Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1116/6.0002529

Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/D2SC07113D

Other Link： https://pubs.rsc.org/en/content/articlelanding/2023/sc/d2sc07113d

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： https://doi.org/10.1021/jasms.2c00382

Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.analchem.2c02997

Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ijms.2022.116845

Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jasms.1c00322

Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

DOI： 10.1384/jsa.27.104

Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jasms.1c00157

Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)   Publisher：The Surface Finishing Society of Japan  

DOI： 10.4139/sfj.72.162

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

A moving string sampling probe and a new ESI based ionization source that can be readily incorporated into the existing endoscopes are developed for performing in vivo mass spectrometry during the endoscopic procedure. The medical-grade silk suture driven by a stepping motor is used to perform the sampling on the region of interest when the probe head is brought gently into contact with the surface of the gastrointestinal tissue. The tissues and the compounds adhered to the sampling string are transported to an ionization region inside the ion inlet tube in which they are extracted and ionized by the charging droplets generated from an electrospray outside the ion inlet. Since the extraction/ionization and sampling processes are isolated, organic solvents, high voltage (HV), and heating can be used for the optimization of ionization without compromising the biocompatibility of the sampling probe. The demonstration of the in vivo analysis of the gastric mucosa of a mouse is performed using a 2 m long gastrointestinal endoscope.

DOI： 10.1021/jasms.0c00366

PubMed

Other Link： https://doi.org/10.1021/jasms.0c00366

Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jms.4583

Other Link： https://onlinelibrary.wiley.com/doi/full/10.1002/jms.4583

Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Mass Spectrometry Society of Japan  

DOI： 10.5702/massspectrometry.A0092

Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jasms.0c00052

Other Link： https://doi.org/10.1021/jasms.0c00052

Language：Japanese   Publishing type：(MISC) Summary of the papers read (national conference and other science council)  

J-GLOBAL

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Real-time and in-situ mass-spectrometry analyses of living animal and biological sample were performed using a novel remote sampling electrospray ionization (RS-ESI) probe. Unlike conventional ESI, in which injection or syringe loading is required for sample introduction, the RS-ESI probe ionizes the samples when the sampling capillary is in contact with the sample. As the sampling capillary is electrically held at ground potential, the safety of the animal and operator is assured. The liquid sample is aspirated to the ESI emitter at the other end of the capillary by the Venturi effect. Subsequently, the electrospray is generated when a high voltage is applied to the counter electrode placed inside the ion source chamber. The probe unit is attached to the mass spectrometer with a long flexible tube and its position can be freely manipulated during the analysis. In this report, we demonstrate a real-time analysis of a living mouse liver and an automatic analysis of 138 serum samples using this new technique.

DOI： 10.1016/j.jpba.2019.04.050

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/sia.6558

Other Link： https://www.onlinelibrary.wiley.com/doi/abs/10.1002/sia.6558

Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.5702/massspectrometry.S0079

Language：Japanese   Publishing type：(MISC) Summary of the papers read (national conference and other science council)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry  

DOI： 10.1039/C8AN01113C

Other Link： https://pubs.rsc.org/en/content/articlelanding/2018/an/c8an01113c

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

High-pressure nanoelectrospray ionization (nanoESI) source is a recently developed technique in which the electrospray ionization is generated inside an enclosed chamber with gas pressure higher than the atmospheric pressure. In this paper, the performance of nanoESI under different gas pressures, emitter position, ion inlet temperature, additive for desalination are presented. Under a pressure of 2 bars, the nanoESI is almost eased from the electrical discharge problem, and that offers a wider tuning window for the emitter potential to produces a higher and more stable ion signal. With optimized ion inlet temperature, the high-pressure operation facilitates the generation of ion species of higher charge-state from the highly aqueous solution, and produced less sodium adducts. A preparation method for the high-throughput analysis of raw biological samples using disposable plastic nanoESI emitter is also described.

DOI： 10.1016/j.aca.2018.03.026

Scopus

Other Link： http://www.sciencedirect.com/science/article/pii/S0003267018304057

Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Electrochemical Society  

© The Author(s) 2018. Published by ECS. Unveiling dissolved species in electrodeposition baths helps our understanding of electrodeposition behavior, such as growth orientation. A highly concentrated aqueous alkaline copper(II)-lactate solution is used for the electrodeposition of copper(I) oxide (Cu2O) thin films with <111> orientations; the semiconductor properties of these films facilitate their use in solar-cell materials, photocathodes, and photocatalysts. However, the dissolved species, presumably copper(II)-lactate complexes, cannot be deduced on the basis of known thermodynamic data, and have not been convincingly determined yet. In this work, we determine these cupric complexes by pH titration, ultraviolet-visible spectroscopy, and electrospray-ionization mass spectrometry (ESI-MS), including probe-ESI-MS (PESI-MS). Using PESI-MS, we successfully analyzed a highly concentrated solution without sample dilution. The determined complexes are Cu(H-1L)L- and Cu(H-1L)22-, where the H-1L2- (CH3CH(O-)COO-) is a lactate ion with a deprotonated α-hydroxyl group. As far as we know, this is the first direct experimental observation of H-1L2- ions in a highly concentrated aqueous alkaline copper(II)-lactate solution. We also propose that H-1L2- is stabilized by the high concentration and through coordination to copper(II) ions.

DOI： 10.1149/2.0831810jes

Scopus

Other Link： http://jes.ecsdl.org/content/165/10/D444

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1380/vss.61.286

Other Link： https://www.jstage.jst.go.jp/article/vss/61/5/61_20180079/_article/-char/ja/

Language：English   Publishing type：(MISC) Summary of the papers read (international conference)  

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Mass Spectrometry Society of Japan  

DOI： 10.5702/massspec.S18-12

Other Link： https://www.jstage.jst.go.jp/article/massspec/66/2/66_S18-12/_article/-char/en

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Ltd  

A new electrospray source design is introduced by having an extractor electrode placed at 1 to 2 mm behind the emitter tip. The extractor was integrated into the sprayer body as a single device. An insulating tube was used to isolate the emitter from the extractor and to deliver the sheath gas for the electrospray. The electric field strength at the emitter was primarily determined by the relative position and the potential between the needle and the extractor
therefore, the spraying condition was insusceptible to the change of sprayer position or orientation with respect to the ion sampling inlet. Such design allowed the use of much lower operating voltage and facilitated the optimization of sprayer position by keeping the electric field parameter constant. Using an emitter capillary of 150 and 310 μm in inner and outer diameters, strong ion signal could still be acquired with 2-kV emitter potential even if the distance between the emitter and ion inlet was extended to &gt
70 mm. Charge reduction of protein ions using 2 extractor-based electrosprays of opposite emitter polarities was also demonstrated.

DOI： 10.1002/jms.4072

Scopus

Other Link： https://onlinelibrary.wiley.com/doi/full/10.1002/jms.4072

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1380/vss.61.440

Other Link： https://www.jstage.jst.go.jp/article/vss/61/7/61_20180115/_article/-char/en

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.5702/massspectrometry.A0069

Other Link： https://www.jstage.jst.go.jp/article/massspectrometry/7/1/7_A0069/_article/-char/ja/

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AVS Science and Technology Society  

The relatively new electrospray droplet impact method is based on electrospray at atmospheric pressure and has been successful in achieving efficient desorption/ionization of biological molecules, soft etching of polymers, and nonselective etching of metal oxides. However, the beam current and brightness of this method are not practical for surface analyses. To improve the performance of this method, the authors have developed a new droplet ion beam gun using an electrospray of aqueous solutions in a vacuum. This technique could be expected to be a high-intensity massive cluster ion beam and they evaluate the performance of the vacuum-type electrospray droplet ion (V-EDI) gun. In this study, V-EDI and gas cluster ion beam guns were installed in a time-of-flight analyzer to directly compare the relative secondary ion yields of several biomolecules produced by several cluster ion beams.

