Combi-Matrix Based on TiO₂ Aerogel for Diagnosis of Sepsis Using Laser Desorption and Ionization Mass Spectrometry

Abstract

To apply semiconductor nanostructures as a solid matrix for laser desorption/ionization-mass spectrometry, the nanostructures should exhibit ionization activity through photocatalytic reactions and desorption enhancement through photothermal conversion. Herein, TiO 2 aerogels were synthesized using titanium(IV) butoxide as a precursor, and a controlled porous structure was obtained by adjusting the ethanol content and annealing temperatures. The photocatalytic activity of the TiO 2 aerogel was estimated using pseudofirst-order kinetics on methylene blue degradation reactions. To achieve further desorption/ionization properties, a combi-matrix was produced using the TiO 2 aerogel and a conventional organic matrix, αcyano-4-hydroxynnamic acid (CHCA). The enhanced ionization efficiency of the TiO 2 aerogel combi-matrix was demonstrated along with an improved signal-to-noise ratio from other solid matrix combi-matrix systems. Meanwhile, the distribution of CHCA crystals in TiO 2 aerogel with various annealing conditions was investigated by differential scanning calorimetry with the Gibbs−Thomson equation. The radius of CHCA crystals was minimized at 550 °C but increased steeply at heat treatment temperatures higher than 600 °C, implying a collapse in the pore structure of the TiO 2 aerogel. Furthermore, the activation energy for melting the CHCA nanocrystals was calculated using the Arrhenius equation. These results showed that CHCA nanocrystals in a combi-matrix with the TiO 2 aerogel after annealing at 550 °C could be most effectively melted with lower activation energy via the pore structure and the binary phased TiO 2 aerogel. Finally, the combi-matrix based on TiO 2 aerogel was applied for the analysis of the sera from sepsis patients (n = 40), systemic inflammatory response syndrome (SIRS) patients (n = 20), and healthy controls (n = 20), finding that the combi-matrix based on TiO 2 aerogel could be effectively used for the diagnosis of sepsis using lysophosphatidylcholine (LPC-16) as a biomarker.