Project Summary
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.
