Lab-on-a-Chip & Microfluidics Europe 2019 Agenda

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

Morning Coffee, Tea and Networking in the Exhibit Hall

Networking Lunch in the Exhibit Hall and Poster Viewing

Luminescent Solar Concentrator Photomicroreactors
Timothy Noël, Professor, University of Amsterdam, Netherlands

In this lecture, we will discuss a novel device integrating the luminescent solar concentrator (LSC) concept with photomicroreactors (LSC-PM), allowing the direct use of solar light in photochemistry without the need for any intermediate energy conversion. This device is capable of capturing direct and diffuse sunlight, converting it into a narrow wavelength and delivering it to the embedded microchannels.

Afternoon Coffee and Tea Break and Networking in the Exhibit Hall

An Open Platform For Microfluidic Sample Prep
Richard Chasen Spero, CEO, Redbud Labs

Developing a new lab-on-chip device is inherently risky. The best way to mitigate technical risk is to prototype each step in the assay using cartridge-compatible methods before assembling the full analytic chain into a single cartridge. Modules exist that enable prototyping of many assay operations, such as reagent storage, mixing, droplet generation, fluid handling, and analyte detection. Development of cartridge-compatible sample prep, however, remains a major challenge. Methods that are ubiquitous at the bench, such as magnetic beads and centrifugation, translate poorly to cartridge formats. Meanwhile, microfluidic sample prep methods are generally proprietary and challenging to customize. We present an open platform for microfluidic sample prep that aims to deliver for lab-on-a-chip developers what magnetic beads enabled in the development of traditional lab assays.

Scalable Wafer Level Production of Consumables for Life Science and Diagnostics Applications Made of Non-CMOS Compatible Materials on Glass. Challenges and Opportunities by Addressing Manufacturing and Standardization in a Foundry Concept
Alexios Tzannis, Business Development Manager Life Sciences, IMT Microtechnologies

In this presentation, we discuss the challenges and solutions of implementing WLP processes for LOAC products. The overall complexity is addressed by transferring MEMS standardization protocols, methodologies and equipment available in the MEMS into the field of microfluidics.

All in One – Advanced Technologies For Complex Low Cost Microfluidic Devices in Glass, Silicon and Quartz
Klaus Kadel, Business Development, Little Things Factory GmbH

The Little Things Factory covers the whole portfolio to set up new functionalities for microfluidic systems in glass and we describe recent innovations in this field. The talk will introduce new possibilities to combine microfluidics with hermetically sealed electrical connectors for various applications that needs electrodes in contact with fluids or electrodes isolated from fluids.

Networking Reception with Beer and Wine in the Exhibit Hall -- Meet Colleagues and Network with Exhibitors

Close of Day 1 of the Conference

Morning Coffee and Tea Plus Networking in the Exhibit Hall

Photochemical Generation of Biofunctionalized Micro Sponges Via Two Phase Flow for Lab-on-a-Chip Applications
Thomas Brandstetter, Group Leader, Freiburg University, Germany

We report on a new approach for the simple, fast and reproducible one-step generation of spongelike cryogelparticles, enabling a large surface area equipped with biofunctional molecules. Addressing Lab-on a-chip applications this grants ultra-fast binding kinetics even for rare capture of biomolecules.

Microfluidic Assay for the Diagnosis of Sepsis from a Drop of Blood
Daniel Irimia, Associate Professor, Surgery Department, Massachusetts General Hospital (MGH), Shriners Burns Hospital, and Harvard Medical School, United States of America

Sepsis is a deadly condition which ends the life of more than 5 million people worldwide every year, more than heart disease and stroke combined.  Sepsis is often misdiagnosed, delaying treatment.  To improve the survival of sepsis patients, new capabilities for diagnosis and monitoring of sepsis are needed.  Towards this goal, we focused on neutrophils, the most numerous white blood cells and earliest responders to infections and sepsis.  Recently, we uncovered a unique neutrophil phenotype during sepsis.  The phenotype can only be measured while neutrophils are still in blood and vanishes after neutrophils are isolated from blood. Newly designed microfluidic assays that use blood directly were instrumental for this discovery.  So far, we validated the new neutrophil phenotype as an accurate biomarker for sepsis in three cohorts of patients in intensive care.  Further studies will enhance our understanding of the roles that neutrophils play before and during sepsis and will facilitate the design of new strategies for the diagnosis, monitoring, and prevention of sepsis.

