Biomedical Applications of Terahertz Spectroscopy and Imaging.

Terahertz (THz) technology has attracted great worldwide interest and novel high-intensity THz sources and plasmonics are two of the most active fields of recent research. Being situated between infrared light and microwave radiation, the absorption of THz rays in molecular and biomolecular systems is dominated by the excitation of intramolecular and intermolecular vibrations. This indicates that THz technology is an effective tool for sensing applications. However, the low sensitivity of free-space THz detection limits the sensing applications, which gives a great opportunity to metamaterials. Metamaterials are periodic artificial electromagnetic media structured with a size scale smaller than the wavelength of external stimuli. They present localized electric field enhancement and large values of quality factor (Q factor) and show high sensitivity to minor environment changes. In the present work, the mechanism of THz metamaterial sensing and dry sample and microfluidic sensing applications based on metamaterials are introduced. Moreover, new directions of THz metamaterial sensing advancement and introduction of two-dimensional materials and nanoparticles for future THz applications are summarized and discussed.

Mechanisms and applications of terahertz metamaterial sensing: a review

Terahertz and millimeter waves penetrate various dielectric materials, including plastics, ceramics, crystals, and concrete, allowing terahertz transmission and reflection images to be considered as a new imaging tool complementary to X-Ray or Infrared. Terahertz imaging is a well-established technique in various laboratory and industrial applications. However, these images are often two-dimensional. Three-dimensional, transmission-mode imaging is limited to thin samples, due to the absorption of the sample accumulated in the propagation direction. A tomographic imaging procedure can be used to acquire and to render three-dimensional images in the terahertz frequency range, as in the optical, infrared or X-ray regions of the electromagnetic spectrum. In this paper, after a brief introduction to two dimensional millimeter waves and terahertz imaging we establish the principles of tomography for Terahertz Computed tomography (CT), tomosynthesis (TS), synthetic aperture radar (SAR) and time-of-flight (TOF) terahertz tomography. For each technique, we present advantages, drawbacks and limitations for imaging the internal structure of an object.

https://hal.archives-ouvertes.fr/hal-00968839/document

Review of Terahertz Tomography Techniques

Terahertz biophotonics as a tool for studies of dielectric and spectral properties of biological tissues and liquids

Terahertz (THz = 1012 Hz) spectroscopy has shown great potential in biomedical research due to its unique features, such as the non-invasive and label-free identification of living cells and medical imaging. In this review, we summarized the advantages and progresses achieved in THz spectroscopy technology for blood cell detection, cancer cell characterization, bacterial identification and biological tissue discrimination, further introducing THz imaging systems and its progress in tissue imaging. We also highlighted the biological effects of THz radiation during its biological applications and the existing challenges and strategies to accelerate future clinical applications. The future prospects for THz spectroscopy will focus on developing rapid, label-free, and convenient biosensors for point-of-care tests and THz in vivo imaging.

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The medical application of terahertz technology in non-invasive detection of cells and tissues: opportunities and challenges

Terahertz time-domain attenuated total reflection spectroscopy, in combination with a two-interface model, is used to determine the complex dielectric constants of cultured human cancer cells (DLD-1, HEK293 and HeLa). Picosecond and sub-picosecond water dynamics are dominant in the measured complex dielectric constants of these cells. We demonstrate that dielectric responses below 1.0 THz best characterize the particular water dynamics of cancer cells when compared with extracellular water. Debye-Lorentz fitting revealed that this is due to a significantly attenuated slow relaxation mode and enhanced fast relaxation mode of the water in these cancer cells. These findings could lead to a new procedure to digitally evaluate cellular activities or functions, in terms of intracellular water dynamics, and remove the veil from the mysterious intracellular milieu.

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Characterization of Dielectric Responses of Human Cancer Cells in the Terahertz Region

Evaluation of the hydration state of saccharides using terahertz time-domain attenuated total reflection spectroscopy.

An apparatus for measuring optical characteristics includes a variable-wavelength light source for generating a variable-wavelength light, having an identification waveform when the wavelength changes, the identification waveform being distinguishable from a normal waveform before and after the wavelength changes, an optical modulator for modulating the variable-wavelength light at a predetermined frequency and inputting it to an optical fiber; and an identification waveform detector for detecting the identification waveform of light transmitted through the optical fiber, wherein since the identification waveform detector detects when the waveform starts to change, it is possible to obtain synchronization between an incidence side and an exit side of the optical fiber. Accordingly, it is possible to obtain synchronization between an incidence side and an exit side of a device-under-test even if the wavelength of light source is continuously swept, whereby characteristics such as chromatic dispersion and the like can be measured.

Optical characteristic measuring apparatus, the method thereof and recording medium

We present a method to determine the complex dielectric constant of a cell monolayer using terahertz time-domain attenuated total reflection spectroscopy combined with a two-interface model. The imaginary part of the dielectric constant of the cell monolayer shows a lower absorption of slow relaxation mode than that of the liquid medium. This result allows us to estimate the intracellular water dynamics on a picosecond time scale, and the existence of weakly hydrated water molecules inside the cell monolayer was indicated. This method will provide a perspective to investigate the intracellular water dynamics in detail.

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Determination of the complex dielectric constant of an epithelial cell monolayer in the terahertz region

We performed a THz absorption spectroscopy study on liquid water confined in mesoporous silica materials, MCM-41-S-18 and MCM-41-S-21, of two different pore sizes at room temperatures. We found that stronger confinement with a smaller pore size causes reduced THz absorption, indicating reduced water mobility due to confinement. Combined with recent theoretical studies showing that the microscopic structure of water inside the nanopores can be separated into a core water region and an interfacial water region, our spectroscopy analysis further reveals a bulk-water-like THz absorption behavior in the core water region and a solid-like THz absorption behavior in the interfacial water region.

Motoki Imamura

Papers

Characterization of Dielectric Responses of Human Cancer Cells in the Terahertz Region

Evaluation of the hydration state of saccharides using terahertz time-domain attenuated total reflection spectroscopy.

Optical characteristic measuring apparatus, the method thereof and recording medium

Determination of the complex dielectric constant of an epithelial cell monolayer in the terahertz region

Pore-size dependent THz absorption of nano-confined water.