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New Scripps Research Mass Spectrometry NanoTechnology Delivers Significant Advances

Ultra-Sensitive Technique Offers Ease of Use and Minimal Sample Preparation

LA JOLLA, CA, October 25, 2007—Scientists at The Scripps Research Institute have developed a new mass spectrometry technology for studying small biomolecules. The new highly sensitive and robust technology, called Nanostructure-Initiator Mass Spectrometry (NIMS), enables the analysis of single cells, tissue imaging, and rapid blood and urine analysis with no advanced sample preparation. 

The study was published in the October 25, 2007, issue of the journal Nature.

"NIMS has several advantages over current mass spectrometry techniques," said Gary Siuzdak, Ph.D., director of the Scripps Research Center for Mass Spectrometry and associate professor of molecular biology at Scripps Research. "NIMS offers high sensitivity and can directly analyze biofluids or tissues with little or no preparation-all of which is extremely positive in terms of its potential utility in biochemical research and in clinical diagnostics."

Mass spectrometry has been described as the smallest scale in the world, not because of the mass spectrometer's size but because of the size of what it weighs-molecules. A mass spectrometer determines the mass of a molecule by measuring the mass-to-charge ratio 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 mass-to-charge ratio 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.

According to the authors of the new study, their new mass spectrometry technology will be particularly useful in advancing the study of metabolites, the products of an organism's metabolic processes that are the "chemical fingerprints" that specific cellular processes leave behind. A profile of a cell's metabolites, the end products of an organism's gene expression, can give scientists a snapshot of the physiology of that cell.

"For the growing field of metabolomics, the two most widely used mass spectrometry techniques-electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI)-have serious limitations, including time-consuming sample preparation and a limited ability to detect small compounds," said Oscar Yanes, Ph.D., of Scripps Research, a lead author of the study. "NIMS complements these other techniques in many ways."

Trent Northen, Ph.D., of Scripps Research, also a lead author, added, "In the near future, the ability to study large numbers of metabolites directly from cells, tissues, and biofluids will give us new insights into biological processes and diagnostics, particularly in combination with increasingly available genetic and proteomic information. NIMS will be an important platform for these studies."

While mass spectrometry of metabolites is already a well-established tool in fundamental biochemistry and clinical diagnostics, higher throughput and higher sensitivity mass-based platforms could help identify additional metabolites involved in disease states. NIMS can also be used in tissue imaging, providing the location of metabolites in tissues. NIMS has provided images of small metabolites within tissue sections, for example, revealing a number of anatomical details such as the localized placement of lipids.

Currently, the Scripps Research scientists are focused on further developing NIMS in metabolomics by interfacing the technique with high resolution and tandem mass spectrometry. The primary challenges include broadening the scope of NIMS through developing new nanostructure surfaces to enhance desorption/ionization.

Other authors of the study, Clathrate Nanostructures for Mass Spectrometry, are

Oscar Yanes, Anders Nordström, Winnie Uritboonthai, Junefredo Apon of The Scripps Research Institute and the Scripps Center for Mass Spectrometry; Dena Marrinucci of The Scripps Research Institute; Michael T. Northen of the University of California at Santa Barbara; and Stephen L. Golledge of the University of Oregon.

The study was supported by the U.S. Department of Energy, the National Science Foundation, the National Cancer Institute, the National Institutes of Health, and the Swedish Research Council.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Currently operating from temporary facilities in Jupiter, Scripps Florida will move to its permanent campus in 2009.

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