Emulate, Inc.

Cedars-sinai Medical Center

S Jordan Kerns

Daniel Levner

Antonio Varone

Geraldine A Hamilton

Jacob Fraser

Christopher David Hinojosa

Norman Wen

Carolina Lucchesi

Clive N Svendsen

Catherine Karalis

Dhruv Sareen

Kyung Jin Jang

Carol Lucchesi

Jefferson Puerta

Dongeun Huh

Magdalena Kasendra

Riccardo Barrile

Robert N Barrett

Justin Nguyen

Remi Villenave

Gad Vatine

Stephen R Targan

Michael Workman

Uthra Rajamani

Lina Williamson

Josiah Daniel Sliz

David Conegliano

Samuel Sances

Brian Zuckerman

Tanvi Shroff

Grace Ahn

Michael Salmon

Jenifer Obrigewitch

Jonathan Rubins

Victor Antontsev

Benjamin Richards Umiker

Chris Hinojosa

Sonalee Barthakur

Ville Kujala

Anjoscha Kaus

Berhan Mandefro

Samuel Sanees

Hyoung Shin Park

The invention relates to culturing brain endothelial cells, and optionally astrocytes and neurons in a fluidic device under conditions whereby the cells mimic the structure and function of the blood brain barrier. Culture of such cells in a microfluidic device, whether alone or in combination with other cells, drives maturation and/or differentiation further than existing systems.

Microfluidic model of the blood brain barrier

Organs-on-chips are microfluidic devices for culturing living cells in micrometer sized chambers in order to model physiological functions of tissues and organs. Engineered patterning and continuous fluid flow in these devices has allowed culturing of intestinal cells bearing physiologically relevant features and sustained exposure to bacteria while maintaining cellular viability, thereby allowing study of inflammatory bowl diseases. However, existing intestinal cells do not possess all physiologically relevant subtypes, do not possess the repertoire of genetic variations, or allow for study of other important cellular actors such as immune cells. Use of iPSC-derived epithelium, including IBD patient-specific cells, allows for superior disease modeling by capturing the multi-faceted nature of the disease.

Systems and methods for growth of intestinal cells in microfluidic devices

The present invention is related to the field of microfluidics and compound distribution within microfluidic devices and their associated systems. In one embodiment, present invention aims to solve the problem of molecule and compound absorbency into the materials making up laboratory equipment, microfluidic devices and their related infrastructure, without unduly restricting gas transport within microfluidic devices.

Compound distribution in microfluidic devices

Development of spinal cord on a microfluidic chip

A microfluidic device is contemplated comprising an open-top cavity with structural anchors on the vertical wall surfaces that serve to prevent gel shrinkage-induced delamination, a porous membrane (optionally stretchable) positioned in the middle over a microfluidic channel(s). The device is particularly suited to the growth of cells mimicking dermal layers.

Open-top microfluidic device with structural anchors

An in vitro microfluidic 'organ-on-chip' is described herein that mimics the structure and at least one function of specific areas of the epithelial system in vivo. In particular, a multicellular, layered, microfluidic culture is described, allowing for interactions between lamina propria-derived cells and the associated tissue specific epithelial cells and endothelial cells. This in vitro microfluidic system can be used for modeling inflammatory tissue, e.g., autoimmune disorders involving epithelia and diseases involving epithelial layers. These multicellular, layered microfluidic 'organ-on-chip', e.g. 'epithelia-on-chip' further allow for comparisons between types of epithelia tissues, e.g., lung (Lung-On-Chip), bronchial (Airway-On-Chip), skin (Skin-On-Chip), cervix (Cervix-On-Chip), blood brain barrier (BBB-On-Chip), etc., in additional to neurovascular tissue, (Brain-On-Chip), and between different disease states of tissue, i.e. healthy, pre-disease and diseased areas. Additionally, these microfluidic &#x201c;organ-on-chips&#x201d; allow identification of cells and cellular derived factors driving disease states in addition to drug testing for reducing inflammation effecting epithelial regions.

In vitro epithelial models comprising lamina propria-derived cells

The present invention contemplates compositions, devices and methods of simulating biological fluids in a fluidic device, including but not limited to a microfluidic chip. In one embodiment, fluid comprising a colloid under flow in a microfluidic chip has a fluid density or viscosity similar to a bodily fluid, e.g. blood, lymph, lung fluid, or the like. In one embodiment, a fluid is provided as a Theologically biomimetic blood surrogate or substitute for simulating physiological shear stress and cell dynamics in fluidic device, including but not limited to immune cells.

Rheologically biomimetic fluid surrogate

Compositions, devices and methods are described for improving adhesion, attachment, and/or differentiation of cells in a microfluidic device or chip. In one embodiment, one or more ECM proteins are covalently coupled to the surface of a microchannel of a microfluidic device. The microfluidic devices can be stored or used immediately for culture and/or support of living cells such as mammalian cells, and/or for simulating a function of a tissue, e.g., a liver tissue, muscle tissue, etc. Extended adhesion and viability with sustained function over time is observed.

Compositions and methods of cell attachment

Growing community of inventors

Reading, MA, United States of America

S Jordan Kerns