# US 10,767,225 B2 · Valved cartridge and system > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,767,225 B2 - Document ID: US10767225B2 - Status: Granted - Kind: B2 - Application number: 16/264,389 - Filed: 2019-01-31 - Published: 2019-08-01 - Granted: 2020-09-08 - Earliest claimed: 2015-06-19 - Assignees: IntegenX Inc. - Applicants: IntegenX, Inc. - Inventors: Philip Justus Wunderle; Chungsoo Charles Park; David King; Dennis Lehto - Web page: https://patentgrep.com/patent/US10767225B2 ## CPC - C12Q 1/6874: involving nucleic acid arrays, e.g. sequencing by hybridisation - B01L 3/502738: {characterised by integrated valves (throttle valves in microfluidic sample containers B01L3/502746)} - C12Q 1/686: Polymerase chain reaction [PCR] - F16K 99/0015: {Diaphragm or membrane valves} - F16K 99/0034: {Operating means specially adapted for microvalves} - B01F 33/30: Micromixers - B01F 33/40: Mixers using gas or liquid agitation, e.g. with air supply tubes - B01L 3/502753: {characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation} - B01L 7/52: {with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples} - B01L 2200/04: Exchange or ejection of cartridges, containers or reservoirs - B01L 2200/0668: Trapping microscopic beads - B01L 2200/16: Reagents, handling or storing thereof - B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions - B01L 2300/0887: Laminated structure - B01L 2300/123: Flexible; Elastomeric - B01L 2400/043: magnetic forces - B01L 2400/0478: pistons - B01L 2400/0655: pinch valves - F16K 2099/0078: {using moulding or stamping} - F16K 2099/0084: {Chemistry or biology, e.g. "lab-on-a-chip" technology} - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE - 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)} - B01F: MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING (mixing paints B44D3/06) ## Abstract This disclosure provides, among other things, a cartridge comprising: (a) a cartridge body comprising a malleable material and having, disposed on a surface of the body, at least one valve body comprising a valve inlet and a valve outlet, each fluidically connected to a fluidic channel; and (b) a layer comprising a deformable material bonded to a surface of the cartridge body and sealing the at least one valve body at points of attachment, thereby forming at least one valve; wherein the at least one valve body is depressed in the cartridge body relative to the points of attachment and wherein the deformable material covering the at least one valve body retains sufficient elasticity after deformation such that in a ground state the valve is open. Also disclosed is an instrument comprising a cartridge interface and a cartridge as described herein engaged with the cartridge interface, wherein (II) the cartridge interface comprises: (A) at least one mechanical actuator, each mechanical actuator positioned to actuate a valve; and (B) at least one motor operatively coupled to actuate a mechanical actuator toward or away from a valve. ## Claims ### Claim 1 An instrument comprising a cartridge interface and a cartridge engaged with the cartridge interface, wherein: (I) the cartridge comprises: (a) a cartridge body comprising a malleable material and having, disposed on a surface of the body, at least one valve body comprising a valve inlet and a valve outlet, each fluidically connected to a fluidic channel, the at least one valve body comprising a groove, the groove comprising a wall including an upper part and a floor, wherein the wall is curved or sloped in a direction that is non-normal to a plane defined by the surface of the body; and (b) a layer comprising a deformable material attached to a surface of the cartridge body and sealing the at least one valve body at points of attachment, thereby forming at least one valve, wherein the at least one valve body is depressed in the cartridge body relative to the points of attachment, wherein the deformable material retains sufficient elasticity after deformation such that in a ground state the valve is open, and wherein, while the valve is open, the layer is in contact with the upper part, but is not in contact with the floor; and (II) the cartridge interface comprises: (A) at least one mechanical actuator, each mechanical actuator positioned to actuate a valve; and (B) at least one motor operatively coupled to actuate a mechanical actuator toward or away from a valve. ### Claim 2 (depends on 1) The instrument of claim 1, wherein the cartridge comprises at least one fluidic circuit, wherein the at least one fluidic circuit comprises, as