ShEEP Request for Imaging Mass Spectrometry System

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Abstract The Bedford VA hospital requests for funds to acquire the Imaging Mass Spectrometer (IMS) rapifleX, manufactured by Bruker. This is based on the request from two ORD-sponsored field based meetings organized by the PI to foster collaborative multi-site studies. More than half of the 14 VA speakers who presented their works at the conference are using MS located at the Bedford VAMC, which is currently equipped with a Q Exactive hybrid Orbitrap MS, a Quantiva Triple Quadrupole MS, and a CyTOF MS system. These MS instruments are designed to analyze fluid samples but not tissue sections and fixed samples. The new IMS rapifleX will combine Imaging with Matrix Assisted Laser Desorption/Ionization Time-Of-Flight MS into a single instrument, Imaging MALDI-TOF MS. It is completely different from existing MS instruments in the PI’s lab. With the addition of IMS rapifleX, we will expand core analytic capability from one-dimensional identification to two-dimensional spatial detection of the targets of interest. This instrument will play an important role in multi-disciplinary clinical studies that are supported by VA, providing us with an unparalleled ability to phenotypically and functionally profile cells, rodent material and human tissue from both normal and diseased states. The IMS rapifleX will be used for multiple VA funded studies directed by Drs. Xia, Stein and McKee (major users), along with other principal investigators (minor users) at the Bedford VA Hospital (Dr. Smith) and Boston VA Health System (Dr. Kowall). The IMS rapifleX MS will be used to analyze a large variety of biological samples for studies related to central nervous system disorders. Specifically, it will be used to determine spatial distribution of pathological proteins in induced pluripotent stem cell-derived 3D human neurons and mouse brains, and then validate them in postmortem brain tissue (Dr. Xia; Aim 1). The IMS rapifleX will be used to image pathological proteins in brains from subjects with chronic traumatic encephalopathy (Dr. Stein and Dr. McKee; Aim 2). Images obtained by IMS rapifleX will be used to characterize biomarkers in neurons and mouse brains and relate them to pathological alteration in brains (Aim 3). In conclusion, acquisition of the new IMS rapifleX will allow the PI to establish an MS core and fulfill the goal of fostering collaborative multi-site studies.