Methods and systems for control of microfluidic devices

• US 8,473,104 B2
• Filed: 07/22/2011
• Issued: 06/25/2013
• 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): MERKLING, SALLY ANNE
• Application Number:
  US13/189,453
• Publication Number:
  US 20120022695A1
• Time in Patent Office: 704 Days
• Field of Search: 422/509, 422501-504, 422/68.1, 700/174, 700/266, 436/180, 436/43, 436/53
• US Class Current: 700/266
• 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 2200/14 : Process control and prevention of errors
• 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 2400/0493 : Specific techniques used
• 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 3/502792 : for moving individual droplets on a plate, e.g. by locally altering surface tension
• 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 35/1083 : with one horizontal degree of freedom
• CPC Class Codes: Y10T 436/12 : Condition responsive control
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

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 system for controlling the operation of a microfluidic device comprising a substrate having a micropassage configured for holding a micro-volume of liquid having a volume between one nano-liter and one micro-liter, a reaction chamber, and one or more active components, wherein one of the one or more active components comprise a hierarchical organization of device level components, the system comprising:

a processor configured for receiving a user request for the microfluidic device to perform a reaction program;

memory comprising stored instructions corresponding to hierarchical signals configured to direct the microfluidic device to perform the user-requested reaction program the hierarchical signals corresponding to;

a component level instruction directing the generation of a control signal for an individual component of the microfluidic device;

an actuator level function corresponding to an actuator operation, wherein the actuator level function comprises a plurality of component level functions;

a microdroplet level function corresponding to an operation performed on a micro-volume of liquid contained within a microfluidic device, wherein the microdroplet level function comprises a plurality of actuator level functions;

a user level function corresponding to the reaction program, the user level function corresponding to a plurality of microdroplet level functions; and

a programmable digital acquisition unit comprising;

a heater driver circuit;

a temperature sensor driver circuit; and

a detection driver circuit wherein the detection driver passes signals to at least one active component configured to detect reaction products in the reaction chamber;

wherein the programmable digital acquisition unit generates control signals for the at least one active component corresponding to a component level instruction and responsive to the user-requested reaction program; and

wherein the control signals of the programmable digital acquisition unit control (i) heating the micro-volume of liquid, (ii) detecting a temperature related to the micro-volume of liquid, and (iii) detecting reaction products in the micro-volume of liquid.

2. A system for controlling the operation of a microfluidic device as recited in claim 1, further comprising at least one receptacle for receiving the microfluidic device, wherein the receptacle provides for transfer of control signals between the programmable digital acquisition unit and the microfluidic device.

3. A system for controlling the operation of a microfluidic device as recited in claim 1, further comprising a light emitter driving circuit and a light detector driving circuit.

4. A system for controlling the operation of a microfluidic device as recited in claim 1, wherein the actuator level function comprises instructions to detect the presence or absence of the micro-volume of liquid.

5. A system for controlling the operation of a microfluidic device as recited in claim 1, wherein the hierarchical signals provide instructions to the microfluidic device to (i) move the micro-volume of liquid to the reaction chamber, (ii) close a valve, (iii) perform thermal cycling within the reaction chamber, and (iv) detect reaction products in the reaction chamber.

6. A system configured for controlling a microfluidic device, wherein the microfluidic device comprises a substrate comprising a micro-channel configured to contain a micro-volume of liquid having a volume between one nano-liter and one micro-liter, a reaction chamber, and an actuator comprising a grouping of active components, said active components configured for coordinated operation to achieve a desired functionality, the system comprising:

memory comprising stored instructions corresponding to a user-selected reaction program, wherein the stored instructions comprise;

a user level function corresponding to the reaction program;

a microdroplet level function corresponding to an operation performed on a micro-volume of liquid contained within a microfluidic device;

an actuator level function corresponding to an actuator operation, wherein the actuator level function comprises instructions to detect the presence or absence of the micro-volume of liquid; and

a component level instruction directing the generation of a control signal for an individual component of the microfluidic device;

an interface configured for allowing an operator to select a desired reaction program for the microfluidic device, wherein the desired reaction program corresponds to a user level function comprising a microdroplet level function, wherein the microdroplet level function comprises an actuator level function, and the actuator level function comprises a component level function; and

control circuitry configured for creating and transmitting the control signal responsive to a component level function for controlling the component of the microfluidic device.

7. The system for controlling a microfluidic device as recited in claim 6, further comprising at least one receptacle for receiving the microfluidic device, wherein the receptacle provides for transfer of the control signals between the control circuitry and the microfluidic device.

8. The system for controlling a microfluidic device as recited in claim 6, wherein one of the active components comprises a light emitter and one of the active components comprises a light detector.

9. The system for controlling a microfluidic device as recited in claim 6, further comprising stored instructions directing a laboratory robot to introduce a micro-volume of liquid into the microfluidic device.

10. The system for controlling a microfluidic device as recited in claim 6, wherein the stored instructions comprise instructions for the microfluidic device to (i) move the micro-volume of liquid to the reaction chamber, (ii) close a valve, (iii) perform thermal cycling within the reaction chamber, and (iv) detect reaction products in the reaction chamber.

11. The system for controlling a microfluidic device as recited in claim 10, wherein reaction products in the reaction chamber are detected by measuring fluorescence of the contents of the reaction chamber.

12. The system for controlling a microfluidic device as recited in claim 11, wherein the actuator level function actuates a light source to illuminate a portion of the reaction chamber.

13. The system for controlling a microfluidic device as recited in claim 11, wherein the actuator level function actuates a light detector to detect fluorescent emissions from the contents of the reaction chamber.

14. The system for controlling a microfluidic device as recited in claim 6, wherein the stored instructions comprise instructions to determine the local heat capacity of a portion of the microfluidic device to determine the presence or absence of the micro-volume of liquid.