Bio-MS

Courtesy: Human Genome Program, U.S. Department of Energy, Genomics and Its Impact on Science and Society: A 2008 Primer, 2008. (Original version 1992, revised 2001 and 2008.) http://genomicscience.energy.gov.

Now the biological research community had not one, but two powerful analytical tools at their disposal: ESI and MALDI-ToF. Each provided a different approach to research, leading to an explosion of “omics” methods for each class of biological compounds. MALDI and ESI furthered the reach of mass spectrometry within biological research, as the techniques allowed for analysis of peptides, proteins, carbohydrates, and oligonucleotides. Vestal, whose thermospray method was the method for ionization, saw the potential of the new techniques as an opportunity:

I decided that the days of thermospray were numbered, but we needed to move into this new technology. So we did some work on both electrospray and MALDI, but it was pretty clear after we put [the] electrospray source on our dedicated system that we’d done thermospray on. But it was pretty clear to me right then . . . you know, everybody was jumping on electrospray and [. . .] there wasn’t much incentive for us to try to compete on that level. But nobody was doing that much with MALDI. So we decided to build MALDI systems. (63)

By the 1990s, with the help of Vestal and others, the price and size of these new instruments had decreased, and more labs could have an instrument of their own for proteomics research projects. Mass spectrometry could at last identify proteins both rapidly and accurately, making mass spectrometry an integral part of cutting-edge biological research. Researchers noted that both MALDI and ESI were significant for their speed, accuracy, sensitivity, and mass range when gaining information on the molecular weight of biological samples. Today, mass spectrometry is able to provide information about complex nonvolatile biological molecules with masses ranging up to 100,000 daltons, a feat unimaginable several decades ago. The capabilities of mass-spectrometry instrumentation continued to change in favor of greater sensitivity toward molecules that were more difficult to detect. One mass-spectrometry professional noted, “The question changed from ‘How much protein do you need?’ to ‘How little protein can you work with and still tell me what I need to know?’” (Nawrocki, “Mass Spectrometry”).

 

Marvin Vestal discusses MALDI and Electrospray.

The developments in both mass-spectrometry instrumentation and proteomics built on that early period of work by pioneers like Biemann:

Mass spectrometry may be the only technique that is sensitive enough to structurally analyze proteins. Much of Klaus Biemann’s early work plays in to that field. It involved the interpretation of mass spectra and the concept of deciphering a definite structure that may only result from a particular group of masses. His concepts have advanced rapidly since their inception, and now the field of proteomics relies heavily on this work. I assume that some of the employees of Perkin-Elmer, who are now in Foster City, must have some thoughts about the growth and advancement of the mass-spectrometry field. (Vincent Coates, 41)

Today, mass-spectrometry instrumentation is a given in any proteomics lab. Mass spectrometry’s central role in proteomics has moved the field forward in a variety of ways: proteomics’ practical applications are far-reaching. Identifying and sequencing the human genome has allowed researchers to identify proteins associated with various diseases—along with potential drugs to treat those diseases. Personalized medicine becomes a reality as more proteins are sequenced. Even conditions like heart disease and Alzheimer’s have protein biomarkers that can now be studied for future treatment possibilities.

 

Mass spectrometry and biology: moving forward

The disciplinary lines often blur between the chemistry, biology, and proteomic uses of mass spectrometry. Indeed, the fields of biology, chemistry, and mass spectrometry have been interwoven for the past 50 years. However, today’s practitioners are not perhaps as hands-on or as knowledgeable about the intricate details of the instrumentation as were the pioneers of the field who built and modified their own instruments:

Hear Klaus Biemann: Today’s mass spectrometry is so different from what it was 50 years ago, 30 years ago, or even 20 years ago. Now it’s so highly automated to the point that when you put in the sample and click the “on” button, it tells you what it is by searching the NIST [National Institute of Standards and Technology] library right away. Then even in protein chemistry, what’s now called proteomics, you don’t have to interpret anything anymore because it’s all automated with the human genome and many other genes of many other classes of organisms known. You can, as you know, digest the protein with trypsin and separate it on a gel. Then run it either by ESI or MALDI to get all the molecular weights or at least two-thirds of the molecular weights, and then it’s purely a computer problem to match those with all the proteins which the genome information contains, and you’ll find out what it is. And then all you need to find out is how it was modified. But again, just look at the shifts in molecular weights to see whether there is a phosphate group or not, and if so, whether it’s one or two, and things like that. It’s not that you look at the data and have to use your experience to interpret it. It’s all very much faster. It produces so much more data that the human mind could not possibly do it in the intellectual way. You have to use computers to help, and it’s certainly a great help. It solves the problems and you don’t have to have five years’ experience in basic mass spectrometry. Most of the people nowadays push the “on” button and don’t know what’s behind the panel. If it doesn’t work, you call in the service man or push another button, and it tells you to check this or check that or tells you that you don’t have accelerating voltage and you better check that connection. It has changed very much. Now, I think the largest use is routine applications of the method. It’s like milk where the cream is on the top. There is a small layer of people who do actual research in mass spectrometry, and it would be an interesting paper study to see in what kind of institutions and departments that layer is. I think that there would be relatively few of them found in an analytical division at a university. (Biemann, 40–41)

While many of today’s users of mass spectrometry in biological applications may not be as familiar with their instrument as Biemann, Field, or Cohn, the work of these pioneers has set this ease of research in motion. No longer does a researcher need to worry about building his or her own instrument, and the instrumentation is far more stable than it was over 60 years ago. Mass spectrometry is now an instrument of the scientific masses. With that ease of research and a history of hardy pioneers and innovative researchers, the possibilities for the instrument within the discipline of biology continue to grow.

Alfred Nier, Another View

Beginning in the 1960s Alfred Nier teamed with NASA to send mass spectrometers into space, as featured on the Periodic Tabloid. Read More >

Mass Spectrometry Applications

Listen to the CHF podcast, Distillations, episode 144: Mystery of Mass (Spec), 
discuss achievements in mass spectrometry from the Manhattan Project to the present. Featuring excerpts 
from Alfred Nier’s oral history. Listen >

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