NEW YORK (GenomeWeb) – Sample prep firm Ceres Nanosciences said this week it has received a $430,000 grant from the Bill & Melinda Gates Foundation for development work on a saliva-based test for the Ebola virus.
The grant will fund feasibility studies investigating the usefulness of Ceres' Nanotrap technology for preparation of saliva samples upfront of both nucleic acid and protein-based assays for the disease. The studies will be conducted in collaboration with George Mason University and the US Army Medical Research Institutes of Infectious Diseases.
Launched in 2008 to commercialize technology developed by Emmanuel Petricoin and Lance Liotta, Ceres uses hydrogel nanoparticles functionalized with internal affinity baits to enrich target analytes for downstream analysis. The technology is intended for biomarker work in a variety of conditions, but Ceres has focused much of its early work in infectious disease, CEO Ross Dunlap told GenomeWeb.
In fact, in addition to the Ebola project, the company plans within the next few months to release its first commercial product, a Nanotrap-based urine test for Lyme disease. Ceres plans to launch the assay as a laboratory-developed test out of GMU's CLIA facility.
The Nanotrap system uses chemical dyes to bind to various analytes, concentrating them inside the nanoparticles.
Different dyes have affinities for different classes of analytes, Dunlap said. "So we have a menu of Nanotrap particles with different dye chemistries, and the way we approach every project is we screen the particles against the analyte of interest."
The dyes are not typically highly specific to the target analyte, so the nanoparticles capture a variety of other molecules, as well. The particles are built, however, to exclude analytes over 40 kD, so, Dunlap said, they eliminate high-abundance proteins like albumin that commonly present a challenge to protein biomarker discovery and detection.
They also serve to protect target analytes once captured from enzymatic degradation, he said. "So [the technology] is a powerful tool for getting at the labile, low-concentration biomarkers that are good analytes for a number of infectious diseases and cancer."
The key, Dunlap notes, is the particles' ability to offer highly concentrated collections of analytes. While the chemical dye baits don't provide especially high specificity, by concentrating the captured analytes in the Nanotrap particles, researchers can significantly improve the sensitivity of their more specific downstream assays, like an ELISA.
"Typically you can't just take a droplet of urine and get anything of value out of it with mass spec," Dunlap said. "And sometimes you can't get much value out of a blood sample on mass spec or immunoassay because there is only so much volume an immunoassay or [mass spec] device can handle."
With the Nanotrap "we're able to take 20, 40, 60 ml of urine and concentrate it into the range of sample input for a particular assay," he said, noting that the technology is able to provide in some cases up to a 1,000-fold concentration factor.
That means more target analytes in a smaller sample volume, making for more sensitive assays.
In the case of Ebola, this raises the possibility of detecting the disease in saliva, which, Dunlap notes, would be desirable given the safety implications of drawing blood to test for the disease.
In the case of the company's forthcoming Lyme disease test, the Nanotrap system allows clinicians to perform a direct test for the disease, assaying levels of an outer surface protein, OspA, of Borrelia burgdorferi, the organism that causes the disease.
The current gold standard for detecting Lyme disease is serological testing offered by Laboratory Corporation ofAmericaand Quest Diagnostics that measure patients' immune response. These tests, however, are neither very sensitive nor specific for the disease, Dunlap said.
In fact, he noted, last yearVirginiapassed the Lyme Disease Testing Information Disclosure Act which mandates that due to the poor performance of serological tests for Lyme disease, doctors performing these tests must inform patients that a negative test result doesn't necessarily mean they don't have the disease. The bill was opposed by the Medical Society of Virginia on the grounds that it interfered with the physician-patient relationship.
Ceres recently completely a three-year, three-site, clinical study of the test in which they studied several hundred patients, and is currently preparing a manuscript based on this data, Dunlap said.
In addition to detection of the disease, he said it might also prove useful for tracking the effectiveness of antibiotic treatment for the condition.
"Because it is a direct test we can actually use it during the course of antibiotic treatment to determine if the disease has been eliminated," he said. "We have data from longitudinal samples where we show the spike in the antigen in the urine during the treatment and then following treatment we show it has been completely eliminated."
The company plans to release the test initially on a small scale, targeting regional hospitals in the Northern Virginia area, Dunlap said. In the future, though, Ceres hopes to take the test through US Food and Drug Administration clearance.
Thus far the company has signed a partnership deal with one Northern Virginia clinic that Dunlap said "sees a lot of Lyme disease. That will be our first point of patient intake."
In addition to its Lyme disease and Ebola work, Ceres earlier this year established a collaboration with the Translational Genomics Research Institute focused on incorporating the NanoTrap technology into TGen's automated mass spectrometry workflows with the aim of discovering and developing protein biomarkers for conditions including cancer and infectious disease.
The company has also inked a global distribution deal for the Nanotrap particles with Thermo Fisher Scientific, Dunlap said.