# US 11,986,299 B2 · Diagnostic system > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,986,299 B2 - Document ID: US11986299B2 - Status: Granted - Kind: B2 - Application number: 17/087,479 - Filed: 2020-11-02 - Published: 2021-08-19 - Granted: 2024-05-21 - Earliest claimed: 2019-08-15 - Assignees: Talis Biomedical Corporation - Applicants: Talis Biomedical Corporation - Inventors: Sayeed Andeshmand; Thomas H. Cauley, III; John Dixon; David Glade; Hédia Maamar; Michael John McAdams; Dzam-Si Jesse Ng; David Alexander Rolfe - Web page: https://patentgrep.com/patent/US11986299B2 ## CPC - A61B 5/150961: {Means for the detection of the presence or absence of a module, a component or an abnormal condition; detection of leaks} - B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces} - A61B 5/150755: {Blood sample preparation for further analysis, e.g. by separating blood components or by mixing} - B01L 3/502761: {specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules} - C12Q 1/689: for bacteria - A61B 5/150221: {Valves} - B01L 2200/04: Exchange or ejection of cartridges, containers or reservoirs - B01L 2200/0605: Metering of fluids - B01L 2200/10: Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept - B01L 2200/16: Reagents, handling or storing thereof - B01L 2300/021: Identification, e.g. bar codes - B01L 2300/047: Additional chamber, reservoir - B01L 2300/0681: Filter - B01L 2300/0809: rectangular shaped - B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions - B01L 2300/0864: comprising only one inlet and multiple receiving wells, e.g. for separation, splitting - B01L 2400/043: magnetic forces - B01L 2400/0457: passive flow or gravitation - B01L 2400/0644: rotary valves - C12Q 1/6844: Nucleic acid amplification reactions - C12Q 1/6888: for detection or identification of organisms - G01N 35/00029: {provided with flat sample substrates, e.g. slides (G01N35/028 takes precedence)} - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE - 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 - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract Methods and systems are provided for point-of-care nucleic acid amplification and detection. One embodiment of the point-of-care molecular diagnostic system includes a cartridge and an instrument. The cartridge can accept a biological sample, such as a urine or blood sample. The cartridge, which can comprise one or more of a loading module, lysis module, purification module and amplification module, is inserted into the instrument which acts upon the cartridge to facilitate various sample processing steps that occur in order to perform a molecular diagnostic test. ## Claims ### Claim 1 An integrated diagnostic cartridge, comprising: a loading module; a lysis module; a purification module comprising a rotary valve comprising: a. a stator comprising a stator face and a plurality of passages, each passage comprising a port at the stator face; b. a rotor operably connected to the stator and comprising a rotational axis, a rotor valving face, and a flow channel having an inlet and an outlet at the rotor valving face; c. a retention element biasing the stator and the rotor together at a rotor-stator interface to form a fluid tight seal; d. a gasket interposed between the stator face and the rotor valving face having a pair of openings in fluidic communication with the flow channel inlet and the flow channel outlet; a reaction module, wherein the loading module is in fluidic communication with the lysis module and the purification module is in fluidic communication with the reaction module; and the rotary valve further comprising a storage configuration and an operational configuration wherein in the operational configuration the gasket forms a fluid tight seal between the stator face and the rotor valving face. ### Claim 2 (depends on 1) The integrated diagnostic cartridge of claim 1 wherein the loading module, the lysis module, the purification module and the reaction module are arranged for use while the cartridge is in a vertical orientation. ### Claim 3 (depends on 1) The integrated diagnostic cartridge of claim 1 wherein the flow channel comprises a porous solid support. ### Claim 4 (depends on 1) The integrated diagnostic cartridge of claim 1 wherein the flow channel is not concentric with a rotational axis of the rotary valve. ### Claim 5 (depends on 1) The integrated diagnostic cartridge of claim 1 the lysis module further comprising a lysis chamber wherein the operational configuration further comprises a zero valving position permitting a dead end fill of the lysis chamber with a sample within the loading module, the sample suspected of containing one or more target pathogens. ### Claim 6 (depends on 1) The integrated diagnostic cartridge of claim 1 the flow channel further comprising a porous solid support, wherein the operational configuration further comprises a first valving position providing fluidic communication between