Porous Silicon Mass Spectrometry Research Articles

Fluorocarbon Plasma Gas Passivation Enhances Performance of Porous Silicon for Desorption/Ionization Mass Spectrometry.

Desorption/ionization on porous silicon mass spectrometry (DIOS-MS) is shown to be a powerful technique for the sensing of low-molecular-weight compounds, including drugs and their metabolites. Surface modification of DIOS surfaces is required to increase analytical performance and ensure stability. However, common wet chemical modification techniques use fluorosilanes, which are less suitable for high-throughput manufacturing and analytical repeatability. Here, we report an alternative, rapid functionalization technique for DIOS surfaces using plasma polymerization (ppDIOS). We demonstrate the detection of drugs, metabolites, pesticides, and doping agents, directly from biological matrices, with molecular confirmation performed using the fragmentation capabilities of a tandem MS instrument. Furthermore, the ppDIOS surfaces were found to be stable over a 162 day period with no loss of reproducibility and sensitivity. This alternative functionalization technique is cost-effective and amenable to upscaling, ensuring avenues for the high-throughput manufacture and detection of hundreds of analytes across various applications while still maintaining the gold-standard clinical technique using mass spectrometry.

Mapping insoluble indole metabolites in the gastrointestinal environment of a murine colorectal cancer model using desorption/ionisation on porous silicon imaging

Indole derivatives are a structurally diverse group of compounds found in food, toxins, medicines, and produced by commensal microbiota. On contact with acidic stomach conditions, indoles undergo condensation to generate metabolites that vary in solubility, activity and toxicity as they move through the gut. Here, using halogenated ions, we map promising chemo-preventative indoles, i) 6-bromoisatin (6Br), ii) the mixed indole natural extract (NE) 6Br is found in, and iii) the highly insoluble metabolites formed in vivo using desorption/ionisation on porous silicon-mass spectrometry imaging (DIOS-MSI). The functionalised porous silicon architecture allowed insoluble metabolites to be detected that would otherwise evade most analytical platforms, providing direct evidence for identifying the therapeutic component, 6Br, from the mixed indole NE. As a therapeutic lead, 0.025 mg/g 6Br acts as a chemo-preventative compound in a 12 week genotoxic mouse model; at this dose 6Br significantly reduces epithelial cell proliferation, tumour precursors (aberrant crypt foci; ACF); and tumour numbers while having minimal effects on liver, blood biochemistry and weight parameters compared to controls. The same could not be said for the NE where 6Br originates, which significantly increased liver damage markers. DIOS-MSI revealed a large range of previously unknown insoluble metabolites that could contribute to reduced efficacy and increased toxicity.

Rapid detection of nicotine from breath using desorption ionisation on porous silicon.

Desorption ionisation on porous silicon (DIOS) was used for the detection of nicotine from exhaled breath. This result represents proof-of-principle of the ability of DIOS to detect small molecular analytes in breath including biomarkers and illicit drugs.

Mass spectrometry imaging of fingerprint sweat on nanostructured silicon.

Desorption ionisation on porous silicon mass spectrometry imaging (DIOS-MSI) was used on fingerprints to map the distribution of exogenous and endogenous molecules present in sweat. Our attention was focused on the proof-of-principle to detect illicit drugs and their metabolites to exemplify the technique's potential in the area of forensic and workplace testing.

Mass Spectrometry Imaging on Porous Silicon: Investigating the Distribution of Bioactives in Marine Mollusc Tissues

Desorption/ionization on porous silicon-mass spectrometry (DIOS-MS) is an attractive alternative to conventional matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) for the analysis of low molecular weight compounds. Porous silicon (pSi) chips are also suitable as support for mass spectrometry imaging (MSI). Here, we report an implementation of DIOS-MSI using the biosynthetic organs of a marine mollusc for proof of principle. The tissue section is stamped onto a fluorocarbon-functionalized pSi chip, which extracts and traps small hydrophobic molecules from the tissue under retention of their relative spatial distribution. The section is subsequently removed and the chip is imaged without any remaining tissue. We apply this novel tissue contact printing approach to investigate the distribution of biologically active brominated precursors to Tyrian purple in the hypobranchial gland of the marine mollusc, Dicathais orbita, using DIOS-MSI. The tissue contact printing is also compatible with other types of desorption/ionization surfaces, such as nanoassisted laser desorption/ionization (NALDI) targets.

