Key technology: mass spectrometry

A mass spectrometer determines the mass of a (bio)molecule by measuring the mass-to-charge ratio (m/z) of its ion. Ions are generated by inducing either the loss or gain of a charge from a neutral species. Once formed, ions are electrostatically directed into a mass analyzer where they are separated according to m/z and finally detected. The result of molecular ionization, ion separation, and ion detection is a spectrum that can provide molecular mass and even structural information.



Soft ionization methods: revolutionary tools

Over the past decades, mass spectrometry has undergone tremendous technological improvements allowing for its application to proteins, peptides, carbohydrates, DNA, drugs, and many other biologically relevant molecules. Due to ionization sources such as electrospray ionization (ESI) and matrix-assisted laser desorption/ ionization (MALDI), mass spectrometry has become an irreplaceable tool in the biological sciences. According to the late John B. Fenn, the inventor of electrospray ionization for biomolecules and the 2002 Nobel Laureate in Chemistry:

Mass spectrometry is the art of measuring atoms and molecules to determine their molecular weight. Such mass or weight information is sometimes sufficient, frequently necessary, and always useful in determining the identity of a species. To practice this art one puts charge on the molecules of interest, i.e., the analyte, then measures how the trajectories of the resulting ions respond in vacuum to various combinations of electric and magnetic fields. Clearly, the sine qua non of such a method is the conversion of neutral analyte molecules into ions. For small and simple species the ionization is readily carried by gas-phase encounters between the neutral molecules and electrons, photons, or other ions. In recent years, the efforts of many investigators have led to new techniques for producing ions of species too large and complex to be vaporized without substantial, even catastrophic, decomposition.



Further reading & teaching material

Introductory book about the concepts of protein mass spectrometry: 

Reviews on mass spectrometry based proteomics:

Book chapters on quantitative proteomics:

Advanced reading material:

A lot of information on proteomics and mass spectrometry can be found on the websites of the American Society for Mass Spectrometry (ASMS) and the Human Proteome Organization (HUPO). See also this useful links page.