07:00 | Morning Coffee, Tea and Networking |
| Session Title: Methodologies and Approaches in Lab-on-a-Chip Device Development and Commercialization |
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07:30 | | Keynote Presentation Integrated Optofluidic Devices for Manipulation and Imaging of Cells Roberto Osellame, Professor, Politecnico di Milano; Senior Researcher, Institute for Photonics and Nanotechnologies (IFN) – National Research Council (CNR), Milan, Italy
Single cell analysis aims at unravelling the biological complexity due to the well-recognized diversity in cell populations. The integration of optical forces with microfluidic networks, in so-called optofluidic chips, allows advanced cell manipulation and characterization. In addition, the development of microscopy on a chip for the 3D tomography of single to few cells agglomerates paves the way to rapid analysis of a large quantity of samples for drug screening and personalized medicine. |
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08:00 | Modelling and Characterisation of Droplet Generation, Trapping and Detection in Impedance-Based Cell Analytical Microfluidic System Peter Furjes, Principal Scientist, Hungarian Academy of Sciences, Hungary
Present work focuses on the design, modelling and characterisation of a two-phase microfluidic device with integrated electrode system for impedance based cell analysis. The developed system is capable of creating, manipulating, trapping and detection droplets with cell-size fitted diameter. |
08:15 | SERS Active Periodic 3D Structure for Trapping and High Sensitive Raman-Spectroscopy of Molecular Surface Analysis of Particles or Cells Peter Furjes, Principal Scientist, Hungarian Academy of Sciences, Hungary
In this work the applicability of special periodic 3D structure was demonstrated for simultaneous size selective trapping, fluorescent identification and extremely sensitive Surface-Enhanced Raman Spectroscopy based detection of characteristic molecules immobilized on the surfaces of the particles or cells.
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08:30 | Tissue Microprocessing: Shaping Sub-nanoliter Volumes of Liquids on Tissue Sections for Multimodal Analysis Govind V Kaigala, Research Staff Member, IBM Research Laboratory-Zurich, Switzerland
In contrast to standard microfluidics, which are typically closed, we are developing a scanning, non-contact microfluidic technology that can shape liquids in the "open space" over surfaces. This technology utilizes a microfluidic probe (MFP) having microfabricated structures for localizing a liquid of interest on a surface using hydrodynamic flow confinement. MFP permits patterning surfaces with proteins and other biomolecules in an additive and subtractive manner, forming complex gradients on surfaces, and interacting with cells on surfaces. With flow confinement operating at volumes smaller than 1 nanoliter, a few cells can be targeted in a human tissue section for the specific staining of disease markers. This confinement concept has also been scaled for targeting 1000’s of cells. Flow confinement and efficient use of chemicals can be further optimized using a concept called "hierarchical" hydrodynamic flow confinement. I will show how this family of liquid scanning probe devices is evolving as a 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 for interrogating tumor heterogeneity and spatially resolved molecular profiling which may contribute to the multi-modal analysis of critical biopsy samples in the context of next-generation pathology. |
09:00 | | Keynote Presentation Microtubular NEMS for On- and Off-Chip Microfluidic Applications Oliver Schmidt, Professor & Director, Leibniz-Institut für Festkörper- und Werkstoffforschung, Germany
Microtubular MEMS with outstanding properties are self-assembled into fully functional and integrative microtubular architectures. This makes them attractive for a broad range of applications and scientific research fields ranging from novel hybrid heterostructure devices to 3D microsystems both on and off the chip. Microtubular MEMS are exploited to construct ultra-compact and ultra-sensitive advanced electronic circuitry, sensors and optofluidic components around fluidic channels towards the implementation of a lab-in-a-tube system. They are also useful to study basic mechanisms of single cancer and stem cell migration, growth and mitosis in realistic 3D confined environments. Off-chip applications include biomimetic microelectronics for regenerative cuff implants and the development of hybrid microbiorobotic motors for paradigm shifting reproduction technologies. |
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09:30 | | Keynote Presentation Whole Blood Microfluidics: Fractionation and Isolation of Cells Ian Papautsky, Richard and Loan Hill Professor of Bioengineering, Co-Director, NSF Center for Advanced Design & Manufacturing of Integrated Microfluidics, University of Illinois at Chicago, United States of America
Inertial microfluidics is receiving considerable attention for applications in liquid biopsy. However, while these devices have been widely explored for cell separation, sample dilution is necessary. Here, we report on a novel approaches to achieve cell separation directly from unprocessed whole blood based solely on cell size. The separation is achieved through coupling of inertial effects with shear-induced diffusion. Our results from high-speed imaging reveal that focusing of larger cells near the channel centerline is possible, leading to easy separation. Whole blood spiked with fluorescently labeled beads and cells was used to demonstrate the separation principle and its performance without any sample pretreatment. Results confirm the high quality of performance in terms of efficiency (>90%) and RBC rejection rate (> 96%). Ultimately, we successfully demonstrate the use of an inertial microfluidic device as a laboratory tool for sorting target cells from undiluted whole blood.
