Controlling the expansion into vacuum—the enabling technology for trapping atmosphere-sampled particulate ions

Abstract

A new inlet has been designed to control the kinetic energy distributions of ions into a large-radius, frequency-adjusted, linear quadrupole ion trap. The work presented here demonstrates trapping singly-charged, intact proteins in the 10 to 200 kDa range injected from the atmosphere. The trapped ions were held while collisions with a buffer gas removed the remaining amounts of expansion-induced kinetic energy. The ions were then ejected from the trap on-demand into an awaiting detector. There is no low mass limit for ion injection and trapping. The upper limit presented in this study was defined by the limit of the conversion dynode-based detector at ϳ1.5 MDa. Trapping larger masses should be achievable. The transmission and capture efficiency across the entire mass range should be very high because the entire flow from the inlet empties directly into the trap. The kinetic energy distribution of massive ions is the primary reason for the working range limitation of mass spectrometers. Trapping ions with collisional cooling before mass analysis permits the motion of the ions to be completely defined by the applied fields. For this reason, this new inlet and trapping system represents a large step toward sensitive, high-resolution mass spectrometry into the megadalton range and beyond. (J Am Soc Mass Spectrom 2010, 21, 242-248) © 2010 American Society for Mass Spectrometry A rguably, the greatest advances in mass spectrometry of large molecules came with the introduction and development of electrospray ionization (ESI) [1] and matrix-assisted laser desorption ionization (MALDI) [2]. The creation of massive ions in vacuum was the start of a revolution in biological analysis using mass spectrometry. Unfortunately, the molecular weight range of mass specific biological species, such as proteins, RNA, DNA, and even viruses was much larger than the mass range of the mass spectrometer from which useful information could be obtained. Yet, the information was so valuable that a multitude of techniques and an entire industry was developed over the past 20-plus years so that these biological species could be analyzed using mass spectrometry. The essential thrust of the advances (beyond ionization) that have permitted the use of mass spectrometry for biological analysis has been in areas of sample preparation and analysis techniques, which allow analytes that are larger than the range of the mass spectrometer to be characterized with it anyway.The thrust of our efforts has been to increase the range of mass spectrometers where they achieve good resolution, mass accuracy, and sensitivity. Our analysis suggested that the overarching reason for the limitation of mass spectrometers in general was the expansioninduced kinetic energy distribution of the ions as they are injected in the mass spectrometer. The average and spread of the kinetic energy distribution of the ions expanding into vacuum monotonically increases with increasing mass. It is not difficult to compensate for the average increase for a particular type of ion; ho...

High Resolution Time-of-Flight Mass Analysis of the Entire Range of Intact Singly-Charged Proteins

“…It consists of a kinetic energy reducing inlet 8 and a large radius linear quadrupole ion trap 9 (25.4 mm rods) that is used to transfer the ions into vacuum and capture them to remove the residual expansion-induced kinetic energy. The details of the inlet and trapping systems for capturing massive singly charged ions are covered in references 8 and 9 respectively. A second smaller radius linear quadrupole ion guide/trap (12.5 mm rods) was added after the large trap to collect the ions before they are introduced to the orthogonal acceleration time-of-flight mass analyzer (oa-TOF) (RM Jordan Co. Inc.).…”

“…For the first time we show that intact singly-charged proteins over the entire range can be mass analyzed with high resolution and mass accuracy with our newly developed inlet, 8 trapping system 9 and digital waveform technology that permits trapped ions be injected into the TOF in a well-collimated ion beam 10 to obtain high resolution and mass accuracy at any protein mass. Rapid quantitation of complex protein distributions is now feasible by mass spectrometry.…”

Increasing the trapping mass range to m/z=109—A major step toward high resolution mass analysis of intact RNA, DNA and viruses

“…Our inlet and trapping system were designed on the premise of using aerodynamics to limit the effect of expansion into vacuum. [5] We step the expansion into vacuum. After each expansion step, we use collisions with a buffer gas to “stop” the expansion-induced motion of the ions so that their motion is defined by the carrier gas movement or the applied fields.…”

“…In our design, the ions undergo three separate expansions, the first at the flow limiting orifice, the second at the slit created by the spacing between the cylinder and the end plate and the final expansion normal to the expansion through the slit into the quadrupole where the kinetic energy from the final expansion is eliminated by collisions with the buffer gas inside the quadrupole before the ions reach the end of the guide. [5] The mass limit of the inlet/trapping system is defined by the stopping distance[12] of the ions after the expansion through the flow limiting inlet orifice. The distance between the flow limiting orifice and the entrance to the plenum chamber was approximately 25 cm.…”

“…[5] Later, we integrated our inlet and trapping system with an orthogonal acceleration time-of-flight mass analyzer and demonstrated that resolved mass analysis of singly-charged intact proteins could be obtained [6] using digital waveform manipulation [7] to inject the trapped ions into the mass analyzer in well-collimated temporally discrete ion packets. The mass range of the prototype instrument is limited by the detector (Photonis Bipolar Detector).…”