PNNL

PNNL scientist and Battelle Fellow Richard D. “Dick” Smith, an internationally recognized voice in using mass spectrometry, will receive the 2019 Marcel Golay Award on May 14, 2019, during the 43rd International Symposium on Capillary Chromatography (ISCC) in Fort Worth, Texas.

He is being recognized for his contributions involving various kinds of separations with mass spectrometry (MS).

The ISCC meeting is the preeminent annual event for researchers who use analytical separations for a broad range of applications.

In the case of MS, Smith’s specialty, ions are generally formed by attaching a charge to compounds after their separation, such as by using liquid chromatography—a process that needs to be done in a gas or in vacuum.

In more recent contributions, he is using ion mobility, where the separations take place after ionization. That has the benefit of being more than a hundred times faster than in liquids, and more sensitive as well. Such separations also allow researchers to make previously impossible measurements with MS. 

Smith, who holds 66 patents and has received 12 R&D 100 awards (the most for anyone), is known for his breakthrough applications and inventions, and especially for those that enable the broad biological measurements of proteins, metabolites, lipids, and more—which are important in essentially all areas of biological research.

He called the Golay Award an honor—“recognition for developments in the separations themselves, as well as their combination with mass spectrometry.”

Smith also sees the award as “reflective of the growing appreciation that progress often occurs at the interface of different fields, as well as in ways that can be surprising from the perspective of one of the fields.”

The prestigious annual award is named after gas chromatography pioneer Marcel Jules Edouard Golay (1902-1989). In the 1950s, Golay—a Swiss national working in the United States—invented open-tubular (capillary) columns that made separating chemical samples faster and more accurate. He also developed a related theory of sample dispersion at the head of such columns.

Golay improved the way gas chromatography (GC) could be coupled with MS. The first vaporizes, and then separates, the sample component compounds. The second ionizes the compounds by adding electrical charge, and separates them by mass to provide a spectrum of compounds. (Hence: “mass” and “spec.”)

Together, GC/MS have provided much better analyses than previously possible for the volatile compounds that can be separated by GC.

Smith’s developments have been in broadening the applicability of mass spec to other compounds, such as those of biological interest. (Nonvolatile compounds must be separated by methods other than GC.)

A ‘Visionary’

Still, all his roles and even all his papers hardly express the magnitude of Smith’s impact on a field he started mastering in 1976, the year he arrived at PNNL. Soon after getting to the lab he constructed a mass spectrometer and combined it with another separation technique called liquid chromatography.

Smith went on to oversee advances at PNNL, starting in the 1980s with other novel mass spectrometry combinations, especially those with supercritical fluid chromatography and capillary electrophoresis. The latter, which was enabled by a then-new technology called electrospray ionization, began an era at PNNL where analyzing biological samples took off.

Among colleagues in the mass spec world at large, Smith is called a “visionary,” a term used in the introduction to a 2014 special issue of the Journal of the American Society for Mass Spectrometry that celebrated his accomplishments with eight papers inspired by his work.

Just the year before, in 2013, Smith had received an American Society for Mass Spectrometry award for his development of the electrodynamic “ion funnel,” now widely used in high-performance mass spectrometers.

Much earlier, in 1999, the device earned Smith and his team an R&D 100 award.

“We built it initially to increase the sensitivity of mass spectrometry,” said Smith. “But its fundamental concepts, and the actual implementations, have continued to open more doors.”

Boosts to Biological Sampling

The ion funnel increased the sensitivity of MS analyses to the degree that they became profoundly useful for biological and biomedical applications.

Biological samples are often very small and come in concentrations so low that the mass spec technologies of 20 years ago could not have detected them.

Today, mass spec analyses are possible even down to the level of single cells. Smith’s ion funnel was one key to making all this possible.

More recently, by employing the same ion-confinement physics that informed the ion funnel, Smith’s efforts further enhanced the sensitivity of mass spec analyses as well as separations after ionization. He did that by using ion mobility in what he calls Structures for Lossless Ion Manipulations, or SLIM.

Among other things, SLIM allows fast ion mobility separations to be done with more resolution and more sensitivity than previously possible. In addition, the ions can pass through without any loss. “SLIM is opening new avenues for analytical measurements,” said Smith.

The innovative technology, still being enhanced today, won an R&D 100 award in 2017.

The technology will also be the subject of a nearly hour-long presentation Smith will make after receiving the Golay Award on May 14.

SLIM will help personalize medicine, he said, and could soon improve analyses needed for environmental management and clean-energy research.

Eventually, scientists at the lab will hitch SLIM mass spec to a separation technology capable of manipulating vanishingly small samples.

“That’s the aim, the ultimate challenge,” said Smith, “to do really detailed analysis on even the smallest samples, such as single biological cells. It’s something that would provide research insights we could not obtain in any other way, and would lead to many practical benefits in health and medicine.”