The world's smallest aquarium bridges the gap between cell assays and whole animal testing

Scientists in the Netherlands and the UK have shown for the first time that an animal embryo can develop in a microfluidic environment. Their discovery could find application in high-throughput, low-cost assays for drug screening and life sciences research.

Zebrafish embryos are becoming important animal models, bridging the gap between cell culture assays and whole animal testing, and have found use in disease modelling and drug safety prediction assays. These assays are currently performed in microtitre plates and require periodic replacement of the buffer solution, which can cause stress or damage to the embryos. Now, Michael Richardson, from Leiden University, and coworkers have developed a microfluidic lab-on-a-chip device in which the buffer solution can flow continuously through the system, and have successfully raised zebrafish embryos under these conditions. 

The team made the device from three layers of borosilicate glass with an array of temperature-controlled wells connected by channels; each well houses a single zebrafish embryo. The growth and development of embryos in the microchip was investigated following a five-day culture. Some minor phenotypic variations, such as reduced body length, were found in the microchip-raised embryos; however, there was no significant increase in other abnormalities compared with control experiments. 


More than 100 embryos could be cultured in an area smaller than a credit card

They demonstrated the device’s potential for application in drug screening assays by releasing ethanol into the wells to induce embryonic abnormalities. The small volume of the microchip wells (10ul) means that short exposure experiments will consume far less reagent than traditional drug screening assays. ’This makes the biochip promising for drug discovery in which only small quantities of compound are available, or in which the compound is very expensive,’ says Richardson. 

’We have a limited repertoire for automating many of the processes of drug discovery,’ remarks Randall Peterson, an expert in zebrafish chemical genetics at the Cardiovascular Research Centre, Massachusetts General Hospital, US. ’This work helps to further the goal of making tools accessible for high-throughput studies and as we gain more tools like this, we can accelerate the pace of discovering new drugs.’ 

Richardson and his colleagues are now working on validating the new technology, performing screening assays with existing drugs. The next challenge will be to enable compatibility between the microchip and the machinery currently used by pharmaceutical companies in automated screening assays. Richardson also hopes that the system could be used in other applications, such as 3D cell culture and mammalian tissue growth and regeneration.

Sarah Farley

Link to journal article

Zebrafish embryo development in a microfluidic flow-through systemEric M. Wielhouwer, Shaukat Ali, Abdulrahman Al-Afandi, Marko T. Blom, Marinus B. Olde Riekerink, Christian Poelma, Jerry Westerweel, Johannes Oonk, Elwin X. Vrouwe, Wilfred Buesink, Harald G. J. vanMil, Jonathan Chicken, Ronny van ’t Oever and Michael K. Richardson,?Lab Chip, 2011, 11, 1815DOI:10.1039/c0lc00443j