Desorption/ionization on porous silicon mass spectrometry (DIOS-MS) of perfluorooctane sulfonate (PFOS)

Desorption/ionization on porous silicon mass spectrometry (DIOS-MS) was introduced as a matrix-free LDI-TOF-MS, which succeeded at almost eliminating the background ion interference and offered a new technology for high-speed analysis of low mass compounds. In this study, we first demonstrated that the DIOS-MS is very useful for environmental analysis of perfluorooctane sulfonate (PFOS). In particular, DIOS can detect PFOS with the high sensitivity and the detection limit was 1 ppt without the extraction operation. At the very low concentration of 1 ppt, the PFOS was not detectable with the use of the traditional MS methods such as MALDI-MS and ESI-MS. The quantitative analysis of PFOS in the tap water was also performed from the calibration curve in the low concentration range from 2.5 to 10 ppb. In contrast, it was found that DIOS-MS has a low sensitivity for PFOA. This suggests that the DIOS plate has a high sensitivity for perfluorochemicals of sulfonic acid than that of carboxylic acid as the ionized group.

Impacts of Surface Morphology on Ion Desorption and Ionization in Desorption Ionization on Porous Silicon (DIOS) Mass Spectrometry

Ordered silicon nanocavity arrays were prepared with e-beam lithography to yield systematically varied pore features and porosity (4−92%). These substrates were used to investigate the effects of substrate morphology on desorption ionization on porous silicon-mass spectrometry (DIOS-MS). Five benzylpyridinium salts, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and angiotensin III were used as the model molecules in the study. For substrates of the same pore depth, MS results suggested that the pore size and the interpore spacing had little impact on the laser irradiation threshold required for ionization. Instead, the laser threshold was found to be highly dependent on the overall porosity for all substrates investigated—the higher the porosity the lower the threshold. Moreover, the substrates with deeper pores but of similar porosity showed significantly reduced laser thresholds. This close relationship between laser threshold and substrate morphology was attributed to the thermal confinement prop...

Halohydrination of epoxy resins using sodium halides as cationizing agents in MALDI‐MS and DIOS‐MS

Halohydrination of epoxy resins using sodium halides as cationizing agents in matrix-assisted laser desorption/ionization (MALDI) and desorption ionization on porous silicon mass spectrometry (DIOS-MS) were investigated. Different mass spectra were observed when NaClO(4) and NaI were used as the cationizing agents at the highest concentration of 10.0 mM, which is much higher than that normally used in MALDI-MS. MALDI mass spectra of epoxy resins using NaI revealed iodohydrination to occur as epoxy functions of the polymers. The halohydrination also occurred using NaBr, but not NaCl, due to the differences in their nucleophilicities. On the basis of the results of experiments using deuterated CD(3)OD as the solvent, the hydrogen atom source was probably ambient water or residual solvent, rather than being derived from matrices. Halohydrination also occurred with DIOS-MS in which no organic matrix was used; in addition, reduction of epoxy functions was observed with DIOS. NaI is a useful cationizing agent for changing the chemical form of epoxy resins due to iodohydrination and, thus, for identifying the presence of epoxy functions.

Laser Desorption/Ionization Mass Spectrometry on Porous Silica and Alumina for Peptide Mass Fingerprinting

We investigated a variant of desorption/ionization on porous silicon (DIOS) mass spectrometry utilizing an aqueous suspension of either porous silica gel or porous alumina (pore size of 60 and 90 A, respectively). Laser desorption/ionization (LDI) from samples directly deposited on a stainless steel surface without any inorganic substrates was also achieved. Synthetic peptides designed to cover large sequence diversity constituted our model compounds. Sample preparation, including material conditioning, peptide solubilization, and deposition protocol onto standard matrix-assisted laser desorption/ionization (MALDI) probe, as well as ionization source tuning were optimized to perform sensitive reproducible LDI analyses. The addition of either a cationizing agent or an alkali metal scavenger to the sample suspension allowed modification of the ionization output. Comparing hydrophilic silica gel to hydrophobic reversed-phase silica gel as well as increasing material pore size provided further insights into desorption/ionization processes. Furthermore, mixtures of peptides were analyzed to probe the spectral suppression phenomenon when no interfering organic matrix was present. The results gathered from synthetic peptide cocktails indicated that LDI mass spectrometry on silica gel or alumina constitutes a promising complementary method to MALDI in proteomics for peptide mass fingerprinting.

Matrix-Free Laser Desorption/Ionization-Mass Spectrometry Using Self-Assembled Germanium Nanodots

A novel ionization platform for matrix-free laser desorption/ionization-mass spectrometry (LDI-MS) was developed using self-assembled germanium nanodots (GeNDs) of uniform size (approximately 150 - 200-nm width and approximately 50-nm height) grown on a silicon wafer produced by molecular beam epitaxy. The performance of LDI-MS using GeNDs (GeND-MS) was investigated through measurements of a broad range of analytes, including peptides, proteins, synthetic oligomers, and polymer additives. Mass spectra of tryptic digests were clearly observed even for the mass range lower than m/z 800 without obstructive peaks. A detection limit of subfemtomole level was achieved for angiotensin-I. The upper limit of detectable mass range was approximately 17 kDa (myoglobin). GeND-MS also has potential for application to the characterization of industrial compounds. Almost accurate molecular weight distribution was obtained for a nonionic surfactant (Triton X-100) and for poly(ethylene glycol) oligomer. Furthermore, a brominated flame retardant, tetrabromobisphenol-A bis(2,3-dibromopropyl ether), was successfully ionized with less fragmentation, a result not obtainable by matrix-assisted laser desorption/ionization-mass spectrometry or desorption/ionization on porous silicon-mass spectrometry.

