Organ-on-Chip Systems to Probe Extracellular Vesicle Transport Across Biological Barriers
Steven C. George, Edward Teller Distinguished Professor and Chair, Department of Biomedical Engineering, University of California-Davis, United States of America

Extracellular vesicles (EVs) are small (50-150 nm diameter) composite particles secreted by cells and comprised of a lipid-based membrane surrounding an aqueous core.  The membrane and core can each incorporate a wide range of molecules (e.g., proteins, nucleic acids) that can impact cellular function; thus, EVs can impact in vivo biology, but have also generated significant excitement for their potential theranostic (therapeutic and diagnostic) applications in cancer. How EVs are transported (convection, diffusion, and binding) across biological barriers including the vascular endothelium and extracellular matrix is poorly understood.  Our early work demonstrates that a subpopulation of EVs are transported across the endothelium using receptor-mediated transcytosis, and predominantly by convection (not diffusion) through the extracellular space. During transport through the ECM, the EVs can bind (and unbind) to form a spatial gradient which may have biological implications for cell migration and tumor progression. Examination of EV transport across biological barriers will not only enhance our understanding of the dynamic tumor microenvironment, but also provide the framework to design artificial nanovesicles as novel drug delivery vehicles.

Microfluidic Immunoengineering
Abraham Lee, Chancellor’s Professor, Biomedical Engineering & Director, Center for Advanced Design & Manufacturing of Integrated Microfluidics, University of California-Irvine, United States of America

The COVID-19 pandemic, and the subsequent successful development of the mRNA vaccine has ushered in an era of immunoengineering. Immunoengineering involves the “reprogramming” of the immune system to overcome limitations of the innate or adaptive immune responses that the body naturally produces. Recent developments of microfluidics for precision medicine applications such as liquid biopsy, cell therapy, single cell analysis, and microphysiological systems have contributed to the general field of immunoengineering. Specifically, adoptive cell therapy (ACT) is a type of immunotherapy that involves the processing of blood from a donor to isolate immune cells (e.g. T cells) for genetic manipulation followed by reinfusion of the cells into patients. This process that starts from blood drawn from one person and ends with specialized engineered cells delivered to the patient includes multiple tedious and costly steps, and can require a long time that the patient may not have. Microfluidic technologies can address most steps of this complex cell manufacturing process, including cell harvesting, cell isolation, cell activation and expansion, and cell transfection. In this talk I will introduce two microfluidic platforms in my lab applied to the cellular engineering processes, one is the lateral cavity acoustic transducer (LCAT) and the other is droplet microfluidics. Based on LCAT, we developed the acoustic electric shear orbiting poration (AESOP) device to uniformly deliver genetic cargos into a large population of cells simultaneously. We demonstrate high quality transfected cells with controlled dosage delivery as well as serial delivery of different genetic cargos. These capabilities can be used to optimize the therapeutic efficacy of the engineered cells and also combine it with promising gene editing tools to further condition the cells for more specific in vivo targeting. Based on droplet microfluidics we constructed bottom-up artificial antigen presenting cells (aAPCs) for antigen-specific T cell activation. By trapping single cells in microfluidic droplet compartments, we are able to study the 3D cell morphology of both the cell surface and also its intracellular constituents to further understand immune cell activation and immune cell synapses.

Title to be Confirmed.
Valérie Taly, CNRS Research Director, Professor and Group leader Translational Research and Microfluidics, Université Paris Cité, France

Brain Neurovascular Models and Their Application to Modeling Transport in Health and Disease
Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, Massachusetts Institute of Technology (MIT), United States of America

Despite recent FDA approval of two drugs to reduce amyloid beta (A-beta) plaque in Alzheimer’s patients, a true cure of the disease remains elusive since they simply reduce the rate of cognitive decline.  Also, there is a need for deeper understanding of drug and toxin transport across the blood-brain barrier (BBB), which is difficult to obtain from animal experiments or human testing.  To meet this need, a variety of in vitro microphysiological models have been developed that can accurately recapitulate the barrier properties of the brain vasculature in the context of A-beta clearance from, and toxin or drug entry into, brain tissues.  This talk will focus on a progression of models developed to mimic both the healthy and diseased brain and to predict transport properties.  Cells used in these models can be either primary or iPS cell-derived with the latter being increasingly used to produce standardized models with greater consistency over time and appropriate for screening by pharma and biotech companies.

New Technologies for Accelerating Progress in Cancer Immunotherapies
Jim Heath, President, Institute for Systems Biology, United States of America

Integrating Innovations for the Advancement of Single Cell Analysis
Eric Diebold, WW Vice President, Research and Development, BD Biosciences, United States of America

2024 represents the 50th anniversary of the first commercial cell sorter, commercialized by BD Biosciences. In this presentation, I will cover some of the key innovations in flow cytometry over this period, and discuss some of the more recent innovations in our industry that are catapulting high parameter single cell analysis into the future.

