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SELECTBIO Conferences Organ-on-a-Chip World Congress 2019

Organ-on-a-Chip World Congress 2019 Agenda

Co-Located Conference Agendas

3D-Culture & Organoids 2019 | 3D-Printing in the Life Sciences | Organ-on-a-Chip World Congress 2019 | Stem Cells in Drug Discovery Tox & Organoids 2019 | The Space Summit 2019 | 

Print Agenda

Monday, 14 October 2019


Conference Registration, Materials Pick-Up, Morning Coffee and Pastries in the Exhibit Hall

Welcome and Introduction to the Conference by Conference Chairpersons

Plenary Session Venue: Coronado Ballrooms A & B


Nancy AllbrittonConference Chair

Conference Chairperson
Nancy Allbritton, Kenan Professor of Chemistry and Biomedical Engineering and Chair of the Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, United States of America


Y. Shrike ZhangConference Chair

Conference Chairperson
Y. Shrike Zhang, Assistant Professor of Medicine, Harvard Medical School, Associate Bioengineer, Division of Engineering in Medicine, Brigham and Women’s Hospital, United States of America


Modeling Immune Mediated Beta Cell Destruction in Human Type 1 Diabetes with Organoids
Matthias von Herrath, Vice President and Senior Medical Officer, Novo Nordisk, Professor, La Jolla Institute, United States of America

In the past 15 years we have been studying the pathology of human type 1 diabetes with access to donor pancreata through the human pancreatic organ donor consortium (nPOD). These studies have led to several findings, for example that certain cytokines are generated by beta cells themselves, sometimes under stress, and also that there are probably key factors that render beta cells susceptible to immune attacks. Mechanistically, the importance and meaning of these observations needs to be addressed in a suitable and easily manipulable in vitro system consisting of human islets and immune cells. We have built such a system in collaboration with the company InSphero and will discuss emerging findings.


John WikswoKeynote Presentation

Pumps, Valves, and Fluidic Connectors for Automating and Integrating Microphysiological Systems
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

Much of the organ-on-chip and tissue-chip research to date has relied on very simple perfusion schemes that include surface tension, hydrostatic pressure, rocking plates, syringe pumps, pressurized reservoirs, and on-chip pneumatic or electromagnetic peristaltic pumps. A number of commercial microphysiological systems are moving towards high-throughput well-plate formats. Each of these fluid handling technologies presents different advantages in cost, convenience, and simplicity, and disadvantages regarding reservoir filling, media change, recirculation and volume minimization, organ-organ integration, bubble- and microbe-free addition and removal of chips from multi-organ microphysiological systems, temporal control of drug concentrations, adjusting/balancing flow rates, and controlling sensors for long-term use. While a common trend is towards high throughput and low cost, there are critical applications where high content is more important than high throughput, particularly those requiring multi-omic characterization of physiological responses over time to drugs and toxins for both single and multiple organs. We review how our computer controlled, modular, rotary planar peristaltic micropumps and twenty-five port rotary planar valves can be used to create autocalibrating electrochemical MicroClinical Analyzers, multi-well MicroFormulators that can create in vivo the pharmacokinetics observed in animals and humans, and perfusion controllers for multiple NeuroVascular Unit, Gut-in-a Puck, and Thick Tissue Mammary Bioreactors. Pumps and valves are useful for compact perfusion controllers that operate in microgravity environments. Miniature rotary valves will enable bubble-free, sterile connection and disconnection of individual organ chips to other organs and analyzers. Ongoing and future applications include 100-port valves and systems for optimizing the differentiation of induced pluripotent stem cells, a 10,000 channel yeast MicroChemostat, and a MicroDialysis imager, all with direct injection into a mass spectrometer. The cost and complexity of these systems over present technologies is balanced by sophisticated computer control and sensor integration, reduced technician effort, high content results, and parallelization.


