Nanotechnology-based biochip and biodevice techniques will be key technologies in the post-genome sequencing era, since they are applicable to the analysis of a wide variety of biomolecules, e.g., DNA, mRNA, proteins, glycoproteins and metabolites ; they can also be used to analyze cells. In this review article, I will describe recent developments in nano-biodevices for genomic and proteomic research that is aimed at future personalized medicine, systems biology, and new drug discovery technology. A nanoball, fabricated with molecular nanotechnology, is developed and successfully applied to the fast separation of DNA fragments ranging from 100 bp to 15 kbp. An array of nanopillars 200 nm wide and 5000 nm tall is successfully applied to the fast separation of DNA within 10-25s. These technologies are applied to single nucleotide polymorphism (SNPs) analysis, mutation analysis, haplotyping and DNA diagnosis. Nano-biodevices are extremely useful for the fast (within 15 seconds) separation of protein samples that are from several kDa to 200 kDa. Utilizing this technique, a complex protein mixture extracted from the human T cell line, composed of lymphoblastic Jurkat cells, was separated within 15s with a high reproducibility. The target proteins of the Jurkat cells, which increase in number after heat-shock apoptosis, were detected and identified by this method, while several hours are required to do the same with conventional 2-DE analysis. The coupling of quantum dots and siRNA is applied to the functional analysis of bcr-abl tyrosine kinase in chronic myelogenous leukemia (CML). We found that quantum dot anti-CD conjugates are a potential photosensitizer in photodynamic cancer therapy.

The novel concept of a genetic field effect transistor (FET) is proposed for the detection of DNA molecular recognition events. The potentiometric detection method for DNA molecules using genetic FETs is in principle based on a charge density change at the gate insulator. The electrical characteristics of the genetic FET were found to shift after hybridization, the introduction of intercalators, and the primer extension reaction. Moreover, we demonstrated experimentally that SNP genotyping could be achieved by the use of the genetic FETs in combination with intercalation or allele specific extension reaction. In addition, we have found the possibility of DNA sequencing using the genetic FET combined with one-base extension. The genetic FET platform based on the direct transduction of DNA-recognition events into electrical signal is suitable for use in a simple, accurate and inexpensive system for SNP genotyping and DNA sequencing in clinical diagnostics.

Scanning probe microscopes (SPMs) scan a sharp probing tip over a solid sample while monitoring the physical properties between the tip and the sample surface. Among them, the atomic force microscope (AFM) has been used in the biological fields because it has the advantage of being able to obtain three-dimensional images of the sample surfaces at high resolution in various environments (i.e., vacuum, air or liquid). Thus, in this paper, we introduce our results on the application of AFM to studies of various biomedical samples (including DNA, collagen molecules, collagen fibrils, chromosomes and living cells). We also showed the usefulness of the combination technique of AFM with a scanning near-field optical microscope (SNOM) for the simultaneous collection of both topographic and fluorescent images of human chromosomes stained with fluorescent dyes.

In order to elucidate biological phenomena, we need to develop novel sensing techniques for the analysis of biological functions of biomaterials such as DNA, proteins, and cells ; in particular, analytical methods to investigate in-vitro and in real time biological functions and the relationships among a variety of biomolecules and living cells are required. In this report, research trends in the development of infrared spectroscopic methods for the biological analysis are briefly described, and our recent investigations of the behavior of DNA molecules in aqueous solutions by surface infrared spectroscopy are presented.

Non-lithographic fabrications of devices such as electronics and sensor have been studied extensively by assembling nanometer-sized building blocks into the device configurations. We have been functionalizing biological nanotubes by metal and semiconductor nanocrystals and assembling them to devices for photonics, electronics, and sensor applications. By using peptides and proteins on the nanotubes as templates, peptide nanotubes with a variety of electric properties can be grown by coating them with various metals/semiconductors via their mineralization function. In addition, peptides’ molecular recognition functions enable one to add functionalities to various positions on the nanotubes (e.g., inside, outside, edges) or anchor them to desired places on device substrates such as integrated circuits. Over all, these features provide peptide nanotubes multi-functionality, and they can be applied to build complex geometries of nanoscale devices.

