Microfluidic Device Could Determine Efficacy of Neurodegenerative Disease Drugs
A new device images thousands of roundworms to determine how effectively a drug treats neurodegenerative diseases.
Researchers have developed a novel drug discovery platform that may help determine the effectiveness of treatments for neurodegenerative diseases.
The researchers from the Cockrell School of Engineering at the University of Texas at Austin have created a large-scale in vivo platform that uses ring worms to analyze new drugs. They believe that this novel platform will allow the image-based analysis of thousands of live roundworms (Caenorhabditis elegans) at the speed and cost of in vitro cell-based platforms, according to the study published by Nature Communications.
The platform is the size of a cellphone and is a chip that has the ability to immobilize and examine models using a microscope, which is similar to current screening platforms for cells. However, the novel platform screens whole organisms by immobilizing them inside micro-traps.
This microfluidic device also is able to interpret data through an imaging analysis software, and can image 3600 Caenorhabditis elegans (C. elegans) simultaneously in a 12 to 16-minute time span. Other devices are unable to image high numbers of animals within this time.
The platform can also analyze up to 96 different drug compounds at the same time, and current platforms can only analyze 1 at a time, according to the study.
These worms are particularly useful in studies of neurodegenerative diseases since they have nervous systems and many different neurons. They also have a completely sequenced genome, and one-third of their genes are the same disease-causing genes found in humans.
“The C. elegans are thousands of times bigger than cells, 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,” said researcher Adela Ben-Yakar, PhD.
The microfluidic device is capable of high-throughput screening, studying up to hundreds of thousands of compounds rapidly and in a high-resolution manner. It can also perform high-content fluorescent screening that analyzes the animals’ phenotype, which sets it apart from existing devices, according to the study.
It is made from a flexible polymer, and has 96 wells for the roundworms to be trapped inside of. The tapered design of the microchannels allows the roundworms to be flattened and easily imaged.
The gasket system within the microfluidic chip applies pressure to the chambers so the roundworms become immobilized.
“This proof-of-principle study opens the door to using this technology to identify and develop treatments for some of the most intractable human diseases,” said Anne Hart, PhD, neuroscience professor at Brown University who has followed the development of the chip.
In the study, researchers examined the efficacy of 1000 drugs that received FDA-approval for conditions that involve protein aggregation associated with neurodegenerative diseases. They were able to demonstrate the efficiency of their device and discover a potential treatment for Huntington’s disease.
“Four of the drugs we tested were effective at treating a protein aggregation model that is directly related to Huntington’s, and 1 of these drugs became even more effective at increased doses without causing toxicity,” Dr Ben-Yakar said.
The microfluidic device is now being developed for commercial production, and could potentially assist numerous other researchers to discover new treatments for neurodegenerative diseases.