Imaging Embryonic Development by Microfluidics

The preclinical animal study of drugs can be a costly and lengthy process. However, owing to some basic similarities with humans and their short development time, the zebrafish has emerged as a useful model for drug screening and disease profiling. For these experiments, zebrafish embryos are usually contained in the wells of a ‘multi-well plate’ — however, controlling the medium in which they are submerged and the addition of other chemicals, as well as imaging of the tissues and organs inside the zebrafish, are not straightforward using this setup.

Hanry Yu at the A*STAR Institute of Bioengineering and Nanotechnology and co-workers have devised a new and efficient microfluidic device for the growth, live imaging and monitoring of tissues and organs of zebrafish1. The researchers show how the multichannel platform, which they call ‘fish and chips’, can detect abnormalities in the tail morphology and eye of the zebrafish, in the presence of valproic acid — a drug known to cause birth defects if taken by the mother during pregnancy.

The fish and chips platform created by Yu and co-workers has three sections (see image): eight fish tanks that can each hold one zebrafish; a gradient generator that controls the administration of drugs and chemicals to the tanks; and eight outlet channels for the removal of waste products. Zebrafish have been monitored in microfluidic setups in the past, but the new platform allows the diagonal flow of solutions. As a result, the embryos remain within a consistent flow of growth medium and drugs. Yu and co-workers are able to monitor developmental changes under the influence of different concentrations of drug molecules because of this gradient method.

Another advantage is the 1.4-millimeter diameter of the individual tanks — a size that sufficiently restricts the movement of the zebrafish to allow fluorescence imaging of the fish without the need for complex manipulation of the zebrafish with needles and anaesthesia.

Using imaging methods, Yu and co-workers are able to see various tissues and organs of the zebrafish including the brain, eye, ear, olfactory bulbs, melanophores, notochord, epidermis, trunk and the distinct chambers of the heart. These detailed imaging possibilities, together with the ability to monitor long-term development of the zebrafish embryo from eight to 92 hours post-fertilization, make the fish-and-chips platform an attractive tool in drug discovery.

“Toxicity is a major cause of drug failures in clinical trials and our novel fish-and-chips device can be used as the first step in drug screening during the preclinical phase to complement existing animal models and improve toxicity testing. Our next step will involve investigating cardiotoxicity and hepatoxicity on the chip,” says Yu.