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10:00 | Morning Coffee Break and Networking in the Exhibit Hall |
10:30 | Challenges and Solutions of Lab-on-a-Chip and In Vitro Diagnostic Devices: From Test Development to High Throughput Production Hans Dijk, Senior Account Manager, Scienion AG
Diagnostic test production might currently face several challenges. Among them, the high price of the capturing molecules and their precise immobilisation within a given surface. Therefore, saving precious samples and reagents are key to minimize costs. Handling small amounts of liquids with tiny dead volumes is a key part to achieve this. Advances in technology have allowed over the years to dispense less and less reagent per test in a very precise location and to dispense multiple other analytes onto the same test area. In other words, ultra-low volume handling technology has enable a significant decrease in production costs by miniaturising and multiplexing these tests. Scienion provides a single picoliter liquid handling technology to address all miniaturization aspects of rapid tests from early research to full scale production technologies.
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11:00 | Multimaterial Integration for Lab-on-a-Chip Devices Holger Becker, Chief Scientific Officer, Microfluidic ChipShop GmbH
Highly integrated microfluidic devices usually consist out of components made out of different materials such as thermoplastic polymers for the cartridge body, membranes and filters, blister pouches for liquid reagents and/or silicon dies for sensors. The presentation will discuss challenges and solutions for developing and manufacturing of such multimaterial cartridges. |
11:30 | High Resolution 3D Printing Inside a Chip 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 for microfluidic applications. In this context, multiphoton lithography (MPL) is an outstanding approach, since photosensitive material formulations and cells are delivered by perfusing the channels, thus enabling 3D printing within already assembled microfluidic chips. The latter aspects implies that different materials, construct geometries and cell types can be tested with the same set of chips without changing their initial design or fabrication process. In addition MPL offers high spatial resolution, unmatched by other 3D printing approaches, and can produce features down to sub-100 nm level directly in the volume of the material, without the necessity to deposit it layer by layer. 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 applications and the development of according materials will be presented. |
12:00 | 3D-Printed Microfluidic Systems Built From Functional Modular Elements Noah Malmstadt, Professor, Mork Family Dept. of Chemical Engineering & Materials Science, University of Southern California, United States of America
The integration of functional components into microfluidic systems is necessary for building compact analytical devices. Optical detection and measurement, electromechanical fluid switching, active mixing, and magneto- and electrophoretic separations all require the integration of components on top of the underlying fluidic architecture. There has been significant work towards integrating such functional components by including them directly in the microfabrication process. This approach, however, leads to expensive fabrication workflows that are often limited to a narrow set of applications. To overcome these limits, we are designing a microfluidic architecture that is easily adaptable to a wide variety of applications. This architecture is based on 3D-printed elements that can be assembled into analytical devices. Functional components are integrated into these elements; the structures are printed to directly accommodate off-the-shelf components including photodiodes, heaters, sensors, and fiber optic fittings. We have demonstrated the utility of this approach by assembling a system capable of performing automated ELISA assays from 3D-printed blocks with integrated functional components. |
12:30 | Networking Lunch -- Meet the Exhibitors and View Posters |
13:10 | Enhanced Flow Control & Microfluidics François Mazuel, Head of R&D & Production, Elvesys
Introduction to enhanced flow control solutions and applications in microfluidics. |
13:15 | Lunch Technology Spotlight Presentation: Precise Contactless Spotting for Lab-on-Chip Applications Wilhelm Meyer, Managing Director, 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. |
13:30 | Frontier in Direct Observation and Visualization of Molecular Interactions Gijs Wuite, Professor, Vrije Universiteit Amsterdam, Netherlands
