What is GCxGC?

GCxGC (2D GC or multi-dimensional GC)

Comprehensive two-dimensional gas chromatography, commonly known as GCxGC, separates a sample using two chromatographic columns with different properties, run in tandem.

Having two dimensions of separation means that GCxGC provides greater separation capacity than conventional (one-dimensional) GC, enabling complex mixtures to be resolved, and revealing minor components that would otherwise be ‘hidden’ under larger peaks.

In GCxGC, the use of two columns with different properties results in a greater ability to separate complex mixtures.

How does GCxGC work?

GCxGC involves two columns: a primary column that is typically 20–30 m long, and a short secondary column that is 1–5 m long. The two columns are connected with a modulator. As in one-dimensional GC, the sample is introduced into a heated port and swept through the primary column by a carrier gas. The peaks that elute are then sampled (ideally three or four times per peak) and each fraction is re-injected as a narrow chromatographic band into the secondary column. Passage through the secondary column is quick to ensure sharp peaks and no band overlap, with elution usually taking place in under 10 seconds. Following elution from the second column, detection takes place, and the signal is processed to generate a three-dimensional ‘surface plot’ (which can alternatively be viewed as a two-dimensional ‘contour plot’).

The operation of GCxGC. The sample passes through a primary column, before being split up by a modulator and passed into a secondary column.

Importantly, the primary and secondary columns used in GCxGC have different stationary phases, allowing a mixture to be separated on the basis of two different properties – typically volatility (molecular weight) and polarity. These can be set up in one of two ways:

Normal-phase GCxGC uses a non-polar primary column and a polar secondary column, and is the standard approach for most applications.
Reverse-phase (or inverse-phase) GCxGC uses a polar primary column and a non-polar secondary column. This setup provides better separation of analyte groupings in certain cases.

What’s the purpose of a GCxGC modulator?

The most critical part of the GC×GC system is the modulator, which samples the analytes eluting from the primary column and injects them as narrow bands into the faster-eluting secondary column. This preserves the separation achieved in the primary column and prevents the short secondary column from becoming overloaded.

There are two main types of GCxGC modulators:

Thermal modulators use hot and cold jets to retain or desorb analytes eluting from the primary column.
Flow modulators use precise control of carrier and auxiliary gas flows to fill and flush a sampling channel or loop.

Thermal modulators provide sharp peaks to maximise sensitivity and chromatographic resolution. However, they suffer from the drawback that they cannot trap analytes boiling below C₅ (even when they use liquid cryogen in the cold jet), limiting the application scope. Flow modulators, in contrast, can cope with the most volatile analytes, while at the same time avoiding the need for expensive cryogen. Modern flow modulators, such as our INSIGHT^® flow modulator, also use ‘reverse fill/flush’ dynamics to overcome the issue of analyte breakthrough that was a problem with earlier ‘forward fill/flush’ designs.

What are the benefits of GCxGC?

Compared to one-dimensional methods, GCxGC offers several benefits:

Increased peak capacity, meaning better ability to analyse complex mixtures and detect ‘hidden’ components.
More effective removal of background signals, meaning improved signal-to-noise ratios and better sensitivity.
Simultaneous monitoring of multiple compound classes, meaning simplified sample preparation (and no need for prior fractionation).
Structured elution of compound groups, meaning easier identification.

Just like one-dimensional methods, GCxGC is quantitative, highly reproducible, and compatible with a range of detectors, including FID and TOF MS.

What applications is GCxGC used for?

GCxGC began as a highly specialised tool for researchers, but as the technology and software have been improved, and the user experience become more streamlined, applications have expanded.

Today, GCxGC is increasingly being used for many routine applications that can benefit from the technique’s ability to separate highly complex mixtures. These include: