Identification of Panax notoginseng origin using terahertz precision spectroscopy and neural network algorithm.

Panax notoginseng (P. notoginseng), a Chinese herb containing various saponins, benefits immune system in medicines development, which from Wenshan (authentic cultivation) is often counterfeited by others for large demand and limited supply. Here, we proposed a method for identifying P. notoginseng origin combining terahertz (THz) precision spectroscopy and neural network. Based on the comparative analysis of four qualitative identification methods, we chose high-performance liquid chromatography (HPLC) and THz spectroscopy to detect 252 samples from five origins. After classifications using Convolutional Neural Networks (CNNs) model, we found that the performance of THz spectra was superior to that of HPLC. The underlying mechanism is that there are clear nonlinear relations among the THz spectra and the origins due to the wide spectra and multi-parameter characteristics, which makes the accuracy of five-classification origin identification up to 97.62%. This study realizes the rapid, non-destructive and accurate identification of P. notoginseng origin, providing a practical reference for herbal medicine.

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.

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.

The collective vibrational modes of dihydropyridine in nifedipine studied by terahertz spectroscopy.

Cardiovascular pharmaceuticals have drawn huge attention in drug development. Nifedipine (NFD) is an important member of calcium channel blockers (CCB) with the structural characteristic of dihydropyridine (DHP), but the binding mechanism to its target remains an open question. Even though several analytical techniques have been used for structural characterizations, the information of collective vibrational behavior is still lacking. In this work, we use terahertz (THz) spectroscopy to investigate the spectral fingerprints of NFD, and quantitatively evaluate the temperature-induced frequency shifts. Combined with quantum chemical calculations, each THz fingerprint is attributed to specific collective vibrational modes. The collective vibrations of DHP are mainly distributed below 2.5 THz, which provides complementary information to understand the behavior of rigid DHP ring. The rotation of methyl group and the wagging of nitrophenyl group are widely distributed in the range of 1.0-4.0 THz, which is helpful for the conformational recognition between NFD and target molecule. THz spectroscopy is demonstrated to be suitable for characterizing the collective vibrational modes of DHP and elucidating the drug-target binding behavior from the perspective of noncovalent interactions. It has the potential to become a non-invasive technology for conformational analysis and pharmaceutical development.

Discrimination of Pericarpium Citri Reticulatae in different years using Terahertz Time-Domain spectroscopy combined with convolutional neural network.

Pericarpium Citri Reticulatae (PCR) in longer storage years possess higher medicinal values, but their differentiation is difficult due to similar morphological characteristics. Therefore, this study investigated the feasibility of using terahertz time-domain spectroscopy (THz-TDS) combined with a convolutional neural network (CNN) to identify PCR samples stored from 1 to 20 years. The absorption coefficient and refractive index spectra in the range of 0.2-1.5 THz were acquired. Partial least squares discriminant analysis, random forest, least squares support vector machines, and CNN were used to establish discriminant models, showing better performance of the CNN model than the others. In addition, the output data points of the CNN intermediate layer were visualized, illustrating gradual changes in these points from overlapping to clear separation. Overall, THz-TDS combined with CNN models could realize rapid identification of different year PCRs, thus providing an efficient alternative method for PCR quality inspection.

Terahertz spectroscopy detection of zinc citrate in flour and milk powder mixtures.

Zinc citrate (ZC) has been widely used in food as an important nutritional supplement. Accurate detection of ZC in food is important for health and safety. In this study, THz time-domain spectroscopy (THz-TDS) is used to quantitatively detect ZC in flour and milk powder mixtures. In our research, 15 different contents of ZC in flour and milk powder mixtures were prepared and measured by THz-TDS. A partial least squares (PLS) model was established based on the quantitative analysis of the absorption coefficient data of these two mixtures at 0.5-3.0 THz. The R2 and rms error (RMSE) given by the PLS model prediction were, respectively, 0.999 and 0.14% ZC in flour and 0.999 and 0.20% ZC in milk mixtures, indicating the predictions of the PLS model are in excellent agreement with the experimental measurements. The results show that combining THz-TDS with the PLS model can be used for accurate, quantitative analyses of ZC in food mixtures.

Rapid determination of capsaicin concentration in soybean oil by terahertz spectroscopy.