Nancy AllbrittonKeynote Presentation

Intestinal Epithelium for Basic Physiology and Drug Assays
Nancy Allbritton, Kenan Professor of Chemistry and Biomedical Engineering and Chair of the Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, United States of America

Organ-on-chips are miniaturized devices that arrange living cells to simulate functional subunits of tissues and organs. These microdevices provide exquisite control of tissue microenvironment for the investigation of organ-level physiology and disease. Human organ-on-chips are expected to transform biomedical research providing platforms that accurately replicate human tissues, enable a better understanding of human-to-human physiologic variations, and even permit patient-specific organ mimics. These human organ facsimiles will fundamentally alter drug discovery and development by providing human constructs for screening assays, toxicity measurements and investigation of molecular-level drug actions. Breakthroughs in stem-cell biology now enable single stem cells or intestinal crypts isolated from primary mouse or human intestine or differentiated from induced pluripotent stem cells (iPSCs) to grow and persist indefinitely in defined 3D culture conditions to form organotypic structures generically termed enteroids. We have developed a long-lived, self-renewing monolayer culture format from primary intestinal cells. A surface matrix and chemical factors sustain the epithelial cell monolayers so that they possess all cell repertoires found in vivo. This technical advance has made it possible to create primary tissues on platforms that are compatible with high-content screening strategies. For example, the screening of 77 dietary compounds revealed that these compounds altered proliferation to increase stem cell numbers or increased cell differentiation with formation of increased numbers of goblet cells or enterocytes. Measurement of drug transport and metabolism has also been demonstrated in these human intestinal monolayer systems as well as formation of physiologic mucus layers many hundreds of microns thick. Culture of these monolayers on a shaped scaffold under chemical gradients replicates much of the cell compartmentalization and physiology observed in vivo. This bioanalytical platform is envisioned as a next-generation system for assay of microbiome-, drug- and toxin-interactions with the intestinal epithelia. Finally, intestinal biopsy samples can be used to populate these constructs with cells producing patient-specific tissues for personalized medicine that can be applied to emerging areas of disease modeling and microbiome studies.


Albert FolchKeynote Presentation

Digital Manufacturing of Microfluidic Tissue Chips
Albert Folch, Professor of Bioengineering, University of Washington, United States of America

The microfluidics field is at a critical crossroads. The vast majority of microfluidic devices are presently manufactured using micromolding processes that work very well for a reduced set of biocompatible materials, but the time, cost, and design constraints of micromolding hinder the commercialization of many devices. PDMS, in particular, is extremely popular in academic labs, yet the fabrication procedures are based on cumbersome manual methods and the material itself strongly absorbs lipophilic drugs. As a result, the dissemination of many cell-based microfluidic chips – and their impact on society – is in jeopardy. Digital Manufacturing (DM) is a family of computer-centered processes that integrate digital 3D designs, automated (additive or subtractive) fabrication, and device testing in order to increase fabrication efficiency. Importantly, DM enables the inexpensive realization of 3D designs that are impossible or very difficult to mold. The adoption of DM by microfluidic engineers has been slow, likely due to concerns over the resolution of the printers and the biocompatibility of the resins. We have developed microfluidic devices by SL in PEG-DA-based resins with automation and biocompatibility ratings similar to those made with PDMS. I will also present our work on our microfluidics platform (digitally-manufactured in thermoplastics) for cancer diagnostics using live tumor biopsies and I will review the bright future ahead for the promising, fertile field of DM.


Morning Coffee Break and Networking in the Exhibit Hall


Roger KammKeynote Presentation

Models of Neurological Disease
Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, Massachusetts Institute of Technology (MIT), United States of America

Many of the most debilitating and life-threatening diseases are associated with the central nervous system. Some, such as neurodegenerative diseases, predominately afflict our aging population. Yet others such as brain cancers and ALS are prevalent among young and old alike. In this presentation, models will be presented that attempt to recapitulate certain aspects of the brain and these diseases, both to probe the disease process, and as a platform to screen for new therapeutics. Three examples will be presented. First, a model for the healthy blood-brain barrier and neurovascular unit have been developed in order to capture the essential aspects associated with these diseases. Second, the blood-brain barrier model is used to study metastasis of cancers to the brain, as well as primary glioblastoma. In the third part of the talk, a model for the healthy and diseased neuromuscular junction will be presented as a step toward developing therapeutic strategies for treating ALS.