DOI： 10.1116/1.5019182

Scopus

Other Link： https://avs.scitation.org/doi/10.1116/1.5019182

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

The temporal profiles of ion signals were measured for probe electrospray ionization (PESI) and nanoelectrospray ionization (nESI) by changing the pulse width of the high voltage applied to the emitters (PESI: 0.12 mm o. d. and 700 nm tip diameter metal needle; nESI: metal-coated 15 mm i. d. silica capillary). The ion signals started to be detected at similar to 400 ms and 5 ms, respectively, for PESI and nESI (solution: 10 (- 5) M cytochrome c and 0.1- 1% acetic acid in H2O/MeOH (1/1)). With the addition of 10 mM ammonium acetate in 10 (-5) M cytochrome c solution, the threshold for the signal appearance became about one order of magnitude longer with weaker signal intensities than those for acidic solutions. PESI was applied to real samples such as mayonnaise, natto (fermented soybeans), tomato ketchup and salmon eggs. Marked sequential electrospray was observed for these samples.

DOI： 10.1039/C7AY01275F

Web of Science

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Mass Spectrometry Society of Japan  

<p>In this paper, we briefly review the remote mass spectrometric techniques that are viable to perform "endoscopic mass spectrometry," i.e., in-situ and in-vivo MS analysis inside the cavity of human or animal body. We also report our experience with a moving string sampling probe for the remote sample collection and the transportation of adhered sample to an ion source near the mass spectrometer. With a miniaturization of the probe, the method described here has the potential to be fit directly into a medical endoscope.</p>

DOI： 10.5702/massspectrometry.S0070

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

At present, endoscopy relies almost exclusively on optical microscopy and the accurate analysis such as MS interrogation is performed ex situ using biopsy. In this work, a novel probing system is developed to perform in situ and in vivo endoscopic mass spectrometry using a moving string for the sampling and transportation of material. A prototype of a mass spectrometric endoscope is constructed using an industrial endoscope and a commercial mass spectrometer. The sampling system consists of a moving cotton thread driven by motorized pulleys. When the target surface is touched by the sampling probe, the cotton thread "wipes" and transports the adhered sample to the ion source. Depending on the target analytes, desorption electrospray and atmospheric pressure chemical ionization sources are employed interchangeably for the desorption and ionization. The surface under analysis is not subjected to heat, organic solvents, high voltage or charged droplets. In situ endoscopic MS of a living mouse and surface analysis inside a volunteer subject's mouth are demonstrated.

DOI： 10.1039/C7AN00650K

Web of Science

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Mass Spectrometry Society of Japan  

<p>We report on combining a self-aspirated sampling probe and an ESI source using a single metal capillary which is electrically grounded and safe for use by the operator. To generate an electrospray, a negative H.V. is applied to the counter electrode of the ESI emitter to operate in positive ion mode. The sampling/ESI capillary is enclosed within another concentric capillary similar to the arrangement for a standard pneumatically assisted ESI source. The suction of the liquid sample is due to the Venturi effect created by the high-velocity gas flow near the ESI tip. In addition to serving as the mechanism for suction, the high-velocity gas flow also assists in the nebulization of charged droplets, thus producing a stable ion signal. Even though the potential of the ion source counter electrode is more negative than the mass spectrometer in the positive ion mode, the electric field effect is not significant if the ion source and the mass spectrometer are separated by a sufficient distance. Ion transmission is achieved by the viscous flow of the carrier gas. Using the present arrangement, the user can hold the ion source in a bare hand and the ion signal appears almost immediately when the sampling capillary is brought into contact with the liquid sample. The automated analysis of multiple samples can also be achieved by using motorized sample stage and an automated ion source holder.</p>

DOI： 10.5702/massspectrometry.S0068

Language：English   Publishing type：Research paper (scientific journal)  

In mass spectrometry, analytes must be released in the gas phase. There are two representative methods for the gasification of the condensed samples, i.e., ablation and desorption. While ablation is based on the explosion induced by the energy accumulated in the condensed matrix, desorption is a single molecular process taking place on the surface. In this paper, desorption methods for mass spectrometry developed in our laboratory: flash heating/rapid cooling, Leidenfrost phenomenon-assisted thermal desorption (LPTD), solid/solid friction, liquid/solid friction, electrospray droplet impact (EDI) ionization/desorption, and probe electrospray ionization (PESI), will be described. All the methods are concerned with the surface and interface phenomena. The concept of how to desorb less-volatility compounds from the surface will be discussed.

DOI： 10.5702/massspectrometry.S0059

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Tissue samples from renal cell carcinoma patients were analyzed by electrospray droplet ion beam-induced secondary ion mass spectrometry (EDI/SIMS). Positively- and negatively-charged secondary ions were measured for the cancerous and noncancerous regions of the tissue samples. Although specific cancerous species could not be found in both the positive and negative secondary ion spectra, the spectra of the cancerous and noncancerous tissues presented different trends. For instance, in the m/z range of 500-800 of the positive secondary ion spectra for the cancerous tissues, the intensities for several m/z values were lower than those of the m/z+2 peaks (indicating one double bond loss for the species), whereas, for the noncancerous tissues, the inverse trend was obtained. The tandem mass spectrometry (MS/MS) was also performed on the tissue samples using probe electrospray ionization (PESI), and some molecular ions produced by PESI were found to be fragmented into the ions observed in EDI/SIMS analysis. When the positive secondary ion spectra produced by EDI/SIMS were analyzed by principal component analysis, the results for cancerous and noncancerous tissues were separated. The EDI/SIMS method can be applied to distinguish between a cancerous and a noncancerous area with high probability.

DOI： 10.5702/massspectrometry.A0053

PubMed

Language：Japanese   Publishing type：(MISC) Book review and document introduction, etc.   Publisher：Vacuum Society of Japan  

Atmospheric pressure electrospray had been used previously in our laboratory to generate massive cluster ion beam for charged droplet ionization
a method we called electrospray droplet impact (EDI). Previous ion gun that employed atmospheric pressure electrospray lacks adequate beam current and density for surface and interface analysis. To improve the EDI beam performance, we have proposed a technique for producing a stable electrospray of aqueous solution under vacuum. It is well known that vacuum electrospray of volatile liquids is dificult because of the freezing of the liquids by evaporative cooling under vacuum. Vacuum electrospray of aqueous solution was achieved by irradiating the tip of the electrospray emitter with infrared or near-infrared laser to prevent the freezing under high vacuum (&lt
0.05 Pa). A stable and large beam current was also obtained by optimizing the vacuum electrospray conditions. On the basis of these results, the vacuum electrospray can be expected to be a high-performance massive cluster ion gun.

