All living organisms on the earth rely solely on a single molecule as an energy currency, ATP (adenosine triphosphate). This small molecule supports nearly all the activities that require energy, and our body synthesizes roughly as much ATP every day as our body weight. In the biological world, ATP synthesis is certainly the most prevalent chemical reaction and the enzyme, ATP synthase, responsible for most of this task, is one of the most ubiquitous, abundant proteins on the earth. ATP synthase uses physical rotation of its own subunits as a step of catalysis － a novel mechanism, different from any other known enzymes. Rotation is not a favourite motion in living organisms; there is no animal with wheels, no bird with a propeller, and no fish with a screw. The crystal structures of the main part of ATP synthase show in atomic detail how the appearance of this world tiniest motor made of protein is remarkably reminiscent of the man–made motors. The driving force that spins ATP synthase is trans-membrane gradient of hydrogen ion concentration that is generated by respiration (burning the food) or by sunshine. We have videoimaged the rotary motion of ATP synthase that spins as fast as several hundred revolutions per second. The mechanism of the motor is completely different from the man–made motor. ATP synthase is bi–particle structure with a common rotary shaft. The flow of hydrogen ions through the lower particle drives the rotation of the central rotor that then forces upper particle to make the bending motion for synthesis of ATP. Imagine billions of billion rotary motors are spinning in our body, day and night, without rest. When the motors stop, we die.

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Conventional method of cell–based assays in life science and medical application can be difficult to duplicate in vivo situation. Microfluidics is an emerging technology with potential to provide integrated environments for cell maintenance, continuous perfusion, and monitoring. In this paper, we introduce possibility of microfluidics to become a novel cell–based assay system with its concept. Then, we show a chip–based coculture system for cytotoxicity test, as our continuous effort to develop a multi–functional micro culture system realized by integration of fluidic control and detection functionalities. The culture zone in the chip was divided into two compartments separated by a microporous membrane through which substances in culture medium can freely come-and-go to induce the mutual interactions between the cells cultured at each compartment. Performances of the chip were examined 1) monitoring of polarized transport activity of intestinal tissue models, 2) cytotoxicity model through oral intake by coculture. As a result, we conclude that microfluidics may have applications in toxicity test and drug screening.

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Recently, we developed novel liposomal nanobubbles (Bubble liposomes) containing perfluoropropane, which is an ultrasound imaging gas. Here, we used ultrasound to induce cavitation in Bubble liposomes and then investigated their ability to deliver gene and drug. The combination of Bubble liposomes and ultrasound could deliver plasmid DNA into many cell types without cytotoxicity. Additionally, in cancer gene therapy, this system could effectively deliver interleukin–12 (IL–12) corded plasmid DNA into tumor tissue and effective anti–tumor effect was achieved. Moreover, this system could be utilized as an effective anti–cancer agent delivery system into the cancer cells which had the resistance for the agent. Thus, this system might be a novel and efficient gene and drug delivery system.

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This review describes recent progress in molecular imprinting for proteins. Molecular imprinting is one of the available template polymerization techniques and has emerged as a method for the preparation of synthetic receptors mimicking naturally occurring molecular recognition phenomena. This technique may offer a means of creating binding sites bearing bio–like functions and substitutes of natural receptors, enzymes and antibodies. Proteomics is an important technology in medicine and biotechnology. Protein-imprinted polymers could be a new tool for protein analysis in this area.

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Blood–derived products are composed of blood cell products and plasma component products. Contaminated white blood cells in blood cell products are causes of various kinds of transfusion side effects. Currently, 99.99% of these white blood cells are removed in production process by fiber filters made of non–woven web of ultra–fine fibers. Possible virus contamination during production process of plasma component products are reduced by virus removal membrane filtration to the extent of 1/1,000 –1/1,000,000. Prions are considered to cause variant Creutzfeldt–Jakob disease. Recently, studies on prions removal from blood–derived products cause many researches interests. Biopharmaceuticals have many advantages over conventional pharmaceuticals and are growing rapidly. MF membranes, UF membranes and virus removal membranes are actively adopted in production process of biopharmaceuticals.

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It was previously considered that the practical application of liposomal medicines was very difficult. The pharmaceutical technologies for mass production, long term stability during storage, encapsulation efficiency of the drug, etc. were seemed big problems to be solved, and it was well known that the liposomal particles are apt to be entrapped in vivo by the reticuloendothelial system (RES) such as liver, spleen, etc. Fortunately, owing to the progress of science, about 10 liposomal medicines containing the anticancer agents, the antifungal agents, etc. were launched out and are now contributed to medical treatment in the world. Recently liposomes are expected to be useful as the vectors for in vivo nucleic acid (plasmid DNA, siRNA, etc.) therapy and as the tools for target validation in the area of drug discovery. There are already many liposomal reagents for transfection, and some clinical trials are performed using liposomes. It is considered that liposomes, the membrane–structure particles, have unlimited potential in the medical field.

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We used nanofiltration membranes to study the purification of physiologically active chitosan oligosaccharides (pentamers and hexamers). Calculations based on the experimental data of batch filtration suggested that the content of the target oligosaccharides in the product mixture could be improved from 30% to 77% by continuous diafiltration under optimized conditions.

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The liposome immobilized on indium tin–oxide (ITO) electrode was prepared to evaluate the liposome–liposome interaction to develop “Membrane Chip”. Three kinds of standard liposomes entrapping the fluorescence probe, calcein, were used for their immobilization, where the immobilized liposomes show the different characteristics in their phase transition temperature and membrane fluidity. Membrane Chip could give the set of the quantitative information relating to the membrane–membrane interaction. The interaction between three immobilized liposomes and 22 kinds of liposomes as samples was then systematically investigated on a basis of the calcein release from the immobilized liposomes, which could give the information in relation to “Membranome”. It was, therefore, found that the Membrane Chip as a means of Membranomics research was effective to evaluate the Membranome information of liposomes.

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Silver ions, while being lethal to single-celled microorganisms, are known to be harmless to human cells. We have adopted highly active fine organic silver grains, developed by combining our long accumulated fine organic synthesis and fine particle technologies, to the filter. Antibodies (also known as immunoglobulin) are used by the immune system to identify and neutralize foreign objects, such as viruses. For the antiviral function, we have applied the specific antibody ‘immunoglobulin yolk (IgY)’ for the filter, and the filter has proved to dramatically reduce the infectivity of type A (H1N1, H3N2) and type B influenza viruses and also of the Avian flu A(H5N1).

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