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Aug 1, 2008 (Vol. 28, No. 14)

Novel MS Systems Expedite Workflow

Time-of-Flight Leads the Way in Emerging Devices

  • Thermo Fisher Scientific launched several new mass spec systems at the ASMS conference on “Mass Spectrometry and Allied Topics” held recently in Denver. The introductions upped the ante for high-end systems, added a new benchtop system to Thermo Fisher’s product line, as well as biosoftware for advanced proteomics research.

    Emerging devices, many involving advances in time-of-flight, also were discussed by Virgin Instruments, MDS Analytical Technologies, Bruker Daltonics, Photek, and many other companies.

    The TSQ Vantage™ LC/MS/MS was the new system launched by Thermo Fisher at the meeting. This triple quadrupole instrument is 10 times more sensitive than any other machine of that type on the market and also boasts a 10:1 signal-to-noise ratio when compared to the TSQ Quantum series, according to Iain Mylchreest, Ph.D., vp and general manager at Thermo.

    “That’s possible,” explained Dr. Mylchreest, “because of the way the new system was designed.” The TSQ Vantage system features “a new ion optical system that sprays solvent more effectively and reduces clustering by changing the physical geometries.”

    Its S-Lens ion optics system uses an electrostatic field to capture “virtually every ion” and transfer it to the HyperQuad™ quadrupole mass analyzer. The advantage, said Dr. Mylchreest, is that it eliminates mass discrimination and lowers the gas load on the turbo molecular pumps, while keeping the ion optical path cleaner to maintain sensitivity. Therefore, scientists working with small molecules, biomolecules and peptides can detect compounds at ultralow quantitation levels with great precision, he added.

    The optical interface also has been simplified, noted Dr. Mylchreest, removing the need for direct intervention. Although, he pointed out, users do have the option of fine-tuning the optics themselves.

    Exactive™, a new benchtop LC-MS system is another “very significant launch,” said Dr. Mylchreest. This new system leverages the mass analyzer technology used in the LTQ Orbitrap™ and is designed for compound screening and identification in analytical laboratories routinely performing toxicology, environmental, and drug development workflows. It offers between-peak resolutions up to 100,000, Dr. Mylchreest said. To put that in perspective, TOF resolution typically is 10,000 to 15,000, he added. In tests, “130 points were measured with 1–2 ppm mass accuracy with only one outlier.”

    Thermo Fisher Scientific also launched its “massinformatics” software at the ASMS conference. Dubbed the Proteome Discoverer, it provides a comprehensive view of quantitative and qualitative proteomic data that includes the ability to combine and compare data from multiple search engines, public databases, and dissociation methods. “It was developed to provide a more flexible platform and workflow environment,” Dr. Mylchreest explained. “The proteomics research world is moving fast,” so this software is built to be forward-compatible.

  • Fine-Tuning Accuracy

    Bruker Daltonics has developed a new API-Qq-TOF MS system capable of identifying and quantifying trace compounds in complex matrices, according to Carsten Baessmann, Ph.D., head of applications development, LC-MS systems, and solutions. This ultrahigh resolution TOF system, called maXis™, offers a mass resolution of 40,000 to 60,000 FWHM and MS and MS/MS mass accuracy at less than 1 ppm without compromise regarding sensitivity and acquisition speed, he reported.

    The development strategies, according to Dr. Baessmann, were to either increase flight time or decrease variances in flight time due to issues with turnaround, energy distribution, detectors, and mechanical precision, etc. The design includes a source, dual-ion funnel, quadrupole, collision cell, ion cooler, orthogonal accelerator with a focusing lens, and a dual-stage reflectron.

    The ion-cooling segment reduces turnaround time and provides a precise starting position in orthogonal reflection, while the dual-stage reflectron offers better correction of energy errors and second order space focus.

    “The focusing lens increases the number of ions on the detector by fivefold,” and the adjusted trajectories increase resolution to greater than 60,000, Dr. Baessmann elaborated. “Where you’d expect mass accuracy of maybe 2 ppm, we had accuracy below 200 ppb (in MS mode), which shows the kind of precision you can achieve with this instrument,” he added.

