Method for Molecular Layer Deposition Using Gas Cluster Ion Beam Sputtering with Example Application In Situ Matrix-Enhanced Secondary Ion Mass Spectrometry

Abstract

We introduce a technique for the directed transfer of molecules from an adjacent reservoir onto a sample surface inside the vacuum chamber of a ToF-SIMS instrument using gas cluster ion beam (GCIB) sputtering. An example application for in situ matrix-enhanced secondary ion mass spectrometry (ME SIMS) is provided. This protocol has attractive features since most modern SIMS instruments are equipped with a GCIB gun. No solvents are required that would delocalize analytes at the surface, and the transfer of matrix molecules can be interlaced with SIMS depth profiling and 3D imaging sputtering and analysis cycles, which is not possible with conventional ME SIMS strategies. The amount of molecular deposition can be finely tuned, which is important for such a surface sensitive technique as SIMS. To demonstrate the concept, we used 2,5-DHB as a matrix for the enhancement of three drug molecules embedded in a tissue homogenate. By automatic operation of sputter deposition and erosion (cleanup) cycles, depth profiling could be achieved with ME SIMS with good repeatability (<4% RSD). Furthermore, we explored several different matrix compounds, including α-CHCA and aqueous solutions of Brønsted acids (formic acid) and 3-nitrobenzonitrile, a volatile compound known to spontaneously produce ions. The latter two matrix compounds were applied at cryogenic measurement conditions, which extend the range of matrices applicable for ME SIMS. Enhancement ratios range from 2 to 13, depending on the analytes and matrix. The method works in principle, but enhancement ratios for the drug molecules are rather limited at this point. Further study and optimization is needed, and the technique introduced here provides a tool to perform systematic studies of matrix compounds and experimental conditions for their potential for signal enhancement in ME SIMS.

Matrix‐enhanced secondary ion mass spectrometry: Effects of aliphatic carboxylic acid matrices on the sensitivity enhancement of biological phospholipids

“…23,24 The most recent developments in ME-SIMS involve the in-situ transfer of matrices such as DHB and CHCA using a gas cluster ion beam, making them compatible with three-dimensional imaging. 25,26 These matrices constitute a partial molecular structure of benzene, in which the conjugated double bonds can absorb ultraviolet light from the MALDI laser probe. 27 Furthermore, protonated matrix molecules are important chemical species for analyte ionization in MALDI measurements.…”

“…Furthermore, ionic liquids such as 1‐methylimidazolium CHCA, tripropylammonium CHCA, and graphene oxide, which have been used as MALDI matrices, are similarly effective for TOF‐SIMS measurements 23,24 . The most recent developments in ME‐SIMS involve the in‐situ transfer of matrices such as DHB and CHCA using a gas cluster ion beam, making them compatible with three‐dimensional imaging 25,26 …”

Enhancing Ion Signals and Improving Matrix Selection in Time-of-Flight Secondary Ion Mass Spectrometry with Microvolume Expansion Using Large Argon Clusters

“…Recently, Lorenz et al showed that large argon clusters could be used to transfer an organic material from one surface onto another with a reduced fragmentation. 31,32 This transfer of intact molecule was extended by our group to larger proteins to develop a softlanding technique in situ a ToF-SIMS instrument. Lysozyme, a protein of 14 kDa, was successfully landed on a silicon wafer with retention of its activity, as was verified afterward via a bioassay in solution.…”

A Microscopic View of Macromolecule Transfer in the Vacuum Using Gas and Bismuth Clusters

“…One drawback is that direct patterning with the beam is impossible (the deposition pattern mirrors the angular distribution of sputtered molecules), but on the other hand, much larger fluxes can be attained than by selecting only charged molecules. Beside lysozyme, a range of MALDI matrices , and kilodalton molecules including polystyrene oligomers, Irganox 1010, angiotensin, and insulin could also be transferred undamaged. − The fraction of intact molecules was inversely proportional to the energy per atom ( E / n ) of the impinging cluster ions. Though this variant of soft landing appears to be a promising new technique for building up complex molecular or hybrid multilayers on virtually any substrate material, a number of fundamental questions still remain open.…”