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Mass General, Harvard Study Shows Potential of NanoMosaic's Platform for Biomarker Development


NEW YORK — A team led by researchers at Massachusetts General Hospital and Harvard Medical School has used NanoMosaic's Tessie proteomic platform to identify a pair of biomarkers for predicting and diagnosing post-operative delirium.

Detailed in a study published last week in the Annals of Surgery, the findings could help clinicians better manage patients with postoperative delirium, a condition that is among the most common complications of surgery, affecting up to 50 percent of elderly patients.

The study also provides some of the first data published on NanoMosaic's Tessie platform, which uses arrays of silicon "nanoneedles" functionalized with antibodies or other affinity reagents to detect and quantify proteins. The system's measurements are based on changes in optical resonances that occur when target molecules bind to the functionalized needles.

The Woburn, Massachusetts-based company placed a Tessie instrument in the lab of MGH researcher Zhongcong Xie, senior author on the Annals of Surgery paper, in October 2020. It formally launched sales of the instrument at the beginning of this year and has since placed "close to 10 systems," according to John Boyce, the company's cofounder, president, and CEO.

The Tessie system's nanoneedles 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, according to the company, 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, letting researchers quantify the amount of target present at these higher abundances, as well.

NanoMosaic has touted its technology as being potentially capable of proteome-scale measurements, with the ability to multiplex up to 94,000 analytes per experiment. Those multiplexing capabilities are constrained by the availability of suitable affinity reagents, however, and, to date, the system has seen uptake primarily for more targeted assays like those run by Xie and his colleagues in their post-operative delirium work.

In the study, the MGH researchers used the Tessie instrument to measure preoperative plasma levels of two forms of phosphorylated tau protein — tau-PT217 and tau-PT181 — in 139 patients 65 years or older who were undergoing either a knee replacement, hip replacement, or laminectomy.

Eighteen of the 139 patients developed delirium following surgery, with those patients having higher preoperative levels of tau-PT217 and tau-PT181 than those who didn't develop delirium. After adjusting for factors including age, education status, and a preoperative test of mental status, tau-PT217 and tau-PT181 levels were independently associated with the development of delirium.

Tau-PT217 predicted delirium with an area under the receiver operating curve of .97, while tau-PT181 predicted it with an AUC of .89. In patients who experienced post-operative delirium, pre-operative tau-PT217 levels were roughly fivefold higher than in those who did not. Pre-operative tau-PT181 were roughly two-fold higher.

NanoMosaic's Boyce said that while the company expected pharma and academia to drive initial uptake of the platform, it has also seen substantial interest from researchers like the MGH team interested in diagnostics development as well as from diagnostic laboratories.

"We have a number of diagnostic labs that have bought systems from us and are now getting them up and running," he said, though he declined to name any specific institutions.

Boyce said these customers have been attracted by the low cost of the system (which starts at around $50,000) and the ability to get up and running quickly with custom panels of proteins.

Researchers can in a matter of hours manually spot antibodies to up to 20 proteins on the company's chips and begin running their assays, Boyce said. He added that the Tessie system is currently able to read out a 96-well plate in 13 minutes.

NanoMosaic has also highlighted its platform's sensitivity and wide dynamic range, which it says spans seven orders of magnitude, as selling points for the system. The ability to detect neurological markers like tau-PT217 and tau-PT181 in plasma speaks to these capabilities, as these markers are typically present at low concentrations in plasma.

Xie said that he learned of NanoMosaic's technology when looking for an approach sensitive enough to measure the plasma phosphorylated tau proteins he targeted in his work.

"Usually we use ELISAs or western blots, but those technologies are limited due to sensitivity issues," he said. "For low concentration proteins like phosphorylated tau we needed a very high-sensitivity technology."

Xie said he and his colleagues now plan to test the biomarkers further, exploring whether they could be used to better target interventions that have been proposed for treating patients at risk for post-operative delirium.

"We have combinations of drug and non-drug interventions under investigations to reduce post-operative delirium, but they could be costly, and we can't use them for every single person," he said. "If we can identify high-risk patients, we would use these approaches in this high-risk population."

Measurement of neurological markers in plasma has become a particularly active area in Alzheimer's disease research, with plasma tau-PT217 and tau-PT181 also showing promise for early detection of that condition. The MGH researchers noted that the linkage of these markers to postoperative delirium suggests that the condition could be an indication a patient is suffering from preclinical Alzheimer's.

Plasma markers for Alzheimer's and other neurodegenerative conditions have been a major area of emphasis for high-sensitivity immunoassay firm Quanterix, which last year received US Food and Drug Administration breakthrough device designation for its Simoa phospho-Tau 181 (pTau-181) blood test. NanoMosaic recently hired, as its VP of sales for North America, Quanterix's former VP of sales, Curt Akers.

Beyond the MGH work, NanoMosaic is currently involved in companion diagnostics development projects with several pharma companies, Boyce said, though he did not name the companies. He said that as part of those deals, the firm retained some intellectual property rights. While the company may engage in internal diagnostics work using the Tessie platform, it does not have a CLIA lab and would likely aim to license out any assays it developed as opposed to commercializing them itself.