Introduction to mass spectrometry 2

Welcome. My name is Brandon Ruotolo, professor of chemistry at the University of Michigan. This is part two of a two-part lecture that is an introduction to Mass Spectrometry in part one. We covered basic principles and vocabulary in mass spectrometry and a little bit of the history of this diverse area of scientific endeavor as well as something about the ion sources used to produce ions for mass spectrometry experiments.

Now in part two, we're going to begin by looking at mass analyzers. These are devices that exist after the ion source in the mass spectrometer. There's a wide array of these types of devices that are all designed to separate and evaluate the mass-to-charge ratio of the ions that we produce in the ion source.

There is a wide array of mass analyzers available to the modern mass spectrometrist. I don't have the time to go through all of these different types of instruments. So I selected some of the most popular instruments to talk about. On these slides, I'm going to cover the basic principles of the mass analysis at play in each of these instruments and then I'm going to talk about the advantages and disadvantages of these devices in reference to the other mass analyzers that are available in the modern mass spectrometry area. The first instrument I'm going to cover is Time-of-Flight mass spectrometry, or ToF for short. This is probably at least from a design principle amongst the simplest forms of mass analyzers. Its operation is based on kinetic energy. Kinetic energy, as we all know, equals one-half times the mass of our, in this case, ion times its velocity squared. So in a time of flight mass spectrometer, we can define the kinetic energy. We can measure the velocity of that ion in an evacuated tube. Then from that velocity measurement, we can determine the mass or mass charge, because we need a charge, in this case, to have the molecule field the electric field we're going to be using to push the ion into our chamber and define that kinetic energy. The advantage of this type of mass analyzer is that it has an unlimited mass range. You can measure ions over any mass range you want. All you have to do is wait for a little bit longer to measure larger and larger ions. Modern instruments have excellent mass resolving powers and resolutions. The values I'm showing you here are mass resolutions between 40-100000 are very commonly encountered in commercial instruments, and do these measurements very, very quickly. They can take microseconds to be complete, and it's not a scanning instrument. You just push the ions in, and you measure their time, and there's no need to scan a potential. Disadvantages for this instrument include quantitation over broad mass ranges can be a challenge. We'll cover that a bit more when we get to detectors, and higher-order mass spectrometry experiments, which we'll cover later on, can be challenging to implement on these types of analyzers as well. The next mass analyzer I wanted to cover is the quadrupole. This is a device that's constructed of four rods in two different sets that are oriented perpendicular to each other as you can see from the diagram. These rod sets are connected electrically, and we apply both a DC potential, in other words, a time-invariant potential as well as a time-varying potential, which is a cosine-type waveform, applied to these rod sets in this instance. And it's a combination between this DC potential and this RF or radio frequency potential that allows us to collimate ions into the middle of this device and transmit only those ions that are of one mass charge value. Only that mass charge value under a certain combination of RF and DC fields will be transmitted through this device. Other ions will not have a stable orbit instead these devices pass in the device and hit the rods instead. As you can tell from that description, this device operates as a mass filter, a mass charge-based filter. Individual RF and DC combinations will allow you to observe different mass charge values here. It's a highly sensitive and selective instrument, and it can be combined with other quadrupoles. For example, in tandem, we'll cover this a little bit later on, but you can put a number of these quadrupoles in tandem to create a very powerful form of tandem mass spectrometry. The analysis is relatively fast, on the millisecond timescale. Disadvantage, however, is that this is a scanning instrument. So you don't get a complete mass spectrometry dataset under a single set of conditions. You have to scan a potential. Usually, it's a ratio of the DC and RF potentials. Mass ranges are usually limited to around 4000 mass charge, but that can be altered in some cases, usually by altering the peak-to-peak amplitude of the RF or the frequency of the RF in place. The mass resolution is often limited, usually to something less than 4000. The next instrument I wanted to cover is the ion trap. Ion traps use a principle similar to the quadrupole in that the same field that's keeping the ions in the middle of that quadrupole rod set, that's the same field that's keeping the ions inside the device I'm showing you here in this diagram, which is comprised of a single ring electrode and on either end of that ring electrode is a cap electrode. The cap electrode uses a DC potential to confine the ions along that Z dimension and then that ring electrode has an RF potential that keeps the ions confined in the XY plane of that instrument. What we do in this instrument is we keep the ions all confined in the middle, and then we use a sweep of a potential, usually, it's a sweep of an RF amplitude that then kicks the ions out of that trap, usually along that Z dimension, in a manner that's dependent upon their mass charge. This is a device that allows for facile high dimensionality mass spectrometry experiments. In other words, we can take a mass spectrometer, select one ion in the ion trap to then keep in the trap, and then eject all the rest to subsequent mass spectrometry experiments after maybe subsequent activation steps. It's a robust analyzer that operates well at higher pressures, which the rest of the instruments we've talked about so far require high vacuum, and it's easy to miniaturize. Ion trap arrays are certainly possible, and have been implemented in multiple instruments that you can find in literature. Disadvantages include the fact that this is another scanning instrument. The acquisition rate for the data is sometimes a bit lower. These are often lower resolution instruments even lower than the quadrupole. And we often have a limited mass range for the same principles we talked about in the quadrupole.