Waters filters out the matrix
ionisation source to broaden the number of applications the
instrument can be used in - including MALDI imaging.
Waters' latest release the MALDI Synapt high definition mass spectrometer (HDMS) is a dual ionisation mass spectrometer (MS) that includes both matrix-assisted laser desorption ionisation (MALDI) and electrospray ionisation (ESI) ion sources to increase the utility of the Synapt instrument that won the Gold award at Pittcon 2007 earlier this year. The introduction of the new ion source increases the number of proteins that can be ionised and analysed by 20 per cent, as well as opening up the possibility of conducting MALDI ion-mobility MS imaging for the first time. This has the potential to allow researchers to look for mis-folded proteins in tissue samples and could enhance our understanding of various diseases such as Alzheimer's. "This instrument takes MALDI to a whole new level by combining it with ion mobility for the first time," said Ronan O'Malley, product manager for the MALDI Synapt at Waters. "We have a quite a few collaborations with pharmaceutical companies and academic institutions that are focussing on MALDI imaging and there's quite a lot of excitement about what ion mobility can bring to the world of imaging," he continued. O'Malley was keen to stress that the MALDI Synapt is a dual source instrument with the sources being engaged by an automated tool-free switching process - allowing operators switch between the two sources rather than needing an engineer. Owners of the original Synapt instrument will be pleased to know that it can be upgraded to include the MALDI source in the field. The system can be run in two modes: time-of-flight (TOF) mode for exact mass MS/MS experiments and ion-mobility/TOF mode for performing novel ion mobility based separations that can separate ions not only by charge and mass but also by size and shape. "You can run the instrument in two ways; the first is by passing all the ions through the device and this is what we call TOF mode, and in TOF mode you can use all our dedicated application software and in this mode you get sub-5ppm mass accuracy," said O'Malley. "The second is with the ion mobility device engaged - the way you do that is by introducing nitrogen into the ion mobility T-wave to allow the ion mobility separation." According to O'Malley, the instrument has the ability to filter out interfering matrix or background signals which is particularly useful when looking for small molecules in complex mixtures. Systems such as Applied Biosystems FlashQuant MS use quadrupole's (Q) to filter out these matrix peaks when looking for drug metabolites. "If you look at a typical MALDI spectrum you see a lot of background noise from the matrix below 900Da and that can really hinder the study of drug metabolites and other small molecules, but this instrument enables the separation of your peaks of interest from the matrix ions - and this is a first," said O'Malley. "One of the advantages of Waters' MALDI Q-TOF Premier was that you got superior precursor ion resolution was done using a quadrupole rather than an ion gate giving you a greater level of selectivity over using TOF-TOF techniques. This instrument takes us another step further because you can separate by ion mobility in addition to what you can do with the quadrupole," he continued. While being able to perform MALDI MS imaging is an obvious advantage to the instrument, the ability to conduct MALDI MS analysis on samples after liquid chromatography (LC) separations is also an attractive proposition for those researchers who need to analyse specific proteins from complex mixtures that cannot be ionised by methods other than MALDI. "LC-MALDI is becoming increasingly important as it addresses the dynamic range issue; you do an off-line separation and use a robotic spotting device to spot the fractions that elute from the LC onto a MALDI target plate which is then introduced into the instrument" said O'Malley. In addition, the ability to conduct 'time aligned parallel' (TAP) fragmentation studies that provide detailed structural information from first and second generation ions in a single experiment. The unique thing about the Synapt is that the ion mobility device is integrated into the heart of the instrument, unlike some competing ion mobility device such as the FAIMS device from Thermo Fisher Scientific. These systems act somewhat like an additional chromatography step that has the potential to exclude ions of interest from the MS if an operator is not careful. "Unlike the Synapt these systems don't measure the ions drift time so they don't tell you anything new about the ions," said O'Malley Because the instrument can be run in several modes the instrument can be used as a more traditional MS which should help the uptake of the technology. "The thing that is really groundbreaking about this instrument is that we've added a new dimension of separation, but in contrast to previous advances in MS technology there's no risk because you can run all the old applications emulating a high end Q-TOF instrument and then when you've found the limits of that technology you can engage the ion mobility separation device and that opens up a world of new possibilities," said O'Malley.
