NEW YORK – Proteomics firm Somalogic is exploring quantum biosensing technology under a $1 million grant from the National Science Foundation's Convergence Accelerator program.
The effort, which involves collaborators at the University of Chicago, University of California, Los Angeles, University of California, Santa Barbara, and University of Washington could allow the company to explore more portable applications of its SomaScan technology while also potentially improving the specificity of its proteomic measurements, said Jason Cleveland, principal fellow at Somalogic.
The company and its partners are investigating a sensing approach that uses flaws in diamonds called nitrogen vacancy (NV) centers that emit fluorescence that varies with the magnetic states of the electrons within this vacancy, Cleveland said. The basic notion is that these diamonds could be functionalized with an affinity agent like one of Somalogic's Somamers, and binding of targets to that agent could be detected by observing changes in the magnetic state of the vacancy.
This could allow the company to take its SomaScan platform, which is currently a lab-based system capable of measuring 5,000 proteins per sample, and shrink it down to the size of a chip, which would open up the sort of point-of-care and health monitoring applications the company has long envisioned.
In addition to shrinking the platform to a more POC-amenable device, the quantum sensing approach could also improve the performance of the system. Cleveland said that Somamers could be designed to include a paramagnetic spin label, which could improve the specificity of these reagents. Consisting of an organic molecule missing an electron, spin-labels have been used in research into proteins and other molecules allowing scientists to collect information on, for instance, the mobility or structure of tagged molecules by observing changes in the spin of the electron in these labels in response to changes in its environment.
A spin label included in a Somamer might experience changes in its spin upon binding of a target to the Somamer, and those changes could also be read out through the diamond nitrogen vacancy, Cleveland said.
The nature of this signal could vary depending on what molecule was bound to the spin-labeled Somamer, which might allow researchers to distinguish between true binding events and off-target binding, improving the specificity of the reagents.
Somalogic's SomaScan panel allows researchers to measure 5,000 proteins per sample with high throughput, capabilities that have drawn substantial interest from scientists looking to do large-scale proteomic discovery experiments. However, a number of researchers have voiced concerns about the platform's specificity and how well-validated the individual assays are.
For instance, as part of the UK's Interval study researchers used the platform to quantify plasma protein levels of 3,301 apparently healthy, genotyped subjects, with 14 percent of the Somamers showed non-specific binding, either to a protein other than the target protein (7 percent) or to a protein isoform (7 percent).
Cross-reactivity and non-specific binding is an issue inherent in any highly multiplexed affinity agent-based proteomic platform, which Cleveland said was one of the reasons he found the quantum sensing approach so intriguing.
"In the current [SomaScan] assay there is all this stuff to fight non-specific binding," he said. "You do these two catches where the Somamers catch the proteins and then that complex gets photocleaved away and you then catch the proteins on another set of beads which allows you to do all this aggressive washing to help with non-specific binding."
As data like that from the Interval study indicates, though, this doesn't eliminate the problem. And, Cleveland noted, performing these washing procedures in a POC device might not be feasible.
"What I was looking for was a technology where, on a molecule-by-molecule basis you could ask a Somamer, did you catch a protein, and beyond that you can actually ask, did you catch the right protein?" he said. "That is the interesting thing about the [diamond-based approach]. You get more than a yes-no answer, you can actually do a little magnetic resonance experiment."
Cleveland said he hoped the company could use this magnetic resonance data to identify non-specific binders by distinguishing between the magnetic resonance signature of true hits versus off-targets.
Peter Maurer, assistant professor of molecular engineering at the University of Chicago and one of Somalogic's collaborators on the grant, said that researchers have shown that they are able to detect DNA binding to complementary spin-labeled DNA on the surface of a diamond. He noted, though, that this has not yet been done with affinity agents like aptamers and that there are "a number of fundamental hurdles that need to be overcome."
To start, no one yet knows how to functionalize diamond surfaces with these affinity agents in a controlled way. Then there is the challenge of generating enough signal from the diamond NV to provide the required sensitivity. Finally, Maurer said, it remains to be seen if the signal from such a system will actually allow researchers to identify binding events.
The NSF grant is aimed at addressing these three challenges, Maurer said.
Cleveland similarly said that the goal of the effort, which is slated to last nine months, would be to construct a sensor for a single Somamer-protein pair to provide a proof-of-principle for the idea. If that is successful, the collaborators could potential receive a $5 million Phase II grant from NSF, which Cleveland said they would likely use to try to multiplex a small number of sensors.
"It is very early stage," Maurer said. "It is something that in maybe five or ten years could be applied to an actual product. But it is exciting for me because we are using quantum technology to start actually thinking about applications, and I think it is exciting for Somalogic because it is a technology that could bring them from needing a pipetting robot and a standard molecular biology lab down to chip-scale measurements."