Steven C. GeorgeKeynote Presentation

“Bone Marrow-on-a-Chip”: A Strategy to Replicate Hematopoiesis and Cancer Cell Dormancy
Steven C. George, Edward Teller Distinguished Professor and Chair, Department of Biomedical Engineering, University of California-Davis, United States of America

Tissue engineering holds enormous potential to not only replace or restore function to a wide range of tissues, but also to capture and control 3D physiology in vitro (e.g., microphysiological systems or “organ-on-a-chip” technology).  The latter has important applications in the fields of drug development, toxicity screening, modeling tumor metastasis, and repairing damaged cardiac (heart) muscle. In order to replicate the complex 3D arrangement of cells and extracellular matrix (ECM), new human microphysiological systems must be developed.  The past decade has brought tremendous advances in our understanding of stem cell technology and microfabrication producing a rich environment to create an array of “organ-on-a-chip” designs.  Over the past six years we have developed novel microfluidic-based systems of 3D human microtissues (~ 1 mm3) that contain features such as perfused human microvessels, primary human cancer, mouse tumor organoids, stem cells, and spatiotemporal control of oxygen.  The technologies are part of two early start-up companies, Kino Biosciences and Immunovalent Therapeutics, based in Irvine, CA and St. Louis, MO.  This seminar will describe our approach and early results on a strategy to create a 3D in vitro model of human bone marrow with applications in hematopoiesis and cancer cell dormancy.


Kevin HealyKeynote Presentation

Human Tissue Chips for Drug Development, Disease Modeling, and More…
Kevin Healy, Jan Fandrianto and Selfia Halim Distinguished Professorship in Engineering, University of California, Berkeley, United States of America

Our work has emphasized creating both healthy and diseased model organ systems, we call microphysiological systems or ‘tissue chips’, to address the costly and complex drug discovery process. The average time to develop and launch a new drug in the United States is 10-15 years, and costs ~ $2-5b. The poor efficiency and high failure rates are attributed to the heavy reliance on non-human animal models employed during safety and efficacy testing that poorly reflect human disease states. With the discovery of human induced pluripotent stem cells, we can now develop tissue chips to be used for high content drug screening, disease modelling, and numerous other applications. While tissue chips are poised to disrupt the drug development process and significantly reduce the cost of bringing a new drug candidate to market, tissue chip technology is much more robust and creates a whole new paradigm in how to conduct biological science, and advances medicine in revolutionary ways. Ultimately, the vision is to reduce or eliminate the use of animals in drug discovery, and conduct ‘clinical trials’ in patient-specific tissue chips that can accommodate variations in genetics, environment, and lifestyle.


Networking Lunch in the Exhibit Hall, Exhibits and Poster Viewing


Delegates Welcomed to Attend Afternoon Concurrent Sessions: The Space Summit (Ballroom C) or Organoids (Ballroom D)


Networking Reception with Beer Wine and Dinner in the Exhibit Hall -- Sponsored by ATCC


Close of Day 1 of the Conference

Tuesday, 15 October 2019


Morning Coffee, Pastries and Networking in the Exhibit Hall

Session Title: Emerging Themes and Technologies in the Organs-on-Chips Field, circa 2019

Venue: Coronado Ballroom A


Merging Human Microphysiological Systems with Quantitative Systems Pharmacology for In Vitro In Vivo Translation
Murat Cirit, CEO & Co-Founder, Javelin Biotech, United States of America

A large percentage of drug candidates fail at the clinical trial stage due to a lack of efficacy and unacceptable toxicity, primarily because of translational gap between human physiology and preclinical models including both in vitro culture and animal models. This need for more human-physiology relevant in vitro systems for preclinical efficacy and toxicity testing has led to a major effort to develop “Microphysiological Systems (MPS)”, aka tissue chips (TC) or organs on chips (OOC), based on engineered human tissue constructs.

