How the J105 SIMS works: An introductory guide

The J105 SIMS is a state-of-the-art 3D imaging ToF SIMS combining innovative design with cutting-edge science that has redefined ToF SIMS. Designed to exploit the benefits of cluster ion beams, the J105 delivers exceptional sensitivity to molecular ions, 3D MS imaging, and consistent performance across all samples.

In this article, we aim to give you an overview of how the J105 SIMS works, as it is quite different to other ToF SIMS. We will guide you through the various features of the instrument and explain their purpose, how they work, and what the benefits are.

How the J105 SIMS works: an introductory guide

1.      The Ion Beam

The J105 was designed to get around many of the limitations faced by traditional ToF SIMS instruments, particularly for biological samples. One of the ways this is achieved is by not pulsing the primary ion beam, but instead running it in DC, or continuous mode. This is a major advantage and is what makes the J105 a very different instrument to most other ToF SIMS.

One of the biggest advantages of having a continuous beam is that any ion beam, no matter what size, can be used as the primary source. This gives the user a lot of choice when designing their experiment. We’ll cover the intricacies of different ion beams in a different article, but for the purposes of this discussion we’ll focus on gas cluster ion beams (GCIB).

A GCIB typically consists of thousands of constituent atoms, giving it a collective molecular weight anywhere from 100,000 g/mol upwards. Under typical acceleration voltages (kV), such a large ion moves very slowly, requiring longer pulses and on a conventional ToF would result in poor mass resolution. By running in continuous (or long pulsing) mode, the J105 is able to get around this issue and take full advantage of the benefits of using GCIBs.

The other major advantage of running in DC mode is that focusing the ion beam to a fine spot can be prioritized without affecting the performance of the mass spectrometer. With our most powerful GCIB, the GCIB SM, the optics have been designed to enable spot sizes of just 1.5 µm, combining greater spatial resolution with high-sensitivity mass spectrometry. The benefits of this are clear, and have been highlighted recently by the pioneering work published in Science.

Benefits: Simultaneous high-sensitivity mass spectrometry with high-spatial resolution.

View of a sample through a window

2.      The Extraction Optics

As the primary beam is not pulsed, in order to determine a time-of-flight the secondary ion beam is pulsed instead. This is done by the Buncher, but the extraction optics play a key role is controlling the secondary ion beam prior to that step.

Secondary ions extracted from the surface contain a lot of energy making them difficult to control. In order to form the secondary ions into a controlled beam, they enter an RF quadrupole filled with N2, which slows the ions down through the process of collisional cooling.

This is a crucial step, as it decouples the effects of the primary beam and the sample from the secondary ions. By effectively wiping the memory of any interaction on the surface, this step enables the J105 to analyse samples with complex topography without any loss of mass spec performance.

Benefits: Consistent performance that is independent of ion beam or sample topography.

The analysis chamber of the J105 SIMS

3.      The Buncher

In many ways the heart of the instrument, the Buncher is what takes a continuous stream of secondary ions coming from the quad and forms them into a very short pulse. In order to measure the time-of-flight without pulsing the primary beam or the extraction, the Buncher creates an asymmetric pulse that focuses all ions of the same mass to a single time focus, T0. This is an essential step, and is what ultimately determines the mass resolution.

Benefits: High mass accuracy, high mass resolution.

J105 SIMS reflectron & mass analyser

4.      Tandem MS & Time-of-Flight

As with any form of mass spectrometry, definitively assigning peaks requires a secondary validation step. One way to do this is through tandem MS, whereby a parent ion is selected to undergo fragmentation and the resulting spectrum is used to determine the exact form of the parent. The J105 SIMS was the first SIMS instrument to introduce tandem MS, and is included as standard on all our instruments.

When a user selects an ion of interest, it is directed into a high-energy collision cell filled with N2, producing characteristic fragment ions. Whether running an MS1 or MS2 experiment, ions then enter the 1500 mm long reflectron before being detected.

Benefits: Tandem MS for accurate peak identification, high mass resolution.

