December 15, 2004
| In the past couple of decades, the mass spectrometer has moved out of its original domain in the chemistry lab to become an important tool for the biological sciences. New studies suggest that the technique may be on the cusp of another great leap forward, according to a study published in the October 15 issue of Science by Graham Cooks and colleagues at Purdue University (Takáts, Z. et al. Science 306, 471-3; 2004).
The study describes a new mass spectrometry ionization method called DESI — desorption electrospray ionization — which seems poised to springboard mass spectrometry (MS) to wider markets and even perhaps the consumer market.
Sample preparation has long been the limiting factor for MS analysis. Generally, samples are mixed with a matrix and ionized in a vacuum by laser ablation, or they are ionized under atmospheric conditions by an ion spray. Once ionized, the molecules are identified by their charge-to-mass ratio. Both procedures require complicated methods of sample preparation, making them unsuitable for application in the field.
DESI obviates sample preparation by ionizing the sample directly off a surface with a stream of solvent, under ambient temperature and pressure. The ionized sample is then sucked into the mass spectrometer and analyzed. The method works for a variety of compounds — including peptides and proteins — present on metal, mineral, or polymer surfaces, as well as small organic molecules.
In the Science paper, the Purdue group shows that they could detect an antihistamine on the skin of a person who had taken a pill 40 minutes earlier, and even traces of the explosive RDX present on a leather surface.
AMBIENT MS: DESI's trick of ionizing a sample using an electrospray offers myriad applications.
SOURCE: TAKÁTS, Z. ET AL. SCIENCE 306, 471-3; 2004
The potential applications of the new technology include environmental screening, healthcare, and homeland defense. According to John Hurrell, president of Inproteo LLC, an Indiana-based venture aiming to commercialize DESI, applications also exist in the food industry and in online process control for manufacturing of pharmaceuticals. Discussions are under way with major diagnostics companies and manufacturers of MS equipment.
Other advances in MS technology were announced in October at the 2004 Human Proteome Organisation (HUPO) Conference, held in Beijing. Bruker Daltonics introduced the Prespotted AnchorChip, a disposable AnchorChip MALDI (matrix-assisted laser desorption/ionization) target for gel-based and LC-MALDI-based expression proteomics, also aimed at facilitating sample preparation.
The Prespotted AnchorChip is available in a 384-sample microtiter plate format — and includes an additional 96 calibrant spots that have all been pre-spotted with matrix. Each chip is packaged under inert gas in a container that can also be used for sample archiving after the analysis. The Prespotted matrix and the calibrant spots are designed such that users can apply aqueous peptide and protein digest samples directly to the target for analysis. Each chip has individual bar codes to facilitate sample tracking.
According to Michael Schubert, vice president for R&D at Bruker Daltonics, the new disposable format is crucial for high-throughput validation and comparison studies in the pharmaceutical industry because it reduces the problem of cross-contamination and makes MALDI sample preparation simpler and less labor intensive.
Bruker also unveiled the ultraflex II, a MALDI-TOF and TOF/TOF mass spectrometer that the company says offers further advances in the sensitivity, resolution, and mass accuracy of TOF/TOF systems. The new unit is aimed at expression proteomics, quantitative proteomics, and biomarker discovery. The ultraflex II can be used for peptide de novo sequencing, the analysis of post-translational modifications, and even top-down protein primary structure determination. (Details of the Prespotted AnchorChip and the ultraflex II can be found at www.bdal.com.)
Robert M. Frederickson is a biotech writer based in Seattle. E-mail: firstname.lastname@example.org.