Label-free laser spectroscopy for respiratory virus detection: A review.

Infectious diseases are among the most severe threats to modern society. Current methods of virus infection detection based on genome tests need reagents and specialized laboratories. The desired characteristics of new virus detection methods are noninvasiveness, simplicity of implementation, real-time, low cost and label-free detection. There are two groups of methods for molecular biomarkers' detection and analysis: (i) a sample physical separation into individual molecular components and their identification, and (ii) sample content analysis by laser spectroscopy. Variations in the spectral data are typically minor. It requires the use of sophisticated analytical methods like machine learning. This review examines the current technological level of laser spectroscopy and machine learning methods in applications for virus infection detection.

Malignant and benign thyroid nodule differentiation through the analysis of blood plasma with terahertz spectroscopy.

The liquid and lyophilized blood plasma of patients with benign or malignant thyroid nodules and healthy individuals were studied by terahertz (THz) time-domain spectroscopy and machine learning. The blood plasma samples from malignant nodule patients were shown to have higher absorption. The glucose concentration and miRNA-146b level were correlated with the sample's absorption at 1 THz. A two-stage ensemble algorithm was proposed for the THz spectra analysis. The first stage was based on the Support Vector Machine with a linear kernel to separate healthy and thyroid nodule participants. The second stage included additional data preprocessing by Ornstein-Uhlenbeck kernel Principal Component Analysis to separate benign and malignant thyroid nodule participants. Thus, the distinction of malignant and benign thyroid nodule patients through their lyophilized blood plasma analysis by terahertz time-domain spectroscopy and machine learning was demonstrated.

Terahertz radiation and the skin: a review.

SIGNIFICANCE: Terahertz (THz) radiation has demonstrated a great potential in biomedical applications over the past three decades, mainly due to its non-invasive and label-free nature. Among all biological specimens, skin tissue is an optimal sample for the application of THz-based methods because it allows for overcoming some intrinsic limitations of the technique, such as a small penetration depth (0.1 to 0.3 mm for the skin, on average). AIM: We summarize the modern research results achieved when THz technology was applied to the skin, considering applications in both imaging/detection and treatment/modulation of the skin constituents. APPROACH: We perform a review of literature and analyze the recent research achievements in THz applications for skin diagnosis and investigation. RESULTS: The reviewed results demonstrate the possibilities of THz spectroscopy and imaging, both pulsed and continuous, for diagnosis of skin melanoma and non-melanoma cancer, dysplasia, scars, and diabetic condition, mainly based on the analysis of THz optical properties. The possibility of modulating cell activity and treatment of various diseases by THz-wave exposure is shown as well. CONCLUSIONS: The rapid development of THz technologies and the obtained research results for skin tissue highlight the potential of THz waves as a research and therapeutic instrument. The perspectives on the use of THz radiation are related to both non-invasive diagnostics and stimulation and control of different processes in a living skin tissue for regeneration and cancer treatment.

Cellular effects of terahertz waves.

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.

Terahertz spectroscopy of diabetic and non-diabetic human blood plasma pellets.

SIGNIFICANCE: The creation of fundamentally new approaches to storing various biomaterial and estimation parameters, without irreversible loss of any biomaterial, is a pressing challenge in clinical practice. We present a technology for studying samples of diabetic and non-diabetic human blood plasma in the terahertz (THz) frequency range. AIM: The main idea of our study is to propose a method for diagnosis and storing the samples of diabetic and non-diabetic human blood plasma and to study these samples in the THz frequency range. APPROACH: Venous blood from patients with type 2 diabetes mellitus and conditionally healthy participants was collected. To limit the impact of water in the THz spectra, lyophilization of liquid samples and their pressing into a pellet were performed. These pellets were analyzed using THz time-domain spectroscopy. The differentiation between the THz spectral data was conducted using multivariate statistics to classify non-diabetic and diabetic groups' spectra. RESULTS: We present the density-normalized absorption and refractive index for diabetic and non-diabetic pellets in the range 0.2 to 1.4 THz. Over the entire THz frequency range, the normalized index of refraction of diabetes pellets exceeds this indicator of non-diabetic pellet on average by 9% to 12%. The non-diabetic and diabetic groups of the THz spectra are spatially separated in the principal component space. CONCLUSION: We illustrate the potential ability in clinical medicine to construct a predictive rule by supervised learning algorithms after collecting enough experimental data.

Study on the effects of terahertz radiation on gene networks of Escherichia coli by means of fluorescent biosensors.

Three novel fluorescent biosensors sensitive to terahertz (THz) radiation were developed via transformation of Escherichia coli (E. coli) cells with plasmids, in which a promotor of genes matA, safA, or chbB controls the expression of a fluorescent protein. The biosensors were exposed to THz radiation from two sources: a high-intensity pulsed short-wave free electron laser and a low-intensity continuous long-wave IMPATT-diode-based device. The threshold and dynamics of fluorescence were found to depend on radiation parameters and exposure time. Heat shock or chemical stress yielded the absence of fluorescence induction. The biosensors are evaluated to be suitable for studying influence of THz radiation on the activity of gene networks related with considered gene promoters.

Optimal hyperosmotic agents for tissue immersion optical clearing in terahertz biophotonics.

In this work, a thorough analysis of hyperosmotic agents for the immersion optical clearing (IOC) in terahertz (THz) range was performed. It was aimed at the selection of agents for the efficient enhancement of penetration depth of THz waves into biological tissues. Pulsed spectroscopy in the frequency range of 0.1 to 2.5 THz was applied for investigation of the optical properties of common IOC agents. Using the collimated transmission spectroscopy in visible range, binary diffusion coefficients of tissue water and agent in ex vivo rat brain tissue were measured. IOC agents were objectively compared using two-dimensional nomogram, accounting for their THz-wave absorption coefficients and binary diffusion coefficients. The results of this study demonstrate an interplay between the penetration depth enhancement and the diffusion rate and allow for pointing out glycerol as an optimal agent among the considered ones for particular applications in THz biophotonics.

Terahertz spectroscopy of gelatin-embedded human brain gliomas of different grades: a road toward intraoperative THz diagnosis.

We applied terahertz (THz)-pulsed spectroscopy to study ex vivo the refractive index and absorption coefficient of human brain gliomas featuring different grades, as well as perifocal regions containing both intact and edematous tissues. Glioma samples from 26 patients were considered and analyzed according to further histological examination. In order to fix tissues for the THz measurements, we applied gelatin embedding, which allows for sustaining their THz response unaltered, as compared to that of the freshly excised tissues. We observed a statistical difference between the THz optical constants of intact tissues and gliomas of grades I to IV, while the response of edema was similar to that of tumor. The results of this paper justify a potential of THz technology in the intraoperative label-free diagnosis of human brain gliomas for ensuring the gross-total resection.

From Allostatic Load to Allostatic State-An Endogenous Sympathetic Strategy to Deal With Chronic Anxiety and Stress?

The concepts of allostatic load and overload, i. e., a dramatic increase in the allostatic load that predisposes to disease, have been extensively described in the literature. Here, we show that rats engaging in active offensive response (AOR) behavioral strategies to chronic predator scent stress (PSS) display less anxiety behavior and lower plasma cortisol levels vs. rats engaging in passive defensive response (PDR) behavioral strategies to chronic PSS. In the same chronic PSS paradigm, AOR rats also have higher lactate and lower glutamate levels in amygdala but not in control-region hippocampus vs. PDR rats. The implications of these findings for regulation of allostatic and stress responses, and post-traumatic stress disorder (PTSD) are discussed.