The J105 SIMS contains several innovative design features that combine to produce an instrument like no other, optimized to enable both maximum sensitivity and maximum spatial resolution simultaneously from any ion beam. Consistent performance is guaranteed, as the mass spectrometer delivers high mass resolution (> 10,000) and mass accuracy (< 5 ppm) that are completely independent of the ion beam and the sample environment.

The J105 SIMS is the ideal tool for a wide range of applications and sample types, including biological research, pharmaceuticals, thin films, polymers, energy applications and many more. To find out if the J105 might be the right instrument for you, or to arrange a demonstration, please get in touch via our Contact Page.

Drug detection with high-sensitivity using ToF SIMS

The high attrition rate of pharmaceutical drug compounds adds enormously to the cost of those that make it to market, so there is an urgent and growing need to identify failure at earlier stages of drug development.

In order to do so, researchers require as much information as possible. Specifically, there is a need to measure the concentration of a drug at the target in order to accurately predict its pharmacological effect. This then requires a means of generating label-free sub-cellular imaging, as fluorescent labels may affect drug chemistry, altering results.

Time of flight secondary ion mass spectrometry (ToF SIMS) is a powerful tool for label-free chemical imaging, having typically very high lateral resolution capable of resolving sub-cellular features with 3D analysis capabilities.

ToF SIMS is thus a potentially powerful analysis tool for the screening of new drug compounds. However, the use of high energy projectiles for ToF SIMS analysis can cause molecules to fragment, preventing the molecular ion from being detected. This can lead to a lot of ambiguity, for example distinguishing between a drug compound and its metabolites.

Another possible stumbling block is the issue of sensitivity, particularly for those compounds of most interest. In a recent study by the National Physical Laboratory (NPL), Vorng et al. demonstrate that the sensitivity in ToF SIMS is proportional to the Log P of that compound, such that compounds with low or negative Log P values are extremely difficult to detect.  

Log P, or partition coefficient, is a measure of hydrophobicity, and is a major factor used in pre-clinical assessment of a compound’s druglikeness.  It is advisable that a drug candidate be as hydrophilic as possible while still retaining adequate binding affinity to the therapeutic protein target, i.e. that the Log P be as low (or negative) as practicable. This presents an obvious problem for the use of ToF SIMS as an analytical tool in this context.

Cluster beam colliding with a surface.

We have recently led the development of a new type of ion source for ToF SIMS that provides unparalleled sensitivity particularly for organic species. Available exclusively on the J105 SIMS, the Water Cluster Source simultaneously reduces fragmentation while increasing ionization, for truly unparalleled sensitivity of drugs, metabolites, biomarkers, lipids, peptides and more.

Combining this new ion source with the already impressive sensitivity of the J105 SIMS, even low Log P compounds can be detected in tissue and cells, with direct, label-free imaging of the molecular compounds at sub-cellular resolutions.

To demonstrate this, we doped tissue homogenate with 4 different pharmaceutical compounds that span the range of Log P from -0.8 to 7.6. The relationship between sensitivity and Log P reported by NPL is observed in this data, however the slope of the line is greatly reduced, with only a factor of 40 between the highest and lowest values.

ToF SIMS sensitivity to drugs as a function of Log P
ToF SIMS sensitivity of four different drugs using the Water Source. Sensitivity shows a linear relationship to the partition coefficient, Log P, though the slope is not steep.

As a comparison, we performed the same experiments with a state-of-the-art Ar gas cluster ion beam and plotted the yield against that of the new Water Source. The Water Source increased sensitivity by an order of magnitude in most cases, with the largest increase being for those compounds with the lowest Log P values. This indicates that the improvement in sensitivity is greatest for those compounds that need it the most.

Comparing sensitivity of argon and water cluster beams for four different drugs
Comparing sensitivity of a state-of-the-art Ar cluster source with the Water Source. Sensitivity improves by roughly an order of magnitude when using water, with the largest increase for those compounds with lower Log P values.

