NSF Funding Awarded to CMU Scientist

When most people think of a chemistry lab, they imagine beakers of smoky green liquid, Bunsen burners, and the occasional explosion. Mark Bier’s lab looks more like the engine room of the starship Enterprise. Located on the top floor of the Mellon Institute, the lab’s main features are three giant mass spectrometers, all built in part by Bier. These machines are used to measure the mass of extraordinarily small particles, and Bier’s specialty is pushing the envelope of how massive a molecule he can measure.

In fact, Bier, director of the Center for Molecular Analysis in the Department of Chemistry, is so good that the National Science Foundation’s Instrument Development for Biological Research program has recently granted him $546,000 to build a novel mass spectrometer. At most, “mass-specs” can measure particles in the kiloDalton mass range. Bier’s proposal is for a novel machine that could measure molecules in the megaDalton mass range.

According to a January 10 CMU press release, Bier is very excited about the potential of this new technology in a variety of fields. “This is a new frontier in mass spectrometry research. We anticipate that this work will help to advance research in proteomics, virology, molecular biology and nanotechnology.”

Mass spectrometers are used to determine the weight, structure, and composition of molecules. These machines are best at measuring masses on the atomic level. Due to the physics of their design, the larger the mass of the particle in question, the worse the performance. Thus chemists and biologists who seek to understand molecules of larger size and complexity, such as proteins and viruses, are forced to break these molecules into much smaller pieces. This “bottom-up” approach is both time-consuming and inaccurate.

With his new mass spectrometer, Bier hopes to enable a “top-down” approach to molecular analysis. A scientist initially analyzes the intact particle, and then breaks it into smaller pieces for further investigation. This technique reduces sample loss and provides a powerful new research tool for scientists to characterize large molecules such as proteins with masses over 150 kiloDaltons — about twice the mass of the hemoglobin molecule.

To communicate the significance of this project, Bier calls his quest “Project Flora,” after Flora, a “flying” African circus elephant. The name was suggested by a colleague who noted the similarity between a flying elephant and the particles Bier proposes to measure. Bier now keeps a picture of Flora in the front of his logbook.

Bier has already made a large contribution to the field of mass spectroscopy. Before coming to CMU, Bier worked for the Thermo Electron Corporation, where he co-invented the linear ion trap. The linear ion trap was a breakthrough over older ion traps because it was faster and offered improved sensitivity. Bier’s invention was commercialized in 2002, and is now used around the world.

Now Bier hopes to push the limit even further. By combining components that he has built or modified himself, Bier hopes to build a mass spectrometer that can efficiently characterize large viral complexes and ribosomal particles. To the layman, this may not seem remarkable, but to Carnegie Mellon biologist John Woolford, it is very important. “Mark’s new generation machine might enable us to detect essential but small modifications of pre-ribosomes and mature ribosomes. We could do these experiments in much less time without having to fractionate the complexes into their many components. Mark’s facility and his help and advice have significantly empowered biological research here [in Pittsburgh].” The new spectrometer will allow scientists like Woolford to better study the parts of ribosomes, molecules in the cell responsible for making proteins. By effectively analyzing large molecules without having to break them into smaller components, the novel machine will allow biologists to better study large protein and ribosomal complexes.

A typical mass spectrometer works by electrically charging sample particles, linearly accelerating them through an electric field, and then passing the particles through a magnetic field, which curves their path. The amount of path curvature is directly related to the mass of the particle. The key to Bier’s new mass spectrometer is the combination of a special mass analyzer of his own invention with a cutting-edge cryodetector.

Cryodetector technology, originally developed for particle physicists to detect charged particles, was further developed by engineers at Comet AG in Flamatt, Switzerland, for use with mass spectrometry. The key feature of this intrument is its sensitivity to kinetic energy instead of velocities. Therefore, large particles will no longer have to be accelerated to the high velocities required in a typical mass-spec, which would cause their disintegration. The other key component to Bier’s plan is a custom-designed mass analyzer, which will be used to vaporize and then separate charged particles by their unique mass-to-charge ratio without destroying them.

Although Bier estimates that it will take at least 18 months to build the device, he has already started ordering parts. He is seeking interested science undergraduates from CMU to help in the machine’s construction this summer.

Ultimately, Bier dreams of building a mass spectrometer that can analyze cell-sized particles. He admits that this will not happen for years, but given his past success, we might be hearing about something — called, perhaps, “Project Blue Whale” — in the future.