@article{kostelic_ryan_brown_jackson_hsieh_zak_sanders_liu_chen_byrne_et al._2022, title={Stability and Dissociation of Adeno-Associated Viral Capsids by Variable Temperature-Charge Detection-Mass Spectrometry}, volume={8}, ISSN={["1520-6882"]}, DOI={10.1021/acs.analchem.2c02378}, abstractNote={Adeno-associated viral (AAV) vectors have emerged as gene therapy and vaccine delivery systems. Differential scanning fluorimetry or differential scanning calorimetry is commonly used to measure the thermal stability of AAVs, but these global methods are unable to distinguish the stabilities of different AAV subpopulations in the same sample. To address this challenge, we combined charge detection-mass spectrometry (CD-MS) with a variable temperature (VT) electrospray source that controls the temperature of the solution prior to electrospray. Using VT-CD-MS, we measured the thermal stabilities of empty and filled capsids. We found that filled AAVs ejected their cargo first and formed intermediate empty capsids before completely dissociating. Finally, we observed that pH stress caused a major decrease in thermal stability. This new approach better characterizes the thermal dissociation of AAVs, providing the simultaneous measurement of the stabilities and dissociation pathways of different subpopulations.}, journal={ANALYTICAL CHEMISTRY}, author={Kostelic, Marius M. and Ryan, Jack P. and Brown, Levi S. and Jackson, Tyler W. and Hsieh, Chih-Chieh and Zak, Ciara K. and Sanders, Henry M. and Liu, Yang and Chen, Victor Shugui and Byrne, Michael and et al.}, year={2022}, month={Aug} }
 @article{kostelic_hsieh_sanders_zak_ryan_baker_aspinwall_marty_2022, title={Surface Modified Nano-Electrospray Needles Improve Sensitivity for Native Mass Spectrometry}, volume={33}, ISSN={["1879-1123"]}, DOI={10.1021/jasms.2c00087}, abstractNote={Native mass spectrometry (MS) and charge detection-mass spectrometry (CD-MS) have become versatile tools for characterizing a wide range of proteins and macromolecular complexes. Both commonly use nanoelectrospray ionization (nESI) from pulled borosilicate needles, but some analytes are known to nonspecifically adsorb to the glass, which may lower sensitivity and limit the quality of the data. To improve the sensitivity of native MS and CD-MS, we modified the surface of nESI needles with inert surface modifiers, including polyethylene-glycol. We found that the surface modification improved the signal intensity for native MS of proteins and for CD-MS of adeno-associated viral capsids. Based on mechanistic comparisons, we hypothesize that the improvement is more likely due to an increased flow rate with coated ESI needles rather than less nonspecific adsorption. In any case, these surface-modified needles provide a simple and inexpensive method for improving the sensitivity of challenging analytes.}, number={6}, journal={JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY}, author={Kostelic, Marius M. and Hsieh, Chih-Chieh and Sanders, Henry M. and Zak, Ciara K. and Ryan, Jack P. and Baker, Erin S. and Aspinwall, Craig A. and Marty, Michael T.}, year={2022}, month={Jun}, pages={1031–1037} }