Highly deformable porous membrane culture system and actuation methods for studying the effects of biomechanical stretch on cultured tissue

Inventors

Isenberg, Brett • Charest, Joseph • Williams, Corin • Soonho, Ernest Kim • Pilkenton, Morgan • Davis, Patrick • Marr, Elizabeth Ellen • Vedula, Else Marie

Assignees

Charles Stark Draper Laboratory Inc

Abstract

The systems and methods of the present disclosure provide highly deformable porous membrane culture systems and actuation methods for studying the effects of biomedical stretch on cultured tissue. A well plate can include a well having a first opening configured to receive an insert coupled to a deformable membrane. The well plate can include a gasket positioned within the well and configured to create a seal between the insert and the well when the insert is positioned in the well. The well plate can include a chamber defined beneath the well, the chamber configured to receive fluid media and to expose the fluid media to a surface of the deformable membrane when the insert is positioned in the well. The well plate can include an actuator configured to stretch the deformable membrane by a target amount of strain.

Core Innovation

The systems and methods provide highly deformable porous membrane culture systems and actuation methods for studying the effects of biomechanical stretch on cultured tissue. A well plate can include a well having a first opening configured to receive an insert coupled to a deformable membrane, a gasket positioned within the well to create a seal between the insert and the well, a chamber defined beneath the well configured to receive fluid media and to expose the fluid media to a surface of the deformable membrane, and an actuator configured to stretch the deformable membrane by a target amount of strain. The disclosure describes integration of membrane deformation with controlled fluid shear stress applied by moving fluid across the face of the membrane.

The background identifies a need for human-relevant in vitro models that better mimic the bladder's biophysical environment (for example, urine, flow, stretch) and notes that existing models often use murine infection models or static culture and have poorly studied the effects of mechanical stimulation on infection progression. The disclosure states that stretch is an element of many human and mammalian tissues and that an apparatus to provide stretch to cultured tissue provides a means to better mimic in vivo conditions. The systems and methods are presented to address the lack of in vitro high-throughput, complex culture platforms that can accurately and repeatedly apply such stimulation to cultured tissues.

The disclosure describes multiple actuation techniques including pneumatic actuation, mechanical actuation (for example, hoop-and-rim, pin-array, mechanical iris), and magnetic actuation, and options to provide controlled fluid flow to either side of the membrane to induce shear stimulation. The deformable porous membranes are described as having pores that allow transport between compartments and as being constructible from materials including polydimethylsiloxane, polyurethane, natural rubber, and 'tough' hydrogels. [procedural detail omitted for safety]

Claims Coverage

One independent claim is identified and the inventive features are extracted from that claim.

Claim 1 covers a well plate assembly combining a well, a flexible-walled insert with a deformable membrane, a fluid-exposed chamber beneath the membrane, and an actuator coupled to the insert wall that deforms the wall to stretch the membrane by a specified amount of strain.

Stated Advantages

Documented Applications