The genetic information of an organism is encoded in the base pair sequence of its DNA. Many specialized proteins are involved in organizing, preserving and processing the vast amounts of information on the DNA. In order to do this swiftly and correctly these proteins have to move quickly and accurately along and/or around the DNA constantly rearranging it. In order to elucidate these kind of processes we perform single-molecule experiments on model systems such as restriction enzymes, DNA polymerases and repair proteins. The data we use to extract forces, energies and mechanochemistry driving these dynamic transactions. The results obtained from these model systems are then generalized and thought to be applicable to many DNA-protein interactions. In particular, I will report on a new single molecule methods. I’ll introduce Acoustic Force Spectroscopy (AFS). With AFS we extend the force-spectroscopy toolbox with an acoustic manipulation device that allows exerting acoustic forces on tethered molecules. AFS is a Lab-on-a-chip device consisting of a flow cell of two glass plates with a fluid chamber in between and a piezo element glued on top. While applying an alternating voltage to the piezo element, forces from sub-pN to hundreds of pNs are exerted to thousands of biomolecules in parallel, with sub-millisecond response time and inherent stability. AFS distinguishes itself by its relative simplicity, low cost and compactness, which allow straightforward implementation in lab-on-a-chip devices. I’ll discuss the application of this technique to DNA-protein interaction as well as for antibody-protein interaction detection and for its use to quantify cell adhesion. |
14:00 | Gut on-a-Chip: Towards a More Predictive and Physiological Human Intestinal Barrier Model Evita Steeg, Researcher, TNO Quality Of Life, Netherlands
A majority of the preclinical intestinal models do not properly reflect the complex physiology of the human intestinal tract, resulting in low translational value. We have developed the InTESTine model, using fresh ex vivo (human) intestinal tissue mounted into a 2-compartmental microfluidic model with luminal and basolateral flow. Using InTESTine on-a-chip model the human intestinal tissue remains functional for 24 hours during incubations, as presented by proper transport and metabolic functionality and remained barrier integrity, and the model shows additional value in predicting human intestinal absorption of pharmaceuticals and nutrients. Besides ex vivo intestinal tissue, (human) intestinal stem-cell derived organoids possess promising features, especially when cultured as an epithelial monolayer. By applying microfluidic flow we stimulated growth of a confluent epithelial monolayer by showing an increase in TEER, limited vectorial leakage of FD4, while remaining phenotypic properties like cell proliferation and differentiation into the distinct cell types of the intestinal epithelium. In conclusion, we now can successfully use the human intestinal tissue and intestinal organoid monolayers for longer-term incubations, which can be applied as a reliable tool for studying processes that determine human intestinal permeability as well as (anaerobic) host-microbe-immune responses when mounted in the microfluidic device. |
14:30 | Scale-up and Sustainability for Large and Small Microfluidic Laboratories Maiwenn Kersaudy-Kerhoas, Professor of Microfluidic Engineering, Heriot-Watt University, United Kingdom
The rapid translation of research from bench to bedside, as well as the generation of commercial impact, has never been more important for both academic and industrial researchers. We propose low-capital investment and sustainable rapid-prototyping solutions for almost all LOAC applications, with potential to accelerate microfluidic research and technology acceptance dramatically. |
15:00 | Thermoplastic Elastomer Microfluidic Platform For Methylation-specific Digital Droplet PCR Lidija Malic, Research Officer, Industrial Materials Institute / National Research Council Canada, Canada
A thermoplastic polymer based microfluidic droplet generator platform is presented that enables digital droplet PCR (ddPCR) for determining degree of methylation as an epigenetic measure of WBC differential count. |
15:30 | Rapid Prototyping in Microfluidics: New Perspective by New Materials Bastian Rapp, Principal Investigator and Head of NeptunLab, Karlsruhe Institute of Technology, Germany