DOI： 10.3131/jvsj2.60.321

Scopus

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

RATIONALE: We previously developed a massive cluster ion beam gun for secondary ion mass spectrometry (SIMS) in which the primary beam source is a vacuum electrospray. The secondary ion yields produced by this method had not yet been measured with a commercial time-of-flight (TOF) secondary ion mass spectrometer, and the ionization performance was unknown.
METHODS: A vacuum-type electrospray droplet ion gun was connected to a triple-focus TOF analyzer. The flight time of the secondary ions was measured using a sample-bias pulsing method, because a short pulse of the electrospray droplet beam could not be obtained. The secondary ion yields of an amino acid sample produced by the electrospray droplet beams and atomic Ga ion beams were compared.
RESULTS: TOF secondary ion spectra were measured for the amino acid and peptide samples with a mass resolution of similar to 500 using the sample-bias pulsing method. The secondary ion yield of the amino acid sample produced with the 10 kV vacuum-type electrospray droplet beams was much higher than that produced by 10 kV Ga ion beams. In addition, the secondary ion yields for the peptide sample and amino acid samples were almost similar.
CONCLUSIONS: This is the first report on secondary ion yields produced with vacuum-type electrospray droplet ion beams and measured with a semi-commercial TOF analyzer. The enhancement of secondary ion yields, in particular for relatively high-mass molecules, would be very useful in the SIMS analysis of a wide variety of biological samples. Copyright (C) 2016 John Wiley & Sons, Ltd.

DOI： 10.1002/rcm.7703

Web of Science

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Ion source pressure plays a significant role in the process of ionization and the subsequent ion transmission inside a mass spectrometer. Pressurizing the ion source to a gas pressure greater than atmospheric pressure is a relatively new approach that aims to further improve the performance of atmospheric pressure ionization sources. For example, under a super-atmospheric pressure environment, a stable electrospray can be sustained for liquid with high surface tension such as pure water, because of the suppression of electric discharge. Even for nano-electrospray ionization (nano-ESI), which is known to work with aqueous solution, its stability and sensitivity can also be enhanced, particularly in the negative mode when the ion source is pressurized. A brief review on the development of super-atmospheric pressure ion sources, including high-pressure electrospray, field desorption and superheated ESI, and the strategies to interface these ion sources to a mass spectrometer will be given. Using a recent ESI prototype with an operating temperature at 220 degrees C under 27atm, we also demonstrate that it is possible to achieve an online Asp-specific protein digestion analysis in which the whole processes of digestion, ionization and MS acquisition could be completed on the order of a few seconds. This method is fast, and the reaction can even be monitored on a near-real-time basis. Copyright (c) 2016 John Wiley & Sons, Ltd.

DOI： 10.1002/jms.3779

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Ion/molecule reactions of saturated hydrocarbons (n-hexane, cyclohexane, n-heptane, n-octane and isooctane) in 28-TorrN(2) plasma generated by a hollow cathode discharge ion source were investigated using an Orbitrap mass spectrometer. It was found that the ions with [M+14](+) were observed as the major ions (M: sample molecule). The exact mass analysis revealed that the ions are nitrogenated molecules, [M+N](+) formed by the reactions of N-3(+) with M. The reaction, N-3(+) + M[M+N](+) + N-2, were examined by the density functional theory calculations. It was found that N-3(+) abstracts the H atom from hydrocarbon molecules leading to the formation of protonated imines in the forms of RRCNH2+ (i.e. C-H bond nitrogenation). This result is in accord with the fact that elimination of NH3 is the major channel for MS/MS of [M+N](+). That is, nitrogen is incorporated in the C-H bonds of saturated hydrocarbons. No nitrogenation was observed for benzene and acetone, which was ascribed to the formation of stable charge-transfer complexes benzeneN(3)(+) and acetoneN(3)(+) revealed by density functional theory calculations. Copyright (c) 2016 John Wiley & Sons, Ltd.

DOI： 10.1002/jms.3765

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：A V S AMER INST PHYSICS  

In the secondary ion mass spectrometry, cluster ion beams are used for efficient ionization and low-damage etching of organic materials. In earlier studies, the authors have suggested a new cluster ion beam method using electrospray droplet impacts in atmospheric pressure conditions. Recently, the authors have developed a technique for electrospraying aqueous solutions in vacuum, which improved the performance of this technique for practical use. In this study, the mass-to-charge (m/z) values of the electrospray droplets produced by vacuum electrospray were measured by the time-of-flight technique and were found to be between 10(3) and 10(6). In addition, the secondary ions produced by these droplets were measured on indium and arginine samples, and the effect that the m/z value of the primary droplets has upon the secondary ion emission was investigated. (C) 2016 American Vacuum Society.

DOI： 10.1116/1.4943024

Web of Science

Scopus

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

In this work, a low-pressure air dielectric-barrier discharge (DBD) ion source using a capillary with the inner diameter of 0.115 and 12mm long applicable to miniaturized mass spectrometers was developed. The analytes, trinitrotoluene (TNT), 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), 1,3,5,7-tetranitroperhydro-1,3,5,7-tetrazocine (HMX), pentaerythritol tetranitrate (PETN), nitroglycerine (NG), hexamethylene triperoxide diamine (HMTD), caffeine, cocaine and morphine, introduced through the capillary, were ionized by a low-pressure air DBD. The ion source pressures were changed by using various sizes of the ion sampling orifice. The signal intensities of those analytes showed marked pressure dependence. TNT was detected with higher sensitivity at lower pressure but vice versa for other analytes. For all analytes, a marked signal enhancement was observed when a grounded cylindrical mesh electrode was installed in the DBD ion source. Among nine analytes, RDX, HMX, NG and PETN could be detected as cluster ions [analyte+NO3](-) even at low pressure and high temperature up to 180 degrees C. The detection indicates that these cluster ions are stable enough to survive under present experimental conditions. The unexpectedly high stabilities of these cluster ions were verified by density functional theory calculation. Copyright (c) 2016 John Wiley & Sons, Ltd.

DOI： 10.1002/jms.3732

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jms.3890

Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Mass Spectrometry Society of Japan  

In a tutorial paper on the application of free-jet technique for API-MS, John Fenn mentioned that "…for a number of years and a number of reasons, it has been found advantageous in many situations to carry out the ionization process in gas at pressures up to 1000 Torr or more" (Int. J. Mass Spectrom. 200: 459–478, 2000). In fact, the first ESI mass spectrometer constructed by Yamashita and Fenn had a counter-flow curtain gas source at 1050 Torr (ca. 1.4 atm) to sweep away the neutral (J. Phys. Chem. 88: 4451–4459, 1984). For gaseous ionization using electrospray plume, theoretical analysis also shows that "super-atmospheric operation would be more preferable in space-charge-limited situations."(Int. J. Mass Spectrom. 300: 182–193, 2011). However, electrospray and the corona-based chemical ion source (APCI) in most commercial instrument are basically operated under an atmospheric pressure ambient, perhaps out of the concern of safety, convenience and simplicity in maintenance. Running the ion source at pressure much higher than 1 atm is not so common, but had been done by a number of groups as well as in our laboratory. A brief review on these ion sources will be given in this paper.

