The biological world is staggeringly complex, so in many cases, one needs high-throughput technology in order to perform screening experiments. In vitro techniques lend themselves to automation, but they cannot mimic all aspects of real life. In vivo methods, on the other hand, are more realistic but are often slow. Seeking to combine the advantages of automation with those of using real organisms, the laboratory of Mehmet Fatih Yanik, PhD, is developing high-throughput chips for small-animal screening experiments.

The nematode C. elegans is a powerful model organism used to study many biological processes and to model many human diseases. It is a small, transparent worm, and it is amenable to many types of screening experiments. In a forward genetic screen, worms are subjected to a mutagen, and each resulting mutant is studied to determine what mutation is responsible for its phenotype. In a reverse genetic screen, each gene is silenced in turn, and the phenotype is observed. Finally, in a compound screen, the nematodes are treated with a number of chemical compounds, and the resulting phenotypes are observed. All these screens have traditionally been time-consuming, and most have led only to qualitative results.

This situation could change, however, thanks to work being done by researchers in Yanik's lab. These scientists have designed microfluidic chips capable of conducting screening experiments with limited human involvement. The chips are fabricated using conventional methods and consist of many micro-channels through which C. elegans can pass. The worms move into chambers, and suction is applied at one small hole in each chamber wall. One worm is sucked to the side of each chamber, and the other worms are washed out. The chamber is then sealed, and the captured worm is released by turning off the suction. A linear array of suction points can be used to immobilize the nematode in any given chamber, and the immobilized organism can be examined using two-photon fluorescent imaging, a technique that provides sub-cellular resolution in three dimensions. Compounds can be delivered to the chambers, and their effects on the nematodes can be observed. Bacteria engineered to excrete interfering RNA molecules capable of silencing specific genes can also be introduced into the chambers.

Professor Yanik's team is using these chips to study neurodegenerative diseases such as Alzheimer's and Parkinson's. They have even been able to cut individual neurons using femto-second laser nano-surgery, allowing them to study the ability of neurons to recover after injury.

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