Capsaicin is the key composition of pepper and can be used as a marker of gutter oil for detection. The feasibility of rapid detection of capsaicin concentration in soybean oil was studied by terahertz spectroscopy. Genetic algorithm (GA) and principal component analysis (PCA) as the pretreatment method were used to obtain the best spectral features. Least square-support vector machine (LS-SVM), back propagation neural network (BPNN), and partial least squares (PLS) were combined with the pretreatment method to obtain the best determination model. The BPNN was combined with GA to obtain the best quantitative prediction results with the correlation coefficient of prediction (RP ), prediction root mean square error (RMSEP), the ratio of prediction to deviation (RPD), and range error ratio (RER) were 0.9309, 0.4030 µg/kg, 17.0421, and 2.4813, respectively. Furthermore, the detection limit of capsaicin could achieve 1.25 µg/kg in soybean oil and the accuracy of discrimination was up to 100% in the prediction set using the LS-SVM combined with GA pre-treatment. The results suggested that terahertz spectroscopy together with chemometric methods would be a promising technique for rapid determination of capsaicin concentration in soybean oil. Meanwhile, it is necessary to perform further experiments with real gutter oil samples before applying the method in practice. PRACTICAL APPLICATION: The combination of terahertz spectroscopy technology and chemometrics is a promising method for the rapid determination of capsaicin concentration in soybean oil with high efficiency.

[Progress on application of terahertz time-domain spectroscopy in identification of traditional Chinese medicine].

With the increasing demand for traditional Chinese medicines(TCMs), the resources of TCMs are gradually rare, and the phenomenon that TCMs fake is a common occurrence. Consequently, we need to urgently improve identification technique of TCMs. Terahertz time-domain spectroscopy(THz-TDS) is a newly emerging spectroscopy technology that has been widely used in image, security inspection, biological detection, medicine, material technology, aerospace, oil exploration and other fields. Which is currently used as a simple and quick method to identify the origins, fake products, processed products and pesticide residues of TCMs, hence, it plays a significant role in supplementing and improving the quality control levels of TCMs. In this paper, the composition principle of THz-TDS and its advantages in authentification of TCMs have been summarized. Additionally, the current situation and application prospects of THz-TDS in the field of TCM identification have also been reviewed.

Rapid in situ analysis of l-histidine and α-lactose in dietary supplements by fingerprint peaks using terahertz frequency-domain spectroscopy.

A simple, green and nondestructive method based on terahertz fingerprint peaks has been developed for rapid in situ analysis of l-histidine and α-lactose in dietary supplements. Fingerprint absorption peaks of l-histidine and α-lactose located at 0.77 and 0.53 THz could be directly used for identification and quantitation of these analytes in commercial dietary supplements. Compared with the partial least squares regression model (PLSR), the linear least squares regression (LLSR) method based on peak areas presented better performance, with the linear correlation coefficients of 0.9899 and 0.9910 for l-histidine and α-lactose, respectively. Furthermore, analysis time per sample can be shortened to less than 1 min due to the narrower spectral acquisition region. The accuracies were 94.8-110% and 98.9-110%, comparable to those of ion chromatography for l-histidine and high-performance liquid chromatography for α-lactose. The results presented great potential of the developed method for rapid in situ analysis of nutrients in dietary supplements.

Rapid determination of aflatoxin B1 concentration in soybean oil using terahertz spectroscopy with chemometric methods.

Soybean oil is often contaminated by aflatoxin B1 (AFB1) which is regarded as a class I carcinogen. The feasibility of rapid determination of AFB1 in soybean oil with terahertz spectroscopy was examined. t-SNE, as the pre-treatment method was used to get the best features and combined with different chemometrics including least squares-support vector machines (LS-SVM), back propagation neural network (BPNN), random forest (RF) and partial least squares (PLS) to find the best determination model. The excellent prediction results could be obtained using BPNN combined with t-SNE with correlation the coefficient of prediction (Rp) was 0.9948 and the root-mean-square error of prediction (RMSEP) was 0.7124 µg/kg. Besides, THz spectroscopy was proved to be feasible to detect AFB1 at 1 µg/kg in soybean oil (over 90% accuracy). It was concluded that THz spectroscopy together with chemometrics would be a promising technique for rapid determination of the AFB1 concentration in soybean oil.

Toward theoretical terahertz spectroscopy of glassy aqueous solutions: partially frozen solute-solvent couplings of glycine in water.

