• Mass Spectrometry Letters
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• v.14 no.4
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• pp.147-152
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• 2023

The increasing demand for two-dimensional imaging analysis using optical or electronic microscopic techniques has led to an increase in the use of simple one-dimensional and two-dimensional mass spectrometry imaging. Among these imaging methods, secondary-ion mass spectrometry (SIMS) has the best spatial resolution using a primary ion beam with a relatively insignificant beam diameter. Until recently, SIMS, which uses high-energy primary ion beams, has not been used to analyze molecules. However, owing to the development of cluster ion beams, it has been actively used to analyze various organic molecules from the surface. Researchers and commercial SIMS companies are developing cluster ion beams to analyze biological samples, including amino acids, peptides, and proteins. In this study, a water droplet ion beam for surface analysis was realized. Water droplets ions were generated via electrospraying in a vacuum without desolvation. The generated ions were accelerated at an energy of 10 keV and collided with the target sample, and secondary ion mass spectra were obtained for the generated ions using ToF-SIMS. Thus, the proposed water droplet ion-beam device showed potential applicability as a primary ion beam in SIMS.

• Applied Science and Convergence Technology
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• v.24 no.6
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• pp.203-214
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• 2015

We have been developing a new label-free nanobio imaging platform using non-linear optics such as Coherent Anti-Stokes Raman Spectroscopy (CARS) and ion beam techniques based on sputtering and scattering such as Secondary Ion Mass Spectrometry (SIMS) and Medium Energy Ion Scattering Spectroscopy (MEIS), which have been widely used for atomic and molecular level analysis of semiconductors and nanomaterials. To apply techniques developed for semiconductors and nanomaterials for biomedical applications, the convergence of nano-analysis and biology were tried. Our activities on label-free nanobio imaging during the last decade are summarized in this review about non-linear optical 3D imaging, ellipsometric interface imaging, SIMS imaging, and TOF-MEIS nano analysis for cardiovascular tissues, collagen thin films, peptides on microarray, nanoparticles, and cell adhesion studies and finally the present snapshot of nanobio imaging and the future prospect are described.

• Proceedings of the Korean Vacuum Society Conference
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• 2015.08a
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• pp.51.2-51.2
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• 2015

Understanding interfacial phenomena has been one of the main research issues not only in semiconductors but only in life sciences. I have been trying to meet the atomic scale surface and interface analysis challenges from semiconductor industries and furthermore to extend the application scope to biomedical areas. Optical imaing has been most widely and successfully used for biomedical imaging but complementary ion beam imaging techniques based on mass spectrometry and ion scattering can provide more detailed molecular specific and nanoscale information In this presentation, I will review the 27 years history of medium energy ion scattering (MEIS) development at KRISS and DGIST for nanoanalysis. A electrostatic MEIS system constructed at KRISS after the FOM, Netherland design had been successfully applied for the gate oxide analysis and quantitative surface analysis. Recenlty, we developed time-of-flight (TOF) MEIS system, for the first time in the world. With TOF-MEIS, we reported quantitative compositional profiling with single atomic layer resolution for 0.5~3 nm CdSe/ZnS conjugated QDs and ultra shallow junctions and FINFET's of As implanted Si. With this new TOF-MEIS nano analysis technique, details of nano-structured materials could be measured quantitatively. Progresses in TOF-MEIS analysis in various nano & bio technology will be discussed. For last 10 years, I have been trying to develop multimodal nanobio imaging techniques for cardiovascular and brain tissues. Firstly, in atherosclerotic plaque imaging, using, coherent anti-stokes raman scattering (CARS) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) multimodal analysis showed that increased cholesterol palmitate may contribute to the formation of a necrotic core by increasing cell death. Secondly, surface plasmon resonance imaging ellipsometry (SPRIE) was developed for cell biointerface imaging of cell adhesion, migration, and infiltration dynamics for HUVEC, CASMC, and T cells. Thirdly, we developed an ambient mass spectrometric imaging system for live cells and tissues. Preliminary results on mouse brain hippocampus and hypotahlamus will be presented. In conclusions, multimodal optical and mass spectrometric imaging privides overall structural and morphological information with complementary molecular specific information, which can be a useful methodology for biomedical studies. Future challenges in optical and mass spectrometric imaging for new biomedical applications will be discussed.

