Monday, 28 September 2020


Start and Introduction to the Virtual Conference [All Times are Pacific Times]

13:30

Leanna LevineConference Chair

Welcome, Introduction, Topics Addressed and Conference Opening by Conference Chairperson
Leanna Levine, Founder & CEO, ALine, Inc., United States of America

14:00

Albert FolchKeynote Presentation

Microfluidics for Interrogating Intact-Tumor Biopsies
Albert Folch, Professor of Bioengineering, University of Washington, United States of America

Cancer remains a major healthcare challenge worldwide. It is now well established that cancer cells constantly interact with fibroblast cells, endothelial cells, immune cells, signaling molecules, and the extracellular matrix in the tumor microenvironment (TME). Present tools to study drug responses and the TME have not kept up with drug testing needs. The number of clinical trials of combination therapies has been climbing at an unsustainable rate, with 3,362 trials launched since 2006 to test PD-1/PD-L1-targeted monoclonal antibodies alone or in combination with other agents. We have developed a microfluidic platform (called Oncoslice) for the delivery of multiple drugs with spatiotemporal control to live tumor biopsies, which retain the TME. We have developed the use of Oncoslice for the delivery of small-molecule cancer drug panels to glioblastoma (GBM) xenograft slices as well as to slices from patient tumors (GBM and colorectal liver metastasis). In addition, we have developed a precision slicing methodology that allows for producing large numbers of cuboidal micro-tissues (“cuboids”) from a single tumor biopsy. We have been able to trap cuboids in arrays of microfluidic traps in a multi-well platform. This work will potentially allow for the high-throughput application of drugs to intact human tumor tissues.

14:30

Daniel ChiuKeynote Presentation

Microfluidic Technologies For Liquid Biopsy
Daniel Chiu, A. Bruce Montgomery Professor of Chemistry, University of Washington, United States of America

This presentation will describe microfluidic technologies we developed for liquid biopsy and precision medicine. Specifically, a rare-cell isolation instrument we call eDAR (ensemble decision aliquot ranking), a nanofluidic technology for the high-sensitivity sorting of exosomes, and a digital-nucleic-acid detection and analysis platform based on our SD (self-digitization) chip. I will outline the workings of these microfluidic platforms, describe their performance, and discuss the clinical questions we are addressing with these technologies.

15:00

Amy HerrKeynote Presentation

Precision Biology: Deep Profiling of Single Cells Using Electrophoretic Cytometry
Amy Herr, Professor, University Of California Berkeley, United States of America

Underpinning single-cell measurement tools, microfluidic design offers the throughput, multiplexing, and quantitation needed for rich, multi-dimensional data. Genomics and transcriptomics are leading examples. Yet, while proteins are the dynamic, downstream effectors of function, the immunoassay remains the de facto standard (flow cytometry, mass cytometry, immunofluorescence). We posit that to realize the full potential of high-dimensionality cytometry, new approaches to protein measurement are needed. I will describe our ‘electrophoretic cytometry’ tools that increase target selectivity beyond simple immunoassays. Enhanced selectivity is essential for targets that lack high quality immunoreagents – as is the case for the vast majority of protein forms (proteoforms).  I will share our results on highly multiplexed single-cell western blotting and single-cell isoelectric focusing that resolves single charge-unit proteoform differences. In fundamental engineering and design, I will discuss how the physics and chemistry accessible in microsystems allows both the “scale-down” of electrophoresis to single cells and the “scale-up” to concurrent analyses of large numbers of cells. Precise reagent control allows for integration of cytometry with sophisticated sample preparation – the unsung hero of measurement science. Lastly, I will link our bioengineering research to understanding the role of protein signaling and truncated isoforms in development of breast cancer drug resistance and understanding protein signaling in individual circulating tumor cells. Taken together, we view microfluidic design strategies as key to advancing protein measurement performance needed to address unmet gaps in quantitative biology and precision medicine.

