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Delivery of microfluidic devices, especially for those associated with clinical measurements, must go through several steps prior to delivery to the clinical market. These include prototyping through an iterative process to home in on a device concept optimal for the intended application, medium scale production for testing to secure the analytical and clinical figures-of-merit, and finally large scale production for commercial dissemination. In this presentation, I will present the fabrication techniques used to move through the production pipeline using thermoplastics as the substrate of choice for generating microfluidic devices for in vitro diagnostics. Fabrication techniques that will be discussed for prototyping include high precision micromilling that has a device turnaround time < 1 day and is a maskless process not requiring a cleanroom. Excimer laser machining will also be discussed. In terms of medium scale production, micromilling of embossing tools and the use of hot-embossing will be discussed as a methodology for medium scale production to produce devices appropriate for securing the necessary figures-of-merit. Finally, I will discuss the use of photolithography and Ni electroplating to form mold inserts for the high-scale production of devices for commercial applications using injection molding. I will also discuss appropriate assembly processes that can be implemented to generate finished devices containing cover plates with high process yield rates. I will also discuss surface modification strategies that can be implemented on plastic devices to allow for increasing surface wettability as well as attaching functional biomolecules to the surfaces required for the intended application. Finally, I will show some examples of plastic devices that went through this production pipeline for clinical measurements, such as the processing of liquid biopsy markers.

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This presentation will describe efforts in our lab to develop lung microphysiological systems (MPSs). The talk will start with microfluidic small airway models that combine in-channel air-liquid interface culture with liquid plug propagation and rupture under conditions of surfactant dysfunction. Novel fluidic switching mechanisms for lung-on-a-chip applications will also be described. For higher-throughput studies, Transwell-96 based air-blood barriers model will be described that facilitates virus infections studies and also promises to accelerate studies of inhalation toxicity on lung inflammation. Finally, development and use of Airway Organoids with Reversed Biopolarity (AORBs) in 384 well plate single-organoid-per-well format drug testing for SARS-CoV-2 drugs will be described.

Additive manufacturing—or three-dimensional (3D) printing—has gained significant traction within the microfluidics community as a means to fabricate sophisticated system architectures that are challenging or impossible to produce using conventional microfabrication methods. Among the most promising 3D manufacturing technologies is Direct Laser Writing (DLW), which uses two-photon (or multiphoton) polymerization phenomena to achieve high geometric versatility and rapid print speeds at length scales down to the 100 nm range. In this Keynote Presentation, Prof. Ryan D. Sochol will discuss how his Bioinspired Advanced Manufacturing (BAM) Laboratory is leveraging DLW for emerging microfluidic applications, including: (1) microneedle technologies for embryo and brain microinjections, (2) 3D organ-on-a-chip systems, and (3) soft microrobotic surgical instruments for endovascular interventions.

Explore cutting-edge advancements in PDMS mold technologies—from traditional multi-layer SU-8 molds and innovative 3D-printed and metal mold solutions to specialized mold designs that enable reliable, high-volume PDMS manufacturing. This talk will highlight practical strategies, services, and cost structures for transitioning your PDMS devices seamlessly from laboratory prototypes to mass-produced clinical and diagnostic products.

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Microfluidic devices are very attractive for analysis of biological samples due to their unique capabilities ranging from highly localized and deterministic cell manipulation to integration with highly sensitive micromachined sensors/actuators. As such, differences in various biomarkers including biophysical (i.e., size, density, electrical permittivity, stiffness) and biochemical (surface antigen expression) properties among cells can be used to effectively detect a subpopulation of interest with these devices. However, while highly effective in discriminating cells, microfluidic devices often lack an on-chip readout and require a benchtop instrument such as a flow cytometer, optical microscope or a mass spectrometer in the downstream for actionable quantitative data. The reliance on external instruments negates the portability and cost benefits of these devices and limits their translation for use in point-of-need settings, where they can be truly transformative.

In this talk, I will present microfluidic devices with built-in electrical sensor networks that perform high-throughput physical and chemical measurements by digitally monitoring the trajectory of every individual cell under test. Specifically, we create a network of coded Coulter counters distributed across a microfluidic chip by micromachining the electrodes in distinct shapes. In our assays, the microfluidic structure acts to spatially map each cell based on a parameter of interest (not limited to a parameter that can be measured electrically), while the electronic sensor array quantifies subpopulation fractions by detecting individual cells at strategic locations on the microfluidic chip. Moreover, by designing the Coulter counters to produce mathematically distinguishable digital signals, we compress on-chip cell manipulation data into an electrical waveform, substantially eliminating the instrumentation complexity and data redundancy associated with microscopy imaging.

