Massachusetts Institute of Technology

Other

Percardia, Inc.

The General Hospital Corporation

Arizona State University

The Brigham and Women's Hospital, Inc.

Children's Medical Center Corporation

National University of Singapore

Roger Dale Kamm

Seok Chung

Eun Bo Shim

Peter J Wilk

Kwang Ho Lee

Richard Joseph Renati

Haruhiko Harry Asada

Stephen C Evans

Simon M Furnish

Greg R Furnish

Todd A Hall

Gerald Melsky

David Y Phelps

Scott J Wolf

William P Santamore

Daniel Burkhoff

Mehdi Nikkhah

Michael Raghunath

Waleed Ahmed Farahat

Sebastien G M Uzel

Jeffrey D Macklis

Danh Truong

Sei Hien Lim

Nancy M Briefs

Edwin Tomoya Ozawa

Levi B Wood

Louis Fine

Sharon Wei Ling Lee

Ioannis K Zervantonakis

Jonathan Gertler

Huu Tuan Nguyen

Suzanne Tharin

Tatsuya Osaki

Vivek Sivathanu

Chandrasekhar Kothapalli

Johanna Varner

Sebastien Guy Marcel Uzel

Young Kum Park

Le Thanh Tu Nguyen

Choong Kim

Vernella V Vickerman-Kelley

Jeffrey Macklis

Microfluidic devices with open ports and gel channels for forming perfusable hydrogel vascular networks with holes or ports for samples, and methods of making and using, are provided which integrate interstitial flows to an ex vivo vascularized tissue model. Samples of cells, spheroids, organoids, and tissues can be used for screening of agents for efficacy, toxicity and dosage. The devices create interstitial flow from the top of the gel hole, through the sample toward the vascular networks, and/or luminal flows generated by a pressure difference between two media channels across the vascular network. This system is useful for studying angiogenesis, immune cell migration and testing new immunotherapy drug candidates.

Fluidic platforms for perfusable vascularized tissues with infiltrates

Microfluidic devices with neuronal cells, muscle cells, and optionally other cell types co-cultured therein are provided. Typically one or more the cells has a mutation that contributes to or causes a neuronal or muscular disease or disorder. For example, in some embodiments, one or more of the cultured cells are derived from a subject with a neuronal or muscular disease or disorder. The microfluidic device can facilitate formation of a 3D motor unit and a neuromuscular junction in vitro, and be used to monitor the molecular, biochemical, cellular, and morphological differences in the formation of such structures by healthy and diseased cells, and for testing compounds, dosages of compounds, dosing regimes, and combinations thereof, that may improve or worsen their formation. An exemplary combination drug therapy identified in this way is also provided.

Micro physiological model for neuronal and muscular diseases and disorders

Provided herein are methods and compositions for increasing muscle strength, and for treating muscle wasting disorders, muscle degenerative disease, or exercise-induced weakness, and cancer.

Compositions and methods to increase muscular strength

The present subject matter provides a microfluidic device that enables the precise and repeatable three dimensional and compartmentalized coculture of muscle cells and neuronal cells. Related apparatus, systems, techniques, and articles are also described.

Microfluidic device for three dimensional and compartmentalized coculture of neuronal and muscle cells, with functional force readout

A microfluidic device for more accurately modeling the in vitro environment in which cancer occurs is disclosed. The device comprises a surface defining one or more microfluidic channels that may further comprise one or more endothelial cells, a first three dimensional scaffold comprising one or more cancer cells that is spatially separated from the one or more microfluidic channels, and a second three dimensional scaffold comprising one or more stromal cells, at least a portion of which is interposed between the one or more microfluidic channels and the first three dimensional scaffold. The second three dimensional scaffold is in fluid communication with both the first three dimensional scaffold and the one or more microfluidic channels. The device can be used to assay anti-cancer agents, or as a system for modeling the growth, behavior, or metastasis and tumor formation of cancer cells.

Engineering of a novel breast tumor microenvironment on a microfluidic chip

The invention is directed to a method of inducing angiogenesis at a site in an individual in need thereof comprising administering locally to the site an effective amount of one or more agents that induce hypoxia induced factor 1&#x3b1; (HIF-1&#x3b1;). In another aspect, the invention is directed to a method of inducing angiogenesis at a site in an individual in need thereof comprising administering locally to the site an effective amount of one or more agents that induce hypoxia induced factor 1&#x3b1; (HIF-1&#x3b1;) and one or more lysophospholipids. In addition, the invention is directed to methods of generating prevascularized tissue, methods of generating a vascular network in a device and compositions thereof.

