Micro-fluidic devices for assaying biological activity

Inventors

Chapman, Kevin T.Malleo, DanieleNevill, J. TannerShort, Steven W.White, Mark P.Loureiro, M. Jimena

Assignees

Bruker Cellular Analysis Inc

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Publication Number

US-11998914-B2

Patent

Publication Date

2024-06-04

Expiration Date


Abstract

Biological activity in holding pens in a micro-fluidic device can be assayed by placing in the holding pens capture objects that bind a particular material of interest produced by the biological activity. The biological material of interest that binds to each capture object can then be assessed, either in the micro-fluidic device or after exporting the capture object from the micro-fluidic device. The assessment can be utilized to characterize the biological activity in each holding pen. The biological activity can be production of the biological material of interest. Thus, the biological activity can correspond to or arise from one or more biological cells. Biological cells within a holding pen can be clonal cell colonies. The biological activity of each clonal cell colony can be assayed while maintaining the clonal status of each colony.

Core Innovation

The invention provides a micro-fluidic platform and process for assaying biological activity of one or more biological cells in a holding pen of a micro-fluidic device. The biological activity includes production of a biological material of interest by the cells. The micro-fluidic structure disposed on a base defines a flow region and the holding pen, where the holding pen comprises a single opening to the flow region and an unswept region.

Capture micro-objects are introduced into the holding pen, and each capture micro-object comprises a binding substance that specifically binds to the biological material of interest. The produced biological material of interest is allowed to bind to the capture micro-object, and the process assesses whether the biological material of interest is bound to the capture micro-object.

The documented approach includes culturing cells in the holding pen and using capture micro-objects to capture and assess produced biological materials of interest in a correlated manner to the specific pen/colony. Multi-target assays are supported by introducing n different types of capture micro-objects, where each type includes a binding substance that specifically binds to one of the n different biological materials of interest, or by introducing one or more y-material capture micro-objects, where each y-material capture micro-object comprises y different binding substances, each specifically binding to one of the n different biological materials of interest.

Claims Coverage

The independent claims cover three inventive features for assaying biological activity in a micro-fluidic device holding pen.

Holding pen micro-fluidic architecture with single opening and unswept region

A micro-fluidic device comprising a base and a micro-fluidic structure disposed on said base, wherein said micro-fluidic structure and said base define a flow region and said holding pen, and wherein said holding pen comprises a single opening to said flow region and an unswept region.

Capture micro-object binding and assessment of bound biological material of interest

Introducing a capture micro-object into said holding pen, wherein said capture object comprises a binding substance that specifically binds to said biological material of interest; allowing said biological material of interest produced by said one or more biological cells to bind to said capture micro-object; and assessing whether said biological material of interest is bound to said capture micro-object.

Parallel n-material assay using n different capture micro-object types

Culturing one or more biological cells in a holding pen of a micro-fluidic device, wherein said one or more biological cells produce n different biological materials of interest; introducing n different types of capture micro-objects into said holding pen, each said type of capture micro-object comprising a binding substance that specifically binds to one of said n different biological materials of interest; allowing said n different biological materials of interest produced by said one or more biological cells to bind to said n different types of capture micro-objects; and assessing binding between said n different biological materials of interest and said n different types of capture micro-objects.

Parallel n-material assay using y-material capture micro-objects with multiple binding substances

Culturing one or more biological cells in a holding pen of a micro-fluidic device, wherein said one or more biological cells produce n different biological materials of interest; introducing one or more y-material capture micro-objects into said holding pen, each y-material capture micro-object comprising y different binding substances, each of which specifically binds to one of said n different biological materials of interest; allowing said n different biological materials of interest produced by said one or more biological cells to bind to said y-material capture micro-objects; and assessing binding between said n different biological materials of interest and said y-material capture micro-objects.

The claim coverage centers on the holding pen architecture, the use of capture micro-objects with binding substances that specifically bind produced biological materials of interest, and assessment of binding in single-material and multi-material configurations.

Stated Advantages

Documented Applications

Assaying biological activity of one or more biological cells by assaying production of biological material of interest in a micro-fluidic device holding pen using capture micro-objects and assessing whether the biological material of interest is bound.

Multi-target assaying of biological activity in a holding pen by producing n different biological materials of interest and assessing binding with n different capture micro-object types.

Multi-target assaying of biological activity in a holding pen by producing n different biological materials of interest and assessing binding using one or more y-material capture micro-objects, each containing y different binding substances.

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