15:30

Afternoon Break

16:00

Nancy AllbrittonKeynote Presentation

Microengineering a Physiologic Colon Replica
Nancy Allbritton, Frank and Julie Jungers Dean of the College of Engineering and Professor of Bioengineering, University of Washington in Seattle, 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. A 3D polarized epithelium using primary human gastrointestinal stem cells was developed to fully recapitulate gastrointestinal epithelial architecture and physiology. A planar monolayer comprised of stem/proliferative and differentiated primary cells is cultured on a shaped hydrogel scaffold with an array of crypt-like structures replicating the intestinal architecture. These planar layers display physiologic drug transport and metabolism and immunologically appropriate responses. Facile co-culture with other cell types such as immune cells or myofibrolasts is readily achieved. A dense mucus layer is formed on the luminal epithelial surface that is impermeable to bacteria and acts a barrier to toxins. The in vitro mucus has remarkably similar in its biophysical properties to that produced in vivo. Imposition of chemical gradients across the crypt long axis yields a polarized epithelium with a stem-cell niche and differentiated cell zone. The stem cells proliferate, migrate and differentiate along the crypt axis as they do in vivo. An oxygen gradient across the tissue mimic permits luminal culture of anaerobic bacteria while maintaining an oxygenated stem cell niche. This in vitro human colon crypt array replicates the architecture, luminal accessibility, tissue polarity, cell migration, and cellular responses of in vivo intestinal crypts. This bioanalytical platform is envisioned as a next-generation system for assay of microbiome-behavior, drug-delivery and toxin-interactions with the intestinal epithelia.

16:30

Anita RogacsKeynote Presentation

Workflow Automation with Digital and Customizable Microfluidics: Challenges and Opportunities
Anita Rogacs, Head of Life Sciences Strategy and R&D, HP Labs, United States of America

Life Sciences analytical workflows benefit greatly from microfluidic automation, leading to improvement in accuracy, multiplexing, efficiency, and cost. Yet microfluidics has faced significant barriers to adoption in both diagnostics and drug discovery, due to constrained designs and long and costly development pipelines. HP is addressing this challenge by leveraging our digital and customizable mode of microfluidics, eliminating the need to design a “new chip” for every new workflow, target and reagent.

17:00

ALine, Inc.Valves in Microfluidics – Past, Present & Future
Leanna Levine, Founder & CEO, ALine, Inc.

Managing fluid movement in a controlled way is conveniently done with on-board valves that are actuated externally with the support of an instrument. In this talk, I will review the types of valves available and the pros and cons of different approaches and their consequences for complexity in the supporting instrument.

17:30

Kevin HealyKeynote Presentation

Exploiting Cardiac Microphysiological Systems For COVID-19 Drug Screening
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 cardiac and liver microphysiological systems (MPS) or ‘organ chips’, to address the costly and inefficient drug discovery process. While MPS are poised to disrupt the drug development process and significantly reduce the cost of bringing a new drug candidate to market, the technology is more robust and creates a whole new paradigm in how to conduct safety pharmacology science, and advances medicine in revolutionary ways. An emerging use of MPS is in the evaluation of repurposed drugs to treat COVID-19. While repurposed drugs are typically FDA-approved for monotherapy, most have not been tested in polytherapy with  anti-inflammatory or antibiotic medications typically employed as part of intensive care protocols. Since COVID-19 patient morbidity is highly correlated with myocardial injury, independent of pre-existing cardiovascular disease, this presentation will address examples of exploiting our human cardiac MPS as unique testbeds for rapidly assessing the cardiac liability of polytherapy of repurposed COVID-19 drugs. Preclinical data generated will inform clinical trial design for polytherapies for COVID-19 patients, particularly regarding risks of potential drug-drug interactions or identifying appropriate exclusion criteria, monitoring strategies, and dose adjustments to minimize cardiac liabilities.

18:00

Close of Day 1 of the Conference

Tuesday, 29 September 2020


Day 2 of the Conference [All Times are Pacific Times]


Session Title: Emerging Themes in Microfluidics in 2020

09:00

Yole DéveloppementPoint-of-Care Testing and COVID-19: One-Shot or Long-Term Opportunity?
Sébastien Clerc, Technology & Market Analyst, Microfluidics & Medical Technologies, Yole Développement

Abstract: The past few months have seen a new biological threat, the COVID-19 infection, caused by the SARS-CoV-2 virus, reshape the entire diagnostics ecosystem. Numerous companies rapidly started developing tests to detect the pathogen. But is point-of-care testing the real solution to identify early cases and stop the pandemic? Will there be a change in the use cases in the near future, like testing at the workplace, at the airport or in public transportation or public places? In this talk, Sébastien Clerc will share Yole’s vision of the point-of-care landscape and how the pandemic has impacted it.

