METHODS AND SYSTEMS FOR CONTROL OF GENERAL PURPOSE MICROFLUIDIC DEVICES

• US 20150142186A1
• Filed: 11/21/2014
• Published: 05/21/2015
• Est. Priority Date: 03/28/2001
• Status: Active Grant

• Current Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Original Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Inventors: Handique, Kalyan, Ganesan, Karthik, Brahmasandra, Sundaresh N.
• Granted Patent: US 10,571,935 B2
• Time in Patent Office: Days
• US Class Current: 700/282
• 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

1-38. -38. (canceled)

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

a digital store for 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,

a first digital processing element for selecting a next micro-droplet processing request from the stored pre-selected group of micro-droplet processing requests until no processing requests remain to be selected, and

a second digital processing element for accepting each selected processing request, and for generating control signals that, when applied to the microfluidic processor, cause that processor to perform the micro-droplet creation or the micro-droplet transformation specified by the accepted processing request,

whereby the controller causes the microfluidic processor to perform the pre-selected group of processing requests in response to the generated control signals.

40. The controller of claim 39 wherein the stored, pre-selected group of processing requests further cause the microfluidic processor to carry out a predetermined chemical process to occur in at least one micro-droplet.

41. The controller of claim 40 wherein the stored pre-selected group of processing requests further cause the microfluidic processor to carry out:

formation of a micro-droplet having a composition suitable for a preselected chemical process or chemical reaction, and

performing the pre-selected chemical process in the suitable micro-droplet.

43. The controller of claim 39 wherein at least one programmed microprocessor comprises the first and the second digital processing elements, and

wherein the digital store is operatively coupled to the microprocessor.

44. The controller of claim 39 wherein the at least one microprocessor is a single microprocessor.

64. The controller of claim 39, wherein the microfluidic processor 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.

42. (canceled)

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

a digital store for 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,

a first digital processing element for (i) receiving sense signals provided by the microfluidic processor, and (ii) selecting 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

a second digital processing element for accepting the selected processing request, and for generating control signals that, when applied to the microfluidic processor, cause that processor to perform the micro-droplet creation or transformation specified by the processing request.

46. The controller of claim 45 wherein a 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 first digital processing element selects the next position to move to from the plurality of next positions in response to at least one received sense signal.

47. The controller of claim 45 wherein at least one micro-droplet processing request is associated with a plurality of possible next processing requests, and wherein the first digital processing element selects the particular next processing request from the plurality of next requests in response to at least one received sense signal.

48. The controller of claim 45 wherein at least one sense signal received by the first digital processing element is responsive to a characteristic of at least one micro-droplet when confined in the processor.

49. The controller of claim 48 wherein the characteristic comprises the position of the micro-droplet.

50. The controller of claim 48 wherein the characteristic comprises the composition of the micro-droplet.

51. The controller of claim 45 wherein at least one sense signal received by the first digital processing element is responsive to a temperature in the microfluidic device.

65. The controller of claim 45, wherein the microfluidic processor 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.

52. A digital controller 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:

a digital store for a plurality of predetermined processes, wherein each predetermined process is associated with a stored 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 in the microfluidic processor

a first digital processing element for selecting a process from the plurality of stored predetermined processes,

a second digital processing element for selecting a next micro-droplet processing request from the stored group of processing requests associated with the selected process until no processing requests remain to be selected from the group, and

a third digital processing element for accepting each selected processing request, and for generating control signals that, when applied to the microfluidic processor, cause the processor to perform the micro-droplet creation or the micro-droplet transformation specified by the accepted processing request,

whereby the controller causes the microfluidic processor to perform the selected group of processing requests, and thereby to carry out the selected process.

53. The controller of claim 52 wherein the first digital processing element is further for:

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

accepting user input representing selection of one of the available processes, whereby the controller then causes the microfluidic processor to carry out the user-selected process.

54. The controller of claim 52 wherein each predetermined process is further associated with indicia representing one or more types of microfluidic processors capable of performing the micro-droplet processing requests in the associated group of processing requests, and wherein the controller further comprises:

a fourth digital processing element for displaying a request that a microfluidic processor of one of the associated types be made available.

56. The controller of claim 52 wherein at least one programmed microprocessor comprises the first, the second, and the third digital processing elements, and

wherein the digital store is operatively coupled to the microprocessor.

57. The controller of claim 52 wherein a first programmed microprocessor comprises the first digital processing element,

wherein a second programmed microprocessor comprises the second digital processing element and the third digital processing element,

wherein the digital store is operatively coupled to at least the first microprocessor, and further comprising

a user input and a user output device operatively coupled to at least the first microprocessor.

66. The controller of claim 52, wherein the microfluidic processor 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.

55. (canceled)

58-63. -63. (canceled)