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Terahertz absorption spectroscopy based on attenuated total reflection (ATR) from a microfluidic sample cell was designed and implemented to detect gene mutations leading to Huntington's disease (HD). The self-developed compact ATR microfluidic system was employed to detect two groups of base-repeated DNA molecules combined with a terahertz time-domain spectrometer in a marker-free manner. The first group featured different repetition patterns of oligonucleotide fragments, and the second group included the HD gene. For the oligonucleotides of different repetition patterns, there were significant differences among the three oligonucleotides with three repeats of the double bases, which could be unambiguously classified and identified; For the HD gene, it was found that the magnitude of the terahertz absorption coefficients of the four oligonucleotide solutions was, in ascending order, CAG-4 < CAG-16 < CAG-32 < CAG-40 (the numbers are the repeat times of the CAG base segment, with 40 repeats belonging to the HD gene), when the concentration of oligonucleotide was 1 mg/mL. Principal component analysis result indicated that the spectral differences of the four oligonucleotide solutions with different CAG repeat times were statistically significant and clearly distinguishable. These results demonstrate the potential of terahertz spectroscopy as a noninvasive, unmarked, fast and low-cost assay for gene diagnosis and clinical disease detection., (© 2020 Wiley-VCH GmbH.)

A rapid method for detecting fatty acids (FAs) using terahertz time-domain spectroscopy (THz-TDS) technology combined with a metamaterial-based THz sensor was developed. We measured the THz responses to oleic acid, linoleic acid and α-linoleic acid with different numbers of double-bond, α-linoleic acid and γ-linoleic acid with different conformations. In addition, in order to explore the reason for the observed redshifts of the resonance frequencies of the four FAs, the dielectric constants of the FAs were measured in the THz region. Furthermore, the four fatty acids were also attempted to be identified by Raman spectroscopy, which was difficult to accomplish unambiguously because of the effect of fluorescence. This result thus demonstrates the power and usefulness of metamaterial-assisted THz-TDS in the rapid determination of the FAs, and its potential as a versatile tool for investigation of biological metabolism, and for food product quality, safety inspection and control., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2019. Published by Elsevier B.V.)

DNA oligonucleotides with a 5-base mutation at the 3'-terminus were investigated by terahertz (THz) spectroscopy in a marker-free manner. The four single-stranded oligonucleotides with 17nt have been detected with specificity on a microfluidic chip, and corroborated by spectral measurements with split-ring resonators. The number of hydrogen bonds formed between the oligonucleotide and its surrounding water molecules, deemed a key contribution to the THz absorption of biological solutions, was explored by molecular dynamics simulations to explain the experimental findings. Our work underlies the feasibility of THz spectroscopy combined with microstructures for marker-free detection of DNA, which may form the basis of a prospective diagnostic tool for studying genic mutation.

A terahertz (THz) spectroscopic study is carried out to analyze DNA mutations in a label-free manner. Three newly designed liquid sample cells are considered and the best is selected as the sample carrier for THz transmission spectroscopic analyses. Discrimination based on spectral signatures of single-base mutations on single-stranded 20 nt oligonucleotides has been shown possible experimentally. The results clearly attest the ability of this promising approach for label-free analyses of single-base mutations of DNA molecules. This study has demonstrated that the THz spectroscopic technology can be considered as a potential diagnostic tool for investigating molecular reactions, such as DNA mutations.

Scattering-type scanning near-field optical microscopy (s-SNOM) has been playing more and more important roles in investigating electromagnetic properties of various materials and structures on the nanoscale. In this technique, a sharp tip is employed as the near-field antenna to measure the sample's properties with a high spatial resolution. As the scattered near-field signal from the tip is extremely weak and contaminated by strong background noise, the effective detection, and subsequent extraction of the near-field information from the detected signals is the key issue for s-SNOM. In this review, we give a systematic explanation of the underlying mechanisms of s-SNOM, and summarize and interpret major signal detection techniques involved, including experimental setups, theories for signal analysis and processing, and exposition of advantages and disadvantages of such techniques. By this, we hope to provide a practical guide and a go-to source of detailed information for those interested in and/or working on s-SNOM. [ABSTRACT FROM AUTHOR]

Terahertz reflection imaging is considered as a potential diagnostic tool for the investigation of polymethacrylimide foam defects. Using terahertz time-domain spectroscopy (TDS) and detection methods based on terahertz spectroscopic analysis, the reflection imaging results of different thicknesses of polymethacrylimide foam with two kinds of detections (cracks and voids) are studied. The samples (Degussa Rohacell WF71) are planar slabs of polymethacrylimide foams with thicknesses of 35 mm, 60.5 mm and 10 mm. It is found that the same kinds of polymethacrylimide foam defects with different foam thicknesses have similar spectral characteristics, with marked differences only in the amplitude and phase of the reflected wave. In view of this, we focus our study on the defective spectral characteristics of one of the foams (35 mm thickness). The characteristics of void and crack defects are analyzed in the time domain, which is based mainly on the variation of the reflected waveform. In particular, the imaging and clear identification of voids of less than 2.4 mm in diameter, fine cracks (0.3 mm wide), and the quantification of defects can be readily achieved using the terahertz non-destructive testing technique described here. [ABSTRACT FROM AUTHOR]

• Protein folding or unfolding in solution bring about terahertz spectrum changes. • Terahertz spectrum can indicate protein denaturation induced by pH or temperature. • Terahertz spectroscopy is a potential label-free protein drugs' quality control tool. Polypeptides and protein drugs have received enormous attention from pharmaceutical industry, medical sector and consumer groups because of a favourable combination of their bioactivity, specificity and overall success rate for the treatment of a variety of diseases. The efficacy and safety of drugs may be degraded due to fluctuating environmental factors, accompanied by changes of the natural conformation of protein. Thus, it is necessary and meaningful to evaluate drug status before use. To that end, the evolving new and pre-existing protein activity/conformation technologies have proven to ensure the safety of drug use consistently. Recently, terahertz time-domain spectroscopy (THz-TDS) has demonstrated suitability for label-free and non-destructive detection of polypeptide and protein conformational changes. In this paper, THz optical parameters of pepsin solutions under different temperatures and with varying pH are measured to demonstrate the feasibility and the considerable potential of THz spectroscopic method in detecting protein drugs. In cases where temperature or pH change is apparent, the THz absorption coefficient, the refractive index, and the dielectric loss tangent change noticeably, independently verified by enzyme activity testing. These findings strongly support the conclusion that THz spectroscopy of pepsin solutions can be used for qualitative analysis to identify the folding or unfolding of protein drugs caused by changes of environmental factors, laying the foundation of a new label-free method for quality control of protein drugs. [ABSTRACT FROM AUTHOR]