SIMS2015 Session IN1-TuM: Instrument Development

A new tandem TOF-TOF imaging mass spectrometer exploiting the unique characteristics of the TRIFT analyzer used in the PHI nanoTOF II has been developed [1]. This design allows for conventional TOF-SIMS spectra and product ion spectra of a specific precursor to be acquired in parallel, providing the maximum information from a given analytical volume. It has been recognized for many years that MS/MS was required to unambiguously identify peaks above 200 m/z due to the limitations of mass resolution and mass accuracy in commercial TOF-SIMS instrumentation. Previous tandem mass spectrometry designs used for TOF-SIMS [2,3] and MALDI [4] have discarded all secondary ions except the precursor in MS1 when performing an MS/MS experiment [2,3]. In the design reported here, a single nominal mass can be picked from the stream of secondary ions after it emerges from the third ESA and deflected into a collision cell for collision induced dissociation (CID). The entire TOF-SIMS spectrum, minus the precursor, is acquired in the standard way in MS1. The selected precursor ion and fragment ions that emerge from the collision cell are further accelerated into a linear TOF mass spectrometer (MS2). A full mass spectrum at both MS1 and MS2 are simultaneously acquired for each pixel in the image. Advantages of this new approach for imaging experiments will be demonstrated.

References:

1. P.E. Larson, J.S. Hammond, R.M.A. Heeren and G.L. Fisher, Method and Apparatus to Provide Parallel Acquisition of MS/MS Data, U.S. Patent 20150090874, April 2015.

2. A. Carado, M.K. Passarelli, J. Kozole, J.E. Wingate, N. Winograd, Anal. Chem., 2008, 80, 7921-7929.

3. R. Hill, P. Blenkinsopp, S. Thompson, J. Vickerman, and J.S. Fletcher, Surf. Interface Anal., 2011, 43, 506-509.

4. “MALDI MS, A Practical Guide to Instrumentation, Methods, and Applications”, edited by F. Hillenkamp and J. Peter-Katalinic, Wiley-Blackwell , 2014.

We have shown that energetic impacts of electrosprayed massive clusters can eject intact molecular ions of lipids, peptides and small proteins with ion yields sufficient to enable bioimaging with few-µm resolution [1]. This paper will address progress in developing MCI bioimaging of intact molecular species as a viable tool for tissue imaging with sub-cellular spatial resolution. Quantitative evaluation of matrix effects can illustrate the limits of quantitative imaging with cluster sputtering and may illuminate the ionization process. The influence of cluster chemistry, size and velocity on ionization and ion yields will be examined. Design parameters for optimal instrumentation will be discussed.

[1] “Imaging with biomolecular ions generated by massive cluster impact in a time-of-flight secondary ion microscope”, Jitao Zhang, Klaus Franzreb, Peter Williams, Rapid Commun. Mass Spectrom. 2014, 28, 2211–2216

Many types of mass analyzers are widely spread and used in various fields. In this study, we will demonstrate a new principle mass analyzer by introducing two rotating electro fields (REFs). The mass analyzer can be applied for a mass filter for cluster ion beam or a potable bio mass analyzer. We described the principle of new mass analyzer below.

1. Ions travel into a first REFs. On exit of the first REFs, ions are mass separated slightly.

2. We select a typical ion of a native mass number.

3. The flight time of the ion is controlled to be just one cycle on each REF.

4. Between the two REFs, ions travel different trajectories on their mass.

5. The second REF is drawn opposite phase with the first REF.

6. In the second REF, typical ions are conversed to center axis and the other ions travel different trajectory. Mass separations are strongly promoted at the exit of the second REF.

The new principle mass analyzer has been designed for organic materials. In principle, its mass range has no limits, the analyzer can be modified for bio molecules, proteins, lipids or a mass filter for cluster ion beam and so many high mass applications. And also the optics of mass analyzer can be designed within PET bottle size. So it can be applied for a potable bio mass analyzer.

