Takeaki Itsuji

Micro Strip Line-Based On-Chip Terahertz Integrated Devices for High Sensitivity Biosensors

We have achieved label free DNA hybridization detection at the level of a few femto-moles using on-chip terahertz (THz) integrated devices. The devices consist of two photoconductive switches for the generation and detection of THz pulses. A DNA specimen placed in a reservoir on the micro strip line (MSL) connecting the switches delays the propagating THz pulses. Different delay times were observed depending on the DNA conformation. The high sensitivity achieved is due to MSL design adjustment and the use of a specimen reservoir. Both simulations and experimental results indicate that devices with a narrower MSL have higher sensitivity.

Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

Fabrication of Three-Dimensional Photonic Crystal Device for Terahertz Wave

We have fabricated a simple-cubic-lattice photonic crystal (PhC) device based on high-resistivity silicon in the terahertz (THz) range by micro-electro-mechanical system (MEMS) techniques. The lattice constant of the three-dimensional (3D) PhC device is 120 µm, resulting in a photonic band gap (PBG) centered at 1 THz. The 3D PhC device was constructed by stacking ten 120-µm-thick chips with periodic pillars and holes patterned respectively on both of their sides by Si deep reactive ion etching. By THz time-domain spectroscopy, the PBG of the device was observed between 0.83 and 1.17 THz in the Γ–Z direction with a transmittance attenuation of about 35 dB, which is in good agreement with a numerical calculation result.

Terahertz spectroscopy and detection of brain tumor in rat fresh-tissue samples

Terahertz (THz) spectroscopy and imaging of biomedical samples is expected to be an important application of THz analysis techniques. Identification and localization of tumor tissue, imaging of biological samples, and analysis of DNA by THz spectroscopy have been reported. THz time-domain spectroscopy (TDS) is useful for obtaining the refractive index over a broad frequency range. However, THz-TDS spectra of fresh tissue samples are sensitive to procedures such as sample preparation, and a standardized measurement protocol is required. Therefore, in this work, we establish a protocol for measurements of THz spectra of fresh tissue and demonstrate reliable detection of rat brain tumor tissue. We use a reflection THz-TDS system to measure the refractive index spectra of the samples mounted on a quartz plate. The tissue samples were measured immediately after sectioning to avoid sample denaturalization during storage. Special care was taken in THz data processing to eliminate parasitic reflections and reduce noise. The error level in our refractive index measurements was as low as 0.02 in the frequency range 0.8–1.5 THz. With increasing frequency, the refractive index in the tumor and normal regions monotonically decreased, similarly to water, and it was 0.02 higher in the tumor regions. The spectral data suggest that the tumor regions have higher water content. Hematoxylin-eosin stained images showed that increased cell density was also responsible for the observed spectral features. A set of samples from 10 rats showed consistent results. Our results suggest that reliable tumor detection in fresh tissue without pretreatment is possible with THz spectroscopy measurements. THz spectroscopy has the potential to become a real-time in vivo diagnostic method.

Terahertz Integrated Transmission Line Sensors Using a Bonded Epitaxial GaAs Layer on Silicon Substrates

We have developed a novel process of transmission line type terahertz (THz) devices for biological sensing. A low-temperature-grown (LT) GaAs layer side is bonded onto silicon substrates using Au-Sn solder, then the GaAs substrate is removed by selective wet etching. Photoconduetive switch elements for generating and detecting THz signals are fabricated on the transferred LT-GaAs layer. This process results in robust integrated devices against biological solutions. Sequential measurement of THz time domain spectroscopy is available for biological molecules such as DNA samples. We observe clear difference in delay time shifts according to change of quantity and the state of applied molecules.

Terahertz tomography system using fiber lasers and applications

High depth-resolution terahertz three-dimensional tomography was developed by monocycle-like terahertz pulses using ultra-short pulse fiber lasers. We designed novel photoconductive devices such as a thin-film LT-GaAs detector on Si substrates and an LT-InGaAs emitter for the monocycle waveforms. The depth resolution exhibited under 20 µm in the air and three-dimensional imaging was successfully obtained for multi-layer semiconductor devices.

Origin and quantification of differences between normal and tumor tissues observed by terahertz spectroscopy

The origin of the differences in the refractive index observed between normal and tumor tissues using terahertz spectroscopy has been described quantitatively. To estimate water content differences in tissues, we prepared fresh and paraffin-embedded samples from rats. An approximately 5% increase of water content in tumor tissues was calculated from terahertz time domain spectroscopy measurements compared to normal tissues. A greater than 15% increase in percentage of cell nuclei per unit area in tumor tissues was observed by hematoxylin and eosin stained samples, which generates a higher refractive index of biological components other than water. Both high water content and high cell density resulted in higher refractive index by approximately 0.05 in tumor tissues. It is predicted that terahertz spectroscopy can also be used to detect brain tumors in human tissue due to the same underlying mechanism as in rats.

Terahertz integrated device using a transferred thin-film GaAs layer on silicon substrates

We developed thin-film GaAs transfer technique for integrated terahertz (THz) generating and detecting devices. Photoconductive switch elements on Si substrate are important for avoiding GaAs absorption to measure in wide frequency range. THz emission amplitude and Fourier transform spectrum band range become larger by replacing GaAs substrate with Si substrate. Transmission line device with the transferred GaAs layer on Si substrate is also fabricated for high sensitive sensors. It was found that peak shift of THz pulse was proportional to apply volume of samples and the sensitivity strongly depended upon the width of the transmission line.