Developmental studies of a parallel flow trapped ion mobility spectrometer | Daniel Rickert

Описание: Abstract: One of the more recent ion mobility spectrometry (IMS) techniques, which serves as the basis for the instrument I have designed and built, is known as trapped ion mobility spectrometry (TIMS). In TIMS instruments, radio frequency (rf) potentials are used to radially confine ions of interest within the TIMS separation region. The ions are also trapped axially by balancing an applied DC electric field gradient against a reverse flow of neutral carrier gas flowing towards the detector. Trapped ions are separated, and then eluted from the separation region of the instrument based on their unique 3-dimensional shape (i.e. collision cross section, CCS) by gradually reducing the DC field gradient. This technology has immense analytical potential because a particular analyte can be rapidly separated in the gas based on its CCS, and then studied further with a mass spectrometer to characterize its mass and fragmentation pattern.
My research project is focused on the development of a new prototype parallel flow TIMS (pfTIMS) instrument. Over the first three years of my graduate studies, I have worked closely with the Science Technical Services (STS) machine shop to build the internal mechanical components and vacuum chamber, collaborated with the STS electronics shop to design the electrical boards and other hardware needed to power the instrument, and continue to work with our collaborators at GAA Custom Electronics to design the software and user interface that controls the instrument.
There is significant potential in operating the pfTIMS as a standalone instrument in a healthcare setting. The instrument can be moved close to the emergency room to directly analyze biofluid samples obtained from a patient, providing health care professionals with lifesaving information during a suspected opioid overdose. This is of particular importance in cases where a patient arrives at the hospital non-responsive and is unable to communicate about what substances they may have knowingly or unknowingly taken.
Alternatively, the pfTIMS can be incorporated into conventional analytical workflows that utilize solid phase microextraction techniques and commercial mass spectrometric instruments. For instance, steroid hormones comprise a class of structurally diverse small molecules, spanning a wide range of polarities, and are commonly analyzed for their significant role in numerous physiological processes. Standard liquid chromatography - MS methods are unable to accurately quantify these analytes due to the confounding effects of various isomers, and more specifically, stereoisomers, which are present in biological samples. Using the instrument that I have been developing, small variances in the structural conformations of the steroid isomers can be exploited such that the target molecules can be effectively separated from one another using the pfTIMS prior to MS detection, ensuring accurate results. The underlying motivation for developing the instrument is to demonstrate that our design can vastly improve the mobility resolution (i.e. the ability to discriminate between two molecules with similar CCSs) over other IMS devices, while also providing greater tunability and multiplexing capabilities for ion mobility measurements.