As a final demonstration of the capabilities of the J105 with the Water Source, we performed tandem MS analysis on the homogenate samples. Tandem MS is an important step for confirming any assignment in mass spectrometry, however the inefficiency of the process often means it can only be performed on high intensity peaks. With the boost in sensitivity provided by the Water Source, tandem MS analysis is possible even on compounds with relatively low Log P values, such as ciprofloxacin.

Tandem MS analysis of the drug ciprofloxacin
Tandem MS performed on the J105 SIMS with a Water Source. Greater sensitivity allows definitive confirmation of many more peaks.

ToF SIMS is a potentially powerful analysis tool for the screening of new drug compounds, however research is hampered by the inherently low sensitivity to many drug candidates. The J105 SIMS in combination with the Water Cluster Source provides unparalleled sensitivity to drug compounds, particularly in complex matrices such as tissue and cells, even for low Log P compounds. This unprecedented sensitivity combined with sub-cellular imaging and high-resolution 3D imaging mean the J105 SIMS is a powerful tool for drug analysis.

To learn more about how the J105 SIMS can benefit your research or to set up a demonstration, get in touch via our Contact Page.

Employee Spotlight: Dr Naoko Sano

As a small company, Ionoptika is very proud of its skilled and dedicated staff, who together with our loyal users make up our global community. So each month we will be putting the spotlight on one of our talented colleagues to introduce you to some of the people behind Ionoptika.

The first to be in the spotlight is one of most recent hires, Dr Naoko Sano, our new Applications Scientist. We asked Naoko about her career and what she enjoys about working at Ionoptika.

Employee spotlight - quote

Where were you before you started at Ionoptika?

I joined Ionoptika from Nara Women’s University in Japan where I was Associate Professor in textile science.

What does a typical day look like for you?

Most days I spend my time working on new applications and processing SIMS data. At lunch time I sometimes like to go for a walk with friends from the office, which really helps me refresh. The rest of the time I can be found running samples on the J105 ToF SIMS instrument for existing and potential customers. I’m also involved in testing new software and providing feedback back to the software team.

What do you love most about your job?

One of the most exciting parts of my job is the great variety of applications that I’m involved in, from investigating neurotransmitters in brain tissue, to analysing the frictional properties of lubricants. This makes the job of Application Scientist immensely challenging but hugely rewarding!

Why did you decide to study science when you were at school or university?

A working experience with the Surface Analysis group at NPL in 2006-7 gave a great impact to me in a good way and I really enjoyed UK/London life whilst I was there. Fortunately, around the end of the working experience, Prof. John F. Watts offered a PhD studentship, so I decided to study surface science in University of Surrey, which was my big turning point in my life.

What’s it like working at Ionoptika?

All colleagues here in Ionoptika are friendly, so I enjoy chatting with them at the office. So I miss it very much because of the current WFH situation…

What has been your best memory or achievement in your career?

It would be my first poster award in SIMS-XVII. On the day for the award ceremony, I was late to get to the venue, because I didn’t care for the ceremony at all (a naughty student!). When I got into the venue and tried to find a space to sit, the chairman (coincidentally it was John, my supervisor) on the stage, said ‘Naoko, you are there!’. Everybody turned back and looked at me. I was so proud of my work on the stage, but I felt so embarrassed as well…

What do you enjoy doing in your spare time?

Aromatherapy and reading books.

Have you been doing anything interesting/different/new to cope with the lockdown?

I’ve started online yoga lessons. I still prefer to do it in an actual studio with people, but online yoga class works at least. 

What are you looking forward to most once the lockdown is over?

Travel to see my family and friends all over the world. Miss you all very much!


You can catch up with Naoko and the rest of the Ionoptika team at various conferences throughout the year. Interested in becoming part of our team? Visit our Careers page.

Cocaine metabolite imaging in fingerprints with Water Cluster SIMS

Detection of drug compounds and their metabolites in natural environments is a critical topic for both forensic and pharmaceutical applications, and requires overcoming some of the limitations in existing microscopic and analytical techniques.