09:30

STRATEC Consumables GmbHInnovative Methods in the Characterization of Microfluidic Devices for High Volume Manufacturing
Magdalena Schimke, Business Development and Sales, Single Cell Diagnostics, STRATEC Consumables GmbH

The range of applications for microfluidic devices is constantly expanding and so are the challenges for manufacturing. There is always exitement for the development of new manufacturing methods, but the importance of new analytical methods is often underestimated by contract manufacturers. Here we present our latest advances in the metrology for injection molded microfluidic devices. Especially in the development of nm-sized fluidic channels, µm-sized fluidic channels with nm-precision, and devices with a combination of inorganic and organic coatings we came across challenges that required new analytical methods. The questions range from a simple "how deep is a microfluidic channel after bonding", to "what manufacturing process has the biggest impact on channel roughness - from Mastering to the finished device". To answer these questions, we had to find new ways to characterize the different processes along the manufacturing chain. The analytical methods that we developed opened up the door to new types of devices, or made it possible to mass manufacture new high complexity consumables.

10:00

Holger SchmidtKeynote Presentation

Optofluidic Systems For On-Chip Molecular Diagnostics
Holger Schmidt, Narinder Kapany Professor of Electrical Engineering, University of California-Santa Cruz, United States of America

Optofluidic devices have emerged as the basis for ultra-sensitive, amplification-free analysis of single molecules. We will describe the core features and capabilities of this approach and discuss recent advances in the areas of integration of multiple functions on a single chip, optical detection and analysis with maximized efficiency, and representative examples such as multiplex detection of single antibiotic resistant bacteria and SARS-CoV-2 detection.

10:30

Dino Di CarloKeynote Presentation

Microfluidic-based Diagnostic Approaches for COVID-19
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

Microfluidic technologies have laid a foundation for a number of diagnostic solutions that are especially relevant during the COVID-19 pandemic. I will discuss technological platforms being applied to rapidly detect the SARS-CoV-2 virus, characterize antibodies produced by individuals in response to infection, and triage patients based on detection of abnormal host immune activation. Integration of microfluidic and machine learning approaches enable these tests to have rapid turnaround times which are critical for  clinical scenarios involving diagnosing infected individuals at the point-of-care, broadly screening for immunity / vaccination effectiveness, and triaging patients entering the emergency room based on the amount of care needed.

14:30

Steve SoperKeynote Presentation

Plastic-based Nanofluidic Sensor for the Detection of Rare Nucleic Acids and Determining Their Sequence Variations from Liquid Biopsy Markers
Steve Soper, Foundation Distinguished Professor, Director, Center of BioModular Multi-Scale System for Precision Medicine, The University of Kansas, United States of America

Liquid biopsy markers (circulating tumor cells, CTCs; extracellular vesicles, EVs; and cell free DNA, cfDNA) are becoming extremely popular to manage a variety of cancer-related diseases due to the minimally invasive nature of their acquisition. However, the challenge with liquid biopsy markers is their rarity; for example, it is not uncommon to secure 1-100 CTCs per mL of whole blood supplying about 6-600 pg of genomic DNA. Because platforms like next generation sequencing require >30 ng of input DNA, significant amounts of amplification of the input are required that can generate a biased representation of the genome. To mitigate this issue, we have produced a mixed-scale nanofluidic sensor featuring a baffle area, high surface area pillar arrays, and nanometer flight tubes.  The pixel arrays can perform solid-phase ligase detection reactions (spLDRs) to score the presence of DNA mutations found in a diseased patient even when the mass of the marker is low (<1 ng), but does not require PCR amplification for the analysis. The spLDR can also expression profile mRNAs following reverse transcription. Successfully formed spLDR products are identified using a molecular-dependent time-of-flight (TOF) through a polymer nanofluidic channel flanked by two in-plane nanopores. Simulations (COMSOL) were used to guide the design and fabrication of the nanofluidic sensor to determine the loading efficiency and transport patterns of spLDR products from the pillar array into the flight tubes by evaluating operational parameters when using either hydrodynamic or electrokinetic flow. The nanofluidic sensor was fabricated from a Si master patterned using a combination of focused ion beam (FIB) milling and photolithography with inductively coupled plasma reactive ion etching. The Si master was used to produce resin stamps that were then used to transfer the relevant structures to a plastic via thermal nanoimprint lithography (NIL). The operational features of the device will be presented as well as detecting point mutations in KRAS genes from CTCs’ genomic DNA as well as mRNA expression profiling.