Microfluidic Platforms with Bioinspired Functionalities: New Concepts for Future Devices
Dermot Diamond, Professor, Principal Investigator, Insight Centre for Data Analytics, National Centre for Sensor Research, Dublin City University, Ireland

Through developments in fabrication technologies in recent years, it is now possible to build and characterize much more sophisticated 3D platforms than was formerly the case.  Regions of differing polarity, binding behaviour, flexibility/rigidity can now be incorporated into these fluidic systems.  Furthermore, materials that can switch these characteristics can be incorporated, enabling the creation of microfluidic building blocks that exhibit switchable characteristics such as programmed microvehicle movement (chemotaxis), switchable binding and release, switchable soft polymer actuation (e.g. valving), and selective uptake and release of molecular targets.  These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required and what science can currently deliver for many challenging applications. Recent developments now enable complex 3D arrangements of soft, switchable polymer gel structures to be created with sub-micron feature size resolution, opening completely new possibilities for control of the chemistry of liquid-solid system.  This emerging transition from existing engineering-inspired 2D to bioinspired 3D fluidic concepts appears to represent a major turning point in the evolution of microfluidics. For example, implementation of these disruptive concepts may open the way to realising biochemical sensing systems with performance characteristics far beyond those of current devices.

Digital Microfluidics, Droplet Microfluidics, Centrifugal Microfluidics: Non-Contact Liquid Handling in the pL- and nL-Volume Range
Eckhard Nordhoff, Chief Scientific Officer, M2-Automation

Reducing costs of lab-on-a-chip-based devices involves miniaturization and pre-loading chips with reagents. For liquid handling steps involved, volumes are reduced from µL to nL and pL amounts. If, for instance, only 100 pL of an expensive reagent solution is required, only 1 µL is consumed for the production of 10,000 devices. This is best achieved with low volume non-contact dispensing of liquids either as individual droplets or as short jets.  It is now common practice for ink-jet printers to deposit materials into LOAC devices. High quality depositions, however, require that the printer, printer driver, composition of the buffer ink and properties of the surfaces have all been optimized for these tasks. In LOAC projects, a wide range of biological or chemical solutions must be dispensed. Surfaces are most often polymer-modified plastics or glass. Obvious challenges are to provide printing tools that can handle the range of solution properties, and to optimize liquid and deposition surface properties. Our presentation will discuss such printing tools, how they work and how they are used.  In particular, we will focus on their implementation in the automated production of lab-on-a-chip-based devices. Recommendations for surface design and liquid properties will also be presented.

FPC@DCU's Platform Strategy For Enabling Efficient Development of Robust and Manufacturable Lab-on-a-Chip Solutions for the Life Sciences
Jens Ducree, Professor of Microsystems, Dublin City University, Ireland

The dynamically emerging trend of decentralised sample prep and testing of biosamples such as blood, water and industrial fluids in the life sciences at the point-of-use spurred the emergence of a plethora of microfluidic technologies. Based on a thorough market analysis, this presentation will illustrate the approach of FPC@DCU - the Fraunhofer Project Centre for Embedded Bioanalytical Systems at Dublin City University - to accelerate and de-risk development of microfluidics-enabled solutions, mainly in the context of the life-science, towards high-technology-readiness levels (TRLs). In a platform-based design-for manufacture approach adopted from established industries, manifold applications can swiftly be derived from a single set of design rules, and quasi seamlessly be scaled-up from prototyping to pilot series and eventual mass production. This strategy will be explained along FPC@DCU’s centrifugal microfluidic “Lab-on-a-Disc” platform which integrates and automates multiplexed multi-step / multi-reagent bioassay protocols in a robust, user-friendly and cost-efficient manner.

