# US 2019/0168212 A1 · Methods and apparatus for controlling flow in a microfluidic arrangement, and a microfluidic arrangement > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0168212 A1 - Document ID: US20190168212A1 - Status: Published application - Kind: A1 - Application number: 16/326,134 - Filed: 2017-08-16 - Published: 2019-06-06 - Earliest claimed: 2016-08-18 - Assignees: Oxford University Innovation Limited - Applicants: Oxford University Innovation Limited - Inventors: Edmond WALSH; Alexander FEUERBORN; Peter Richard COOK - Web page: https://patentgrep.com/patent/US20190168212A1 ## CPC - B01L 3/502707: {characterised by the manufacture of the container or its components} - B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces} - B01L 3/50273: {characterised by the means or forces applied to move the fluids} - B01L 3/502784: {specially adapted for droplet or plug flow, e.g. digital microfluidics} - B01L 3/5088: {confining liquids at a location by surface tension, e.g. virtual wells on plates, wires (B01L3/50857 takes precedence)} - C12M 23/16: {Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093)} - C12M 29/14: {Pressurized fluid} - B01L 2200/0673: Handling of plugs of fluid surrounded by immiscible fluid - B01L 2200/0694: Creating chemical gradients in a fluid - B01L 2200/12: Specific details about manufacturing devices - B01L 2300/047: Additional chamber, reservoir - B01L 2300/06: Auxiliary integrated devices, integrated components - B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions - B01L 2300/0867: Multiple inlets and one sample wells, e.g. mixing, dilution - B01L 2300/089: Virtual walls for guiding liquids - B01L 2400/0463: Hydrodynamic forces, venturi nozzles - B01L 2400/0469: Buoyancy - B01L 2400/0475: specific mechanical means and fluid pressure - B01L 2400/0487: fluid pressure, pneumatics - B01L 2400/088: by specific surface properties - B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE - C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS} ## Abstract Methods and apparatus for controlling flow in a microfluidic arrangement are disclosed. In one arrangement, a microfluidic arrangement comprises a first liquid held predominantly by surface tension in a shape defining a microfluidic pattern on a surface of a substrate. The microfluidic pattern comprises at least an elongate conduit and a first reservoir. A second liquid is in direct contact with the first liquid and covers the microfluidic pattern. A flow of liquid is driven through the elongate conduit into the first reservoir. The microfluidic pattern and the depth and density of the second liquid are such that the first reservoir grows in volume during the flow of liquid into the first reservoir, without either of the size and shape of an area of contact between the first reservoir and the substrate changing, until an upper portion of the first reservoir detaches from a lower portion of the first reservoir due to buoyancy and rises upwards through the second liquid, thereby allowing the first reservoir to continue to receive liquid from the flow of liquid without any change in the size and shape of the area of contact between the first reservoir and the substrate. ## Claims ### Claim 1 A method of controlling flow in a microfluidic arrangement, wherein the microfluidic arrangement comprises: a first liquid held predominantly by surface tension in a shape defining a microfluidic pattern on a surface of a substrate, the microfluidic pattern comprising at least an elongate conduit and a first reservoir; and a second liquid in direct contact with the first liquid and covering the microfluidic pattern; the method comprises driving flow of liquid through the elongate conduit into the first reservoir; and the microfluidic pattern and the depth and density of the second liquid are such that the first reservoir grows in volume during the flow of liquid into the first reservoir, without either of the size and shape of an area of contact between the first reservoir and the substrate changing, until an upper portion of the first reservoir detaches from a lower portion of the first reservoir due to buoyancy and rises upwards through the second liquid, thereby allowing the first reservoir to continue to receive liquid from the flow of liquid without any change in the size and shape of the area of contact between the first reservoir and the substrate. ### Claim 2 (depends on 1) The method of claim 1, further comprising: providing a delivery member having an internal lumen leading to a distal opening through which liquid can be delivered, wherein: the driving of flow of liquid through the elongate conduit into the first reservoir is at least partially and/or intermittently performed by pumping liquid from outside of the microfluidic pattern into the microfluidic pattern via the distal opening. ### Claim 3 (depends on 2) The method of claim 2, wherein the liquid is pumped into the microfluidic pattern while the distal opening is held in a delivery position, the delivery position being below an upper interface of the second liquid. ### Claim 4 (depends on 3) The method of claim 3, wherein at least a selected portion of the outer surface of the delivery member proximate to the distal opening is configured such that a surface energy density is lower in respect of contact with the first liquid than in respect of contact with the second liquid. ### Claim 5 (depends on 3) The method of claim 3, wherein at least a selected portion of the outer surface of the delivery member proximate to the distal opening is configured such that a surface energy density is higher in respect of contact with the first liquid than in respect of contact with the second liquid. ### Claim 6 (depends on 3) The method of claim 3, wherein: the area of contact between the substrate and a portion of the first liquid that forms the elongate conduit defines a conduit footprint; the area of contact between the substrate and a portion of the first liquid that forms the first reservoir defines a first reservoir footprint; the size and shape of each of the conduit footprint and the first reservoir