Coffee Ring Effect Free TiO₂ Nanotube Array for Quantitative Laser Desorption/Ionization Mass Spectrometry

Abstract

Quantitative analysis using laser desorption/ionization mass spectrometry (LDI-MS) has been limited because of the nonuniform distribution of analytes caused by the “coffee ring effect”. In this study, a TiO2 nanotube array with hydrophilic dot patterns surrounded by hydrophobic areas (HB/HL-patterned TiO2 NTA) is presented to distribute analytes uniformly as well as to concentrate them within a sample spot. The HB/HL-patterned TiO2 NTA is fabricated by (1) electrochemical anodization, (2) silane functionalization, and (3) hydrophilic patterning with a photomask under ultraviolet radiation. Suppression of the coffee ring effect on this wettability-controlled TiO2 NTA is experimentally elucidated in terms of a capillary penetration of analyte solution into the selectively permeable TiO2 NTA. The morphology of a dried fluorescein on the HB/HL-patterned TiO2 NTA demonstrates homogeneous fluorescein deposition without lateral spreading. The feasibility of HB/HL-patterned TiO2 NTA for quantitative LDI-MS is demonstrated using two types of sepsis biomarkers, lysophosphatidylcholine 16:0 (LPC 16:0) and LPC 18:0 as model analytes. Further, LDI-MS based on the HB/HL-patterned TiO2 NTA matrix is applied to the medical diagnosis of sepsis by analyzing LPC 16:0 and LPC 18:0 with the sera from sepsis-negative and -positive groups. These results reveal that the HB/HL-patterned TiO2 NTA can be a remarkable platform for quantitative analysis. Furthermore, LDI-MS based on the HB/HL-patterned TiO2 NTA matrix has the potential to be a practical approach for sepsis diagnosis.

Inorganic Matrices Assisted Laser Desorption/Ionization Mass Spectrometry for Metabolic Analysis in Biofluids

“…Lysophosphatidylcholine 16:0 (LPC 16:0) and Lysophosphatidylcholine 18:0 (LPC 18:0) have been known as biomarkers for sepsis. Kim et al [74] . presented a TiO 2 nanotube array with hydrophilic dot patterns surrounded by hydrophobic areas (HB/HL‐patterned TiO 2 NTA) to detect LPC 16:0 and LPC 18:0 for the direct diagnosis of sepsis in the serum.…”

Laser desorption/ionization mass spectrometry of L-thyroxine (T4) using combi-matrix of α-cyano-4-hydroxycinnamic acid (CHCA) and graphene

“…Depending on the position of the laser radiation, different amounts of analyte ions occur even for the crystals of the same concentration. Thus, the quantitative analysis of small molecules has been restricted by MALDI-TOF MS (Park et al 2019;Kim et al 2017;Kim et al 2020;Choi et al 2018;Noh et al 2017).…”

Laser‐Induced Surface Reconstruction of Nanoporous Au‐Modified TiO2 Nanowires for In Situ Performance Enhancement in Desorption and Ionization Mass Spectrometry

“…[ 1–3 ] However, the organic matrices directly exposed to the laser create intense fragmented ions in the low m/z region (<1000 Da) of the mass spectrum, which severely limits the mass analysis of small molecules. [ 4–6 ] Additionally, the analyte–matrix mixture solution forms a non‐uniform crystallization on a sample plate and the mass peaks from the same sample spot exhibit different intensities depending on the sample position where the laser is exposed. Thus, to overcome the background interference and sweet spot issue, organic matrix‐free approaches were introduced by utilizing inorganic nanostructures as solid matrices and this strategy is termed as laser desorption/ionization (LDI)‐mass spectrometry (MS).…”

“…Further, various types of TiO 2 nanostructures have been used for LDI‐MS, including nanotubes, nanowires, and nanoparticles. [ 6,25,26 ]…”