• Bulletin of the Korean Chemical Society
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• v.30 no.11
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• pp.2661-2664
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• 2009

Photodissociation of nitrous oxide near 203 nm has been studied by a combination of high resolution slice ion imaging technique and (2+1) resonance-enhanced multiphoton ionization (REMPI) spectroscopy of $N_2(X^1{{\Sigma}_g}^+)$ via the (a″$^1{{\Sigma}_g}^+$) state. We have measured the recoil velocity and angular distributions of $N_2$ fragments by ion images of the state-resolved photofragments. The $N_2$ fragments were highly rotationally excited and the NN-O bond dissociation energy was determined to be 3.635 eV. Also, we investigated the photofragment images from the photodissociation of $N_2O$ clusters with various stagnation pressures.

• Proceedings of the Korean Vacuum Society Conference
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• 2013.02a
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• pp.85-85
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• 2013

Label-free, sensitive and selective detection methods with high spatial resolution are critically required for future applications in chemical sensor, biological sensor, and nanospectroscopic imaging. Here I describe the development of Plasmon Resonance Energy Transfer (PRET)-based molecular imaging in living cells as the first demonstration of intracellular imaging with PRET-based nanospectroscopy. In-vivo PRET imaging relied on the overlap between plasmon resonance frequency of gold nanoplasmonic probe (GNP) and absorption peak frequencies of conjugated molecules, which leads to create 'quantized quenching dips' in Rayleigh scattering spectrum of GNP. The position of these dips exactly matched with the absorption peaks of target molecules. As another innovative application of PRET, I present a highly selective and sensitive detection of metal ions by creating conjugated metal-ligand complexes on a single GNP. In addition to conferring high spatial resolution due to the small size of the metal ion probes (50 nm in diameter), this method is 100 to 1,000 folds more sensitive than organic reporter-based methods. Moreover, this technique achieves high selectivity due to the selective formation of Cu2+complexes and selective resonant quenching of GNP by the conjugated complexes. Since many metal ion ligand complexes generate new absorption peak due to the d-d transition in the metal ligand complex when a specific metal ion is inserted into the complex, we can match with the scattering frequency of nanoplasmonic metal ligand systems and the new absorption peak.

• Bulletin of the Korean Chemical Society
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• v.34 no.3
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• pp.815-819
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• 2013

Micropatterns of streptavidin and human epidermal carcinoma A431 cells were successfully imaged, as received and without any labeling, using cluster $Au_3{^+}$ ion beam-based time-of-flight secondary ion mass spectrometry (TOF-SIMS) together with a principal component analysis (PCA). Three different analysis ion beams ($Ga^+$, $Au^+$ and $Au_3{^+}$) were compared to obtain label-free TOF-SIMS chemical images of micropatterns of streptavidin, which were subsequently used for generating cell patterns. The image of the total positive ions obtained by the $Au_3{^+}$ primary ion beam corresponded to the actual image of micropatterns of streptavidin, whereas the total positive-ion images by $Ga^+$ or $Au^+$ primary ion beams did not. A PCA of the TOF-SIMS spectra was initially performed to identify characteristic secondary ions of streptavidin. Chemical images of each characteristic ion were reconstructed from the raw data and used in the second PCA run, which resulted in a contrasted - and corrected - image of the micropatterns of streptavidin by the $Ga^+$ and $Au^+$ ion beams. The findings herein suggest that using cluster-ion analysis beams and multivariate data analysis for TOF-SIMS chemical imaging would be an effectual method for producing label-free chemical images of micropatterns of biomolecules, including proteins and cells.

