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Approximately 14 million people die from infectious diseases annually, inflicting severe societal and economic burdens disproportionally affecting the Global South. The current standard for pathogen identification is blood culture which is too slow to guide the effective and targeted management of patients, and prevent the administration of broad-spectrum antibiotics. The analysis of microbial cell-free DNA (cfDNA), released from lysed pathogens in the infected human blood circulation, is an unbiased and sensitive way to detect infectious pathogens, including those that cannot be cultured such as viruses, fungi and protozoa. We have developed a cfDNA assay, named iSEP-SEQ, which combines a patented microfluidic system for cfDNA extraction, and real-time sequencing. The sample preparation module has been demonstrated on over 400 human samples and the iSEP-SEQ workflow is currently being piloted on clinical samples from septic patients to demonstrate its ability to identify pathogens in under six hours from blood draw.

Resistive Pulse Sensing (RPS) is a label-free and single-molecule detection approach that requires simple instrumentation to implement and as such, can be mobilized to be integrated into in vitro diagnostic assays for not only detecting but identifying key disease-associated biomarkers with high analytical sensitivity. Thus, RPS is a logical choice for coupling with liquid biopsy markers for the precision management of a variety of diseases due to the significant mass limits imposed on any assay in which a liquid biopsy marker is used. We have developed a unique measurement modality and sensor technology (dual in-plane nanopore sensor) that couples RPS to nanoscale electrophoresis, which has recently garnered attention due to unique molecular-dependent information it can provide. Not does it generate the typical RPS measurement parameters, but also the molecular-dependent electrophoretic mobility, which we call the time-of-flight (ToF). The RPS parameters coupled with the ToF and machine learning leads to high detection efficiency and classification accuracy of single molecules harvested from liquid biopsy markers, including nucleic acids and proteins. Our devices, which are made from plastics via high-scale production modalities (injection molding), consist of channels with dimensions ranging from 1 to 100 nm (effective diameter) that are 10’s of microns in length. In this talk, I will discuss the operational parameters and unique applications of our dual in-plane nanopore sensor for three compelling applications: (1) determining the fill status (empty versus full) of adeno-associated viruses (AAVs), which serve as carriers of gene therapy drugs; (2) peptide fingerprinting of single protein molecules; and (3) DNA/RNA single-molecule sequencing.

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As a person’s physiological regulation of biomarker molecules is challenged by acute illness, exposure to toxins or even surgery, the concentration these molecules can give important information about their health. For premature infants their regulation systems have yet to mature, so they can also suffer rapid changes in biomarker concentrations. Our view is that to monitor such biomarker changes effectively ideally requires moment-by-moment measurement of blood or tissue concentrations. The person acts as their own control allowing acute deterioration to be noticed quickly.

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 coupled to novel biosensors provide a valuable means of clinical sampling and robust quantification of measured biomarkers.

I will describe the key challenges in the development of such integrated microfluidic sensing devices and present our recent data from the neonatal intensive care unit amongst other projects.

Advancements and applications of microfluidic measurement technologies depend on better tools to integrate uncertainty quantification (UQ) and to resolve dynamics in measurements of small volumes and small particles. I will describe my lab’s projects in nanoflow metrology and optofluidic cytometry that are built upon robust microfluidic control and integrated measurement regions that incorporate optical waveguides to deliver and collect light interacting with materials passing through the microchannel. Our best-in-the-world flow meter uses the timescale associated with photobleaching to perform flow measurements in the nanoliters per minute regime. We have demonstrated flow measurements with 5% uncertainty down to 1 nL/min (approx 200-fold reduction in absolute accuracy over the best commercial flow meters) and the ability to resolve time-dependent changes in flow with time constants of 100 ms (many times faster than gravimetric or thermal flow meters). I will also discuss our efforts to develop UQ for flow cytometry. By integrating repeated measurements along a microfluidic channel, the “serial cytometer” allows quantification of each object’s fluorescence to better than 2 % measurement uncertainty. Coupled with novel optical profiles and new signals analysis techniques, the technology also enables estimation of particle size, doublet separation, elasticity, and even dynamic measurements of reactions confined to microdroplets created in flow.

