Improved ion detection sensitivity in mass spectrometry imaging using tapping-mode scanning probe electrospray ionization to visualize localized lipids in mouse testes.

Mass spectrometry imaging (MSI) is a promising analytical method to visualize the distribution of lipids in biological tissues. To clarify the relationship between cellular distribution and lipid types in a tissue, it is crucial to achieve both an improvement in ion detection sensitivity and a reduction in the ionization area. We report methods for improving the efficiency of ion transfer to a mass spectrometer and miniaturizing the extraction area of a sample for tapping-mode scanning probe electrospray ionization (t-SPESI), atmospheric pressure sampling, and ionization methods.

Probe oscillation control in tapping-mode scanning probe electrospray ionization for stabilization of mass spectrometry imaging.

Mass spectrometry imaging (MSI) is used for visualizing the distribution of components in solid samples, such as biological tissues, and requires a technique to ionize the components from local areas of the sample. Tapping-mode scanning probe electrospray ionization (t-SPESI) uses an oscillating capillary probe to extract components from a local area of a sample with a small volume of solvent and to perform electrospray ionization of those components at high speed. MSI can be conducted by scanning the sample surface with a capillary probe.

A Method for High Throughput Free Fatty Acids Determination in a Small Section of Bovine Liver Tissue Using Supercritical Fluid Extraction Combined with Supercritical Fluid Chromatography-Medium Vacuum Chemical Ionization Mass Spectrometry.

A novel ionization technique named medium vacuum chemical ionization (MVCI) mass spectrometry (MS), which is a chemical ionization using oxonium (HO) and hydroxide (OH) formed from water, has excellent compatibility with the supercritical fluid extraction (SFE)/supercritical fluid chromatography (SFC). We have studied a method to determine free fatty acids (FFAs) in a small section of bovine liver tissue using SFE/SFC-MVCI MS analysis without further sample preparation. A series of FFA molecules interact with the C18 stationary phase, exhibiting broad chromatographic peaks when using a non-modified CO as the mobile phase.

Estimation of the Spatial Extent of the Transient Gain Drop in a Microchannel Plate.

The gain of the microchannel plate temporally drops after an ion initiates an electron avalanche. Electron multiplication was expected to deplete the charge from the microchannel wall and produce the depleted charge (wall charge). Moreover, it was reported that the gain drop occurred not only in the activated channels, where the electrons are multiplied, but also in the surrounding channels.

Aeromicelle-A new form of liquid aerosol for delivering aqueous samples into a single-particle mass spectrometer.

For applying highly sensitive mass spectrometry to chemical analysis of aqueous samples, we have developed a novel technique using a new form of liquid droplets, which we call "aeromicelle" (AM), to deliver aqueous sample solutions directly into the vacuum region of a single-particle mass spectrometer in liquid form and conduct immediate mass analysis. AMs are generated by spraying an aqueous solution containing a surfactant at a concentration significantly lower than its critical micelle concentration (CMC). When the solution is sprayed, liquid droplets containing the surfactant are formed, which gradually dry in an air flow.

Rapid Analysis of α-Tocopherol and Its Oxidation Products Using Supercritical Carbon Dioxide and Proton Transfer Reaction Ionization Mass Spectrometry.

We have developed a rapid and sensitive analytical method for α-tocopherol and its oxidative products by combining online hyphenation of supercritical fluid extraction-supercritical fluid chromatography (SFC) with proton transfer reaction (PTR) ionization mass spectrometry (MS). α-Tocopherol is a well-known antioxidant that plays a vital role in the antioxidant defense system in plant cells. However, studies on the cellular mechanisms of α-tocopherol have been limited owing to the lack of a rapid analytical method, which limits the comparison of plant cells incubated in various conditions.

Attempts to Detect Lipid Metabolites from a Single Cell Using Proton-Transfer-Reaction Mass Spectrometry Coupled with Micro-Scale Supercritical Fluid Extraction: A Preliminary Study.

Proton-transfer-reaction (PTR) mass spectrometry (MS), a widely used method for detecting trace-levels of volatile organic compounds in gaseous samples, can also be used for the analysis of small non-volatile molecules by using supercritical fluid as a transporter for the molecules. Supercritical fluid extraction (SFE) is a method that permits lipophilic compounds to be rapidly and selectively extracted from complex matrices. The combination of the high sensitivity of PTR MS with the SFE is a potentially novel method for analyzing small molecules in a single cell, particularly for the analysis of lipophilic compounds.

