The 4700 includes the matrix-assisted laser desorption/ionization (MALDI)-TOF/TOF instrument, a computer, an embedded Oracle database, and instrument control and data analysis software. Optional accessories include a 24-plate autoloader, which allows the instrument to handle nearly 1,200 samples per hour in an unattended run, a 16-tip robotic spotter, and proteomics-specific application software.
According to Hicks, the 4700's TOF/TOF configuration provides "the high resolution, high sensitivity, and high mass accuracy that TOF-based instruments give you, combined with true MS/MS capability." This tandem MS capability allows researchers to select a specific peptide ion in the first TOF MS, fragment it by collision-induced dissociation, and obtain peptide sequence data in the second MS. But unlike other tandem configurations, such as the more common quadrupole-TOF, the 4700 uses high-energy fragmentation, which generates additional molecular information such as the difference between leucine and isoleucine side chains.
ABI made several enhancements to improve the system's throughput. Whereas most MALDI lasers fire between 3 and 20 Hz, the 4700's MALDI laser ionization source fires at 200 Hz. But Hicks says that a faster laser alone would not speed up the system appreciably; to really enhance the throughput, ABI coupled the laser to a high-speed sample stage and to high-speed data acquisition and processing software on the back end.
According to Hicks, sales have been brisk since the 4700 debuted. One system went to Phil Andrews, professor of biological chemistry at the University of Michigan Medical School and senior director of the Michigan Proteome Consortium. Andrews says he chose the 4700 for its ability to provide MS/MS of large peptides. Generally, he says, mass spectrometers work with peptides below 3,000 daltons (Da). But ABI demonstrated that its system could handle fragments up to 16,000 Da. "That was the deciding factor for us," he explains, "because we could see the potential role this would play in our services." Andrews says his clients have already benefited from this feature.
Andrews describes his experience with the 4700 as "extremely positive thus far," though he notes that his group hasn't yet pushed all the limits of the instrument to see what it can do, simply because they've spent most of their time learning to use and optimize it for their requirements. Now, his team is awaiting a visit from an ABI field representative to install the optional autoloader.
Andrews says that in two short months, the 4700 has "changed the way we think about ... solving proteomics problems." But with so much sample capacity, Andrews wonders how long it will take to get the sample pipeline filled. It's a question, he says, of "feeding the beast."