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LBNL Researchers Launch Firm to Commercialize Multinozzle Emitter Technology for Nanoflow-ESI-MS


Researchers at the Lawrence Berkeley National Laboratory have launched a company, Newomics, to commercialize their lab's multinozzle emitter array, or MEA, chip technology.

The technology, which they detailed in a paper published last month in Analytical Chemistry, improves the throughput and sensitivity of nanoLC mass spectrometry and could prove useful as part of clinical proteomics workflows, LBNL researcher and Newomics founder Daojing Wang told ProteoMonitor.

The MEA device presented in the paper is a 4-inch silicon-based chip consisting of 24 discrete units, each of which includes an input for sample injection, a nanoLC channel, and a multinozzle electrospray emitter.

Each of the 24 units serves as a separate LC input, allowing for significantly higher multiplexing than traditional devices, while the use of multiple nozzles on each emitter increases the sensitivity of the mass spec analysis.

The work builds on two previous Analytical Chemistry papers published by Wang and his colleagues – one in 2007 (PM 5/31/2007) and one in 2011 (PM 7/15/2011). In the 2011 paper, the researchers presented an MEA chip consisting of 96 10-nozzle emitters arranged on a 3-inch silicon chip. The most recent paper advances on this device by integrating nanoLC technology into the system so that separations can be done within the chip itself.

In order to achieve this integration, Wang and his team brought the number of emitters per chip down to 24 from the previous 96, enabling them to fit the LC columns into the 4-inch device.

"We can't do as close spacing" of the emitters with the LC columns and fluidic connections included, he said. He added that the researchers have considered moving to a device containing 96 emitters on a 6-inch chip, but that this larger chip could prove more difficult to interface with the mass spectrometer.

In theory, the MEA devices' use of multiple nozzles per emitter offers an increase in mass spec sensitivity roughly proportional to the square root of the number of nozzles per emitter. However, Wang noted, in both the 2011 paper and the most recent study the 10-nozzle models underperformed.

Although these versions should offer a roughly 3.3-fold improvement in sensitivity, in practice they only provided a two-fold increase, he said. "So right now we are not getting the full potential."

This result was likely due to insufficient voltage from their existing mass spectrometer – a Waters Q-TOF API US – and the larger spray plume generated by the 10-nozzle device, Wang suggested, noting that the researchers could "increase the voltage [of the mass spec] or modify the ion cone to maximize the increase in sensitivity."

With the current design, however, the researchers did see the expected sensitivity increase for emitters containing up to six nozzles, he said. "So without any modifications we're able to achieve around a two-fold increase in sensitivity."

Leigh Anderson, CEO of SISCAPA Assay Technologies and a longtime proponent of mass spec-based clinical proteomics, said that the sensitivity increase provided by the MEA chips was a "legitimate potential improvement," telling ProteoMonitor that "anything you can do for sensitivity is highly desirable from a clinical perspective."

Anderson also noted that "one can imagine [the device] might be usable in such a way that increases the throughput of samples through a system significantly." One such implementation, Wang said, would be to use "a multicolumn LC gradient running scheme so that the mass spec… could be constantly detecting analyte signals."

"While one column is doing the elution, the other column is doing a wash, and the other column is doing an injection," he said.

Anderson suggested, however, that robustness – typically a problem for nanoflow systems – could prove an obstacle to clinical implementation. "I think the real engineering issue to getting something like [the MEA] system into a clinical environment centers around the robustness question and how much that can be improved compared to the existing nanoflow systems," he said.

Wang and Newomics are currently collaborating with a hardware company – which he declined to name – to improve the robustness of the device, he said. "What we have published [in the Analytical Chemistry paper] is more or less a prototype."

One major goal of this collaboration is to automate control of the chip's fluidics, Wang said, since each of the 24 columns' fluidics are currently controlled manually. Once that is achieved, the researchers hope to work with mass spec vendors on modifications that would enable the instruments to fully take advantage of the 24-column, 10-nozzle chip's predicted sensitivity and throughput gains, he said.

In a proof-of-concept experiment, Wang and his co-authors used their MEA prototype to analyze hemoglobin in human blood samples, detecting the heme group, as well as several multiply charged species of Hb α and β subunits.

One immediate clinical application of the MEA chips, they wrote, may be "low-cost and high-throughput detection of Hb variants using a pinprick of blood in newborn screening."

Currently, Newomics consists of Wang and his LBNL colleague and co-author Pan Mao. The pair launched the company in hopes that a startup might prove a quicker route to market for the technology than a licensing deal with an established firm, Wang said.

"I feel like it might be faster to get this into the commercial or clinical space," he said, noting that he was told that "licensed technology typically takes a longer time to be developed by the big companies than by a start-up… if it's developed at all."

The firm is considering various ways to raise funding, Wang said, adding that at the moment they aim to support their work primarily through federal sources like Small Business Innovation Research awards. The company is currently working under a $250,000 SBIR Phase I grant from the National Institutes of Health that it received in September.