Mask-aligners have been used for decades as key technological equipments to manufacture microchips, in particular in semiconductor industry. More recently, these equipments, historically based on the use of mercury lamps as the UV-source, have also been considered as relevant systems to enable the fabrication of chips in microfluidics (molds / PDMS casting, Lab On a Chip, Organ on A Chip…) in particular thanks to the cost effective use of plastic/flexible photomasks (before considering the use of chrome photomasks to achieve higher resolution). However, the use of mercury lamps, that was already very energy consuming, is also now worldwidely compromised in a very near future by considering the global ban of using mercury in fluorescent lighting (Minamata Convention on Mercury) that entered into force in 2017, and that has been ratified by 140 countries, while the last use exemptions remain presently in effect later by 2027. Without waiting for this recent decision dedicated to protect human health and the environment from the adverse effects of mercury, our company KLOE SAS introduced UV-KUB3 on the market since 2015 as the very first range of UV-LED based mask-aligners and this presentation highlights the major advantages of using this range of innovative lithography equipments as the new generation of mask-aligners.

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Realizing the full potential of 3D printing for microfluidic device fabrication requires achieving feature sizes in the truly microfluidic regime (<100 μm), a task complicated by the dominance of negative space features that impose unique resolution demands compared to the positive features typical in conventional 3D printing. To address this, we have developed custom Digital Light Processing (DLP) 3D printers and tailored materials optimized for high-resolution microfluidics. In this presentation, we explore two pivotal innovations. First, we introduce a generalized 3D printing approach that expands the parameter space for high-resolution microfluidics without requiring proportional increases in physical resolution. We demonstrate this with a test print featuring 1,600 valves, showcasing solutions like miniaturized valves with active areas as small as 15 μm x 15 μm and isoporous membranes with 7 μm pores. Second, we present a multi-resolution 3D printing technique that achieves dual resolution scales across all three dimensions. This method enables rapid fabrication by using a lower-resolution optical engine for the bulk of the device, while a higher-resolution engine targets select regions needing extreme resolution. We highlight its effectiveness with examples, including a high-surface-area triply periodic minimal surface (TPMS) structure integrated into a microfluidic channel and an ultra-compact mixer (0.0017 mm³). These advancements illustrate how 3D printing can be a transformative tool for microfluidic fabrication.

It has long been recognized that electrical circuit models can be used to describe the operation of microfluidic circuits under laminar flow. For pneumatic, valve-control circuits and microfluidic applications, these analogies are useful, although air compressibility can introduce deviations in practice. A significant bottleneck between design and implementation of these pneumatics to real-world applications has been the need for device fabrication through standard photolithography, which is a time-consuming process with low design iteration throughput. In this work, inexpensive resin-based 3D printers (US $600-800) were used to rapidly design and prototype pneumatic and microfluidic circuits, removing the lithography-based bottleneck. Modular circuit designs included single- or multiple- valve packages, resistors, capacitors, tubing interfaces, T-junctions, vacuum manifolds, fluidic channels, droplet generators, pumps, and mixers. With plug-and-play connectors, these elements could be easily connected or disconnected, allowing various complex configurations such as oscillators (0.5 – 120 Hz operation), delay buffers (20 – 150 ms timing), and custom pneumatic logic circuits to reshape pulse signals. These pneumatic circuits can be used without any software or electrical control, using only a single vacuum input, providing autonomous control over applications such as droplet generation or mixing for biosensors. In one example, multiple valves (aqueous and oil) are triggered with custom timing, allowing automatic and cyclic gating of a sample droplet, an oil spacer, a reference droplet, and another oil spacer. These ordered steps are used in our devices for adipose tissue secretion sampling at high temporal resolution. In this presentation, pneumatic circuits and their microfluidic applications will be discussed from the modeling stage using simple circuit analogies, through design, to the final applications that include the aforementioned droplet devices as well as mixers for electrochemical sensors. We envision a variety of other applications, such as autonomous control of tissue-on-a-chip microdevices, could be made accessible to non-experts in this way.

This presentation will cover our progress toward developing and characterizing a high resolution and biocompatible polydimethylsiloxane 3D printing resin and its use to create therapeutic microfluidic artificial lungs.

3D printing brings with it a plethora of advantages for microfluidic applications. Principle among these are rapid prototyping, iterative design, and the ability to avoid the cost and overhead of cleanrooms. However, there is also an inherent advantage in being able to design and build devices in a truly three-dimensional, rather than layer-by-layer, geometry. One simple domain in which the advantages of true 3D routing are clear is in mixing. Control over a 3D geometry allows for multiple complex mixing configurations--herringbones, relamination mixers, chaotic advection--to be trivially constructed and recombined.

