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With Sights Set on Assay-Specific Devices, Newomics Builds MEA Chip for Diabetes Monitoring

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Using its multinozzle emitter array technology, biotech firm Newomics has developed a top-down proteomics assay for diabetes monitoring.

The assay measures glucose along with the intact forms of glycated hemoglobin, glycated HSA, and glycated apolipoprotein A-I for monitoring blood sugar, as well as intact cysteinylated HSA, S-nitrosylated HbA, and methionine-oxidized apoA-I to gauge oxidative stress and cardiovascular risk.

Newomics' MEA technology allows for measurement of these analytes in a single mass spec run, putting into a single assay a series of measurements that would typically be performed using several different techniques and platforms, Daojing Wang, the company's founder and president, told ProteoMonitor.

"If you look at the technologies out on the market right now, there is no way to simultaneously measure glucose along with multiple proteins and multiple protein modifications in one shot," he said.

The MEA device consists of a series of multinozzle emitters arranged in a circular array on a silicon chip. The multiple emitters allow for higher-throughput experiments, as each emitter can be interfaced to a separate LC system allowing for rapid sequential or parallel mass spec analysis. The increase in nozzles provides an improvement in sensitivity proportional to the square root of the number of nozzles per emitter.

In a paper published last year in Analytical Chemistry, Wang and his Newomics co-founder Pan Mao presented an MEA chip consisting of 24 discrete units, each including an input for sample injection, a nanoLC channel, and a multinozzle electrospray emitter.

In this recent work, which was detailed in a paper published this week in the Journal of Proteome Research, the researchers used a chip integrating guard and nanoLC columns with multinozzle emitters, allowing them to analyze small molecules, proteins and post-translational modifications in a single LC-MS run, Wang said. For the assay, the researchers used 5 μl of blood and a one-hour separation gradient.

Using the assay to analyze a set of eight type 2 diabetics and eight healthy controls, the researchers were able to distinguish between the two cohorts, Wang said. Acknowledging the small size of the cohorts, he said that, having demonstrated proof of concept, Newomics now hoped to test the assay in larger sets of patients.

"You have to show proof of principle for the assay before you can launch a bigger study," he said, noting that "you can't just order all the samples commercially for a large-scale study." The company will likely seek out collaborators to help with putting together larger clinical studies, he added.

Launched in 2011 as a spinout from the Lawrence Berkeley National Laboratory – where Wang and his team invented the MEA technology – Newomics was started to commercialize MEA. But the firm doesn't aim to be simply a device manufacturer, Wang said. Rather, he said, its "long-term goal is to develop assay-specific devices for precision medicine."

"We are not just developing new devices or just developing new assays," he said. "We are integrating them – developing application-specific devices for specific clinical assays."

While Wang said that the company may in the future move on to other diseases, diabetes will remain its focus in the near term. "We want to focus on one disease at a time – to show that this works in diabetes. Then we can move on to other diseases," he said.

Wang said that Newomics will continue to focus on top-down proteomics as it explores new assays, noting that he believes there are significant clinical opportunities for top-down analysis of high abundance proteins. Biomarker research has largely focused on bottom-up analysis of lower abundance proteins – for which, Wang said, the MEA technology is also suited. These analytes, however, can be quite difficult to measure, particularly with the throughput and reproducibility required for clinical assays.

These challenges have led some scientists, such as Geneva University Hospital researcher Denis Hochstrasser, to suggest that clinical proteomics look into tests for indications where high abundance proteins could be informative – such as hemoglobinopathies or diabetes.

The MEA chip offers throughput and sensitivity gains for bottom-up proteomic experiments as well, Wang noted, but, he said, "I feel like right now top-down proteomics has tremendous unexplored opportunity for clinical applications."

In addition to testing their assay in larger cohorts, Wang and Mao need also to address a variety of clinical chemistry issues such as day-to-day variability and inter- and intra-patient variability, he said.

The researchers are also continuing to refine the MEA technology itself, with the goal of launching a commercial MEA device by the end of this year, Wang said. The company is currently testing the device with machines from several mass spec vendors including Waters and Thermo Fisher Scientific.

With an eye on clinical and biotech/pharmaceutical markets, the company is also exploring integrating microflow LC with its emitters. These markets, Wang said, "like normal flow [LC] because of the robustness and speed" compared to nanoLC. Because of the increased sensitivity offered by the multinozzle design, the MEA chips could potentially enable microflow LC with nanoflow sensitivity, he said.

The company is currently supported by three Small Business Innovation Research grants from the National Institutes of Health: a $250,000 award that ends Feb. 28, 2014; a $300,000 award that ends June 12, 2014; and a $225,000 award that ends Aug. 31, 2014.

Wang said that for now he is not actively seeking out alternative funding such as venture capital. "I feel that we still need to push the technology further and make a stronger case before we move to that stage," he said.

Currently he and Mao are Newomics' only two full-time employees, though he said that they may look to add several more employees in the near future.

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