Systems and methods for modeling veins and associated blood vessel components

Inventors

Jain, Abhishek • Rajeeva Pandian, Navaneeth Krishna

Assignees

Texas A&M University System

Abstract

A microfluidic chip for modelling flow through a vein includes a body including a microchannel extending between a fluid inlet and a fluid outlet, wherein at least a portion of the microchannel is coated with endothelial cells that form vascular lumen, and a venous valve formed in the body and positioned along the microchannel, wherein the venous valve includes a pair of leaflets defining a pair of cusps of the venous valve, and a flow channel positioned between the leaflets.

Core Innovation

The invention provides a microfluidic vein-on-a-chip for modelling blood flow through a vein. The chip comprises an artificially fabricated microchannel extending between a fluid inlet and a fluid outlet, where at least a portion of the microchannel is coated with endothelial cells that form a vascular lumen. A venous valve is positioned along the microchannel to define flow behavior within the lumen.

The venous valve includes a pair of leaflets that define a pair of cusps of the venous valve, and a flow channel positioned between the leaflets. The endothelial-cell coated vascular lumen and the valve structure are integrated into the artificially fabricated body to create a microfluidic representation of venous flow through a valve-containing microchannel. In related aspects, endothelial features can include HUVECs and can be supported by ECM.

The disclosure further integrates a venous-valve actuation concept using paired actuation chambers positioned adjacent channel walls. In response to pressurization and depressurization of the actuation chambers, the system decreases and increases a width of the valve flow channel, respectively. Reported modelling and experiments indicate formation of venous thrombi preferentially within valve cusps under endothelial activation, linking the valve geometry and endothelial treatment to thrombus deposition behavior.

The document characterizes thrombus formation and endothelial activation within the microphysiological system and compares behaviour predicted by computational fluid dynamics, including vortices and stasis within valve cusps. It also relates to related macroscale or 3D-printed venous valve models with pneumatic or syringe actuation and mechanical pumping to mimic valve opening and closing. The stated motivation is improved modelling of deep vein thrombosis and related thromboembolism and improved evaluation of anticoagulants relative to animal or volunteer studies.

Claims Coverage

The independent claim set covers three aspects of the invention: (i) a microfluidic chip with an endothelial-coated microchannel and a venous valve with leaflets and cusps; (ii) a method for forming such a chip by forming the microchannel/valve in a master mold and coating the microchannel with endothelial cells; and (iii) an actuatable microfluidic venous-valve chip having actuation chambers configured to reversibly decrease and increase valve flow-channel width. Across the independent claims, the core inventive features involve the endothelial-coated vascular lumen, the valve leaflet/cusp flow-channel geometry, and, in one independent claim family, the reversible actuation chamber-driven modulation of flow-channel width.

Overall, the independent claims cover microfluidic venous-flow modelling by combining an artificially fabricated microchannel or fluid channel, an endothelial-cell coated vascular lumen, and a venous valve with paired leaflets defining paired cusps and a valve flow channel; additionally, one independent claim adds paired actuation chambers that reversibly decrease and increase the valve flow-channel width in response to pressurization and depressurization.

Stated Advantages

Documented Applications