Matrix-Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry Imaging of L-4-Phenylalanineboronic Acid (BPA) in a Brain Tumor Model Rat for Boron Neutron Capture Therapy (BNCT).

Boron neutron capture therapy (BNCT) is a cell-selective particle therapy for cancer using boron containing drugs. Boron compounds are accumulated in high concentration of tens ppm level of boron in target tumors to cause lethal damage to tumor tissue. The examination of boron distribution in target tumor and normal tissue is important to evaluate the efficiency of therapy.

Distinct diurnal chemical compositions and formation processes of individual organic-containing particles in Beijing winter.

Organic aerosols (OA) are major components of fine particulate matter, yet their formation mechanism remains unclear, especially in polluted environments. In this study, we investigated the diurnal chemical compositions and formation processes of OA in carbonaceous particles during winter in Beijing using aerosol time-of-flight mass spectrometry. We found that 84.

Space and Time Coherent Mapping for Subcellular Resolution of Imaging Mass Spectrometry.

Space and time coherent mapping (STCM) is a technology developed in our laboratory for improved matrix-assisted laser desorption ionization (MALDI) time of flight (TOF) imaging mass spectrometry (IMS). STCM excels in high spatial resolutions, which probe-based scanning methods cannot attain in conventional MALDI IMS. By replacing a scanning probe with a large field laser beam, focusing ion optics, and position-sensitive detectors, STCM tracks the entire flight trajectories of individual ions throughout the ionization process and visualizes the ionization site on the sample surface with a subcellular scale of precision and a substantially short acquisition time.

Microscale supercritical fluid extraction combined with supercritical fluid chromatography and proton-transfer-reaction ionization time-of-flight mass spectrometry for a magnitude lower limit of quantitation of lipophilic compounds.

The application of proton transfer ionization reaction mass spectrometry (PTR MS) combined with microscale supercritical fluid extraction (SFE) and supercritical fluid chromatography (SFC) aiming to quantitate single-cell fatty acid analysis levels was investigated. Using a microscale extraction vessel, the obtained low limits of quantitation (LLOQs) of arachidonic acid and arachidic acid were 1.2 and 2.

A Method for Expanding Mass Range on a Multi-Turn Time-of-Flight Mass Spectrometer by a Lap Superimposed Spectrum.

A time-of-flight mass spectrometer that uses a closed-orbit flight path can achieve a high mass resolving power and a high mass accuracy with a small instrument footprint. It has long been known that a drawback to a closed flight path is an obtained spectrum may contain peaks by ions at a different number of laps. A lower / ion may overtake higher / ions, resulting in the peak being superimposed on an acquired mass spectrum; therefore, such a mass bandwidth of the analyzer is limited to a narrow range given the current situation.

Analysis of Nonvolatile Molecules in Supercritical Carbon Dioxide Using Proton-Transfer-Reaction Ionization Time-of-Flight Mass Spectrometry.

Proton-transfer-reaction (PTR) mass spectrometry (MS) is capable of detecting trace-level volatile organic compounds (VOCs) in gaseous samples in real time. Therefore, PTR-MS has become a popular method in many different study areas. Most of the currently reported PTR-MS applications are designed to determine volatile compounds.

Evaluation of microchannel plate gain drops caused by high ion fluxes in time-of-flight mass spectrometry: A novel evaluation method using a multi-turn time-of-flight mass spectrometer.

Use of a two-stage microchannel plate (MCP) detector is common in time-of-flight (TOF) mass spectrometry because it shows excellent time resolution with sufficient gains. However, the gain drops significantly when the detector detects intense ion fluxes, such as matrix ions, by matrix-assisted laser desorption/ionization mass spectrometry. As a result, significant ion signals corresponding to analytes, such as proteins, are hidden, thereby hampering the mass spectral interpretation.

Selective Extraction of a Monoisotopic Ion While Keeping the Other Ions in Flight on a Multi-Turn Time-of-Flight Mass Spectrometer.

Using a multi-turn time-of-flight (TOF) mass spectrometer, we have extracted a single xenon isotope ion, Xe, from its orbit at given a lap number without disturbing the rest of isotopes. After detecting the Xe at 20 laps, the rest of the xenon isotope spectrum was obtained at 30 laps, which generated a TOF spectrum where the TOF difference between Xe and Xe was 87.4 μs while Xe and Xe were 1.

