New instruments featuring time-of-flight (TOF) liquid chromatography/mass spectrometry technology improve on their predecessors in terms of speed and mass accuracy.

The first generation of quadrupole time-of-flight (Q-TOF) liquid chromatography/mass spectrometry (LC/MS) instruments provided excellent quality data, but the quality of the instrument and the analytical horsepower were both lacking. These issues, along with the increased use of accurate mass and MS/MS to solve difficult qualitative problems, led Agilent Technologies Inc., Santa Clara, Calif., to design a new Q-TOF system, the Agilent 6520 Accurate-Mass Q-TOF.

Agilent added 32 Gbit/sec high-speed data acquisition electronics that improve mass resolution to 20,000. Additionally, they incorporated dual-gain analog to digital (ADC) TOF electronics for a tenfold improvement of dynamic range over conventional instruments—now approaching up to five orders of magnitude.

“These improvements will enable scientists in metabolomics, proteomics, and complex qualitative analyses to find and identify more lower-abundance compounds faster than ever,” says Ken Miller, Agilent marketing director, LC/MS division. “All of this performance is achieved without significantly compromising rapid analysis time for higher-quality data.”

Improving productivity

The new Agilent 6520 Q-TOF provides high mass accuracy and dynamic range without sacrificing speed. Image: Agilent Technologies

Innovation in ion optics in the Agilent 6520 is what delivers the high sensitivity across the broad mass range due to the small diameter octopole ion guide and the lens optimization for higher mass transmission. These TOF innovations enable automated sub-ppm mass accuracy and a wide dynamic range with internal reference mass (IRM) correction for all ion sources in a thermally stable TOF design.

The Agilent 6520 Q-TOF has attomole sensitivity with better than 2-ppm MS mass accuracy and better than 5-ppm MS/MS mass accuracy. The 6520 shows tenfold improvement in in-spectra dynamic range without loss of sensitivity—approaching 5 decades in-scan. The mass resolution is 20,000 and is not dependent on spectral acquisition rate.

Fast data acquisition (10 MS/MS spectra/sec) is compatible with fast LC chromatographyacross the broad mass range from m/z 25 to 20,000.

The Agilent 6520 provides improved productivity through less down time, less calibration and optimization, and fewer repeat analyses. Proteomics users will be able to identify more proteins more rapidly with this system.

Another instrument recently released by Agilent is the 6220 Accurate-Mass TOF. Similar to the 6520, when operating in MS mode only, the Agilent 6220 TOF incorporates the same high-speed ADC TOF technology to deliver the same benefits as when operating in MS/MS mode. Targeted applications include product degradation studies, biomarker discovery, metabolomics, and confirmation of compounds in synthetic chemistry labs. Its recent enhancements deliver better than 2-ppm mass accuracy combined with 20,000 mass resolution and 40 spectra/sec acquisition speed. The 6220 TOF uses the Agilent MassHunter Workstation software with advanced data acquisition and qualitative and quantitative data analysis capabilities. These capabilities include unique data-mining functionality based on powerful molecular feature extraction and molecular formula generation algorithms, facilitating the identification of compounds in complex mixtures.

Improving analysis with software

Agilent also offers application-specific software packages for the new Accurate-Mass instruments. Users can use MassHunter Profiling to find variations between two samples or sample groups. The molecular feature extraction (MFE) algorithm reduces complex data sets into a simple list of all detectable compounds with accurate mass, retention time (RT), and intensity, with a list of all ions associated with each compound. The molecular formula generator (MFG) algorithm calculates molecular formulas using accurate mass MS and MS/MS information for unknowns, while the MassHunter Metabolite ID correlates MS/MS spectra from precursor drugs and metabolites.

Spectrum Mill quickly and accurately identifies proteins, and GeneSpring MS has a full range of tools for statistical profiling and related data-mining of very large sets. Combining the high sensitivity of the new 6520 Accurate-Mass Q-TOF and Accurate-Mass 6220 TOF with Agilent’s powerful software will give robust results in high-throughput expression studies in metabolomics, proteomics, drug discovery and development, biomarker discovery, and product degradation.

—Martha Walz

Resources
• Agilent Technologies Inc., Santa Clara, Calif., 877-424-4536, www.agilent.com