Sample-to-answer microfluidic system and method including vertical microfluidic device and automated actuation mechanisms

Inventors

Pais, Andrea Maria DominicPais, Rohan Joseph AlexanderWatkins, NicholasJoda, Hamdi

Assignees

Novel Microdevices Inc

Publication Number

US-12370544-B2

Publication Date

2025-07-29

Expiration Date

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Abstract

A sample-to-answer microfluidic system and method including vertical microfluidic device and automated actuation mechanisms, such as, but not limited to, automated mechanical and/or magnetic actuation, is disclosed. In some embodiments, the sample-to-answer microfluidic system includes a vertically oriented microfluidic device and a rotating actuator in relation to the microfluidic device, and wherein the microfluidic device and the rotating actuator are operating in the XZ plane. Additionally, methods of using the sample-to-answer microfluidic system are provided.

Core Innovation

The invention is a sample-to-answer microfluidic system and method including a vertical microfluidic device and automated actuation mechanisms, such as, but not limited to, automated mechanical and/or magnetic actuation. The sample-to-answer microfluidic system includes a vertically oriented microfluidic device and a rotating actuator in relation to the microfluidic device, and wherein the microfluidic device and the rotating actuator are operating in the XZ plane. The microfluidic cartridge includes a primary channel containing an oil/immiscible reagent phase situated in an XZ plane, a plurality of wells interconnected by said primary channel to form a fluidic circuit, and magnetic beads that are moved through said primary channel and resuspended sequentially in said plurality of wells at various stages of operation.

The problem being solved is that conventional microfluidic devices with primary channels oriented in the XY plane require an out of plane oil reagent container for generating the pressure head, which increases the overall height of the microfluidic device and complicates assembly and manufacturing. Conventional devices additionally require a minimum of two actuator plates to spatially orient magnets to resuspend and transfer magnetic particles, increasing component count and assembly complexity. Therefore, new approaches are needed for processing biological materials in a microfluidic system and/or device.

The disclosed vertical configuration and related instrument and cartridge designs address these issues by orienting the primary channel and oil/immiscible reagent container in the XZ plane so the oil reagent container height along the Z axis generates the required pressure head while not increasing the dimensions of the cartridge in a Y axis, and by enabling operation with a minimum of one actuator plate in the XZ plane with spatially oriented magnets to resuspend and transfer magnetic particles. The disclosure further provides that on-chip magnetic particle-based sample processing can be performed using a single rotational motion during which capture, resuspension and transfer of magnetic particles takes place, and describes additional features such as baffles to constrain magnetic particles, wick valves, reagent pouches, and a portable instrument configured to receive the microfluidic cartridge.

Claims Coverage

One independent claim was identified with four main inventive features extracted from claim 1.

Primary channel oriented in the XZ plane

A primary channel oriented in the XZ plane that interconnects a plurality of wells to form a fluidic circuit.

In-plane immiscible reagent container positioned to generate pressure head

An immiscible reagent container in plane with and fluidly connected to the primary channel, wherein the immiscible reagent container is positioned at a height along a Z axis sufficient to generate a pressure head that drives the immiscible reagent into the microfluidic cartridge.

Magnetic-particle-compatible cartridge architecture

A microfluidic cartridge configured to receive magnetic particles, wherein the primary channel is configured such that the magnetic particles are capable of being transferred through the primary channel and resuspended sequentially in the plurality of wells at various stages of operation.

Plurality of wells forming a fluidic circuit

A plurality of wells interconnected by the primary channel to form a fluidic circuit.

Claim 1 centers on a vertically oriented microfluidic cartridge architecture combining an XZ-plane primary channel with an in-plane immiscible reagent container positioned to generate a Z-axis pressure head, a plurality of interconnected wells forming a fluidic circuit, and configuration for magnetic particle transfer and sequential resuspension.

Stated Advantages

Reduced number of components and assembly steps required for the microfluidic cartridge and actuation instrument compared with conventional microfluidic systems.

Simplified assembly and manufacturing processes because the oil reagent container is in plane with the primary channel, allowing increased pressure head without increasing cartridge dimensions in the Y axis.

Operation with a minimum of only one actuator plate in the XZ plane, with spatially oriented magnets able to resuspend and transfer magnetic particles.

Ability to generate a smooth, bubble-free oil/immiscible reagent overlay driven by a pressure head from the in-plane immiscible reagent container.

Single rotational motion used to perform multiple actuation steps that define a sample-to-answer assay sequence, enabling capture, resuspension and transfer of magnetic particles during one rotation.

Documented Applications

Sample-to-answer nucleic acid amplification test (NAAT) performed on the microfluidic cartridge.

On-chip magnetic particle-based sample processing including capture, resuspension, transfer, mixing, washing, and elution steps.

Point of care (POC) sample-to-answer applications and devices.

Loop Mediated Isothermal Amplification (LAMP) assays and associated on-chip amplification and lateral flow detection for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG).

Lateral flow-based detection of amplified products using a lateral flow strip integrated in the microfluidic cartridge.

Use with immunoassay microfluidic cartridges, lateral flow immunoassay cassettes, and other cartridge types tailored to different assay formats.

Insertion into a portable instrument configured to receive the microfluidic cartridge and perform automated actuation including crushing reagent pouches and rotating actuator plates.

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