New Method for Improving LC/Time-of-Flight Mass Spectrometry Detection Limits Using Simultaneous Ion Counting and Waveform Averaging.

Simultaneous ion counting and waveform averaging implemented on a field-programmable gate array compiled with a high-speed digitizer was applied to ultraperformance liquid chromatography-time-of-flight mass spectrometric analysis of sulfa drugs. Ion counting was carried out by a "Peak Detection" (PKD) function that works together with signal averaging (AVG). Sulfadimidine (SDD) and sulfadimethoxine (SDMX) were measured in human serum (HS) model sample matrix.

Improved Quantitative Dynamic Range of Time-of-Flight Mass Spectrometry by Simultaneously Waveform-Averaging and Ion-Counting Data Acquisition.

Two different types of data acquisition methods, "averaging mode" and "ion-counting mode", have been used in a time-of-flight (TOF) mass spectrometry. The most common method is an averaging mode that sums waveform signals obtained from each flight cycle. While it is possible to process many ions arriving at the same TOF in one flight cycle, low-abundance ions are difficult to measure because ion signals are overwhelmed by noises from the detection system.

A new approach for accurate mass assignment on a multi-turn time-of-flight mass spectrometer.

A simple, effective accurate mass assignment procedure for a time-of-flight mass spectrometer is desirable. External mass calibration using a mass calibration standard together with an internal mass reference (lock mass) is a common technique for mass assignment, however, using polynomial fitting can result in mass-dependent errors. By using the multi-turn time-of-flight mass spectrometer infiTOF-UHV, we were able to obtain multiple time-of-flight data from an ion monitored under several different numbers of laps that was then used to calculate a mass calibration equation.

Instrumentation and Method Development for On-Site Analysis of Helium Isotopes.

Helium isotope determination may be useful in measuring volcanic activity and issuing earlier warnings of possible eruptions. A method is presented for measuring the He/He ratio in a gas sample using a multiturn time-of-flight mass spectrometer "infiTOF". In contrast to conventional waveform averaging, peaks are determined by counting ion pulses from each time-of-flight trigger.

High Spatial Resolution Laser Desorption/Ionization Mass Spectrometry Imaging of Organic Layers in an Organic Light-Emitting Diode.

To improve the durability of organic materials in electronic devices, an analytical method that can obtain information about the molecular structure directly from specific areas on a device is desired. For this purpose, laser desorption/ionization mass spectrometry imaging (LDI-MSI) is one of the most promising methods. The high spatial resolution stigmatic LDI-MSI with MULTUM-IMG2 in the direct analysis of organic light-emitting diodes was shown to obtain a detailed mass image of organic material in the degraded area after air exposure.

N-Terminal Derivatization with Structures Having High Proton Affinity for Discrimination between Leu and Ile Residues in Peptides by High-Energy Collision-Induced Dissociation.

sequencing is still essential in the identification of peptides and proteins from unexplored organisms whose sequence information is not available. One of the remaining problems in sequencing is discrimination between Leu and Ile residues. The discrimination is possible based on differences in side chain fragmentation between Leu and Ile under high-energy collision-induced dissociation (HE-CID) conditions.

Metabolomic Analysis of Gingival Crevicular Fluid Using Gas Chromatography/Mass Spectrometry.

Periodontitis is one of the most prevalent threats to oral health as the most common cause of tooth loss. In order to perform effective treatment, a clinical test that detect sites where disease activity is high and predicts periodontal tissue destruction is strongly desired, however, it is still difficult to prognose the periodontal tissue breakdown on the basis of conventional methods. The aim of this study is to examine the usefulness of gas chromatography/mass spectrometry (GC/MS), which could eventually be used for on-site analysis of metabolites in gingival crevicular fluid (GCF) in order to objectively diagnose periodontitis at a molecular level.

Technical note: signal-to-noise performance evaluation of a new 12-bit digitizer on time-of-flight mass spectrometer.

Rapid acquisition of time-of-flight (TOF) spectra from fewer acquisitions on average was investigated using the newly introduced 12-bit digitizer, Keysight model U5303A. This is expected to achieve a spectrum acquisition 32 times faster than the commonly used 8-bit digitizer for an equal signal-to-noise (S/N) ratio. Averaging fewer pulses improves the detection speed and chromatographic separation performance.