INNOLAB magazine #632

Page 50

āļ•āđˆāļēāļ‡āļĻāļąāļāļĒāđŒāļŠāļđāļ‡āļœāđˆāļēāļ™āļĨāļ‡āđ„āļ›āđƒāļ™āļ‚āļ­āļ‡āđ€āļŦāļĨāļ§āļ—āļĩāđˆāđ€āļ„āļĨāļ·āđˆāļ­āļ™āļ—āļĩāđˆ āļœāđˆāļēāļ™āļ—āđˆāļ­āļ‚āļ™āļēāļ”āđ€āļĨāđ‡āļāļ—āļĩāļŠāđˆ āđ€āļ›āļĢāļĒāđŒāļĨāļ°āļ­āļ­āļ‡āļŠāļēāļĢāđ€āļ›āđ‡āļ™āļŦāļĒāļ” āļ‚āļ™āļēāļ”āđ€āļĨāđ‡āļāļ—āļĩāļ›āđˆ āļĨāļēāļĒāļ—āđˆāļ­ āđāļĨāļ°āļŠāđ€āļ›āļĢāļĒāđŒāđ‚āļ”āļĒāļ•āļĢāļ‡āļŠāļđāļ—āđˆ āļēāļ‡ āđ€āļ‚āđ‰āļēāđ€āļ„āļĢāļ·āđˆāļ­āļ‡āđāļĄāļŠāļŠāđ€āļ›āļ„āđ‚āļ•āļĢāļĄāļīāđ€āļ•āļ­āļĢāđŒ āļ‚āļ­āļ‡āđ€āļŦāļĨāļ§āļ–āļđāļ āđāļĒāļāļ­āļ­āļāļˆāļēāļāļŦāļĒāļ”āļŠāļēāļĢāđ‚āļ”āļĒāđƒāļŠāđ‰āļ„āļ§āļēāļĄāļĢāđ‰āļ­āļ™āļ—āļģïŋ―āđƒāļŦāđ‰ āđ€āļāļīāļ”āđ€āļ›āđ‡āļ™āļĨāļģïŋ―āļ­āļīāļ­āļ­āļ™ ESI āļˆāļ°āļŠāļĢāđ‰āļēāļ‡āļ›āļĢāļ°āļˆāļļāđ€āļžāļīāđˆāļĄāđƒāļŦāđ‰ āļāļąāļšāļ­āļīāļ­āļ­āļ™ āļˆāļķāļ‡āļŠāđˆāļ§āļĒāļĢāļąāļšāļ›āļĢāļ°āļāļąāļ™āļ§āđˆāļēāļ„āđˆāļēāļĄāļ§āļĨāļ•āđˆāļ­ āļ›āļĢāļ°āļˆāļļ (m/z) āļ‚āļ­āļ‡āļŠāļēāļĢāđ‚āļĄāđ€āļĨāļāļļāļĨāđƒāļŦāļāđˆāļˆāļ°āļ­āļĒāļđāđˆāđƒāļ™ āļŠāđˆāļ§āļ‡ 800-1,000 āļŦāļ™āđˆāļ§āļĒāļĄāļ§āļĨāļ­āļ°āļ•āļ­āļĄ āļ‹āļķāļ‡āđˆ āđ€āļŦāļĄāļēāļ° āļāļąāļšāļ„āļ§āļēāļĄāļŠāļēāļĄāļēāļĢāļ–āđƒāļ™āļāļēāļĢāļ•āļĢāļ§āļˆāļˆāļąāļšāļ‚āļ­āļ‡āđ€āļ„āļĢāļ·āđˆāļ­āļ‡ āđāļĄāļŠāļŠāđ€āļ›āļ„āđ‚āļ•āļĢāļĄāļīāđ€āļ•āļ­āļĢāđŒāđƒāļ™āļ›āļąāļˆāļˆāļļāļšāļąāļ™

Mass spectrometry has become an essential tool for the pharmaceutical industry.

