Organ-on-a-Chip and Body-on-a-Chip: In Vitro Systems Mimicking In Vivo Functions Agenda

Conference Registration, Materials Pick-Up and Continental Breakfast in the Exhibit Hall

Coffee Break and Networking in the Exhibit Hall

Networking Lunch, Discussions with Exhibitors and View Posters

Organs on Chips for Drug development, Toxicology, and Systems Biology: A Distributed yet Interconnected Modular Approach
John Wikswo, Gordon A. Cain University Professor, A.B. Learned Professor of Living State Physics; Founding Director, Vanderbilt Institute for Integrative Biosystems, Vanderbilt University, United States of America

Organs-on-chips are undergoing rapid development to better recapitulate in vitro the function of human organs in vivo. Their application to a variety of fields suggests the need to create large numbers of different organs and operate them either independently or interconnected, or both. This places economic and topological constraints on the physical hardware systems that keep these organs alive, monitors their performance, and controls their interaction. A promising approach is to utilize different low-cost modules, made from a simple set of common components, to provide these functions in a plug-and-play manner, thereby spanning the range of applications of organs on chips pursued from organizations as small as a single-investigator biology lab to government toxicology screening programs to pharmaceutical groups evaluating the efficacy and toxicity of drugs and drug cocktails.

The Patent Landscape of Organs-On-A-Chip
Deborah Sterling, Director, Sterne, Kessler, Goldstein & Fox PLLC, United States of America

Organs-on-a-chip have present-day real-world uses such as for the preclinical testing of drugs. Thousands of patents have been filed on various aspects of organs-on-a-chip, including their manufacture.  A company seeking to make, use or sell an organ-on-a-chip must consider the patent landscape.  This talk will focus on ways to protect organs-on-a-chip innovation, patent filings directed to organs-on-a-chip technology, certain exceptions to patent infringement, as well as the possibility of future litigation.

Coffee Break and Networking

Panel Discussion Focusing on Challenges and Opportunities in the Organs-on-Chip Space Moderated by Dr. David Hughes, CN Bio Innovations Ltd.

Networking Cocktail Reception for All Delegates, Speakers, Sponsors and Exhibitors: Enjoy Beer, Wine, Appetizers and a View of the Charles River and Boston from the 15th Floor Conference Center

Close of Day 1 of the Conference

Morning Coffee, Breakfast Pastries, and Networking

Human Physiome-on-a-Chip: A Systems Pharmacology Approach
Murat Cirit, Director at Translational Center of Tissue Chip Technologies, Massachusetts Institute of Technology (MIT), United States of America

A systems pharmacology perspective in the human body on a chip field problem incorporates more mechanistic detail than traditional pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) models yet within broadly comprehensive scope. These systems pharmacology approaches offer new insight into design of experiments, data interpretation and organ-specific responses, which can be translated to in vivo responses, such as drug efficacy and toxicity. For example, ADME, pharmacodynamic and toxicodynamic properties of a drug can be experimentally investigated in multi-MPS platforms under various physiological conditions.  Complex experimental results can be interpreted using mechanistic pharmacokinetic & pharmacodynamics (PK/PD) models allowing us to predict clinical outcomes more accurately than existing preclinical animal models.

Medical Device-on-a-Chip: The Future of Performance and Safety Testing?
K. Scott Phillips, Biofilms Research Group Leader, US FDA Center for Devices and Radiological Health, United States of America

Organ-on-a-chip models combine lab-on-a-chip technology with tissue culture techniques to more accurately mimic human physiology. In the field of pharmaceuticals, organ-on-a-chip in vitro models have seen rapid development. Although medical devices and pharmaceuticals have a number of similar testing needs, there has been no recognition of the potential for lab-on-a-chip models to transform performance and/or safety testing of medical devices. In this talk, we will describe the potential advantages of medical-device-on-a-chip (MDOC) technology to help increase the speed of performance and safety testing for medical devices, while decreasing the overall burden required to bring new technologies to market. We will discuss efforts in our laboratory to miniaturize current test methods, and  solutions that were developed to overcome unique challenges associated with combining macroscale device materials and microscale fluidics.

Microfluidic Spatiotemporal Control Technology for Organ-on-a-Chip
Hiroshi Kimura, Professor, Micro/Nano Technology Center, Tokai University, Japan

Conventional cell-based assays in life science and medical application can be difficult to maintain cell functionally. Microfluidics is an emerging technology with potential to provide integrated environments for maintenance, control, and monitoring of surround of cells. Our research group works in mainly in fundamental technologies of microfluidic devices and systems, and their applications to biological sciences including and Organ-on-a-chip and Tissue-on-a-chip. In this presentation, we introduce integrated microfluidic platforms, which allow precisely control of the cell culture environment on Organ-on-a-chips. The microfluidic structure in the devices can mimic a physiological environment in vitro. Moreover, functional components, such as membranes, sensors, valves and pumps, can be integrated into the devices by microfabrication. We have applied the devices to organ cell assay, embryo culture, and tissue culture. Performance of the devices was examined through cell and tissue culture. These devices may have applications in drug screening and toxicity testing.

