Call for Speakers 2024

Limited emulation of human blood flow characteristics of microfluidic-based MOC platform presents current technical and biological challenges of microphysiological systems. This study aims to generate the necessary flow conditions in the rectangular microchannel to enhance endothelialization, including the formation of continuous endothelial barrier in the entire microfluidic system. It focuses on improving the on-chip micropump design of the investigated MOC (TissUse GmbH, Berlin). New pump designs are developed and experimentally characterized using μPIV to analyze effects of geometric modifications on microfluidic flow conditions. The developed design improves representation of physiological flow characteristics using cell culture media in the microfluidic system but faces challenges with blood (models) due to agglutinations. Finally, specific solutions for future pump design developments are recommended.

In the past decade, lab-on-a-chip biological platforms have seen significant development due to advancements in emerging technologies, allowing for reliable devices with enhanced spatial resolution and 3D configurations. Despite challenges in material choice and fabrication, 3D printing with biocompatible polymers offers a solution, speeding up prototype creation and enabling intricate geometries. Two-photon polymerization (2PP) facilitates the fabrication of complex microstructures with exceptional resolution, showing promise in bioprinting and biochips for tissue engineering and biomedical research. Vital3D Technologies integrates stereolithography with 2PP printing, utilizing FemtoBrush™ technology to dynamically adjust printing resolution, enabling the creation of sophisticated 3D structures. This innovation finds application in bioprinting and microfluidic device fabrication, offering the potential for advanced therapeutic strategies and disease models in biomedical research.

Surface-modification platforms that are universally applicable are vital for the development of new materials, surfaces, and nanoparticles. Mussel-inspired materials (MIMs) are widely used in various fields because of their strong adhesive properties and post-functionalization reactivity. However, conventional MIM coating techniques have limited deposition selectivity and lack structural control, which has limited their use in microdevices that require full control over deposition. To overcome these limitations, we developed a micropatterning technique for MIMs using multiphoton lithography, which does not require photomasks, stamps, or multistep procedures. This method enables the creation of MIM patterns with micrometer resolution and full design freedom and paves the way for innovative applications of MIMs in various multifunctional systems and microdevices, such as microsensors, MEMS, and microfluidics.

Immunotherapy with genetically engineered T cells has achieved some spectacular success in clinical trials addressing tumors. A key need is the widespread availability of small-scale bioreactors providing in-process monitoring. TITAN platform aims to the continuous sampling of critical quality attributes, to quickly recognize deviations from the desired range and take appropriated corrective actions. Parameters to verify and related tools include: bacterial contamination; counting cells by microfluidic and electrical detection; ratio live/dead cells on a capacitive sensor; cytokines production identified by electrochemical methods; T-cell function tests through the production of spheroids into droplet microfluidic devices. The integration of sensors, microfluidics and control system has been achieved through the development of TITAN platform using microcontroller and Labview interface as user-friendly management.

BiProMicro uses dynamic microfluidic single-cell cultivation (dMSCC) to simulate large-scale bioreactors (up to 300 m³) on-chip. To date predicting the performance of producer cells under industrially relevant cultivation conditions is not possible since current approaches are not able to resemble the highly dynamic environments of large-scale bioreactors. Consequently, the performance of cells diverges massively between development and final industrial application. Exploiting the possibilities of a multi-inlet structure, various cultivation media are introduced into our cultivation device by pressure-driven pumps. By changing the respective pumping pressures, media conditions can be exchanged within seconds. This way, the dynamic cultivation conditions of large-scale bioreactors can be emulated on-chip and via live-cell-imaging the resulting cellular behavior becomes assessable.

