Ion chemistry research earns NSF funding

A recently awarded grant from the National Science Foundation is supporting Washington State University chemistry researchers as they design, fabricate, and assemble a new class of analytical instrumentation.

The project is being led by WSU chemistry professor Brian Clowers, who specializes in metrology and analytical chemistry focusing on the precise characterization of molecules. His team will use the funding to develop instruments capable of performing controlled chemistry during ion mobility measurements.

"Ion mobility spectrometry is a common technique, which assesses how fast a molecule moves through a gas and is often used in security screening in airports," said Clowers. "We're trying to create a scenario of ion mobility systems where we can perform chemistry inside our instrument rather than using simply a pure gas."

Those scenarios envision an instrument in which selective chemistry is performed on certain molecular classes followed by additional measurements using mass spectrometry. These combined measurement techniques help scientists identify molecular differences among complex mixtures, proteins, and isomers, ensuring accurate chemical and elemental identification. Beyond applications such as airport security screening, the approach could help researchers track pollutants or trace chemicals in environmental samples, and detect subtle molecular differences that matter for drug development and disease diagnostics.

To rapidly evaluate different molecular configurations, Clowers and his research team have been manufacturing their own measurement platforms using printed circuit boards, crafting a technical solution where there was none before.

We're using these fabrication techniques to create thousands of electrodes to realize chemical separations and control chemical reactions.

"We're leveraging these economies of scale, these printed circuit board manufacturing techniques, which are very precise and very mature," said Clowers. "We're using these fabrication techniques to create thousands of electrodes to realize chemical separations and control chemical reactions."

The printed circuit boards feature serpentine channels and pathways with pixelated surfaces. In these new devices, two circuit boards are sandwiched together, forming a channel for ionized molecules. The pixelated surfaces on the circuit board are digitally controlled to create a traveling wave, pushing the ions down the channel and along the surface of the circuit boards.

"To realize separation based on size, the number of times a molecule rolls over the wave is indicative of the molecule's shape," said Clowers. "It's similar to surfing - some surfers might roll right over a wave, while others will be pushed along by the wave."

This information is useful for researchers since the molecular size is distinct from the molecular mass. "You can have two objects that have approximately the same weight, but can have radically different shapes," said Clowers. "By achieving complementary separation before the mass spectrometry analysis, we can more precisely characterize the chemical system."

The purpose of these new analytical tools and techniques is to enhance the information being derived from molecular biopolymers like glycans, peptides, proteins, and carbohydrates - all complex molecules that exhibit similar properties but behave very differently. Clowers also indicated lipids are another challenging class of molecules which require advanced approaches for accurate identification.

"It's very difficult to use mass spectrometry alone to determine the identity of a lipid, which typically has a long polymer-like tail that can hold many different isomers all with similar mass," said Clowers. "There are also other complexities, like the degree of unsaturation or where certain double-bond positions are on the lipid, that could be included in the measurement."

WSU's efforts to augment mass spectrometry analysis run parallel to similar research projects at the Pacific Northwest National Laboratory, housed in Richland, Washington. While PNNL focuses on making higher resolution components, Clowers believes that including selective chemistry in mass spectrometry analysis may increase the tool's effectiveness.

"One of the biggest challenges in the bioanalytical world is the idea of throughput, and how many samples you can run per unit time," said Clowers. "Our approach is to add controlled, targeted chemistries to the workflow that doesn't slow down the analysis process but does add more information alongside the mass measurement."

For now, Clowers and his research lab are enthusiastic to move forward with these analytical techniques. "There are a number of collaborators at other research institutions that are starting to build these devices based on the concepts we've developed," he said. "We're one of the few research groups developing this new class of instrumentation, and we're excited to see broader adoption of this technique."