footprint are such that a maximum Laplace pressure supportable by the first liquid in the elongate conduit without any change in the conduit footprint is higher than a maximum Laplace pressure supportable by the first liquid in the first reservoir without any change in the first reservoir footprint; and the delivery position is such that the liquid pumped into the microfluidic pattern enters the microfluidic pattern via the elongate conduit. ### Claim 7 (depends on 6) The method of claim 6, wherein the conduit footprint and the first reservoir footprint are wholly on a substantially planar portion of the surface of the substrate. ### Claim 8 (depends on 6) The method of claim 6, wherein the driving of the flow of liquid into the first reservoir is performed without any change in the conduit footprint or the first reservoir footprint. ### Claim 9 (depends on 3) The method of claim 3, wherein the delivery position is such that the delivery member would not be in contact with the first liquid of the microfluidic pattern in the absence of any flow of liquid out of the distal opening, and wherein the liquid is pumped into the first liquid of the microfluidic pattern via a liquid bridge formed between the distal opening and the first liquid of the microfluidic pattern by a flow of liquid out of the distal opening. ### Claim 10 (depends on 9) The method of claim 9, wherein during a period of uninterrupted flow out of the distal opening a stable liquid bridge is maintained between the distal opening and the first liquid of the microfluidic pattern, thereby providing an uninterrupted flow of liquid into the microfluidic pattern. ### Claim 11 (depends on 9) The method of claim 9, wherein during a period of uninterrupted flow out of the distal opening an unstable liquid bridge is periodically formed in a cyclical process comprising growth of a globule of liquid at the distal opening, contact of the globule with the first liquid of the microfluidic pattern to establish the liquid bridge, and subsequent collapse of the liquid bridge, thereby providing a pulsatile flow, as a result of a pulsatile pressure generated by the cyclical process, of liquid into the microfluidic pattern. ### Claim 12 (depends on 1) The method of claim 1, wherein the microfluidic pattern further comprises a second reservoir, the second reservoir being integrally connected with the elongate conduit; and a difference in Laplace pressure between the second reservoir and the first reservoir at least partially drives the flow of liquid through the conduit into the first reservoir. ### Claim 13 (depends on 12) The method of claim 12, wherein: the flow of liquid through the elongate conduit into the first reservoir comprises a flow of liquid from the second reservoir to the first reservoir; and during the driving of the flow and while the first reservoir is growing: a Laplace pressure acting on the second reservoir is decreasing and a hydrostatic pressure acting on the second reservoir is increasing; and a hydrostatic pressure acting on the first reservoir is decreasing. ### Claim 14 (depends on 1) The method of claim 1, wherein the first liquid is in contact exclusively with a substantially planar portion of the surface of the substrate and the second liquid. ### Claim 15 (depends on 1) The method of claim 1, wherein the first liquid, second liquid and substrate are selected such that an advancing contact angle of the first liquid on the substrate is higher when the microfluidic pattern is overlaid with the second liquid than if the microfluidic pattern were overlaid with air. ### Claim 16 A microfluidic arrangement, comprising: a first liquid held predominantly by surface tension in a shape defining a microfluidic pattern on a surface of a substrate, the microfluidic pattern comprising at least an elongate conduit and a first reservoir; and a second liquid in direct contact with the first liquid and covering the microfluidic pattern, wherein: the microfluidic pattern and the depth and density of the second liquid are such that when a flow of liquid is driven through the elongate conduit into the first reservoir the first reservoir grows in volume, without either of the size and shape of an area of contact between the first reservoir and the substrate changing, until an upper portion of the first reservoir detaches from a lower portion of the first reservoir due to buoyancy and rises upwards through the second liquid, thereby allowing the first reservoir to continue to receive liquid from the flow of liquid without any change in the size and shape of the region of contact between the first reservoir and the substrate. ### Claim 17 An apparatus for driving flow in a microfluidic arrangement, comprising: a microfluidic arrangement comprising a first liquid held predominantly by surface tension in a shape defining a microfluidic pattern on a surface of a substrate, the microfluidic pattern comprising at least an elongate conduit and a first reservoir; and a second liquid in direct contact with the first liquid and covering the microfluidic pattern; and a pumping mechanism comprising a delivery member having an internal lumen leading to a distal opening through which liquid can be delivered; and a control system configured to control the pumping mechanism to drive flow of liquid through the elongate conduit into the first reservoir by pumping liquid from outside of the microfluidic pattern into the microfluidic pattern via the distal opening, wherein: the microfluidic pattern and the depth and density of the second liquid are such that the first reservoir grows in volume during the flow of liquid into the first reservoir, without either of the size and shape of an area of contact between the first reservoir and the substrate changing, until an upper portion of the first reservoir detaches from a lower portion of the first reservoir due to buoyancy and rises upwards through the second liquid, thereby allowing the first reservoir to continue to receive liquid from the flow of liquid without any change in the size and shape of the area of contact between the first reservoir and the substrate.