Experimental Design of SIFT-MS (Slow Ion Flow Tube Mass Spectroscopy)

What is SIFT-MS

Slow Ion Flow Tube Mass Spectrometry (SIFT-MS) has been commercially available for some decades now, and we have been taking advantage of the fruits of its chemistry ever since. SIFT-MS is a form of spectroscopic analysis that can examine a myriad of varying volatile organic compounds within different pharmaceutical products.

The optimization of this tool allows for real-time selective analysis of trace gases, and headspace analysis. What differentiates this experimental design from other forms of mass spectroscopy is how it incorporates its ionization process. This is what gives this apparatus its key characteristics.

Investigations using SIFT-MS are achieved using eight atomic ions, incorporating very soft ionization processes. These ions are generated for moist or dry air and are interchangeable using the quadrupole mass filter. This optimized form of mass spectroscopy permits the sample medium to be introduced directly into the device without any requirement for preparation, workup, or pre-concentration, delivering quantitative measurements to the parts per trillion.

How Does SIFT-MS Work?

The SIFT-MS Apparatus

This device is comprised of three sequential steps: reagent ion selection, analyte ionization, and analyte quantitation.

Firstly, microwave plasma is used to achieve the energy threshold required for ionization to occur. This is accomplished through the use of four cationic and four anionic species. It is assumed that these charged species will not interreact with the carrier gas that flows through the apparatus (typically helium or nitrogen). This optimization in experimental design ensures that no membrane or column is required to filter. This carrier gas is used to cool the ions through collisions, controlling the thermal energies of all species.

Once the sample has been properly ionized, a quadrupole mass filter is then used to individually apply one of the eight reagent ions. This will allow for a mass to charge ratio (m/z) to be taken of the vast majority of analytes. From the (m/z) ratio of each analyte, using the kinetics database stored in the instrument library, the concentrations of target VOCs can be obtained nearly instantaneously.

Analyte quantitation then terminates the process, with filtering of the reagent and product ions towards the downstream end. This is achieved through the particle multiplier tube that is fixed to the SIFT-MS instrumentation, using a single ion counting mode (SIM).

The application of gas-phase kinetics and continuous measurements of remaining reagent and product ions provides a major boon. This form of chemistry results in data that can be delivered in real-time.

How SIFT-MS Compares to Traditional Chromatography, GC-MS, and LC-MS

In the real world, medicinal solutions and organic matter typically contain a substantial number of different volatile organic compounds (VOCs). This presents a problem for traditional chromatographic methods. The fact that each VOC can differ in polarity and molecular weight, infers that different column chemistries are required to elute.

To achieve optimum separation, a thermal or polar gradient is often incorporated, whether it be used in standard liquid chromatography, or high-performance liquid chromatography (HP-LC). This aspect of experimental design will sacrifice throughput and will require additional computations to be made, depriving the researcher of valuable lab time.

The speed at which chromatography can be performed is also dwarfed by a direct gas-phase analyzer. The experimental design of chromatography can be optimized using narrow broad columns, however, the loading of the device, the dead volume time, and the time it takes for analytes to pass through the column can all be circumvented using SIFT-MS.

For smaller nonpolar molecules, GC-MS or gas chromatographic methods are usually the methods of choice. If larger molecules were the given analyte, with higher polarities, we would traditionally use a liquid chromatographic method. But what about molecules of higher polarity and lower molecular weight, such as formaldehyde?

One could derivatize the analyte using a chromophore containing molecule like DNPH effectively increasing the molecular weight. However, altering the chemistry of the parent molecule will yield less accurate results.

Fortunately, SIFT-MS can allow for high polar, low molecular weight molecules to be analyzed through the gas medium, requiring small alterations in charge rather than the addition of substantially larger functional groups.

SIFT-MS Methodologies of Non-invasive Detection of Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common form of cancer worldwide, with approximately 630,000 new cases diagnosed each year. Though blood tests can be run, the detection of said illness typically occurs only when the disease is very advanced.

Squamous-cell Carcinoma

Squamous Cell Carcinoma. Image Credit: Designua/Shutterstock.com

MRI imaging can be incorporated, though devices such as these are not widely available. The most accurate tool to assess this disease would be a brain biopsy, though the removal of cerebral tissue has a fairly high mortality rate, with quite a lot of risk involved.

Results have shown that the experimental design of SIFT-MS could be used to classify potential breath biomarkers for the non-invasive detection of HNSCC. Using SIFT-MS SIM scan analysis, breath samples were analyzed by measuring all product ions with masses ranging from 10 to 250 atomic mass units, over 50 cycles. 91 different VOCs were detected within the gas phase medium, emphasizing the useful chemistry that encompasses breath biomarkers.

High concentrations of hydrogen cyanide were discovered in the breath samples of HNSCC patients compared to non-cancer controls. VOCs previously associated with HNSCC, such as hydrocarbons, alkanes, alkanes, and nitriles, were not elevated above the levels of non-cancer groups in several studies. Findings using SIFT-MS have added to the growing body of evidence of the detection of VOCs in HNSCC.

Overall, the initial pilot study demonstrated the feasibility of SIFT-MS technology to identify VOCs for the detection of HNSCC. SIFT-MS is shown to be an effective technique for the real-time analysis of volatile compounds. The versatility and optimization of SIFT-MS is unparalleled in the current market and fit a niche that desperately needed to be filled.


  • Technologies, Sponsored by Syft, and In association with Commonwealth Chemistry. “Rapid Volatile Impurity Analysis in Pharmaceutical Products Using SIFT-MS.” Chemistry World, SYFT Technologies, 20 Aug. 2018, www.chemistryworld.com/webinars/rapid-volatile-impurity-analysis-in-pharmaceutical-products-using-sift-ms/3009396.article?adredir=1#/.
  • Chandran, Dhinashini, et al. “The Use of Selected Ion Flow Tube-Mass Spectrometry Technology to Identify Breath Volatile Organic Compounds for the Detection of Head and Neck Squamous Cell Carcinoma: A Pilot Study.” Medicina (Kaunas, Lithuania), MDPI, 25 June 2019, www.ncbi.nlm.nih.gov/pmc/articles/PMC6631766/.
  • Ioannidis, K. et al. Quantification by SIFT-MS of volatile compounds produced by the action of sodium hypochlorite on a model system of infected root canal content. (2018). Available at:  https://storage.googleapis.com  
  • Hewitt, M. Using selective ion flow tube mass spectrometry (SIFT-MS) to find biomarkers for liver disease. https://www.youtube.com/ (2021). Available at: https://www.youtube.com/watch?v=2LNIVn-acwI.

Further Reading

Last Updated: Apr 27, 2021

Vasco Medeiros

Written by

Vasco Medeiros

Obtaining an International Baccalaureate Degree at Oeiras International School, with higher levels in Chemistry, Biology, and Portuguese, Vasco Medeiros is now a Senior enrolled in Providence College. He will attain his degree on May 20 th , 2021. Before his work as an undergraduate, he first began his vocational training at the HIKMA Pharmaceuticals PLC plant in Ribeiro Novo. Here he worked as a validation specialist, tasked with monitoring the gauging and pressure equipment of the plant, as well as the inspection of weights and products.


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