Title to be Confirmed.
David Weitz, Mallinckrodt Professor of Physics and Applied Physics, Director of the Materials Research Science and Engineering Center, Harvard University, United States of America

Accelerating Life Science Research: From Lab-on-a-Chip to Lab-on-a-Particle
Dino Di Carlo, Armond and Elena Hairapetian Chair in Engineering and Medicine, Professor and Vice Chair of Bioengineering, University of California-Los Angeles, United States of America

Building on the successes of Lab on a Chip technologies, a new frontier is emerging in the form of Lab on a Particle (LoP) platforms. These innovative technologies complement traditional microfluidic systems by utilizing microparticles to confine samples and facilitate microscale reactions. Unlike the static nature of microfluidic chips, LoP platforms offer dynamic and flexible solutions where microparticles act as discrete, suspendable compartments capable of performing highly parallelized assays. This advancement significantly enhances the ability to analyze molecules and cells with higher throughput, while incorporating sophisticated assays. The microparticles used in LoP assays are meticulously engineered with unique shapes and chemistries, providing functionalities that were previously unattainable with conventional microfluidic chips. These particles can template droplets, capture specific molecules, cells, and secretions, or even barcode reactions for multiplexed analysis. The integration of essential assay materials and structures directly into each particle eliminates the dependency on custom chips or specialized instrumentation. As a result, LoP platforms are compatible with standard laboratory instruments such as flow cytometers, fluorescence activated cell sorters (FACS), microscopes, and other imaging devices. This compatibility positions LoP technologies akin to software applications, or apps, operating on commonly available life science instrument hardware. This analogy highlights the transformative potential of LoP platforms in democratizing access to advanced assay capabilities. By circumventing the need for specialized equipment, these microparticle-based systems can accelerate adoption and broaden the impact of microfluidic innovations across diverse research fields. In this keynote presentation, we will explore some recent Lab on a Chip innovations developed in our lab, including Ferrobotics, and introduce recent Lab on a Particle platforms and applications. We will discuss demonstrated applications, such as in antibody discovery, elucidating links between cell secretions and gene expression, and identifying therapeutically optimal cells, ultimately highlighting the future prospects of LoP technologies in accelerating all life sciences.

High-Throughput Mapping of Functional Proteins and Pathways
Adam Abate, Professor of Bioengineering and Therapeutic Sciences, University of California-San Francisco, United States of America

Despite advances in AI for predicting protein structures from sequences, predicting function remains challenging due to the dynamic nature of protein mechanics. High-throughput experimentation is a powerful method to study proteins, allowing the generation of empirically-based functional maps. However, this process requires analyzing hundreds of thousands of variants to thoroughly scan the mutational landscape for even a single protein. This talk will discuss methods for high-throughput characterization of functional proteins and pathways, including enzymes, membrane transporters, and antibodies. High-throughput sequence-function mapping will enable the generation of empirical datasets necessary for building accurate computational models of proteins and pathways and, ultimately, enabling the in silico design of proteins with new functions.

Title to be Confirmed.
Steve Soper, Foundation Distinguished Professor, Director, Center of BioModular Multi-Scale System for Precision Medicine, The University of Kansas, United States of America

Pushing Boundaries: High Resolution 3D Printing for Microfluidics
Gregory Nordin, Professor, Brigham Young University, United States of America

Interest in 3D printing for microfluidic device fabrication is high, but routinely achieving sub-100 µm features remains a challenge. This is because microfluidic devices primarily consist of negative space features, which require different considerations compared to positive space features common in other 3D printing applications. To address this, we have developed our own stereolithographic 3D printers and materials tailored to these requirements to explore what is possible with 3D printing for high resolution microfluidics. Our approach can create channels as small as 2 µm x 2 µm. We have also developed active elements, such as valves and pumps, with the smallest valves having an active area of just 15 µm x 15 µm. With these capabilities, we have demonstrated highly integrated 3D printed microfluidic components, such as a 10-stage 2-fold serial dilutor within a 2.2 mm x 1.1 mm footprint. Additionally, we have created a fast (~1 ms) and compact (<1 mm^3) 3D printed mixer using a new multi-resolution 3D printing method. These advancements position 3D printing as an attractive alternative to costly cleanroom fabrication processes. They offer the added benefit of fast (~5-15 minute), parallel fabrication of multiple devices in a single print run due to their small size, facilitating a path to mass manufacturing.

Understanding Three-Dimensional Microfluidic Design to Optimize Lipid Nanoparticle Fabrication
Noah Malmstadt, Professor, Mork Family Dept. of Chemical Engineering & Materials Science, University of Southern California, United States of America

3D printing brings with it a plethora of advantages for microfluidic applications. Principle among these are rapid prototyping, iterative design, and the ability to avoid the cost and overhead of cleanrooms. However, there is also an inherent advantage in being able to design and build devices in a truly three-dimensional, rather than layer-by-layer, geometry. One simple domain in which the advantages of true 3D routing are clear is in mixing. Control over a 3D geometry allows for multiple complex mixing configurations--herringbones, relamination mixers, chaotic advection--to be trivially constructed and recombined. We have deployed these principles of 3D design to design simple, compact devices for the high-throughput manufacture of lipid nanoparticles (LNPs). LNPs are drug delivery vehicles of increasing importance: they have demonstrate effectiveness and scalability as the delivery vehicles for mRNA-based vaccines against SARS-CoV-2 and emerging research is demonstrating that they have broad applications in vaccine delivery and beyond. This talk discusses how microfluidic mixing controls the size, structure, and uniformity of LNPs with several drug-like payloads including mRNA and therapeutic peptides.