DOI： 10.5702/massspectrometry.A0041

Language：English   Publishing type：Research paper (scientific journal)   Publisher：IM PUBLICATIONS  

Probe electrospray ionization (PESI) using a 0.2 mm outside diameter titanium wire was performed and the generated ions were introduced into the mass spectrometer via a discontinuous atmospheric pressure interface using a pinch valve. Time-lapse PESI mass spectra were acquired by gradually increasing delay time for the pinch valve opening with respect to the start of each electrospray event when a high voltage was applied. The opening time of the pinch valve was 20 ms. Time-resolved PESI mass spectra showed marked differences for 10 mM NaCl, 10(-5) M gramicidin S and insulin in H2O/CH3OH/CH3COOH (65/35/1) with and without the addition of 10 mM CH3COONH4. This was ascribed to the pH change of the liquid attached to the needle caused by electrochemical reactions taking place at the interface between the metal probe and the solution. NaCl cluster ions appeared only after the depletion of analytes. For the mixed solution of 10(-5) M cytochrome c, insulin, and gramicidin S in H2O/CH3OH/CH3COOH (65/35/1), a sequential appearance of analyte ions in the order of cytochrome c -&gt; insulin -&gt; gramicidin S was observed. The present technique was applied to three narcotic samples, methamphetamine, morphine, and codeine. Limits of detection for these compounds were 10 ppb in H2O/CH3OH (1/1) for the single sampling with a pinch valve opening time of 200 ms.

DOI： 10.1255/ejms.1309

Web of Science

Scopus

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Recently, we reported a new ESI ion source that could electrospray the super-heated aqueous solution with liquid temperature much higher than the normal boiling point (J. Am. Soc. Mass Spectrom. 25, 1862-1869). The boiling of liquid was prevented by pressurizing the ion source to a pressure greater than atmospheric pressure. The maximum operating pressure in our previous prototype was 11atm, and the highest achievable temperature was 180 degrees C. In this paper, a more compact prototype that can operate up to 27atm and 250 degrees C liquid temperatures is constructed, and reproducible MS acquisition can be extended to electrospray temperatures that have never before been tested. Here, we apply this super-heated ESI source to the rapid online protein digestion MS. The sample solution is rapidly heated when flowing through a heated ESI capillary, and the digestion products are ionized by ESI in situ when the solution emerges from the tip of the heated capillary. With weak acid such as formic acid as solution, the thermally accelerated digestion (acid hydrolysis) has the selective cleavage at the aspartate (Asp, D) residue sites. The residence time of liquid within the active heating region is about 20s. The online operation eliminates the need to transfer the sample from the digestion reactor, and the output of the digestive reaction can be monitored and manipulated by the solution flow rate and heater temperature in a near real-time basis.

DOI： 10.1007/s13361-015-1111-4

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Mass Spectrometry Society of Japan  

Ambient ionization mass spectrometry is one of the most challenging analytical tools in the field of biomedical research. We previously demonstrated that probe electrospray ionization mass spectrometry (PESI-MS) could potentially be used in the rapid diagnosis of cancer. Although this technique does not require a tedious sample pretreatment process, it was not possible for our previously reported setup to be applied to cases involving the direct sampling of tissues from living animal and large animal subjects, because there would not be enough room to accommodate the larger bodies juxtaposed to the ion inlet. To make PESI-MS more applicable for the real-time analysis of living animals, a long auxiliary ion sampling tube has been connected to the ion inlet of the mass spectrometer to allow for the collection of ions and charged droplets from the PESI source (hereafter, referred to as non-proximate PESI). Furthermore, an additional ion sampling tube was connected to a small diaphragm pump to increase the uptake rate of air carrying the ions and charged droplets to the ion inlet. This modification allows for the extended ion sampling orifice to be positioned closer to the specimens, even when they are too large to be placed inside the ionization chamber. In this study, we have demonstrated the use of non-proximate PESI-MS for the real-time analysis for biological molecules and pharmacokinetic parameters from living animals.

DOI： 10.5702/massspectrometry.S0048

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

The high-sensitive detection of explosives is of great importance for social security and safety. In this work, the ion source for atmospheric pressure chemical ionization/mass spectrometry using alternating current corona discharge was newly designed for the analysis of explosives. An electromolded fine capillary with 115 mu m inner diameter and 12mm long was used for the inlet of the mass spectrometer. The flow rate of air through this capillary was 41ml/min. Stable corona discharge could be maintained with the position of the discharge needle tip as close as 1mm to the inlet capillary without causing the arc discharge. Explosives dissolved in 0.5 mu l methanol were injected to the ion source. The limits of detection for five explosives with 50 pg or lower were achieved. In the ion/molecule reactions of trinitrotoluene (TNT), the discharge products of NOx- (x= 2,3), O-3 and HNO3 originating from plasma-excited air were suggested to contribute to the formation of [TNT - H](-) (m/z 226), [TNT - NO](-) (m/z 197) and [TNT - NO+HNO3] (-) (m/z 260), respectively. Formation processes of these ions were traced by density functional theory calculations. Copyright (C) 2015 John Wiley & Sons, Ltd.

DOI： 10.1002/jms.3552

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

The probe electrospray ionization (PESI) is an ESI-based ionization technique that generates electrospray from the tip of a solid metal needle. In the present work, we describe the PESI mass spectra obtained by in situ measurement of soybeans and several nuts (peanuts, walnuts, cashew nuts, macadamia nuts and almonds) using different solid needles as sampling probes. It was found that PESI-MS is a valuable approach for in situ lipid analysis of these seeds. The phospholipid and triacylglycerol PESI spectra of different nuts and soybean were compared by principal component analysis (PCA). PCA shows significant differences among the data of each family of seeds. Methanolic extracts of nuts and soybean were exposed to air and sunlight for several days. PESI mass spectra were recorded before and after the treatment. Along the aging of the oil (rancidification), the formation of oxidated species with variable number of hydroperoxide groups could be observed in the PESI spectra. The relative intensity of oxidated triacylglycerols signals increased with days of exposition. Monitoring sensitivity of PESI-MS was high. This method provides a fast, simple and sensitive technique for the analysis (detection and characterization) of lipids in seed tissue and degree of oxidation of the oil samples. Copyright (C) 2015 John Wiley & Sons, Ltd.

DOI： 10.1002/jms.3575

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

RATIONALE: For public security and safety, it is highly desirable to develop an ion source for the detection of explosives that is highly sensitive, compact in size, robust, and does not use any special carrier gases such as helium. In this work, a hollowcathode discharge (HCD) ion source was developed for the detection of explosives using ambient air as a carrier gas.
METHODS: To detect nonvolatile and thermally unstable explosives with high sensitivities, a new HCD ion source was designed and coupled with an ion trap mass spectrometer.
RESULTS: Five explosives - hexamethylene triperoxide diamine (HMTD), 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), pentaerythritol tetranitrate (PETN), nitroglycerin (NG) and trinitrotoluene (TNT) - were detected with limits of detection of lower than ng. The intensities of the NO3- adduct ions with RDX, PETN, and NG showed a marked increase with increase in ion source pressure in the range of 1-28 Torr.
CONCLUSIONS: Because the major NOx- ions (x = 2, 3) produced in the plasma act as reagent ions in ion-molecule reactions of explosives, air is best suited as a carrier gas for the detection of explosives. It is proposed that the NOx- (x = 2, 3) and O-3 contributed to the formation of [TNT-H](-) and [TNT-NO](-) ions, via the reactions NOx- + TNT -&gt; [TNT-H](-) + HNOx and [TNT](-) + O-3 -&gt; [TNT-NO](-) + NO2 + O-2. Copyright (C) 2015 John Wiley & Sons, Ltd.

