Vol 3. Issue 31 / October 18, 2004
Mass Spectrometry Down to the "Yoctomole"
By Jason Socrates Bardi
We are a culture obsessed with superlatives: the most expensive apartment in New York City; the fastest man alive; the most home runs in a baseball season; the best Italian restaurant in San Diego; the most people in a VW Bug. Most compelling is a record being broken. There is something fundamentally human about pushing limits we find once we have established them—the highest mountain, the deepest ocean depths, furthest reaches of the universe.
For mass spectrometry, the analytical tool for weighing molecules, the question is: how few molecules can you have in a sample and still be able to detect them?
Two decades ago, mass spectrometers were detecting nanomoles of material. A mole is an extraordinarily huge number (6.022 x 1023, as any former student of chemistry can rattle off). So a nanomole (10-9 moles), while much smaller, is still a very large number (a nanomole of salt ions is more than 600 trillion ions).
As technologies and techniques of mass spectrometry improved, scientists began to detect picomole amounts of substances (10-12 moles), and today's mass spectrometers can routinely detect such low amounts. Ten years ago, attomole detection (10-18 moles) was announced, and this was soon followed by hundreds of zeptomole detection (10-21 moles).
Recently, individuals in the Center for Mass Spectrometry at The Scripps Research Institute reached the level of the zeptomole (10-21 moles). They then decided to take it even further, and in an article appearing in a recent issue of the journal Analytical Chemistry, they announce a new record detection limit for mass spectrometry—the lonely yoctomole.
They were able to detect a mere 800 yoctomoles of an inflammatory peptide called bradykinin—a standard benchmark molecule used in mass spectrometry today.
Achieving this limit was certainly a noteworthy accomplishment, but the paper also hails an advance of a technique that has been pioneered in the Center called desorption-ionization on silicon (DIOS). DIOS is a technique where small volumes of liquid sample are placed on a porous silicon surface and then blasted with a laser, which desorbs the molecules off the surface as ions. These ionized molecules are then detected by the instrument and their mass is analyzed by software, which can usually determine automatically what molecules the sample contained.
In order to achieve the sensitivity reported in the Analytical Chemistry paper, the silicon was modified with chemicals called fluorinated silanes, which permitted the bradykinin molecules to be more efficiently desorbed and ionized. This allowed bradykinin to be detected with fewer molecules in the sample.
This record of 800 yoctomoles was 50-fold more sensitive than the previous reported limits of detection, and is close to the limit of detection for any analytical method. In fact, 800 yoctomoles is only 480 molecules, which means that the members of the Center cannot do much better and will not keep setting new records indefinitely—unless they plan to all jump inside a VW bug and ride around the block.
To read the article "High Sensitivity and Analyte Capture with Desorption/Ionization Mass Spectrometry on Silylated Porous Silicon" by Sunia A. Trauger, Eden P. Go, Zhouxin Shen, Junefredo V. Apon, Bruce J. Compton, Edouard S. P. Bouvier, M. G. Finn, and Gary Siuzdak, see the journal Analytical Chemistry, 76, 4484–4489 (2004); or go to http://dx.doi.org/10.1021/ac049657j.
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Team Yoctomole—investigators Eden Go, Jon Apon and Sunia Trauger (left to right)—in a VW Bug.