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High-Quality Chemical Detection Where It Is Needed Most

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Although ion mobility spectrometry (IMS) has been extensively used for chemical analysis in security and forensic applications, performance issues have limited its wider use. The development of high-performance ion mobility spectrometry (HPIMS) has enabled significantly enhanced detection capabilities at the point-of-need, expanding the range of potential applications that can benefit from the technique.

To find out more about HPIMS, Technology Networks spoke with Dr. Ching Wu, founder and chief executive officer at Excellims and a pioneer of HPIMS. In this interview, Dr. Wu talks about the advantages that the technique can offer in applications ranging from pharma PAT to clinical diagnostics, and discusses how Excellims is increasing accessibility to the technology.

Anna MacDonald (AM): Can you give us an overview of ion mobility spectrometry (IMS) and some of the traditional uses of the technology? What limitations are associated with the technique?

Dr. Ching Wu (CW):
An ion mobility spectrometer can measure ion mobility of a gas phase molecule, which is related to the molecular size and shape, indicating structure characteristics. This is different from a mass spectrometer that measures the mass (mass-to-charge ratio) of the molecule. Integrated ion mobility spectrometry - mass spectrometry offers more than one way to understand a gas phase molecule: now we not only know how heavy (mass) the molecule is, we also know how big (collision cross section) the molecule is. IMS and MS provide complementary information on the structure and composition of analytes. 

Traditional applications for the technique are in chemical detection as a portable device, such as for the identification of explosives, illicit drugs, adulterants in drugs and food, contaminants in the environment and more. However, the portable devices all suffer from poor performance and limited volatile chemicals.

Several large lab-scale ion mobility mass spectrometry instruments have been introduced in recent years. These are high-performance analytical instruments, but they are cumbersome when trying to take a measurement at the point-of-need and are fixed to one research site only. For separations in complex matrices, liquid chromatography combined with mass spec has been the technology of choice. These technologies are separating molecules based on the molecular polarity or mass of the molecule. However, they can only be used in a lab setting. IMS can separate molecules from a different angle, the molecular size (collisional cross-section), and with greater speed, which gives you another powerful tool to separate molecules in a complex mixture.

AM: How does HPIMS address these shortcomings and expand the range of applications that can benefit from the technique?

HPIMS enables commercial fieldable IMS for point-of-need analysis with significant performance enhancement. It maintains performance (sensitivity and resolution) in a compact size. HPIMS delivers resolution as good as HPLC, but is much faster. Ion mobility spectrometers historically lack the performance specifications required by many analytical labs for routine analysis.  With a resolution greater than 70 and sensitivity down to the single ppb (ng/mL) level, HPIMS brings the speed of IMS into the hands of the analytical scientist. HPIMS technology significantly enhances detection capabilities at the point-of-need. With the robustness of IMS and performance beyond some of the miniaturized mass spec, HPIMS overcomes the traditional limitations of IMS and brings it to the center stage for point of analysis. The performance capabilities of HPIMS means it can be deployed for applications in the lab, in the field or on the production floor.

With the electrospray ionization (ESI) method, the HPIMS expands its range of applications to include large organic and biological molecules.

AM: Can you tell us more about the potential of HPIMS in clinical diagnostics? How does it compare to currently used technologies? What advantages could it offer?

Within life science applications, particularly for human samples, we’re seeing the sample getting more and more complex. No matter what complex sample you are analyzing, you are looking to quantify those target molecules among millions of others. Ion mobility is a non-invasive and reliable solution for clinical diagnostics through the analysis of volatile and non-volatile metabolites and other biomarkers in biological samples such as breath, oral fluid, urine, and blood. The medical diagnostics industry has been calling for non-invasive, robust, secure, fast, real-time, and low-cost methods to diagnose different diseases. Specifically, they require these capabilities in a high sensitivity and compact instrument that can be operated by non-experts.

Typically, users must purchase a lab-based HPLC-MS for clinical diagnostics.  Along with high cost, the laboratory systems require highly trained professional operators. The MC3100 HPIMS-MS combines ambient pressure high performance ion mobility technology with a patented intelligent vacuum system. It is an integrated ion mobility-MS instrument with high ion mobility resolution compared to common HPLC and MS resolution better than unit mass resolution in a small footprint, bringing the technique to the point of care, and into the hands of operators who need the highest quality chemical detection where it is needed most.

AM: How is the adoption of HPIMS impacting the biopharma sector?

HPIMS can be directly used to analyze nonvolatile compounds and biologics, such as the key components in the biomanufacturing process: organic acids, amino acids, carbohydrates, proteins and peptides, and others. This makes HPIMS useful for monitoring bioprocessing. For example, HPIMS was used to monitor a fermentation process.

An HPLC-HPIMS system can be used at-line in bioprocessing. Currently, such a system can provide results in minutes. Such testing only takes microliters of a sample that is filtered, diluted, and injected in the monitoring system.

AM: What makes HPIMS well suited for use in the field?

HPIMS inherited the robustness and resistance to contamination of IMS systems that can be used in harsh environments. In addition, HPIMS opened up the range of samples with new ionization methods, making it a strong in-field performer for not only chemicals but also biologics. In contrast to MS, it operates without a vacuum system, reducing the in-field service needs. Compared to HPLC, it eliminated the need for organic solvent handling and disposal. It is a true “plug and play” standalone point-of-need system for life science applications. 

AM: Why has the power of ion mobility spectrometry remained out of reach to many? How is Excellims increasing accessibility?

IMS used to be made for special applications, namely security, forensic labs, and military applications. The conventional IMS manufacturers have a focused market and had a difficult time trying to expand beyond their conventional markets. Applying IMS to life science, medical applications, and other new application areas requires the conventional IMS to perform to the level of other life science tools. In fact, the lack of performance of conventional IMS limited its acceptance in active applied markets where chromatography and mass spec offer a variety of solutions. Excellims developed and commercialized the high-performance ion mobility spectrometer (HPIMS), which operates like conventional IMS, but delivers performance that is comparable to HPLC, and in some cases superior to portable MS. We have also added the electrospray ionization source. Now the HPIMS can be used as a full featured point-of-need life science tool in the pharmaceutical / biopharmaceutical industry.

Dr. Ching Wu was speaking to Anna MacDonald, Science Writer for Technology Networks.