Immobilizing C. elegans on a microfluidic platform

The nematode C. elegans is one of the most studied model organisms in biological research. In order to be visualized under a microscope, single worms have to be kept in place by sedating them. The development of a new and completely physical immobilization method based on a microfluidic platform now allows the study of live worms without chemical tranquilizing interventions.

17.04.2018 by Joachim Schnabl

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Microfluidic platform for long-term immobilization of <i>C. elegans </i>without pressure or tranquilizing drugs — Microfluidic platform for long-term immobilization of *C. elegans* without pressure or tranquilizing drugs

C. elegans – one of the most studied model organisms

The nematode Caenorhabditis elegans has become one of the most widely studied and well understood eukaryotic organisms in modern biology. The study of C. elegans covers fields as diverse as aging and stress, developmental biology or research into a broad variety of diseases, e.g. cancer or Parkinson’s disease. Key to C. elegans’ success as model organism are two physical features: its transparency and the ease with which it can be genetically modified (genetic tractability). Its transparency has greatly aided biological research, as developmental processes as well as changes due to mutations or environmental factors can be observed directly and easily visualized using transmitted light or fluorescence microscopy. Its genetic tractability has allowed the generation of an immense variety of mutant strains, with many key genes and biological phenomena for the first time described in C. elegans. The similarity between cellular and molecular processes in C. elegans and other animals is of immense importance. Such similarities include metabolism, organelle structure, gene regulation and protein biology. Discoveries made in C. elegans are therefore essential for the study of human development, health and disease.

Immobilization without pressure and tranquilizing drugs

Owing to C. elegans’ high motility, immobilization is an essential step in many microscopy studies, especially when targeting cellular or subcellular features. Immobilization is conventionally accomplished using an agar pad, through a combination of pressure and tranquilizing drugs. This method is however known to severely affect sensitive biological processes, limiting our understanding of these to date. To overcome these methodical limitations Berger and co-workers developed a microfluidic platform capable of immobilizing single worms for extended periods of time, without any negative effects on development or physiological function, all whilst acquiring excellent quality images. Immobilization is achieved by confining worms to a narrow channel, the shape of which mimics the worm’s size and shape. Importantly, the applied pressure is kept to a minimum, so as not to affect normal physiological function, e.g. feeding and egg laying. Furthermore, worms are continuously supplied with a highly concentrated bacteria suspension acting as food source.

<p>Schematic of the adult C. elegans immobilization device. Fluidic channels are marked in red, on-chip valves in black. Gentle immobilization and long-term viability are achieved by mimicking the worms shape and size, as well as a constant food supply. Immobilization and loading are controlled through a set of on-chip valves. Direction during worm loading indicated by black arrow, food flow indicated by red arrow.</p> <p>© Lab on a Chip<sup>1</sup>, Royal Society of Chemistry</p> — Schematic of the adult C. elegans immobilization device. Fluidic channels are marked in red, on-chip valves in black. Gentle immobilization and long-term viability are achieved by mimicking the worms shape and size, as well as a constant food supply. Immobilization and loading are controlled through a set of on-chip valves. Direction during worm loading indicated by black arrow, food flow indicated by red arrow. © Lab on a Chip¹, Royal Society of Chemistry

A technology with international success

In this manner, both adult and larval C. elegans could be efficiently immobilized, allowing the study of a variety of sensitive biological processes previously inaccessible to biologists. Significantly, this platform has now been transferred and adopted by number of biology research groups around the world, including researchers at Harvard University, University of Zurich, the University of Utrecht, EPFL and TU Dresden.

Reference

[1] Simon Berger, Evelyn Lattmann, Tinri Aegerter-Wilmsen, Michael Hengartner, Alex Hajnal, Andrew deMello and Xavier Casadevall i Solvas external page Long-term C. elegans immobilization enables high resolution developmental studies in vivo Lab on a Chip, April 2018.