# US 12,179,190 B2 · Systems and methods for biochemical analysis including a base instrument and a removable cartridge

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- Number: US 12,179,190 B2
- Document ID: US12179190B2
- Status: Granted
- Kind: B2
- Application number: 18/087,499
- Filed: 2022-12-22
- Published: 2023-05-11
- Granted: 2024-12-31
- Earliest claimed: 2014-05-27
- Assignees: Illumina, Inc.
- Applicants: Illumina, Inc.
- Inventors: Alex Aravanis; Boyan Boyanov; M. Shane Bowen; Dale Buermann; Alexander Hsiao; Behnam Javanmardi; Tarun Khurana; Poorya Sabounchi; Hai Quang Tran
- Web page: https://patentgrep.com/patent/US12179190B2

## CPC

- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- B01L 3/502738: {characterised by integrated valves (throttle valves in microfluidic sample containers B01L3/502746)}
- B01L 7/525: {with physical movement of samples between temperature zones}
- F16K 99/0013: {Rotary valves}
- F16K 99/0015: {Diaphragm or membrane valves}
- F16K 99/0028: {Valves having multiple inlets or outlets}
- F16K 99/0059: {actuated by a pilot fluid}
- B01L 2200/025: Align devices or objects to ensure defined positions relative to each other
- B01L 2200/027: for microfluidic devices
- B01L 2200/04: Exchange or ejection of cartridges, containers or reservoirs
- B01L 2200/0689: Sealing
- 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 2300/0663: Whole sensors
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2300/0867: Multiple inlets and one sample wells, e.g. mixing, dilution
- B01L 2300/0874: Three dimensional network
- B01L 2300/0883: Serpentine channels
- B01L 2300/0887: Laminated structure
- B01L 2300/1805: Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
- B01L 2300/1827: using resistive heater
- B01L 2400/0633: with moving parts
- B01L 2400/0638: membrane valves, flap valves
- B01L 2400/0644: rotary valves
- B01L 2400/065: sliding valves
- B01L 2400/0655: pinch valves
- F16K 2099/0074: {using photolithography, e.g. etching}
- F16K 2099/008: {Multi-layer fabrications}
- F16K 2099/0084: {Chemistry or biology, e.g. "lab-on-a-chip" technology}
- 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)}

## Abstract

Systems and methods for conducting designated reactions utilizing a base instrument and a removable cartridge. The removable cartridge includes a fluidic network that receives and fluidically directs a biological sample to conduct the designated reactions. The removable cartridge also includes a flow-control valve that is operably coupled to the fluidic network and is movable relative to the fluidic network to control flow of the biological sample therethrough. The removable cartridge is configured to separably engage a base instrument. The base instrument includes a valve actuator that engages the flow-control valve of the removable cartridge. A detection assembly held by at least one of the removable cartridge or the base instrument may be used to detect the designated reactions.

## Claims

### Claim 1

A system, comprising:
a removable cartridge, comprising:
a cartridge housing having a sample port that opens to an exterior of the cartridge housing and is adapted to receive a biological sample, the cartridge housing having a mating side, a first array of electrical contacts disposed along the mating side, a mechanical interface that is exposed to the exterior, and an access opening of the cartridge housing that permits access to the mechanical interface;
a fluidic network configured to fluidically direct a flow of fluid for conducting an analysis of the biological sample, the fluidic network comprising a plurality of channels, a reaction chamber, and one or more reservoirs for storing reagents, the fluidic network configured to direct the biological sample to the reaction chamber, and the fluidic network configured to direct reagents from the reservoirs to the reaction chamber; and
an imaging device disposed within the cartridge housing and positioned to detect designated reactions within the reaction chamber; and
a base instrument having a valve actuator and a control side configured to engage the mating side of the cartridge housing to removably couple the removable cartridge to the base instrument,
wherein when the removable cartridge is coupled to the base instrument, the valve actuator is aligned with and received by the access opening of the cartridge housing to control the flow of fluid through the fluidic network, and
wherein the imaging device is electrically coupled to the first array of electrical contacts for communicating the detected designated reactions to the base instrument.

### Claim 2 (depends on 1)

The system of claim 1, wherein the control side of the base instrument includes a second array of electrical contacts configured to be electrically connected with the first array of electrical contacts when the removable cartridge is coupled to the base instrument, and wherein the base instrument includes a detection module configured to control the imaging device, via the second array of electrical contacts, to obtain data about the biological sample.

### Claim 3 (depends on 1)

The system of claim 1, wherein the imaging device is positioned immediately adjacent the first array of electrical contacts.

### Claim 4 (depends on 1)

The system of claim 1, wherein the imaging device is positioned between the reaction chamber and the first array of electrical contacts.

### Claim 5 (depends on 1)

The system of claim 1, wherein the cartridge housing has an exterior side that is configured to engage the base instrument when the removable cartridge is coupled to the base instrument, and wherein the first array of electrical contacts is arranged on the exterior side.

### Claim 6 (depends on 1)

The system of claim 1, wherein each electrical contact of the first array of electrical contacts is a flexible contact that is repositionable relative to the exterior of the cartridge housing.