3D Sprouting Lymph-angiogenesis Platform
Noo Li Jeon, Professor, Seoul National University, Korea South

Formation of new lymphatic vessels, lymphangiogenesis, is central in diverse biological processes during development, inflammation and tumor metastasis. Currently there are no reliable models to recapitulate how sprouting lymphangiogenesis is initiated and coordinated. This presentation will describe a microfluidic platform optimized for reconstitution of lymphangiogenesis. With control over chemical and physical factors such as biochemical cues, interstitial flow (IF), and cell-cell interactions (endothelial-fibroblast), we found that coordinated effects of multiple factors are necessary for robust lymphatic sprouting in 3D extracellular matrix.  We observed that IF serves as an important cue that defines lymphangiogenic response and phenotypes of primary lymphatic endothelial cells. When combined with pro-lymphangiogenic factors, IF significantly increase and guide initiation and outgrowth of lymphatic sprouts toward upstream of the flow while suppressing downstream-directed sprouting. The lymphatic sprouts expressed molecular signatures and cellular phenotypes that closely approximate sprouting lymphatic neovessels in vivo, and reflected the modulatory effects of pro- and anti-lymphangiogenic stimuli.  Mechanical cue in the form of IF have profound effect on lymphangiogenic sprouting and thus the microfluidic platform provides a useful in-vitro model for investigation of lymphangiogenesis for organ-on-a-chip applications.

Coffee Break and Networking in the Exhibit Hall

Bioreactors for Megakaryocyte Studies and Platelet Formation: Where Do We Stand?
Jonathan Thon, Assistant Professor, Brigham and Women's Hospital/Harvard Medical School, Co-Founder -- Platelet BioGenesis, United States of America

Platelets are responsible for clot formation and blood vessel repair and are produced by megakaryocytes in the bone marrow. Low platelet count is a significant consequence of transplant and surgery, for which platelets are a critical first-line therapy to prevent mortality due to uncontrolled bleeding. While cancers and their treatments have been shown affect normal platelet production affecting the pathogenesis of disease, the causes are largely unknown. The development of microfluidic platforms that accurately model microvascular niches and offer high-resolution live-cell visualization of biological phenomenon and precise control of individual environmental components are needed to elucidate the mechanism(s) regulating platelet production in vivo. Likewise, the production of lab-generated human platelets is necessary to meet present and future transfusion needs. We have shown that it is feasible to generate functional megakaryocytes from human embryonic, cord blood and induced pluripotent stem cell cultures. The most significant obstacle to ex vivo platelet production has been triggering megakaryocytes to produce platelets at yields necessary to make production of a platelet transfusion unit clinically and commercially feasible. Evidence suggests that key physiological characteristics of the bone marrow environment including extracellular matrix composition, bone marrow stiffness, endothelial cell contacts, and vascular shear stresses trigger platelet release. We recently developed a scalable microfluidic platelet bioreactor that recapitulates these major characteristics of human bone marrow. By exposing megakaryocytes to physiological shear stresses of blood we have improved the rate and extent of platelet production, and reduced the time to initiation of platelet release. Morphology, ultrastructure and function of our bioreactor platelets is consistent with blood platelets. We are separately adapting our platelet bioreactor to: (1) more accurately recapitulate b

Towards Organs-on-Chip Devices in Multiwell Format for Drug Testing, Mechanistic Studies, and Personalized Medicine
Martin Stelzle, Head of BioMEMS & Sensors Department, NMI at University of Tübingen, Germany

Organs-on-chip are envisioned to enable in vivo like answers in preclinical drug testing by establishing cell cultures mimicking the smallest functional units of an organ. We will report on our organs-on-chip technology based on combining microfluidics and dielectrophoresis (DEP) to assemble primary human cells and enabling the automated in vitro construction of micro-organs. As a unique feature of this organ-on-chip technology, the use of DEP selectively assembles only viable cells. Organ-specific 3D cell culture chambers are designed and validated by multiphysics simulations and realized by injection molding of cyclic olefin polymer (COP). Proprietary surface functionalization enables selective deposition of extracellular matrix proteins in a simple perfusion process. High resolution optical imaging of micro-organs along with typical staining technologies can be applied due to the exceptional optical properties of COP. In addition, perfundates and lysates may be collected for biochemical analysis. A particular focus is placed on the design of devices in multiwell plate format in combination with a dedicated periphery system in order to enable assembly and cultivation of multiple micro-organs per chip and integration of the system into existing workflows. In summary, this technology is applicable to the assembly and culture of diverse organ tissues involving complex arrangement of multiple cell types and extracellular matrix and enables continuous perfusion of these micro-organs. A large number of applications in drug testing, mechanistic studies, and in personalized medicine are envisioned to benefit from this technology.

