Multiwell dynamic model for a tumor-immune microenvironment

Inventors

Borenstein, Jeffrey • Moore, Nathan • Doty, Daniel • Haggerty, Timothy • Charest, Joseph • Gimbel, Alla • Mott, Vienna • Isenberg, Brett • Azizgolshani, Hesham • Cain, Brian • Mescher, Mark

Assignees

Charles Stark Draper Laboratory Inc

Abstract

A microfluidic device for modeling a tumor-immune microenvironment can include a multiwell plate defining a plurality of microenvironment units fluidically coupled with a plurality of wells. Each microenvironment unit of the plurality of microenvironment units can include one or more compartments. Each microenvironment unit can include a trapping feature positioned within the one or more compartments. The trapping feature can be defined by a portion of at least one of a sidewall or a floor of the one or more compartments. The trapping feature can restrict movement of a tissue sample introduced into the one or more compartments and to allow fluid to flow past the tissue sample. The microfluidic device can include a plurality of micropumps each coupled with a respective well and configured to control movement of a respective fluid sample through each respective well.

Core Innovation

The disclosed invention provides a multiwell microfluidic platform that models a tumor-immune microenvironment. A well plate includes a plurality of wells that define a plurality of microenvironment units, where each microenvironment unit includes one or more compartments and a trapping feature positioned within a compartment to trap a tissue sample between a top surface of the trapping feature and a ceiling of the compartment while allowing fluid to flow through the compartment at least between the tissue sample and the floor of the compartment.

The device further includes a plurality of micropumps, each configured to control movement of a fluid sample through a respective well of the plurality of wells. This arrangement supports parallel evaluation of candidate immunotherapies by varying fluid delivery across multiple microenvironment units, and the platform provides optical access for observing tissue and interactions over time.

The microenvironment units are described in bilayer modes, including configurations with basal and apical compartments separated by a permeable membrane and corresponding basal and apical channel structures. The trapping feature and compartment architectures include tapered sidewalls, raised and symmetric surfaces, step features, vertical posts, horizontal structures, and tissue-trap pockets with stagnation zones, and the transparent optical layer is coupled to the well plate to provide an optical interface into each microenvironment unit for confocal microscope observation.

Claims Coverage

The document includes one independent claim directed to a multiwell microfluidic device having microenvironment units with a trapping feature and a plurality of independently controlled micropumps. Dependent claims refine the compartment architecture, trapping-feature geometry, membrane/coating options, and an optical interface for confocal microscope observation.

Overall claim coverage centers on a multiwell microfluidic device where each microenvironment unit traps a tissue sample using a floor-extending trapping feature while permitting fluid flow past the trapped sample, combined with micropumps that control fluid movement through corresponding wells. Dependent features further specify basal/apical membrane-separated compartment architecture, trapping-feature geometry, functionalized gel coatings, and a transparent optical layer enabling confocal microscope observation.

Stated Advantages

Documented Applications