Fourier transform–ion cyclotron resonance (FT-ICR) is an advanced form of MS characterized by unrivaled mass accuracy and resolving power. In fact, the systems that use this technology tend to be quite large, and are mostly found in R&D labs where a requirement for extremely high performance can justify the high cost.

In a typical MS, an inlet system sends an appropriate amount of analyte into an ion source, where the analyte molecules are converted into ions. The ions are then manipulated with a mass analyzer that separates them according to their mass-to-charge (m/z) ratio and focused onto a detector that can interpret the data signal.

In FT-ICR MS, the mass analyzer is based on ion cyclotron motion, where a force exerted by a uniform magnetic field onto an ion will always be perpendicular to the ion’s velocity. This phenomenon is known as the Lorentz force. Because of it, a uniform magnetic field will perpetually turn an ion, resulting in a circular orbit that goes uninterrupted until acted on by another force.

This circular orbit, where an ion goes around and around, is referred to as cyclotron motion, in which the frequency of rotation depends on an ion’s m/z ratio and the magnetic field strength. In fact, the performance of an FT-ICR system improves as the strength of the magnetic field increases, which is why the majority of them are designed with superconducting magnets, resulting in instruments that are both very large and very expensive.

In FT-ICR MS, the ions enter cyclotron motion surrounded by detection plates. However, ion detection by these plates is not possible unless the ions are close enough to them. To expand the radii of the orbit and enable proper detection, excitation plates that generate an electric field with opposing sine waves are placed parallel to the magnetic field, one above the ion orbit and one below. This accelerates the ions toward one plate and then the other.

As the frequency of the electric field approaches that of the cyclotron motion frequency, the ion’s motion will resonate with the electric field, increasing its kinetic energy and, in turn, the radius of its orbit. The ions can then be detected as they pass near the detection plates. The ICR cell in which these interactions are confined is known as a Penning trap.

The signal is collected by the detection plates as a sum of various sine waves that represent the superposition of all m/z signals in the time domain. A Fourier transform must be used to convert this signal into frequencies, thereby creating a mass spectrum of the sample.

First developed in 1974 at the University of British Columbia, FT-ICR mass analyzers have the highest-recorded mass resolution of any mass analyzer. As such, these instruments are ideal for analyzing very complex chemical and biological samples, even without the need for a separation method such as GC or LC. They can also be configured with an additional mass analyzer, usually either an ion trap or quadrupole. Common applications include proteomics, metabolomics and lipidomics.

Despite the clear analytical advantages of FT-ICR, market adoption of the technology is inhibited by its high cost, large footprint and slow acquisition rates. This is especially the case as the technological advancement of alternative MS technologies slowly narrow the performance gap. Bruker dominates the market for FT-ICR MS through its solariX series, and there are very few alternative vendors. Thermo Fisher Scientific occupied a moderate market presence several years ago, but its products have since been discontinued. With a market of approximately $60 million in 2017, market growth for this technology is expected to remain flat for the foreseeable future.

FT-ICR at a Glance:

Leading Vendor:

• Bruker

Largest Markets:

• Academia
• Biotechnology
• CROs

Instrument Cost:

• $400,000–$2,000,000