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Dual Channel Electrospray Emitter Turns Taylor Cone into Reaction Chamber Upfront of Mass Spec

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A team led by researchers from New Zealand's Massey University has developed a dual-channel nano-electrospray emitter capable of combining sprays to enable reactions between molecules in the two channels upfront of mass spec analysis.

The emitter, which was detailed in a paper published this week in the European Journal of Mass Spectrometry, has a number of potential uses, including calibration of mass spec runs and chemical probing of samples, Massey researcher Peter Derrick told ProteoMonitor. Perhaps most significantly, he said, the method could streamline and simplify proteomics sample clean-up processes.

Electrospray ionization, or ESI, is one of the primary ionization techniques used in mass-spec based proteomics. In the method, liquid sample is channeled through a narrow capillary and out through an electric field at the capillary tip, which converts the sample into charged droplets that can then be injected into a mass spec for analysis.

As the liquid exits the capillary tip, it takes a cone shape from which emerge the charged droplets. The characteristic shape is named a Taylor cone in recognition of its first observer, British physicist Geoffrey Ingram Taylor.

In the EJMS paper, Derrick and his colleagues presented a dual-channel nano-electrospray device that combines the two sprays to create a shared Taylor cone that can then act as a reaction chamber for the contents of the two channels.

The researchers demonstrated the device via a series of reactions involving the antibiotic vancomycin, first combining flows containing vancomycin and the KAA molecule to which it binds and then combining flows containing vancomycin and deuterated vancomycin. In the first example, vancomycin-KAA complexes were subsequently detected by mass spec. In the second, the researchers detected heterodimers formed by interactions between normal vancomycin and deuterated vancomycin.

The publication follows a 2010 paper, also in EJMS, by a University of Geneva team led by Gerard Hopfgartner that presented a dual-channel microchip and demonstrated the formation of an organometallic complex in the resulting combined Taylor cone.

That device used channels roughly 200 μm in width, suitable, Derrick noted, for "pre-formed inorganic ions" but too wide for protein and peptide work. The Massey researchers brought the width down to 1 μm in their device, which "is what is needed for proteomics," he said.

The technique could have a number of practical applications, Derrick said, suggesting, for instance, use of the secondary channel to include a calibrant. Perhaps most interesting, he said, would be using the technique to simplify proteomics sample cleanup workflows.

Electrospray, Derrick noted, is a delicate process, occurring only under specific conditions. "Depending on the solution, it won't take place," he said. "If the ionic strength is wrong, if certain species are there, you won't get any spray. It's finely balanced, and so you can spend a lot of time getting a solution to spray."

Many of the reagents used by biologists in protein research don't work with electrospray, meaning that before mass spec analysis, considerable clean-up of proteomic samples is often required.

The Massey team's dual-channel approach could aid this process, Derrick said, by allowing researchers to do the clean-up in the Taylor cone.

"What you could do is just take a sample and put it down one [channel] and then create the right conditions for [electrospray] by tinkering with the solutions in the other channel," he said. "If we can put in the sample in any old form and out of the tip of the Taylor cone come the droplets that have the proteins we're interested in with all the detergents and salts and all the rest left behind, that would be tremendous."

He added that it could be particularly useful given the small sample sizes researchers often work with as it would minimize sample loss during the preparation process.

Derrick and his team are currently working to implement such a sample prep approach and plan to publish on it in the future, he said. "It's quite tricky, but it can be done."

Hopfgartner, who was not involved in the Massey researchers' study, agreed that such an idea was interesting, but suggested that further work was needed to demonstrate its feasibility. He added, though, that he could imagine a variety of applications for such a dual-channel device, including for online peptide derivatization and protein-protein interaction work.

"For example, you could put in additives to see if you could normalize the electrospray response… special additives not possible to add on the chromatography side," he said.

Hopfgartner added that the small size and timescale of the Taylor cone reaction chamber allowed for the study of very brief interactions, where, "if you mix it beforehand, by the time it comes to the sprayer it is far too late."

"People might criticize [the approach] and say, 'Well, I could just do everything by mixing it before [and running it through a] single electrospray,' but that is not the same process," he said. "This is really a microsecond type of reaction. It's a very small reaction chamber and the residence time is very short, so only certain interactions can occur."

Given the early stages of the technology, however, Hopfgartner was skeptical of its current commercial potential. "The problem with many analytical tools in proteomics is that people like to have finished solutions," he said. "Here you still have to do some fundamental studies to really understand the benefits."

Derrick said his team's dual-channel emitter was "quite tricky" to build but could be mass produced fairly easily were a vendor interested in doing so. He added that he had not patented the technique and thought that given the amount of information on it that had been disclosed it was no longer possible to do so.

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