Massachusetts Institute of Technology

Battelle Memorial Institute

University of Pittsburgh

Karel Domansky

Jun Liu

Linda G Griffith

Glen E Fryxell

Suresh Baskaran

Steven R Tannenbaum

Nathan J Kohler

Xiaohong Shari Li

Alan H Wells

Samuel Walker Inman

Jerome C Birnbaum

Christopher Andrew Coyle

Suntharampillai Thevuthasan

Mark J Powers

Charles D Thompson

A system has been constructed that recapitulate the features of a capillary bed through normal human tissue. The system facilitates perfusion of three-dimensional (3D) cell monocultures and heterotypic cell co-cultures at the length scale of the capillary bed. A major feature is that the system can be utilized within a 'multiwell plate' format amenable to high-throughput assays compatible with the type of robotics commonly used in pharmaceutical development. The system provides a means to conduct assays for toxicology and metabolism and as a model for human diseases such as hepatic diseases, including hepatitis, exposure-related pathologies, and cancer. Cancer applications include primary liver cancer as well as metastases. The system can also be used as a means of testing gene therapy approaches for treating disease and inborn genetic defects.

Perfused three-dimensional cell/tissue disease models

The present invention is a method of dehydroxylating a silica surface that is hydroxylated having the steps of exposing the silica surface separately to a silicon organic compound and a dehydroxylating gas. Exposure to the silicon organic compound can be in liquid, gas or solution phase, and exposure to a dehydroxylating gas is typically at elevated temperatures. In one embodiment, the improvement of the dehydroxylation procedure is the repetition of the soaking and dehydroxylating gas exposure. In another embodiment, the improvement is the use of an inert gas that is substantially free of hydrogen. In yet another embodiment, the present invention is the combination of the two-step dehydroxylation method with a surfactant templating method of making a mesoporous film.

Method of dehydroxylating a hydroxylated material and method of making a mesoporous film

The present invention is a mesoporous silica film having a low dielectric constant and method of making having the steps of combining a surfactant in a silica precursor solution, spin-coating a film from this solution mixture, forming a partially hydroxylated mesoporous film, and dehydroxylating the hydroxylated film to obtain the mesoporous film. It is advantageous that the small polyoxyethylene ether surfactants used in spin-coated films as described in the present invention will result in fine pores smaller on average than about 20 nm. The resulting mesoporous film has a dielectric constant less than 3, which is stable in moist air with a specific humidity. The present invention provides a method for superior control of film thickness and thickness uniformity over a coated wafer, and films with low dielectric constant.

Mesoporous silica film from a solution containing a surfactant and methods of making same

Systems including (1) a micromatrix and perfusion assembly suitable for seeding and attachment of cells within the matrix and for morphogenesis of seeded cells into complex, hierarchical tissue or organ structures, wherein the matrix includes channels or vessels through which culture medium, oxygen, or other nutrient or body fluids can be perfused while controlling gradients of nutrients and exogenous metabolites throughout the perfusion path independently of perfusion rate, and (2) sensor means for detecting changes in either cells within the matrix or in materials exposed to the cells, have been developed. Methods for making the micromatrices include micromachining, micromolding, embossing, laser drilling, and electro deposition machining. Cells can be of one or more types, either differentiated or undifferentiated. In a preferred embodiment, the matrix is seeded with a mixture of cells including endothelial cells which will line the channels to form &ldquo;blood vessels&rdquo;, and at least one type of parenchymal cells, such as hepatocytes, pancreatic cells, or other organ cells. The system can be used to screen materials for an effect on the cells, for an effect of the cells on the materials (for example, in a manner equivalent to tissue metabolism of a drug), or to test a material on a biological that must first infect cells or tissues, such as viruses. The apparatus also can be used to provide a physiological environment for expansion of stem cells, or for enabling gene therapy in vitro.

Vascularized perfused microtissue/micro-organ arrays

Growing community of inventors

Cambridge, MA, United States of America

Karel Domansky