In this presentation we will demonstrate the state of the art of newly developed mass analyzer. The first prototype mass analyzer was developed to demonstrate the own potential by separation of isotopes; ⁶⁹Ga⁺ and ⁷¹ Ga+. Ga-focused ion beam (FIB) column and the mass analyzer were connected in tandem. Acceleration voltage of FIB was 10 keV, sinusoidal signal voltage and frequency of REFs were 80 ~ 120 V and 1.115 MHz. On this condition, ⁶⁹Ga⁺ is converged to center axis and ⁷¹ Ga⁺ draws coaxial circle pattern on the exit of the second REF. We also obtained a mass spectrum of ⁶⁹Ga⁺ and ⁷¹ Ga⁺ by sweeping the frequencies of REFs. The frequencies of REFs were swept from 1120 kHz to 1090 kHz on 1 kHz steps. ⁶⁹Ga⁺ and ⁷¹ Ga⁺ were clearly separated on the mass spectrum using the new principle mass separation theory. The mass resolution was estimated to 158 by FWHM.

We are now estimating mass filtering abilities for gas cluster ion beam (GCIB). This study is supported by Japan Science and Technology agency (JST)-SENTAN program.

In recent years, massive clusters such as gas clusters and charged droplets have been used as a primary ion beam in SIMS. For further improvement in SIMS analysis, it is required to develop a new cluster beam source capable of producing massive ions at higher current density with a smaller beam spot size.

From the viewpoint of generating such massive ions, vacuum electrospray of ionic liquids is expected to have a great potential. Actually, we have developed a vacuum-electrospray beam source using room-temperature ionic liquids, subsequently demonstrating that an ionic-liquid primary ion beam was applicable to SIMS analysis. However, there still remain some issues to be solved; a top priority issue is to increase secondary ion intensities of organic samples.

In the present study, we have performed two kinds of SIMS experiments, in which ionic liquids were used (i) as liquid matrices and (ii) as primary ion beams. First, we have tested ionic liquids as liquid matrices in SIMS. The following three ionic liquids have been tested: N,N-diethyl-N-methyl-N-(2-methoxyethyl)ammonium bis(trifluoromethanesulfonyl) amide ([DEME][TFSA]), 1-ethyl-3-methyl imidazolium bis(trifluoromethanesulfonyl) amide ([EMIM][TFSA]), and diethylmethylammonium trifluoromethanesulfonate ([dema][TfO]). The former two, [DEME][TFSA] and [EMIM][TFSA], have ionic conductivity, but these do not have protonic conductivity. In contrast, the latter, [dema][TfO], has protonic conductivity. Experimental results showed that [dema][TfO] functioned as an effective matrix to increase the secondary ion intensity of protonated arginine.

Next, we have generated an ionic-liquid beam of [dema][TfO], thereby performing SIMS analysis. Obtained results showed that the primary ion beam of [dema][TfO] produced more effectively protonated secondary ions of arginine. We expect that proton-conducting ionic liquids will have a great potential in SIMS analysis of organic and biological materials.

Secondary ion mass spectrometry (SIMS) has been used for the analysis of inorganic materials and also organic and biological samples. One of the most serious problems in SIMS is its low ionization efficiency for biological molecules. The higher ionization efficiency has been obtained when primary cluster ion beams such as C₆₀⁺ and Bi₃²⁺ are used, and an improvement of sensitivity for imaging mass spectrometry for biological samples has been reported. However, ionization efficiency in SIMS is still not enough for imaging with high spatial resolution. Therefore, development of a new ion beam source is one of the most important issues for improving the overall quality of SIMS. Recently, massive cluster ion sources such as Ar gas clusters have been developed in order to improve the efficiencies of secondary ion formation and achieve damage-less etching. Compact Ar gas cluster ion guns are now commercially available in surface analytical instruments. Electrosprayed droplet impact (EDI) method based on atmospheric pressure electrospray technique was developed as a new massive cluster ion beam source by Hiraoka et al., and it has been successful in achieving efficient ionization of biological molecules, soft etching of polymers, and non-selective etching of metal oxides. However, the beam diameter (~0.2 mm) and beam density (~3µA/cm²) of this atmospheric pressure type EDI (A-EDI) gun need to be much improved as a SIMS probe. The reason for the relatively large beam diameter and the resulting small beam density originates mainly from the use of “atmospheric pressure electrospray” as a beam source. In order to improve the performance of this A-EDI gun, we have developed a technique using electrospray of aqueous solutions in vacuum as a beam source. This vacuum electrospray technique could be expected to be a high-intensity massive cluster beam source, and we are now evaluating the performance of the vacuum-type electrosprayed droplet impact (V-EDI) gun. In the previous study, the mass-to-charge (m/z) ratio distributions of the V-EDI beams were measured by the time-of-flight technique. Maximum m/z value was found to be around 10⁶. However, the optimization of the m/z ratios of charged droplets for efficient secondary ion emission is not achieved. In this study, the characteristics of secondary ion emission produced by V-EDI with m/z selection from 10³ to 10⁶ will be presented.