The basis of my talk is polymer microarray technology which has been developed in the Bradley group.
In my talk I will introduce polymer microarray technology and describe how this approach has been used in a number of applications – ranging from sensor optimisation/immobilisation to the provision of cellular substrates/scaffolds for a variety of screening applications. Specifically I will cover:

The use of polymer microarray technology to discover substrates with optimal binding and responsiveness of fluorescent reporters and their immobilisation onto the ends of optical fibres for measuring pH around tumours

The use of polymer microarray technology to discover polymers that bind cancer stem cells and control their differentiation) (with Tetsuya Tega, Stem Cells, 2016) with application in cancer screening.

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The detection of ultra-rare variants in liquid biopsy samples is often hindered by the highly fragmented nature and low concentrations of cell-free (cf) DNA and circulating tumor (ct) DNA. In non-advanced, non-metastatic cancers, ctDNA constitutes only 1–2% of total cfDNA, making its extraction and analysis particularly challenging. However, current DNA extraction and purification methods are limited by high costs, complex instrumentation requiring routine maintenance, and lengthy processes that reduce DNA recovery and compromise integrity for downstream applications such as PCR and sequencing. To address this critical gap, our team has developed a patented DNA extraction and isolation (DEI) membrane and assay, designed to efficiently capture and retain more DNA from liquid biopsy samples. Our technology enhances DNA yield and integrity, offering a cost-effective and scalable solution for integration into point-of-care diagnostic systems, including microfluidic platforms, laboratory diagnostic systems, and PCR-based workflows. Here we have demonstrated a microfluidic-based digital PCR platform where the DEI membrane was integrated into our current platform towards effective and efficient quantification of viral load.

The generation of tissue models that reproduce the key three-dimensional (3D) features of the cellular and matrix environment of organs is one of the most important challenges in the entire field of biology. Cell behavior in a tissue is indeed governed by the 3D microenvironment and involves a dynamic interplay between biochemical and mechanical signals provided by the extracellular matrix (ECM), cell–cell interactions, and soluble factors. The physical attributes (dimensions, topology, stiffness, etc.) of the microenvironment work in concert with biochemical signals to profoundly impact cell fate and tissue functionality. In this context, 3D bioprinting has emerged as a new paradigm in the fields of drug screening, tissue engineering, and regenerative medicine. It promises precise control over the creation of scaffolds with controlled architectures and in the spatial deposition of cells, spheroids, and organoids in 3D. This presentation will showcase several examples of light-assisted fabrication technologies that have been developed to overcome the challenges associated with reconstructing microenvironment models, particularly focusing on multi-material and multi-scale printing. The discussion will highlight the fabrication of hydrogel scaffolds specifically tailored for intestinal tissue models. Additionally, we will demonstrate how the selection of appropriate biomaterials as matrix models—facilitating cellular adhesion, proliferation, and eventual remodeling—is crucial for the successful reconstruction of tissue architecture and functionality. Notably, we have developed a tissue engineering process that meticulously controls the biomechanical and biochemical microenvironment to guide the in vitro formation of functional mesenchymal organoids of significant size. This approach has been validated through the successful generation of functional human beige adipose organoids.

Harnessing 3D printing for microfluidic device fabrication is challenged by the need for sub-100 μm features, especially the negative space structures central to microfluidics. This presentation showcases custom Digital Light Processing (DLP) 3D printers and optimized materials developed to tackle these demands and push the boundaries of resolution. We introduce a photopolymerization simulation tool to explore the enhanced parameter space created by our generalized 3D printing method. This method expands the available parameter space to achieve negative feature resolutions approaching the printer’s physical limits. We demonstrate the application of these innovations to high-resolution passive structures (e.g., channels, mixers) and active components (e.g., valves, pumps), integrated into functional devices such as dose-response assays and cell chemotaxis chips. Example achievements include channels with 2 μm x 2 μm cross-sections and valves with 15 μm x 15 μm active areas, highlighting the potential of these innovations to redefine microfluidic fabrication.

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Scaling up microfluidic innovations from laboratory prototypes to large-scale manufacturing presents unique technical and operational challenges. This presentation addresses critical considerations for transitioning microfluidic designs from proof-of-concept devices to mass-produced commercial products. Leveraging Hicomp's expertise in microfluidic chip prototyping, fabrication, and process optimization, we will discuss practical strategies for selecting suitable materials, optimizing chip designs for manufacturability, ensuring robust quality control, and streamlining production workflows. Real-world examples and insights will illustrate common pitfalls, effective solutions, and best practices to facilitate successful scale-up. This session aims to provide attendees with actionable guidance on bridging the gap between laboratory innovation and high-volume commercial fabrication.

