Advancements in Ion Mobility Spectrometry (IMS)

By Stefano Tommasone Ph.D.Reviewed by Danielle Ellis, B.Sc.

Ion mobility spectrometry (IMS) involves the separation of ions based on their mobility in a carrier gas under the influence of an electric field. It is a powerful technique that has proven valuable in detecting and identifying various chemical compounds. This technique has applications in different fields, including environmental analysis, food and process control, security, and forensics.

Ions are accelerated by an electric field, which forces them to migrate through a drift tube filled with a buffer gas. The ions’ velocity is correlated to their mobility and characteristic collision cross-section (CCS). Larger ions experience more collisions with the buffer gas and, therefore, take longer to migrate through the drift tube compared to smaller ions, which conversely undergo fewer collisions and, hence, have greater mobility.

The origins of IMS go back to the early 1900s – with the initial work by Thomson and Rutherford on the relationship between electrical conductivity and gaseous media – although it was in the 1960s that IMS experienced rapid growth and found practical applications.

Advances in instrumental design pushed the popularity of IMS forward by enhancing its sensitivity and selectivity, and over the last few decades, it has been particularly used as a standalone technique in the detection of explosives and hazardous materials.

In its classic version, also known as drift-tube IMS (DTIMS), the reduced mobility can be used to calculate the CCS of ions. Other methods have been developed, such as differential mobility analysis (DMA) and transversal modulation IMS (TMIMS), or traveling wave IMS (TWIMS) and trapped IMS (TIMS), where the CCS can be obtained through calibrations.

Recent Advancements in IMS Technology

Technological breakthroughs have significantly enhanced the capabilities of IMS. Although standalone instruments are powerful devices, coupling with gas chromatography, liquid chromatography, or mass spectrometry enables the achievement of multidimensional separation with increased levels of selectivity and sensitivity.

Since IMS separations only take a few milliseconds, they can be easily carried out after chromatographic separations or hyphenated with mass spectrometry analysis. GC-IMS hyphenation has been widely applied to the analysis of volatile compounds and is particularly effective on food samples where standalone IMS normally suffers of low resolution.

The integration of IMS in LC-MS is becoming very popular. This approach introduces a third separation dimension, thus improving peak capacity at least 2 or 3-fold, allowing the separation of isomers.

Remarkable advancements have been achieved with the integration of IMS and mass spectrometry (IMS-MS). The two techniques provide complementary information, enhancing the overall sensitivity of the analysis and achieving higher accuracy in compound identification and quantification, particularly in complex sample matrices.

Applications of Enhanced IMS in Various Fields

There are several fields that can benefit from the advancements in IMS technology. For instance, in the pharmaceutical industry, the ability to separate isomers and closely-related species can enable researchers to characterize complex mixtures, facilitating the drug development process. In addition, IMS methods have been used to resolve isomeric mixtures of biomolecules, including peptides, carbohydrates, and lipids.

Thanks to an almost real-time monitoring capacity, ion mobility spectrometers are frequently used at security checkpoints in airports for the detection of explosives such as pentaerythritol tetranitrate, 2,4,6-trinitrotoluene (TNT) and 1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) with detection limits in the nanogram range.

Environmental monitoring is another field where the technique finds several applications, particularly for the detection of trace levels of pollutants in air and water. IMS is well suited for the analysis of volatile organic compounds (VOCs) for air quality assessment both indoors and outdoors.

Through in-situ measurements from multiple locations, it was possible to identify several VOCs, including ethanol, 1-propanol, 2-propanol, and ethyl acetate. Similarly, the use of GC-IMS allowed the analysis of α-pinene, limonene, and acetone, with detection limits below 0.7 ng.

Impact of Improved Sensitivity in IMS

The increased sensitivity of IMS technology has opened opportunities in previously challenging areas. As technology continues to evolve, there are exciting possibilities for future applications, such as the detection of low-abundance metabolites in biological samples, with implications for understanding disease pathways, biomarker discovery, and personalized medicine.

Advances in IMS have improved the quality control processes in manufacturing. For instance, in the food and beverage industry, IMS is used to detect and quantify contaminants. In environmental safety, governments and regulatory bodies rely on IMS to ensure compliance with environmental standards and regulations.

Over the past decade, efforts have been focused on the production of commercial instrumentation. Moreover, the ability to operate at atmospheric or reduced pressure makes IMS ideally suited for the development of small portable devices – more accessible and user-friendly – eliminating the need for complex sample preparation.

Challenges and Future Directions

Since ions can collide with the buffer gas in a number of different orientations, a caveat is that the CCS data give a rotationally averaged value. This can impair the capacity to analyze molecules that have a complex three-dimensional structure, such as proteins. However, it has been shown that the issue can be overcome when IMS is used in conjunction with mass spectrometry.

Another limitation of the technique is linked to the complexity of data analysis, particularly in high-dimensional datasets generated by advanced IMS-MS instruments. Research efforts are currently focused on developing algorithms and data processing tools to address this challenge.

IMS is experiencing constant innovation, such as the integration of ultra-high-resolution mass analyzers. Future developments may also focus on improving the speed of analysis and increasing the robustness of instruments.

Conclusion

Over the last few decades, IMS has proven to be a versatile analytical technique with great sensitivity and specificity for the study of different types of compounds. Although it was initially mostly used for basic research, IMS has played a relevant and innovative role in various fields, from food analysis to environmental safety, pharmaceuticals, and structural biology.

Technological advancements have started to broaden the scope of IMS and drive its use in real-life applications, particularly thanks to the development of commercial, portable devices. As the technique continues to evolve, it holds the potential to achieve greater accessibility, speed, and accuracy.

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