Here we will present the potential of a novel microfabrication method: Direct Atomic Layer Processing (DALP). Developed by Atlant 3D, DALP utilizes spatial atomic layer deposition (ALD) for precise control in 3D manufacturing of thin films directly on microfluidic chips. This technology simplifies the integration of sensors into microfluidic systems. We showcase a variety of sensors (interdigitated Pt temperature and capacitive sensors, a piezoelectric ZnO pressure sensor, and a TiO2 electrochemical sensor) fabricated using DALP. These sensors are created with the same machine in an automated process. This innovation has the potential to significantly advance 3D microfabrication, enhancing the prototyping, development, and integration of new microfluidic technologies.

Precision medicine allow to tailor the clinical approach, depending on the makeup of patients’ DNA and expression issues. Liquid biopsy and the chance to use selected biomarkers from biological fluids, could strongly contribute to the improvement of an increasingly patient-oriented method. Among the most important effectors of cellular interplay, Extracellular Vesicles (EVs) are on the rise for their multiple roles, encompassing physiological functions, cancer progression and invasiveness modulation, neurodegeneration. RESOLVE platform by means of the integration of electrochemical sensing and microfluidic tools for the characterization of subpopulation of EVs will provide researchers and clinicians a new approach with features of ease-of-use, plug-n-play, sample-in/answer-out operation mode. Finally, RESOLVE will enable non-invasive liquid biopsy through a cost-effective, disposable and customizable system.

The research focuses on a dynamic metastasis model containing a cultivation and a capturing chamber. The cultivation chamber was engineered to culture cancer spheroids within an extracellular matrix under controlled flow conditions. The capturing chamber was equipped with a magnet and an engineered magnetic flux concentrator for balancing the magnetic force and spreading out the magnetic beads evenly in the capturing chamber. This integrated setup recreates the metastasis process; invading cells leaving the spheroids and ECM are promptly captured by the EPCAM-Dynabeads™ inside the capturing chamber. Beyond its ability to capture fresh circulating tumor cells for further study, this system holds potential for investigating the efficacy of anticancer drugs on metastatic cells, contributing to advancements in cancer treatment approaches.

Bloodstream Infections (BSI) remain a major cause of mortality and morbidity worldwide. Blood cultures (BC) are considered the gold standard for diagnosis of such diseases. Recently, real-time genome sequencing of pathogens from positive blood cultures emerged as an advanced diagnostic tool for bacteremia. Blood culture purification is vital to achieve the best analytical results from DNA sequencing for pathogen identification potentially reducing the time of analysis. In addition, inertial microfluidics has become a reliable tool in the purification of samples. This work aimed at developing a novel microfluidic platform for the efficient separation of the bacterias from human blood cells and their identification. Finally, the purified samples were efficiently analyzed by real-time DNA sequencing for the platform validation

The Berlin research initiative PolyChrome introduces PolyBoard, a hybrid integration platform for photonic integrated circuits (PIC) enabling versatile material selection within a single PIC. The platform incorporates various on-chip features and supports a wide wavelength range, from visible to near-infrared. Innovative material concepts and technologies such as nano imprint lithography, are explored to overcome challenges like optical losses due to surface roughness. Additionally, the project investigates silicon nitride (SiN) based PICs for sensitive biomolecule sensing in point-of-care settings, integrating microfluidic structures using UV-curing techniques. Automated PIC assembly processes are developed to enhance production scalability, addressing industry needs for efficient manufacturing.

Ultrafast laser machining is a versatile microfabrication technique capable of volume processing of glass with sub-micrometric resolution. The technique relies on non linear absorption of the pulsed beam to trigger a material modification that is confined to the focal volume. In fused silica, this may result in an increase in the refractive index or turn the machined volume more selective to etching in HF, thereby enabling the design of integrated optics or microfluidic devices. The high resolution and 3D capability of the technique also enables integration of both systems in a single monolithic platform. Our recent work on integrated spherical lenses and optical resonators, 2D and 3D hydrodynamic flow focusing and optical cell sorting/trapping will be discussed.

