Emulate, Inc.

Harvard College

Janssen Biotech, Inc.

Antonio Varone

Daniel Levner

Geraldine A Hamilton

Catherine Karalis

Norman Wen

S Jordan Kerns

Riccardo Barrile

Justin Nguyen

Jacob Fraser

Christopher David Hinojosa

Kyung Jin Jang

David Conegliano

Dongeun Huh

Carolina Lucchesi

Hyoungshin Park

Andries Van Der Meer

Monicah Otieno

Remi Villenave

Donald Elliot Ingber

Richard Novak

Magdalena Kasendra

Carol Lucchesi

Lori McPartlin

Youngjae Choe

Lina Williamson

Lian Leng

Athanasia Apostolou

Raymond Luc

Sonalee Barthakur

Tanvi Shroff

Janna Nawroth

Hyoung Shin Park

Jordan Kerns S

Justin K Nguyen

Debora Barreiros Petropolis

A device for simulating a function of a tissue includes a first structure, a second structure, and a membrane. The first structure defines a first chamber. The first chamber includes a matrix disposed therein and an opened region. The second structure defines a second chamber. The membrane is located at an interface region between the first chamber and the second chamber. The membrane includes a first side facing toward the first chamber and a second side facing toward the second chamber. The membrane separates the first chamber from the second chamber.

Open-top microfluidic devices and methods for simulating a function of a tissue

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

An in vitro microfluidic intestine on-chip is described herein that mimics the structure and at least one function of specific areas of the gastrointestinal system in vivo. In particular, a multicellular, layered, microfluidic intestinal cell culture, which is some embodiments is derived from patient's enteroids-derived cells, is described comprising L cells, allowing for interactions between L cells and gastrointestinal epithelial cells, endothelial cells and immune cells. This in vitro microfluidic system can be used for modeling inflammatory gastrointestinal autoimmune tissue, e.g., diabetes, obesity, intestinal insufficiency and other inflammatory gastrointestinal disorders. These multicellular-layered microfluidic intestine on-chips further allow for comparisons between types of gastrointestinal tissues, e.g., small intestinal duodenum, small intestinal jejunum, small intestinal ileum, large intestinal colon, etc., and between disease states of gastrointestinal tissue, i.e. healthy, pre-disease and diseased areas. Additionally, these microfluidic gut-on-chips allow identification of cells and cellular derived factors driving disease states and drug testing for reducing inflammation.

Physiology and pathophysiology of human gut: intestine-on-chip

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

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

West Roxbury, MA, United States of America

Antonio Varone