Modeling and Simulation of Microfluidic Organ-on-Chip Devices
Matthew Hancock, Managing Engineer, Veryst Engineering, LLC, United States of America

Modeling and simulation are key components of the engineering development process, providing a rational, systematic method to engineer and optimize products and dramatically accelerate the development cycle over a pure intuition-driven, empirical testing approach. Modeling and simulation help to identify key parameters related to product performance (“what to try”) as well as insignificant parameters or conditions related to poor outcomes (“what not to try”). For microfluidic organ-on-chip devices, modeling and simulation can inform the design and integration of common components such as micropumps, manifolds, and channel networks. Modeling and simulation may also be used to estimate a range of processes occurring within the fluid bulk and near cells, including shear stresses, transport of nutrients and waste, chemical reactions, heat transfer, and surface tension & wetting effects. I will discuss how an array of modeling tools such as scaling arguments, analytical formulas, and finite element simulations may be leveraged to address these microfluidic organ-on-chip device development issues.

Networking Lunch in the Exhibit Hall: Visit Exhibitors and Poster Viewing

Prostate-on-a-Chip
Nathalie Picollet-D’Hahan, Senior Project Manager, Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA) Grenoble, France

3D Cell-Printed Brain Cancer-on-a-Chip Recapitulates Pathophysiology in vitro
Hee-Gyeong Yi, Researcher, Pohang University of Science and Technology, Korea, Korea South

Establishment of in vitro glioblastoma model by recreating the heterogeneous microenvironment with spatial control of oxygen and cellular arrangement.

Immunotherapy on Chip: “Under the Microscope” Drug-Induced Modulation of the Immune Response
Luca Businaro, Scientist, Italian National Research Council, Italy
Adele De Ninno, Post-Doc, University of Rome "Tor Vergata", Italy

Reconstitution of the immune system through organ-on-chip (OOC) approach opens a new window to live observation of the immune response to insults with or without drug treatments, making OOC a cornerstone for dissecting complex biological phenomena and pre-clinical testing of drugs.

Coffee Break and Networking

Controlled Drug Release and Cell Response with a 3D Acoustofluidic Tumor Model
Ioannis Zervantonakis, Research Fellow in Cell Biology, Harvard Medical School, United States of America

We developed a novel acoustofluidic platform by integrating a physiologically relevant 3D microfluidic device and a FUS system with a closed-loop controller to study drug transport and assess the response of cancer cells to chemotherapy in real time using live cell microscopy. Our 3D platform enables the accurate control of the drug-release area in order to establish chemotherapeutic agent concentration gradients in a physiologically relevant environment. This acoustofluidic platform that can aid the discovery of new therapeutic protocols for non-invasive cancer treatments that target tumor cells regionally without damaging adjacent normal cells.

Towards the Growth of Blood Vessel Networks in Microfluidic Culture
Muhammad Ibrahim, Researcher, Institute of Biology, Leiden University, Netherlands

One of the major limitations in culturing complex tissues or organs is the lack of vascularization in the cultured tissue. Development of a functional capillary bed in 3D microfluidic culture could overcome this problem. Unlike static culture systems, microfluidic cultures allow the flow of medium to mimic blood flow in vivo, hence allowing the endothelial cells in culture to develop into functional blood vessels with lumina. In this presentation the importance of 3D cell culture and microfluidic technology for development of in vitro vascular network will be discussed.  We are using zebrafish embryonic cells as a low-cost, high-throughput replacement for mammalian cell culture models, currently used for in vitro vasculogenesis and angiogenesis studies. Aggregates of embryonic blastocyst cells (embryoid bodies), containing differentiated endothelial cells, were embedded in a 3D hydrogel and plated into a microfluidic channel. The channel was then connected to a medium reservoir and a microfluidic pump to start the flow of medium through the channel. The results showed significant effects of microfluidic flow on the morphology of blood vessel-like structures formed by the differentiated endothelial cells.

Increased Stiffness of Lung Fibroblast Cell Aggregates in Idiopathic Pulmonary Fibrosis
Fernando Rafael Jativa, Research Scientist, The University of Melbourne, Australia

The present study show 3D fibroblast spheroids are an effective tool to study idiopathic pulmonary fibrosis (IPF). Spheroid stiffness was assessed by microfluidics and micropipette aspiration, revealing an increase of 64% in stiffness when using primary cells from IPF patients to make spheroids, whereas stiffness of individual cells was not altered by IPF.

Close of Day 2 of the Conference