Time of Flight Secondary Ion Mass Spectrometry (ToF SIMS) is a powerful analytical technique capable of providing detailed chemical and spatial information about a surface, and as such has recently been employed in a number of forensic studies for drug and metabolite detection. However, ToF SIMS can suffer from low sensitivity due to insufficient ionisation efficiency, and this is particularly true for complex biomaterials, i.e. those of most interest to forensic and medical analysts.

Recently, we have led the development of a powerful unique gas cluster ion beam (GCIB) using water clusters. The Water Cluster Source is capable of enhancing ion yields by many orders of magnitude compared to other conventional ion beams (C60+, Bi3+ etc.), and is particularly effective for biomolecular imaging and 3D analysis of organics such as tissue, cells, fingerprints, etc.

Plot displaying increase in signal intensity using water clusters
Water clusters enhance sensitivity to intact biomolecules such as lipids, even compared to current state-of-the-art GCIB technology.

In this application note, an experimental fingerprint detection approach using the Water Cluster Source identifies traces of ingested cocaine on human skin. The use of the J105 SIMS equipped with the Water Cluster Source (Water Cluster SIMS) provides both visualisation of the latent fingerprint as well as discrimination between contact-only and ingested cocaine by looking for metabolites of the drug excreted through the skin.

Detectable levels of metabolite in a fingerprint are extremely low, for instance 25 mg of ingested cocaine excretes less than 2.5 ng/mL in sweat,1 and previous attempts using other mass spectrometry imaging (MSI) techniques such as MALDI and DESI were unsuccessful. Using Water Cluster SIMS, it was possible not only to detect the metabolite, but also to generate a high-contrast chemical map of the entire fingerprint.

The fingerprint specimen, provided by University of Surrey, was collected on a piece of silicon wafer from a donor who had previously ingested cocaine,2 then a ToF-SIMS analysis was acquired on an 18×6 mm2 area with a 70 kV (H2O)29k+ primary ion beam in the J105 SIMS.

Figure 1(a) shows the chemical image of the 290.14 m/z signal, demonstrating the characteristic fingerprint features with ridges, valleys, as well as sweat pores. Due to the high mass accuracy of the J105 SIMS, this signal is confidently annotated as the cocaine metabolite benzoylecgonine (BZE, C16H20NO4+). Figure 1(b) shows a colour overlay of BZE (magenta) and the cocaine molecular ion (C17H22NO4+, 304.15 m/z – yellow). As expected, cocaine was observed in particulate form (see arrow) due to direct contact of the donor with the powder, and is not co-localised with BZE.

ToF SIMS image of cocaine metabolite BZE in a fingerprint.
Figure 1(a) Positive ion image of BZE (C16H20NO4+, 290.14 m/z) in a fingerprint. (b) Overlay positive ion image with BZE (magenta) and cocaine (C17H22NO4+, 304.15 m/z – yellow). (c) BZE peak, with high mass accuracy and high mass resolution.

These images, with the small amounts of BZE and cocaine present, demonstrate the benefits of Water Cluster SIMS for enhancing sensitivity, particularly for trace detection of organic compounds in complex sample matrixes.

The J105 SIMS is a powerful tool for 2D and 3D molecular imaging, providing high sensitivity analysis with a range of powerful features. Now featuring the new Water Cluster Source, the J105 takes another leap forward to offer even greater sensitivity and to intact molecular ions. This exciting new technology has been shown to dramatically improve the imaging of drug metabolites ingested by the body, and is a powerful tool for visualising molecular information in a wide range of applications.

To find out more about how the J105 SIMS can benefit your research, get in touch via our Contact Page.


References

  1. Kacinko, S. L., Barnes, A.J. et al. , Disposition of Cocaine and Its Metabolites in Human Sweat after Controlled Cocaine Administration, Clinical Chemistry, 51, 2085 (2005). https://doi.org/10.1373/clinchem.2005.054338
  2. Jang, M., Costa, C., Bunch, J. et al. On the relevance of cocaine detection in a fingerprint. Sci Rep 10, 1974 (2020). https://doi.org/10.1038/s41598-020-58856-0