Microfluidics For Biotech Applications: Overview of Technologies and Market Trends
Sébastien Clerc, Technology & Market Analyst, Microfluidics & Medical Technologies, Yole Développement

The rise of biotechnologies enable significant progress in drug development, paving the way for personalized medicine. Complex processes can benefit from microfluidic technologies, both at research and production scales. Indeed, microfluidics allow precise control of culture conditions, enable single-cell isolation, permit to sequence DNA, and can even be leveraged for cell engineering, facilitating the development of cell and gene therapies and monoclonal antibodies, among others. This presentation will give an overview of microfluidic solutions for biotech applications along with main market trends, with a focus on DNA sequencing technologies.

Morning Coffee and Tea Break and Networking in the Exhibit Hall

3D-Printed Microfluidics For Automation of Large-Library Molecular Selection Against Cancer Targets
Noah Malmstadt, Professor, Mork Family Dept. of Chemical Engineering & Materials Science, University of Southern California, United States of America

Diagnosing and treating cancer requires having a reliable set of affinity reagents that can specifically and strongly bind to cancer-related protein targets. These reagents are the necessary molecular tools that will enable next-generation technologies for studying, diagnosing, and fighting cancer. Current approaches to producing such reagents, however, are unreliable, expensive, and slow. mRNA display is a molecular selection technology that is uniquely capable of searching libraries of more than a trillion unique compounds to develop ultrahigh affinity reagents against cancer-relevant targets. While this technology has an impressive demonstrated track record of producing such reagents, it has so far been limited to the laboratory scale.

We have built a microfluidic platform that automates the key steps of mRNA display, allowing it to be deployed in a high-throughput fashion. The system is based on modular components manufactured by 3D printing. This manufacturing approach minimizes the cost of the system, allows for rapid design iterations, and facilitates complex fluid routing in three dimensions. The modular architecture isolates the various steps of mRNA display into distinct physical and logical locations.  These steps include selection of mRNA display library members that bind to a target, photoligation of the encoded mRNA library to puromycin constructs for peptide generation, sample optical interrogation for quantification of results, and various oligonucleotide processing reactions. Physical isolation allows for modules that are sensitive to surface adhesion to be disposable while the rest of the system can be reused. We have demonstrated the performance of this modular microfluidic system in the selection of molecules for binding multiple cancer-related target proteins. This approach will eventually facilitate the use of mRNA display by non-expert uses: an laboratory that can produce a cancer target protein will be able to simply input this protein into the system and in a matter of hours generate a molecule that binds the target with extraordinarily high affinity.

High Resolution 3D Printing For Microfluidic and Organ-on-Chip Applications
Aleksandr Ovsianikov, Professor, Head of Research Group 3D Printing and Biofabrication, Technische Universität Wien (TU Wien), Austria

3D printing opens exciting perspectives towards rapid engineering of complex 3D structures and cell-containing constructs for microfluidic and organ-on-chip applications. In this context, multiphoton lithography (MPL) is an outstanding approach, allowing to produce complex 3D constructs with features down to sub-µm level directly in the volume of the photosensitive material, without the necessity to deposit it layer by layer. Furthermore, photosensitive material formulations and cells can be delivered by perfusing the channels, thus enabling 3D printing within already assembled microfluidic chips.

An increasing portfolio of available materials enables utilization of the versatile capabilities of MPL, from producing complex volumetric 3D structures by means of cross-linking, to creating void patters within hydrogels already containing living cells.
 
In this contribution, our recent progress on MPL for microfluidic and organ-on-chip applications and the development of according materials will be presented.

3D Bioprinting of Human Soft Tissues
Jim Engström, Global Application Specialist, CELLINK

3D Bioprinting has gained attention in tissue engineering due to its ability to spatially control the placement of cells, biomaterials and biological molecules. The development of new hydrogel bioinks with good printability and bioactive properties has made it possible to 3D bioprint and accelerate the maturation of complex 3D tissue-like models. In this talk, we present our recent work in bioink development for 3D bioprinting and culture of healthy tissues such as skin, bone and cartilage, as well as cancer tissues, such as breast cancer and osteosarcoma tissue models.

