The combination of molecular biology and optelectronics has given rise to open a new field, biophotonics, in the 21st century. In this review, recent advances in several in vitro and in vivo single-molecule detection methods for animals are discussed. The possible applications of optical diagnosis are also included, which are optical mammography, diffuse optical tomography and fluorescence endscopy. The potential of the light use of in diagnosis is emphasized.

Nonlinear Raman spectroscopy is a unique and powerful method because it enhances weak Raman signals and detects Raman-inactive vibrational modes through the nonlinear interaction between light and matter. Recently, various nonlinear Raman processes have been applied to microscopy, and nonlinear Raman microspectroscopy is now attracting much attention as a cutting-edge tool for the future generation. In this article, we will review the recent progress in nonlinear Raman microspectroscopy. In particular, we describe two types of nonlinear Raman microspectroscopy, namely multiplex coherent anti-Stokes Raman scattering (CARS) microspectroscopy and hyper-Raman microspectroscopy, both of which have been developed by our group.

One of the great challenges in the post-genome era is to clarify the biological significance of intracellular molecules directly in living cells. If we can visualize a molecule in action, it is possible to acquire biological information unavailable from cell homogenates. One possible approach is to design and synthesize sensor molecules that can convert biological information to chemical reactions that can be easily monitored. For this purpose, fluorescence sensor molecules for intracellular messengers have been developed and successfully applied to living cells. Ratiometric measurement is a technique of reducing artifacts by minimizing the influence of extraneous factors on the fluorescence of a sensor molecule. Fluorescence resonance energy transfer (FRET) is a mechanism applicable to ratiometric measurement. We have designed two FRET sensor molecules, one for changing donor-acceptor distance and the other for changing overlap integral. Protein tyrosine phosphatase activity was successfully monitored using designed sensor.

The movement in living organisms is produced by motor proteins, for example, myosin in muscle contraction and kinesin in vesicle transport. We reviewed the mechanism of motility of individual motor molecules employing nanotechnology. A kinesin molecule was adsorbed onto a nanobead or a quantum dot, which was captured by an optical trap and brought into contact with rail proteins. The displacement of motor molecules during force generation was determined with nanometer accuracy. These nanomeasurements and fluorescence technology were applied in nanomedicine to detect the position of proteins in cultured cells and in mice.

In the past decade, the blood flow visualizing system, laser speckle flowgraphy (LSFG), was developed for use in various medical fields as a new diagnostic tool. The system is capable of displaying the blood flow distribution in the target tissue in real time, as well as indicating the change in blood flow before and after treatment. Since the measuring area of old LSFG models used in ophthalmologic research is very small (less than 1mm²), they have been used only in animal experiments. However, the increase in the measuring area of the new version has allowed us to observe the entire retinal blood flow without the need for angiography, which has made it possible for ophthalmologists to quantitatively study blood circulation in the retina.

We have directly determined the spectral shape of the complex conductivities of Bloch oscillating electrons by the time-domain terahertz (THz)-electrooptic sampling technique and have presented experimental evidence of dispersive Bloch gain in superlattices. This unique dispersive gain without population inversion arises from the nonclassical nature of Bloch oscillations ; that is, the phase of Bloch oscillation is shifted by π/2 from that of the semiclassical charged harmonic oscillation when driven by the same ac field. The present result provides a firm physics basis for the realization of Bloch oscillators/amplifiers.

The resent development of Fourier domain optical coherence tomography (FD-OCT) is summarized in this review. A comparison of time-domain optical coherence tomography (TD-OCT) and FD-OCT is given. The principles of 830-nm-band spectral domain optical coherence tomography (SD-OCT) and 1.3um swept-source optical coherence tomography (SS-OCT) are described. The sensitivity properties of TD-OCT and FD-OCT, and a comparison of SD-OCT and SS-OCT are discussed. A possible new OCT band of 1.04um is also discussed.

Material design for obtaining multiferroic materials that have multiple states of spin ordering and dipole ordering is reviewed. Although it is very difficult to obtain a material with both ferromagnetic and ferroelectric properties, a more important issue, particularly for practical applications, is whether there is cross-interaction between magnetics and dielectrics in the material. We also review the recently reported novel cross-interaction phenomena, including the suppression of ferroelectric domain switching by magnetic ordering and magnetic control of dielectric permittivity, observed in epitaxial films of the YMnO₃.

Molecular dynamics (MD) calculation which simulates structure and dynamics of materials at a molecular level has been utilized in various fields such as physics, chemistry, material science, mechanical engineering, and pharmacology. Here, we present an introduction to the MD calculation for classical systems focusing our attention on the method.