Correlation between Hydration States and Self-assembly Structures of Phospholipid and Surfactant Studied by Terahertz Spectroscopy.

Phospholipids and surfactants form membranes and other self-assembled structures in water. However, it is not fully understood how the surrounding water (hydration water) is involved in their structure formation. In this paper, I summarize the results of our investigation of the long-range hydration state of phospholipids and surfactants at their surfaces by means of terahertz spectroscopy. By observing the collective rotational dynamics of water in the picosecond time scale, this technique allows us to observe not only the water directly bound to the solute, but also the weakly affected water outside of it. For example, PC phospholipids inhibit water dynamics over long distances, whereas PE phospholipids make water more mobile than bulk water. The causes of this difference in hydration and how it is involved in the structural formation of the membrane are reviewed.

Comprehensive Similarity Algorithm and Molecular Dynamics Simulation-Assisted Terahertz Spectroscopy for Intelligent Matching Identification of Quorum Signal Molecules (N-Acyl-Homoserine Lactones).

To investigate the mechanism of aquatic pathogens in quorum sensing (QS) and decode the signal transmission of aquatic Gram-negative pathogens, this paper proposes a novel method for the intelligent matching identification of eight quorum signaling molecules (N-acyl-homoserine lactones, AHLs) with similar molecular structures, using terahertz (THz) spectroscopy combined with molecular dynamics simulation and spectral similarity calculation. The THz fingerprint absorption spectral peaks of the eight AHLs were identified, attributed, and resolved using the density functional theory (DFT) for molecular dynamics simulation. To reduce the computational complexity of matching recognition, spectra with high peak matching values with the target were preliminarily selected, based on the peak position features of AHL samples. A comprehensive similarity calculation (CSC) method using a weighted improved Jaccard similarity algorithm (IJS) and discrete Fréchet distance algorithm (DFD) is proposed to calculate the similarity between the selected spectra and the targets, as well as to return the matching result with the highest accuracy. The results show that all AHL molecular types can be correctly identified, and the average quantization accuracy of CSC is 98.48%. This study provides a theoretical and data-supported foundation for the identification of AHLs, based on THz spectroscopy, and offers a new method for the high-throughput and automatic identification of AHLs.

Terahertz spectra reconstructed using convolutional denoising autoencoder for identification of rice grains infested with Sitophilus oryzae at different growth stages.

Rice grains are often infected by Sitophilus oryzae due to improper storage, resulting in quality and quantity losses. The efficacy of terahertz time-domain spectroscopy (THz-TDS) technology in detecting Sitophilus oryzae at different stages of infestation in stored rice was employed in the current research. Terahertz (THz) spectra for rice grains infested by Sitophilus oryzae at different growth stages were acquired. Then, the convolutional denoising autoencoder (CDAE) was used to reconstruct THz spectra to reduce the noise-to-signal ratio. Finally, a random forest classification (RFC) model was developed to identify the infestation levels. Results showed that the RFC model based on the reconstructed second-order derivative spectrum with an accuracy of 84.78%, a specificity of 86.75%, a sensitivity of 86.36% and an F1-score of 85.87% performed better than the original first-order derivative THz spectrum with an accuracy of 89.13%, a specificity of 91.38%, a sensitivity of 88.18% and an F1-score of 89.16%. In addition, the convolutional layers inside the CDAE were visualized using feature maps to explain the improvement in results, illustrating that the CDAE can eliminate noise in the spectral data. Overall, THz spectra reconstructed with the CDAE provided a novel method for effective THz detection of infected grains.

Application of terahertz Time-Domain spectroscopy and chemometrics-based whale optimization algorithm in PDE5 inhibitor detection.

Combating the illicit use of PDE5 inhibitor drugs is a focal point in forensic science research. In order to achieve rapid identification of such drugs, this study applies terahertz time-domain spectroscopy combined with chemometrics to establish a fast and accurate detection method for PDE5 inhibitors. The optimal detection method is determined by comparing the spectral performance of three optical parameters, namely absorption coefficient, refractive index, and dielectric constant. Linear discriminant models based on different spectral parameters, whale optimization algorithm optimized extreme learning machine models, and whale optimization algorithm optimized random forest models are established. The effectiveness and performance of principal component analysis and competitive adaptive reweighted sampling algorithm for spectral feature data selection are also investigated. The PDE5 inhibitor identification model based on the competitive adaptive reweighted sampling - whale optimization algorithm - random forest (CARS-WOA-RF) model achieves an accuracy of 98.61%, and the identification model for two concentrations of Sildenafil achieves 100% accuracy. The results demonstrate that terahertz time-domain spectroscopy combined with chemometrics can effectively detect various common types of PDE5 inhibitor drugs and different concentrations.