Compositions and methods for neovascularization

Provided herein are microfluidic devices that can be used as a 3D bioassay, e.g., for drug screening, personalized medicine, tissue engineering, wound healing, and other applications. The device has a series of channels {e.g., small fluid channels) in a small polymer block wherein one or more of the channels can be filled with a biologically relevant gel, such as collagen, which is held in place by posts. As shown herein, when the device is plated with cells such as endothelial cells, new blood vessels grow in the gel, which is thick enough for the cells to grow in three dimensions. Other channels, e.g., fluid channels, allow drugs or biological material to be exposed to the 3D cell growth. Cells, such as endothelial cells, can be cultured and observed as they grow on the surface of a 3D gel scaffold, where e.g., rates of angiogenesis can be measured, as well as intervascularization and extravascularization of cancerous cells.

Device for high throughput investigations of multi-cellular interactions

Provided are methods and devices for formation and study of three-dimensional biological systems, including prokaryotic and eukaryotic cell migration, proliferation, and differentiation.

Three-dimensional microfluidic platforms and methods of use thereof

A stent suitable for implantation in myocardial tissue to enhance perfusion therein may include a tubular member having first and second ends and a lumen. The first end of the stent may be configured to pierce myocardial tissue and the lumen may be configured to be placed in flow communication with a coronary vessel. The stent may further include a means for retaining the tubular member within the myocardial tissue. A method for implanting the stent may include positioning the first end of the stent at a desired implantation site and applying force to the second end of the stent to implant the stent within the myocardial tissue. The method may further include engaging the means for retaining with the myocardial tissue to retain the stent in position.

Left ventricular conduits to coronary arteries and methods for coronary bypass

A bypass conduit and related methods include implanting a bypass in the heart between a heart chamber and an at least partially occluded artery to directly flow blood from the chamber to the artery. The bypass conduit is configured to have a higher resistance to blood flow in a first direction than in a second direction without any active flow control mechanism. The bypass conduit may have a first end defining a first opening and a second end defining a second opening and a wall extending between the two ends that defines a lumen extending between the two openings. The ends and the wall of the conduit are configured to have a higher resistance to blood flow in a first direction than in a second direction. A method of bypassing an at least partially occluded artery includes determining a resistance to blood flow of the artery at a location of an at least partial occlusion and selecting a conduit having a configuration based on the resistance to blood flow of the artery at the location of the at least partial occlusion. The method further includes implanting the conduit in a heart wall between the heart chamber and the artery downstream of the at least partial occlusion to directly flow blood between the chamber and the artery.

Conduit designs and related methods for optimal flow control

A method and apparatus for deriving a physiological description and clinically-useful data reboarding the cardiovascular system of an individual subject. The method includes obtaining a measurement sample associated with cardiovascular flow and utilizing a model, which may be distributed and/or non-linear to derive a description and data. The model generates and uses functions of source parameters and may, in an embodiment, match measurement samples against a library of stored predicted samples. A best-matching, predicted sample may then be associated with a measurement sample. An apparatus is provided which, according to an embodiment, includes an input for obtaining a measurement sample, a processor to derive the description and data, and an output. The apparatus may also include a digital storage medium to store a library of predicted samples.

Method and apparatus for noninvasive assessment of a subject's

A catheter-filter set in an embodiment may be used in a vas through which a biological fluid may flow. This embodiment includes a tubular member, having a lumen disposed along its length and an insertion end for insertion into the vas. The lumen defines a longitudinal axis and a radial direction perpendicular thereto. The embodiment also has a filter, coupled to the tubular member and having a circumference, for trapping undesired particles. Finally, the embodiment includes a resilient member, having compliance in the radial direction, disposed circumferentially about the filter and, when deployed in the vas, forms a seal against the interior wall of the vas. Other embodiments are also provided.

Catheter-filter set having a compliant seal

A tobacco smoke article holder for a testing machine and a method of mounting a tobacco smoke article in the holder to simulate the human smoking process including an inflatably lined flow-through conduit having a depth substantially equal to the average width of a human lip and a cross-section in liner-relaxed state approximating the cross-section of the tobacco smoke article to accommodate normal insertion depth of the tobacco smoke article.

Tobacco smoke article holder and method therefor

A method and apparatus for testing pressure applied to a smoking article is provided and is particularly useful in testing lip pressure applied to cigarettes. The system includes a pressure sensor adapted to be positioned on a predetermined portion of the smoking article that is to be subjected to external pressure. A pressure transducer is connected to the sensor. The output of the transducer responsive to the pressure applied to the smoking article and sensed by the sensor is displayed. Additionally, a method and apparatus for calibrating the pressure sensor is included. The calibration system includes a rigid enclosure and an elastomeric tube positioned in a recess in the enclosure and connected to a pressure regulator. The enclosure includes a recess conforming to the configuration of the smoking article with a pressure sensor mounted thereon and positioned so that the smoking article in the recess is in communication with the elastomeric tube so that when the tube is pressurized it exerts a measured contact stress on the smoking article and pressure sensor. Thus, the calibration can take place over a range of anticipated pressures.

Method and apparatus for testing lip pressure applied to a smoking

Growing community of inventors

Cambridge, MA, United States of America

Roger Dale Kamm