Fast, Practical GC and GC-MS

Shortening run times is a welcome exercise for many laboratories, especially when sample throughput needs to be increased. In the past decade, the use of 0.10-mm-i.d. columns has been proposed.¹ However, in practice this diameter does not meet today’s expectations with respect to robustness, capacity, ease of use, and instrumentation. A good intermediate diameter that provides a practical alternative is 0.15 mm i.d. Such a diameter permits reasonable backpressures, efficiency, and robustness for handling different sample types.

The peak widths that are produced can also be measured sufficiently with current mass spectrometer systems. If required, loadability can easily be extended since 0.15-mm columns can be coated with up to 2 μm of stationary phase.

State-of-the-art stationary phase technology has resulted in a new generation of low-bleed GC capillary columns. FactorFour™ technology (Varian Inc., Middelburg, The Netherlands) has been implemented successfully with 0.15-mm-i.d. fused-silica capillary columns, offering a practical solution for faster analysis while maintaining the tight specifications needed. This paper discusses the application of 0.15-mm-i.d. fused-silica columns from both the theoretical and practical viewpoints, with the aim of reducing the run times by a factor of 2 simply by replacing the column. The key benefits of 0.15-mm-i.d. columns are: 

• Reduction in analysis time by a factor of 2 without loss of separation
• Ability to operate in existing instrumentation (GC and MS)
• Minimal changes to the method; ease of implementation
• Very low bleed, which provides high signal-to-noise
• Use of ferrules similar to 0.25-mm-i.d. columns
• Percent- as well as ppm-level analysis.

Analysis times

The analysis time of a GC application can be shortened, depending on the existing separation. There are two possibilities:

1. The sample components are well resolved (resolution factor >1.5) in the typical concentrations, and the faster solution allows a reduction in separation efficiency.
2. The sample components are just baseline resolved (resolution factor of 1.5). The faster solution must offer similar or better separation power without a compromise in resolution.

Many users prefer a column with extra separation power, which permits greater flexibility in daily operation, because maintenance intervals are longer.

Faster analysis with reduced separation efficiency

If the separation allows it, the first choice is to use a higher flow rate. This enables the components to elute faster, reducing the analysis time. Additionally, the benefit is that a lower elution temperature is obtained. Low elution temperature translates into reduced background, providing improved S/N. At a higher flow rate, the injection becomes more challenging. It is therefore recommended that the operator introduce the sample at optimal settings and use a pressure/flow program to elute the late-eluting components. Some systems can program up to 800–1000 kPa, which will challenge other parts of the system. With higher pressures, the risk of septum leakage will increase exponentially, which can cause many problems.

It is also possible to use a stronger temperature program or start the application at a higher temperature. This reduces the analysis time and leads to higher elution temperatures. At higher elution temperatures, the background will be higher, and the response of thermolabile components will decrease.

Shorter columns also generate faster results. Many applications can be performed on a shorter column with reduced separation efficiency. The user can benefit from additional separation power in order to run more samples before performing column/system maintenance. Also, vacuum outlet gas chromatography using short 0.53-mm columns with a restriction on the front (Rapid MS [Varian])² speeds up analysis significantly; however, a detector under vacuum (mass spectrometer) is required, which limits the application to MS systems.

Selective detection devices also allow the use of short columns since detection is specific for a limited number of compounds. Selective detection is usually sensitive, but is restricted with respect to quenching, linearity, stability, and ease of operation. Cost plays a role as well.

The run time of some applications can be reduced considerably by using a different stationary phase. Optimizing the selectivity of stationary phases for a targeted separation will provide the best starting point for the shortest possible analysis time. Optimization is possible by choosing a different phase or by coupling columns of different lengths and selectivities. This approach requires a full validation procedure, which is often lengthy.

Faster analysis with similar separation efficiency

The easiest ways to speed up analysis while maintaining the separation power of the existing solution are as follows:

1. Usinghydrogen as carrier gas. Optimum gas velocities are 1.5–2 times higher compared to helium, while separation efficiency remains the same. It seems like the logical choice, but issues of safety using hydrogen still exist and must be resolved. The biggest concerns are the danger of leakage, accumulation in the oven, and possible explosion in the GC. These matters cannot be ignored. However, the risks can be minimized considerably if proper precautions are taken. For instance, using the digital flow regulating systems, flow settings can be maximized that will never allow a buildup of hydrogen up to the explosion level. (If a leak is present, the pressure will not reach the desired value and an alarm will sound.) Also, there are hydrogen monitoring systems that measure hydrogen levels in the oven and will close the supply line when the level exceeds a certain threshold. UltiMetal-type capillary columns (Varian) are available that are virtually unbreakable, reducing the risk of column breakage considerably. On the practical side, operators must be aware of the safety precautions necessary when using hydrogen. The general trend in many laboratories is that GC operators are becoming less experienced in operating and troubleshooting GC, and this results in increased risk factors. In mass spectroscopy, the application of helium is standard. In addition, in some countries it is relatively inexpensive to use helium. On the other hand, hydrogen can be produced in the laboratory using hydrogen generators; thus, more laboratories are working with hydrogen. Of course, split flows must be safely vented.
2. Using a smaller-i.d. capillary column. The plate number increases linearly with decreasing column diameter. A column with a 2× smaller i.d. can also be 2× shorter, while producing similar separation efficiency. Theoretically, the column diameter can be made very small. However, there are also practical considerations that must be considered, for instance, the width of the eluting peaks, loadability, flow rates, injection techniques, ease of use, and robustness. Columns with i.d.’s of 0.10 mm have long been promoted by several manufacturers; however, the 0.10-mm capillary has not been used to replace 0.25/0.32-mm-i.d. capillaries. Proper implementation requires investment in a GC that is dedicated to using 0.10-mm columns. A good intermediate has been found in the 0.15-mm-i.d. capillary. This dimension provides an easy way to speed up applications by a factor of 2 while maintaining separation power. In addition, the 0.15-mm-i.d. columns can be used in existing GC as well as GC-MS hardware, which offers the option for accelerating many applications with minor investment and risk.