Lab-on-a-Chip and Microfluidics Europe 2024 Agenda

Conference Co-Chairperson's Introduction and Welcome
Claudia Gärtner, CEO, microfluidic ChipShop GmbH, Germany

Conference Co-Chairperson's Introduction and Welcome
Nicole Pamme, Professor in Analytical Chemistry, Stockholm University, Sweden

Real-Time Viscoelastic Deformability Cytometry
Andrew J deMello, Professor of Biochemical Engineering & Institute Chair, ETH Zürich, Switzerland

Differences in the mechanical properties of diseased cells and their benign counterparts means that mechanical phenotyping of cells can be used to report both cellular state and function. Accordingly, the ability to perform such measurements in a robust and high-throughput manner suggests potential utility in the detection and diagnosis of disease. Whilst different methods for cellular mechanophenotyping have been described, the ability to perform high-throughput single-cell deformability measurements on liquid or solid tissue biopsies remains an unmet challenge within clinical settings. To address this issue, we have developed viscoelastic deformability cytometry (vDC), a microfluidic method able to measure the mechanical properties of single cells at rates of up to 100,000 cells per second. Fluid viscoelasticity is used to both focus and deform cells without the need for sheath fluids. We have used vDC for cell phenotyping of both liquid and solid tumor biopsies, cytoskeletal drug analysis, and identifying malignant lymphocytes in peripheral blood samples. vDC offers new opportunities for high-throughput, label-free single cell analysis, with diverse applications in clinical diagnostics and personalized medicine.

Microfluidics in Liquid Biopsy and Integration in Functional Studies
Lorena Diéguez, Leader of the Medical Devices Research Group, INL- International Iberian Nanotechnology Laboratory, Portugal

Microfluidics has demonstrated numerous advantages for isolation and characterization of liquid biopsy biomarkers in oncology, with increased sensitivity and throughput, enabling their implementation in clinical routine. Microfluidics is also very relevant to build biomimetic and dynamic 3D models to better understand the process of metastasis. In this talk, we present our most recent work for the development of holistic liquid biopsy assays, by integrating microfluidic extraction of CTCs, cfDNA, and EVs; and application of viable CTCs in functional models for the study of metastasis.

Droplet-based Microfluidics for Biomarker Detection and Quantification
Valérie Taly, CNRS Research Director, Professor and Group leader Translational Research and Microfluidics, Université Paris Cité, France

Droplet-based microfluidic has led to the development of highly powerful tools with great potential in High-Throughput Screening where individual assays are compartmentalized within aqueous droplets acting as independant microreactors. Thanks to the combination of a decrease of assay volume and an increase of throughput, this technology goes beyond the capacities of conventional screening systems. Added to the flexibility and versatility of platform designs, such progresses in the manipulation of sub-nanoliter droplets has allowed to dramatically increase experimental level of control and precision.

The presentation will aim at demonstrating through selected examples, the great potential of this technology for patient monitoring in infectious diseases and cancers. A specific focuss will be made on the application of droplet-based digital PCR for the detection of blood-based methylation biomarkers (liquid biopsy). The results of several prospective clinical studies will be presented highlighting great potential of this technology for the follow-up of both advanced and localized cancers.

Investigating Endothelium Permeability in vitro Under Healthy and Diabetic Conditions
Elisabeth Verpoorte, Chair of Analytical Chemistry and Pharmaceutical Analysis, University of Groningen, Netherlands

Microfluidic systems incorporating endothelial cell monolayers were among the earliest examples of organs-on-chips, with examples dating back almost two decades. This was to be expected, as microchannels are an obvious (though perhaps not perfect) mimic for the (micro)vascular system in terms of geometry. Moreover, microchannel-based in vitro systems also allow controlled application of shear stress, a crucial parameter in vivo that dictates endothelium properties. We have worked primarily with human umbilical vein endothelial cell (HUVEC) culture in gelatin-coated glass or PDMS channels, and more recently, with cells cultured on a gelatin substrate. This has allowed us to construct microflow systems to study the permeability of endothelial cell monolayers in diabetes-associated microenvironments, by tracking the transport of fluorescently labelled albumin across these barriers into a gelatin layer underneath. We have observed the appearance of protective effects of cell-extracellular matrix interactions on endothelial cell morphology under shear stress (10 dyn/cm²). More specifically, the endothelial cells maintained their typical cobblestone morphology. In addition, we recorded increased basal permeability values, compared to our results from static experiments, results that aligned well with literature data. We were then able to model a DKD milieu in our endothelium-on-a-chip to test a pharmaceutical compound, finerenone, a mineralocorticoid receptor antagonist (MRA) used in the treatment of diabetic kidney disease patients. We observed a statistically significant improvement in endothelial barrier properties for cells protected by finerenone in comparison to measured barrier permeability in DKD milieu without finerenone.

