# US 8,465,706 B2 · On-demand microfluidic droplet or bubble generation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,465,706 B2 - Document ID: US8465706B2 - Status: Granted - Kind: B2 - Application number: 12/642,434 - Filed: 2009-12-18 - Published: 2010-07-01 - Granted: 2013-06-18 - Earliest claimed: 2007-06-20 - Assignees: The Trustees of Columbia University in the City of New York - Applicants: Daniel Attinger; Jie Xu - Inventors: Daniel Attinger; Jie Xu - Web page: https://patentgrep.com/patent/US8465706B2 ## CPC - F16K 99/0001: {Microvalves (microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006)} - B01L 3/502707: {characterised by the manufacture of the container or its components} - B01L 3/502784: {specially adapted for droplet or plug flow, e.g. digital microfluidics} - C07K 1/14: Extraction; Separation; Purification - F16K 99/0019: {Valves using a microdroplet or microbubble as the valve member} - F16K 99/0026: {Valves using channel deformation} - B01L 3/0268: {using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries} - B01L 2200/0647: Handling flowable solids, e.g. microscopic beads, cells, particles - B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions - F16K 2099/0084: {Chemistry or biology, e.g. "lab-on-a-chip" technology} - Y10T 137/0324: With control of flow by a condition or characteristic of a fluid - Y10T 436/11: Automated chemical analysis - Y10T 436/2575: Volumetric liquid transfer - F16K: VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING {(devices for emptying and evacuating the excess liquid in valves or conduits F16L55/07)} - B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION ## Abstract Microfluidic systems and methods can dispense single or multiple fluid particles (such as a gas or other fluid bubble) or an encapsulated particle (e.g., a bead or biological cell) into a microchannel. ## Claims ### Claim 1 An apparatus comprising: a microfluidic chip including a microchannel that includes a microchannel inlet and a microchannel outlet and a first reagent chamber that includes a first chamber inlet, a first reagent chamber outlet configured to provide fluid communication between the first reagent chamber and the microchannel, and a first compliant wall, wherein the first chamber inlet is separated from the first chamber outlet and the microchannel by a portion of the first reagent chamber that includes the first compliant wall; a first actuator coupled to the first compliant wall of the first reagent chamber and configured to actuate a volume change of the first reagent chamber in response to a first control signal; and a controller configured to apply the first control signal to the first actuator to perform the actuating of the first compliant wall of the first reagent chamber to controllably and individually dispense a first fluid particle on-demand from the first reagent chamber into an immiscible fluid in the microchannel. ### Claim 2 (depends on 1) The apparatus of claim 1, wherein the controller is configured to provide an actuation control signal having a timing accuracy on the order of nanoseconds. ### Claim 3 (depends on 1) The apparatus of claim 1, wherein the controller is configured to apply the first control signal to dispense particles on-demand at a repetition rate in excess of a value that is on the order of kiloHertz. ### Claim 4 (depends on 1) The apparatus of claim 1, wherein the first fluid particle has a volume that is between about 25 pL and about 4.5 nL. ### Claim 5 (depends on 1) The apparatus of claim 1, wherein the first chamber outlet includes a first nozzle having a first nozzle width that is in a range between about 25 μm and about 100 μm. ### Claim 6 (depends on 1) The apparatus of claim 1, wherein the first compliant wall includes a PDMS membrane and the first reagent chamber further includes compliant PDMS sidewalls supported on a rigid substrate. ### Claim 7 (depends on 1) The apparatus of claim 1, comprising: a second reagent chamber that includes a second chamber inlet, a second chamber outlet located within a particle dispensing range of the first chamber outlet and configured to provide fluid communication between the second chamber and the microchannel, and a second compliant wall; a second actuator coupled to the second compliant wall of the second reagent chamber and configured to actuate a volume change of the second reagent chamber in response to a second control signal; and wherein the controller is configured to apply the second control signal to the second actuator, independently from the first control signal applied to the first actuator, to perform the actuating to controllably and individually dispense a second fluid particle on-demand from the second reagent chamber into the immiscible fluid in the microchannel. ### Claim 8 (depends on 7) The apparatus of claim 7, wherein the first reagent chamber is configured to carry a gaseous substance, the second reagent chamber is configured to carry a liquid or other substantially non-gaseous fluid substance, and wherein the controller is configured to operate at least one of the first and second actuators to expel a gas bubble into the microchannel. ### Claim 9 (depends on 8) The apparatus of claim 8, wherein the controller is configured to operate the second actuator for expanding the second reagent chamber to draw gas from the first reagent chamber, and wherein the controller is configured to expel the gas bubble by providing the second control signal for actuating a compressing of the second reagent chamber. ### Claim 10 (depends on 7) The apparatus of claim 7, wherein the first and second chamber outlets are located across and opposite the microchannel from each other. ### Claim 11 (depends on 7) The apparatus of claim 7, wherein the first compliant wall is an overlying membrane that is affixed to a top surface of the microfluidic chip and configured to seal the microfluidic chip. ### Claim 12 (depends on 11) The apparatus of claim 11, wherein a portion of the overlying membrane is positioned over the microchannel. ### Claim 13 (depends on 1) The apparatus of claim 1, wherein the first reagent outlet tapers to the first reagent outlet. ### Claim 14 An apparatus comprising: a microfluidic chip including a microchannel that includes a microchannel inlet a microchannel outlet, and an immiscible fluid; a first reagent chamber that includes a first fluid, a first chamber inlet, a first chamber outlet providing fluid communication between the first reagent chamber and the microchannel, a first fluid; and a compliant membrane affixed to a top surface of the microfluidic chip forming a first compliant wall of the first reagent chamber; a first actuator coupled to the first compliant wall of the first reagent chamber and configured to actuate a volume change of the first reagent chamber in response to a first control signal; and a controller configured to apply the first control signal to the first actuator to perform the actuating to controllably and individually dispense a first fluid particle on-demand from the first reagent chamber into the immiscible fluid in the microchannel.