MPSs hold promise for improving therapeutic drug approval rates by providing more physiological, human-based, in vitro assays for preclinical drug development activities compared to traditional in vitro and animal models. The full impact of MPS technologies to bridge the gap preclinical and clinical gap will be realized only when robust approaches for in vitro–in vivo (MPS-to-human) translation are developed and utilized.


Michael ShulerKeynote Presentation

Human In Vitro Models to Improve Preclinical Testing of Drugs
Michael Shuler, Samuel B. Eckert Professor of Engineering, Cornell University, President Hesperos, Inc., United States of America

Human microphysiological or “Body-on-a-Chip” systems are powerful tools to assess the potential efficacy and toxicity of drugs in pre-clinical studies.  Having a human based, multiorgan system, that emulates key aspects of human physiology can provide important insights to complement animal studies and in vitro studies using human cells from a single organ in the decision about which drugs to move into clinical trials1.  Our human surrogates are constructed using a low cost, robust “pumpless” platform.  We use this platform in conjunction with “functional” measurements of electrical and mechanical activity of tissue constructs (in collaboration with J. Hickman, University of Central Florida). Also by combining PBPK-PD models2 with these devices we can enhance our predictive power for anticipating human responses. Using a system with four or more organs we can predict the exchange of metabolites between organ compartments in response to various drugs and dose levels. We have constructed models incorporating barrier tissues such as GI tract, blood brain barrier, and skin with internal organs such as liver, cardiac, and neuromuscular junctions. With these systems, we can predict both efficacy and toxicity of drugs in humans from preclinical studies3.  Further, we can use these systems to investigate temporal concentration relationships of drugs during preclinical development4. We believe that these “Body-on-a-Chip” systems have great potential to increase the efficiency of conversion of drug candidates into successful projects.


InSphero AGImplementing a Scalable Body-on-a-Chip Metabolic Disease Model based on Human Liver and Islet Microtissues
Olivier Frey, Vice President Technologies and Platforms, InSphero AG

Liver and pancreas constitute key organs in the metabolic syndrome and are highly interacting through different endocrine factors to maintain glucose homeostasis in the human body. An impaired function of one of the organs can cause metabolic diseases, such as diabetes or NASH. Studying these diseases requires a systemic model that can reproduce organ-organ-interactions. The practical implementation of human in-vitro multi-tissue systems in a scalable format includes several challenges. Key aspects encompass biological and technical reproducibility, availability of tissue models, possibility of on-demand production, their usability in suitable treatment windows, access to clinically relevant readouts, and system compatibility with standard lab processes. We implemented a human in-vitro multi-tissue system in a scalable format using 3D organotypic microtissues for establishing organ-organ interactions. The liver model consisted of a primary human hepatocyte/Kupffer cell co-culture with preserved metabolic and inflammatory function over at least two weeks. The primary human islet microtissues comprised all pancreatic endocrine cells at physiological ratio and remained glucose responsive over the same culturing period. The different microtissues were assembled in a microfluidic chip using a pipetting robot enabling an adequate number of replicates at minimal operational complexity for compound testing with access to a wide range of readouts.


Microfluidic ChipShop GmbHIt’s the Economy – Industrial Aspects of Organ-on-a-Chip Device Manufacturing
Holger Becker, Chief Scientific Officer, Microfluidic ChipShop GmbH

While academic activities in the organ-on-a-chip field have multiplied in recent years, it becomes apparent that translating academic results into commercially viable products can be challenging. This is even more true for such devices which require a generically multidisciplinary approach, combining application know-how with surface chemistry, microfabrication and materials technology. In this presentation, we will give an overview over available solutions for such products and explain classical pitfalls on the way from the academic laboratory bench to an industrial product.


