Methods and systems for control of microfluidic devices
First Claim
1. A method for controlling the operation of a digital-type microfluidic (“
- MF”
) device (i) wherein an ME device comprises one or more passages for confining one or more micro-droplets, the passages having one or more stable positions for the micro-droplets, and (ii) comprises one or more internal components responsive to control signals, the internal components operatively associated with the passages for control and monitoring the MF device, the method comprising;
(a) providing one or more micro-droplet processing requests, wherein a micro-droplet processing request specifies performing at least one action on at least one micro-droplet, each provided micro-droplet processing request comprising two or more actuator processing requests, each specifying performing at least one action associated with at least one passage of the ME device, the micro-droplet processing requests comprising at least one of;
(i) creating one or more new micro-droplets at selected stable positions, or(ii) moving one or more micro-droplets from current stable positions to selected next stable positions, or(iii) combining two or more micro-droplets into one or more new micro-droplets at selected stable positions, or(iv) mixing one or more micro-dropletsthe actuator processing requests comprising;
(i) providing a gas pressure in a selected passage by an internal component configured to heat a gas to generate a gas pressure;
(ii) determining, utilizing at least one internal component, the presence or absence of a micro-droplet at a selected position;
(iii) after determining the presence or absence of the microdroplet, determining reaction products of one or more components of the microdroplet, if the microdroplet was determined to be present; and
(b) generating control signals, which are provided to the MF device, wherein the control signals are generated in a pattern and sequence that is responsive to each micro-droplet processing request so that the internal components of the MF device that are responsive to the control signals function together to perform the requested micro-droplet processing in the MF device.
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Accused Products
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.
364 Citations
40 Claims
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1. A method for controlling the operation of a digital-type microfluidic (“
- MF”
) device (i) wherein an ME device comprises one or more passages for confining one or more micro-droplets, the passages having one or more stable positions for the micro-droplets, and (ii) comprises one or more internal components responsive to control signals, the internal components operatively associated with the passages for control and monitoring the MF device, the method comprising;(a) providing one or more micro-droplet processing requests, wherein a micro-droplet processing request specifies performing at least one action on at least one micro-droplet, each provided micro-droplet processing request comprising two or more actuator processing requests, each specifying performing at least one action associated with at least one passage of the ME device, the micro-droplet processing requests comprising at least one of; (i) creating one or more new micro-droplets at selected stable positions, or (ii) moving one or more micro-droplets from current stable positions to selected next stable positions, or (iii) combining two or more micro-droplets into one or more new micro-droplets at selected stable positions, or (iv) mixing one or more micro-droplets the actuator processing requests comprising; (i) providing a gas pressure in a selected passage by an internal component configured to heat a gas to generate a gas pressure; (ii) determining, utilizing at least one internal component, the presence or absence of a micro-droplet at a selected position; (iii) after determining the presence or absence of the microdroplet, determining reaction products of one or more components of the microdroplet, if the microdroplet was determined to be present; and (b) generating control signals, which are provided to the MF device, wherein the control signals are generated in a pattern and sequence that is responsive to each micro-droplet processing request so that the internal components of the MF device that are responsive to the control signals function together to perform the requested micro-droplet processing in the MF device. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 38)
- MF”
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25. A method for controlling the operation of a digital-type microfluidic (“
- MF”
) device (i) wherein an MF device comprises one or more passages for confining one or more micro-droplets, the passages having one or more stable positions for the micro-droplets, and (ii) comprises one or more internal components responsive to control signals, the internal components operatively associated with the passages for control and monitoring the MF device, the method comprising;(a) providing one or more micro-droplet processing requests, wherein a micro-droplet processing request specifies performing at least one action on at least one micro-droplet, the requests comprising either (i) creating one or more new micro-droplets at selected stable positions, or (ii) moving one or more micro-droplets from current stable positions to selected next stable positions, or (iii) combining two or more micro-droplets into one or more new micro-droplets at selected stable positions, or (iv) mixing one or more micro-droplets, wherein each provided micro-droplet processing request further comprises one or more actuator processing requests, wherein an actuator processing request specifies performing at least one action physically associated with at least one passage of the MF device, and wherein the actuator processing requests comprise, (i) opening or closing a selected controlled passage by internal components acting as a controllable valve by melting at least one aliquot of a meltable material, wherein the aliquot of the material is positionable for occluding the controlled passage, (ii) providing controllable gas pressure in a selected passage by internal components acting as pressure generator by heating at least one gas micro reservoir communicating with the passage (iii) sensing the presence or absence of a micro-droplet at a selected position in a selected passage by internal components acting as a micro-droplet presence sensor by sensing an indicator of the thermal capacity in a region about the position, and (iv) after sensing the presence of the microdroplet at the selected position, sensing the composition of the micro-droplet at the selected position in the selected passage by internal components acting as a micro-droplet presence sensor by sending optical signals to the MF device and receiving optical signals returned from the MF device, and (b) generating control signals, which are provided to the MF device, wherein the control signals are generated in a pattern and sequence that is responsive to each micro-droplet processing request so that the internal components of the MF device that are responsive to the control signals function together to perform the requested micro-droplet processing in the MF device, wherein the generated pattern and sequence of control signals that is responsive to a micro-droplet processing request further comprises sub-patterns and sub-sequences that are responsive to each actuator processing request of the micro-droplet processing request, and wherein the sub-pattern and sub-sequence of control signals that is responsive to each actuator processing request cause the responsive internal components of the MF device to function together to perform the requested action. - View Dependent Claims (39)