DOI： 10.1002/rcm.7142

Web of Science

Language：Japanese   Publishing type：(MISC) Summary of the papers read (national conference and other science council)   Publisher：The Surface Science Society of Japan  

DOI： 10.14886/sssj2008.35.0_201

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Direct sampling probe mass spectrometry (DSP-MS) enables fast and direct profiling of metabolites in biological samples. However, because the solvent amount for the online dissolution of acquired analytes is difficult to control, the detection sensitivity is not satisfactory. In this study, we present a modified version of the DSP-MS system for direct mass spectrometric profiling of metabolites in plant single cells. Two major improvements are introduced in this work, including a pointed-tip probe with high surface wetting properties, which is ten times finer than the previous version, and a piezoelectric inkjet system working as the auxiliary solvent delivery means. The probe tip can be controlled to insert into a cell through the cell wall. Metabolites loaded on the tip surface can be extracted by the auxiliary solvent and electrosprayed after applying a high direct current voltage. The unique features such as low cost, disposability and versatility make this technique a competitive tool for single cell analysis.

DOI： 10.1039/C4AN01068J

Web of Science

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

The heating of electrospray ion source under atmospheric pressure is limited to the normal boiling point of the solution. The boiling takes place when the vapor pressure of the liquid at a given temperature equals the ambient pressure. By using a high pressure ESI source, which has been developed previously in our laboratory, a stable electrospray ionization of super-heated aqueous solution is performed up to a solution temperature of 180 degrees C. The ion source is pressurized with pure nitrogen to a maximum pressure of 11 atm, and it is coupled to a commercial mass spectrometer via a custom-made ion transport capillary. A booster pump with variable pumping speed is added to the pumping system to regulate the pressure in the first pumping stage at 1 similar to 1.3 Torr. High pressure mass spectrometry is performed on several peptides and proteins to demonstrate its application in the temperature-controlled thermally induced denaturation and dissociation.

DOI： 10.1007/s13361-014-0974-0

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

In this work, desorption of nonvolatile analytes induced by friction was studied. The nonvolatile compounds deposited on the perfluoroalkoxy substrate were gently touched by an ultrasonic cutter oscillating with a frequency of 40 kHz. The desorbed molecules were ionized by a dielectric barrier discharge (DBD) ion source. Efficient desorption of samples such as drugs, pharmaceuticals, amino acids, and explosives was observed. The limits of detection for these compounds were about 1 ng. Many compounds were detected in their protonated forms without undergoing significant fragmentation. When the DBD was off, no ions for the neutral samples could be detected, meaning that only desorption along with little ionization took place by the present technique.

DOI： 10.1007/s13361-014-0899-7

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

The electrospray droplet impact (EDI) method based on ambient electrospray technique was developed as a novel massive cluster beam gun, but in its current status, the EDI method lacks adequate beam focusing and brightness. To improve the performance of the current EDI method, we developed a technique for producing electrospray of aqueous solutions under vacuum. In a previous study, the tip of the electrospray emitter was irradiated with an infrared (IR) CO2 laser (wavelength: 10.6 mu m) to prevent freezing of the aqueous solutions. In this paper, a near-IR diode laser (wavelength: 808nm) was adopted for heating the tip of the electrospray emitter as an alternative to the IR laser. A stable vacuum electrospray of aqueous solutions was obtained, whereas the 808nm light was poorly absorbed by water compared with the 10.6-mu m IR laser. The characteristics of the vacuum electrospray assisted by a near-IR laser are presented. Copyright (c) 2014 John Wiley & Sons, Ltd.

DOI： 10.1002/sia.5532

Web of Science

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.5702/massspectrometry.S0024

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

CiNii Books

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

CiNii Books

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

RATIONALEAlthough alternating current (ac) corona discharge has been widely used in the fields of material science and technology, no reports have been published on its application to an atmospheric pressure chemical ionization (APCI) ion source. In this work, ac corona discharge for an APCI ion source has been examined for the first time.
METHODSThe ambient atmospheric pressure ac corona discharge (15kHz, 2.6 kV(ptp)) was generated by using a stainless steel acupuncture needle. The generated ions were measured using an ion trap mass spectrometer. A comparative study on ac and direct current (dc) corona APCI ion sources was carried out using triacetone triperoxide and trinitrotoluene as test samples.
RESULTSThe ac corona discharge gave ion signals as strong as dc corona discharge for both positive and negative ion modes. In addition, softer ionization was obtained with ac corona discharge than with dc corona discharge. The erosion of the needle tip induced by ac corona was less than that obtained with positive mode dc corona.
CONCLUSIONSA good 'yardstick' for assessing ac corona is that it can be used for both positive and negative ion modes without changing the polarity of the high-voltage power supply. Thus, ac corona can be an alternative to conventional dc corona for APCI ion sources. Copyright (c) 2013 John Wiley & Sons, Ltd.

DOI： 10.1002/rcm.6744

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Mass Spectrometry Society of Japan  

The present paper demonstrates the detection of explosives in solution using thermal desorption technique at a temperature higher than Leidenfrost temperature of the solvent in combination with low temperature plasma (LTP) ionization. Leidenfrost temperature of a solvent is the temperature above which the solvent droplet starts levitation instead of splashing when placed on a hot metallic surface. During this desorption process, slow and gentle solvent evaporation takes place, which leads to the pre-concentration of less-volatile explosive molecules in the droplet and the explosive molecules are released at the last moment of droplet evaporation. The limits of detection for explosives studied by using this thermal desorption LTP ionization method varied in a range of 1 to 10 parts per billion (ppb) using a droplet volume of 20 μL (absolute sample amount 90–630 fmol). As LTP ionization method was applied and ion–molecule reactions took place in ambient atmosphere, various ion–molecule adduct species like [M+NO₂]⁻, [M+NO₃]⁻, [M+HCO₃]⁻, [M+HCO₄]⁻ were generated together with [M−H]⁻ peak. Each peak was unambiguously identified using 'Exactive Orbitrap' mass spectrometer in negative ionization mode within 3 ppm deviation compared to its exact mass. This newly developed technique was successfully applied to detect four explosives contained in the pond water and soil sample with minor sample pre-treatment and the explosives were detected with ppb levels. The present method is simple, rapid and can detect trace levels of explosives with high specificity from solutions.

DOI： 10.5702/massspectrometry.S0008

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Nano electrospray with a solution flow rate below 100 nL min(-1) is usually performed using a metallized pulled glass capillary with an inner diameter tip of &lt;10 mm. In this paper, we demonstrated that it was possible to achieve a stable solution flow rate of similar to 10 nL min(-1) for an aqueous solution using a disposable plastic pipette tip with an inner diameter of 100 mm as an ESI emitter. This pipette tip (gel loading tip) was originally designed for the loading of sample onto the gel in gel electrophoresis. The inner and outer diameters were much larger than those of a nanoESI emitter, but the low solution flow rate could be sustained by conducting the electrospray under a super-atmospheric gas pressure. The high pressure condition ensured the absence of electrical discharge which was essential for stable electrospray of aqueous solution. ESI with this low cost tip was equally as sensitive as the standard nanoESI emitter and capable of producing a long lasting signal from a small amount of sample liquid. Due to a small initial droplet size under the low flow rate regime, ESI with the present method exhibited the property of nanoESI where the ion suppression of the hydrophilic analyte by the hydrophobic compound present in the solution was greatly reduced. Furthermore, owing to its larger inner diameter, the tip relatively easily avoided the clogging problem often encountered when dealing with "dirty" samples when compared with a nanoESI emitter made from a fine glass capillary.

