Despite the prevalence and expense of parasitic worm (helminth) infection worldwide, the helminth-specific pharmacopeia is extremely limited. This is historically due, in part, to the paucity of objective high-throughput drug screening methods amenable to the life cycle of these parasites. Though hampered by observer subjectivity and low throughput capacity, for many years the gold standard assay for anthelmintic drug screening involved manual in vitro assessment of worm motility using a microscope. However, it was recently shown that xCELLigence® real-time impedance monitoring is able to quantify parasitic worm motility (which is a surrogate of viability).
When a helminth is placed within an E-Plate® well, its movement/writhing changes the electrode surface area being contacted, and the resultant impedance changes can be used to quantify worm motility/viability (see figure). Since this initial discovery, xCELLigence® has been adopted within this research community for looking at multiple helminth species and different developmental stages. The ability to quantitatively monitor multiple developmental stages is particularly important as it allows a broader net to be cast during drug screening efforts: as each stage in a parasitic worm’s life cycle may display differential drugability, being able to monitor multiple stages increases the chances of success.
Application of xCELLigence® to parasitic worm studies serves to further expound upon a theme already well established in the area of cell-based assays: the sensitivity and flexibility of real-time impedance measurement using xCELLigence® enables researchers to easily and cheaply study phenomena that were previously either inaccessible or very laborious, costly, inefficient, and poorly reproducible.
Key Benefits of xCELLigence®
- Objective quantification: Subjective human observations of worm motility are replaced with objective real-time data.
- Reduced workload: Once worms are placed in the wells of an E-Plate® and data acquisition has been initiated, no further involvement is required. Data is continuously recorded for anywhere from minutes to days/weeks.
- Flexibility: A wide range of buffer compositions can be used, and multiple developmental stages of the worm can be evaluated. Moreover, the frequency of the AC current used to measure impedance can be adjusted, enabling optimization of signal to noise ratio.