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New Multinozzle Emitter Could Increase Throughput and Sensitivity of Nanoflow-ESI-MS


By Adam Bonislawski

Researchers at Lawrence Berkeley National Laboratory have developed silicon-based multinozzle emitter arrays for integrating lab-on-a-chip technology with electrospray mass spectrometry that they say could offer significant improvements in both the sensitivity and throughput of nanoflow-ESI-MS systems.

In a study published online last week in Analytical Chemistry, they detailed an MEA chip consisting of 96 identical 10-nozzle emitters in a circular array on a 3-inch silicon chip, demonstrating a potential three-fold improvement improvement over standard capillary nanoflow sensitivity and achieving flow rates of up to 10 microliters per minute.

The work follows on research the group published in 2007 also in Analytical Chemistry, on a microfabricated multinozzle system (PM 05/31/2010), said LBNL scientist Daojing Wang, the senior author on the study. Since that publication, he said, technological improvements have allowed the team to increase the number of emitters per chip from one to the current 96 and the number of nozzles per emitter from four to a possible 40 or even higher.

The increase in emitters allows for higher-throughput experiments, as each emitter can be interfaced to a separate LC system allowing for rapid sequential or parallel mass spec analysis, while the increase in nozzles provides an improvement in sensitivity proportional to the square root of the number of nozzles.

"Multiple nozzles increase sensitivity, and multiple emitters increase throughput, so with one design we're able to solve two problems at the same time," Wang told ProteoMonitor.

The increase in emitters was enabled by a circular array design that allowed the researchers to fit 96 on the 3-inch chip. That design can also be scaled up to 384 emitters on a 6-inch chip, Wang noted.

The additional nozzles were made possible by sharpening the shape of emitter stems, he said, which improved the electric fields required for electrospray ionization, letting the device run at significantly reduced operating voltages.

"Previously we could only do four or five nozzles [per emitter] because of the constraints on the voltage supply," he said. "Now, though, because we were able to sharpen the emitter so that the electric field was dramatically improved, we're able to do as many as 40."

Taking full advantage of the sensitivity improvement offered by the increased nozzle number will require some tweaks on the input side of the mass spectrometer the MEAs are interfacing, however.

Although the 10-nozzle emitter should theoretically give a sensitivity improvement of roughly three-fold over the single-nozzle emitter, in the study it only showed a two-fold increase experimentally. This, Wang said, is because the inputs on conventional mass spectrometers aren't wide enough to match the multinozzle and collect ions from all the nozzles.

If the group were able to team up with a mass spec vendor to widen the ion cone slightly, he suggested, they could achieve "a dramatic increase in sensitivity."

"We just need to modify the [mass spectrometer's] ion cone a little bit," he said. "It would be very small adjustment."

While the separations performed as part of the current Analytical Chemistry study were done using an offline LC system, the researchers have since managed to do the separations on the chip itself, Wang noted.

"We've actually achieved that, but we haven't published it yet," he said.

Wang said his team has yet to get in touch with any mass spec vendors about the device. He noted that they had previously had discussions with Thermo Fisher Scientific following their 2007 publication detailing the original multinozzle device.

The group has filed patents related to the technology and are "thinking about multiple strategies" for commercialization, he added.

Have topics you'd like to see covered in ProteoMonitor? Contact the editor at abonislawski [at] genomeweb [.] com.