Microfluidics is a very important discipline for many disciplines including, among others, synthetic and analytical chemistry, biochemistry and biology. However, the design of most microfluidic systems has remained largely unchanged since the introduction of soft lithography. In academia, microfluidic systems made from polydimethylsiloxane (PDMS) have become the de-facto standard. These are usually created in a replication process from a photolithographically structured layer of photoresist. However, in many applications fast concept-to-chip intervals are required for efficient experimental throughput and optimization. This is where 3D printing and additive manufacturing (AM) can make a significant contribution. We recently introduced “Computer Aided Microfluidics (CAMF)” a process that allows the conversion of digital chip layout to a testable physical structure in less than a day [1]. Using digital models allows a streamlined manufacturing process with digital models first being evaluated by numerical simulation before being transferred to a physical structure in a one-step manufacturing process. We recently expanded the material choice for CAMF to include glass [2] (which is created by sintering from photocurable glass prepolymers) and thermoplasts, most notably polymethylmethacrylate (PMMA) for which we created photostructurable precursors. This allows the rapid manufacturing of microfluidic systems in materials which have a long history in microfluidics and have been thoroughly investigated. We will demonstrate the advantages of this prototyping method and its potential use in many aspects of life sciences and analytics. |
16:00 | Single Cell Manipulation and Detection Marine Verhulsel, Life Sciences Product Manager, Fluigent SA
Microfluidics has emerged as a powerful tool to manipulate cells at single cell level. These manipulations have been extensively used to evaluate the degree of heterogeneity of a population. Cell to cell variability can be quantified in terms of genetics, transcriptomics or biomechanics. In this context, Fluigent has developed highly sensitive and stable instruments which allow for the measurement of single cell tension within a tissue through pipette micro-aspiration. This technique is economical, easy to use and non-invasive compared to traditional AFM, cytoindenter and optical tweezers. Regarding proteomic and genetic analysis, Fluigent has also designed a droplet chip for single cell encapsulation. Decreased volumes (down to picoliters), reduced costs, higher sensitivity and throughput, faster sample processing and readout are valuable benefits of this technology. Finally, identifying specific single cells out of a patient sample can also be determinant for diagnostic applications. High surface to volume ratio related to microfluidics enables detection of rare biomarkers. Increased sensitivity and ability to fully automate protocols using Fluigent products will be presented in the context of circulating tumor cell (CTC) detection.
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16:30 | Key Enabling Functionalities for Point-of-Care Diagnostics Aliki Tsopela, R&D Scientist, Micronit Microtechnologies, Netherlands Rui Carvalho, R&D Scientist, Surfix BV, Netherlands
This presentation will focus on the work performed during the Coat PoCKET project, where Micronit Microtechnologies and Surfix join forces to bring the technology for fabricating advanced point-of-care diagnostic tests to the next level. The project aims at the development of a polymer-based microfluidic chip enabling sequential flow of liquids without using external pumps. This is achieved through an innovative combination of local surface modification and electrostatically actuated capillary valves. |
17:00 | LSC-PM: A Biomimetic Approach to Increase Solar Harvesting for Synthetic Chemistry 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. |
17:30 | Single-cell Imaging in Novel 3D Hydrodynamic Focusing Microfluidic Devices Iordania Constantinou, Postdoctoral Fellow, Zentrum für Molekulare Biologie der Universität Heidelberg, Germany
This presentation will discuss the development of a novel microfluidic device and its use in continuous-flow, high-resolution, single-cell imaging. |
17:45 | Single Molecule Microfluidic Methods to Characterise Vesicle-based Cell Mimetics Ali Salehi-Reyhani, Fellow, Imperial College London, United Kingdom
We have developed single molecule microfluidic methods to absolutely quantify the biomolecular constituents of an artificial cell and measure their encapsulation efficiency. We show how the heterogeneity in their synthesis must be accounted for when used as simplified biological models. |
18:00 | Low Cost Thermoplastic Microfluidic Devices to Investigate the Ribosome Biogenesis and DNA Synthesis in Yeast Elif Gencturk, Researcher, Bogazici University, Turkey
The aim is to fabricate a thermoplastic made microbioreactor that is capable of cell trapping. Yeasts are treated with RNA and DNA syntheses inhibitors to investigate ribosome biogenesis and DNA damage response. The device can be used for therapeutic applications. |
18:15 | Bone Marrow Scaffolds For Hematopoietic Stem Cell Utilizing the BioLithoMorphie®-Approach Joerg Hampl, Researcher, Ilmenau University Of Technology, Germany
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18:30 | BioLithoMorphie® Approaches to Gain 3D-Structures Including Fluidic Entities Andreas Schober, Head of Department Nano-biosystem Technology, University of Technology Ilmenau, Technische Universitat Ilmenau, Germany
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18:45 | Close of Day 2 of the Conference. |