The broad impact that surface science has had on so many technologies is mirrored by the contributions of Professor David Castner to many sub-fields dependent upon surface science. Dave’s earliest contributions to the scientific literature were associated with the surface science of rhodium, iron and cobalt catalysts. Papers were published addressing CO hydrogenation, Fischer-Tropsch polymerization and related topics with relevance to energy consumption and chemical production. With Dave’s arrival at the University of Washington in 1986, the subjects of his research shifted from catalysis to biomedical surfaces. Dave and I have always shared a common interest (maybe passion). That is, generating quality data and extracting maximum information from that data. We both had extensive experience with early HP5950 electron spectroscopy for chemical analysis (ESCA) instruments. These monochromatized instruments generated exceptionally high resolution spectra for that era, and the instruments had effective charge compensation for insulators. This allowed us to make great strides in highlighting the use of ESCA for bio-relevant surfaces and biological materials. The theme of data quality has persisted into the present with newer ESCA instruments and then SIMS instrumentation. Dave Castner has taken surface analysis into the 21st century with studies on cells, proteins, novel polymer surfaces and nano-materials. This talk will highlight Dave Castner’s remarkable contributions to surface science with particular emphasis on his contributions to the evolution of methods available to analyze complex surfaces and morphologies.

Secondary ion mass spectrometry (SIMS) is now widely used for chemical analysis of polymers and biological materials that have a rather complicated molecular structure. Various types of primary ion beams and mass spectrometers have been developed and used in an attempt to improve sensitivity, as well as lateral and mass resolution. Large gas cluster ion beams (GCIB) have been commercialized for surface analysis techniques, such as SIMS and XPS. Molecular depth profiling and three-dimensional analysis have been applied on organic devices and biological materials. A large cluster ion beam could overcome the limitation of ion dose, which is the biggest obstacle for obtaining more signals in static SIMS.

To expand the applications of the SIMS technique, we have developed a finely focused large cluster ion beam (~1mm) for the primary ion beam for use in SIMS [1] and combined it with mass spectrometers of the quadrupole time-of-flight mass spectrometry (Q-TOF) type without pulsing primary ions. This mass spectrometer is equipped with MS/MS capability and allows to determine the structure of the secondary ion by using the collision-induced dissociation (CID) technique. This is a new SIMS instrument that helps in the characterization of biomolecules in cells, tissue and medicine. For instance, the detection limit of a drug molecule is improved by using the MS/MS technique, because of a much-reduced background.

In this paper, we demonstrate the capability of SIMS with the MS/MS spectrometer to determine the structure of molecular-related ions and discuss the benefits and drawbacks of this technique.

[1] J. Matsuo, S. Torii, K. Yamauchi, K. Wakamoto, M. Kusakari, S. Nakagawa, M. Fujii, T. Aoki, and T. Seki, Appl. Phys. Express, 7 (2014), 056602

Most of biological story tellings are mainly based on proteins and their interactions. Therefore protein imaging and their interaction studies have been the key interest in bio imaging. Most of protein bioimaging have been based on confocal fluorescence microscopy for 2 or 3 proteins. We have developed a new multiplex protein imaging method for TOF-SIMS with metal oxide nanoparticle (MONP) conjugated with proteins up to 9 proteins, in theory, several tens, and a single protein imaging technique based on He Ion Microscopy (HIM)

In SIMS analysis, MONPs provide high secondary ionization yield and amplification of ion yields. We systhesized 9 MONPs working right such as CoO, CdO, Fe3O4, TiO2, PbO, In2O3, SiO2, Al2O3, La2O3. In addition to protein imaging, SIMS intrinsically provides tens of bio-molecular imaging including lipids and metabolites, and metals with a TOF mass analyzer, which makes this new methodology to be an omni-molecular mass spectrometric imaging technique. Sliced and cultured mouse hippocampal tissues were imaged with typical spatial resolution of 2 µm, which can be improved down to 300 nm for 9 neuronal proteins. Proteins chosen to image mouse hippocampal tissues are NeuN for all nuclei, Cav1,3 for neuron cells, Iba1 for microglia cells, GFAP for astrocytes, AMPA receptor, phosphorylated Tau, amyloid beta (Aß) 1-42, amyloid precursor protein, and APOE, which were selected to visualize important proteins as landmarks of Alzheimer Disease (AD). With multiplex proteins imaging, we could estimate the proximity of associated proteins in mouse hippocampal tissues, which changes with aging and AD progression.

Since HIM has a spatial resolution of 0.5 nm, HIM can observe single proteins in theory but in practice, it may be very dfficult to observe a single protein molecule due to the similar secondary electron yields of proteins compared to other proteins or extracellular matrix molecules. We demonstrated that HIM can image each MONP conjugated with proteins from a mouse hippocampal tissue revealing the distribution of single proteins in synapses, neuronal soma, amyloid plaques, and neurofibrillary tangels with their changes along aging and AD.

With the co-development of multiplex protein SIMS imaging and single protein HIM imaging technology, I expect we can improve our understanding on the role of proteins and their interactions in biology, biomaterials, and medicine.

Control and the ability to elicit specific responses from a biological system lies at the heart of most bioengineering. We want to immobilize proteins on biosensors but ask them to behave as they would in the body, stimulate cells to assemble tissues, form new blood vessels and replicate structures in the lab just as well as they can in our bodies. We want methods that prevent bacteria forming biofilms and better still we would like them to stop attaching to surfaces full stop. We have an armada of techniques at our disposal, surface engineering, macro, micro and nanomaterials, drugs and biomolecules, light, electricity and a plethora of analysis tools to give us new insight into how the systems we build behave. But as we increase the complexity of the system, we need to be able to match this with combinations of characterisation techniques that probe both the biological and physicochemical processes occurring at the biointerface.

This talk will explore how we utilise QCM, XPS, ToF-SIMS, florescence imaging and biological assays to investigate the influence of surface chemistry and micro and nanoscale topography on interactions with lipid vesicles and bacteria.

Surface and interface science is critical to many applications across many industries, spanning from advanced technologies in microelectronics and biomaterials to everyday household goods such as laundry detergents and shampoos. Micro and nanoscale phenomena at surfaces and interfaces, including adsorption, wetting, self-assembly, and many others, drive macroscale performance, resulting in significant benefits when done well and significant failures when poorly understood or controlled. At all scales, measurement science specific to surfaces and interfaces is critical to understanding these phenomena.

In the field of biomaterials science (and beyond), protein adsorption is a foundational step in all interactions between biological systems and synthetic materials. Many surface analysis techniques have been applied to the characterization of adsorbed protein films, including understanding the amount, composition, spatial distribution, and orientation of adsorbed proteins. In this special session in honor of Dave Castner, this presentation will review key contributions from the Castner group on the application of multi-technique surface analysis techniques to adsorbed protein films. In particular, the use of ToF-SIMS and multivariate data analysis techniques in conjunction with complementary surface spectroscopies including XPS, NEXAFS, SPR, and others, will be reviewed. The broader impact of these developments in surface analysis methodologies on the fields of surface and interface science across industries will be discussed.