Worms-On-A-Chip Drug Screening System Designed

Adela Ben-Yakar (University of Texas, Austin)

11 October 2016. A system using live roundworms on a microfluidics chip and high-speed image analysis can quickly and simultaneously screen nearly 100 drug compounds. The team led by engineering professor Adela Ben-Yakar at University of Texas in Austin describe its system in today’s issue of the journal Nature Communications.

Ben-Yakar and colleagues are seeking better tools to screen drug candidates for neurological disorders, where organisms, even lower animal forms, provide better indicators of full nervous system responses than individual cells. The organisms in this case, Caenorhabditis elegans or roundworms, are frequently and thoroughly studied as models for some human functions and share one-third of disease-causing genes as humans. Previous attempts could employ only a few organisms at a time for screening drugs, which made these devices too small in scale for real-world demands.

C. elegans are nematodes that cause no harm to humans, and live in the soil or rotting vegetation in many parts of the world.  They grow to about 1 mm in length and feed on microbes, such as bacteria. Other than their research potential, C. elegans have no other economic value.

“The C. elegans are thousands of times bigger than cells,” says Ben Yakar in a university statement, “so now that we have developed a way to capture and immobilize so many of them so quickly, we can determine much more information about the efficacy of drugs in a whole organism rather than the limited information that is derived when we used isolated individual cells.”

The researchers designed a microfluidics chip about the same size as a mobile phone, made with a flexible polymer material, having 96 wells about 9 millimeters apart. Each of the 96 wells connects to tiny micro-scale channels containing about 40 roundworms. The microchannels are designed to keep the worms flat and immobilized, to enable better images of their reactions to the test compounds.

Microscopes with automated high-speed cameras are positioned over the chip to take up to 15 images a second. These images are then processed with image-analysis algorithms and further analyzed statistically. The system, say the authors, can simultaneously record images of some 3,600 roundworms at high resolution in about 16 minutes. Configuring 25 of these devices makes it possible to take images of about 100,000 roundworms.

The team tested the system with 983 compounds approved by the Food and Drug Administration to screen for efficacy in treating the polyglutamine, or polyQ, protein associated with a number of neurological disorders, including Huntington disease. Huntington disease is an inherited disorder where nerve cells in certain parts of the brain degenerate. It is caused by a defect in a chromosome where a portion of the DNA repeats many more times than normal, and because the disease starts in the DNA, it is passed along from parents to children.

The screening revealed 4 compounds for treating cardiovascular or psychiatric diseases as potential therapies with polyQ proteins. One drug, dronedarone, approved to treat irregular heartbeat, also appeared effective at higher doses, without causing toxicity.

University of Texas filed a patent application for the technology, with Ben-Yakar and 5 colleagues as inventors. Ben-Yakar and co-author Evan Hegarty are founders of a start-up company, Newormics LLC in Austin, that plans to commercialize the technology.

The following brief video shows images from the chip.

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