Systems, devices, and methods for ultra-sensitive detection of molecules or particles

Inventors

Fournier, DavidCampbell, ToddKan, Cheuk W.Lawson, JohnRivnak, AndrewKagan, MichaelDuffy, David C.

Assignees

Quanterix Corp

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Publication Number

US-11977087-B2

Patent

Publication Date

2024-05-07

Expiration Date


Abstract

Described are systems, devices, and methods which related to various aspects of assays for detecting and/or determining a measure of the concentration of analyte molecules or particles in a sample fluid. In some cases, the systems employ an assay consumable comprising a plurality of assay sites. The systems, devices, and/or methods, in some cases, are automated. In some cases, the systems, devices, and/or methods relate to inserting a plurality of beads into assay sites, sealing assay sites, imaging assay sites, or the like.

Core Innovation

The invention describes an automated ultra-sensitive bead-based assay system that uses an assay consumable disc having a surface comprising wells. The wells have a very small volume range, and the apparatus includes a first liquid injector positioned to apply a sealing liquid to the disc surface and a second liquid injector positioned to load an assay sample into the wells. A fluid pump creates a flow of a liquid containing a suspension of beads over the disc surface to insert beads into the wells, and a motor operated by a computer implemented controller rotates the assay consumable disc about a central axis.

The system is configured to use a camera to acquire an image of the wells of the assay consumable disc containing assay sample. The computer implemented controller is programmed to operate the first liquid injector, the second liquid injector, and the fluid pump, and to receive the image acquired from the camera. The imaging is used to determine which wells contain beads/analyte and to compute analyte concentration, supporting ultra-sensitive detection using sealed, fluidically isolated assay sites.

The disclosed architecture includes additional described components and configurations, including assay consumable handlers and mechanisms for bead loading and optional removal or isolation of beads in individual wells. The disclosure also includes sealing approaches using sealing liquids and sealing components that fluidically isolate contents of assay sites, and imaging modalities such as fluorescence and white light with bright-field/dark-field illumination.

Claims Coverage

The document identifies one independent claim (clm-00001). It covers an apparatus for performing a bead-based assay with a rotating assay consumable disc, including sealed well handling, bead insertion by pumping a bead suspension over the disc, and camera-based imaging under computer implemented control. Dependent claims refine the independent claim by adding constraints on well volume and bead/well occupancy, specifying certain sealing materials/fluids, and specifying selectable camera device types.

Rotating disc handler with ultra-small wells

A disc handler operatively coupled to an assay consumable disc having a surface comprising wells formed in the surface of the assay consumable disc that have a volume between about 1 femtoliter and about 1 picoliter, the motor operated by the computer implemented controller rotating the assay consumable disc about a central axis of the assay consumable disc.

Sealing liquid application and sample loading injectors

A first liquid injector positioned to apply a sealing liquid to the surface of the assay consumable disc and a second liquid injector positioned to load an assay sample into the wells of the assay consumable disc.

Bead insertion by pumping bead suspension over the disc

A fluid pump positioned to create a flow of a liquid, which contains a suspension of beads, over the surface of the assay consumable disc to insert beads into the wells.

Camera imaging with computer implemented controller operation and image reception

A camera configured to acquire an image of the wells of the assay consumable containing assay sample, and a computer implemented controller configured and programmed to operate the first liquid injector, the second liquid injector, and the fluid pump, and to receive the image acquired from the camera.

Zero or one bead occupancy behavior per well

The apparatus is configured so that each well is sized and/or shaped to each contain only zero or one of the beads inserted by the flow of the liquid, which contains the suspension of beads, over the surface of the assay consumable disc.

Fluorinated oil sealing liquid with cyclic olefin polymer disc surface

The apparatus of claim 1 is configured such that the assay consumable disc has a surface made of cyclic olefin polymer and the sealing liquid includes a fluorinated oil.

Selectable imaging sensor types for the camera

The apparatus of claim 1 is specified such that the camera includes one or more of the following image-sensing camera types/devices: CCD camera, charge injection device (CID), complementary metal oxide semiconductor (CMOS) device, scientific CMOS (sCMOS) device, time delay integration device, photomultiplier tube (PMT), and avalanche photodiode (APD).

Overall, the claim coverage centers on operating a rotating assay consumable disc with ultra-small wells, applying sealing liquid, loading assay sample, inserting beads by pumping a beads suspension over the disc, and using camera imaging under a computer implemented controller that operates injectors and pump and receives images. Dependent refinements further constrain well occupancy to zero-or-one beads per well, specify cyclic olefin polymer with a fluorinated oil sealing liquid, and limit or define allowable camera sensor device types.

Stated Advantages

Not explicitly described in patent.

Documented Applications

Not explicitly described in patent.

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