Liquid distribution system
First Claim
1. A liquid distribution system for selectively distributing liquid from two or more liquid sources to a plurality of cells, the system comprising, within a substrate:
- (a) the liquid sources;
(b) for each liquid source, a channel of capillary dimensions addressable by the liquid source, wherein the channel has at least one outlet to one outlet to one of said cells;
(c) for each outlet, a capillary barrier interposed between the liquid source and the outlet for inhibiting flow out of the outlet;
(d) a plurality of electrically operated micropumps, each for pumping liquid through at least one of the capillary barriers,wherein the pumps can be selectively operated such that liquid flows through a capillary barrier when a corresponding micropump is operated.
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Abstract
The present invention provides a liquid distribution system, which is useful in a number of contexts, including in accomplishing various synthetic, diagnostic and drug screening reactions. The distribution system can comprise an alpha reservoir and a beta reservoir, a first set of parallel and adjacent first and second feeder channels and a second set of parallel and adjacent third and fourth feeder channels which are offset from the first and second feeder channels, wherein (a) the first and third feeder channels are connected to the alpha reservoir via a first connector channel that is situated above or below the second and fourth feeder channels and are independent of the beta reservoir and (b) the second and fourth feeder channels are connected to the beta reservoir via a second connector channel that is situated above or below the first and third feeder channels and are independent of the alpha reservoir. The distribution system is preferably a microscale distribution system. Various particular mechanisms for controlling flow into a liquid distribution system are described.
600 Citations
59 Claims
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1. A liquid distribution system for selectively distributing liquid from two or more liquid sources to a plurality of cells, the system comprising, within a substrate:
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(a) the liquid sources; (b) for each liquid source, a channel of capillary dimensions addressable by the liquid source, wherein the channel has at least one outlet to one outlet to one of said cells; (c) for each outlet, a capillary barrier interposed between the liquid source and the outlet for inhibiting flow out of the outlet; (d) a plurality of electrically operated micropumps, each for pumping liquid through at least one of the capillary barriers, wherein the pumps can be selectively operated such that liquid flows through a capillary barrier when a corresponding micropump is operated. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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11. A liquid distribution system for selectively distributing liquid from two or more liquid sources to a plurality of cells, the system comprising:
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(a) liquid sources; (b) a substrate comprising a network of fluid channels of capillary dimensions for directing liquid from the liquid sources to a plurality of outlets for outputting liquid at the cells; (c) pumps that move liquid by means of electrodes for each outlet, wherein the electrodes are incorporated into the substrate, the pumps for selectively pumping liquid from a liquid source and out of the outlet; and (d) a receiving plate, on which the cells are located, that can be releasably positioned below the distribution plate, wherein the pumps can be selectively operated, and at least one said cell can receive liquid from either a first liquid source or a second liquid source depending on the operation of the pumps.
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12. A liquid distribution system for directing two or more liquids to each of two or more cells comprising:
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(a) a distribution substrate comprising sequentially, in order from top to bottom, a first plate, one or more intermediate plates and a second plate, at least one intermediate plate formed of material susceptible to microfabrication methods for forming channels of capillary dimensions on the surface of the plate, each plate having a top and bottom surface, wherein each pair of adjacent top and bottom surfaces are bonded together, and wherein the distribution substrate comprises; at least two first liquid sources, at least one first feeder channel segment of capillary dimensions connected to each of the first liquid sources, each first feeder channel segment formed along a first junction between two of the first, second or intermediate plates; and at least one distribution channel, of capillary dimensions and having an outlet at one or more of said cells, wherein the distribution channel is connected to each feeder channel and formed along a second junction, distinct from the first, of two of the first, second or intermediate plates, wherein filling each first source with a liquid results in filling connected first feeder channel segments and connected distribution channels, and wherein distribution channels connected to one first feeder channel segment avoid intersecting with other first feeder channel segments due to being formed along the second junction instead of along the first junction where the first feeder channel segments are formed. - View Dependent Claims (13, 14, 15, 16, 17, 18, 31, 32, 33)
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19. The liquid distribution system of claimed 13, further comprising:
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(b) electrically operated micropumps embedded in the distribution substrate for regulating the flow of liquid through channels; (c) a controller for controlling the micropumps so that liquids can be selectively directed to said cells, wherein the first plate comprises supply channels extending through the first plate to the first liquid sources and electrical leads extending through the first plate, wherein micropumps are located at each distribution channel and are connected to and operated by means of the controller by the electrical leads extending through the first plate. - View Dependent Claims (20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30)
