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Linear ion trap/Orbitrap mass spectrometer FT ion cyclotron resonance (FTICR) MS is known for its high resolving power and analytical performance, but it comes with a hefty price tag. A large part of that cost is due to the need for a superconducting magnet. Would it be possible to develop a mass spectrometer with all the advantages of FTICR without an expensive magnet? Researchers at Thermo Electron believe the answer is yes. In this issue of Analytical Chemistry (pp 2113–2120), Alexander Makarov and colleagues at Thermo Electron Bremen (Germany) describe the design and performance of a hybrid linear ion trap (LTQ)/Orbitrap mass spectrometer. The cost of the instrument is significantly lower than that of an LTQ /FTICR mass spectrometer because of the absence of a superconducting magnet. The performance is not quite as high as that of FTICR, but it is much higher than that of other hybrid mass spectrometers, such as quadrupole/ TOF or ion trap/ TOF, says Makarov. Instead of trapping ions in a magnetic field, the LTQ /Orbitrap mass spectrometer traps them in a compact structure created by an inner electrode sustained at high voltage and outer electrodes kept at almost ground voltage. “As a result, this system allows very high performance, but we have to pay for this by employing very narrow ion beams,” says Makarov. The need for narrow ion beams was initially a big problem. “We were not able to find the way to inject all these huge numbers of ions into such a small volume in a short time,” explains Makarov. Enter the so-called C-trap, a technology that transforms incoming beams into very short pulses suitable for an Orbitrap mass analyzer. In the beginning, the transfer of ions into the Orbitrap was a hurdle that needed to be overcome, says Makarov. “Instead of interfacing the linear ion trap directly to the Orbitrap, we had to use this additional storage.” It turned out that, in some cases, this ad-
API ion source
Linear ion trap
C-trap
Differential pumping Orbitrap
Schematic of a hybrid linear ion trap/Orbitrap mass spectrometer.
ditional storage improved the analytical capabilities of the instrument. For example, it enabled the researchers to add an internal calibrant and use several injections from the linear trap into this C-trap, says Makarov. “As a result, even though we introduce one more trap into the system, in exchange we get . . . some ability to carry out new analytical experiments not available before,” he says. In terms of performance, FTICR is still the winner, in large part because it can trap and detect ions for much longer times than the Orbitrap, says Makarov. However, for on-line separations, the hybrid LTQ /Orbitrap mass spectrometer is faster because of shorter accumulation times, especially in MS/MS experiments. For both FTICR and the Orbitrap, speed comes at the expense of resolving power, but over the same time period, the LTQ/ Orbitrap provides 60–70% of the resolving power of LTQ / FTICR, claims Makarov. FTICR also has more than a quarter of a century of development behind it, says Makarov. As a result, a multitude of fragmentation techniques, such as electron capture dissociation and IR multiphoton dissociation, exist for FTICR. Such techniques, which allow for the analysis of proteins directly in the cell, are currently not available for the Orbitrap. “Therefore, we cannot offer topdown proteomics using the Orbitrap,” says Makarov. Top-down proteomics is an approach in which intact proteins are
analyzed instead of peptide fragments. The LTQ /Orbitrap system can be used with a wide range of separations, even really fast ones, says Makarov. “We have the ability to transmit a very high proportion of ions into the ion trap. So, waiting times for ions of a particular mass to be stored and then fragmented [are] much lower than usual,” he explains. Thus far, the LTQ /Orbitrap mass spectrometer has been used primarily for pharmaceutical and proteomics applications, which benefit from the instrument’s high speed and transmission. “In proteomics, the number of analyses per LC run is really limited by the necessity to wait for a particular signal to accumulate,” says Makarov. The Orbitrap needs less time than other accurate mass analyzers to accumulate the same amount of ions. Another important aspect of the LTQ /Orbitrap system is its high dynamic range, which is quite rare to see in hybrid instruments, says Makarov. Small peaks, which are barely visible above the noise, can be accurately determined along with huge peaks (S/N = 5000 –10,000). Both sets of peaks provide meaningful information for identification. “We could use both of them in a database search. This is something which was introduced by the LTQ / FTICR hybrid, but it is even more pronounced in the LTQ /Orbitrap instrument,” he says. a —Britt Erickson
A P R I L 1 , 2 0 0 6 / A N A LY T I C A L C H E M I S T R Y
2089