質量分析法を用いたポリマー材料の構造解析

The development of new polymer characterization techniques is constantly required to understand the various properties of polymers and create new functional polymers. In this study, two mass spectrometry (MS) approaches have been investigated: temperature programmed pyrolysis-mass spectrometry (TPPy-MS) and soft laser desorption/ionization-mass spectrometry (SLD-MS). The study can be summarized as follows: 1) A TPPy-MS system was developed to overcome the limitations of conventional evolved gas analysis (EGA) systems such as thermogravimetry/MS (TG/MS). The TPPy-MS system was used to investigate the mechanisms of thermal degradation of an engineering polymer with a brominated flame-retardant, and the intermolecular interaction mechanisms of miscible polymer blends and polymer/clay hybrids. 2) Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) was employed to characterize the chemical structure of each polymer chain. A new data processing method for size exclusion chromatography (SEC)/MALDI-MS was proposed to determine the accurate molecular weight distribution of polymers based on individual oligomer compositions. MALDI-MS was also used to investigate the biodegradation behavior of polymers. Based on the structural changes in each polymer chain, enzymatic degradation mechanisms of a biodegradable polyester and bacterial degradation of surfactants have been proposed. 3) To avoid the use of matrix reagents that frequently interfere with the mass spectra of oligomer and polymer additives, novel ionization platforms for matrix-free SLD-MS were investigated. The etching conditions of porous silicon spots for desorption/ionization on porous silicon-mass spectrometry (DIOS-MS) were optimized to determine the accurate molecular weight distribution of a certified reference polystyrene. Finally, two ionization platforms were developed using a pyroelectric ceramic plate and germanium nanodot deposited on a silicon wafer. The latter method was preferred for characterization of brominated flame-retardants.

Desorption/ionization on porous silicon mass spectrometry (DIOS) of model cationized fatty acids

Desorption/ionization on porous silicon (DIOS) is a very useful technique in the case of small molecular weight compounds, compared to the matrix-assisted laser desorption ionization (MALDI). This is because MALDI generates matrix-related ions that overlap with the mass range of interest. The aim of our work was to investigate the suitability of the DIOS technique in the case of fatty acids in negative ion mode. The analysis of the chosen fatty acid models, nonadecanoic acid (C(19)H(38)O(2)) and heneicosanoic acid (C(21)H(42)O(2)), gave rise to the observation of the deprotonated monomeric species and selective cationized multimeric species. This cation selectivity was further elucidated by complementary studies based on the addition of various metals such as Ag(I), Zn(II), Fe(II), and also Cu(II). Specific behavior, depending upon the introduced metal, was highlighted by different redox reaction processes and also metastable decompositions (in PSD mode).

The use of desorption/ionization on porous silicon mass spectrometry for the detection of negative ions for fatty acids

The study of low molecular weight compounds by matrix-assisted laser desorption/ionization (MALDI) is difficult because of the presence of ions originating from the matrix in the low-m/z range. In order to resolve these problems, new matrix-free approaches were developed based on laser desorption/ionization from the surface of various materials such as graphite and porous silicon. Our work involves the use of 'desorption ionization on porous silicon mass spectrometry' (DIOS-MS) in the negative ion mode to study fatty acid compounds. The potential of the DIOS-MS technique is shown and an insight into the ionization mechanism provided.

Desorption/Ionization on Porous Silicon Mass Spectrometry Studies on Pentose−Borate Complexes

Desorption/ionization on porous silicon mass spectrometry (DIOS-MS) was used to investigate the binding affinities between aldopentose isomers and boron. Boron has been recognized for its importance in pentose synthesis and stabilization in prebiotic conditions. Boron may also account for the fact that ribose, among other aldopentoses, is the favored building block in RNA synthesis. This research started with the detection of aldopentoses in the positive mode through cationization and the aldopentose-borate complexes in the negative mode. Then two competition schemes, one using a pentose structure analogue and the other using 13C-labeled ribose, were designed to compare the relative binding affinities of four aldopentoses (xylose, lyxose, arabinose, and ribose) to boron. Both approaches determined the binding preference to be ribose > lyxose > arabinose > xylose. This work illustrates the potential of DIOS-MS in the analyses of nonvolatile, small molecules in delicate chemical equilibria. Without externally introduced matrices, background signals are not a limiting factor. Furthermore, the possible dramatic change of pH associated with the matrix introduction, which may disturb the equilibria of interest, is avoided.