By synthesizing ferrite (Fe₃O₄-γFe₂O₃)nanoparticles from an aqueous solution (T=4-25°C, pH=7-9) containing functionalorganic molecules, we developed a novel, one-step method by which we can prepareferrite nanobeads with bioactive substances (eg., antibodies and drugs) immobilizedon the surface. The organic molecules are strongly coupled to the ferrite surfaceby chemical bonds. We established a methodology to encapsulate magnetic nanoparticlesin functional polymers more firmly than by conventional methods, and to immobilizephysiologically active molecules on the bead surface.

Since the declaration that the whole human genome had been deciphered, research has been focused on the differences in the human genome sequences between different subjects (polymorphisms). Technologies are now being developed for obtaining the polymorphisms from individuals, and we will soon be able to observe most of the polymorphisms of separate individuals. Trait-mapping technology performed using polymorphisms has identified many causes of genetic diseases with Mendelian inheritance using parametric linkage analysis. Complex traits, on the other hand, have been dissected by use of the linkage-disequilibrium-based method in regions where nonparametric linkage analysis had localized the trait. Recently, a method has been developed using this linkage-disequilibrium-based method directly on the whole human genome for the trait mapping.

This paper describes microfluidic devices for membrane protein analysisｗ:ｗmembrane protein chips. Membrane proteins play very important roles in various fields, including next-generation diagnosis techniques, drug discovery, and highly sensitive ion-channel-based biosensors. Here, we introduce our research on a method to reconstitute giant liposomes or planar membranes using microfabricated devices. These devices are useful for an efficient analysis of single-species-specific membrane proteins.

The Relationship between the rheology and topology of immiscible polymer blends under electric and shear flow fields was studied. The blend was composed of a liquid crystalline polymer (LCP) and modified polydimethylsiloxane (DMS). By using a confocal scanning laser microscope and a specially designed shear-applying apparatus, we observed a structural change from an LCP droplet-dispersed structure to a network structure while the blend was being subjected to electric and shear flow fields. Corresponding to this structural change, the viscosity increased. The rheology is discussed from a topological point of view.

Recent developments in theoretical and experimental studies on current-driven domain wall motion are reported. Analytical theory, numerical simulation and experiment all indicate the existence of a threshold current for wall motion, and the three methods are in qualitative agreement with each other. For device application, the lowering of the threshold current is necessary.

The surface plasmon resonance (SPR) optical technique combined with electrochemical measurements has been demonstrated as a powerful technique for the simultaneous characterization and manipulation of electrode/electrolyte interfaces. In electrochemical-SPR (EC-SPR) measurements, the gold substrate that carries the optical surface mode is simultaneously used as the working electrode in the electrochemical experiments. One of the advantages in using the EC-SPR technique is that the electrochemical and optical properties are simultaneously obtained from nanometer scale surfaces and ultrathin films. This article summarizes our results on EC-SPR techniques. Examples are given for in-situ investigations of conducting polymer ultrathin films and their sensor applications.

Bioinformatics entails computational approaches to the analysis of biological data. This field naturally evolved from the combination of two of the biggest fields of the 20th century : molecular biology and computer science. In this section, we introduce the aims of bioinformatics, particularly in terms of recent trends such as systems biology. As such, the role of applied physics in bioinformatics is emphasized as a driving force in this promising field.

Almost ten years has passed since the initial development of GaN-based violet laser diodes (LDs) at 405nm wavelength range. Now, the development of optical memory devices that use violet LDs has progressed significantly and these devices have been commercialized. The need for high-speed recording and multilayer recording is increasing, and it is expected that even higher power LDs will be necessary in the future. In this paper, the current state of GaN-based LD research for the next generation optical memory devices is reported, and next targets are discussed.