Vibrational spectroscopic detection and analysis of salicylic acid and aspirin binary cocrystal.

Salicylic acid is a raw material for preparing aspirin and holds an important position in medical history. Studying the crystallization of these two drugs is of great significance in improving their dissolution rate, bioavailability, and physical stability. Although various techniques have been used for structural characterization, there is still a lack of information on the collective vibrational behavior of aspirin and salicylic acid eutectic compounds. Firstly, two starting materials (salicylic acid and aspirin) were ground in a 1:1 M ratio to prepare eutectic compounds. The eutectic composition was studied using vibrational spectroscopy techniques, such as X-ray powder diffusion (XRPD), terahertz time-domain spectroscopy (THz-TDS), and Raman spectroscopy. Additionally, the structure of the aspirin and salicylic acid eutectic was simulated and optimized using density functional theory. It was found that the eutectic type II was the most consistent with the experiment, and the corresponding vibration modes of each peak were provided. These results offer a unique method for characterizing the structural composition of eutectic crystals, which can be utilized to enhance the physical and chemical properties, as well as the pharmacological activity, of specific drugs at the molecular level.

An innovative detection technique for capillary electrophoresis: Localized terahertz emission-time domain spectroscopy.

Terahertz (THz) time-domain spectroscopy (TDS) is a recently emerging analysis method which can provide unique information on molecular vibration and rotation induced by inter/intra-molecular interactions. Although the application of THz-TDS to high-performance microscale separation methods like capillary electrophoresis (CE) has been anticipated, it has been hindered due to the diffraction limit of THz wave (typically, hundreds µm). In order to realize CE-THz-TDS, in this study, we placed a narrow open-tubular capillary on the surface of a GaAs semiconductor substrate as a "localized" THz-emitter. By focusing femtosecond pulsed laser beams at the surface of a gallium arsenide (GaAs) substrate closest to the capillary, THz waves were locally generated to pass through the capillary, so that THz absorbance spectra were obtained from the capillary which has narrower inner diameter than the diffraction limit. As a typical result from acetic acid analysis in the CE-THz-TDS platform, information on the refractive index and extinction coefficient was obtained, which showed non-linear and linear concentration dependence, respectively, similar to conventional THz-TDS using large liquid cells. Finally, CE-THz-TDS analysis of several carboxylic acids was demonstrated. Two acids were successfully separated and detected with THz-TDS, where their electrophoretic mobility values were estimated as close to those obtained with conventional contactless conductivity detection. Our proposed CE-THz-TDS showed the potential for the systematic analysis of inter/intra-molecular weak interactions like hydrogen bonds, which are unable to obtain with conventional detectors.

Terahertz Attenuated Total Reflection Spectral Response and Signal Enhancement via Plasmonic Enhanced Sensor for Eye Drop Detection.

With chronic ocular diseases such as glaucoma and dry eye syndrome, patients have to apply eye drops over the long term. The therapeutic effects of eye drops depend on the amount of drug contained and the stability of the solution. In addition, contamination during usage and transport can also negatively affect the quality and efficacy of eye drops. The current techniques for the characterization of eye drops are often complicated and time-consuming. Developing a fast and non-invasive way of accurately measuring eye drop quality remains an ongoing challenge. The biggest challenge and primary prerequisite for the application of this new detection technique for eye drops is the obtention of a sufficient spectral response and resolvable signal, considering the large background signal contributed by water. In this work, we use terahertz (THz) attenuated total reflection (ATR) spectroscopy combined with a sensitive hybrid graphene oxide (GO) and carbon nanotube (CNT) thin-film sensors to obtain distinct THz spectral signals in commercial eye drops. Various commercial eye drop products have been tested, and we show that they can be differentiated via their spectral signals. Our results provide a solid foundation for the future fine analysis of eye drops and the detection of their quality. Furthermore, THz spectroscopy combined with GO/CNT films has significant potential and advantages for the non-destructive characterization of aqueous pharmaceutical products.

Deep-Learning Terahertz Single-Cell Metabolic Viability Study.