DOI： 10.1039/C3AN01635H

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Real-time analyses of hepatocellular carcinoma were performed in living mice to assess the applicability of probe electrospray ionization-mass spectrometry (PESI-MS) in medical diagnosis. The number of peaks and the abundance of ions corresponding to triacylglycerols (TAGs) were higher in cancerous tissues than in noncancerous tissues. Multiple sequential scans of the specimens were performed along a predetermined line extending over the noncancerous region to detect the boundary of the cancerous region. Our system successfully discriminated the noncancerous and cancerous tissues based on the intensities of the TAG ions. These results highlight the potential application of PESI-MS for clinical diagnosis in cancer. (c) 2013 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ab.2013.06.017

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

This study presents a novel direct analysis strategy for rapid mass spectrometric profiling of biochemicals in real-world samples via a direct sampling probe (DSP) without sample pretreatments. Chemical modification is applied to a disposable stainless steel acupuncture needle to enhance its surface area and hydrophilicity. After insertion into real-world samples, biofluid can be attached on the DSP surface. With the presence of a high DC voltage and solvent vapor condensing on the tip of the DSP, analyte can be dissolved and electrosprayed. The simplicity in design, versatility in application aspects, and other advantages such as low cost and disposability make this new method a competitive tool for direct analysis of real-world samples.

DOI： 10.1007/s13361-013-0697-7

Web of Science

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Nanoelectrospray ionization (nanoESI) with a very fine emitter and nanoliter solution flow rate is known to be suitable for aqueous solutions. However, under atmospheric pressure, its stability with aqueous solutions is not always guaranteed particularly in the negative ion mode where corona and arc discharge tend to occur more easily. Electrical discharge can be quenched to a certain extent by adding electron scavenging gases like SF6 or CO2 to the ion source. The onset potential that is required to induce the discharge also increases with an increase of gas pressure. Recently, we have reported on a series of high pressure electrospray ion sources that were stable in both positive and negative ion modes using air or N-2 as the working gas. In this paper, we compare the performance of nanoelectrospray under atmospheric pressure and super-atmospheric pressure for the analysis of samples in aqueous solution. The comparative study was performed using the same ion source chamber that could be pressurized up to 6 bar. The pressure in the first pumping stage of the mass spectrometer was kept constant when the ion source pressure was changed by using an additional pump with variable pumping speed. High pressure nanoESI optimized at 2-3 bar demonstrated a 3-5 times improvement in ion signal intensity compared to atmospheric pressure nanoESI, and the signal stability was significantly improved particularly in the negative mode.

DOI： 10.1039/C3AN00699A

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Probe electrospray ionization (PESI) uses a sharp solid needle as electrospray emitter. This method was found to be applicable to the analysis of real-world samples with high concentrations of salts and detergents without sample pretreatment. Since PESI is only applicable to wet samples but not to dry samples, sheath-flow PESI (SF-PESI) has been developed. The metal needle was inserted into the fine plastic capillary with a protrusion of 0.1-0.2mm from the capillary terminus. The solvent was supplied continuously through the capillary. At the lowest position of the probe, solvent flowing out from the capillary makes the sample wet and extracts the analytes from the surface. The extracted analytes were electrosprayed at the highest position of the needle. SF-PESI was successfully applied to samples such as narcotics, tablets, bill, fruits, potatoes, etc. Copyright (c) 2013 John Wiley & Sons, Ltd.

DOI： 10.1002/jms.3226

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

There have been no reports about the formation of metallic ions below the threshold of ablation, i.e. ∼1 J/cm2. In this work, generation of ions under the irradiation of 532 nm laser on the Au, Ag, Cu, and Pt targets under 4.6 × 103 Pa helium gas has been studied. The fluence was changed from the threshold of ion formation to the start of ablation. We have found that metallic ions started to be observed with the fluence that was about two orders of magnitude lower than that of the ablation threshold, ∼10 mJ/cm2, for all the surface-roughened metal targets investigated. The surface plasmon resonance excitation was provoked for the ion formation. Desorption of neutral species was suggested to be minor for the mass transfer from the surface to the gas phase below the threshold of the ablation. © 2013 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.ijms.2013.02.009

Scopus

Language：English   Publishing type：(MISC) Summary of the papers read (international conference)  

Language：English   Publishing type：Research paper (scientific journal)  

This work describes the development and application of a new thermal desorption technique that makes use of the Leidenfrost phenomenon in open ion sources at atmospheric pressure for direct mass spectrometric detection of ultratrace levels of illicit, therapeutic, and stimulant drugs, toxicants, and peptides (molecular weight above 1 kDa) in their unaltered state from complex real world samples without or with minor sample pretreatment. A low temperature dielectric barrier discharge ion source was used throughout the experiments and the analytical figures of merit of this technique were investigated. Further, this desorption technique coupled with other ionization sources such as electrospray ionization (ESI) and dc corona discharge atmospheric pressure chemical ionization (APCI) in open atmosphere was also investigated. The use of the high-resolution 'Exactive Orbitrap' mass spectrometer provided unambiguous identification of trace levels of the targeted compounds from complex mixtures and background noise
the limits of detection for various small organic molecules and peptides treated with this technique were at the level of parts per trillion and 10-9 M, respectively. The high sensitivity of the present technique is attributed to the spontaneous enrichment of analyte molecules during the slow evaporation of the solvent, as well as to the sequential desorption of molecules from complex mixtures based on their volatilities. This newly developed desorption technique is simple and fast, while molecular ions are observed as the major ions. © 2013 American Society for Mass Spectrometry.

DOI： 10.1007/s13361-012-0564-y

Scopus

PubMed

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Super-atmospheric pressure chemical ionization (APCI) mass spectrometry was performed using a commercial mass spectrometer by pressurizing the ion source with compressed air up to 7 atm. Similar to typical APCI source, reactant ions in the experiment were generated with corona discharge using a needle electrode. Although a higher needle potential was necessary to initiate the corona discharge, discharge current and detected ion signal were stable at all tested pressures. A Roots booster pump with variable pumping speed was installed between the evacuation port of the mass spectrometer and the original rough pumps to maintain a same pressure in the first pumping stage of the mass spectrometer regardless of ion source pressure. Measurement of gaseous methamphetamine and research department explosive showed an increase in ion intensity with the ion source pressure until an optimum pressure at around 45 atm. Beyond 5 atm, the ion intensity decreased with further increase of pressure, likely due to greater ion losses inside the ion transport capillary. For benzene, it was found that besides molecular ion and protonated species, ion due to [M+2H]+ which was not so common in APCI, was also observed with high ion abundance under super-atmospheric pressure condition. Copyright (c) 2013 John Wiley & Sons, Ltd.

