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Georgia Tech Team's Mass Spec Ionization Device Could Significantly Boost Sensitivity

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NEW YORK (GenomeWeb) – Researchers at the Georgia Institute of Technology have developed a new power source for mass spectrometry ionization that could significantly improve instrument sensitivity.

Described in a paper published last month in Nature Nanotechnology, the power source uses triboelectric nanogenerators (TENGs) to more precisely control mass spec ionization, allowing researchers to analyze a higher percentage of generated ions and, thereby, increase the sensitivity of their analyses, said Facundo Fernández, chair of bioanalytical chemistry at Georgia Tech and senior author on the study.

While the Nature Nanotechnology study investigated ionization of proteins using the device, Fernández said that his group has not studied its application to proteomic workflows. However, he said that he believed it could be useful for such research, particularly in cases where researchers are dealing with small or precious samples.

"I would love to see a group active in proteomics take this idea and test it for their applications," he said.

When samples are introduced to a mass spectrometer for analysis, they undergo ionization, in which a charge is applied to convert neutral molecules into gas-phase ions. However, as Fernández and his co-authors note, current ionization devices offer researchers little control over how highly charged the produced ions and cannot be configured to match their ionization patterns to the duty cycle of mass spectrometers using technologies like ion traps, Orbitraps, and ion mobility.

A conventional "nanospray ion source generates ions all the time," Fernández said. "You basically turn it on, and it just generates ions." However, many mass spec analyzers measure ions not continuously but in discrete cycles, which means that many of the ions produced by such a system are never measured, which reduces instrument sensitivity.

"You're making ions all the time, but the mass spectrometer is only looking at those ions a fraction of the time," he said. "And when the mass spec is not looking at the ions, the ions are being lost."

The TENG-based ionization approach developed by Fernández and his colleagues, on the other hand creates pulsed ion sprays that can be matched to the mass spec's duty cycle.

"It creates a tiny little spray for only a few milliseconds, and then it stops," he said. "So that's why it's more efficient, because you can generate a little bit of the spray, get some information from that, and then the instrument can have time to process that information before you generate the next spray."

"You can time [ion production] properly so you don't lose any sample and you get much better sensitivity," he said.

TENGs consist of pairs of electrodes and triboelectric layers. The devices produce charge when the triboelectric layers move relative to each other, which leads to a redistribution of charge in the electrodes. Using TENGs to power a mass spec ion source, the researchers could control "the amount of charge available for ionization" as well as "the duration, polarity, and frequency of the downstream ion signal."

The researchers used the TENG device coupled to a Thermo Fisher Scientific Q Exactive instrument to analyze molecules including drugs of abuse, proteins, peptides, and DNA, finding that the approach performed well across various classes of analytes.

Fernández said that he and his colleagues have not yet done many direct comparisons against mass specs using conventional nanospray but noted that the device enabled "incredibly low detection limits." In the case of cocaine, they were able to detect sample at a concentration of 10 pg/ml, below what they were able to detect with a conventional nanospray source.

He said they were aiming in the study to provide a general demonstration of the technique, "and so we didn't focus on one specific application." However, he said, "nanospray is a technique that is used regularly in protein analysis, so I think it will be a no-brainer for that particular field."

For the technique to be used in proteomics work, researchers will have to interface the TENG device with liquid chromatography, something Fernández said they didn't do in the Nature Nanotechnology study.

"I think that it's very doable," he said of linking the system to LC. "I honestly don't have any concerns. But we haven't done it yet."

Fernández said he and his colleagues have a provisional patent on the technology and have been contacted by several mass spec firms regarding potential commercialization plans. He said, though, that groups with experience in nanospray mass spec could build their own TENG-based device for less than $60.

"If you already have a mass spectrometer and a nanospray source, changing to this type of device is not difficult," he said.