15:00

Abraham LeeKeynote Presentation

Microfluidic Cell Engineering for Precision Therapy
Abraham Lee, Professor, University of California Irvine, United States of America

Precision medicine is the paradigm to develop treatments for patients based on molecular-targets that are effective in vivo when administered.  That is, one must not only be able to identify molecular and cellular targets that are the source of disease but also understand how these targets behave in the body based on physiological principles.  Recent developments in microfluidics have contributed to burgeoning precision medicine fields such as liquid biopsy, immunotherapy, single cell analysis, genotyping and gene sequencing, and microphysiological systems.  A specific focus of my talk would be on microfluidic devices for engineering cells for developing targeted cell therapies and immunotherapies. These microfluidic technologies have the potential to close the loop from detection to diagnosis, to therapy.

15:30

Veryst Engineering, LLCModeling and Simulation of Microfluidic 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 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 device development issues. I will also work through a few examples in detail.

16:00

Plastic Design Corporation (PDC)Plastic Design Corporation—American Production of Microfluidic Systems for Life Science Applications
Chris Becker, Sales and Marketing, Plastic Design Corporation (PDC)

PDC sets itself apart from other companies in the field of injection-molded healthcare consumables in that it is an American manufacturer, does all of its tooling in-house, and manufactures exclusively in cleanroom conditions.  Nearly 30 years’ experience in the production of critical lab-ware and microfluidic components for the Life Sciences have earned PDC a justifiably excellent reputation as a reliable and progressive partner for biotech and pharmaceutical companies.

16:30

Carl MeinhartKeynote Presentation

Free-Surface Microfluidics and SERS for High Performance Sample Capture and Analysis
Carl Meinhart, Professor, University of California-Santa Barbara, United States of America

Nearly all microfluidic devices to date consist of some type of fully-enclosed microfluidic channel. The concept of ‘free-surface’ microfluidics has been pioneered at UCSB during the past several years, where at least one surface of the microchannel is exposed to the surrounding air.  Surface tension is a dominating force at the micron scale, which can be used to control effectively fluid motion. There are a number of distinct advantages to the free surface microfluidic architecture.  For example, the free surface provides a highly effective mechanism for capturing certain low-density vapor molecules.  This mechanism is a key component (in combination with surface-enhanced Raman spectroscopy, i.e. SERS) of a novel explosives vapor detection platform, which is capable of sub part-per-billion sensitivity with high specificity.

17:00

Extracellular Vesicles: Challenges and Opportunities for Single Particle Analysis
John Nolan, CEO, Cellarcus Biosciences, Inc., United States of America

Extracellular vesicles (EVs) are released by all cells and represent a rich source of potential biomarkers. However, EVs in biofluids such as plasma are extremely heterogeneous, and discriminating informative signal from obscuring noise limits the usefulness of bulk analysis methods such as PCR or Western blot. Single vesicle analysis has the potential to resolve this heterogeneity, but small size and low analyte abundance challenges conventional single particle analysis approaches. Overcoming these challenges will require new measurement tools, including instruments, reagents, and standards that can be integrated into assays with improved sensitivity, specificity, and reproducibility. I will review the state of EV analysis, and highlight new insights provided by high resolution single vesicle flow cytometry (vFC) into the compositional and functional diversity of EVs.

