16 February / March 2021
Figure 4. Mass spectrum of cocaine in MS-only mode of operation (left) and mobility-selected mass spectrum of cocaine. The IMS reactant ion peak is excluded from the trap, greatly reducing chemical noise from the ion trap MS.
HPIMS-MS Instrumentation
Arguably, a hyphenated HPLC-MS system is the most powerful analytical tool currently employed in most analytical laboratories. However, when an analytical tool is needed at the point of analysis, e.g. in a clinical setting or a biomanufacturing plant, HPLC-MS is not always practical. The instrumentation is big and bulky and not designed to be used outside a laboratory environment; it has a slow analysis time (minutes to hours); is complex to operate and requires a highly skilled user; and in addition, it is normally associated with higher instrument and operational costs.
HPIMS achieves, for example, isomer separation based on ion mobility. In layman’s terms, ion mobility based separation is commonly considered to be based on molecular size. While there is a general relationship between molecular size and molecular weight, as a larger molecule is normally heavier, structural differences produce deviations from that overall trend. Efforts have been made to build libraries of molecular collision cross section [8] for large biomolecules.
Figure 2 shows a block diagram of a HPIMS-MS system, comprised of an atmospheric pressure drift tube ion mobility analyser coupled to a linear ion trap mass spectrometer with traditional hyperbolic geometry. After ion mobility separation, one or more ion packets may be selectively passed to the mass analyser. Similar to the HPLC-MS, a two-dimensional separation based on ion mobility and mass (m/z) can be achieved. For in-field applications, the
device is commonly used for targeted analysis, i.e. a targeted chemical can first be detected by IMS based on its mobility and then further confirmed by MS based on its mass; all of this occurs in one instrument, using a single sample.
1.Enabling MS to Perform at the Laboratory Level in the Field The HPIMS-MS system provides lab- quality performance in an AC powered, compact, field portable unit with a small footprint. Outer dimensions are 17”H x 16”W x 26”L for the complete system, including all vacuum pumps, HPIMS analyser and linear ion trap mass analyser, instrument control and data processing hardware and software. During analysis of the HPIMS-MS system, a sample can be introduced via thermal desorption and a corona discharge ionisation source, or an ESI source. Ionised samples are first separated by the HPIMS, detected by the detector of the HPIMS, and then introduced into the MS.
Figure 3 shows the mass spectrum of Venlafaxine, a pharmaceutical drug sample, which was introduced to the HPIMS-MS via an ESI source. Unit mass resolution was achieved with scan rates slower than 12 kDa/s. The HPIMS-MS system is sensitive enough to detect less than ppb level of sample, and the mass accuracy is ±0.15 Da. The instrument also performs well at high mass, with a confirmed mass range above m/z 2800. The resolving power does not appear to deteriorate across the working range.
2.HPIMS-MS Operation The HPIMS can be used in IMS-only, MS-only, or IMS-MS modes of operation. For the IMS-only mode of operation, ion mobility is measured outside the vacuum chamber, completely independently from the MS. For the MS-only mode, the ion gate is open; all sample ions are transported through the IMS and enter the MS. The most powerful operating mode of the IMS-MS is when performing a linked scan, i.e. tandem IMS-MS measurement. In this mode of operation, the sample is first measured by the IMS; once a targeted chemical is detected, the chemical with a certain mobility (drift time) is introduced into the MS, and the mass analyser performs mass analysis of the mobility selected ions. This mode, also called ‘detection and confirmation’ mode, and offers chemical identification based on two orthogonal principles.
HPIMS-MS Applications
With the clear advantages of in-field operation, HPIMS-MS is one of the most powerful instruments available, providing high specificity, sensitivity and speed. With a small footprint and self-contained packaging, HPIMS-MS can be placed anywhere electrical power is available, for example, in field applications including security check points for explosive and drug detection, inspection laboratories for food quality and in hospital testing laboratories for biomarker analysis. The system can also potentially be used in a mobile laboratory
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