NEW YORK – Harvard University spinout NanoMosaic is looking to tackle the proteomics research market with its label-free biosensing system.
The Woburn, Massachusetts-based company is planning a beta rollout of its platform, which uses arrays of silicon "nanoneedles" functionalized with antibodies or other affinity reagents to detect and quantify proteins. According to Qimin Quan, NanoMosaic's co-founder and CSO, the system can measure analytes over a larger dynamic range than existing proteomic technologies and at considerably lower cost.
Quan developed the technology in his lab while a junior fellow at Harvard's Rowland Institute. It is based on observing the changes in optical resonance that occur when target molecules bind to the functionalized antibodies.
Because the needles are close in scale to the targets they are measuring, the perturbation of a needle's light scattering spectrum upon binding of the target protein to the antibody "is enough to trigger a color change in the needle," Quan said. This change can be detected using an inexpensive color camera and correlated to the amount of the protein present.
The needles are arrayed in sub-500-µm sections each devoted to a single target. Within each of these sections are thousands of nanoneedles divided between a "digital detection" region and an "analog" region. In the digital region, the nanoneedles capture one target molecule per needle, which Quan said allows the platform to detect very low-abundance proteins and quantify them at the single-molecule level.
At higher concentrations, however, the nanoneedles in the digital region become saturated. At this point, the platform begins using the analog section, which consists of larger nanoneedles that can capture multiple proteins each. The amount of protein captured by these nanoneedles correlates with their change in color, allowing researchers to quantify the amount of target present at these higher abundances, as well.
By combining these two modes of detection, the nanoneedle technology is able to quantify proteins across seven orders of magnitude, Quan said.
The platform should also allow for high levels of protein multiplexing, he said, using different colored needles to correspond to different protein targets or printing chips with different sections functionalized to detect different proteins. He said that currently the company has managed to build chips capable of multiplexing around 1,000 protein targets but that it ultimately envisions producing chips capable of measuring entire proteomes. The company said that in theory it could produce a proteome-wide assay using 5 billion nanoneedles arrayed across a 70-mm chip.
Quan acknowledged that multiplexing at this level will face challenges with regarding to antibody cross-reactivity.
"Cross-reactivity is something that we are fighting against, always," he said. He added, though, that he believed the flexibility of the platform would allow the company to produce chips that could minimize the problem, including by physically separating reactions to avoid cross-reactivity.
Quan said NanoMosaic planned to target its platform, named Tessera, to both diagnostic and discovery applications, suggesting that its sensitivity could allow it to compete with high-sensitivity immunoassay technologies like Quanterix's Simoa while its multiplexing capabilities and ability to run samples at low cost and high throughput would let it compete in the discovery space with companies like Somalogic and Olink, and with mass spectrometry approaches.
John Boyce, NanoMosaic's president and CEO, as well as the managing director and cofounder of venture capital firm TigerGene, which has funded NanoMosaic to this point, also highlighted the technology's low cost as a key selling point.
He said that the system runs samples at a cost of around $0.25 "per protein interrogation," which he noted compares favorably to many other platforms in the space that cost $1 or more per protein.
Joe Wilkinson, the company's COO added that this cost should come down as the company ramps up its multiplexing capabilities.
NanoMosaic has not yet launched sales of the platform but has launched a pharma services business, Wilkinson said, adding that the system's wide dynamic range has proved attractive to these customers.
"They don't know where in the dynamic range some of their proteins are going to fall, and so they need that full dynamic range in order to see them," he said.
Wilkinson added that the company plans relatively soon to begin placing instruments as part of a beta launch.
Boyce said that NanoMosaic is also seeing a strong initial interest in biomarker discovery. He added that the company has put together a panel of proteins focused on enabling proteome-wide association studies (PWAS), which use measurements of proteins across the proteome to identify relationships between genes and phenotypes mediated by changes in protein function or abundance. This has been an active area of interest for companies like SomaLogic that likewise offer highly multiplexed, high-throughput proteomic platforms.
NanoMosaic presented a pair of posters describing the technology at the American Association for Cancer Research annual meeting this year, one giving an overview of the platform's specifications and the other using the system to measure a panel of protein markers linked to cytokine release syndrome in cancer immunotherapy. In the second poster, they noted the development of assays to cytokines including TNF-alpha, IL6, CRP, IFNγ along with other low-abundance proteins like tau at levels of 50 femtograms per ml.
The company has also used the platform for work on COVID-19, announcing in April that it is collaborating with clinicians at Massachusetts General Hospital to explore whether the technology could help measure patient antibody profiles to assess their likely prognosis as well as their response to treatment.