17:30

On-chip Surface Acoustic Wave and Micropipette Aspiration Techniques to Assess Cell Elastic Properties
Yanqi Wu, Researcher, Department of Biomedical Engineering, The University of Melbourne, Australia

Cells in vivo mechanically interact with the local microenvironment, stressing the important role of cell mechanical properties in cellular behaviours. We built a phase-modulated surface acoustic wave microfluidic device measuring cellular compressibility (or bulk modulus) and a microfluidic micropipette-aspiration device measuring cellular Young’s modulus, facilitating the investigations of cellular elastic properties and cytoskeletal mechanics.

18:00

Close of Day 2 of the Conference

Wednesday, 30 September 2020


Day 3 of the Conference [All Times are Pacific Times]


Session Title: 3D-Printing in Microfluidics and Other Emerging Themes

09:00

Hybrid Laser Platform For Printing 3D Multiscale Multi-Material Hydrogel Structures
Pranav Soman, Professor, Biomedical and Chemical Engineering; IPA Program Director, Advanced Manufacturing (AM), National Science Foundation (NSF), Syracuse University, United States of America

Contrary to structural and material complexities found in nature, man-made manufacturing technologies and associated materials remain relatively simple. Despite continued technological advances in additive manufacturing, current methods remain limited in their capabilities. We report a new technology coined as Hybrid Laser Printing (HLP) that is capable of shaping hydrogel materials into 3D multiscale, multi-material, and functional constructs. Using several proof-of-concept studies, we present that HLP can print 3D structures that are either (i) technically challenging to print, and/or (ii) extremely time consuming to manufacture, and/or (iii) not possible with current technologies.

09:30

Dissecting Morphogen Gradient Control Mechanisms in Micropatterned Cell Cultures
Elliot Hui, Associate Professor of Biomedical Engineering, University of California-Irvine, United States of America

10:00

Shannon StottKeynote Presentation

Tracking Tumor Extracellular Vesicles Using Microfluidics
Shannon Stott, Assistant Professor, Massachusetts General Hospital & Harvard Medical School, United States of America

Advances in microfluidic technologies and molecular profiling have propelled the rapid growth and interest in achieving a ‘liquid biopsy’ in cancer. The ability to manipulate fluidics flows towards the goal of interrogating millions of particles per second provides a significant advantage over other technological approaches. Through a collaborative effort between bioengineers, biologists, and clinicians, my laboratory at Massachusetts General Hospital has developed microfluidic devices to isolate and characterize these EVs from whole blood. For this presentation, data will be presented on our effort to use our devices to serially track EVs in glioblastoma patients over time. Further, we will share details on some of our latest technologies in development. Through the microfluidic isolation of blood based biomarkers from patients, our goal is to obtain complementary data to the current standard of care to help better guide treatment and identify new biomarkers and putative therapeutic targets.

10:30

Title to be Confirmed.
Steven Graves, Professor, University of New Mexico; President & CEO, BennuBio Inc., United States of America

11:00

Synthesis of Temperature-Responsive Soft Microgels of Any Shape Using Stop-Flow Lithography
Hanna Wolff, Research Assistant, Chemical Process Engineering, RWTH Aachen University, Germany

Stop-flow lithography is a microfluidic method for the fabrication of µm-sized particles with complex shapes. Such particles can be used as building blocks for tissue engineering or soft micro-robotics. Especially, soft and responsive materials are beneficial for these applications; yet, the fabrication of soft responsive particles with complex shape has been rarely reported. In the present work, the technique of stop-flow lithography is used to fabricate soft temperature-responsive microgels with a complex shape. This combination of microgel properties is achieved by using N isopropyl acrylamide (NIPAm) monomer along with crosslinker in the reaction solution. Within the investigations, the polymerization parameters and influences on crosslinking the NIPAm monomer are determined and show the necessity of a threshold amount of crosslinker to form stable microgels. Furthermore, by varying the crosslinker concentration, the stiffness of the microgels can be tailored from very soft to comparably stiff. Moreover, these soft microgels of complex shape show a responsive behavior to temperature making them an excellent building block for life-like responsive tissue engineering.

11:30

Close of Day 3 of the Conference