micro-droplet.

16. The controller of claim 1, wherein at least one sense signal is responsive to the composition of the micro-droplet.

17. The controller of claim 1, wherein at least one sense signal is responsive to a temperature in the microfluidic device.

18. A system comprising:

the controller of claim 1, and the microfluidic processor.

19. The system of claim 18, wherein at least one stored micro-droplet processing request includes encoded instructions for causing an obstructing element to move into and close the at least one passage in the microfluidic processor.

20. The system of claim 18, wherein at least one stored micro-droplet processing request includes encoded instructions for exciting the at least one micro-droplet in the microfluidic processor.