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34. A liquid distribution system comprising an alpha liquid source, a beta liquid source and a system of channels of capillary dimensions having a plurality of outlets for delivering liquid to a plurality of cells, wherein the liquid sources and the system are formed within a substrate, the system comprising:
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(A) a first set of parallel and adjacent first and second capillary feeder channels; and (B) a second set of parallel and adjacent third and fourth capillary feeder channels which are offset from the first and second feeder channels, wherein each said feeder channel has a plurality of outlets, and wherein (a) the first and third feeder channels are connected to the alpha liquid source by a first capillary connector channel that is situated above or below the second and fourth feeder channels and are independent of the beta liquid source and (b) the second and fourth feeder channels are connected to the beta liquid source by a second capillary connector channel that is situated above or below the first and third feeder channels and are independent of the alpha liquid source, wherein upon filling the alpha liquid source with a liquid the first and second feeder channels are filled via the first connector channel and wherein upon filling the beta liquid source with a liquid the third and fourth feeder channels are filled via the second connector channel. - View Dependent Claims (35, 36, 37, 38, 39)
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- 40. A liquid distribution system for selectively distributing liquid from two or more liquid sources to a plurality of cells, the system comprising a cell, a channel of capillary dimensions connected to the cell and a pump situated in the channel comprising a first pair of electrodes and a second pair of electrodes, wherein one electrode can be shared between the two pairs, wherein the first pair has a spacing between the electrodes selected for pumping liquids of a low polarity and the second pair has a wider spacing selected for pumping liquids of relatively higher polarity, and wherein the first pair pumps tetrahydrofuran more effectively than the second pair, wherein the electrodes comprise electrical leads made of fused via ink and having an end that intersects the channel, wherein channel intersecting ends of the leads are plated with metal.
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46. A liquid distribution system for selectively distributing liquid from two or more liquid sources to a plurality of cells, the system comprising:
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within a substrate, one or more feeder channels of capillary dimensions each made up of a feeder channel inlet and a feeder channel outlet and, connected to each such feeder channel, a distribution channel, each feeder channel having a three-way junction connecting the feeder channel inlet, the feeder channel outlet and the connected distribution channel, the distribution channel connecting with a cell; within the substrate, for each such three-way junction, a first pump, which moves liquid by means of electrodes, located in the feeder channel inlet or in the feeder channel outlet; within the substrate, for each such three-way junction, a second electrode-based pump, which moves liquid by means of electrodes, located in the distribution channel; and a controller comprising circuitry for generating and selectively delivering voltages across two electrodes of each first pump and two electrodes of each second pump so that (a) fluid in one of the feeder channels can be moved from the feeder channel inlet to the feeder channel outlet of the feeder channel with a first amount of flow into the connected distribution channel or (b) a second amount of flow which is greater than the first amount proceeds via the connected distribution channel. - View Dependent Claims (47, 48, 49, 50)
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51. A liquid distribution system comprising:
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at least one cell, two or more feeder channels of capillary dimensions, a separate conduit for each feeder channel connecting that feeder channel to the cell, and a expansion valve for each conduit, the expansion valve comprising an expandable fluid enclosed within an expandable container, wherein the expansion valve has an expanded state that fills a cross-section of the conduit to prevent fluid flow through the conduit and a contracted state that does not fill a cross-section of the conduit so that flows through the conduit. - View Dependent Claims (52, 53, 54)
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55. A liquid distribution system comprising:
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one or more continuous flow channels of capillary dimensions, each having an upstream end and a downstream end, wherein the continuous flow channels have an open zone at the downstream end, for each continuous flow channel, a branch channel extending off of that continuous flow channel in the open zone, and for each continuous flow channel, an electronically operable alpha constrictor for constricting flow in the open zone located downstream of the branch channel inlet, wherein when a liquid flows through one of the continuous flow channels from the upstream to the downstream end a first ratio amount of fluid is diverted into the branch channel when the alpha constrictor is not operating and a second ratio amount, which is greater than the first ratio amount, flows into the branch channel when the alpha constrictor is in operation. - View Dependent Claims (56, 57, 58, 59)
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Specification