We have used these principles of 3D design to construct devices and systems for bioanalytical assays, for manufacturing biomaterials, and for industrial-scale manufacturing of novel materials. This talk will examine all of these applications and the manner in which 3d-centric microfluidic design can enable them.

The commercialization of microfluidic products requires integrating diverse components made from different materials and fabrication techniques. This process demands advanced fabrication and assembly methods that enhance performance while minimizing production costs. In this presentation, we will explore effective strategies for product development and scaling microfluidic technologies. Through real-world examples, we will share best practices for overcoming challenges in development and transitioning to high-volume manufacturing.

Micro- and nanomaterials, along with portable devices, are transforming the scientific landscape—empowering researchers both in the lab and in the field. From next-generation sequencing and single-cell analysis to environmental monitoring and resource management, cutting-edge science depends on cutting-edge tools.

At RAN Biotechnologies, our team of scientists, technologists, and innovators is dedicated to developing smart, accessible solutions that enable and accelerate discovery. In this presentation, Dr. Nassar will provide an overview of RAN Biotech’s mission and current initiatives, followed by highlights of recent advancements including:

PFAS-free reagents for droplet microfluidics
Porous, compressible gel beads for biological assays
Simplified and versatile microfluidic devices designed to lower barriers to adoption

Together, these innovations aim to make microfluidic and analytical technologies more efficient, customizable, and accessible across a wide range of applications.

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Recent advances in epidermal microfluidic systems have demonstrated capabilities for capturing, routing, and analyzing biomarkers in sweat to assess an individual’s health status without the need for blood sampling. These platforms, while analytically powerful, have traditionally relied on multi-step cleanroom processing techniques that constrain both design possibilities and deployment. Here, we describe our work in developing an alternative approach based on stereolithographic (SLA) 3D printing that enables rapid prototyping of soft, skin-compatible microfluidic networks with fully three-dimensional architectures. This methodology reduces fabrication time to minutes rather than days, while simultaneously expanding the accessible design space to include features such as spatially-graded channel geometries, integrated passive valving structures, and hierarchical reservoir systems—all within a single monolithic fabrication step. We demonstrate further capabilities by combining these printed constructs with direct laser-writing of graphene-based electrodes, yielding hybrid devices that merge fluidic handling with electrochemical sensing modalities.

The performance of many microfluidic, biosensor and wearable devices is intricately intertwined with the materials employed to fabricate them. Functional nanomaterials facilitate devices and instruments with new principles of operation, improved performance, or improved portability. One area of focus is the development of highly flexible polymer composites with different functionalities, such as being magnetic and/or conductive, and their application to microfluidics, biomedical microelectromechanical systems (BioMEMS), and wearable devices. We investigate how such materials can be designed and patterned using inexpensive rapid prototyping methods in order to improve the performance of small actuators for microfluidics devices; to develop highly flexible and wearable biosensors and sensor systems; and to perform other functionality, such as light-activated antimicrobial activity against bacterial and viral pathogens; or gas sensing.

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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A 20 year journey to make Microfluidics mainstream in Clinical Medicine- the science, the scale, the people, the heartbreaks, and the breakthrough moments.

Microfluidic devices based on inertial focusing have garnered significant attention for blood fractionation and liquid biopsy applications due to due to their label-free nature. Nevertheless, these devices often exhibit complexity, limited throughput, and dependence on sample dilution, posing challenges for deployment in clinics. The talk will explore our strategies to address these issues, aiming to develop platforms capable of label-free separation from unmodified whole blood. Comparative analysis with commercial systems will be discussed and applications in clinical studies will be highlighted.

Understanding and measuring cell-to-cell differences will allow many critical needs in human health to be addressed. This is true because a minority of cells with a distinct phenotype can drive both normal function and disease states. Existing platforms that provide resolution at the single-cell level are limited in the nature and number of endpoints that can be measured. Adding to this challenge is the fact that clinical samples often comprise a mixture of cell types, and the methods utilized for isolating cells of interest can compromise cell viability and function. As a consequence, the selection process further limits accessible endpoints that examine native function – such as cell signaling, drug response, or cell-cell interactions. There is therefore a need for methods that maintain cell viability and preserve phenotypic characteristics for downstream assays. We have developed a method for integrated selection, fluidic isolation, optional lysis and assay of single cells in parallel in a unified platform that is sufficiently simple to be adopted broadly. This device captures cells by dielectrophoresis (DEP) at an array of wireless bipolar electrodes (BPEs) aligned to picoliter-scale chambers. We have further quantified its selectivity in the isolation of circulating melanoma cells (CMCs), which lack reliable markers for isolation by prevailing methods. In this presentation, we discuss advancements to this DEP-BPE platform that expand its capabilities. First, we leverage the BPEs as electrochemical sensors and as substrates for in situ formation of microstructures by electro-polymerization. Second, we report an insulator DEP (iDEP) version of this platform that enhances cell viability by preventing cell-electrode contact. Finally, we demonstrate discrimination of melanoma cells that exhibit resistance to chemotherapeutic agents. In concert, these methods allow for selective individual isolation of viable cells in parallel for subsequent sensing or molecular assays.

