The Brigham and Women's Hospital, Inc.

The Charles Stark Draper Laboratory, Inc.

Massachusetts Institute of Technology

California Institute of Technology

Guillermo Garcia-Cardena

Jeffrey T Borenstein

Eli J Weinberg

Peter Mack

Ahmad S Khalil

Malinda M Tupper

Sarah L Tao

Jason Oliver Fiering

Ernest Soonho Kim

William J Adams, Jr

David J Anderson

Michael A Gimbrone, Jr

Stephen L Bellio

Hai U Wang

Mitchell L Hansberry

James Ching-Ming Hsiao

Sarah Tao

William James Adams

Microfluidic structures featuring substantially circular channels may be fabricated by embossing polymer sheets.

Microfluidic structures for biomedical applications

The systems and methods described herein relate to a high-throughput flow apparatus. The apparatus is used with an array of wells, and is configured to impart a predetermined shear stress on cells cultured within each of the wells of the array of wells. The apparatus includes a plurality of mechanical tips. The plurality of mechanical tips each includes a head with a hemispheroid shape. The apparatus also includes a motor associated with at least one of plurality of mechanical tips. The motor is configured to drive the plurality of mechanical tips to impart the shear stress pattern in each of the wells.

Systems and method for high-throughput testing

microfluidic structures for biomedical applications

A high-throughput flow system includes an array of wells and a separate mechanical tip positioned within each well. Each mechanical tip is separately actuated to impart a shear stress pattern. A separate sleeve may be associated with each tip for maintaining a predetermined distance between the tip and a floor of the tip's corresponding well, with each tip being rotatable within its corresponding sleeve. Alternatively, a separate post may be associated with each tip for maintaining a predetermined distance between the tip and a floor of the tip's corresponding well, with each tip being rotatable about its corresponding post.

High-throughput biological screening

Methods of fabricating microfluidic structures featuring substantially circular channels are provided. The methods involve (a) providing a patterned wafer comprising at least one exposed electrically conductive region and at least one exposed electrically insulating region; (b) electroplating an inverse channel portion with substantially semicircular cross section onto the wafer, thereby forming a first master mold; (c) employing the first master mold so as to emboss a channel portion in a first polymer sheet; and (d) aligning and bonding the first polymer sheet with a second polymer sheet having a corresponding channel portion such as to define a first channel with substantially circular cross section between the polymer sheets.

Method of fabricating microfluidic structures for biomedical applications

Arterial and venous smooth muscle cells are molecularly distinct from the earliest stages of angiogenesis through to adulthood. This distinction is revealed by expression on arterial cells (e.g., arterial endothelial cells, arterial smooth muscle cells) of a transmembrane ligand, called EphrinB2 whose receptor EphB4 is expressed on venous cells. Targeted disruption of the EphrinB2 gene prevents the remodeling of veins from a capillary plexus into properly branched structures. Moreover, it also disrupts the remodeling of arteries, suggesting that reciprocal interactions between pre-specified arterial and venous cells are necessary for angiogenesis. Expression of EphrinB2 in arterial cells (e.g., arterial endothelial cells, arterial smooth muscle cells) can be used to advantage in methods for targeting agents and/or encoded polypeptides to arterial smooth muscle cells, altering angiogenesis, assessing the effect of agents on arterial smooth muscle cells, identifying arterial smooth muscle cells, isolating arterial smooth muscle cells and production of artificial vessels, for example.

Artery smooth muscle- and vein smooth muscle-specific proteins and uses therefor

Growing community of inventors

Cambridge, MA, United States of America

Guillermo Garcia-Cardena