The molecular-level understanding of THz spectra of aqueous solutions under ambient conditions has been greatly advanced in recent years. Here, we go beyond previous analyses by performing ab initio molecular dynamics simulations of glycine in water with artificially frozen solute or solvent molecules, respectively, while computing the total THz response as well as its decomposition into mode-specific resonances based on the "supermolecular solvation complex" technique. Clamping the water molecules and keeping glycine moving breaks the coupling of glycine to the structural dynamics of the solvent, however, the polarization and dielectric solvation effects in the static solvation cage are still at work since the full electronic structure of the quenched solvent is taken into account. The complementary approach of fixing glycine reveals both the dynamical and electronic response of the solvation cage at the level of its THz response. Moreover, to quantitatively account for the electronic contribution solely due to solvent embedding, the solute species is "vertically desolvated", thus preserving the fully coupled solute-solvent motion in terms of the solute's structural dynamics in solution, while its electronic structure is no longer subject to solute-solvent polarization and charge transfer effects. When referenced to the free simulation of Gly(aq), this three-fold approach allows us to decompose the THz spectral contributions due to the correlated solute-solvent dynamics into entirely structural and purely electronic effects. Beyond providing hitherto unknown insights, the observed systematic changes of THz spectra in terms of peak shifts and lineshape modulations due to conformational freezing and frozen solvation cages might be useful to investigate the solvation of molecules in highly viscous H-bonding solvents such as ionic liquids and even in cryogenic ices as relevant to polar stratospheric and dark interstellar clouds.

Application of terahertz spectroscopy and chemometrics for discrimination of transgenic camellia oil.

Discrimination of transgenic edible oil has become the focus of attention in the field of food safety. In this paper, we propose a method for discrimination of transgenic edible oils by using terahertz spectroscopy combine with weighted linear discriminant analysis (WLDA). To evaluate the lustiness of the model, we employ successive projection arithmetic (SPA) and partial least squares (PLS) to verify the discrimination performance through variable selection. The results demonstrate that the SPA-WLDA model has higher classification accuracy than PLS-WLDA. In conclusion, terahertz spectroscopy is coupled with chemometrics is an effective method for discriminating various types of transgenic edible oils.

Spectroscopic Analysis of Melatonin in the Terahertz Frequency Range.

There is a need for fast and reliable quality and authenticity control tools of pharmaceutical ingredients. Among others, hormone containing drugs and foods are subject to scrutiny. In this study, terahertz (THz) spectroscopy and THz imaging are applied for the first time to analyze melatonin and its pharmaceutical product Circadin. Melatonin is a hormone found naturally in the human body, which is responsible for the regulation of sleep-wake cycles. In the THz frequency region between 1.5 THz and 4.5 THz, characteristic melatonin spectral features at 3.21 THz, and a weaker one at 4.20 THz, are observed allowing for a quantitative analysis within the final products. Spectroscopic THz imaging of different concentrations of Circadin and melatonin as an active pharmaceutical ingredient in prepared pellets is also performed, which permits spatial recognition of these different substances. These results indicate that THz spectroscopy and imaging can be an indispensable tool, complementing Raman and Fourier transform infrared spectroscopies, in order to provide quality control of dietary supplements and other pharmaceutical products.

Discrimination of Cynanchum wilfordii and Cynanchum auriculatum by terahertz spectroscopic analysis.

INTRODUCTION: Precise identification of botanical origin of plant species is crucial for the quality control of herbal medicine. In Korea, the root part of Cynanchum auriculatum has been misused for C. wilfordii in the herbal drug market due to their morphological similarities. Currently, DNA analysis using the polymerase chain reaction (PCR) method is employed to discriminate between these species. OBJECTIVE: In order to develop a new analytical tool for the rapid discrimination of C. wilfordii and C. auriculatum, terahertz (THz) spectroscopy was employed. METHODOLOGY: Authentic samples of C. wilfordii and C. auriculatum were provided from the National Institute and standardized pellets for each species were prepared to get optimum results with terahertz time-domain spectroscopy (THz-TDS) in frequency range 0.2-1.20 THz. RESULTS: The C. wilfordii pellet showed longer time delay compare to the sample of C. auriculatum and this was due to the difference in permittivity. The pellet samples of C. wilfordii and C. auriculatum showed a permittivity difference of about 0.08 at 0.2-1.20 THz. CONCLUSION: The experimental results indicated that THz-TDS analysis can be an effective and rapid method for the discrimination of C. wilfordii and C. auriculatum, and this application can be expanded for the discrimination of other similar herbal medicines.

[Application of Terahertz Spectroscopy in the Detection of Chinese Medicine Processed Drugs of Rhubarb].

The changes of composition of the processed traditional Chinese medicine will affect the curative effect of drug, such as the four kinds of processed rhubarb. The characteristics data of each rhubarb was measured with terahertz spectroscopy system and analyzed with chemometrics, and the spectral data was classified according to the category of rhubarb. The substance components of anthraquinone and tannins make changes in processed rhubarb by thin layer chromatography (TLC). The correlation among the terahertz spectroscopy of processed rhubarb was in accordance with the variations of content. This means that terahertz spectroscopy is sensitive to the substance components of processed Chinese traditional medicine. It can also pave the way for the study of the structural changes of traditional Chinese medicine.

