Research

○ Acoustic perforation (sonoporation) using microbubbles and pulsed ultrasound: Pulsed ultrasound irradiation of microbubbles in contact with the cell membrane enables temporary perforation only at the attachment site (Fig. 1). We have realized a method to deliver drugs or genes into any desired position in the target cell by adding drugs or genes to the microbubbles and controlling the attachment site with optical tweezers.
○ Succeeding with therapeutic site identification and drug delivery by using microbubbles and an ultrasound system: A microbubble, which has the target function of adhering only to the cells to be treated, is injected into a vein. To identify the therapeutic site, the tissue where the bubbles have accumulated is detected using an ultrasound contrast method. Pulsed ultrasound waves are then generated to break the bubbles, allowing temporary perforation of the cell membrane and drug delivery (Fig. 2). By adding drugs or genes to the bubbles, highly efficient drug delivery only to the target cells can be realized.

Research

Optical information processing, transmission, recording and reproduction are performed using the intensity, polarization and spatially uniform phase of laser light. The transmission capacity can be increased through multiplexing using different frequencies. In contrast, the spatial characteristics of light form an unexplored area that has not been actively utilized until now. Based on this background, information multiplexing using Laguerre-Gaussian (LG) light and quantum information processing using the orbital angular momentum (topological charge) that characterizes LG light have been attracting attention as a step to overcome the limitation of information processing capacity. In this study, we have utilized material interaction and realized the mode control of LG light and the conversion and conservation of orbital angular momentum using short-pulsed light, as well as space-division multiplexing fiber transmission.

Research

A large number of nanoparticle-based drugs are currently investigated, including drug delivery system (DDS) carriers, many of their surface is covered with biocompatible poly(ethylene glycol) (PEG). In this regard, we have found that gold nanoparticles (AuNPs) modified with cyclic PEG exhibit high dispersion stability at high salt concentrations. In other words, AuNPs treated with cyclic PEG with a molecular weight of 4000 retained their dispersion stability for one week or longer in a 180 mM NaCl solution, which is a higher concentration than physiological conditions, whereas AuNPs treated with linear PEG of the same molecular weight started aggregating and precipitating within 3 hours in a solution of only 45 mM NaCl. This novel method using cyclic PEG can be applied to a variety of nanoparticle-based drugs including contrast agents and magnetic nanoparticles.

Research

Based on our previous research results, we have discovered that when a droplet hits a solid surface in a condensable gas (not air), splashing is suppressed and a thin liquid film (lamella) spreads on the solid surface at high speed. Since the high-speed lamellae may generate a strong fluid shear force, it seemed possible to use a mixed jet of steam and water to realize an environmentally friendly cleaning method.
Based on our previous research results, we have confirmed that this cleaning method, which uses only water and steam, can achieve the specified cleaning performance for ultra-precision cleaning required in the manufacturing processes of semiconductors, LEDs, and solar cells. This cleaning method is also safe both for the human body and the environment, because it uses only water and steam instead of detergents or other chemicals that are harmful to the human body.

Research

Hokkaido University’s laboratory facilities, where small accelerators are used, have a history of nearly half a century, and are attracting worldwide attention as pioneering facilities. We mainly produce pulsed neutron beams, and the transmission spectra obtained using these beams enable us to map information on crystal structure, microstructure, internal stress and temperature on a two-dimensional real image as a distribution map of the entire sample. We also use X-ray CT which can measure the three-dimensional structure of the inside of an object, and analyze the combined results from neutrons and X-ray studies to synergistically understand the interior information of an object. In the figure, shown as synergistic imaging based on information from neutrons and X-rays, information on elements that cannot be individually obtained is mapped on the inside structure shown on the X-ray CT image. X-ray CT shows the presence of wires in an Al cylinder, but when neutron information is added, we can see that each wire is a different material.

Research

It is expected that superomniphobic surfaces, which do not get wet with water or oil, will possess antifouling and self-cleaning properties. In this study, we have realized a superomniphobic surface that does not only repel water but also octane and other liquids with a surface tension as low as 20 mN m-1, by using a simple wet process for aluminum, which is a practical metal material. This process can also be applied to aluminum foil, which can be used as an antifouling surface in various places. It can also be used as a filter to separate oil and water by controlling its wettability using aluminum mesh.

Research

The introduction of fluorine atoms into organic compounds is very important in the fields of medicine, agrochemicals, and functional materials. There is a method of synthesizing fluorine-containing organic compounds by using fluorine-containing building blocks, but such compounds are still expensive and limited in quantity, and there is a high need for research and development. In this study, we succeeded in synthesizing fluorine-containing aromatic carboxylic acids with various functional groups from readily available fluorine-containing aromatic compounds and carbon dioxide, and achieved good yields using the organic electrolysis method. The fluorine-containing aromatic carboxylic acids synthesized in this study include a variety of new compounds that are difficult to synthesize by conventional methods, and are expected to be used as promising new fluorine-containing building blocks for the synthesis of pharmaceuticals, agrochemicals, and highly functional materials.