Article info John R Yates III. (2011). A century of mass spectrometry: from atoms to proteomes. Historical commentary. Special feature. Nature methods. Vol.8, No. 8 50

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āļāļēāļĢāļ›āļĢāļēāļāļŽāļ•āļąāļ§āļ‚āļ­āļ‡āđ‚āļ›āļĢāļ•āļĩāđ‚āļ­āļĄāļīāļāļŠāđŒ āļ„āļ§āļēāļĄāļŠāļēāļĄāļēāļĢāļ–āđƒāļ™āļāļēāļĢāļˆāļģïŋ―āđāļ™āļāđ‚āļ›āļĢāļ•āļĩāļ™āđƒāļ™āļ‚āļ­āļ‡āļœāļŠāļĄ āđāļĨāļ°āļŦāļĨāļąāļ‡āļˆāļēāļāļāļēāļĢāļˆāļēāļāļāļēāļĢāļ›āļĢāļąāļšāđāļ•āđˆāļ‡āļ—āļĢāļēāļ™āļŠāđ€āļĨ āļŠāļąāļ™ (Post-translational modification) āđ‚āļ”āļĒāđƒāļŠāđ‰āđāļ—āļ™āđ€āļ”āļĄāđāļĄāļŠāļŠāđ€āļ›āļ„āļ•āļĢāļąāļĄāđāļĨāļ°āļāļēāļ™āļ‚āđ‰āļ­āļĄāļđāļĨ āļĨāļģïŋ―āļ”āļąāļšāđ‚āļ›āļĢāļ•āļĩāļ™ āđ€āļ›āđ‡āļ™āļāļēāļĢāļŠāļĢāđ‰āļēāļ‡āļ„āļ§āļēāļĄāđāļ•āļāļ•āđˆāļēāļ‡ āļˆāļēāļāđāļ™āļ§āļ—āļēāļ‡āđ€āļ”āļīāļĄāđāļĨāļ°āļ™āļģïŋ―āđ„āļ›āļŠāļđāđˆāļ§āļīāļ˜āļĩāļāļēāļĢāļ—āļĩāđˆāđ€āļĢāļĩāļĒāļāļ§āđˆāļē Shotgun proteomic – āļ‹āļķāđˆāļ‡āđ€āļ›āđ‡āļ™āļ§āļīāļ˜āļĩāļāļēāļĢāļ—āļĩāđˆ āļŠāđˆāļ§āļĒāđƒāļŦāđ‰āļŠāļēāļĄāļēāļĢāļ–āļ§āļąāļ”āļ„āđˆāļēāđ‚āļ›āļĢāļ•āļĩāļ™ āđƒāļ™āļŠāļēāļĢāļ›āļĢāļ°āļāļ­āļš āđ‚āļ›āļĢāļ•āļĩāļ™āđ€āļŠāļīāļ‡āļ‹āđ‰āļ­āļ™ āļ­āļ­āļĢāđŒāđāļāđāļ™āļĨ āđ€āļ‹āļĨāļĨāđŒ āđāļĨāļ° āđ€āļ™āļ·āđ‰āļ­āđ€āļĒāļ·āđˆāļ­ āļĢāļ§āļĄāļ—āļąāđ‰āļ‡āļāļēāļĢāļ§āļąāļ”āļ„āđˆāļēāļŦāļĨāļąāļ‡āļˆāļēāļāļāļēāļĢāļˆāļēāļ āļāļēāļĢāļ›āļĢāļąāļšāđāļ•āđˆāļ‡āļ—āļĢāļēāļ™āļŠāđ€āļĨāļŠāļąāļ™ āđ‚āļ”āļĒāđ„āļĄāđˆāļ•āđ‰āļ­āļ‡āđāļĒāļ āđ‚āļ›āļĢāļ•āļĩāļ™āđāļ•āđˆāļĨāļ°āļŠāļ™āļīāļ”āļ­āļ­āļāļĄāļē āļāļēāļĢāļˆāļģïŋ―āđāļ™āļāđ‚āļ›āļĢāļ•āļĩāļ™ āļ—āļĩāļĢāđˆ āļ§āļ”āđ€āļĢāđ‡āļ§āđāļĨāļ°āļ–āļđāļāļ•āđ‰āļ­āļ‡āļˆāļ°āđ€āļžāļīāļĄāđˆ āļ„āļ§āļēāļĄāļāđ‰āļēāļ§āļŦāļ™āđ‰āļēāđƒāļ™ āļāļēāļĢāļ„āđ‰āļ™āļžāļšāļ”āđ‰āļēāļ™āļŠāļĩāļ§āļ§āļīāļ—āļĒāļē āđ‚āļ”āļĒāļāļēāļĢāļ—āļģïŋ―āđƒāļŦāđ‰āļ‚āļ™āļąāđ‰ āļ•āļ­āļ™ āđƒāļ™āļāļĢāļ°āļšāļ§āļ™āļāļēāļĢāļ„āđ‰āļ™āļŦāļēāļĨāļģïŋ―āļ”āļąāļšāđ‚āļ›āļĢāļ•āļĩāļ™āļ—āļĩāđˆāđƒāļŠāđ‰āđ€āļ§āļĨāļē āļĄāļēāļāļ—āļĩāđˆāļŠāļļāļ” āļĄāļĩāļ„āļ§āļēāļĄāđ€āļĢāļĩāļĒāļšāļ‡āđˆāļēāļĒāļĒāļīāđˆāļ‡āļ‚āļķāđ‰āļ™ āļ„āļ§āļēāļĄāļŠāļēāļĄāļēāļĢāļ–āđāļĨāļ°āđāļ­āļžāļĨāļīāđ€āļ„āļŠāļąāļ™āđƒāļŦāļĄāđˆāđ€āļŦāļĨāđˆāļēāļ™āļĩāđ‰ āđ€āļ›āđ‡āļ™āđāļĢāļ‡āļœāļĨāļąāļāļ”āļąāļ™āļ—āļĩāđˆāļĢāļ§āļ”āđ€āļĢāđ‡āļ§ āļ—āļĩāđˆāļ—āļģïŋ―āđƒāļŦāđ‰āđ€āļ—āļ„āđ‚āļ™āđ‚āļĨāļĒāļĩ āđāļ—āļ™āđ€āļ”āļĄāđāļĄāļŠāļŠāđ€āļ›āļ„āđ‚āļ•āļĢāđ€āļĄāļ—āļĢāļĩ āđ€āļāļīāļ”āļāļēāļĢāļžāļąāļ’āļ™āļē āđ€āļ„āļĢāļ·āđˆāļ­āļ‡āđāļĄāļŠāļŠāđ€āļ›āļ„āđ‚āļ•āļĢāļĄāļīāđ€āļ•āļ­āļĢāđŒāđāļšāļšāđƒāļŦāļĄāđˆ āđ€āļŠāđˆāļ™ Linear ion traps, Quadrupole/timeof-flights, Time-of-flight/ time-of-flight, Ion mobility āđāļĨāļ° Orbitrap āļ—āļĩāđˆāļĄāļĩāļāļēāļĢāļ•āļ­āļš āļŠāļ™āļ­āļ‡āļ—āļĩāļ”āđˆ āļ‚āļĩ āļ™āļķāđ‰ āļĄāļĩāļ„āļ§āļēāļĄāđ€āļĢāđ‡āļ§āđƒāļ™āļāļēāļĢāļŠāđāļāļ™āđāļĨāļ°āļ„āļ§āļēāļĄ āļĨāļ°āđ€āļ­āļĩāļĒāļ”āļ—āļĩāđˆāļĄāļēāļāļ‚āļķāđ‰āļ™ āđāļĨāļ°āļĢāļ°āļšāļļāļĄāļ§āļĨāđ„āļ”āđ‰āļ–āļđāļāļ•āđ‰āļ­āļ‡āļ‚āļķāđ‰āļ™ āļāļēāļĢāļžāļąāļ’āļ™āļēāļ‚āļ­āļ‡āđ€āļ„āļĢāļ·āđˆāļ­āļ‡āļĄāļ·āļ­āļ—āļĩāđˆāđ€āļāļīāļ”āļ‚āļķāđ‰āļ™āļĄāļēāļāļĄāļēāļĒāļ™āļĩāđ‰ āđ€āļ›āđ‡āļ™āļāļēāļĢāļžāļīāļŠāļđāļˆāļ™āđŒāđƒāļŦāđ‰āđ€āļŦāđ‡āļ™āļ–āļķāļ‡āļ›āļĢāļ°āđ‚āļĒāļŠāļ™āđŒāļ‚āļ­āļ‡āļāļēāļĢ āļ§āļīāđ€āļ„āļĢāļēāļ°āļŦāđŒāđ‚āļĄāđ€āļĨāļāļļāļĨāļ‚āļ™āļēāļ”āđ€āļĨāđ‡āļāļ­āļĩāļāļ”āđ‰āļ§āļĒ āđ€āļŠāđˆāļ™ āļŠāļēāļĢ āđ€āļĄāļ•āļēāļšāļ­āđ„āļĨāļ—āđŒ āļ›āļąāļˆāļˆāļļāļšāļ™āļą āđ€āļ—āļ„āđ‚āļ™āđ‚āļĨāļĒāļĩāđ€āļŦāļĨāđˆāļēāļ™āļĩāđ‰ āļāļĨāļēāļĒ āđ€āļ›āđ‡āļ™āļŠāļīāđˆāļ‡āļˆāļģïŋ―āđ€āļ›āđ‡āļ™āđƒāļ™āļāļēāļĢāļžāļąāļ’āļ™āļēāļĒāļēāđ€āļžāļĢāļēāļ°āļ•āđ‰āļ­āļ‡āđƒāļŠāđ‰ āđƒāļ™āļāļēāļĢāļ§āļīāđ€āļ„āļĢāļēāļ°āļŦāđŒāļŠāļēāļĢāđ€āļĄāļ•āļēāļšāļ­āđ„āļĨāļ—āđŒāļ‚āļ­āļ‡āļ•āļąāļ§āļĒāļē āļ™āļ­āļāļˆāļēāļāļ™āļĩāđ‰āđ€āļ—āļ„āđ‚āļ™āđ‚āļĨāļĒāļĩ ESI āļĒāļąāļ‡āļŠāđˆāļ§āļĒāļ—āļģïŋ―āđƒāļŦāđ‰ āļ§āļīāļ§āļ’ āļą āļ™āļēāļāļēāļĢāļāļēāļĢāļˆāļģïŋ―āđāļ™āļāļŠāļ™āļīāļ”āļ‚āļ­āļ‡āđ‚āļ›āļĢāļ•āļĩāļ™āļŠāļ āļēāļž āļ›āļāļ•āļīāļ™āļąāđ‰āļ™āļĄāļĩāļ„āļ§āļēāļĄāļ‡āđˆāļēāļĒāļ‚āļķāđ‰āļ™ āđ€āļžāļĢāļēāļ°āđ‚āļ›āļĢāļ•āļĩāļ™āļˆāļ°āļœāđˆāļēāļ™