- MF”
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26. A method for controlling the operation of a digital-type microfluidic (“
- MF”
) device (i) wherein an MF device comprises one or more passages for confining one or more micro-droplets, the passages having one or more stable positions for the micro-droplets, and (ii) comprises one or more internal components responsive to control signals, the internal components operatively associated with the passages for control and monitoring the MF device, the method comprising;(a) providing one or more micro-droplet processing requests, wherein a micro-droplet processing request specifies performing at least one action on at least one micro-droplet, the requests comprising either (i) creating one or more new micro-droplets at selected stable positions by separating the new micro-droplet from an existing micro-droplet or a fluid source in a metered fashion, or (ii) moving one or more micro-droplets from current stable positions to selected next stable positions by applying a gas pressure on the micro-droplet active to move the micro-droplet from the current stable position to the next selected stable position, or (iii) combining two or more micro-droplets into one or more new micro-droplets at selected stable positions by moving the micro-droplets into adjacency at the selected stable position, or (iv) mixing one or more micro-droplets by generating control signals for moving the micro-droplet with sufficient speed to result in laminar mixing, wherein each provided micro-droplet processing request further comprises one or more actuator processing requests, wherein an actuator processing request specifies performing at least one action physically associated with at least one passage of the MF device, and wherein the actuator processing requests comprise, (i) providing controllable gas pressure in a selected passage by at least one internal component configured to heat a gas to generate a gas pressure, and (ii) sensing, utilizing at least one internal component, the presence or absence of a micro-droplet at a first selected position in a selected passage and then determining the presence of a reaction product of at least one component of the microdroplet at a second, different position of the microfluidic device if the microdroplet was sensed at the first selected position, and (b) generating control signals, which are provided to the MF device, wherein the control signals are generated in a pattern and sequence that is responsive to each micro-droplet processing request so that the internal components of the MF device that are responsive to the control signals function together to perform the requested micro-droplet processing in the MF device, wherein the generated pattern and sequence of control signals that is responsive to a micro-droplet processing request further comprises sub-patterns and sub-sequences that are responsive to each actuator processing request of the micro-droplet processing request, and wherein the sub-pattern and sub-sequence of control signals that is responsive to each actuator processing request cause the responsive internal components of the MF device to function together to perform the requested action. - View Dependent Claims (40)
- MF”
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27. A method for performing a chemical reaction in a digital-type microfluidic (“
- MF”
) device (i) wherein an MF device comprises one or more passages for confining one or more micro-droplets, the passages having one or more stable positions for the micro-droplets, and (ii) comprises one or more internal components responsive to control signals, the internal components operatively associated with the passages for control and monitoring the MF device, the method comprising;(a) providing one or more fluid reagents, wherein the fluid reagents comprise the reactants necessary for the reaction, (b) creating at least one final micro-droplet from the fluid reagents by providing control signals to the MF device, wherein the micro-droplet is positioned at a stable position and comprises the reactants necessary for the reaction, (c) determining, utilizing at least one internal component, a presence or absence of the at least one final micro-droplet, (d) moving the at least one final micro-droplet by heating a gas to generate a gas pressure within the MF device, and (e) after the steps of determining, utilizing the at least one internal components the presence or absence of the at least one final microdroplet and moving the at least one final micro-droplet, reacting the at least one micro-droplets. - View Dependent Claims (28, 29, 30, 31, 32, 33, 34, 35, 36)
- MF”
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37. A method for performing a chemical reaction in a digital-type microfluidic (“
- MF”
) device (i) wherein an MF device comprises one or more passages for confining one or more micro-droplets, the passages having one or more stable positions for the micro-droplets, and (ii) comprises one or more internal components responsive to control signals, the internal components operatively associated with the passages for control and monitoring the MF device, the method comprising;(a) providing one or more fluid reagents, wherein the fluid reagents comprise the reactants necessary for the reaction, (b) providing a micro-droplet processing program, wherein a micro-droplet processing program comprises one or more micro-droplet processing requests, wherein a micro-droplet processing request specifies performing at least one action on at least one micro-droplet, and the requests comprising either (i) creating one or more new micro-droplets at selected stable positions by heating a gas to generate a gas pressure within the MF device, or (ii) moving one or more micro-droplets from current stable positions to selected next stable positions by heating a gas to generate a gas pressure within the MF device, or (iii) combining two or more micro-droplets into one or more new micro-droplets at selected stable positions by heating a gas to generate a gas pressure within the MF device, or (iv) mixing one or more micro-droplets by heating a gas to generate a gas pressure within the MF device, wherein the micro-droplet processing program provides for the creation of at least one final micro-droplet from the fluid reagents by providing control signals to the MF device, and wherein the micro-droplet is positioned at a stable position and comprises the reactants necessary for the reaction, (c) determining, utilizing at least one internal component, the presence or absence of a micro-droplet within a region of the MF device, (d) selecting an indicated micro-droplet processing request from the provided processing program, (e) generating control signals for the selected micro-droplet processing request, which are provided to the MF device, wherein the control signals are generated in a pattern and sequence that is responsive to each micro-droplet processing request so that the internal components of the MF device that are responsive to the control signals function together to perform the requested micro-droplet processing in the MF device, (f) repeating the steps of providing a request and generating signals with each micro-droplet processing request until the provided program indicates that no further requests are available for selection, and g) reacting the micro-droplet by waiting for a time sufficient for occurrence of the reaction or by exciting the final micro-droplet by providing control signals to the MF device, wherein the excitation is sufficient to cause occurrence of the reaction and where the reacting step is performed after the determining, utilizing the at least one internal component, the presence of the micro-droplet within a region of the ME device.
- MF”
Specification