# US 11,008,627 B2 · Diagnostic system

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- Number: US 11,008,627 B2
- Document ID: US11008627B2
- Status: Granted
- Kind: B2
- Application number: 16/655,028
- Filed: 2019-10-16
- Published: 2021-02-18
- Granted: 2021-05-18
- 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/US11008627B2

## 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

A method of testing a sample suspected of containing one or more target pathogens, comprising:
accepting a cartridge having a sample port assembly containing the sample suspected of containing the one or more target pathogens;
advancing the sample suspected of containing the one or more target pathogens to a lysis chamber within the cartridge having at least one lysis reagent therein;
mixing the sample with the at least one lysis agent to generate a lysed sample;
passing the lysed sample through a first porous solid support within the cartridge to capture a nucleic acid on the porous solid support;
releasing the captured nucleic acid from the first porous solid support to generate an enriched nucleic acid;
introducing the enriched nucleic acid into a rehydration chamber within the cartridge containing one or more dried reagents;
after introducing the enriched nucleic acid into a metering channel, mixing the contents of the rehydration chamber to produce an analyte/reagent solution;
distributing the analyte/reagent solution to two or more assay chambers within the cartridge;
combining the analyte/reagent solution with one or more amplification reagents after performing the distributing step;
sealing each one of the two or more assay chambers within the cartridge containing analyte/reagent solution from each one of all the other two or more assay chambers within the cartridge containing analyte/reagent solution and a waste chamber; and
performing an isothermal amplification reaction within each one of the two or more assay chambers in the cartridge while simultaneously detecting amplification product, wherein presence of an amplification product is an indication of a presence, an absence or a quantity of the one or more target pathogens in the sample suspected of containing the one or more target pathogens.

### Claim 2 (depends on 1)

The method of testing a sample according to claim 1, wherein in mixing the sample with the at least one lysis agent, the lysis agent is a mechanical agent.

### Claim 3 (depends on 2)

The method of testing a sample according to claim 2, wherein the mechanical agent is ceramic beads, glass beads or steel beads, and the mixing the sample step comprises rotating a stir bar within the lysis chamber at at least 1000 rpm.

### Claim 4 (depends on 3)

The method of testing a sample according to claim 3, wherein mixing the sample comprises rotating the stir bar or the ceramic, glass or steel beads along with a chemical lysis agent.

### Claim 5 (depends on 1)

The method of testing according to claim 1, wherein the at least one lysis agent is a chemical lysis agent.

### Claim 6 (depends on 5)

The method of testing a sample according to claim 5, wherein the one or more target pathogens is a virus or a gram-negative bacterium and the lysis reagent is a chaotropic agent.

### Claim 7 (depends on 1)

The method of testing a sample according to claim 1, wherein prior to passing the lysed sample through the porous solid support, the method further comprises passing the lysed sample through a size-exclusion filter, wherein nucleic acid passes through the filter.

### Claim 8 (depends on 1)

The method of testing a sample according to claim 1, wherein reagents comprises a primer set specific to one of the one or more target pathogens.

### Claim 9 (depends on 1)

The method of testing a sample according to claim 1, wherein a first assay chamber contains a primer set specific to a first nucleic acid sequence.

### Claim 10 (depends on 9)

The method of testing a sample according to claim 9, wherein the first nucleic acid sequence is present in one of the one or more target pathogens.

### Claim 11 (depends on 9)

The method of testing a sample according to claim 9, wherein prior to mixing the sample with at least one lysis agent, a process control is added to the sample and the first nucleic acid sequence is present in the process control.

### Claim 12 (depends on 9)

The method of testing a sample according to claim 9, wherein prior to passing lysed sample through the porous solid support, a process control is added to the lysed sample and the first nucleic acid sequence is present in the process control.

### Claim 13 (depends on 9)

The method of testing a sample according to claim 9, wherein a second assay chamber contains a primer set specific to a second nucleic acid sequence, wherein the second nucleic acid sequence is present in one of the one or more target pathogens.

### Claim 14 (depends on 1)

The method of testing a sample according to claim 1, wherein the performing an isothermal amplification reaction step is completed in less than 15 minutes.

### Claim 15 (depends on 1)

The method of testing a sample according to claim 1, further comprising: providing a result containing a determination made during the performing step relating to the presence, the absence or the quantity of the one or more target pathogens in the sample suspected of containing the one or more target pathogens.

### Claim 16 (depends on 1)

The method of testing a sample according to claim 1, wherein the method further comprises, prior to advancing the sample to a lysis chamber, pretreating the sample with a chemical reaction.

### Claim 17 (depends on 16)

The method of testing a sample according to claim 16, wherein the sample is sputum and the chemical reaction is incubation with a mucolytic agent.

### Claim 18 (depends on 1)

The method of testing a sample according to claim 1, wherein the method further comprises, prior to advancing the sample to a lysis chamber, pretreating the sample with an enzymatic reaction.

### Claim 19 (depends on 18)

The method of testing a sample according to claim 18, wherein the enzymatic reaction is incubation of the sample with a nuclease, a protease, an amylase, a glycosylase, or a lipase.

### Claim 20 (depends on 1)

The method of testing a sample according to claim 1, wherein the method further comprises, prior to advancing the sample to a lysis chamber, pretreating the sample with a physical treatment.

### Claim 21 (depends on 20)

The method of testing a sample according to claim 20, wherein the physical treatment comprises passing the sample through a size-exclusion filter in a first direction.

### Claim 22 (depends on 20)

The method of testing a sample according to claim 20, wherein the physical treatment comprises exposing the sample to a capture agent immobilized on a solid substrate.

### Claim 23 (depends on 22)

The method of testing a sample according to claim 22, further comprising, after exposure, separating the solid substrate from the sample.

### Claim 24 (depends on 22)

The method of testing a sample according to claim 22, wherein the capture agent is an antibody with affinity for red blood cells.

### Claim 25 (depends on 1)

The method of testing a sample according to claim 1, wherein the sample is sputum and the method further comprises, prior to mixing the sample with the at least one lysis reagent, bead beating the sputum to liquify the sample.

### Claim 26 (depends on 25)

The method of testing a sample according to claim 25, wherein the bead beating comprises mixing the sputum with ceramic, glass, or steel beads.

### Claim 27 (depends on 1)

The method of testing a sample according to claim 1, wherein prior to introducing the enriched nucleic acid into the rehydration chamber and distributing the analyte/reagent solution to two or more assay chambers, the method further comprises passing the enriched nucleic acid through a second porous solid support.