Celebrating 30 years of the Kore “BioTOF” TOF-SIMS for biological samples

Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS) is a highly surface-sensitive analytical technique, enabling non-destructive analysis of the top three to five atom layers of a sample. Kore manufactures a range of TOF-SIMS instruments, each optimised for different sample types and providing a unique combination of performance characteristics:

  • High surface sensitivity
  • High chemical and isotopic specificity
  • High spatial resolution in two and three dimensions

Our TOF-SIMS instruments have been used globally in diverse scientific fields, including biochemistry.

Looking back to the year 1995, the Kore team took on the challenge of developing the first biochemical microscope for cell surface analysis, which is still in use today. Kore’s Managing Director, Dr Steve Mullock, says: “30 years ago, Kore started development of the ‘BioTOF’, to provide a window into the underlying biochemical mechanisms of single cells. Building on initial exploratory studies with Professor John Vickerman at UMIST and colleagues at Penn State University, our primary goal was to develop the sample processing and software for freeze-fracture in-situ surface analysis of individual microbial cells and for spatial localisation of microbial metabolites at the sub-µm scale.”

The design was led by Kore’s Mechanical Engineer, Clive Corlett, who has been designing systems and components for Kore since its inception in 1991. Clive recalls “We needed to prepare biological samples in a form which stabilises the hydration state of the cellular material. This then had to be introduced into the vacuum system in a matter of seconds, without damage to its structure. We designed sample manipulation facilities which enabled the cell surface to be held in a stable state. Once our freeze-fracture system had been developed and tested on model liposomes, our BioTOF clients were able to carry out all sorts of interesting research.”

One of Kore’s long-term clients of the BioTOF is the Surface Analysis Research Centre at the University of Manchester (previously UMIST), UK. The world-renowned group, established by Professor John Vickerman and currently led by Professor Nick Lockyer, has used Kore-derived instrumentation as the ideal platform to test and develop advances in SIMS technology. Professor Lockyer says: “For 30 years, the BioTOF SIMS instrument has been a workhorse for demonstrating a range of advances, such as freeze-fractured sample preparation, polyatomic sputtering for 3D molecular imaging, laser post-ionisation and high-mass detection. Analytes have ranged from isotopic elements to metabolites and other biological molecules up to several hundred mass units. Among our group’s most significant outputs were the first 3D molecular SIMS image of a single biological cell, and the first molecular TOF-SIMS characterisation of cancer cells. The instrument has showcased the advantages of novel primary ion beams (Aun and C60), contributing to significant upgrades in SIMS performance in industry and academia.”

Kore celebrates three decades of enhanced support for our BioTOF users around the world. “The BioTOF-SIMS has been a great example of Kore’s flexibility and experimental approach to instrument development, taking on the new design risk so that others can follow”, says Professor Lockyer. “Science is driven through measurement. SME instrument manufacturers bring disruptive technologies and concepts to the marketplace which enable advances in metrology and downstream impacts to society through their widespread uptake.” Kore thrives on this symbiotic relationship between our skilled designers and worldwide visionary scientists, raising the bar for instrument development.

Professor Nick Lockyer seeks to address the most challenging applications and fundamental questions in SIMS. “The Kore BioTOF-SIMS has analysed fossils, biological cells and tissues, advanced materials, textiles, bacteria, atmospheric aerosols, and even Martian meteorite! The design concept of the BioTOF-SIMS, together with the expertise and philosophy of the team at Kore Technology, has provided the means to address these challenges successfully. This includes flexibility in experimental configuration and customisation, together with a willingness from Kore to build long-term, productive customer relations.”

 

 

 

 

 

Martian meteorite
Leaf stomata cells

 

Boron-treated tumour cells

 

Multivariate analysis of cancer cell data 

Prostate cancer cell

 

Further Reading

Quantitative surface analysis of a binary drug mixture—suppression effects in the detection of sputtered ions and post-ionized neutrals.
Gabriel Karras, Nicholas P. Lockyer
Journal of The American Society for Mass Spectrometry 25 (2014): 832-840

Investigating the effect of temperature on depth profiles of biological material using ToF-SIMS.
Alan Piwowar, John Fletcher, Nicholas Lockyer and John Vickerman

Surface and Interface Analysis 43 (2011): 207-210

Effects of Cryogenic Sample Analysis on Molecular Depth Profiles with TOF-Secondary Ion Mass Spectrometry.

Alan M. Piwowar, John S. Fletcher, Jeanette Kordys, Nicholas P. Lockyer, Nicholas Winograd, and John C. Vickerman

Analytical Chemistry 82 (19) (2010): 8291-8299

Explanatory multivariate analysis of ToF-SIMS spectra for the discrimination of bacterial isolates.
Seetharaman Vaidyanathan, John S. Fletcher, Roger M. Jarvis, Alex Henderson, Nicholas P. Lockyer, Royston Goodacre and John C. Vickerman
Analyst 134 (2009): 2352-2360

A cancer research UK pharmacokinetic study of BPA-mannitol in patients with high grade glioma to optimise uptake parameters for clinical trials of BNCT.
Cruickshank, G. S.; Ngoga, D.; Detta, A.; Green, S.; James, N. D.; Wojnecki, C.; Doran, J.; Hardie, J.; Chester, M.; Graham, N.; Ghani, Z.; Halbert, G.; Elliot, M.; Ford, S.; Braithwaite, R.; Sheehan, T. M. T.; Vickerman, J.; Lockyer, N.; Steinfeldt, H.; Croswell, G.; Chopra, A.; Sugar, R.; Boddy, A.