the loading module, the lysis module and the flow channel inlet. ### Claim 7 (depends on 6) The integrated diagnostic cartridge of claim 6 further comprising a filter assembly having an inlet and an outlet, wherein in the first valving position the filter assembly inlet is in fluidic communication with the lysis module and the filter assembly outlet is in fluidic communication with the flow channel inlet. ### Claim 8 (depends on 1) The integrated diagnostic cartridge of claim 1 the flow channel further comprising a porous solid support and the purification module further comprising a wash buffer reservoir and a waste collection element wherein the operational configuration further comprises a second valving position providing fluidic communication between the wash buffer reservoir, the flow channel comprising the porous solid support and the waste collection element. ### Claim 9 (depends on 1) The integrated diagnostic cartridge of claim 1, wherein rotation between the rotor and the stator transitions the rotor into an operational configuration with the rotor, the stator and the gasket held in a fluid-tight manner by the retention element. ### Claim 10 (depends on 1) The integrated diagnostic cartridge of claim 1, the purification module further comprising: a waste collection element, a wash buffer reservoir and an elution buffer reservoir. ### Claim 11 (depends on 1) The integrated diagnostic cartridge of claim 1 further comprising a pneumatic interface in fluidic communication with at least the purification module. ### Claim 12 (depends on 11) The integrated diagnostic cartridge of claim 11 wherein the pneumatic interface is in fluidic communication with the lysis module. ### Claim 13 A method of operating a rotary valve of an integrated testing cartridge for processing a sample suspected of containing one or more target pathogens, comprising: transitioning the rotary valve from a storage configuration into an operational configuration; indexing the rotary valve into a zero valving position for dead end filling a lysis chamber within a lysis module of the integrated testing cartridge with the sample suspected of containing one or more target pathogens; mixing the sample with at least one lysis reagent within the lysis chamber to generate a lysed sample without moving the rotary valve from the zero valving position; indexing the rotary valve to a first valving position to provide fluidic communication between the lysis chamber, a porous solid support within the rotary valve and a waste collection element within the cartridge; and passing the lysed sample through the porous solid support to capture a nucleic acid on the porous solid support. ### Claim 14 (depends on 13) The method of operating the rotary valve according to claim 13 further comprising: indexing the rotary valve to a second valving position to provide fluidic communication for flowing a wash buffer from a wash buffer reservoir within the cartridge through the porous solid support and into the waste collection element. ### Claim 15 (depends on 14) The method of operating the rotary valve according to claim 14 further comprising: indexing the rotary valve to a third valving position for removing residual volatile components of the wash buffer from the porous solid support. ### Claim 16 (depends on 15) The method of operating the rotary valve according to claim 15 further comprising: indexing the rotary valve to a fourth valving position to provide fluidic communication between an elution buffer reservoir within the cartridge, the porous solid support and a rehydration chamber within the cartridge; and flowing an elution buffer through the porous solid support to generate an enriched nucleic acid solution. ### Claim 17 (depends on 16) The method of operating the rotary valve according to claim 16 further comprising flowing the enriched nucleic acid solution into the rehydration chamber. ### Claim 18 (depends on 13) The method of operating the rotary valve according to claim 13 the rotary valve further comprising a rotor and a stator, wherein the transitioning step is performed by rotation between the rotor and the stator. ### Claim 19 (depends on 18) The method of operating the rotary valve according to claim 18 further comprising: forming a fluid tight seal between the rotor and the stator after the transitioning step using a retention element within the rotary valve. ### Claim 20 (depends on 18) The method of operating the rotary valve according to claim 18 the rotary valve further comprising a gasket between the rotor and the stator, further comprising: forming a fluid tight seal between the rotor, the stator and the gasket after the transitioning step using a retention element within the rotary valve. ### Claim 21 (depends on 13) The method of operating the rotary valve according to claim 13 further comprising: Positioning the integrated testing cartridge in a vertical orientation prior to performing the transitioning step.