Cell viability assessment is critical, yet existing assessments are not accurate enough. We report a cell viability evaluation method based on the metabolic ability of a single cell. Without culture medium, we measured the absorption of cells to terahertz laser beams, which could target a single cell. The cell viability was assessed with a convolution neural classification network based on cell morphology. We established a cell viability assessment model based on the THz-AS (terahertz-absorption spectrum) results as y = a = (x - b)c, where x is the terahertz absorbance and y is the cell viability, and a, b, and c are the fitting parameters of the model. Under water stress the changes in terahertz absorbance of cells corresponded one-to-one with the apoptosis process, and we propose a cell 0 viability definition as terahertz absorbance remains unchanged based on the cell metabolic mechanism. Compared with typical methods, our method is accurate, label-free, contact-free, and almost interference-free and could help visualize the cell apoptosis process for broad applications including drug screening.

Optimal frequency determination for terahertz technology-based detection of colitis-related cancer in mice.

Colorectal cancer is a prevalent malignancy globally, often linked to chronic colitis. Terahertz technology, with its noninvasive and fingerprint spectroscopic properties, holds promise in disease diagnosis. This study aimed to explore terahertz technology's application in colitis-associated cancer using a mouse model. Mouse colorectal tissues were transformed into paraffin-embedded blocks for histopathological analysis using HE staining. Terahertz transmission spectroscopy was performed on the tissue blocks. By comparing terahertz absorption differences, specific frequency bands were identified as optimal for distinguishing cancerous and normal tissues. The study revealed that terahertz spectroscopy effectively differentiates colitis-related cancers from normal tissues. Remarkably, 1.8 THz emerged as a potential optimal frequency for diagnosing colorectal cancer in mice. This suggests the potential for rapid histopathological diagnosis of colorectal cancer using terahertz technology.

Investigating the function and design of molecular materials through terahertz vibrational spectroscopy.

Terahertz spectroscopy has proved to be an essential tool for the study of condensed phase materials. Terahertz spectroscopy probes the low-frequency vibrational dynamics of atoms and molecules, usually in the condensed phase. These nuclear dynamics, which typically involve displacements of entire molecules, have been linked to bulk phenomena ranging from phase transformations to semiconducting efficiency. The terahertz region of the electromagnetic spectrum has historically been referred to as the 'terahertz gap', but this is a misnomer, as there exist a multitude of methods for accessing terahertz frequencies, and now there are cost-effective instruments that have made terahertz studies much more user-friendly. This Review highlights some of the most exciting applications of terahertz vibrational spectroscopy so far, and provides an in-depth overview of the methods of this technique and its utility to the study of the chemical sciences.

Application of IRI Visualization to Terahertz Vibrational Spectroscopy of Hydroxybenzoic Acid Isomers.

The characteristic absorption spectra of three positional isomers of hydroxybenzoic acid are measured using a terahertz time-domain spectroscopy system (THz-TDS) in the 0.6-2.0 THz region at room temperature. Significant differences in their terahertz spectra are discovered, which indicates that THz-TDS is an effective means to identify positional isomers. In order to simulate their spectra, the seven molecular clusters of 2-, 3-, and 4-hydroxybenzoic acid (2-, 3-, and 4-HA) are calculated using the DFT-D3 method. Additionally, the potential energy distribution (PED) method is used to analyze their vibration modes. The analysis indicates that the vibration modes of 2-HA are mainly out-of-plane angle bending and bond angle bend in plane. The vibration modes of 3-HA are mainly bond length stretch and dihedral angle torsion. The vibration modes of 4-HA are mainly bond angle bend in plane and dihedral angle torsion. Interaction region indicator (IRI) analysis is used to visualize the location and type of intermolecular interactions in 2-, 3-, and 4-HA crystals. The results show that the weak interaction type of 2-, 3-, and 4-HA is dominated by van der Waals (vdW) interaction. Therefore, we can confirm that terahertz spectroscopy detection technology can be used as an effective means to identify structural isomers and detect the intermolecular interactions in these crystals. In addition, it can explain the absorption mechanism of terahertz waves interacting with matter.

Analyzing the effects of nonthermal pretreatments on the quality of microwave vacuum dehydrated beef using terahertz time-domain spectroscopy and near-infrared hyperspectral imaging.

Both nonthermal pretreatment and nondestructive analysis are effective technologies in improving drying processes. This study evaluated the effects of different pretreatment methods on the quality of beef dehydrated by microwave vacuum drying (MVD) and compared the MVD process performance comprising real-time moisture content (MC), MC loss, colour content, and shrinkage rate using different optical sensing methods including terahertz time-domain spectroscopy (THz-TDS) and near-infrared hyperspectral imaging (NIR-HSI). Results indicated that osmotic pretreatment improved the drying rate of MVD beef with lower changes in colour and shrinkage rate. Both THz-TDS-based and NIR-HSI-based on-site direct scanning and in-situ in-direct sensing showed accurate prediction results, with best R2p of 0.9646 and 0.9463 for MC and R2p of 0.9817 and 0.9563 for MC loss prediction, respectively. NIR-HSI visualisation of MC results showed that ultrasound pretreatment curbed but osmotic pretreatment promoted nonuniform distribution during MVD. This research should guide improving the industrial MVD drying process.

