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SUMMARY:LMB Seminar - Cryo-OrbiSIMS – high resolution mass spectrometry 
 imaging in the native biological state - Ian Gilmore\, National Physical L
 aboratory
DTSTART:20250303T110000Z
DTEND:20250303T120000Z
UID:TALK225703@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Nuclear magnetic resonance and high-performance liquid chromat
 ography mass spectrometry are the “gold standards” for molecular ident
 ification. However\, they have limited spatial information. Conversely\, t
 echniques with high spatial resolution such as electron microscopy\, have 
 low molecular identification information. Generally\, from an analytical p
 erspective\, this creates what can be termed the “Molecular Uncertainty 
 Principle”\, where the more certain we are about a molecule’s identity
 \, the less certain we are about its localization. This is a frustrating l
 imit for measurements at the frontiers. \n\nIn 2017\, we introduced the Or
 biSIMS technology [1] bringing the performance of an Orbitrap mass spectro
 meter together with the high-resolution imaging capability of secondary io
 n mass spectrometry (SIMS). [2] We were able to map the distribution of li
 pids and neurotransmitters in mouse brain with sub-cellular resolution. We
  also demonstrated the ability for single-cell metabolic profiling of macr
 ophage cells incubated with the anti-arrhythmia drug\, amiodarone\, reveal
 ing strong heterogeneity of drug uptake. However\, with single-cell resolu
 tion a clear correlation of drug uptake with upregulation of specific lipi
 ds was found. The unique ability of OrbiSIMS to simultaneously provide hig
 h-confidence in a molecule’s location and identity has led to strong upt
 ake in a wide range of science and technologies\, with now over 20 instrum
 ents installed worldwide. \n\nInspired by advances in Cryo-EM\, we introdu
 ced the cryo-OrbiSIMS which allows imaging in the native biological state 
 [3]. For example\, we demonstrated the ability to undertake in-situ metabo
 lomics of biofilm formation [3] and in collaboration with the Francis Cric
 k Institute we mapped the distribution of metabolites on the cuticular sur
 face of drosophila. [4] An introduction to the cryo-OrbiSIMS will be given
  along with example biological applications from us and others. In a look 
 to the future\, the concept for a quantum detector to boost Orbitrap sensi
 tivity by an order of magnitude will be presented [5].\n\nReferences\n\n[1
 ] 	M K Passarelli et al.\, The 3D OrbiSIMS-label-free metabolic imaging wi
 th subcellular lateral resolution and high mass-resolving power\, Nature M
 ethods\, 2017. 14 (12): p. 1175\n[2]	N. P. Lockyer et al. Secondary ion ma
 ss spectrometry\, Nat Rev Methods Primers 2024\, 4\, 32 \n[3]	J. Zhang et 
 al.\, Cryo-OrbiSIMS for 3D molecular imaging of a bacterial biofilm in its
  native state”\, Anal. Chem. 2020\, 92\, 13\, 9008–9015.\n[4]	C. L. Ne
 well et al\, Cryogenic OrbiSIMS Localizes Semi-Volatile Molecules in Biolo
 gical Tissues\,\nAngewandte Chemie Int. 2020\, 59 (41)\, 18194-18200\n[5]	
 PCT/GB2024/050690 - Improved Spectrometer or Imaging Assembly (2024).\n\n\
 n
LOCATION:In person in the Max Perutz Lecture Theatre (CB2 0QH) and via Zoo
 m link https://mrc-lmb-cam-ac-uk.zoom.us/j/92454273602?pwd=kKpRjV53ALrNtk3
 FXYDG1jqaNTjGa4.1
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