Shining Light on Ebola Virus for Faster Diagnosis
Posted on by Dr. Francis Collins
Caption: A rapid Ebola detection system consisting of a microfluidic chip (left) and an optofluidic chip (right), connected by a curved tube (center).
Credit: Joshua Parks, University of California, Santa Cruz
Many lessons were learned during last year’s devastating outbreak of Ebola virus disease in West Africa. A big one is that field clinics operating in remote settings desperately need a simple, rapid, and accurate test that can tell doctors on the spot—with just a drop of blood—whether or not a person has an active Ebola infection.
A number of point-of-care tests are under development, and it’s exciting to see them moving in the right direction to fill this critical need [1]. As a recent example, a paper published in Nature Scientific Reports by a team of NIH-supported researchers and colleagues shows early success in rapid Ebola detection with an automated lab on a chip [2]. The hybrid system, which combines microfluidics for sample preparation with optofluidics for viral detection, identifies Ebola at concentrations that are typically seen in the bloodstream of an infected person. It also distinguishes between Ebola and the related Marburg and Sudan viruses, suggesting it could be used to detect other infectious diseases.
Most lab-on-a-chip technologies must squeeze the necessary biology, chemistry, and electronics into just a few millimeters of real estate. It can be a really tight fit. What’s cool about this device engineered by a multidisciplinary team of scientists—led by NIH grantee Holger Schmidt at the University of California, Santa Cruz—is it’s a two-chip system. The chips are connected and can be either stacked or placed side by side.
Here’s how it works: First, a drop of genomic material extracted from Ebola-infected cells is loaded into the microfluidic chip. The sample gets routed through tiny channels and undergoes a series of preparatory steps to expose genetic material, including RNA from the Ebola virus. Any bits of exposed genetic material from the virus then bind to matching synthetic sequences attached to magnetic microbeads in the chip. A small magnet collects the microbeads and any extraneous molecules are washed away, enabling Ebola RNAs to be labeled with fluorescent markers. The microbeads then move along to the optofluidic chip, where light is used to read the fluorescently labeled sequences, one by one, to render a test result.
Because the system is still in the process of being fully optimized, the exact testing time has yet to be determined. But the team is aiming to get the entire process, from collecting blood to diagnosis, down to under an hour. Schmidt notes that the actual optical sensing takes less than 5 minutes. The test also should cost substantially less than the current go-to laboratory test (based on the polymerase chain reaction, or PCR), because it can be mass fabricated and requires no expensive chemicals.
The team—which includes researchers from Brigham Young University, Provo, UT; University of California, Berkeley; and Texas Biomedical Research Institute, San Antonio—is now preparing to take the next developmental step and test their system on patient blood samples with unknown viral concentrations. It will be interesting to watch this system and others as they push ahead to the ultimate goal of providing a point-of-care diagnostic test for the Ebola virus. These portable, easy-to-use tests will be key in containing future outbreaks, saving a lot of lives from this deadly virus.
Reference:
[1] Toward detection and diagnosis of Ebola virus disease at point-of-care. Kaushik A, Tiwan S, Jayant RD, Marty A, Nair M. Biosens Bioelectron 2016 Jan 15. [Epub ahead of print]
[2] Optofluidic analysis system for amplification-free, direct detection of Ebola infection. Cai H., Parks JW, Wall TA, Stambaugh A, Alfson K, Griffiths A, Mathies RA, Carrion R, Patterson JL, Hawkins AR, Schmidt H. Sci. Rep. 2015 Sept 25 [Epub ahead of print].
Links:
Ebola and Marburg (National Institute of Allergy and Infectious Diseases/NIH)
Ebola data and statistics (World Health Organization)
Holger Schmidt (University of California, Santa Cruz)
NIH Support: National Institute of Allergy and Infectious Diseases
As if the detecting probe is labelled and specific. Is the target RNA amplified? If not, I wonder about the sensitivity.
good point, not so easy to detect small amounts of virus. we’re doing Norovirus now from the food supply with the USDA.
My recommendation would be to skip the beads and simply fit a small DNA microarray into the microfluidic. It would cost less and the long term storage of the arrays themselves would be stable for many years.