Applied Radiation and Isotopes 67 (2009): S31-S33

TOF-SIMS investigation of Streptomyces coelicolor, a mycelial bacterium.
Seetharaman Vaidyanathan, John S. Fletcher, Nicholas P. Lockyer and John C. Vickerman
Applied Surface Science 255 (2008): 922-925

ToF-SIMS PC-DFA analysis of prostate cancer cell lines.
Baker M.J., Gazi E., Brown M.D., Clarke N.W., Vickerman J.C. and Lockyer N.P.
Applied Surface Science 255 (2008): 1084-1087

Mass spectral imaging of glycophospholipids, cholesterol, and glycophorin A in model cell membranes.
Matthew J. Baker, Leiliang Zheng, Nicholas Winograd, Nicholas P. Lockyer and John C. Vickerman
Langmuir 24 (2008): 11803-11810

Discrimination of prostate cancer cells and non-malignant cells using secondary ion mass spectrometry.
Matthew J. Baker, Michael D. Brown, Ehsan Gazi, Noel W. Clarke, John C. Vickerman and Nicholas P. Lockyer
Analyst 133 (2008): 175-179

Depth profiling brain tissue sections with a 40 keV C60+ primary ion beam.
Emrys A. Jones, Nicholas P. Lockyer, John C. Vickerman
Analytical Chemistry 80 (2008): 2125-2132

Subsurface biomolecular imaging of Streptomyces coelicolor using secondary ion mass spectrometry.
Seetharaman Vaidyanathan, John S. Fletcher, Roy Goodacre, Nicholas P. Lockyer, Jason Micklefield, and John C. Vickerman
Analytical Chemistry 80 (2008): 1942-1951

Properties of C84 and C24H12 molecular ion sources for routine TOF-SIMS analysis.
Biddulph, Gregory X.; Piwowar, Alan M.; Fletcher, John S.; Lockyer, Nicholas P.; Vickerman, John C.
Analytical Chemistry 79 (2007): 7259-7266

Suppression and enhancement of secondary ion formation due to the chemical environment in static-secondary ion mass spectrometry.
Jones, Emrys A.; Lockyer, Nicholas P.; Kordys, Jeanette; Vickerman, John C.
Journal of the American Society for Mass Spectrometry 18 (2007): 1559-1567

TOF-SIMS 3D biomolecular imaging of Xenopus laevis oocytes using Buckminsterfullerene (C60) primary ions.
Fletcher, John S.; Lockyer, Nicholas P.; Vaidyanathan, Seetharaman; Vickerman, John C.

Analytical Chemistry 79 (2007): 2199-2206

Mass spectral analysis and imaging of tissue by ToF-SIMS—The role of Buckminsterfullerene, C60 +, primary ions.
Jones, Emrys A.; Lockyer, Nicholas P.; Vickerman, John C.
International Journal of Mass Spectrometry 260 (2007): 146-157

TOF-SIMS analysis using C60. Effect of impact energy on yield and damage.
Fletcher, John S.; Conlan, Xavier A.; Jones, Emrys A.; Biddulph, Greg; Lockyer, Nicholas P.; Vickerman, John C.
Analytical Chemistry 78 (2006): 1827-1831

Is proton cationization promoted by polyatomic primary ion bombardment during time-of-flight secondary ion mass spectrometry analysis of frozen aqueous solutions?
Conlan, Xavier A.; Lockyer, Nicholas P.; Vickerman, John C.

Rapid Communications in Mass Spectrometry 20 (2006): 1327-1334

Molecular depth profiling of organic and biological materials.
Fletcher, John S.; Conlan, Xavier A.; Lockyer, Nicholas P.; Vickerman, John C.

Applied Surface Science 252 (2006): 6513-6516

Application of TOF-SIMS with chemometrics to discriminate between four different yeast strains from the species Candida g labrata and Saccharomyces cerevisiae.
Jungnickel, Harald; Jones, Emrys A.; Lockyer, Nicholas P.; Oliver, Stephen G.; Stephens, Gill M.; Vickerman, John C.

Analytical Chemistry 77.6 (2005): 1740-1745

Urban PM2.5 surface chemistry and interactions with bronchoalveolar lavage fluid.
Kendall, Michaela; Guntern, Jodok; Lockyer, Nicholas P.; Jones, Frances H.; Hutton, Bernie M.; Lippmann, Morton; Tetley, Teresa D. Inhalation Toxicology 16 (2004): 115-129