Come On Baby Light My Fire – Combining Photonics and Microfluidics
Holger Becker, Chief Scientific Officer, Microfluidic ChipShop GmbH

Practically all microfluidic systems contain a detection module as a central system component. For many years, fluorescence has been the gold standard, both due to its sensitivity as well as versatility. In recent years however, alternative detection methods have been emerging which offer different approaches especially for microfluidic systems with applications in point-of-care diagnostics. In this presentation, we will focus on two approaches: a) the integration of silicon photonic devices (so-called PICs) which utilize the semiconductor fabrication methods for silicon but make use of the optical properties of silicon instead of its electronic functionalities and b) the use of ink-jet printed integrated photonic elements such as light-sources and detectors which can be directly integrated in a disposable microfluidic cartridge.

Networking Lunch in the Exhibit Hall and Poster Viewing

Luncheon Technology Spotlight Presentation: Precise Contactless Spotting for Lab-on-Chip Applications
Beate Poulson, Sales Manager, microdrop Technologies GmbH

Lab-on-chip devices are used for a wide variety of health care applications, especially in the area of point-of-care diagnostics. These small microfluidic devices equipped with microchannels, chambers and other features carry out diagnostic tests by enabling reactions between patient samples and reagents. The devices deliver test results with very small sample volumes and in a short period of time.

For production of lab-on-chip devices a precise and fast material deposition method is needed. Typically, the devices are produced at high numbers under high throughput conditions. The substrates may be made of different materials e.g. polystyrene or silicone, but in common is that these substrates typically have a structured surface which may consist of channels, mixing chambers or even wells which are used for precise detection. Also, different coating materials may be used as pretreatment for better adhesion of reagents or confinement of fluids. Deposition or Spotting of reagents onto the chip is a demanding task and requires the filling of small cavities and microchannels with a high accuracy. This can efficiently be done with a microspotting platform based on in inkjet technology. The flexibility of this technology allows for custom-made solutions adapted to the specific customer needs. Especially how high accuracy concerning volume of spotted reagents and also precision of placement is achieved under high throughput production conditions is demonstrated by examples.

Tunable Flow Confinements For Microscale Molecular Analysis on Tissues
Govind V Kaigala, Research Staff Member, IBM Research Laboratory-Zurich, Switzerland

Traditionally, compartments are formed with hydrogels, multi-phase systems (droplets), or inkjets. In contrast, we are developing ‘flow confinements’ which comprise compartments formed on a surface by the flow of a shaping liquid around a processing liquid. We termed these implementations collectively as tunable flow confinements (TFC). In contrast to standard microfluidics, which are typically closed, we are developing scanning, non-contact microfluidic technology that can shape liquids in the "open space" over surfaces. TFCs are implemented using a liquid scanning probe called the microfluidic probe and function on standard biological substrates such as Petri dishes, slides, and tissue sections when the substrate is kept wet. In this talk, I will show how this family of liquid scanning probe devices is evolving as a versatile bioanalytical tool to alter the physics and chemistry of biological interfaces at the micrometer to centimeter-length scales. I will also propose concepts pertaining to tissue microprocessing encompassing local phenotyping and molecular profiling, which may contribute to the multi-modal analysis of critical biopsy samples.

Afternoon Coffee and Tea Break and Networking in the Exhibit Hall

Poster Awards

High-Precision Overmolding as New Fully Automated, Integrated Method to Seal Microfluidic Devices for Demanding High-Volume Applications
Andreas Schäfert, Director Business Development Medical Devices, Wilhelm Weber GmbH, Germany

The new attempt to use overmolding as bonding technique enables production and sealing of the chips in one single process. This allows a fully integrated microfluidic chip production of high volumes by a multi-component injection molding machinery with rotary table.

