MIMETAS BV develops organ-on-a-chip tissue models for evaluating drugs, chemicals and food components. Its unique microfluidic technology, designated OrganoPlates®, enables testing of compounds in high-throughput on miniaturized organ models. These models show better predictivity as compared to laboratory animals and conventional cell culture models.
In 2010, Paul Vulto met Jos Joore for dinner in a Japanese restaurant in Rotterdam. Paul showed the PhaseGuide™ technology that he had invented in Germany and Italy. Jos Joore, who was into diagnostic array technology and protein profiling at the time, was immediately intrigued. Together they brainstormed on creating the phenotypic equivalent of a microarray that could be used for massively parallel testing of individualized (combination) therapies. That same evening Paul called Prof. Thomas Hankemeier from Leiden University to discuss the possibilities of starting up a science-based business. This was the start of MIMETAS. In 2013, MIMETAS was incorporated and acquired its first commercial project on organ-on-a-chip development.
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The OrganoPlate® is a microfluidic 3D culture plate, supporting up to 96 tissue models on a single plate. In an OrganoPlate®, you can grow tissues embedded in an ECM gel or as a perfused tubule against the ECM gel.
For in-gel culture, cells are mixed with an ECM such as Matrigel® and seeded in the gel inlet of an OrganoPlate®. As soon as the ECM-gel has set, you can add medium to the inlet and outlet wells to perfuse the tissue. This in-gel culturing technique works perfectly for example tumours, hepatocytes and neuronal cultures, but also for supporting cells types, such as astrocytes, pericytes and podocytes. For in-gel cultures, the type and density of ECM gel are important as these factors influence the growth and properties of tissues (e.g. hepatocytes form smooth spheroids while neurons form neuronal networks in the gel).
In addition to in-gel cultures, you can deposit monolayers at the interface between lanes. This is achieved by seeding cells against the ECM gel. Supported by perfusion, the cells grow against the gel and the inner wall of the medium channel to form a perfused vessel structure. Examples are renal proximal tubules, intestinal tubules and endothelial tubule or blood vessels, all grown as a tubule against ECM gels.
In the 2-lane OrganoPlate®, 2 tissue lanes can be combined to design tissue setups. The two-lane OrganoPlate® supports perfused epithelial tubules and blood vessels, perfused cells in ECM-gel or combinations of both.
In the 3-lane OrganoPlate®, 3 tissue lanes can be combined to design more complex tissue setups, such as two tubules, flanking a central ECM-gel with cells or two adjacent ECM-gels with cells and a perfusion lane. The three-lane OrganoPlate® allows basal and apical access to epithelial tubules and blood vessels, combinations of tissues growing in ECM and tubules, as well as more advanced transport studies.
Continuous perfusion of media through the microfluidic networks in the OrganoPlate® mimics blood flow and enables the exchange of nutrients, oxygen and metabolites. Our unique gravity-driven levelling technology maintains flow without the use of pumps and tubing, making the OrganoPlate® suitable for any throughput. The Perfusion Rocker™ Mini provides continuous medium flow in the OrganoPlate® with minimal settings required.
The PhaseGuide™ platform is arguably the most cost-effective microfluidic liquid handling platform available. Being a passive technology, no moving parts are required and plate functionality is fully programmed by its geometry. OrganoPlates® make organ-on-a-chip technology affordable and available to non-specialized end-users.
The addition of culture lanes to the microchambers easily increases the complexity of the tissue models in the OrganoPlate®. Patterning additional cell types adjacent to the cell layers allows culturing of complex, non-homogeneous tissues. Application of chemical gradients or exposure to gases is supported. This flexibility is particularly useful for stem cell differentiation and cell motility studies. No other organ-on-a-chip liquid handling platform offers such flexibility combined with ease of handling.
The OrganoPlate® employs a unique patented liquid handling technology, called Phaseguides™. Phaseguides™ are meticulously designed meniscus pinning barriers. They enable precise, barrier-free definition of culture matrices and cells in 3D, supporting cell-cell interactions and unprecedented imaging and quantification. The OrganoPlate® is versatile, supporting chemical gradients of chemical compounds and proteins and co-culture conditions. Complex tissue models can be implemented in a straightforward way.
The OrganoPlate® is very easy to work with, in contrast to many other microfluidic systems. Whether you want to pipette manually for optimal flexibility, or fully automated, you get excellent results in low- and high-throughput. The plates have a straightforward layout and need no special equipment, tubing or pumps. Also, the small footprint of the 384-well plate allows you to perform 100-10.000s of experiments in a standard incubator. OrganoPlates® is compatible with all high-content microscopes, standard microscopes and plate readers. The image quality is excellent, even with the latest high-end confocal laser scanning technologies.