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Microfluidic point-of-care diagnostics facilitate rapid, lab-free assays near the patient. Previously, thermally bonded cyclic olefin polymer (COP) chips effectively detected Vibrio cholerae DNA from pond water within 45 minutes using smartphone-based Loop-mediated Isothermal Amplification (LAMP) and particle diffusometry (PD). PD measures target DNA by tracking reductions in Brownian motion of fluorescent beads, indicating DNA amplification. COP's optical clarity is vital but challenging to maintain during bonding. This study compared four COP bonding methods—thermal, solvent, UV glue, and pressure-sensitive adhesive (PSA)—to optimize optical transparency for fluorescence-based PD assays. Thermal bonding used a hydraulic press at 120°C, solvent bonding involved decahydronaphthalene treatment followed by hot-pressing, PSA utilized double-sided adhesive, and UV bonding combined room-temperature curing with subsequent heating. Image analysis of Vibrio cholerae assays showed that thermal, solvent, and PSA methods maintained adequate clarity with fluorescence intensities of 13–50, whereas UV bonding produced poor optical quality and inconsistent fluorescence due to evaporation issues. This work identifies reliable COP bonding methods ensuring consistent assay performance, thus providing essential guidelines for quality control in PD-based diagnostic devices.

Droplet microfluidics enables handling sub-nanoliter to microliter volumes, finding varied applications in biology and chemistry. The precision and accuracy of droplet volume control can be improved using on-chip valves, but this requires increased cost and complexity of the control systems. Here, we leverage digital circuit analogies to develop pneumatic circuits for autonomous droplet control. The circuits use combinations of NOT and NAND gates to control droplet sizes on a 3D-printed droplet generating device. All parts are printed modularly, and plug-and-play tube interfacing allows fast customization of circuits. Droplet sizes are controlled without any electrical systems, using only the actuation timing of the pneumatic circuit with three NOT gates (clock); twelve NOT gates (delay buffer); four NAND gates (XOR); and one NAND and one NOT gate (AND). The clock oscillator operates autonomously, the buffer functions as a delay timer, and the XOR and AND computations allow selection of buffer outputs for precise and accurate control of the pulse timer (20-150 ms). This autonomous can be programmed to form 12-40 nL droplets with 1 nL precision by simply changing the input of the XOR gate manually. These pneumatic designs are highly adaptable and should be useful for various other automations in microfluidics.

Droplet-based microfluidic devices are powerful tools that can offer precise control over hundreds of tiny droplets (ranging from pico to nanoliter volumes) and are efficient in reducing wastes and reagents. In our group, we use 3D printers to fabricate modular microfluidic devices that allow us to obtain passive aqueous-in-oil droplet formation without the use of external forces such as electric fields in the droplet generator. In our latest device, these droplets are transferred through small tubing to a storage device, which has an attachment to a 3D-printed, normally-closed microvalve (NCV) device. To minimize the risk of leakage and air bubbles, we developed an internal microchannel system with small vents that are exposed to the surface during printing then sealed with tape along the channels for usage. However, when transferring droplets through vents and from chip to chip, it is important to ensure no sample loss during the process, which means the droplet size and volume should remain the same. In an initial study, we validated that droplet volumes were consistent when the device was operated at constant pressure. In a second study, average lengths of the droplets were found to vary depending on location, but after converting to droplet volumes using the varying cross-sectional areas, these deviations were minimized. Our current storage device can store up to 186 droplets, and with a higher resolution 3D-printer (ASIGA MAX 27), we fabricated smaller channels with more layers, increasing the storage by at least 2.5 times. This does not only allow us to store more droplets, but also helps us to control the flow rate. In summary, these 3D-printed modular devices provide simple methods for users to achieve stable droplet formation, to transfer trains of droplets between devices, and to store sampled droplets within a separate device. These features will be helpful in translating droplet sampling technology to other, non-expert laboratories.