GC-MS vendors typically describe and characterize their systems using a small set of specifications that include octafluoronaphthalene (OFN) signal to noise ratio (SNR), mass range and scan speed. As a result, improvements in GC-MS are often focused on the incremental increase of these few specifications. However, GC-MS is characterized by many additional features and operational parameters that contribute to its performance, and their improvements can make a big impact on the GC-MS analytical capabilities. Many such GC-MS aspects are improved by incorporating the new Cold-EI GC and MS interface and ion source technology and by using "out of the box" thinking. In LC-MS, the biggest revolution was brought not by LC or MS improvements but rather by the development of a new interface and ionization method namely Electrospray. Similarly, Cold EI with its supersonic molecular beams interface and fly-through ion source brings multiple benefits and improvements into GC-MS which can initiate a new GC-MS revolution. This blog post lists 62 GC-MS improvements brought forth by the Cold EI interface and ion source, encompassing any and every important aspect of GC-MS, and explains how the unique features of GC-MS with Cold EI enable these benefits.
|Figure 1. A schematic diagram of the 5975-SMB GC-MS with Cold EI. It is based on the Aviv Analytical conversion of Agilent 7890 GC + 5975 MSD (or 5977 MSD) into GC-MS with Cold EI. The various elements are indicated by their names.|
- Fast chromatography separation for improved mixtures analysis.
- Library based sample identification is enabled combined with isotope abundance analysis software for best identification.
- Cold EI uniquely provides uniform compound independent response for improved quantitation. Furthermore, quantitation by Cold EI does suffer as ESI or APCI from any ion suppression effects.
- Extended range of thermally labile and low volatility compounds are amenable for analysis.
- Swabs can be used to bring samples from remote surfaces combined with full thermal desorption.
- An in-vacuum ion source is used hence the instrument cost less and the broad install base of Agilent 5975/7 GC-MS can serve for the accommodation of Open Probe Fast GC-MS.
- The same system can be operated with a second injector as GC-MS.
- No solvent is used unlike with DESI while the helium gas consumption is about 50 times lower than in DART.
A) Improved selectivity. Cold EI enhances the abundance of the molecular ion which is the most selective ion in the mass spectrum. Furthermore, when the molecular ion serves in MS-MS as the parent ion the daughter ion mass is typically higher than when a fragment is used as the parent ion. Consequently, the MS-MS selectivity is significantly improved by an estimated two orders of magnitude in the use of molecular ion instead of a fragment ion as the MS-MS parent ion.
B) Improved instrument sensitivity. While MS-MS on the molecular ion further reduces matrix interference it also serves to increase the number of daughter ions signal hence the instrument sensitivity. This improved MS-MS sensitivity emerges in two ways of: 1) Molecular ions as parent MS-MS ions require lower CID voltage and they dissociate in the CID process into lower number of fragment ions which are better retained by the RF only Q2. The molecular ion is easier to dissociate than a stable fragment ion that was formed in the EI process since abundant fragments are abundant as they are typically stable fragments and thus are harder to break. The higher typical CID voltage used with fragments creates more energetic lower mass daughter ions that are harder to retain in Q2. 2) The increased selectivity of MS-MS on the molecular ion can be translated into up to an order of magnitude higher signal via the use of lower Q1 and Q3 resolution.
C) Extended range of compounds amenable for GC-MS-MS analysis. GC-MS-MS is mostly used with groups of target compounds such as pesticides and drugs, which include significant portion of thermally labile compounds. As a result, GC-MS-MS suffers from growing competition with LC-MS-MS on those types of analyses. Cold EI enables the analysis of much greater range of those pesticides and drugs and can even serve for the analysis of pesticides that are difficult to analysis by both GC-MS-MS and LC-MS-MS such as captan, captafol and folpet. Furthermore, GC-MS-MS with Cold EI can uniquely serve for the confirmation of LC-MS-MS labile samples.
D) Faster GC-MS-MS analysis. Since the selectivity against matrix interference is improved with Cold EI, one may wish to translate the added selectivity into faster analysis. Cold EI can serve to achieve faster GC-MS-MS analysis all the way to under one minute ultra-fast GC-MS-MS full analysis cycle time as demonstrated in .
In addition, many of the GC-MS improvements listed in this blog note are applicable for GC-MS-MS.
A) In the analysis of a mixture of compounds that includes a relatively volatile thermally labile compound the transfer line is maintained at a relatively low initial temperature such as 180°C and only after the elution of the thermally labile compound(s) its temperature is increased to prevent peak broadening for the late eluters. A typical example is the analysis of pesticides that include the relatively volatile thermally labile carbamate pesticides (aldicarb, methomyl etc.) as well as less volatile pesticides, and similarly explosives mixtures that include TATP;
B) Lower initial transfer-line temperature results in lower PDMS transfer line bleed, providing lower MS noise and increased sensitivity;
C) Every syringe injection includes about 0.5-1 µL air in the empty portion of the syringe needle. Consequently, even if the column is cooled during the injection, the pure air that is inevitably injected interacts with the column at its transfer line section, induces PFMS bleeding noise and makes this portion of transfer-line column active with exposed silanol groups. The use of temperature programmable transfer-line significantly reduces this problem.
52. Compatibility with hydrogen or nitrogen carrier gases. In certain cases the helium supply could be interrupted and one might wish to consider working with hydrogen or nitrogen as the carrier gas. As described in our blog article. the use of hydrogen with standard EI could lead to the chemical activation of the GC liner and ion source, while the use of nitrogen significantly reduces the ion source ionization yield due to significantly (x7) increased ion source space charge. Cold EI can uniquely operate with nitrogen as the column carrier gas and hydrogen as make up gas with minimal loss in sensitivity as described in our post on the topic.
similarly, the combination of so many improvements creates a new and qualitatively superior technology that actually improves every type of analysis. While GC-MS with Cold EI improves challenging analyses it does not impede on any simple method of analysis (compared with standard EI) and its added cost could be negligible in a fully integrated GC-MS with Cold EI. Consequently, GC-MS with Cold EI is destined to become the future GC-MS revolution.
As a good closure of this article we quote Freeman Dyson from his book "Imagined Worlds":
"New directions in science are launched by new tools much more often than by new concepts. The effect of a concept-driven revolution is to explain old things in new ways. The effect of a tool-driven revolution is to discover new things that have to be explained."