A5085127878- 3D Printing in Biomedical Research
- Neuroscience and Neural Engineering
- Cell Image Analysis Techniques
- Microfluidic and Bio-sensing Technologies
- Innovative Microfluidic and Catalytic Techniques Innovation
- Microfluidic and Capillary Electrophoresis Applications
- Ultrasound and Hyperthermia Applications
- Photoacoustic and Ultrasonic Imaging
- Electrowetting and Microfluidic Technologies
- Barrier Structure and Function Studies
- Pharmacological Effects and Toxicity Studies
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Cardiac electrophysiology and arrhythmias
- Nanopore and Nanochannel Transport Studies
- Angiogenesis and VEGF in Cancer
- Ultrasound and Cavitation Phenomena
- Liver physiology and pathology
- Drug Solubulity and Delivery Systems
- Analytical Chemistry and Sensors
- Cardiac Imaging and Diagnostics
- Ultrasound in Clinical Applications
- Effects and risks of endocrine disrupting chemicals
- Andrographolide Research and Applications
- Chemotherapy-induced organ toxicity mitigation
Mimetas (Netherlands)
2014-2024
Centre for Human Drug Research
2010-2015
Leiden University
2010-2015
Netherlands Metabolomics Centre
2011-2013
Receptor-mediated transcytosis is one of the major routes for drug delivery large molecules into brain. The aim this study was to develop a novel model human blood-brain barrier (BBB) in high-throughput microfluidic device. This can be used assess passage biopharmaceuticals, such as therapeutic antibodies, across BBB.The comprises cell lines brain endothelial cells, astrocytes, and pericytes two-lane or three-lane platform that harbors 96 40 chips, respectively, 384-well plate format. In...
In vitro models that better reflect in vivo epithelial barrier (patho-)physiology are urgently required to predict adverse drug effects. Here we introduce extracellular matrix-supported intestinal tubules perfused microfluidic devices, exhibiting tissue polarization and transporter expression. Forty leak-tight cultured parallel on a single plate their response pharmacological stimuli is recorded over 125 h using automated imaging techniques. A study comprising 357 gut tubes performed, of...
Abstract With recent progress in modeling liver organogenesis and regeneration, the lack of vasculature is becoming bottleneck progressing our ability to model human hepatic tissues vitro. Here, we introduce a platform for routine grafting other on an vitro grown microvascular bed. The consists 64 microfluidic chips patterned underneath 384-well microtiter plate. Each chip allows formation bed between two main lateral vessels by inducing angiogenesis. Chips consist open-top chamber, which...
Human tissues and organs are inherently heterogeneous. Their functionality is determined by the interplay between different cell types, their secondary architecture, vascular system gradients of signaling molecules metabolites. Here we propose a stratified 3D culture platform, in which adjacent lanes gels liquids patterned phaseguides to capture this tissue heterogeneity. We demonstrate HepG2 hepatocytes under continuous perfusion, rifampicin toxicity assay co-culture with fibroblasts. 4T1...
A common bottleneck in any drug development process is finding sufficiently accurate models that capture key aspects of disease and progression. Conventional screening often rely on simple 2D culture systems fail to recapitulate the complexity organ situation. In this study, we show application a robust high throughput 3D gut-on-a-chip model for investigating hallmarks inflammatory bowel (IBD). Using OrganoPlate platform, subjected enterocyte-like cells an immune-relevant trigger order...
Differentiation of hNESC into functional dopaminergic neurons in phase-guided 3D microfluidic cell culture.
Abstract With great advances in the field of vitro brain modelling, challenge is now to implement these technologies for development and evaluation new drug candidates. Here we demonstrate a method culturing three-dimensional networks spontaneously active neurons supporting glial cells microfluidic platform. The high-throughput nature platform combination with its compatibility all standard laboratory equipment allows parallel compound effects.
Proximal tubules in the kidney play a crucial role reabsorbing and eliminating substrates from body into urine, leading to high local concentrations of xenobiotics. This makes proximal tubule major target for drug toxicity that needs be evaluated during development process. Here, we describe an advanced vitro model consisting fully polarized renal tubular epithelial cells cultured microfluidic system. Up 40 leak-tight were on this platform provides access basolateral as well apical side...
Breast cancer is the most common invasive among women. Currently, there are only a few models used for therapy selection, and they often poor predictors of therapeutic response or take months to set up assay. In this report, we introduce microfluidic OrganoPlate® platform extracellular matrix (ECM) embedded tumor culture under perfusion as an initial study designed investigate feasibility adapting technology selection. The triple negative breast cell lines MDA-MB-453, MDA-MB-231 HCC1937 were...
