What is it about?

The emergence of new drugs is often driven by the escalating resistance of parasites to existing drugs and the accessibility of more advanced technology platforms. Microfluidic devices have allowed for quicker testing of compounds, regulated sampling/sorting of entire animals, and automated behavioral pattern detection. In the majority of microfluidic devices, the effects of drugs on small animals (e.g. Caenorhabditis elegans)elegant are quantified by an endpoint, dose response curve that shows one parameter (such as worm velocity or stroke frequency). To expand on this, we present a multi-parameter extraction method to examine the modes of paralysis in C. elegans over an extended period of time.

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Why is it important?

A microfluidic device that includes real-time imaging was utilized to expose C. elegans to four anthelmintic drugs (i.e., pyrantel, levamisole, tribendimidine, and methyridine). We measured worm behavior with parameters such as curls per second, the types of paralysis, the frequency of modes, and the number/duration of active/immobilization periods. Each drug was used at EC75, where 75% of the worm population responded to the drug. While using the same concentrations, we noticed disparities in the way that worms paralyzed in the drug-filled environments. Our study stresses the importance of assessing drug effects on small animals with multiple parameters calculated at regular intervals over a prolonged time span in order to accurately capture the resistance and adaptability in chemical environments.

Perspectives

The resistance of parasites to existing drugs and the availability of better technology platforms has driven the discovery of new drugs. Microfluidic devices have been used to facilitate faster screening of compounds, controlled sampling/sorting of whole animals, and automated behavioral pattern recognition. In most cases, drug effects on small creatures (e.g., Caenorhabditis elegans) are measuredelegant by a single parameter such as worm velocity or stroke frequency. We present a multi-parameter extraction method to characterize modes of paralysis in C. elegans over a longer duration. This was done using a microfluidic device featuring real-time imaging, exposing worms to four anthelmintic drugs at EC75, where 75% of the worm population is affected. We monitored the worms' behavior with metrics such as curls per second, types of paralyzation, mode frequency, and number/duration of active/immobilization periods. Differences were observed in how the worms paralyzed in the various drug environments at equivalent concentrations. This study highlights the importance of assessing drug effects on small animals with multiple parameters, measured at regular intervals over a prolonged period, to accurately detect resistance and adaptability in chemical environments.

Prof Santosh Pandey
Iowa State University

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This page is a summary of: Microfluidics-enabled method to identify modes of Caenorhabditis elegans paralysis in four anthelmintics, Biomicrofluidics, November 2013, American Institute of Physics,
DOI: 10.1063/1.4829777.
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