C. elegans is a model organism for understanding numerous biological processes. At present embryos are extracted from C. elegans by hand. Automated Microfluidics offers an alternative to extracting C. elegans embryos due to its precision control. Automated embryo extraction via Microfluidics would enable large-scale, genome-wide biophysics studies which are at present unfeasible due to the time-consuming embryo extraction process.

Current drug screening assays predominantly rely on traditional static culture in multiwell plates, which often fail to accurately replicate the complex physiological microenvironment. Tremendous efforts have been dedicated to advance technologies that better emulate in vivo conditions, particularly with progress in organ-on-a-chip and mechanobiology technologies. However, most technologies are complex and costly, making them impractical for robotic HTS or HCS drug screening platforms. We present an exceptionally simplified assay featuring mechanical stretching stimulus, designed to mimic microenvironment in heart, lung, muscle, bone, skin and tumor. It is easy to manufacture and can be miniaturized for effortless integration into multiwell plates (96 well or 384 well), thus bringing organ-on-a-chip technology to a practical "organs-on-a-plate" assay. This distinctive high-throughput assay, incorporating mechanical cues, is positioned to significantly impact research and drug development, especially in in vitro models spanning cardiovascular disease, fibrosis, musculoskeletal disorders, cancer, neurodegenerative diseases, stem cell differentiation, tissue engineering and regenerative medicine.

Plasma-assisted processes offer tailored surface functionalities for biosensors, microfabrication and others, yet achieving area-selective and precise modification for micropatterning using atmospheric-pressure plasma (APP) remains challenging. To overcome this, we have developed Surface Atmospheric-Pressure Plasma Printing (SurfAP3®), a novel and flexible direct writing technology for fine surface modification, with the highest resolution available for maskless APP, starting at a linewidth resolution of 40 µm. It allows microprinting of thin films, activation, fine cleaning and layer removal, on diverse materials (e.g. polymers, glass, metals). By permitting the tuning of the process parameters, the open use of precursors and the integration with other technologies, industries and researchers can adjust the platform to their needs and their current processes, flexibly and sustainably.

The development of devices for semi-automated selection of rare cells from biological samples is crucial to enhance the efficiency and affordability of diagnosis in hospital settings. In this study, electrospun nanofiber mats, that offer high surface area to be functionalized with antibodies to selectively capture target cells, were developed in the optics of being used as a substrate for a microfluidic device, which enables precision delivery of fluids and high surface-to-volume ratio that favors mass exchange. Electrospun nanofiber were produced and decorated with antibodies for cell capture. Subsequent release strategies were also studied. Capture of model cells resulted successful holding the potential of the implementation of this nanotechnology for the development of microfluidic devices with diagnostic purposes.

Up to date, nanostructured Ti-based materials have attracted attention due to the unique and diverse physico-chemical properties and the potential for photocatalysis. One of the major advantages of the Ti-based materials is that it remains stable after the repeated catalytic cycles, whereas other materials for photocatalysis such as CdS or GaP suffer degradation and can even produce toxic endproducts. Therefore, those materials affect harm effect on environment, but Ti-based materials are eco-friendly candidate. Among them, nanostructured potassium incorporated titanium oxide films (KTiOxs) represent a promising candidate, in particular due to the possibility to tune the electrical and optical properties by controlling the K content. Therefore, nanostructured titanium oxide materials with the possibility of tuning of the surface charge are promising candidate for high performance photocatalysis. However, currently, the nanostructure fabrication generally involves complicated process, low reproducibility and/or high cost for chemical modification. Hence, a simple method to synthesize and to tune the desired morphology and property is strongly desirable. In this talk, we will demonstrate the wet corrosion process (WCP) which is a simple one-step method for nanostructures fabrication involving treatment with KOH solution. The relation between the nanostructures generated and the function of bioelectrode was systematically investigated as a function of the WCP condition. Pure Ti substrates were used to synthesize on nanostructures fabrication. For WCP, various concentrations of KOH solutions were used.