Tractable Tandem Ion Mobility Technology using Structures for Lossless Ion Manipulations and Photodissociation

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Tractable Tandem Ion Mobility Technology using Structures for Lossless Ion Manipulations and Photodissociation Administrative Supplement NOT-GM-21-030 R01GM140129 Summary. 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. Using widely 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 extended periods of time along with a means to efficiently fractionate the different classes prior to analysis using MS. 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. 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 (UV) photons to induce molecular disruption and yield more information regarding the target biological system. With the added functionality of tandem IMS experiment, 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-UV photodissociation framework capable of interfacing to all mass analyzer classes and ready to address a suite of biological problems ranging from metabolomics to structural biology. Administrative Supplement Request. To fully accommodate the high-density ion populations produced by the SLIM platform and maximize experimental accuracy, an ioniTOF 4000 time-of-flight (TOF) MS equipped with an analog data conversion (ADC) system is requested. In addition to enhancing the pace of each SLIM experiment, this instrumental advance promises to promote the rapid incorporation of the SLIM-UV technology into larger bioanalytical campaigns. The requested TOF-MS and its associated data acquisition system directly address the core limitations of the present mass analyzer used in the project and will facilitate experimental efforts supporting Aims 1, 2, and 3.