We have developed a method of terahertz (THz) solid immersion (SI) microscopy for continuous-wave reflection-mode imaging of soft biological tissues with a sub-wavelength spatial resolution. In order to achieve strong reduction in the dimensions of the THz beam caustic, an electromagnetic wave is focused into the evanescent field volume behind a medium with a high refractive index. We have experimentally demonstrated a 0.15λ-resolution of the proposed imaging modality at λ = 500 μm, which is beyond the Abbe diffraction limit and represents a considerable improvement over the previously-reported arrangements of SI imaging setups. The proposed technique does not involve any sub-wavelength near-field probes and diaphragms, thus, avoiding the THz beam attenuation due to such elements. We have applied the developed method for THz imaging of various soft tissues: a plant leaf blade, cell spheroids, and tissues of the breast ex vivo. Our THz images clearly reveal sub-wavelength features in tissues, therefore, promising applications of THz SI microscopy in biology and medicine.

Terahertz (THz) technology offers novel opportunities in the intraoperative neurodiagnosis. Recently, the significant progress was achieved in the study of brain gliomas and intact tissues, highlighting a potential for THz technology in the intraoperative delineation of tumor margins. However, a lack of physical models describing the THz dielectric permittivity of healthy and pathological brain tissues restrains the further progress in this field. In the present work, the ex vivo THz dielectric response of human brain tissues was analyzed using relaxation models of complex dielectric permittivity. Dielectric response of tissues was parametrized by a pair of the Debye relaxators and a pair of the overdamped-oscillators – namely, the double-Debye (DD) and double-overdamped-oscillator (DO) models. Both models accurately reproduce the experimental curves for the intact tissues and the WHO Grades I–IV gliomas. While the DD model is more common for THz biophotonics, the DO model is more physically rigorous, since it satisfies the sum rule. In this way, the DO model and the sum rule were, then, applied to estimate the content of water in intact tissues and gliomas ex vivo. The observed results agreed well with the earlier-reported data, justifying water as a main endogenous label of brain tumors in the THz range. The developed models can be used to describe completely the THz-wave – human brain tissues interactions in the frameworks of classical electrodynamics, being quite important for further research and developments in THz neurodiagnosis of tumors.

. Significance: An increasing interest in the area of biological effects at exposure of tissues and cells to the terahertz (THz) radiation is driven by a rapid progress in THz biophotonics, observed during the past decades. Despite the attractiveness of THz technology for medical diagnosis and therapy, there is still quite limited knowledge about safe limits of THz exposure. Different modes of THz exposure of tissues and cells, including continuous-wave versus pulsed radiation, various powers, and number and duration of exposure cycles, ought to be systematically studied. Aim: We provide an overview of recent research results in the area of biological effects at exposure of tissues and cells to THz waves. Approach: We start with a brief overview of general features of the THz-wave–tissue interactions, as well as modern THz emitters, with an emphasis on those that are reliable for studying the biological effects of THz waves. Then, we consider three levels of biological system organization, at which the exposure effects are considered: (i) solutions of biological molecules; (ii) cultures of cells, individual cells, and cell structures; and (iii) entire organs or organisms; special attention is devoted to the cellular level. We distinguish thermal and nonthermal mechanisms of THz-wave–cell interactions and discuss a problem of adequate estimation of the THz biological effects’ specificity. The problem of experimental data reproducibility, caused by rareness of the THz experimental setups and an absence of unitary protocols, is also considered. Results: The summarized data demonstrate the current stage of the research activity and knowledge about the THz exposure on living objects. Conclusions: This review helps the biomedical optics community to summarize up-to-date knowledge in the area of cell exposure to THz radiation, and paves the ways for the development of THz safety standards and THz therapeutic applications.