Abstract-Near‐Field Nanoscopic Terahertz Imaging of Single Proteins

 

Zhongbo Yang,  Dongyun Tang,  Jiao Hu,  Mingjie Tang,  Mingkun Zhang,  Hong‐Liang, Cui  Lihua Wang,  Chao Chang,  Chunhai Fan,  Jiang Li,  Huabin Wang,

https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202005814

Terahertz (THz) biological imaging has attracted intense attention due to its capability of acquiring physicochemical information in a label‐free, noninvasive, and nonionizing manner. However, extending THz imaging to the single‐molecule level remains a challenge, partly due to the weak THz reflectivity of biomolecules with low dielectric constants. Here, the development of graphene‐mediated THz scattering‐type scanning near‐field optical microscope for direct imaging of single proteins is reported. Importantly, it is found that a graphene substrate with high THz reflectivity and atomic flatness can provide high THz contrast against the protein molecules. In addition, a platinum probe with an optimized shaft length is found enabling the enhancement of the amplitude of the scattered THz near‐field signals. By coupling these effects, the topographical and THz scattering images of individual immunoglobulin G (IgG) and ferritin molecules with the size of a few nanometers are obtained, simultaneously. The demonstrated strategy thus opens new routes to imaging single biomolecules with THz

Abstract-Detecting melanoma with a terahertz spectroscopy imaging technique

Dandan Li, Zhongbo Yang, Ailing Fu, Tunan Chen, Ligang Chen, Mingjie Tang, Hua Zhang, Ning Mu, Shi Wang, Guizhao Liang,  Huabin Wang

https://www.sciencedirect.com/science/article/abs/pii/S1386142520302079

Transmission mode terahertz time-domain spectroscopy system was employed to image BALB/c mouse skin tissue slices containing melanoma. The melanoma was unambiguously identified in the frequency region of 0.6–1.8 THz because melanoma has a higher refractive index as well as a higher absorption coefficient than the normal region of the skin tissue. Based on the results of hematoxylin-eosin staining and mass weighing, it was further suggested that the higher density of nucleic acids, higher water content, and lower fat content in the melanoma compared to the normal region are major factors responsible for melanoma's higher refractive index and absorption coefficient than normal tissue. The present work validates that terahertz time-domain spectroscopy imaging technique is possible to be used for the diagnosis of melanoma.

Abstract-Terahertz Spectroscopic Signatures of Microcystin Aptamer Solution Probed with a Microfluidic Chip

Mingkun Zhang, Zhongbo Yang, Mingjie Tang , Deqiang Wang , Huabin Wang, Shihan Yan , Dongshan Wei,  Hong-Liang Cui

https://www.mdpi.com/1424-8220/19/3/534

Terahertz signature detection of biological samples in aqueous solution remains a great challenge due to the strong terahertz absorption of water. Here we propose a new preparation process for fabricating a microfluidic chip and use it as an effective sensor to probe the terahertz absorption signatures of microcystin aptamer (a linear single-stranded DNA with 60 nucleotides) dissolved in TE buffer with different concentrations. The microfluidic chip made of silicon includes thousands of 2.4 μm × 2.4 μm square-cross-section channels. One repeatable terahertz absorption signature is detected and recognized around 830 GHz, fitted to a Lorentz oscillator. This signature is theorized to originate from the bending of hydrogen bonds formed between adjacent hydrated DNA bases surrounded by water molecules. Furthermore, the low-lying vibrational modes are also investigated by molecular dynamics simulations which suggest that strong resonant oscillations are highly probable in the 815–830 GHz frequency band

Abstract-Terahertz time-domain spectroscopy of chondroitin sulfate

Changcheng Shi, Yuting Ma, Jin Zhang, Dongshan Wei, Huabin Wang, Xiaoyu Peng, Mingjie Tang, Shihan Yan, Guokun Zuo, Chunlei Du, and Hongliang Cui

https://www.osapublishing.org/boe/abstract.cfm?uri=boe-9-3-1350&origin=search

Chondroitin sulfate (CS), derived from cartilage tissues, is an important type of biomacromolecule. In this paper, the terahertz time-domain spectroscopy (THz-TDS) was investigated as a potential method for content detection of CS. With the increase of the CS content, the THz absorption coefficients of the CS/polyethylene mixed samples linearly increase. The refractive indices of the mixed samples also increase when the CS content increases. The extinction coefficient of CS demonstrates the THz frequency dependence to be approximately the power of 1.4, which can be explained by the effects of CS granular solids on THz scattering.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Abstract-Detection of DNA oligonucleotides with base mutations by terahertz spectroscopy and microstructures

Mingjie Tang,  Mingkun Zhang, Shihan Yan,  Liangping Xia, Zhongbo Yang, Chunlei Du, Hong-Liang Cui, Dongshan Wei,

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191515

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.

Abstract-Cell viability and hydration assay based on metamaterial-enhanced terahertz spectroscopy

Yu Liu,  Mingjie Tang,  Liangping Xia,  Wenjing Yu,  Jia Peng, Yang Zhang,  Marc Lamy de la Chapelle,  Ke Yang,  Hong-Liang Cui,  Weiling Fu

http://pubs.rsc.org/en/content/articlelanding/2017/ra/c7ra09609g#!divAbstract

As a fast-growing technology, terahertz time-domain spectroscopy (THz-TDS) is becoming increasingly pervasive in biological applications, targeting a range of biomaterials from biomolecules to tissues. However, THz-TDS studies at the cellular level are quite limited. Thus, a study to analyze the living state and hydration state of a tumor cell in a label-free manner is carried out and reported here. Combined with a specially designed THz metamaterial, a tumor cell monolayer was detected continuously over a period of time. In addition, in order to explore the possible impact of the metamaterial on tumor cells, the secretion of IL-6, IL-8, GM-CSF and GROα of cell supernatants was detected. The results demonstrated that the technology could characterize the living state by monitoring the extracellular water and investigate the hydration state inside a tumor cell in real time, showing great application potential for the label-free detection of normal cells and tumor cells of diverse malignant degree.