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Microfluidic chips for high-throughput genetic screening


Understanding the mechanisms behind neurodegeneration and neural development is important for developing new therapies to treat various diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease. C. elegans is a nematode model system widely used in neuroscience and genetics because of its comparatively simple nervous system, short life cycle, and genetically identical progeny. A comprehensive knowledge of its neural circuitry and behavioral phenotypes makes the animal a very effective genetic screen for mutations. However, current research suffers from the low-throughput, manual, and nonquantitative nature of such screening.

In the laboratory of Dr. Hang Lu, trainee Ivan Cáceres is designing an automated microfluidic system to perform genetic screens of C. elegans and use it to discover genes involved in neurodegeneration and neural development. Ivan’s training is comprised of a combination of various subject areas including microfluidics, image analysis, bioengineering, neuroscience, C. elegans genetics, and system integration/automation. His training is possible due to the interdisciplinary training he received as an IGERT fellow in the Hybrid Neural Microsystems program.

Recently, Ivan has designed microfluidic chips capable of passively orienting worms into lateral orientations by exploiting device channel geometry. The associated figure displays Ivan’s current design of the chip. By using curved channel devices, Ivan is capable of consistently positioning animals into lateral orientations to facilitate imaging of the ventral and dorsal nerve cords of the animals. Using this device, Ivan performed a preliminary screen of over 10,000 animals on-chip at a speed at least 10 times faster than manual screen. From this screen, Ivan identified several alleles suspected to be involved in neurodegeneration and development. These alleles are currently being evaluated and mapped and to to be further investigated at a collaborator’s laboratory.

In addition to C. elegans, Dr. Hang Lu’s laboratory also uses microfluidics to perform cellular studies concerning cell migration, cancer biology, and cell culture constructs.

Address Goals

Research Infrastructure: This technology is building critical infrastructure that is in high demand. This is a field where almost all screening occurs manually. While the group at Georgia Tech developing the technology has collaborators both using it and evaluating it, there is an unmet demand in the field for more investigators to use the tools being developed. It is anticipated that eventually this technology will be licensed for commercialization.

Discovery: This methodology could potentially enable discoveries of novel mutations underlying the genetic basis of diseases affecting the nervous system. As examples, C. elegans is actively being used by labs to screen for mutations underlying Parkinson’s Disease, Huntington’s Disease, and neurotoxicity by environmental toxins such as mercury.