A handheld medical diagnostic tool, a la the Star Trek tricorder, has been a staple of science fiction for decades. Now, Leonard “Bones” McCoy’s gadget of choice may soon become a reality as a modern plague continues to spread around the globe. A team of researchers at New York University is developing a tricorder of sorts to help mitigate the spread of the coronavirus pandemic. The intricate system involves a bevy of beads, lasers, holography, video cameras, and lots of advanced mathematics. We recently spoke with David G. Grier of NYU’s Department of Physics and the Center for Soft Matter Research about his team’s focus.
There are two main ways to go about coronavirus testing, Grier explained. This involves directly testing for the virus itself or identifying COVID-19 antibodies; telltale signs that a person’s immune system has staged an immune response to the pathogen.
In June, Grier said the team was focused on developing an assay to bind with antibodies rather than the virus. The team’s “bead-based assay” starts with a small vial brimming with a batch of small polystyrene beads, each measuring one micrometer in diameter.
“Once you’ve got the bead you can coat it with your choice of molecules. We happen to put proteins on the surface of those beads. And those proteins bind either the virus or if you choose another protein it binds the antibody,” Grier said.
Serum is removed from the blood and added to the vial of small beads. If the bead is now bigger after the serum has been introduced, the bead has amassed antibody material, signifying a positive test.
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Again, a bead that has amassed antibody proteins is now inherently larger than it was originally. Therefore, a comparatively larger bead would signify a positive test. It sounds simple, right? In theory, yes, although there’s a catch. Remember, the beads are about one micrometer in size. For perspective, one micrometer is one-millionth of a meter.
“When you’re talking about the bead growing because the molecules have stuck to the surface, what you’re really looking for, at best, is a 1% change in size. And probably a .1% change in [the] size of something that’s already at the limit of what you can see with standard microscopy,” Grier said.
These changes are infinitesimally small. To help identify these minute changes to these micrometer beads, the team leverages principles of physics; specifically the Lorenz-Mie theory of light scattering.
“The change is unmeasurably small for most standard technologies and that’s why people haven’t used this approach before. Because it just wasn’t possible. So our secret sauce, the thing that makes it work is a technique called holographic video microscopy,” Grier said.
So what is holographic video microscopy exactly? In its most fundamental form, the technique involves using lasers and scattered light to measure the size of these beads in three dimensions.
“You light these beads up with a laser pointer. If you have a bead in your field of view, then that bead is going to scatter some of that light and that scattered light wave interferes, it adds up with the rest of the laser beam, to make sort of a ripple pattern, an interference pattern, that we magnify and record with an ordinary video camera,” Grier said.
The interference pattern that is created is actually a hologram of the particle and this hologram can be measured to determine changes in the size of the plastic beads, Grier explained.
“The idea then is that you can record this hologram with your video camera and analyze it pixel by pixel and what that analysis tells you is where the particle is in X and Y and Z, all three dimensions and it tells you where it is with ridiculous precision,” Grier said.
This video captured image can then be photographed and analyzed to determine the size of the bead.
“You take a snapshot of the bead. Hey, presto, a few milliseconds later you know everything there is to know about the bead. You know where it is. You know how big it is. And you know what it’s made of,” Grier said.
This technique enables testing with a vast set of advantages compared to other testing methods. For one, the tests results are nearly immediate.
“That measurement goes lickety-split, it’s totally fast. You scatter the light, more or less, in the time that it takes to record the image you also have the answer about whether that bead has grown or that bead has not grown,” Grier said.
Furthermore, the small beads at the center of this technique are also inexpensive and easy to create in bulk. Grier notes that his colleagues in the Department of Chemistry at NYU can create large batches of these beads for very little money. The rest is mostly compact lasers, video cameras, and advanced mathematics.
“Instead of having to do fancy chemistry to make the molecules fluoresce, you just look at them. And you’re looking at them with an ordinary TV camera using a laser pointer. The thing that makes it work is a whole bunch of pretty sophisticated math. But once you’ve done the math once the computer can do it for you very, very fast from now on. And that’s the basis of the assay and it works. We can do an assay for antibodies, a complete assay, in about 15 minutes and it costs almost nothing.”
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Grier and his colleagues have already commercialized the holographic technique and the company Spheryx has created an instrument based on this approach, he explained.
Things have moved quickly for Grier’s team since it first published a paper on the holographic technique for immunoassays in February. Following a National Science Foundation (NSF) call for COVID-19 technology proposals, the team passed along a white paper explaining its work in early March. Within weeks, Grier’s team received NSF RAPID funding to support continued research.
While the team was originally focused predominantly on developing an antibody assay, it is now working to develop a virus assay. Grier hopes to have the virus assay ready for September—this would allow the team to support testing efforts as NYU students return to campus this fall.
As Grier pointed out, testing at NYU could help reduce the testing burden already placed on the New York City public health agencies.
“Assuming everything works in NYU, you could scale up again,” he said. “You can disseminate the technology. It’s not hard to get started and it is inherently scalable.”