Massachusetts Institute of Technology

Vicam L.p.

Other

University of Pittsburgh

Newton Scientific, Inc.

Steven R Tannenbaum

Linda G Griffith

Gerald N Wogan

Thomas L Benjamin

Thomsen J Hansen

Ruth E Shefer

David M Livingston

Barbara J Hughey

Karel Domansky

John Timothy Mehl

Barbara Jackson

Paul L Skipper

John S Wishnok

Joan Chen-Wu

Anthony J Sinskey

Douglas A Lauffenburger

Alan H Wells

Samuel Walker Inman

Naomi A Fried

Miles Aaron Miller

Franz Fiedler

Stephen B Maul

Calvert L Green

Charles D Thompson

Mark J Powers

Evan L Chiswick

Ravindra Kodihalli

Christi Dionne Cook

Caroline Chopko Ahrens

Proteases regulate a wide range of normal cellular functions where dysregulated activity is observed in various diseases. Compositions and methods use protease activity multiplexed bead-based immunoassays to profile protease activity. This platform technology integrates protease activity measurements with total protein quantification techniques. It represents a significant improvement over existing detection techniques by allowing for multiplexed, sensitive active protease measurements in complex biological samples. Exemplary multiplexed detections are realized in a single assay using a minute sample amount (e.g., 5 &#x3bc;l) for active recombinant MMP-1, -2, -3, -7, 9, and 12 and those same MMPs in cell culture supernatant, menstrual fluid effluent, and peritoneal aspirates. This multiplexed platform achieves high level of sensitivities equal to or better than existing leading single-plex detection strategies. It also allows for high throughput screening to identify inhibitors of proteases in complex, donor-derived samples.

Compositions and multiplex assays for characterizing active proteases and their inhibitors

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

An interface for introducing a non-gaseous sample as a predetermined gaseous form into an accelerator mass spectrometer which comprises a nebulizer that receives the non-gaseous sample to provide a fine spray of the sample, a converter that receives at least a portion of said fine spray and converts the desired elements to the predetermined gaseous form and a flow line that transports the predetermined gaseous form to the accelerator mass spectrometer.

Sample introduction interface for analytical processing

An interface system for introducing a non-gaseous sample as a predetermined gaseous form into an analytical instrument which comprises a substrate that receives the non-gaseous sample and a directed energy source that heats at least a portion of said substrate containing the non-gaseous sample to convert the sample to the predetermined gaseous form.

Sample introduction interface for analytical processing of a sample placed on a substrate

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

An assay method is provided to easily and quickly detect the presence of organisms capable of being cultured, such as bacteria, characterized by antibody capture of the organism of interest by use of specialized magnetic beads, incubation of the captured cells to form colonies; removal of material from the colonies with a colony lift membrane; and detection of the colony material on the membrane sheet by use of labeled antibodies, PCR or nucleic acid probes.

Assay method for detecting presence of bacteria

Assay method for detecting the presence of bacteria

An assay method is provided to quickly detect the presence of Listeria strains in samples, characterized by the use of antibodies to selectively capture the peptidoglycan and teichoic acid components of the listeriae bacterial cell wall.

Assay method for detecting listeria

Process for reducing nucleic acid content of yeasts and bacteria comprising heat shocking for a period of time and at a temperature selected to increase effectiveness of enzymes which break down nucleic acids without allowing proteins to break down or leak out of the cell, and incubating the heat-shocked cells at a temperature lower than the heat shock temperature under conditions in which the cells remain intact and nucleic acid fragments permeate the cell walls.

Process for reducing nucleic acid content of yeasts and bacteria

Growing community of inventors

Framingham, MA, United States of America

Steven R Tannenbaum