Morning Coffee Break and Networking in the Exhibit Hall


CellScale Biomaterials TestingA Microphysiological System Without Pumps, Tubes, or Valves
Caleb Horst, President, CellScale Biomaterials Testing

Follow the innovation journey as our team develops a cell culture system that delivers meaningful improvements to standard in vitro culture techniques while keeping the system simple, inexpensive, and high throughput.


Veryst Engineering, LLCModeling and Simulation of Microfluidic Organ-on-a-Chip Devices
Matthew Hancock, Managing Engineer, Veryst Engineering, LLC

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 mixers, 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-a-chip device development issues. I will also work through a few examples in detail.


Networking Lunch in the Exhibit Hall and Poster Viewing


Organs-on-Chips Technology: Applications in Safety Testing for Drug Discovery and Development
Kyung-Jin Jang, Vice President, Emulate, Inc., United States of America

Preclinical animal models used to support selection of drug candidates for clinical trials can sometimes fail to predict potential human toxicity. This translation gap in safety data contributes to drug failures and attrition rates in the clinic. Here, we highlight the application of our microengineered Liver-Chip containing species-specific primary hepatocytes interfaced with liver sinusoidal endothelial cells, with or without Kupffer cells and hepatic stellate cells, cultured under physiological fluid flow for toxicity and safety assessment. We showed that our Liver-Chip detected diverse phenotypes of liver toxicity including hepatocellular injury, steatosis, cholestasis, and fibrosis as well as species-specific toxicities when treated with tool compounds.  The adoption of Organs-on-Chips technology in the pharmaceutical industry may provide a useful platform for prediction of liver toxicity and inform human relevance of liver toxicities detected in animal studies to better determine safety and human risk.


Yole DéveloppementOrgans-on-Chips: Still a Distant Promise or Already a Game Changer?
Sébastien Clerc, Technology & Market Analyst, Microfluidics & Medical Technologies, Yole Développement

Bringing a new drug to market is one of the longest and most costly paths any industry has to walk. The pharmaceutical industry therefore needs more predictive tools to make drug candidates fail earlier and cheaper. Other industries where toxicity testing is a major concern, such as cosmetics, agro-food and consumer goods, also need such solutions, in particular because animal testing is now banned for these industries in certain geographical areas. Organs-on-chips are serious candidates to help solving these bottlenecks.  But despite improving models, the promises that made industrial players dream are now shaded by some skeptic voices. What is the current penetration rate of the technology, does it truly satisfy the industry, and what are the remaining challenges? In this talk, Sébastien Clerc will share Yole’s vision of the organ-on-chip market and technology trends.


The MPS-Db: An Online Tool for the Development and Application of Microphysiology Systems for Toxicity Assessment and Disease Modeling
Albert Gough, Associate Professor, University of Pittsburgh, United States of America

The MPS-Db is a critical centralized internet resource for management and analysis of MPS experimental models and data. The MPS-Db enables users to upload, analyze, review, computationally model and share data and metadata; and enables the unbiased assessment of performance of experimental models.


Danilo TagleKeynote Presentation

The NIH Microphysiological Systems Program: In Vitro Tools for Drug Development and Precision Medicine
Danilo Tagle, Director, Office of Special Initiatives, National Center for Advancing Translational Sciences at the NIH (NCATS), United States of America

Approximately 30% of drugs have failed in human clinical trials due to adverse reactions despite promising pre-clinical studies, and another 60% fail due to lack of efficacy. One of the major causes in the high attrition rate is the poor predictive value of current preclinical models used in drug development despite promising pre-clinical studies in 2-D cell culture and animal models. The NIH Microphysiological Systems (Tissue Chips) program led by NCATS is developing alternative approaches and tools for more reliable readouts of toxicity and efficacy during drug development. Tissue chips are bioengineered microphysiological systems utilizing human primary or stem cells seeded on biomaterials manufactured with chip technology and microfluidics that mimic tissue cytoarchitecture and functional units of human organs.  These platforms can be a useful tool for predictive toxicology and efficacy assessments of candidate therapeutics. Effective partnerships with stakeholders, such as regulatory agencies, pharmaceutical companies, patient groups, and other government agencies is key to widespread adoption of this emerging technology. Tissue chips can also contribute to studies in precision medicine, environment exposures, reproduction and development, infectious diseases, microbiome and countermeasures agents.