Discrimination of genetically modified sugar beets based on terahertz spectroscopy.

The objective of this paper was to apply terahertz (THz) spectroscopy combined with chemometrics techniques for discrimination of genetically modified (GM) and non-GM sugar beets. In this paper, the THz spectra of 84 sugar beet samples (36 GM sugar beets and 48 non-GM ones) were obtained by using terahertz time-domain spectroscopy (THz-TDS) system in the frequency range from 0.2 to 1.2 THz. Three chemometrics methods, principal component analysis (PCA), discriminant analysis (DA) and discriminant partial least squares (DPLS), were employed to classify sugar beet samples into two groups: genetically modified organisms (GMOs) and non-GMOs. The DPLS method yielded the best classification result, and the percentages of successful classification for GM and non-GM sugar beets were both 100%. Results of the present study demonstrate the usefulness of THz spectroscopy together with chemometrics methods as a powerful tool to distinguish GM and non-GM sugar beets.

[Identification of Chinese herbal medicines based on terahertz spectroscopy analysis].

In order to study the feasibility of the identification of Chinese herbal medicines based on terahertz spectroscopy, the optical characteristic of astragalus, angelica, eucommia and three kinds of astragalus samples with different impurities in the frequency range 0.2-2.2 THz were researched by terahertz time-domain spectroscopy (THz-TDS), and their time-domain spectra, the frequency spectra and the absorption spectra were obtained at room temperature. The results indicated that the time-domain spectra, frequency-domain spectra and absorption spectra of astragalus, angelica, and eucommia have large differences in such a frequency range, the frequency-domain spectra and absorption spectra of three kinds of astragalus samples with different impurities are similar but there exists distinct difference. These researches proved that it is feasible to use terahertz time-domain spectroscopy to identify Chinese herbal medicine and provided a new method for Chinese herbal medicine quality control.

Understanding THz spectra of aqueous solutions: glycine in light and heavy water.

THz spectroscopy of aqueous solutions has been established as of recently to be a valuable and complementary experimental tool to provide direct insights into the solute-solvent coupling due to hydrogen-bond dynamics involving interfacial water. Despite much experimental progress, understanding THz spectra in terms of molecular motions, akin to mid-infrared spectra, still remains elusive. Here, using the osmoprotectant glycine as a showcase, we demonstrate how this can be achieved by combining THz absorption spectroscopy and ab initio molecular dynamics. The experimental THz spectrum is characterized by broad yet clearly discernible peaks. Based on substantial extensions of available mode-specific decomposition schemes, the experimental spectrum can be reproduced by theory and assigned on an essentially quantitative level. This joint effort reveals an unexpectedly clear picture of the individual contributions of molecular motion to the THz absorption spectrum in terms of distinct modes stemming from intramolecular vibrations, rigid-body-like hindered rotational and translational motion, and specific couplings to interfacial water molecules. The assignment is confirmed by the peak shifts observed in the THz spectrum of deuterated glycine in heavy water, which allow us to separate the distinct modes experimentally.

Rapid determination of saponification value and polymer content of vegetable and fish oils by terahertz spectroscopy.

A rapid method for determining the saponification value (SV) and polymer content of vegetable and fish oils using the terahertz (THz) spectroscopy was developed. When the THz absorption spectra for vegetable and fish oils were measured in the range of 20 to 400 cm⁻¹, two peaks were seen at 77 and 328 cm⁻¹. The level of absorbance at 77 cm⁻¹ correlated well with the SV. When the THz absorption spectra of thermally treated high-oleic safflower oils were measured, the absorbance increased with heating time. The polymer content in thermally treated oil correlated with the absorbance at 77 cm⁻¹. These results demonstrate that the THz spectrometry is a suitable non-destructive technique for the rapid determination of the SV and polymer content of vegetable and fish oils.

Using modified Kramers-Kronig relations to test transmission spectra of porous media in THz-TDS.

We show that modified Kramers-Kronig relations provide a useful tool to test the validity of the complex refractive index extracted from transmission terahertz spectra of porous matrices containing pharmaceutical materials. The role of scattering of terahertz radiation is qualitatively considered as a reason for the observed discrepancy between experimental data and the values extracted from the inverted complex refractive index. As an example we present an analysis of the terahertz spectra of carbamazepine and lactose alpha-monohydrate.