elements, at least one valve, at least one fluid inlet, at least one fluid outlet and at least one compartment, which elements are fluidically connected through fluidic channels. ### Claim 3 (depends on 1) The instrument of claim 1, wherein the cartridge interface comprises a first port engaged with a fluid inlet and a second port engaged with a fluid outlet, and further comprises a pressure source configured to apply pressure through either port to the fluidic circuit. ### Claim 4 (depends on 1) A method of controlling fluid flow in a fluid channel of fluidic cartridge comprising: (A) providing an instrument of claim 1, wherein at least one of the fluidic channels comprises a liquid; (B) closing a valve by actuating a mechanical actuator against the valve to force the deformable layer against walls of the valve body; and (C) releasing the valve by retracting the mechanical actuator away from the valve body. ### Claim 5 (depends on 4) The method of claim 4, further comprising moving the liquid through the valve by applying pressure to liquid in a fluidic channel. ### Claim 6 (depends on 1) The instrument of claim 1, further comprising a ram adapted to apply mechanical pressure on the deformable material in the direction of the cartridge body and at the at least one valve body to close the at least one valve. ### Claim 7 (depends on 6) The instrument of claim 6, wherein one or more of: (i) the ram has a tip having a shape that conforms substantially to the shape of the at least one valve body offset for the thickness of the deformable material; (ii) the at least one valve body has a cross-sectional shape that exerts a centering action on the ram toward a center of the at least one valve body as the ram applies pressure on the deformable material in the direction of the cartridge body and at the at least one valve body; (iii) the ram comprises a flexible material; (iv) the ram is mounted on a pivot or a rocker arm; or (v) the ram comprises a rotatable wheel mounted at an end of the ram, and wherein the valve body has a cross-sectional shape that conforms substantially to the wheel offset by the thickness of the deformable material. ### Claim 8 (depends on 6) The instrument of claim 6, wherein the ram is configured to translate laterally with respect to the surface of the cartridge body. ### Claim 9 (depends on 1) The instrument of claim 1 further comprising a ram assembly comprising: a ram adapted to apply mechanical pressure on the deformable material in the direction of the cartridge body and at the at least one valve body to close the at least one valve; and a centering arm configured for coarse centering of the ram. ### Claim 10 (depends on 1) The instrument of claim 1, wherein while the valve is open, the layer is bonded to the upper part, but is not bonded to the floor. ### Claim 11 (depends on 1) The instrument of claim 1, wherein the layer is bonded to the surface of the cartridge body. ### Claim 12 (depends on 1) The instrument of claim 1, further comprising a relief adapted to accept a centering arm for guiding a ram head. ### Claim 13 (depends on 1) The instrument of claim 1, wherein the valve body has a depth, from its bottom to the height of the top of a ridge (if present) or a plane generally defined by the cartridge body surface of between 50 microns and 200 microns, e.g., about 100 microns. ### Claim 14 (depends on 1) The instrument of claim 1, wherein the valve body has an aspect ratio of depth-to-width greater than 1. ### Claim 15 (depends on 1) The instrument of claim 1, wherein the aspect ratio (width:depth) of the valve body is between about 1:1.5 and 1:0.1, e.g., 1:1.2 to 1:0.7. ### Claim 16 (depends on 1) The instrument of claim 1, wherein the body further comprises a reagent compartment comprising a reagent. ### Claim 17 (depends on 16) The instrument of claim 16, wherein the reagent is selected from the group consisting of nucleic acid primers, nucleotides, and a DNA polymerase sufficient to perform PCR. ### Claim 18 (depends on 16) The instrument of claim 16, wherein the compartment comprises an openable seal that, when opened, puts the compartment in fluidic communication through a via with a fluidic channel on the surface. ### Claim 19 (depends on 18) The instrument of claim 18, wherein the valve body is wider than the fluidic channel. ### Claim 20 (depends on 1) The instrument of claim 1, wherein the deformable layer retains sufficient elasticity to resist valve closure when negative pressure (e.g., suction) up to about 10 psi is exerted on a fluidic channel communicating with the valve.