With it, it is possible to measure the mass spectrum of complex proteins, extremely fragile molecular assemblies and even intact cells
Mass spectrometry (MS), arguably the most important analytical spectroscopic tool of modern times, is in its centenary year in 2013 along with two other celebrated discoveries of science, the Bohr atom model and the chemical bond of G. N. Lewis; both have profound connections to the first.
Sir J.J. Thomson, a Nobel Laureate, also known for the discovery of electrons, built the first rudimentary mass spectrometer in 1913 (it was built earlier, but a full description appeared in this year) which identified the existence of isotopes — atoms differing in mass but having the same atomic number and therefore occupying the same position in the periodic table (‘isos’ is equal and ‘topos’ is place, in Greek).
His student, Aston, who built more mass spectrometers, expanded the discipline, identified 212 of the 287 naturally occurring isotopes and became the first Nobel Laureate in Chemistry in the area. Five Nobel Prizes have been awarded to MS pioneers.
Mass spectrometry is a way to measure the mass of ions — electrically charged species, derived from atoms or molecules. In the preface of his celebrated book, Rays of Positive Electricity and Their Application to Chemical Analyses (1913) Thomson stated, “I feel sure that there are many problems in Chemistry which could be solved with far greater ease by this than by any other method. The method is surprisingly sensitive — more so even than that of Spectrum Analysis, requires an infinitesimal amount of material, and does not require this to be specially purified…”. The words were prophetic. Today, there is no single area of experimental science where mass spectroscopy is not being used. There is no university or research institution in the developed world without a mass spectrometer; this may even be said about India.
The technique is used to explore the chemical constitution of molecules from this planet and beyond, e.g. the hydrocarbon “seas” of Saturn’s moon Titan.
It is used to understand the fundamental atomic and molecular processes and at the same time those of immediate relevance to events within cells. As a technique, it helps to control processes in chemical and biological industries, diagnose diseases, discover new drugs, protect the environment and explore mysteries of nature.
In 100 years, it has been used to separate much of the uranium 235 used to make the Little Boy (the bomb that was dropped onto Hiroshima in 1945), led to understanding of thousands of chemical reactions, to the discovery of new molecules, to the resolution of protein structures, to solve crimes and to provide answers to complex questions of nature.
Mass spectrometers require a way to produce ions — e.g. remove or add electrons, generally one electron — to the sample, then analyse the mass of the ion formed and detect it.
In each of these areas (forming ions, analysing their mass, detecting them) innovations have led to multiple mass spectrometric techniques.
The most important developments have happened in ion formation. Years ago, it was necessary to evaporate a sample to generate vapours and bombard these with a stream of electrons in order to make ions, a process which required vacuum. This was possible only with simple molecules which can be evaporated, generally by heating. Today it is possible to measure the mass spectrum of complex proteins, extremely fragile molecular assemblies and even intact cells, none of which evaporate normally. It is now possible to measure mass spectra of ultra small volumes, as small as a single human cell.
It is possible to understand the spectrum of molecules from the surface of a rose while the plant is alive. Mass spectra of molecules — metabolites or drugs or cancer markers — can be measured on a patient’s skin or in his/her blood.
Mass spectrometers may soon arrive in physicians’ consulting rooms. It has been demonstrated that they can help in diagnosis during complex surgeries within the operating theatre.
Ions are enjoying a considerable following these days. The mass spectrometry community is probably the largest group of scientists working around a single tool. However, despite this large following, it is surprising that mass spectrometry is being removed gradually from our science curriculum. Mass spectrometry concerns ion chemistry and physics with an emphasis on scientific instrumentation.
However, in the past several years, paralleling the growth of applications of the method, spectrometers have become black boxes for the vast majority. Sadly, in the process, Thomson is forgotten.
Appreciation of instrumentation should be brought back to the curriculum. We must note that Thomson, after considerable work in theoretical physics, moved to experiments. The Nobel committee over many years has demonstrated its appreciation for scientific instrumentation; this is a lesson we in India cannot afford to discard.
(The author is a Professor of Chemistry at IIT Madras)