NIR and THz spectroscopy: An experimental investigation toward nicotine-related devices.

This study examined the content of nicotine-delivery products using terahertz time-domain spectroscopy (THz-TDS) and breath ethylene investigated with CO2 laser photoacoustic spectroscopy (CO2 LPAS) system as a biomarker of oxidative stress after smoking. The THz-TDS method provided valuable information on the transmission spectra of tobacco and nicotine in smoking products. From the CO2 LPAS data it was observed that in cigarette (TC) smoking the mean breath ethylene was 687 parts per billion (ppb), while in electronic cigarettes and tobacco heating devices smoking the mean ethylene was 56 ppb and 48 ppb, respectively. The main finding was that TC showed higher transmission in the THz region producing a higher oxidative stress on the body.

Exploring the Application of Multi-Resonant Bands Terahertz Metamaterials in the Field of Carbohydrate Films Sensing.

Terahertz spectroscopy is a powerful tool for investigating the properties and states of biological matter. Here, a systematic investigation of the interaction of THz wave with "bright mode" resonators and "dark mode" resonators has been conducted, and a simple general principle of obtaining multiple resonant bands has been developed. By manipulating the number and positions of bright mode and dark mode resonant elements in metamaterials, we realized multi-resonant bands terahertz metamaterial structures with three electromagnetic-induced transparency in four-frequency bands. Different carbohydrates in the state of dried films were selected for detection, and the results showed that the multi-resonant bands metamaterial have high response sensitivity at the resonance frequency similar to the characteristic frequency of the biomolecule. Furthermore, by increasing the biomolecule mass in a specific frequency band, the frequency shift in glucose was found to be larger than that of maltose. The frequency shift in glucose in the fourth frequency band is larger than that of the second band, whereas maltose exhibits an opposing trend, thus enabling recognition of maltose and glucose. Our findings provide new insights into the design of functional multi-resonant bands metamaterials, as well as new strategies for developing multi-band metamaterial biosensing devices.

Determination of Vibrational Modes of l-Alanine Single Crystals by a Combination of Terahertz Spectroscopy Measurements and Density Functional Calculations.

Density-functional theory may be used to predict both the frequency and the dipole moment of the fundamental oscillations of molecular crystals. Suitably polarized photons at those frequencies excite such oscillations. Thus, in principle, terahertz spectroscopy may confirm the calculated fundamental modes of amino acids. However, reports to date have multiple shortcomings: (a) material of uncertain purity and morphology and diluted in a binder material is employed; (b) consequently, vibrations along all crystal axes are excited simultaneously; (c) data are restricted to room temperature, where resonances are broad and the background dominant; and (d) comparison with theory has been unsatisfactory (in part because the theory assumes zero temperature). Here, we overcome all four obstacles, in reporting detailed low-temperature polarized THz spectra of single-crystal l-alanine, assigning vibrational modes using density-functional theory, and comparing the calculated dipole moment vector direction to the electric field polarization of the measured spectra. Our direct and detailed comparison of theory with experiment corrects previous mode assignments for l-alanine, and reveals unreported modes, previously obscured by closely spaced spectral absorptions. The fundamental modes are thereby determined.

Estimating Thoracic Movement with High-Sampling Rate THz Technology.

We use a high-sampling rate terahertz (THz) homodyne spectroscopy system to estimate thoracic movement from healthy subjects performing breathing at different frequencies. The THz system provides both the amplitude and phase of the THz wave. From the raw phase information, a motion signal is estimated. An electrocardiogram (ECG) signal is recorded with a polar chest strap to obtain ECG-derived respiration information. While the ECG showed sub-optimal performance for the purpose and only provided usable information for some subjects, the signal derived from the THz system showed good agreement with the measurement protocol. Over all the subjects, a root mean square estimation error of 1.40 BPM is obtained.

Determining changes in crystallinity of rice starch after heat-moisture treatment using terahertz spectroscopy.