    Dr. Baessman also reviewed a proteomics experiment involving 100 nanograms of E. coli digest with a typical 90 minute gradient at 300 nL per minute. “What you see from such a sample is quite a huge dynamic range (4–5 orders of magnitude). When I looked at the data, the most abundant peptides were in the range of 6 x 105, and you even saw the isotopes,” he said. RMS mass accuracy was good at 860 ppb, and all points were below 2 ppm; in addition the system identified 349 unique protein identifiers.

  • High Resolving Power

    At Virgin Instruments, the focus is on developing a MALDI-TOF MS system with high resolving power. Marvin Vestal, Ph.D., CEO, remarked that “MALDI is an infant. The best is yet to come.”

    So far, Virgin’s system has achieved a resolution of more than 40,000 at a 2 gigasamples per second scanning rate in the m/z range between 800 and 3,000 daltons, Dr. Vestal reported. More than 30,000 resolution is routinely achieved in the range between 200 and 600 daltons. Limitations, Dr. Vestal pointed out, are mainly the result of the time resolution of the transient digitizer using a 0.5 nanosecond channel width. “Deflecting the ions and tilting the mirror corrected the trajectory error and minimized the limitations.”

    With that approach, “the dynamic range is good,” he noted, “going from 10 picomoles per microliter to 10 fentomoles per microliter. At the 100, 10, and 1 attamole level, it detects all high mass peaks.” The system uses a 102 x 108 mm sample plate, a 5 kHz laser, and a benchtop catalyst; it can analyze 100 spectra per second. The system will be fully automated for 24/7 operation with minimal maintenance.

    Photek has developed a nanosecond time-resolved ion imaging system that offers 3.5 nanosecond resolution—an improvement from the previous standard 100 ns resolution—on a 25 mm working diameter.

    Such a short imaging window is possible thanks to the vacuum imaging detector, which consists of two microchannel plates and a phosphor screen that gives an accurate electronic signal that corresponds to each ion event, according to James Milnes, Ph.D., research engineer. The Photek VID240 “allows easy temporal location of ion events,” Dr. Milnes noted. “The plates generate an electronic avalanche from an electron or ion input. Using the model of a sealed tube image intensifier with an input window coated in a visible light photocathode and a short laser pulse, we have been able to visually demonstrate the progression of the gating pulse across the MCP surface.”

  • Increasing Collision Energies

    MDS Analytical Technologies has developed a method to increase collision energies from the typical limit of 200 volts per charge to up to 500 volts per charge on QqTOF systems, without modifying the hardware, according to Bruce Thomson, Ph.D., principal research scientist. Although 200 volts is ample for most fragmentations, Dr. Thomson said, the higher voltage may be helpful for fragmenting fullerenes or other stable structures, high energy peptide fragments, singly charged MALDI ions with low charge states, large protein complexes, and multiply charged protein ions.

    “The collision energy in a QqTOF system is equal to the potential difference between the Q0 RF ion guide and the Q2 collision cell,” Dr. Thomson explained. So, to reach high collision energy, he used a trap-and-lift method in which ions entered the system at 360 volts. The Q2 potentials were lowered to -200 volts and the Q0 potential was raised to nearly 300 volts to trap ions in Q2 and generate a collision energy of about 500 volts. “You can also do the same sort of thing on the front end, with Q0, to generate high declustering potential by lowering Q0 to trap and then raising potential to flow ion down into Q2,” Dr. Thomson said. The methods can also be combined.

    In the biodefense sector, Science & Engineering Services has developed a prototype high-throughput, automated, multiplexed assay system for atmospheric pressure MALDI/MS/MS systems to rapidly detect and identify known and unknown bioagents. According to researcher Appavu K. Sundaram, Ph.D., species identification takes only five to ten minutes from sample prep through results. The goal is to generate results in one minute with no false positives.

    The system identifies multiple pathogens simultaneously and can distinguish between close relatives of the pathogens. “Environmental clutter in the sample did not affect detection and identification of the Bacillis globigii spores and bacteriiophage in the MS/MS bacteriaphage,” Dr. Sundaram said.


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