In addition to concentration, the orientation and conformation of proteins, carbohydrates, metabolites, and nucleic acids are essential characteristics differentiating healthy and diseased states. In fact, broadly available advances in mass spectrometry (MS), with unparalleled levels of selectivity, speed, and sensitivity, have armed researchers with new biological insights and prompt additional questions regarding molecular and biophysical parameters that differentiate disease states but transcend MS measurements. Ion mobility spectrometry (IMS) is a gas-phase separation technique that directly complements MS measurements and expands understanding regarding molecular shape and dynamics in biological systems. However, comparatively low sample utilization and separation efficiencies have hindered its broad adoption in the bioanalytical and clinical communities. With recent, broadly available technological advances in the field of printed circuit board (PCB) manufacturing a new class of ion mobility separation is enabled that largely alleviates the drawbacks of its predecessors. The Structures for Lossless Ion Manipulations (SLIM) framework achieves this goal by establishing a dynamic electric field capable of confining ionized molecules for expanded periods of time along with a means to efficiently fractionate the different classes prior to analysis using MS. Contemporary SLIM experiments achieve impressive levels of gas-phase ion separation, but focus only on one dimension of separation due to restrictions largely imposed by the underlying PCB electrode arrangements and control electronics. To cast the SLIM platform into multiple separation dimensions and achieve new levels of biologically relevant diagnostics, the present effort aims to develop and disseminate an economical tandem IMS platform that integrates a series of innovative, simplifying strategies. These include the integration of a low-cost electrode switch that expands the experimental versatility within the SLIM platform and a series of ion compression strategies aimed at creating high-density ion populations. Most importantly, and prior to MS analysis, we will exploit the highly compressed nature of the ion beams within the SLIM by subjecting these species to high intensity ultraviolet photons to induce molecular disruption and yield more information regarding the target biological system. Concurrent efforts using laser irradiation and a new class of UV-C light emitting diodes will be compared with the latter offering considerable cost-savings. The third, composite goal of this project is to address the duty cycle issues of existing SLIM concepts by fully multiplexing the tandem SLIM-ultraviolet photodissociation (UVPD) platform. With the added functionality of IMSn and the extended, multi-channel SLIM paths, the separation power of the system is anticipated to represent the state-of-the-art. At the conclusion of the proposed research we expect to realize a fully functioning, high-efficiency SLIM-UVPD framework capable of interfacing to all mass analyzers classes and ready to address a suite of biological problems ranging from metabolomics to structural biology.
To adequately account for the role of stereochemistry and conformational variation in biological systems and their impact on health, new high resolution, high-throughput separation modalities are necessary. Our research program develops a new tandem ion mobility platform that integrates innovative electrode arrangements and drive electronics to prepare ions for laser dissociation at elevated pressures and provide new levels of analytical detail. With a focus on cost-effective and accessible solutions to enhance analytical performance, we envision broad adoption of this co-planar, traveling wave ion mobility system due to its ultra-high resolution capabilities and integrated fragmentation stages which directly address bioanalytical challenges across disciplines.