To investigate the potential of Fourier-transform terahertz (FT-THz) spectroscopy to follow crystalline structure changes in rice starch after heat-moisture treatment (HMT), we measured the crystallinity by X-ray diffraction (XRD) spectra and found its correlation with THz spectra. According to A-type crystal structure and Vh-type crystalline structure of amylose-lipid complex (ALC) in rice starch, crystallinity is divided into A-type and Vh-type. The intensity of second derivative spectra peak at 9.0 THz was highly correlated with both A-type and Vh-type crystallinity. Additionally, other three peaks at 10.5 THz, 12.2 THz, and 13.1 THz were also sensitive to Vh-type crystalline structure. These results indicate that after HMT, the crystallinity of ALC (Vh-type) and A-type starch can be quantified using THz peaks.

Spectral Characteristics and Functional Responses of Phospholipid Bilayers in the Terahertz Band.

Understanding the vibrational information encoded within the terahertz (THz) spectrum of biomolecules is critical for guiding the exploration of its functional responses to specific THz radiation wavelengths. This study investigated several important phospholipid components of biological membranes-distearoyl phosphatidylethanolamine (DSPE), dipalmitoyl phosphatidylcholine (DPPC), sphingosine phosphorylcholine (SPH), and lecithin bilayer-using THz time-domain spectroscopy. We observed similar spectral patterns for DPPC, SPH, and the lecithin bilayer, all of which contain the choline group as the hydrophilic head. Notably, the spectrum of DSPE, which has an ethanolamine head group, was different. Interestingly, density functional theory calculations confirmed that the absorption peak common to DSPE and DPPC at approximately 3.0 THz originated from a collective vibration of their similar hydrophobic tails. Accordingly, the cell membrane fluidity of RAW264.7 macrophages with irradiation at 3.1 THz was significantly enhanced, leading to improved phagocytosis. Our results highlight the importance of the spectral characteristics of the phospholipid bilayers when studying their functional responses in the THz band and suggest that irradiation at 3.1 THz is a potential non-invasive strategy to increase the fluidity of phospholipid bilayers for biomedical applications such as immune activation or drug administration.

Terahertz Spectroscopy Sheds Light on Real-Time Exchange Kinetics Occurring through Plasma Membrane during Photodynamic Therapy Treatment.

Methods to follow in real time complex processes occurring along living cell membranes such as cell permeabilization are rare. Here, the terahertz spectroscopy reveals early events in plasma membrane alteration generated during photodynamic therapy (PDT) protocol, events which are not observable in any other conventional biological techniques performed in parallel as comparison. Photodynamic process is examined in Madin-Darby canine kidney cells using Pheophorbide (Pheo) photosensitizer alone or alternatively encapsulated in poly(ethylene oxide)-block-poly(ε-caprolactone) micelles for drug delivery purpose. Terahertz spectroscopy (THz) reveals that plasma membrane permeabilization starts simultaneously with illumination and is stronger when photosensitizer is encapsulated. In parallel, the exchange of biological species is assessed. Over several hours, this conventional approach demonstrates significant differences between free and encapsulated Pheo, the latter leading to high penetration of propidium iodide, Na+ and Ca2+ ions, and a high level of leakage of K+ , ATP, and lactate dehydrogenase. THz spectroscopy provides, in a single measurement, the relative number of defects per membrane surface created after PDT, which is not achieved by any other method, providing early, sensitive real-time information. THz spectroscopy is therefore a promising technique and can be applied to any biological topic requiring the examination of short-term plasma membrane permeabilization.

Revolutionary approaches for cancer diagnosis by terahertz-based spectroscopy and imaging.

Most tumors are easily missed and misdiagnosed due to the lack of specific clinical signs and symptoms in the early stage. Thus, an accurate, rapid and reliable early tumor detection method is highly desirable. The application of terahertz (THz) spectroscopy and imaging in biomedicine has made remarkable progress in the past two decades, which addresses the shortcomings of existing technologies and provides an alternative for early tumor diagnosis. Although issues such as size mismatch and strong absorption of THz waves by water have set hurdles for cancer diagnosis by THz technology, innovative materials and biosensors in recent years have led to possibilities for new THz biosensing and imaging methods. In this article, we reviewed the issues that need to be solved before THz technology is used for tumor-related biological sample detection and clinical auxiliary diagnosis. We focused on the recent research progress of THz technology, with an emphasis on biosensing and imaging. Finally, the application of THz spectroscopy and imaging for tumor diagnosis in clinical practice and the main challenges in this process were also mentioned. Collectively, THz-based spectroscopy and imaging reviewed here is envisioned as a cutting-edge approach for cancer diagnosis.