Current in vitro models to test the barrier function of vasculature are based on flat, two-dimensional monolayers. These monolayers do not have tubular morphology found vivo and lack important environmental cues from cellular microenvironment, such as interaction with an extracellular matrix (ECM) exposure flow. To increase physiological relevance vasculature, it is crucial implement these better mimic native three-dimensional vascular architecture. We established a robust, high-throughput...
Proximal tubule epithelial cells (PTEC) are susceptible to drug-induced kidney injury (DIKI). Cell-based, two-dimensional (2D) in vitro PTEC models often poor predictors of DIKI, probably due the lack physiological architecture and flow. Here, we assessed a high throughput, 3D microfluidic platform (Nephroscreen) for detection DIKI pharmaceutical development. This system was established with four model nephrotoxic drugs (cisplatin, tenofovir, tobramycin cyclosporin A) tested eight compounds....
Assessment of epithelial barrier function is critically important for studying healthy and diseased biological models. Here we introduce an instrument that measures transepithelial electrical resistance (TEER) perfused tubes in the microfluidic OrganoPlate platform. The tubules are grown channels directly against extracellular matrix, obviating need artificial filter membranes. We present TEER measurements on Caco-2 intestinal renal proximal tubule epithelium. Forty one single plate were...
The vasculature system plays a critical role in inflammation processes the body. Vascular inflammatory mechanisms are characterized by disruption of blood vessel wall permeability together with increased immune cell recruitment and migration. There is need to develop models that fully recapitulate changes vascular barrier response conditions. We developed scalable platform for parallel measurements trans epithelial electrical resistance (TEER) 64 perfused microfluidic HUVEC tubules under...
A microfluidic passive valving platform is introduced that has full control over the stability of each valve. The concept based on phaseguides, which are small ridges at bottom a channel acting as pinning barriers. It shown angle between phaseguide and sidewall measure phaseguide. relationship phaseguide–wall characterized numerically, analytically experimentally. Liquid routing enabled by using multiple with different values. This demonstrated filling complex chamber matrices. As an...
Liquid droplets can be spontaneously charged in the absence of applied electric fields by spraying. It has been shown computational simulation that charges may influence particle deposition airways. The electrostatic properties jet nebulized aerosols and their potential effects on lung have hardly studied. A modified electrical low pressure impactor (ELPI) was employed to characterize aerosol generated from commercial products.The charge size measurements were conducted at 50% RH 22 degrees...
An assay platform has been developed utilising phaseguide technology to form aqueous lanes solutions through which magnetic particles are pulled.
Ultrasound in the presence of gas-filled microbubbles can be used to enhance local uptake drugs and genes. To study drug delivery potential its underlying physical biological mechanisms, an vitro vessel model should ideally include 3-D cell culture, perfusion flow, membrane-free soft boundaries. Here, we propose organ-on-a-chip microfluidic platform ultrasound-mediated delivery: OrganoPlate. The acoustic propagation into OrganoPlate was determined assess feasibility controlled microbubble...
Elastomeric microvalves in poly(dimethylsiloxane) (PDMS) devices are today's paradigm for massively parallel microfluidic operations. Here, we report that such valves can act as nanochannels upon closure. When tuning nanospace heights between ~55 nm and ~7 nm, the nanofluidic phenomenon of concentration polarization could be induced. A wide range regimes (anodic cathodic analyte focusing stacking) was achieved simply by valve pressure actuation. Electro-osmotic flow generated a...
Reactive oxygen species (ROS) have different properties and biological functions. They contribute to cell signaling and, in excessive amounts, oxidative stress (OS). Although ROS is pivotal a wide number of physiological systems pathophysiological processes, direct quantification vivo quite challenging mainly limited vitro studies. Even though advanced culture techniques, like on-a-chip culture, overcome the lack crucial vivo-like aspects 2D majority studies are generally performed 2D. Here...
Proximal tubule epithelial cells are the main driver of renal transport and secretion xenobiotics, making them susceptible to drug-induced kidney injury. Cell-based assays a meaningful alternative animal testing detect nephrotoxicity contribute 3Rs (refine, reduce, replace experimentation). Here we report on high-throughput, three-dimensional microfluidic platform (Nephroscreen) nephrotoxicity. Toxicologically relevant parameters were used assess cell viability, functional barrier integrity,...
Abstract Understanding the interactions between tumor vascular systems and circulating immune cells is crucial for elucidating mechanisms of cell recruitment in cancer exploring potential immunotherapeutic approaches. However, current vitro models often lack fidelity to replicate these intricate dynamics observed vivo. The OrganoPlate Graft has been developed perfusion peripheral blood mononuclear (PBMCs) through a bed with melanoma monolayer (A375) study aspects such as adhesion,...