• Proceedings of the Korean Vacuum Society Conference
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• 2016.02a
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• pp.105.1-105.1
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• 2016

Many of the complex materials developed today derive their unique properties from the presence of multiple phases or from local variations in elemental concentration. Simply performing analysis of the bulk materials is not sufficient to achieve a true understanding of their physical and chemical natures. Secondary ion mass spectrometer (SIMS) has met with a great deal of success in material characterization. The basis of SIMS is the use of a focused ion beam to erode sample atoms from the selected region. The atoms undergo a charge exchange with their local environment, resulting in their conversion to positive and negative secondary ions. The mass spectrometric analysis of these secondary ions is a robust method capable of identifying elemental distribution from hydrogen to uranium with detectability of the parts per million (ppm) or parts per billion (ppb) in atomic range. Nano secondary ion mass spectrometer (Nano SIMS, Cameca Nano-SIMS 50) equipped with the reactive ion such as a cesium gun and duoplasmatron gun has a spatial resolution of 50 nm which is much smaller than other SIMS. Therefore, Nano SIMS is a very valuable tool to map the spatial distribution of elements on the surface of various materials In this talk, the surface imaging applications of Nano SIMS in KBSI will be presented.

• Nuclear Engineering and Technology
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• v.56 no.5
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• pp.1754-1761
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• 2024

In hadrontherapy, secondary fragments are generated by nuclear interactions of the incident heavy ion beam with the atomic nuclei of the target. It is important to determine the yield of production and the dose contribution of these secondary fragments in order to determine the radiobiological effectiveness more accurately. This work aims to fully identify the secondary fragments generated by nuclear interactions of proton and helium (⁴He) ion beams in a High-Density Polyethylene (HDPE) target and to investigate the dose contributions by secondary fragments. Incident protons with energies of 55.90 MeV and 105.20 MeV and helium ions with energies of 52.55 MeV/u and 103.50 MeV/u in the HDPE phantom have been investigated by the means of Geant4 Monte Carlo (MC) simulations. Simulated results were validated using NASA Space Radiation Laboratory (NSRL) Bragg curves experimental data. The results showed that the dose contribution of secondary fragments deriving from helium ion beams is three times higher than in the case of proton beams. This is due to a higher production of nuclear fragments in the case of helium ion beams. This work contributes to a better understanding of secondary fragments generated by protons and helium ions in the HDPE target.

• Proceedings of the Korean Vacuum Society Conference
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• 2013.02a
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• pp.113-114
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• 2013

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging is a powerful technique for producing chemical images of small biomolecules (ex. metabolites, lipids, peptides) "as received" because of its high molecular specificity, high surface sensitivity, and submicron spatial resolution. In addition, matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) imaging is an essential technique for producing chemical images of large biomolecules (ex. genes and proteins). For this talk, we will show that label-free mass imaging technique can be a platform technology for biomedical studies such as early detection/diagnostics, accurate histologic diagnosis, prediction of clinical outcome, stem cell therapy, biosensors, nanomedicine and drug screening [1-7].

• Applied Microscopy
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• v.43 no.1
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• pp.9-13
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• 2013

The helium ion microscope (HIM) has recently emerged as a novel tool for imaging and analysis. Based on a bright ion source and small probe, the HIM offers advantages over the conventional field emission scanning electron microscope. The key features of the HIM include (1) high resolution (ca. 0.25 nm), (2) great surface sensitivity, (3) great contrast, (4) large depth-of-field, (5) efficient charge control, (6) reduced specimen damage, and (7) nanomachining capability. Due to the charge neutralization by flood electron beam, there is no need for conductive metal coating for the observation of insulating biological specimens by HIM. There is growing evidence that the HIM has substantial potential for high-resolution imaging of uncoated insulating biological specimens at the nanoscale.