### Claim 7 (depends on 1)

The system of claim 1, wherein the fluidic network includes a sample channel in fluid communication with the sample port, wherein the base instrument comprises a thermal block for controlling a temperature of the sample channel, and wherein the cartridge housing further includes an access opening that is exposed to the exterior and is configured to receive the thermal block.

### Claim 8 (depends on 1)

The system of claim 1, wherein the mechanical interface comprises one or more valves disposed within the cartridge housing, and wherein when the removable cartridge is coupled to the base instrument, the one or more valves are movable by the base instrument to change the flow of fluid through the fluidic network.

### Claim 9 (depends on 8)

The system of claim 8, wherein the base instrument comprises a valve actuator configured to operably engage the one or more valves of the removable cartridge, via the access opening, to move the one or more valves to change the flow of fluid through the fluidic network.

### Claim 10 (depends on 8)

The system of claim 8, wherein the fluidic network includes a sample channel in fluid communication with the sample port, wherein one or more valves comprise a channel valve that is movable between first and second positions by the base instrument, and wherein the channel valve blocks flow through the sample channel when in the first position and permits flow through the sample channel when in the second position.

### Claim 11 (depends on 8)

The system of claim 8, wherein the one or more valves comprise a rotatable valve that is rotatable between different positions to change the flow of fluid through the fluidic network.

### Claim 12 (depends on 1)

The system of claim 1, wherein the fluidic network includes a sample channel in fluid communication with the sample port, a network port in fluid communication with the sample channel, a feed port in fluid communication with the reaction chamber, and a reservoir port in fluid communication with the one or more reservoirs, wherein the mechanical interface of the removable cartridge comprises a rotatable valve carried by the cartridge housing, the rotatable valve fluidically coupling the feed port and the network port when in a first rotational position and fluidically coupling the feed port and the reservoir port when in a second rotational position.

### Claim 13 (depends on 12)

The system of claim 12, wherein the rotatable valve rotates about an axis, the feed port being aligned with the axis.

### Claim 14 (depends on 1)

The system of claim 1, further comprising a locking mechanism configured to removably secure the cartridge housing to the base instrument, the locking mechanism comprising a latch engaging element carried by one of the cartridge housing and the base instrument and a rotatable latch carried by the other of the cartridge housing and the base instrument and configured to releasably engage the latch engaging element.

### Claim 15 (depends on 1)

The system of claim 1, wherein the removable cartridge includes a first flow port, wherein the base instrument includes a second flow port and a system pump, wherein the second flow port is fluidly coupled to the first flow port when the removable cartridge is removably coupled to the base instrument, and wherein when the second flow port is fluidly coupled to the first flow port, the system pump is configured to selectively induce the flow of fluid through the fluidic network.

### Claim 16 (depends on 1)

The system of claim 1,
wherein the base instrument comprises:
a light source; and
wherein the removable cartridge comprises:
a plurality of reservoirs for storing the reagents; and
a flow cell assembly comprising a flow channel, ports to enable fluid flow into and out of the flow channel, and an optically transparent portion providing optical access to the flow channel,
wherein the imaging device includes an image sensor;
wherein the mechanical interface includes a rotatable valve that controls fluid flow between the reservoirs and the flow cell assembly;
wherein the system further comprises a pump to control flow of fluid from the reservoirs to the flow cell assembly,
wherein the valve actuator is configured to access the mechanical interface and actuate the rotatable valve; and
wherein the light source is configured to illuminate the flow channel through the optically transparent portion and the image sensor is configured to detect light signals in response to the illumination.

### Claim 17 (depends on 16)

The system of claim 16, wherein the base instrument comprises the pump.

### Claim 18 (depends on 17)

The system of claim 17, wherein the pump provides positive pressure to flow fluid through the removable cartridge under positive pressure.

### Claim 19 (depends on 16)

The system of claim 16, wherein the removable cartridge comprises membrane valves that control fluid flow.

### Claim 20 (depends on 16)

The system of claim 16, further comprising an outlet pump fluidly coupled to and downstream of the flow channel.

### Claim 21 (depends on 20)

The system of claim 20, wherein the removable cartridge comprises the outlet pump.

### Claim 22 (depends on 16)

The system of claim 16, wherein the base instrument comprises a thermal block and the removable cartridge comprises a side having an access opening to receive the thermal block, the thermal block to control a temperature of the flow channel.

### Claim 23 (depends on 16)

The system of claim 16, wherein the base instrument comprises a cartridge receptacle and the removable cartridge is to be received by the cartridge receptacle.

### Claim 24 (depends on 23)

The system, of claim 23, wherein the cartridge receptacle comprises a cartridge-receiving slot and the removable cartridge is to be received within the cartridge-receiving slot.

### Claim 25 (depends on 16)

The system of claim 16, further comprising reagent contained within each of the reservoirs.

### Claim 26 (depends on 25)

The system of claim 25, wherein the reagent comprises liquid reagent.

### Claim 27 (depends on 16)

The system of claim 16, wherein the removable cartridge carries a heater.

### Claim 28 (depends on 27)

The system of claim 27, wherein the removable cartridge comprises a channel coupled to the rotatable valve, the heater adjacent the channel.

### Claim 29 (depends on 28)

The system of claim 28, wherein the removable cartridge comprises a sample supply and wherein the channel is to be coupled between the sample supply and the rotatable valve.