In this paper, we describe a novel technique-ultrasonication-assisted spray ionization (UASI)-for the generation of singly charged and multiply charged gas-phase ions of biomolecules (e.g., amino acids, peptides, and proteins) from solution; this method employs a low-frequency ultrasonicator (ca. 40 kHz) in place of the high electric field required for electrospray ionization. When a capillary inlet is immersed into a sample solution within a vial subjected to ultrasonication, the solution is continually directed to the capillary outlet as a result of ultrasonication-assisted capillary action; an ultrasonic spray of the sample solution is emitted at the outlet of the tapered capillary, leading to the ready generation of gas-phase ions. Using an ion trap mass spectrometer, we found that singly charged amino acid and multiply charged peptides/proteins ions were generated through this single-step operation, which is both straightforward and extremely simple to perform. The setup is uncomplicated: only a low-frequency ultrasonicator and a tapered capillary are required to perform UASI. The mass spectra of the multiply charged peptides and proteins obtained from sample solutions subjected to UASI resemble those observed in ESI mass spectra. Using these techniques, intense laser irradiation is generally required to provide sufficient energy to direct analytes from the condensed phase to the gas phase. Notably, the development of desorption electrospray ionization (DESI) [6]-using a fine spray of charged droplets as the desorption/ionization source for analytes under ambient conditions-has opened up new avenues for progress in desorption/ionization mass spectrometry. Apparently, as long as analyte molecules are provided with sufficient energy, which is not limited to the use of lasers, gas-phase ions can be readily generated from condensed phase samples. Furthermore, this discovery has also provided a fillip to the development of ambient mass spectrometry [7][8][9][10][11]. For example, high-energy laser [8], heated gas jets [9], low-temperature plasma [10], and nitrogen gas [11] were successfully employed to desorb analytes at ambient condition. However, post-ionization was generally required for these techniques.Ultrasonically assisted electrospray ionization [12,13] was first demonstrated more than a decade ago, using an ultrasonic transducer to enhance the nebulization efficiency of analytes eluted from a liquid chromatography column and then subjecting them to ESI. A method, so called sonic spray ionization (SSI), for small organics and drugs [14 -17] has been developed, in which a solution from a fused-silica capillary is sprayed with a sonic gas flow coaxial to the capillary. When analyzing large molecules such as proteins, an electric field is applied to the solution in the capillary to increase the charge density of produced droplets and multiply charged ions of proteins are then generated [18,19]. Lately, ultrasonic transducer-based nebulizers (operated at megahertz frequencies or greater) [20,21] have been e...

In this study, thermal desorption-based ambient mass spectrometry (TDAMS) for the analysis of small organics was explored. A layer-by-layer (LBL) self-assembled multilayer of a gold nanoparticle (AuNP)-based glass chip (Glass@AuNPs) with the absorption capacity in the near-infrared (NIR) region was used as the energy absorber and as the sample holder for sample deposition at ambient condition. An NIR laser diode (808 nm) was successfully employed as the thermal desorption source to liberate only small molecules from Glass@AuNPs chips. Followed by post-ionization, the resultant ions were monitored by an ion trap mass spectrometer. Post-ionization was assisted by a spray consisting of 50% deionized water-acetonitrile containing 0.1% acetic acid generated from a short tapered capillary by employing a high voltage (4 kV). Analytes with different polarities including small acids, amino acids, insecticides, and biodiesel samples such as ethyl esters can be directly analyzed using this approach. We demonstrated that this ambient mass spectrometric method was suitable for selectively analyzing small target organics directly from complex samples without any sample pretreatment.

Ultrasonication-assisted spray ionization mass spectrometry (UASI-MS) [1,2] is a recently developed technique. The UASI-MS requires only an inexpensive ultrasonicator and a tapered capillary for the generation of gas-phase ions from liquid samples at atmospheric pressure. No external voltage is connected to the UASI capillary emitter, which is close (~5 mm) to the orifice of a mass spectrometer. Ultrasonication drives the liquid sample from the inlet to the capillary outlet followed by formation of fine droplets, and gas-phase ions are then generated for MS analysis. UASI-MS is suitable for the analysis of a wide mass range of biomolecules, such as amino acids, peptides, and proteins. [1] A notable advantage of coupling UASI for MS analysis is relatively low ion background observed in the UASI mass spectra. In conventional electrospray ionization (ESI) MS, background ions resulting from electrochemical reduction/oxidation of solvent are unavoidable because of the use of high voltages on the sample emitter to generate electrospray. Alternatively, ultrasonication is used to assist the generation of very fine droplets from the outlet of a tapered capillary in the UASI-MS without applying any electric connection in the UASI capillary emitter. The capillary outlet is close to the orifice of the mass spectrometer, which is applied with a high voltage. Thus, we believe that the generated fine droplets are polarized on the way to the orifice of the mass spectrometer. [3] A floating potential was therefore generated. After subsequent solvent evaporation, the polarized droplets shrink followed by disruption because of coulombic repulsion resulting from the increase of the charge density, leading the formation of smaller droplets with net positive charges, neutral state, and net negative charges. The positively charged droplets tend flying to the orifice of the mass spectrometer applied with a negative potential. After desolvation, gas-phase ions are readily formed for MS analysis. Owing to the ease of polarization, the formation of very fine droplets is a prerequisite for successful generation of multiply/singly charged ions when no electrode/voltage is applied on the sample emitter as demonstrated in several reports. [1,2,[4][5][6][7] In the UASI-MS, ultrasonication is significant for the assistance of the formation of fine droplets. The elimination of the use of high voltages in the UASI approach also leads the reduction of background ions. In this work, UASI-MS is further employed for the analysis of saccharides and samples containing high concentrations of salts. The salt effects of UASI-MS are investigated in this study.An ultrasonicator (2.5 l, 160 W, 42 kHz), generally filled with 2.1 l of water, was used in the UASI setup. A capillary was tapered to have a sharp tip. The tapered capillary (length, 20 cm; tip diameter, ca. 10 AE 3 mm) was filled with the sample solution before being placed in an aqueous sample solution within a vial in the ultrasonicator (Fig. 1). The tapered capillary outlet was close (~5 mm) to th...