mass analyzer that separates ions based on their flight times over a defined distance. ESI provided a very different set of capabilities than MALDI. By placing a high voltage on a liquid flowing through a capillary, a spray containing tiny droplets forms at the exit, and the spray is directed to the entrance of the mass spectrometer. The liquid is removed from the droplet by heat and results in the formation of an ion beam. ESI also results in the formation of multiply charged ions, which ensures that m/z of large molecules are in the range of 800–1,800 atomic mass units, well within the detection capabilities of many mass spectrometers used at the time. The Rise of Proteomics The ability to identify proteins in mixtures and their post-translational modifications, using tandem mass spectra and sequence databases, altered the existing proteinsequencing paradigm and ushered in an approach known as shotgun proteomics—a strategy that makes possible large-scale measurements of proteins in protein complexes, organelles, cells and tissues as well as their post-translational modifications, without the need to isolate individual proteins. Rapid and accurate identification of proteins greatly increased the pace of biological discovery by simplifying what used to be the most time-consuming part of discovery—protein sequencing. These new capabilities and applications in turn drove rapid developments in tandem mass spectrometry technology to create new types of mass spectrometers such as linear ion traps, quadrupole/time-offlights, time-of-flight/ time-of-flight, ion mobility and Orbitrap instruments with greater sensitivity, faster scan speeds, better resolution and higher mass accuracy. Many of these instrumental developments also proved useful for the analysis of small molecules such as metabolites. These technologies have also become essential to the drug-development process to identify and measure drug metabolites.


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