Gas chromatography is a central analytical technology having a large variety of applications in a broad range of fields, especially when used in association with mass spectrometry for improved sensitivity, selectivity and sample identification capability.
However, while gas chromatography (GC) is a powerful analytical tool, GC analysis requires long analysis times, typically in the order of 30-60 min. In addition, the range of compounds amenable to conventional gas chromatography analysis with standard gas chromatography columns (typically 30 m) combined with standard column flow rates such as 1 ml/min is limited to stable and volatile compounds only, since thermally labile compounds can degrade due to overheating while low volatility compounds are unable to elute.
In view of the long time associated with standard GC analysis, several fast GC systems have been developed that incorporate low thermal mass devices that provide fast temperature programmable heating and cooling rates for the GC separation columns.
For example, Rounbehler, et al describe in U.S. Pat. No. 5,808,178 a fast GC module named “Flash GC” which is based on a capillary GC column inside a resistively heated metal tube which can be quickly heated and cooled due to its low thermal mass to achieve rapid separation of analytes. Resistive heating is based on the principle that the temperature of a metal increases when an electrical current is passed through it, and the metal resistance increases, consequently, in a manner that can be predicted. The metal temperature can be determined by its electrical resistance measurements and can be adjusted by controlling the amount of power applied to it to reach a defined temperature set point.
However, as is well known, fast GC is the art of compromises, and speeding up the GC temperature programming rate alone can result in the reduction of GC separation efficiency, column lifetime, range of compounds amenable for analysis, sample capacity, linear dynamic range and sensitivity, combined with increased cost of columns which can be coupled with the cost of the whole fast GC module.
Furthermore, fast GC and particularly fast gas chromatography mass spectrometry (GC-MS), in which a mass spectrometer serves as the GC detector, require much more than just fast temperature programming rate of the GC oven. For example, standard splitless sample injection takes a few minutes, since it requires one minute just for sample cryo-focusing at low GC oven temperatures plus additional time for heating to the analytically useful column temperature and cooling back. While split injection may reduce the time required for sample introduction into the column, it leads to unavoidable and often unacceptable loss in limit of detection and sensitivity. Furthermore, fast GC may give rise to narrow GC peaks which may require fast detector response time and in case of mass spectrometry it requires the combination of fast scan speed and fast ion source response time. Above all, there is a major difference between fast GC and fast GC-MS in that in GC-MS the mass spectrometer adds an additional dimension of sample separation and selectivity which can be further enhanced with tandem mass spectrometry (MS-MS) such as in triple quadrupole mass spectrometry systems. The basic idea is that in fast GC-MS GC separation can be traded (and some chromatographic peaks co-elution can be allowed) for having additional separation of the MS while in fast GC, the GC separation is its prime feature which often cannot be reduced.
Thus, despite the obvious merit of having fast GC and/or fast GC-MS and its availability in the market, the vast majority of GC and GC-MS analysis still takes more than 20 minutes.
In the last 18 years, Applicants' research has been focused on the development of a new type of GC-MS which is based on the use of supersonic molecular beams (SMB) (also named Supersonic GC-MS). Supersonic GC-MS is based on a GC and MS interface with SMB and on the electron ionization (EI) of vibrationally cold analytes in the SMB (cold EI) in a fly-through ion source. This ion source is inherently inert and further characterized by ultra fast response time and vacuum background filtration capability. The same ion source also offers a mode of classical EI. Cold EI, as a main mode, provides enhanced molecular ion combined with effective library sample identification which is supplemented and complemented by a powerful isotope abundance analysis method and software. Applicants note that the feature of enhanced molecular ion also implies enhanced separation power of the mass spectrometer since, as is well known, matrix interference is exponentially reduced with mass. In addition, the range of low volatility and thermally labile compounds amenable for analysis is significantly increased with the Supersonic GC-MS due to the use of contact-free fly-through ion source and the ability to lower sample elution temperatures through the use of high GC column carrier gas flow rates. Another important feature of the Supersonic GC-MS is its compatibility with high column flow rates without any adverse effect on its sensitivity due to the availability of a differential vacuum chamber for the supersonic nozzle. As will be shown below, this feature is very important for the combination of the novel fast GC method and device according to the present invention with the Supersonic GC-MS.
USPTO Backgrounds
USPTO Backgrounds