Laser Desorption/Ionization on Porous Silicon Mass Spectrometry for Accurately Determining the Molecular Weight Distribution of Polymers Evaluated Using a Certified Polystyrene Standard

Desorption/ionization on porous silicon-mass spectrometry (DIOS-MS) is a novel soft ionization MS technique that does not require any matrix reagent, ideally resulting in fewer obstructive peaks in the lower mass region. In this study, the etching conditions of porous silicon spots as an ionization platform of DIOS-MS were investigated for determining the molecular weight distribution (MWD) of polymers. To evaluate the accuracy of DIOS mass spectra observed using porous silicon spots prepared under various etching conditions, a certified polystyrene (PS) standard sample with an average molecular weight of ca. 2400 was used as a model sample. By optimizing the etching conditions, the MWD of the PS sample could be accurately observed by DIOS-MS using both p-type and n-type porous silicon spots. Especially, in the case of a suitable n-type spot, an accurate peak distribution with very fewer obstructive background peaks could be observed using the minimum laser power, comparable to the conventional matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS).

ＤＩＯＳ‐ＭＳによるポリマー用添加剤の分析

Desorption ionization on porous silicon-mass spectrometry (DIOS-MS) was applied to the analysis of various polymer additives, including ultraviolet absorbers (UVA), hindered amine light stabilizers (HALS), hindered phenol type primary antioxidants, and thioether type and phosphite type secondary antioxidants. First, molecular weight distribution and detailed chemical structure of an oligomer type UVA with poly(ethylene glycol) (PEG) main chain could be characterized based on the clearly observed DIOS mass spectrum without interference peaks. Then, to enhance ionization efficiency of the additive samples, the use of cationization salts such as sodium iodide (NaI) and silver trifluoroacetate (AgTFA) was investigated. In spite of the use of cationization salts, nitrogen-containing additives such as UVA and HALS tended to form [M+H]+ peaks. However, for the other additives, the use of cationization salts served to enhance the formation of molecular-related ions: hindered phenol type and thioether type antioxidants preferred the formation of [M+Na]+ in the presence of NaI, whereas phosphite type antioxidants could be observed as [M+Ag]+ ions in the presence of AgTFA.

Quantitative analysis of polypropyleneglycol mixtures by desorption/ionization on porous silicon mass spectrometry

Mixtures of diol and triol types of polypropyleneglycol (PPG) bearing two and three hydroxyl end groups were analyzed quantitatively by matrix-assisted laser desorption/ionization (MALDI) and desorption ionization on porous silicon (DIOS) with the conventional dried droplet method. The reproducibility of MALDI mass spectra depended on the factors regarding sample preparation such as the analyte/matrix ratio, and the type of solvent and/or chemical matrix employed. For DIOS, the analyte concentration and the selection of solvents were important for good reproducibility. Optimization of these factors allowed reliable quantification of the polymer mixtures. Under optimized conditions, DIOS would be suitable than MALDI for this purpose.

Reduction of Cu(II) and Riboflavin in DIOS Mass Spectrometry

Understanding ion-molecular reactions is suggested to be essential to delineating the mechanisms of matrix-assisted laser desorption/ionization (MALDI) and related ionization methods. To examine the implications of matrix-analyte reactions in the reduction observed in MALDI, copper(II) chloride and riboflavin were analyzed by desorption/ionization on porous silicon (DIOS) mass spectrometry. This system does not require a matrix for soft laser desorption/ionization. The two susbstances were reduced by DIOS as well, and the reduction of riboflavin was accelerated using water as a solvent, as reported in MALDI. The results indicated that target-analyte electron transfer occurs in LDI, although the possibility of matrix-analyte electron transfer in MALDI cannot be excluded.

Porous silicon as a versatile platform for laser desorption/ionization mass spectrometry.

Desorption/ionization on porous silicon mass spectrometry (DIOS-MS) is a novel method for generating and analyzing gas-phase ions that employs direct laser vaporization. The structure and physicochemical properties of the porous silicon surfaces are crucial to DIOS-MS performance and are controlled by the selection of silicon and the electrochemical etching conditions. Porous silicon generation and DIOS signals were examined as a function of silicon crystal orientation, resistivity, etching solution, etching current density, etching time, and irradiation. Pre-and postetching conditions were also examined for their effect on DIOS signal as were chemical modifications to examine stability with respect to surface oxidation. Pore size and other physical characteristics were examined by scanning electron microscopy and Fourier transform infrared spectroscopy, and correlated with DIOS-MS signal. Porous silicon surfaces optimized for DIOS response were examined for their applicability to quantitative analysis, organic reaction monitoring, post-source decay mass spectrometry, and chromatography.