A secondary ion mass spectrometer (SIMS) instrument is described that is configured with two SIMS detectors that are both low-field extraction, quadrupole-based filters for simultaneous detection of positive and negative secondary ions (SPN) and that differ from previous designs [1, 2]. Secondary ions are generated by sputtering with a liquid-metal ion gallium source and column of the type that is common on two-beam electron microscopes [3]. The gallium ion beam, or focused ion beam (FIB) achieves sub-100 nm focus with a continuous current of up to 300 Pa. Positive secondary ions are detected by one SIMS detector and simultaneously negative secondary ions are detected by the second SIMS detector. The SIMS detectors are independently controlled for recording mass spectra, concentration depth profiles and secondary ion images. Examples of simultaneous positive and negative (SPN) SIMS are included that demonstrate the performance and advantages of this facility for surface analysis and depth profiling. The SIMS secondary ion collection has been modeled using the ray tracing program SIMION 3D [4] in order to understand the interaction of the secondary ions of opposite polarities in the extraction volume for the purpose of optimizing secondary ion collection.

1. Hayashi, H., et al., Applied Surface Science, 1993. : p. 287-290.

2. Daolio, S., et al., Rapid Communications in Mass Spectrometry, 1999. (9): p. 782-785.

3. Chater, R.J., et al., Surface and Interface Analysis, 2014. (S1): p. 372-374.

4. SIMION. [http://www.simion.com/] . [cited 2014 19th September].

The Sensitive High Resolution Ion Micro Probe (SHRIMP), is a large radius, magnetic sector SIMS instrument designed for measuring trace elements in geologic samples with many mass interferences. Since the early 1980s, SHRIMP has been used for trace elemental and isotopic analysis of geological materials, principally U-Th-Pb geochronology, with the updated more sensitive SHRIMP 2 being built in 1990. Since that time, a cesium primary ion source, electron gun for charge neutralization, and multicollector for precise isotope analyses have been added. However, the primary column and sample-mass spectrometer coupling arrangement on commercially available instruments has not changed in 25 years.

The SHRIMP 4 modernises the front end of the instrument in the following ways: The primary column is redesigned based on Australian and Chinese research instruments currently under development to allow a smaller, brighter spot, using either Köhler or critical illumination. A double deflector system on the primary beam will allow primary beam rastering, enabling raster-based imaging or depth profiling techniques to be applied to SHRIMP. The source chamber is designed to have a harder vacuum, enabling the analysis of volatile species in mineral samples. The secondary column has a dynamic emittance matching system to allow efficient, low-fractionation coupling between the sample and the mass spectrometer. An einzel lens is added after the two stage extraction system to reduce the fractionation caused by topography or conductivity changes near the sputtering site. The quadrupole lenses which match the secondary ion emittance to the acceptance of the mass spectrometer have been separated, to reduce fringing field effects, drawing on the SHRIMP-SI currently operated by the Australian National University. The floating primary column and two-stage extraction system with a low initial extraction field, and user-friendly design will be retained from the SHRIMP 2 design.