A combination nanostructured matrix with metal Au nanoislands and semiconductor TiO 2 nanowires is presented to enhance both desorption and ionization efficiency in laser desorption/ionization (LDI) mass spectrometry. The heterostructure of Au nanoislands on TiO 2 nanowires was fabricated via (1) TiO 2 nanowire synthesis through a modified wetcorrosion method and (2) Au nanoisland formation through thermal annealing of a sputtered Au layer on the TiO 2 nanowires. Herein, the synergistic effect of this heterostructure for highly efficient ion production was experimentally elucidated in terms of the formation of high temperature on the surface of Au and the creation of a Schottky barrier at the Au−TiO 2 interface. Finally, four types of immunosuppressors were analyzed to demonstrate the improved ionization performance of the heterostructure for LDI mass spectrometry.

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In this work, medical diagnosis of sepsis was conducted via quantitative analysis of lysophosphatidylcholine 16:0 (LPC 16:0) by using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry based on a parylene-matrix chip. In the first step, specific mass peaks for the diagnosis of sepsis were searched by comparing MALDI-TOF mass spectra of sepsis patient sera with healthy controls and pneumonia patient sera. Two mass peaks at m/z = 496.3 and 518.3 were chosen as those that are specifically different for sepsis sera to compare with healthy controls and pneumonia patient sera. These mass peaks were identified to be protonated and sodium adducts of LPC 16:0 by using tandem mass spectra (MS2 and MS3) of purely synthesized LPC 16:0 and extracted LPC 16:0 from a healthy control and a sepsis patient. In the next step, a standard curve for LPC 16:0 for the quantitative analysis of LPC 16:0 with MALDI-TOF MS based on the parylene-matrix chip was prepared, and the statistical correlation to the LC-MS analysis results was demonstrated by using the Bland–Altman test and Passing–Bablok regression. Finally, MALDI-TOF MS based on the parylene-matrix chip was used for the quantification of LPC 16:0 with sera from patients with severe sepsis and septic shock (n = 143), pneumonia patients (n = 12), and healthy sera (n = 31). The sensitivity and the selectivity of medical diagnosis of sepsis was estimated to be 97.9% and 95.5% by using MALDI-TOF MS based on the parylene-matrix chip, respectively.

The physicochemical properties of nanostructured substrates significantly impact laser desorption/ionization mass spectrometry (LDI-MS) performance. Fundamental understanding of the substrate properties can provide insights into the design and development of an efficient LDI matrix. Herein, a hybrid matrix of nanoporous Au-modified TiO 2 nanowires (npAu-TNW) is developed to achieve enhanced LDI-MS performance. Its origin is investigated based on hybrid matrix properties including photo-thermal conversion and electronic band structure. Notably, further improvement is obtained in the npAu-TNW than in the pristine TNW and non-porous Au nanoisland-modified TNW (Au-TNW) hybrid, which is attributed to the laser-induced surface restructuring/ melting phenomenon. Noticeable surface restructuring/melting occurs in the npAu by laser exposure through efficient photo-thermal conversion of the highly porous npAu. At this instant of npAu structural changes, internal energy transfer from the npAu to the adsorbed analyte is promoted, which facilitates desorption. Moreover, strain is developed in situ in the TNW adjacent to the restructuring npAu, which distorts the TNW lattice. The strain development reduces recombination rates of charge carriers by introducing shallow trap levels in the bandgap, which enhances the ionization process. Ultimately, the high LDI-MS performance based on the npAu-TNW hybrid matrix is demonstrated by analyzing neurotransmitter.

It has been challenging to detect small analytes in both positive and negative ion modes in MALDI-MS. Herein, TiO2 nanowires are presented as a solid matrix to produce dual-ion of any analytes and to demonstrate the versatile applicability in LDI-MS.

Recently, the parylene-matrix chip was developed for quantitative analysis of small molecules less than 1 kDa. In this study, MALDI-TOF MS based on the parylene-matrix chip was performed to clinically diagnose intrahepatic cholangiocarcinoma (IHCC) and colorectal cancer (CRC). The parylene-matrix chip was applied for the detection of small cancer biomarkers, including N-methyl-2-pyridone-5-carboxamide (2PY), glutamine, lysophosphatidylcholine (LPC) 16:0, and LPC 18:0. The feasibility of MALDI-TOF MS based on the parylene-matrix chip was confirmed via analysis of spot-to-spot and shot-to-shot reproducibility. Serum metabolite markers of IHCC, N-methyl-2-pyridone-5-carboxamide (2PY), and glutamine were quantified using MALDI-TOF MS based on the parylene-matrix chip. For clinical diagnosis of CRC, two water-insoluble (barely soluble) biomarkers, lysophosphatidylcholine (LPC) 16:0 and LPC 18:0, were quantified. Finally, glutamine and LPC 16:0 were simultaneously detected at a range of concentrations in sera from colon cancer patients using the parylene-matrix chip. Thus, this method yielded high-throughput detection of cancer biomarkers for the mixture samples of water-soluble analytes (2PY and glutamine) and water-insoluble analytes (LPC 16:0 and LPC 18:0).

Crystals of monosodium urate monohydrate (MSU) and calcium pyrophosphate dihydrate (CPPD) are known to induce arthropathic diseases called gout and pseudogout, respectively. These crystals are deposited in various joints or tissues, causing severe pain. Correct identification of crystals is crucial for the appropriate treatment of gout and pseudogout, which exhibit very similar symptoms. Herein, a novel approach of laser desorption/ionization time-of-flight (LDI-ToF) mass spectrometry (MS) was introduced to analyze MSU and CPPD crystals with three different types of nanostructured TiO 2 materials including TiO 2 nanoparticles (P25), TiO 2 nanowires synthesized from wet-corrosion method, and the mixture of P25 and TiO 2 nanowires (P25/TiO 2 nanowires) as inorganic solid matrices. Furthermore, the feasibility of LDI-ToF MS based on these TiO 2 nanostructures for the analysis of the two arthropathy-related crystals was tested using spiked samples in synovial fluid at known crystal concentrations. The mass analysis results of MSU and CPPD crystals demonstrated that (1) the electrostatic interaction between analytes and solid matrices was key for the analyte ionization and (2) LDI-ToF MS with nanostructured TiO 2 materials has the potential to be a practical approach for the diagnosis of gout and pseudogout.

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.