Development of Novel Single Cell Analysis Platforms to Dissect Cellular Heterogeneity
Bart Westendorp, Assistant Professor, Faculty of Veterinary Medicine, Utrecht University The Netherlands, Netherlands

The cell is a fundamental unit in the life sciences, and recent breakthrough technologies such as single cell RNA-sequencing have shown that substantial variation exists between cells, even within a seemingly homogenous population. To fully understand the importance and molecular basis of cellular heterogeneity in development, disease progression, and therapy responses, it is essential to combine single cell genomics with behavior or fates of the same individual cells. To achieve this goal, we have been developing innovative platforms that enable us to combine live cell microscopy with single cell RNA- and DNA-sequencing. These platforms include customized fluorescence microscope systems that allow capturing of individual cells of interest. I will discuss our latest approaches and provide examples of biological questions we are answering using our technology.

Single-Cell Dynamic Profiling of Cytokine Secreting Immune Cell
Christophe Vedrine, Head of biological microsystems and advanced optics engineering unit, Bioaster, France

A Droplet-based microfluidics to monitor cell viability, endocytosis and cytokine secretion over time. Optimization of a robust and sensitive workflow to monitor TNF-alpha secretion from single monocytes. Cellular heterogeneity and TNF-alpha secretion dynamics from septic shock patient monocytes.

Image-based Measurement Systems and Image-Processing Tools for Micromixers and Droplet Microfluidics
Gökhan Ergin, Product Manager, CTA & Microfluidics, Dantec Dynamics A/S, Denmark

An overview of current technical possibilities for image-based planar PIV systems and related image processing tools used in droplet microfluidics and micromixer applications. Recommendations on, which technique is more suitable in a given situation are also provided.

Cancer Cell Spheroids as 3D Model For Drug Screening In Droplet-based Microfluidics
Mario Saupe, Researcher, Institut für Bioprozess- und Analysenmesstechnik e.V. Heiligenstadt, Germany

Cancer is one of the leading cause of deaths worldwide. Among others this is owed to limited therapeutic options caused by a high degree of resistances to conventional chemotherapeutics and an aggressive tumor progression. In order to overcome these resistances, new therapeutic targets, e.g. new drugs, have to be identified and investigated. In the last years a lot of microfluidic approaches were developed to improve therapeutic success after cancer diagnosis. To investigate the behavior of cancer cell spheroids under treatment with chemotherapeutics, appropriate cell viability assays is adapted to the droplet based microfluidics. In this presentation, we introduce the microfluidic technological platform and its functional modules as well as first results of the experiments using the alamarBlue®-viability assay.

Design of Deterministic Lateral Displacement Microfluidic Separators for Bioclinical Applications: Where Do We Stand?
Stefano Cerbelli, Associate Professor, Dipartimento di Ingegneria Chimica, Sapienza Università di Roma, Italy

An account of recent theoretical results on transport of suspended mesoscopic particles in microfluidic separators based on Deterministic Lateral Displacement is presented. Implications of these results for the optimized design of the geometry and operating conditions of the microfluidic separators is discussed in some detail for clinical applications ranging from exosome detection to isolation of circulating tumor cells.

Fabrication via DLP® Stereolithography and Characterization of Microfluidic Cartridges Suitable for Polymerase Chain Reaction (PCR)
Charalampos Tzivelekis, Researcher, Newcastle University, United Kingdom

DLP® Stereolithography (SLA) as a high-resolution 3D printing process offers a low-cost alternative for prototyping of polymer microfluidic devices, compared to common fabrication methods. Here, we introduce specific processing routes of DLP® SLA in fabrication of microfluidic devices suitable for Polymerase Chain Reaction (PCR). A fabrication protocol for cartridges with monolithic 2.5D micro-channels was evaluated in the production of disposable flow-through and stationary PCR devices. Those were interfaced with purpose-built PCR thermocyclers and evaluated in-situ by amplification of a 75 bp target sequence from a genomic DNA template. PCR inhibition sources were further analyzed with qPCR. Considering the low unit cost per device and the capability to endow further functionality on printed devices through surface modification, we further examined hydrophobic tuning protocols and analysed their performance in-situ. We finally summarize the advantages of DLP SLA and characterize its potential as a future fabrication technique of lab-on-chip devices.

Close of Day 2 of the Conference