# US 11,028,432 B2 · Induction PCR

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- Number: US 11,028,432 B2
- Document ID: US11028432B2
- Status: Granted
- Kind: B2
- Application number: 15/034,817
- Filed: 2014-11-05
- Published: 2016-10-06
- Granted: 2021-06-08
- Earliest claimed: 2013-11-05
- Assignees: BioFire Diagnostics, LLC; University of Utah Research Foundation
- Applicants: BioFire Diagnostics, LLC; University of Utah Research Foundation
- Inventors: David Jones; Carl T. Wittwer
- Web page: https://patentgrep.com/patent/US11028432B2

## CPC

- C12Q 1/686: Polymerase chain reaction [PCR]
- B01L 7/52: {with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples}
- B01L 7/525: {with physical movement of samples between temperature zones}
- C12Q 3/00: Condition responsive control processes (apparatus therefor C12M1/36; controlling or regulating in general G05)
- G01N 35/00623: {of instruments}
- G01N 35/00871: {Communications between instruments or with remote terminals}
- B01L 2200/147: Employing temperature sensors
- B01L 2300/06: Auxiliary integrated devices, integrated components
- B01L 2300/0609: Holders integrated in container to position an object
- B01L 2300/0627: Sensor or part of a sensor is integrated
- B01L 2300/0819: Microarrays; Biochips
- B01L 2300/0838: Capillaries
- B01L 2300/16: Surface properties and coatings
- B01L 2300/1816: using induction heating
- B01L 2300/185: using a liquid as fluid
- B01L 2300/1894: Cooling means; Cryo cooling
- G01N 2035/00376: {Conductive heating, e.g. heated plates}
- G01N 2035/00396: {where the fluid is a liquid}
- G01N 2035/00445: {Other cooling arrangements}
- 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
- 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, devices, and kits are provided for performing PCR and other thermal cycling reactions in <20 seconds per cycle, using induction heating.

## Claims

### Claim 1

A device for thermal cycling a plurality of samples comprising:
an induction heater and an array of sample wells formed in an electrically conductive material, wherein the induction heater is configured to receive therein the array of sample wells formed in the electrically conductive material, wherein when received, the array is suspended within the induction heater, wherein each of a plurality of the sample wells comprise a target nucleic acid, a thermostable polymerase, and primers configured for amplification of the target nucleic acid sequence, wherein the polymerase is provided at a concentration of at least 0.5 μM and the primers are each provided at a concentration of at least 2 μM,
a power supply for providing the current to the induction heater, and
an air source configured to provide air to cool the array of sample wells.

### Claim 2 (depends on 1)

The device of claim 1, further comprising a switch for controlling the power supply and the air source.

### Claim 3 (depends on 2)

The device of claim 2, wherein the switch is controlled by a heat sensor.

### Claim 4 (depends on 2)

The device of claim 2, wherein the switch is controlled by a fluorescent value from a fluorescent dye in one or more of the sample wells.

### Claim 5 (depends on 2)

The device of claim 2, wherein the samples are PCR samples and the array is thermal cycled between an annealing temperature and a denaturation temperature for a plurality of cycles.

### Claim 6 (depends on 5)

The device of claim 5, wherein each cycle is completed in a cycle time less than 15 seconds per cycle.

### Claim 7 (depends on 5)

The device of claim 5, wherein each cycle is completed in less than 2 seconds per cycle.

### Claim 8 (depends on 1)

The device of claim 1, wherein the polymerase and primers are provided at a ratio of (about 0.03 to about 0.4 polymerase):(total primer concentration).

### Claim 9 (depends on 1)

The device of claim 1, wherein the electrically conductive material is a copper layer having a thickness of about 25 to about 100 μm, and the wells are formed therein.

### Claim 10 (depends on 9)

The device of claim 9, wherein the array further comprises a PCR compatible coating on the copper layer.

### Claim 11 (depends on 1)

The device of claim 1, wherein the air source is selected from the group consisting of a fan and compressed air.

### Claim 12 (depends on 1)

The device of claim 1, wherein the array of sample wells is generally circular.

### Claim 13 (depends on 1)

The device of claim 1, wherein the array of sample wells is elongated, and each sample well is equidistant from an edge of the array.

### Claim 14 (depends on 1)

The device of claim 1, further comprising at least one feature configured to reduce or eliminate a thermal gradient between the array of sample wells.

### Claim 15 (depends on 14)

The device of claim 14, wherein the at least one feature configured to reduce or eliminate a thermal gradient between the array of sample wells comprises a pattern of conductive regions and electrically insulating regions that is configured to provide substantially uniform inductive heating.

### Claim 16

A device for thermal cycling a sample comprising:
an induction heater and a sample well formed in an electrically conductive material, wherein the induction heater is configured to receive therein the sample well formed in the electrically conductive material, wherein when received, the sample well is suspended within the induction heater, wherein the sample well comprises a target nucleic acid, a thermostable polymerase, and primers configured for amplification of the target nucleic acid sequence, wherein the polymerase and primers are provided at a ratio of (about 0.03 to about 0.4 polymerase):(total primer concentration), and the polymerase concentration is at least 0.5 μM,
a power supply for providing the current to the induction heater,
an air source configured to provide air to cool the sample well,
a switch for controlling the power supply and the fan, and
a heat sensor for controlling the switch.

### Claim 17 (depends on 16)

The device of claim 16, wherein the heat sensor does not touch the electrically conductive material or the sample well.

### Claim 18 (depends on 16)

The device of claim 16, wherein the heat sensor is an infrared heat sensor.

### Claim 19 (depends on 16)

The device of claim 16, further comprising a plurality of additional sample wells formed in the electrically conductive material.

### Claim 20 (depends on 16)

The device of claim 16, wherein the sample is a PCR sample and the device cycles the array between an annealing temperature and a denaturation temperature for a plurality of cycles.

### Claim 21 (depends on 16)

The device of claim 16, wherein the electrically conductive material is a copper layer having a thickness of about 25 to about 100 μm, and the well is formed therein.

### Claim 22 (depends on 21)

The device of claim 21, wherein each cycle is completed in less than 5 seconds per cycle.

### Claim 23 (depends on 1)

A method for thermocycling a plurality of samples, comprising:
providing the device of claim 1;
providing the samples in the array, and
thermocycling the array using a conductive sample heating unit heated by the induction heater and cooled by the air source.

### Claim 24 (depends on 23)

The method of claim 23, wherein the array is formed as the sample wells in the conductive sample heating unit.

### Claim 25 (depends on 24)

The method of claim 24, further comprising the step of inserting the samples in the array into the induction heater.

### Claim 26 (depends on 23)

The method of claim 23, wherein the conductive sample heating unit comprises a pattern of conductive regions and electrically insulating regions that is configured to provide substantially uniform inductive heating.

### Claim 27 (depends on 23)

The method of claim 23, wherein the samples include a fluorescent dye and components for PCR, and the method further includes measuring fluorescence during or subsequent to thermocycling.