Methods and systems for control of general purpose microfluidic devices

• US 8,895,311 B1
• Filed: 09/18/2002
• Issued: 11/25/2014
• 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): LUDLOW, JAN M
• Application Number:
  US10/246,814
• Time in Patent Office: 4,451 Days
• Field of Search: 422/67, 422/502, 422/504, 422/509, 436/43, 436/180, 702/22, 702/31
• US Class Current: 436/43
• 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
• 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 microprocessor-based method for controlling a microfluidic device, the method comprising:

selecting a micro-droplet processing request from a pre-selected group of micro-droplet processing requests,

wherein each request in the group specifies the creation or transformation of at least one micro-droplet confined in at least one microchannel in the microfluidic device, and

wherein the microfluidic device comprises at least one resistive temperature detector which provides a sense signal indicative of a result of performing at least one selected micro-droplet processing request, wherein the microfluidic device is configured to perform two or more different processes relating to the micro-droplet processing requests on the micro-droplet contained in the microchannel,

wherein the result comprises a temperature or a position of a micro-droplet;

in response to each selected processing request, generating one or more control signals that, when applied to the microfluidic device, cause the device to perform the micro-droplet creation or the micro-droplet transformation specified by the processing request;

for each sense signal provided for the at least one selected micro-droplet processing request, determining one or more of a position or a temperature of a micro-droplet, wherein selecting the micro-droplet processing request next after the at least one selected request is conditional upon the result of performing the at least one selected request, and

repeating the selecting, the generating, and as applicable the determining, until the process is completed.

2. The method of claim 1 wherein the micro-droplet processing requests each specify one or more micro-droplet manipulations selected from the group consisting of:

(i) creating at least one additional micro-droplet, (ii) moving at least one micro-droplet from a first position to a next position, (iii) combining at least two micro-droplets to form at least one additional micro-droplet, (iv) mixing or dissolving one or more reagents in at least one micro-droplet, (v) metering at least one micro-droplet from a fluid reservoir, (vi) sealing at least one micro-droplet at a position in the at least one microchannel, and (vii) stimulating a reaction in a micro-droplet trapped in the at least one microchannel.

3. The method of claim 2 wherein control signals generated in response to a request for moving a micro-droplet comprise signals for activating a controllable gas pressure generator.

4. The method of claim 2 wherein the moving at least one micro-droplet from a first position to a next position is such that the next position is selected from a plurality of possible next positions.

5. The method of claim 4 wherein, in response to a processing request specifying a move to a selected next position, control signals are generated either to cause obstruction of microchannels from the first position to all the plurality of possible next positions except the selected next position, or to open only a selected microchannel from a plurality of possible selected next positions.

6. The method of claim 5 wherein microchannels are either obstructed by a meltable material that is melted in response to at least one control signal, or are opened by withdrawing a meltable material in response to at least one control signal.

7. The method of claim 1 wherein the microfluidic device further comprises at least one heater for locally heating the microfluidic device, and wherein the control signals comprise signals for activating the heater.

8. The method of claim 1 wherein the process comprises a chemical process to be carried out in at least one micro-droplet.

9. The method of claim 8 wherein the control signals cause:

formation of the at least one micro-droplet wherein the at least one micro-droplet has a composition suitable for the chemical process; and

the chemical process to be carried out in the micro-droplet.

10. The method of claim 9 wherein the causing formation of the micro-droplet comprises combining a plurality of micro-droplets of reagents used in the chemical process.

11. The method of claim 9 wherein the causing the chemical process to be carried out in the micro-droplet further comprises:

(i) waiting for a time sufficient for occurrence of the process, or

(ii) exciting the micro-droplet.

12. The method of claim 11 wherein exciting the micro-droplet comprises applying heat or light thereto.

13. The method of claim 1 wherein the micro-droplet processing requests further comprise requests for creating a micro-droplet by contacting a gel, viscous liquid, semi-solid, or solid-form of a reagent with a liquid solvent so that the reagent disperses in the liquid.

14. The method of claim 13 wherein the solid-form disperses in the liquid by dissolving.

15. The method of claim 1, wherein the at least one resistive temperature detector is configured to sense a position of a micro-droplet by measuring a local specific heat.

16. The method of claim 1, wherein the at least one resistive temperature detector is configured with two pairs of control leads.

17. The method of claim 1, wherein the at least one resistive temperature detector is operatively coupled to a resistive heater.

18. The method of claim 1, wherein the microfluidic device further comprises a Peltier device.

19. The method of claim 1, wherein the microfluidic device further comprises a switching component.

20. A method for controlling a microfluidic device, the method comprising:

selecting a process from a plurality of predetermined processes,

wherein each predetermined process is associated with a group of micro-droplet processing requests for carrying out the predetermined process, and

wherein each micro-droplet processing request specifies the creation or transformation of at least one micro-droplet confined at least one microchannel in the microfluidic device,

selecting a micro-droplet processing request from the group of requests associated with the selected process,

wherein the microfluidic device comprises at least one resistive temperature detector which provides a sense signal indicative of a result of performing at least one selected micro-droplet processing request, wherein the result comprises a temperature or a position of a micro-droplet, and wherein the microfluidic device is configured to perform two or more different processes relating to the micro-droplet processing requests on the micro-droplet contained in the microchannel;

in response to each selected processing request, generating one or more control signals that, when applied to the microfluidic device, cause the device to perform the micro-droplet creation or the micro-droplet transformation specified by the selected processing request;

for each sense signal provided for the at least one selected micro-droplet processing request, determining one or more of a position or a temperature of a micro-droplet, wherein selecting the micro-droplet processing request next after the at least one selected request is conditional upon the result of performing the at least one selected request; and

repeating the selecting a processing request, the generating, and as applicable the determining, until the process is completed.

21. The method of claim 20 wherein the selecting a process further comprises:

displaying to a user indicia representing the predetermined processes available for selection; and

accepting user input representing selection of one of the predetermined processes, whereby the user-selected process is then performed by the microfluidic device.

22. The method of claim 20, further comprising:

displaying indicia representing one or more types of microfluidic devices capable of performing the micro-droplet processing requests in the group of processing requests associated with each process, and

requesting that a microfluidic device of one of the types be made available.

23. The method of claim 20, further comprising:

displaying indicia representing one or more types of reagent packs comprising aliquots of reagents used in the predetermined process,

wherein a reagent pack comprises at least one reservoir in fluid communication with at least one outlet port, wherein the reagent pack can be mated with the microfluidic device so that the outlet port is in fluid communication with an inlet port of the device, and whereby a reagent in the reservoir can be supplied to the microfluidic device, and

requesting that a reagent pack of one of the associated types be made available.

24. The method of claim 20, wherein the at least one resistive temperature detector is configured to sense a position of a micro-droplet by measuring a local specific heat.

25. The method of claim 20, wherein the at least one resistive temperature detector is configured with two pairs of control leads.

26. The method of claim 20, wherein the at least one resistive temperature detector is operatively coupled to a resistive heater.

27. The method of claim 20, wherein the microfluidic device further comprises a Peltier device.

28. The method of claim 20, wherein the microfluidic device further comprises a switching component.