MSVision – Steven Daly

Hyphenating Ion Mobility and Action Spectroscopy in a Synapt G2 to Probe the Structure and Kinetics of Aggregating Peptides

Steven Daly1, Sjors Bakels2, Agathe Depraz2, Iuliia Stroganova2, Jan Commandeur1, Anouk M. Rijs2

1 MS Vision,Televisieweg 40, 1322AM Almere, The Netherlands
2 Division of BioAnalytical Chemistry, AIMMS Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HV, Amsterdam, The Netherlands.

Nature provides us with an impressive array of examples of both function and malfunction arising from extreme complexity. An important example of a highly complex molecular network is that of aggregating peptides and proteins. Aggregation, the transition from soluble functioning proteins into insoluble amyloid aggregates, is directly related to neurodegenerative diseases including Alzheimer’s and Parkinson’s disease. To control and prevent protein aggregation, a full understanding of the initial, neurotoxic steps of the aggregation process is vital. However, the complex, heterogenic and dynamic nature of this process, makes this a huge experimental challenge. To tackle this, we have developed a novel, multidimensional spectroscopy- and mass spectrometry-based method, which allows us to probe the structure and kinetics of the initial steps of aggregation in a single measurement.

MS Vision and Anouk Rijs’s MS-LaserLab group (VU Amsterdam) have collaborated to modify a Synapt G2 such that we can hyphenate droplets-based microfluidics, electrospray ionization, mass spectrometry, ion mobility spectrometry and ion spectroscopy in a single experiment (the Photo-Synapt). To be able to measure mass-and mobility-selected UVPD and IRMPD spectra, the Synapt G2 was modified with two additional hexapoles between mobility and TOF stages. The use of pin traps allows the storing, manipulation and irradiation with UV or IR photons of mass- and mobility selected ions.

In this presentation, we will focus on the design and implementation of the Photo-Synapt, and characterization of its different operational modes. Ion optical simulations were used to guide the design the hexapole length and geometry of the pin traps, and the operation of the different trapping modes.

The pin traps are three sets of six pins positioned between the hexapole rods. Two sets of the pins are form potential well within the hexapole to trap the ions. The first set of pins is used to eject ions from the trap and into the second hexapole for trapping and irradiation or to the TOF. We show that the addition of the additional hexapoles does not affect the standard IM-MS and MSn performance, that we can trap in both pin traps, and transfer the ions between the two traps and to the TOF. The influence of the trapping time, gas pressure and pin trap voltages are explored to find optimal trapping conditions. Successful UVPD experiments of iodotyrosine demonstrate that we can trap and induce photodissociation. We are currently being extended to optimize conditions to perform IRMPD measurements.

Finally, the ability to perform ion mobility slicing is demonstrated. This is achieved by pulsing the IMS exit lens. The trapping and irradiation of a mass and mobility selected population of ions probed by IR or UV photons is the final goal of the characterization experiments. Initial experiments have shown this is possible, although optimisation of the protocol is still required.

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