3D Printing of Porous Membrane Integrated Devices
Rosanne Guijt, Professor, Deakin University, Australia

The integration of chemical functionalities in microfluidic devices can be accomplished by the combination of different materials. 3D printing has readily been proposed as alternative for manufacturing of fluidic devices, in particular for small scale production. Resin-based printers are most suitable for printing small features, however, the combination of different materials remains a challenge. This presentation focuses on the development of resins for digital light projection 3D printing of porous materials, and their integration into fluidic devices by resin exchange and using greyscale masks. Applications of the devices include phase separation, chemotaxis, extraction of DNA and the detection of iron from soil.

Real-Time Point-of-Care Diagnostics Using Microfluidic Sensors and Biosensors
Martyn Boutelle, Professor of Biomedical Sensors Engineering, Imperial College London, United Kingdom

We are investigating technologies that take POC measurements from a moment in time that assists diagnosis to a continuous information stream that guides treatment dynamically. Biomarker molecule concentrations can give important information about the health of a person as they are dynamically challenged by acute illness or for example during clinical treatment. Such an approach would allow individualized treatments to be chosen and optimized. We have been developing a range of sensing and biosensing solutions for the invasive, minimally invasive, and non-invasive monitoring of people in healthcare situations. Microfluidics provide a valuable means of clinical sampling and robust quantification of measured signals.

I will describe the key challenges in the development of such integrated sensing devices and present our recent data obtained during models of cardiac arrest and from the neonatal intensive care unit.

Microfluidics, Lab-on-Chip and Environmental Sustainability: The Limits of the Single-Use
Maiwenn Kersaudy-Kerhoas, Professor of Microfluidic Engineering, Heriot-Watt University, United Kingdom

Many microfluidic point-of-care tests are now ubiquitous tools in rapid methods for human or veterinary diagnostics, or environmental monitoring. Using a microfluidic engineer perspective, and discussions with global health practitioners and anthropologists, I will share what I learned in recent years about the mishaps of point-of-need, single-use and disposable methods. Finally, I will use a recent project in which we produced lateral flow tests using recycled plastics (including derived from discarded chewing-gum!) as a case study for discussion on materials, engineering, supply chains, regulations, and considerations of human behaviour towards creating more sustainable point-of-care medical devices.

Precision Manufacturing of Polymeric Microfluidic Devices: Progress from Fast Prototyping Using High Precision DLP Printing and Defect-Free Production via Self-Lubricating Mould Technology
Nan Zhang, Associate Professor, University College Dublin, Ireland

Microfluidic devices have been used in point-of-care diagnostics, drug development and life science research. After more than 40 years development, microfluidic technology has been becoming a platform technology and reforming the development of the future generation in-vitro diagnostics, bio-pharma and life science. In comparison to the increasing development of advanced applications using microfluidic as a technical base, the manufacturing processes of microfluidic devices is still constrained by the tedious prototyping, which is still time consuming and requires specialized equipment. During production stage, for the high density and high aspect ratio micro structures, demoulding can cause feature damage or distortion, and thus affect the subsequent bonding and overall chip functionality. In the present talk, I would like to share our current progress on high precision prototyping of microfluidics devices by 3D printing based on Digital Light Processing technology, and showcase complex channel 3D printing and hybrid 3D features inside of 2.5D micro channel. Additionally, I would also like to talk about our newly developed novel self-lubricating micro/nano mold technology for defects-free production of plastic microfluidic devices. The demonstration will be highlighted for testing star patterns and microfluidic devices.

Advances in 3D Printing for Microfluidics
Gregory Nordin, Professor, Brigham Young University, United States of America

While there is great interest in 3D printing for microfluidic device fabrication, a main challenge has been to achieve feature sizes that are in the truly microfluidic regime (<100 µm). A key issue is that microfluidic devices are comprised primarily of negative space features, which therefore dominate 3D printing resolution requirements, as compared to positive space features that are typical for many other 3D printing applications. Consequently, we have developed our own stereolithographic 3D printers and materials that are specifically tailored to meet these needs. We have shown 3D printed channels as small as 18 µm x 20 µm, and have recently reduced this to 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 only 15 µm x 15 µm. With these capabilities, we demonstrate highly integrated 3D printed microfluidic components such as a 10-stage 2-fold serial dilutor in an X-Y footprint of only 2.2 mm x 1.1 mm. We also show a fast (~1 ms) and small (<1 mm^3) 3D printed mixer using a new multi-resolution 3D printing technique. These advances open the door to 3D printing as a replacement for expensive cleanroom fabrication processes, with the additional advantage of fast (~5-15 minute), parallel fabrication of many devices in a single print run due to their small size.