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DropletMicroarrays: Ultra High-Throughput Screening of Cells in 3D Microenvironments

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A new miniaturised microarray system personalises drug screening

Despite advances in technology, there is a lack of fast and cheap approaches for drug screening. A high-throughput method comes to revolutionise drug screening, bringing personalised medicine a step closer to reality.

Fundamental Research

Existing methodologies for drug screening are laborious, requiring high numbers of cells and expensive automatic equipment. Furthermore, biopsies often produce insufficient numbers of cells for traditional approaches, demanding further miniaturisation of drug screening assays.

A high-throughput microarray for drug screening

The EU-funded DROPCELLARRAY project exploited the unique properties of superhydrophobic-hydrophilic microarrays to create a novel platform for drug screening. “Our goal was to develop a miniaturised high-throughput system for screening drugs in live cells,″ explains project coordinator Dr Pavel Levkin. The DROPCELLARRAY technology allows up to 300 000 cell experiments in parallel performed in tiny micro-droplets on a single chip. Each droplet is isolated at a defined location on the chip, enabling spatial indexing, time-lapse measurements and screening of either adherent or non-adherent cells. The superhydrophobic barriers allow complete isolation of the micro-reservoirs, preventing cross-contamination and cell migration. Importantly, compared to traditional microplates, the minute volume of droplet material allows the analysis of very few cells such as rare stem and primary cells. At the same time, it saves on cost and required reagents. Researchers advanced the surface chemistry, photochemistry and patterning technology to create transparent and biocompatible patterns on the microarrays. This was paramount for generating superhydrophobic barriers and compartmentalising the thousands of screening reactions on the array. “Bringing a completely new droplet microarray technology, based on superhydrophobic-hydrophilic microarrays, from basic research to real cell applications is undoubtedly the most significant achievement of the project,″ emphasises Dr Levkin. Looking back, he confesses that “this wouldn’t have been possible without the hard work and motivation of the DROPCELLARRAY team who developed a successful product that is now used by many laboratories including several pharmaceutical companies.″

A microarray platform that supports 3D culture of cells

The DROPCELLARRAY platform allows cell culturing in 3D systems such as hydrogels, cell spheroids, or embryoid bodies. 3D culture systems are more physiologically relevant as they mimic the in vivo microenvironment of cells, helping the latter grow more naturally. Hydrogels are soft hydrophilic cross-linked polymers and scientists have used them to generate a culture microenvironment that can support the analysis and expansion of stem cell populations. These cells are difficult to culture as they quickly lose their stem cell potential and differentiate. As a result, DROPCELLARRAY is expected to find application in stem cell research, regenerative medicine and cell biology in general.

Future prospects of the DROPCELLARRAY technology

The droplet microarray platform has been successfully evaluated by collaborators in academia and several pharmaceutical companies. The arrays are available at the spinoff company Aquarray GmbH, which is developing products for personalised medicine, cell screening, and miniaturised cell experiments. The company is actively recruiting scientific personnel and hopes to attract investors to advance the technology and extend its applications. Among the future goals is to ensure that DROPCELLARRAY technology is used in every laboratory and every biotech or pharma company in the world. Ultimately, Dr Levkin envisages the technology “to be adopted by hospitals for personalised medicine applications, to accelerate biological discoveries and be used in material synthesis.″

Keywords

DROPCELLARRAY, drug screening, droplet, superhydrophobic hydrophilic microarrays, aquarray

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