Magnetic Resonance Imaging (MRI) uses hydrogen nuclei in strong magnetic fields to non-invasively sense tissue or structural properties. The interaction between the hydrogen nuclei and distortions of the magnetic field form an essential source of imaging information in clinical MRI. 3D micro-printing enables to manufacture features that create well-controlled magnetic field inhomogeneities in the micrometer scale. This enables a novel test bed to study and develop MRI methods with microstructural sensitivity.

This study develops a long-term circulating tumor cell (CTC)-derived model from a triple-negative breast cancer (TNBC) patient who has developed resistance to standard treatments. CTCs are isolated from blood using a negative enrichment approach and cultured in a basement membrane extract with organoid medium. The resulting organoids proliferate for more than 10 passages, maintain TNBC characteristics, and show high resistance to platinum-based therapy, mirroring the patient’s tumor. Drug screening identifies potential therapeutic vulnerabilities, highlighting the model’s relevance for studying metastasis, therapy resistance, and immune interactions in TNBC. This preclinical tool facilitates the development of targeted therapies and a better understanding of CTC biology.

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Eden Material is at the forefront of innovation in microfluidics, providing solutions that streamline the entire process from design to production. Our technologies, including FLUI'DEVICE for intuitive microfluidic design, FLUI'MOLD for high-resolution mold fabrication, and Flexdym, our alternative to PDMS, address key challenges faced by researchers and engineers. By offering seamless integration between software, materials, and fabrication techniques, we enable cost-effective, scalable, and high-performance microfluidic development. This presentation will explore how Eden Material’s ecosystem accelerates research, enhances reproducibility, and opens new possibilities for biomedical, diagnostic, and industrial applications.

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PP TechSales represents the innovative dispensing technology of PolyPico Technologies Ltd., which simplifies the dispensing process for R&D, small-scale, and fully automated production. Using patented disposable dispensing cartridges (DCs) eliminates cross-contamination, minimizes maintenance, and reduces costs associated with traditional dispensing methods. With the unique precision, PolyPico’s dispensers can generate pico-, nano-, or low microliter volumes at speeds of up to 10,000 droplets per second. Thanks to dispensers’ versatility and multiple DC orifice sizes there are supported various solutions, including DMSO, buffers, oils, glues, and even 100% glycerol. This cutting-edge technology delivers unique accuracy and efficiency, eliminates intensive washing, buffer consumption or carry-over risks, while enabling recovery of unused samples.

Liquid biopsy and organ-on-chips hold tremendous promises for personalized medicine, enabling opportunities for drug development and tailored therapies that could potentially improve or save lives. Both technologies face manufacturing challenges in microfluidics, including the need for high aspect ratio features and - especially for organ-on-chip systems - the use of flexible materials for mimicking the realistic mechanical deformation of organs. In this presentation, we will highlight our manufacturing capabilities overcoming these technical challenges using scalable manufacturing processes like molding, bonding and assembly and demonstrate two examples that underscore the integration of microfluidic structures in liquid biopsy for TellBio, Inc and Organ-on-Chip for Organos, Inc.

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 use quantum sensors in fluidic chips.

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We explored the development of a novel integrated optofluidic system for application like UV-Vis spectroscopy analyte detection. Total Internal Reflection (TIR) approach requires a cladding material with a refractive index (RI) lower than the fluidic core (eg. water, n=1.33). The silica aerogel was chosen as a highly nano-porous material whose RI can be tuned from 1.05 to 2.2 using a thermal densification process. Simple channels were shaped using PET polymer wires inserted during the gelification step and dissolved under the supercritical drying one. After hydrophobic treatment, we built an aerogel-based optofluidic (OFAB) modules, including a manifold system able to integrate both optics and fluidics. First, we studied the detection of multiple concentrations of the dye ’Brilliant Blue FCF’ at 630nm as a function of sample length and channel diameter. Then OFAB approach was used to detect a range of drug concentrations (Ropivacaine), diluted in a biologically relevant medium (PBS) at 263nm.

Our microfluidic components integrate a wide range of functionalities into a single element. Leveraging advanced semiconductor manufacturing techniques, we enable the incorporation of etched microchannels, through-glass vias (TGVs), patterned metallic and dielectric coatings, electronic conductors (electrodes), and optical gratings—all within one compact structure. This technological versatility allows us to combine additional features, resulting in a diverse portfolio to address the various requirements in the life science industry. Our offerings include micro-structured coatings, thin-film waveguides with coupling gratings, calibration plates, integrated electronic components, and much more.