Ali KhademhosseiniKeynote Presentation

Organ-on-a-Chip Systems for Mimicking Human Physiology
Ali Khademhosseini, Professor, Department of Bioengineering, Department of Radiology, Department of Chemical and Biomolecular Engineering, University of California-Los Angeles, United States of America


Afternoon Coffee Break and Networking in the Exhibit Hall


Elizabeth BakerKeynote Presentation

Advancing Nonclinical Regulation, Policy, Science, Education and Training
Elizabeth Baker, Pharmaceutical Policy Program Director, Physicians Committee for Responsible Medicine, United States of America

Recent advances, such as the U.S. Food and Drug Administration’s Predictive Toxicology Roadmap, represent a fundamental shift in how drugs will be developed and regulated. U.S. regulators now state the need to move away from animal testing towards new approach methodologies that are expected to be more predictive for humans, and have mapped their plans for doing so. The Nonclinical Innovation and Patient Safety Initiative (NIPSI) collaboration is addressing the factors that impede the uptake of modern, predictive approaches, such as organ chips. Projects include changing U.S. FDA regulations from requiring “animal” data to “nonclinical,” which encompasses animal in vivo and human and animal-based in vitro and in silico approaches; lobbying the U.S. Congress to increase funding allocated for human-based approaches; and working to establish a qualification pathway that covers in vitro platforms and computer models. The presentation will include results from a recent review of NDAs that found no inclusion of organ chips in U.S. FDA submissions for approved drugs. Results will be updated for the meeting.


Microengineering Human Lung Airway Mimicry: Now and Future
Kambez Benam, Assistant Professor of Medicine and Bioengineering, University of Colorado Denver, United States of America

Development of new therapeutics for pulmonary disorders, and advancement in our understanding of inhalational toxico-pathology have been hindered by challenges to study organ-level complexities of human lung in vitro. Moreover, clinical relevance of widely used animal models of respiratory diseases such as chronic obstructive pulmonary disease (COPD), which poses a huge public health burden, is questionable. Here, we applied a tissue microengineering approach to create a ‘human lung small airway-on-a-chip’ that supports full differentiation of a pseudostratified mucociliary bronchiolar epithelium from normal or diseased donors underlined by a functional microvascular endothelium. Small airway chips lined with COPD epithelia recapitulated features of the disease including selective cytokine hypersecretion, increased neutrophil recruitment, and clinical exacerbations by exposure to pathogens. Using this robust in vitro approach, it was possible to detect synergistic tissue-tissue communication, identify new biomarkers of disease exacerbation, and measure responses to anti-inflammatory compounds that inhibit cytokine-induced recruitment of circulating neutrophils. Importantly, by connecting the small airway chip to a custom-designed electromechanical instrument that ‘breathes’ whole cigarette smoke in and out of the chip microchannels, we successfully recreated smoke-induced oxidative stress, identified new ciliary micropathologies, and discovered unique COPD-specific molecular signatures. Additionally, this platform revealed a subtle ciliary damage triggered by acute exposure to electronic cigarette. Thus, the human small airway-on-a-chip offers a powerful complement to animal models for studying human lung pathophysiology.


Innovative Technique To Reconstruct Thick Tissue with Embedded Microvascular Network on Chip
Thibault Krammer, PhD student, CEA Grenoble, France

Blood capillaries network is formed through a versatile tissue-like construct inside a microfluidic chip. This innovative technique allows to build thick tissues by combining cells of the targeted tissue, biopolymer mimicking the extracellular matrices and micro-vascularization.

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