Research

Glycan patterns on glycoproteins are important biomarkers because they are factors that determine the disposition of protein in the body. Until now, glycan pattern analysis has required complicated operations such as cutting, chemical modification, and purification of glycans. Mass spectrometry is an ultra-sensitive and high-resolution analytical technique that can directly ionize trace amounts of biomolecules. However, there has not been a method to selectively ionize glycoconjugates such as glycoproteins and glycans in complex macromolecules and mixtures such as body fluids, which requires the complicated pretreatment described above. We have achieved the world's first simultaneous selective cleavage and selective ionization of glycoconjugate glycans, and succeeded in the direct analysis of glycan patterns on glycoproteins. We have also demonstrated that this technique can be used to directly analyze glycan patterns in complex mixtures such as egg white.

Research

Microarray technology is a technology that enables simultaneous comparative analysis of the interaction between a large number of compound libraries with well-defined structures and sequences and sample components. We also have the most advanced technology to design and produce our own carbohydrate compound libraries as molecules for microarray analysis based on our automated carbohydrate synthesis technology. The interaction information possessed by carbohydrates is widely used as biomarkers for in vitro diagnostics, such as blood types, serotypes such as O157, and cancer diagnostic markers (CAxx). In addition, we have succeeded in developing an independently powered mobile analyzer that can be used for online diagnosis, such as analysis of infection patterns associated with mutations in infectious diseases and detailed analysis of vaccine effects, by performing specimen collection and microarray analysis on the spot using a smartphone as a terminal.

Research

Visualization of acoustic wave propagation is extremely useful in the evaluation of physical properties and the design, fabrication and evaluation of functional devices using acoustic waves. For this purpose, we excite surface acoustic waves by irradiating the sample with an ultrashort optical pulse of subpicosecond duration (pump light), and observe their propagation with delayed optical pulse (probe light). Time-resolved two-dimensional images of the acoustic waves are obtained by scanning the delay time and the irradiation position of the probe light. The time resolution is in picoseconds, the spatial resolution is 1μm, and the frequency range is in GHz. Since this method uses a periodic optical pulse train, it was previously only possible to excite and detect acoustic waves at integer multiples of the repetition rate. However, with the newly developed technique, we have realized the excitation and detection of acoustic waves of any frequency. By developing this technique, we have also achieved image vibrations that are completely asynchronous to the repetition frequency of the optical pulse, thereby expanding the range of applications.

Research

Thanks to the development of molecular targeted therapies, antiangiogenic agents are now widely used. However, there are problems such as the lack of companion diagnostics to predict therapeutic effects and side effects due to injury to normal blood vessels.
We have successfully isolated and cultured human tumor vascular endothelial cells and have identified specific markers that they express. Tumor vascular endothelial cells expressing these markers are valuable materials for cell-based screening of novel drugs and compounds, and help us identify new therapeutic targets and drugs that cannot be discovered by studies using conventional tumor cell lines or clinical tumor tissue fragments. Markers expressed by these tumor vascular endothelial cells can also be used as companion diagnostics. This will contribute to the realization of personalized treatment by selecting the target cases as well as the timing and duration of administration with angiogenesis inhibitors.

Research

In a seismically-isolated building, the seismic isolators deform softly during an earthquake, greatly reduce response acceleration in the superstructure and improve the seismic safety. On the other hand, ultimate events such as collisions with retaining walls and buckling or rupture of the seismic isolation bearings may occur for the ground motions exceeding design level caused by a mega earthquake such as the Nankai Trough Mega Earthquake. By using analysis technologies to precisely predict the ultimate behavior of seismically-isolated buildings, it is possible to foresee the occurrence of ultimate events and to consider countermeasures to suppress their occurrence.

Research

We have succeeded in obtaining titanium dioxide thin film on a practical metal substrate such as Cu, Al, Zn and Fe by electrolysis from an aqueous solution containing TiF62- within only a few seconds. The obtained titanium dioxide thin film is anatase crystalline and shows photocatalytic activity without heat treatment. The obtained titanium dioxide thin film is anatase crystalline and shows photocatalytic activity without heat treatment. We have confirmed that it has excellent properties such as decomposition of organic contaminants on the surface by UV irradiation and superhydrophilicity. Since the titanium dioxide film is doped with substrate elements, the development of new functions such as visible light responsiveness can be expected. It can also be deposited on a transparent conductive substrate.

Research

As in Fig. 1, which shows the principle of laser-induced excitation force generation, the laser-induced excitation force is caused by laser ablation. Figure 2 shows an example of the application of this technology, a vacuum environmental excitation measurement system for a membrane structure. This system consists of a YAG-pulsed laser, dielectric multilayer mirror, collecting lens, membrane structure, LDV and vacuum chamber. The membrane structure is fixed inside the vacuum chamber, allowing us to conduct the experiment by adjusting the air pressure inside the chamber from the atmospheric to the vacuum environment. Figure 3 shows the measured frequency response of the membrane. As shown in Fig. 3, with an increase in the vacuum level, the resonance frequency of the membrane becomes higher and at the same time the resonant response level increases. In this way, this technology enables the extraction of both mass effect and damping effect caused by the air on the membrane surface. We have conducted experiments to verify the effectiveness of this technology in a vacuum chamber, which assumes a space environment.

Research