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Nanoscale systems for drug delivery have received considerable attention over the past decades, as they have the potential to overcome limits associated with conventional drug therapies, providing a solution to medical challenges that urgently require new therapeutic approaches. Nanodrugs can improve the therapeutic index of the loaded drug by providing protection against degradation, enabling controlled release and distribution, and increasing bioavailability. Advanced functionalization strategies have been used to confer them long-circulating properties and facilitate targeting to specific cells. These efforts have led to the introduction into clinical practice of a few nanoscale systems for tumor therapy. However, their small number, compared to the variety of promising systems proposed, reveals a considerable gap between favorable preclinical results and real clinical performance. Biological barriers, inherent to tumors and their microenvironments, pose formidable challenges. To bridge this gap, our focus turns to three-dimensional (3D) culture methodologies. Unlike conventional 2D cultures, 3D models better replicate the heterogeneity, pathophysiology, and structural architecture of real tumors. Our ongoing efforts involve constructing heterotypic multicellular 3D tumor spheroids, serving as robust screening tools. This approach aims to enhance our understanding of nanodrugs penetration and accumulation within the tumor mass. By identifying key parameters, we strive to maximize therapeutic benefits.

The presentation will focus on the following topics:

Introduction on High-Grade Gliomas (HGGs) and its Tumor microenvironment

To properly study and challenge HGG Tumor microenvironment (TME) is important to recapitulate several aspects: (e.g., brain extracellular matrix, cell-to-cell interactions)

Bioreactor-based culture of neurospheroids: from neural cell differentiation to incorporation of microglia-derived cells: from high batches to miniaturization

HGG 3D cell culture establishment
Inclusion of HGG cells within neurospheroids: building up of immunosuppressive TME and invasive phenotype

Conclusion and future perspectives

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The rheological properties of biological tissues are crucial in wound healing or morphogenesis. We have developed an innovative microfluidic device which enables studying in depth the rheology of model tissues by realizing micropipette aspiration of ~20 spheroids (3D cell aggregates) in parallel. Thanks to dynamic stimulation, we show that the coupling of fluid flow inside the aggregate with its deformation (poroelasticity) needs to been taken in account to properly describe the tissue response: permeability contributes to the transmission of stress, followed by cell deformation and finally cell reorganization in the tissue. Cell scale imaging and immunostaining are also used to assess the relationship between microstructure and rheological properties. Finally, the approach can be extended to other tissues. In collaboration with a team specialized in embryogenesis, we are assessing spatial heterogeneities in cail embryos, in order to relate cell fate and differentiation to biophysical properties.

Inter-individual variability in muscle responses to mechanical stress during exercise is poorly understood. Therefore, new cell culture scaffolds are needed to gain deeper insights into the cellular mechanisms underlying the influence of mechanical stress on human myogenic progenitor cells behavior. To this end, we propose the first in vitro model involving uniaxial mechanical stress applied to aligned human primary muscle-derived cells, employing a biocompatible organic-inorganic photostructurable hybrid material (OIPHM) covalently attached to a stretchable PDMS support. Using a laser printing technique with an additive photolithographic process, we optimally micropatterned the PDMS support to create longitudinal microgrooves, achieving well-aligned muscle fibers without significantly affecting their diameter. This support was biofunctionalized with peptide sequences from the ECM, which interact with cellular adhesion receptors and prevent myotube detachment induced by stretching.

Whenever microfluidics is considered a viable solution to answer key biological questions, we hit several major hurdles. First, regarding the chip itself, commercially available microfluidic chips exist but often must be adapted to our question and adaptation is costly. Geometries need to be altered, new features must be added, another material needs to be used… I will present our capabilities for producing microfluidic chips in various materials for different applications. Second, regarding using the chip in our experiment, (putting aside the plumbery issues about finding the right tubing for the right adapter)… today, there is no unique software combining microscopy hardware and microfluidic hardware (often leading to a home-made solution with a lack of sustainability and stability). I will showcase our development (and available to all) using micro-manager, the open-source software for controlling and automating microscope hardware easing complete microfluidic experiments.

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CEPI are funding projects to develop novel analytical technologies for the purpose of rapid development, decentralized manufacture and release of vaccines including equitable access in LMICs countries, in response to a potential pandemic threat. This presentation will walk you through the current gaps to address as well the application and review process. Each project may be funded up to $1M to reach Design Freeze stage.

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