DOI： 10.1002/jms.3173

Web of Science

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

RATIONALE: Probe electrospray ionization (PESI) is a recently developed method that uses a sharp solid needle as electrospray emitter and the sample is loaded to the needle tip by repetitive movement of the needle probe. This method has been previously used for the analysis of sample with high salt concentration and realworld samples without sample pretreatment. Although PESI is also applicable to aqueous solution, the ion signal stability and reproducibility were not satisfactory due to the spontaneous occurrence of corona discharge taking place on the metallic needle tip. METHODS: In the previous version of PESI, the ionization was performed under an open environment, thus ambient condition such as humidity and the presence of environmental contaminant also affected the performance of PESI. In this paper, we report a modified version of PESI in which the electrospray and the desolvation of charged droplets are performed inside an enclosed chamber which is pressurized to &gt
1 atm with dry air. RESULTS: Under a super atmospheric condition, the dielectric strength of the ambient gas was enhanced and stable electrospray could to be initiated without the occurrence of corona discharge even for liquid sample with high surface tension such as pure water. A comparative study of atmosphericpressure PESI and highpressure PESI (HPPESI) had been performed to demonstrate the improvement of PESI in sensitivity and signal stability for the detection analytes in aqueous solution. CONCLUSIONS: HPPESI offers a higher sensitivity and signal stability over PESI due to the absence of gaseous breakdown, better desolvation, and higher ion sampling rate by the mass spectrometer. Copyright © 2012 John Wiley &amp
Sons, Ltd.

DOI： 10.1002/rcm.6427

Scopus

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

The electrospray droplet impact (EDI) method was developed as a new massive cluster source, but the current EDI method lacks adequate beam focusing and density to achieve imaging and depth profiling with sufficient spatial resolution and within a reasonable time. To improve EDI beam performance, we have developed a technique for stable electrospraying of volatile liquids under vacuum. However, as is well known, vacuum electrospray of volatile liquids is extremely difficult because the evaporative cooling causes freezing of the volatile liquids in vacuum, and to prevent the freezing of these liquids, we irradiated the tip of the electrospray emitter with an infrared (10.6 mu m) laser. The tip of the emitter was directly observed with optical microscopy, and the droplet ion beam current was measured with a Faraday cup. A stable vacuum electrospray of pure water was achieved with continuous laser irradiation. Also, typical modes of electrospray were clearly observed with the microscope even under vacuum conditions. The addition of 0.01 M trifluoroacetic acid to water caused an increase in current by at least one order of magnitude compared with water only. From these results, the vacuum electrospray technique can be expected to be a high-performance massive cluster ion beam source. Copyright (C) 2012 John Wiley & Sons, Ltd.

DOI： 10.1002/sia.4907

Web of Science

Authorship：Lead author   Language：English   Publishing type：Part of collection (book)   Publisher：Springer Berlin Heidelberg  

This chapter describes the use of plasmonic substrates for the laser desorption/ionization in mass spectrometry. Interesting phenomenon such as polarization and wavelength dependence has been observed for the laser desorption/ionization of molecules from gold-coated porous silicon, gold nanorod arrays, and nanoparticles, and these results suggest the presence of near-field effects on the desorption/ionization process.

DOI： 10.1007/978-3-642-31066-9_28

Scopus

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

We have examined several combinations of solvents with the aim of optimizing the ionization conditions for molecular diagnosis of malignant tumours by PESI-MS. Although the best conditions may depend on the actual species in the sample, the optimal conditions for renal cell carcinoma (RCC) were achieved by using alcohols. PESI-MS successfully delineated the differential expression of phospholipids (PCs) and triacylglycerols (TAGs) in noncancerous and RCC tissues by using these solvent systems. This study paves the way for the application of PESI-MS in medical samples.

DOI： 10.1007/s13361-012-0462-3

Web of Science

Language：English  

Language：English   Publishing type：Research paper (scientific journal)  

Immediate diagnosis of human specimen is an essential prerequisites in medical routines. This study aimed to establish a novel cancer diagnostics system based on probe electrospray ionization-mass spectrometry (PESI-MS) combined with statistical data processing. PESI-MS uses a very fine acupuncture needle as a probe for sampling as well as for ionization. To demonstrate the applicability of PESI-MS for cancer diagnosis, we analyzed nine cases of clear cell renal cell carcinoma (ccRCC) by PESI-MS and processed the data by principal components analysis (PCA). Our system successfully delineated the differences in lipid composition between non-cancerous and cancerous regions. In this case, triacylglycerol (TAG) was reproducibly detected in the cancerous tissue of nine different individuals, the result being consistent with well-known profiles of ccRCC. Moreover, this system enabled us to detect the boundaries of cancerous regions based on the expression of TAG. These results strongly suggest that PESI-MS will be applicable to cancer diagnosis, especially when the number of data is augmented.

DOI： 10.1007/s13361-012-0447-2

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

To perform remote and direct sampling for mass spectrometry, solid probe assisted nanoelectrospray ionization (SPA-nanoESI) has been newly developed. After capturing the sample on the tip of the needle by sticking it to the biological tissue, the needle was inserted into the solvent-preloaded nanoESI capillary from the backside. NanoESI gave abundant ion signals for human kidney tissues and the liver of a living mouse. The method is easy to operate and versatile because any biological specimen could be sampled away from the mass spectrometer. Minimal invasiveness is another merit of this method.

DOI： 10.1039/c2an36006c

PubMed

Language：English  

Language：English  

Language：English   Publishing type：(MISC) Summary of the papers read (international conference)  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley & Sons  

DOI： 10.1002/rcm.6181

Language：English  

Language：English  

Language：English  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jms.2965

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s13361-011-0323-5

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jms.3062

Language：English  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

This is a follow-up paper of our previous report on an ion source, which was operated at an operating pressure higher than the atmospheric pressure. Besides having more working gas for desolvation, the reduction of mean free path of electrons in a higher pressure environment increases the threshold voltage for gaseous breakdown, thus enabling a stable electrospray for the sample solution with high surface tension without the occurrence of electric discharge. In our previous work, the ion source was not coupled directly to the mass spectrometer and significant amount of ions were lost before entering the vacuum of the mass spectrometer. In this paper, we report the new design of our second prototype in which, by using a modified ion transport capillary, the pressurized ESI ion source was coupled directly to the first pumping stage of the mass spectrometer without additional modification on the vacuum pumping system. Demonstrations of the new ion source on the sensitive detection of native proteins from aqueous solution in both positive and negative ion modes are presented.

DOI： 10.1007/s13361-011-0253-2

Web of Science

Language：English  

Language：English  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jms.1977

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Probe electrospray ionization (PESI) is one of the most promising methods in biochemical analysis because it enables us to analyze biological samples very quickly without any special pretreatment. Moreover, due to the small size of the needle tip, this method has advantages such as low invasiveness to the samples, making it possible to analyze the biological profiles of organs or tissues in living animal in situ. In this study, we performed a real-time analysis of living mice that delineates the differences in lipid composition of hepatocytes between normal and steatotic mice. In steatotic mice, the number of peaks and the ion abundance for triacylglycerols were much higher compared with those of control mice. All mice used in this study tolerated the procedure well and survived for more than a month until sacrificed for further analysis. To test a potential for medical diagnosis, human tumor tissues were also measured and we obtained discriminative results judged as useful for diagnostics. These results pave the way into the application of PESI to the in vivo analysis of biological molecules.

DOI： 10.1016/j.ab.2011.06.020

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s13361-011-0162-4

Language：English  

Language：English  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry  

DOI： 10.1039/c0an00621a

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s13361-010-0058-8

Language：English  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Mass Spectrometry Society of Japan  

The design of a new type of dielectric barrier discharge (DBD) ion source for ambient ionization is described. In this ion source, the DBD plasma is confined in the DBD tube so that the sample gases can be ionized just outside of the discharge tube by DBD excited helium gas without being exposed to the plasma jet. The findings indicate that the ion source is capable of the soft and high-sensitive ionization of explosives.

