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, TiO2 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 TiO2 aerogel was estimated using pseudo-first-order kinetics on methylene blue degradation reactions. To achieve further desorption/ionization properties, a combi-matrix was produced using the TiO2 aerogel and a conventional organic matrix, α-cyano-4-hydroxynnamic acid (CHCA). The enhanced ionization efficiency of the TiO2 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 TiO2 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 TiO2 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 TiO2 aerogel after annealing at 550 °C could be most effectively melted with lower activation energy via the pore structure and the binary phased TiO2 aerogel. Finally, the combi-matrix based on TiO2 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 TiO2 aerogel could be effectively used for the diagnosis of sepsis using lysophosphatidylcholine (LPC-16) as a biomarker.