Emulate, Inc.

Harvard College

Cedars-sinai Medical Center

Vanderbilt University

Children's Medical Center Corporation

Janssen Biotech, Inc.

Wen, Norman

Novak, Richard

Fernandez-alcon, Jose

Geraldine A Hamilton

Daniel Levner

Christopher David Hinojosa

Norman Wen

Catherine Karalis

Antonio Varone

S Jordan Kerns

Jacob Fraser

Riccardo Barrile

Donald Elliot Ingber

Justin Nguyen

Carolina Lucchesi

Remi Villenave

Clive N Svendsen

Dhruv Sareen

Hyoungshin Park

Carol Lucchesi

David Conegliano

Kevin Kit Parker

Andries Van Der Meer

Anthony Bahinski

Monicah Otieno

Josue A Goss

Gad Vatine

Robert Cunningham

Robert N Barrett

Magdalena Kasendra

Jefferson Puerta

Samuel Sances

Michael Workman

Stephen R Targan

Uthra Rajamani

Kambez Hajipouran Benam

Lina Williamson

Chris Hinojosa

Bryan Hassell

Kyung-Jin Jang

Sauveur Jeanty

Hyoung Shin Park

John P Wikswo

Josiah Daniel Sliz

Ronald S Reiserer

Dmitry A Markov

Kyung Jin Jang

Jose Fernandez-Alcon

Philip C Samson

David Edward Cliffel

Richard Novak

Gang Luo

Lisa J McCawley

Frank Emmanuel Block

Gadi Pelled

Dan Gazit

Guy Thompson

Zulma Gazit

Georg Bauer

Dmitriy Sheyn

Sonalee Barthakur

Alfred Paris

John A Mclean

Michael Salmon

Anna Herland

Tanvi Shroff

Brian Zuckerman

Karel Domansky

Jennifer Robin McKenzie

Akiko Mammoto

Ville Kujala

Janey Ronxhi

Sushma Jadalannagari

Thomas Umundum

Ananth Nookala

Catherine Spina

Daniel Patterson

SJordan Kerns

Janna Nawroth

Joshua Resnikoff

Samuel Sanees

Tadanori Mammoto

Yusuke Torisawa

Donald Mckenzie

Buket Baddal

Jordan Kerns

Magdelena Kasendra

Konstantia Kodelia

Debora Petropolis

Suzette Haney

Payal Patel

Ii Guy Thompson

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

Development of spinal cord on a microfluidic chip

The invention provides integrated Organ-on-Chip microphysiological systems representations of living Organs and support structures for such microphysiological systems.

Integrated human organ-on-chip microphysiological systems

An organomimetic device includes a microfluidic device that can be used to culture cells in its microfluidic channels. The organomimetic device can be part of dynamic system that can apply mechanical forces to the cells by modulating the microfluidic device and the flow of fluid through the microfluidic channels. The membrane in the organomimetic device can be modulated mechanically via pneumatic means and/or mechanical means. The organomimetic device can be manufactured by the fabrication of individual components separately, for example, as individual layers that can be subsequently laminated together.

Organomimetic devices and methods of use and manufacturing thereof

An in vitro microfluidic 'organ-on-chip' device is described herein that mimics the structure and at least one function of specific areas of the epithelial system in vivo. In particular, a stem cell-based Lung-on-Chip is described. This in vitro microfluidic system can be used for modeling differentiation of cells on-chip into lung cells, e.g., a lung (Lung-On-Chip), bronchial (Airway-On-Chip; small-Airway-On-Chip), alveolar sac (Alveolar-On-Chip), etc., for use in modeling disease states of derived tissue, i.e. as healthy, pre-disease and diseased tissues. Additionally, stem cells under differentiation protocols for deriving (producing) differentiated lung cells off-chips may be seeded onto microfluidic devices at any desired point during the in vitro differentiation pathway for further differentiation on-chip or placed on-chip before, during or after terminal differentiation.

Stem cell-based lung-on-chip models

Microfluidic 'organ-on-a-chip' devices have been developed with the aim to replicate human tissues in vitro. However, there is no option to quantitatively monitor biological processes that take place within the chip, over time. Destructive methods in order to analyze, tissue formation, gene expression, protein secretion etc. require the harvest of the “tissue” at a certain time point. Described herein are methods and compositions for non-destructive molecular imaging methods and systems in order to quantitatively monitor specific biological processes, over time, within the chip, without the need to harvest.

Method of osteogenic differentiation in microfluidic tissue culture systems

The invention generally relates to a microfluidic platforms or 'chips' for testing and understanding cancer, and, more specifically, for understanding the factors that contribute to cancer invading tissues and causing metastases. Tumor cells are grown on microfluidic devices with other non-cancerous tissues under conditions that simulate tumor invasion. The interaction with immune cells can be tested to inhibit this activity by linking a cancer chip to a lymph chip.

Devices, systems and methods for inhibiting invasion and metasases of cancer

Provided herein relates to systems and methods for producing and using a body having a central channel separated by one or more membranes. The membrane(s) are configured to divide the central channel into at least one mesochannel and at least one microchannel. The height of the mesochannel is substantially greater than the height of the microchannel. A gaseous fluid can be applied through the mesochannel while a liquid fluid flowing through the microchannel. The systems and methods described herein can be used for various applications, including, e.g., growth and differentiation of primary cells such as human lung cells, as well as any other cells requiring low shear and/also stratified structures, or simulation of a microenvironment in living tissues and/or organs (to model physiology or disease states, and/or to identify therapeutic agents and/or vaccines). The systems and methods can also permit co-culture with one or more different cell types.

Low shear microfluidic devices and methods of use and manufacturing thereof

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 relates to microfluidic fluidic devices, methods and systems as microfluidic kidney on-chips, e.g. human Proximal Tubule-Kidney-Chip, Glomerulus (Kidney)-Chip, Collecting Duct (Kidney)-Chip. Devices, methods and systems are described for drug testing including drug transport and renal clearance. Further, such devices, methods and systems are used for determining drug-drug interactions and their effect upon renal transporter functions. Importantly, they may be used for pre-clinical and clinical drug development for treating kidney diseases and for personalized medicine.

Microfluidic proximal tubule kidney-on-chip

Growing community of inventors

Boston, MA, United States of America

Geraldine A Hamilton