DOI： 10.5702/massspec.58.215

CiNii Books

Other Link： https://jlc.jst.go.jp/DN/JALC/00360532005?from=CiNii

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/c0ay00530d

Language：English  

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jms.1772

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/c0ay00170h

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/rcm.4556

Language：English  

Language：English  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Although being an atmospheric pressure ion source, electrospray ionization (ESI) has rarely been used directly for ambient imaging mass spectrometry because the sample has to be introduced as liquid solution through the capillary. Instead of capillary, probe electrospray ionization (PESI), which has been developed recently, uses a solid needle as the sampling probe, as well as the electrospray emitter, and has been applied not only for liquid solutions but also for the direct sampling on wet samples. Biological tissues are composed of cells that contain 70-90% water, and when the surface is probed by the needle tip, the biological fluid adhering to the needle can be electrosprayed directly or assisted by additional solvent added onto the needle surface. Here, we demonstrate ambient imaging mass spectrometry of mouse brain section using PESI, incorporated with an auxiliary heated capillary sprayer. The solvent vapor generated from the sprayer condensed on the needle tip, re-dissolving the adhered sample, and at the same time, providing an indirect means for needle cleaning. The histological sections were prepared by fixation using paraformaldehyde, and the spatial analysis was automated by maintaining an equal sampling depth into the sample in addition to raster scan. Phospholipids and galactosylceramides were readily detected from the mouse brain section in the positive ion mode, and were mapped with 60 microm lateral resolution to form mass spectrometric images.

DOI： 10.1002/jms.1632

PubMed

Language：English  

Language：English  

Language：English  

Language：English   Publishing type：Research paper (scientific journal)  

Probe electrospray ionization (PESI) is a recently developed technique that uses a fine solid needle as a probe for sampling biological materials. In this study, we quantified the volume of liquid sample picked up by the solid needle with the tip diameter of approximately 700 nm and the apex angle of approximately 60 degrees. The amounts of low-viscosity samples (rat urine) loaded on the tip of the needle by a single stroke were 0.35 +/- 0.09 pl. Interestingly, the amount of liquid adhered to the tip did not significantly depend on the protein concentration, but viscosity and surface tension of the sample. Under these conditions, we successfully obtained mass spectra for each biological sample.

DOI： 10.1002/jms.1576.

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

CiNii Books

Language：English  

Language：English  

Language：English  

Language：English  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Agricultural, Biological and Environmental Engineers and Scientists  

Electrospray has been used as one of the most powerful techniques for the analysis of biological samples. Recently, we have developed the probe electrospray (PESI) (modified version of the conventional electrospray) that uses the fine solid needle. In this method, the probe needle moves up and down along the vertical axis by a motor-driven system. At the highest position of the probe needle, electrospray is generated by applying a high voltage. In this study, we used PESI directly to the biological samples such as human milk, bovine milk, beverages, mouse brains, flower petals, plant leaves, bananas, tulip bulbs, etc. Strong ion signals for almost all samples were obtained. The amount of liquid sample picked up by the needle is as small as a few pL or less, making the PESI one of the most promising less-invasive analysis and imaging for biological samples. PESI may be useful as versatile and ready-to-use semi-on line analyses in the fields of agriculture, food science, medicine, pharmaceutical, etc. An example of imaging for mouse brain is demonstrated.

DOI： 10.2525/ecb.47.73

CiNii Books

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ijms.2008.10.005

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jms.1569

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/rcm.3877

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1246/cl.2009.520

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jasms.2009.08.023

Language：English  

Language：English  

Language：English  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Recently, we have developed probe electrospray ionization (PESI) that uses a solid needle. In this system, the probe needle moves up and down along the vertical axis by a motor-driven system. At the highest position of the probe needle, electrospray is generated by applying a high voltage. In this study, we applied PESI directly to biological samples such as urine, mouse brain, mouse liver, salmon egg, and fruits (orange, banana, etc.). Strong ion signals for almost all the samples were obtained. The amount of liquid sample picked up by the needle is as small as pL or less, making PESI a promising non-invasive technique for detecting biomolecules in living systems such as cells. Therefore, PESI may be useful as a versatile and ready-to-use semi-online analytical tool in the fields of medicine, pharmaceuticals, agriculture, food science, etc.

DOI： 10.1002/rcm.3626

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/978-3-540-77895-0_3

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jms.1425

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jp803730x

Language：English  

Language：English  

Language：English  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jms.1165

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jp065540i

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/rcm.3315

Language：English  

Language：English  

Language：English  

Language：Japanese   Presentation type：Poster presentation  

Venue：Online Conference  

Event date： 2021.5

Language：Japanese   Presentation type：Poster presentation  

Venue：Online Conference  

Event date： 2021.5

Language：Japanese   Presentation type：Poster presentation  

Venue：Online Conference  

Language：Japanese   Presentation type：Poster presentation  

Venue：Online Conference  

Event date： 2019.3

Language：English   Presentation type：Oral presentation(invited, special)  

Language：English   Presentation type：Oral presentation(invited, special)  

Venue：大阪大学中の島センター  

Event date： 2019.2

Language：Japanese   Presentation type：Oral presentation(invited, special)  

Venue：名古屋大学東山キャンパス  

Language：Japanese   Presentation type：Oral presentation(invited, special)  

Venue：名古屋大学東山キャンパス  

Event date： 2018.10

Language：English   Presentation type：Oral presentation(general)  

Venue：京都　島津製作所本社・メインホール  

Language：English   Presentation type：Oral presentation(general)  

Venue：京都 島津製作所本社・メインホール  

Event date： 2018.5

Language：Japanese   Presentation type：Oral presentation(general)  

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：ホテル阪急エキスポパーク  

Event date： 2017.12

Language：Japanese   Presentation type：Oral presentation(invited, special)  

Venue：理化学研究所  

Language：Japanese   Presentation type：Oral presentation(invited, special)  

Venue：理化学研究所  

Event date： 2016.10

Language：English   Presentation type：Oral presentation(invited, special)  

Language：English   Presentation type：Oral presentation(invited, special)  

Venue：サントリー生命科学財団 生物有機科学研究所  

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：大阪府吹田市  

Event date： 2016.5

Language：Japanese   Presentation type：Oral presentation(general)  

Event date： 2015.11

Language：Japanese   Presentation type：Oral presentation(general)  

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：島津製作所関西支社マルチホール  

Event date： 2015.10

Language：English   Presentation type：Oral presentation(invited, special)  

Event date： 2015.6

Language：English   Presentation type：Oral presentation(invited, special)  

Event date： 2014.6

Language：English   Presentation type：Other  

Event date： 2013.6

Language：English   Presentation type：Other  

Event date： 2012.7

Language：English   Presentation type：Other  

Event date： 2011.5

Language：English   Presentation type：Other  

Event date： 2010.6

Language：English   Presentation type：Oral presentation(invited, special)  

Event date： 2010.5

Language：Japanese   Presentation type：Other  

Event date： 2009.8

Language：Japanese   Presentation type：Oral presentation(invited, special)  

Event date： 2009.5

Language：Japanese   Presentation type：Oral presentation(general)  

Applicant：山梨大学

Application no：特願2009-543904 ( P2009-543904)  Date applied：2008.11

Patent/Registration no：特許第４９２９４９８号 

Country of applicant：Foreign country  

（活動の内容）
生体の直接MS観測：基礎と応用 に関連するシンポジウムを行なう。
（開催回数）
1