Chirality is a kind of symmetrical structure that exists in nature. A substance has chirality if its mirror image cannot overlap with itself through basic rotations and translations. It is closely related to the phenomenon of life: more than 60% of drugs and 25% of pesticides are chiral compounds. Chiral characteristics significantly affect the function of biochemical substances, chiral isomers have the same chemical composition but may have completely different physical and chemical properties and biological activities, and even a chiral molecule has a therapeutic effect on diseases, while its isomers are toxic. Therefore, accurate and efficient detection of biochemical substances, especially the identification and quantitative analysis of chiral biochemical substances, has practical application needs and crucial scientific significance.

Optical chirality refers to the electromagnetic chirality of photons and their spatial light field distribution. Left- and right-handed circular polarization (LCP and RCP) represent a pair of spin photon states with opposite spin angular momentum. When the wave exhibits a helical spatial phase distribution, it becomes a vortex chiral light field with orbital angular momentum. Chiral molecules have different spectral responses to different chiral photon states or chiral light field distributions, which is one of the important means of molecular stereochemical structure characterization.

Figure 1. The visual diagram of chiral molecules (left) and chiral light fields (right).

Traditional terahertz (THz) time-domain spectral sensing often ignores the polarization information, and can only be used to detect the characteristic spectrum of the sample or achieve refractive index sensing. THz polarization spectrum sensing technology addresses the limitations of traditional detection. Polarization spectrum sensing is to reconstruct the complete polarization state of the detected signal by characterizing the left - and right-handed photon states, thereby obtaining information on polarization ellipsometry and rotation angle that are related to the stereochemical structure of the sample. On this basis, the photon polarization state difference caused by the sample structure is further analyzed, and the circular dichroism spectrum and optical activity spectrum are obtained. The research on polarization spectrum and chiral spectrum sensor detection helps obtain multi-parameter information related to the molecular structure of the sample, and the detection sensitivity and accuracy will be further improved.

Sensor functionalization technology refers to the specific modification of the sensor to make it highly selective to specific target biochemical molecules. The advantage of this technology is that it can give THz sensors with specific sensing capabilities, which can break through the limitations of traditional THz absorption spectrum and refractive index sensing, achieve accurate detection of the target substance, and the sensing sensitivity will be significantly improved.

Prof. Shengjiang Chang and Prof. Fei Fan of Nankai University led the research team of THz Devices and Microscopic Imaging Technology to explore the field of biochemical sensing based on THz metamaterials, focusing on the basic theories and key technologies of polarization spectral sensing and chiral spectral sensing, and applying new strategies of sensor functionalization. The identification of chiral isomers of biochemical substances and the specific identification of target substances were demonstrated. The relevant work was published in Chinese Optics Letters, Volume 21, Issue 11, 2023 (Liang Ma, Weinan Shi, Fei Fan, Ziyang Zhang, Tianrui Zhang, Jiayue Liu, Xianghui Wang, Shengjiang Chang. Terahertz polarization sensing, chirality enhancement, and specific binding based on metasurface sensors for biochemical detection: a review [Invited][J]. Chinese Optics Letters, 2013, 21(11): 110003) and was selected as the Cover of the Current Issue.

The cover shows the application of multifunctional and multitype metasurfaces in biochemical sensing. In the middle of the cover, it is shown that metasurfaces with different functions generate different chiral light fields under the excitation of incident THz waves so that various biomolecules on the surface can be detected.

Highly specific and sensitive biochemical detection technology is particularly important in today's global epidemic and has very important applications in life science, medical diagnosis, and pharmaceutical fields. THz metasurface biochemical substance sensing technology is an emerging technology that can be used for highly sensitive biochemical molecular sensing detection. However, it is difficult to distinguish chiral enantiomers and specifically identify target biomolecules due to the strong resonant patterns generated by the THz metasurface that overwrites the characteristic absorption peaks of the analyte. Recently, the new technology of THz polarization spectrum and chiral spectrum sensing has become an effective way to break through the above detection limitations. In addition, the sensor is functionalized by modification of antibodies or other nanomaterials, giving the sensor specific sensing capabilities of high sensitivity.

Figure 2. (a) Metasurface modified by antibody functionalization to achieve specific antigen detection; (b) Chiral response enhanced by PB metasurface; (c) Detection of protein thermal denaturation by reflection THz time-domain polarization spectroscopy system; (d) Material chirality response enhanced by dielectric metasurface.

This paper reviews the development of THz metasurface sensing technology, introduces the basic theory and key technologies of THz polarization spectrum and chiral spectrum sensing detection in detail, as well as the typical applications in the recognition of chiral isomers of biochemical molecules and specific sensing detection, and covers the latest research progress of our research group to provide readers with the latest reference for this new research topic. In order to realize the high specificity, high sensitivity, and high precision detection of biochemical substances, it is necessary to make full use of the vector characteristics such as polarization and chirality in the wide band spectrum of the THz light field. The significance of the research is that on the one hand, more multi-parameter and multi-dimensional sensing information can be obtained to improve the detection sensitivity and accuracy; On the other hand, the intrinsic electromagnetic interaction between the THz chiral light field and the material structure is used to improve the specificity of detection.

The development of chiral spectroscopy and its sensing technology in the THz band, which has rich specific responses to the chirality and spatial structure of biochemical substances, is not only a major demand for the current global epidemic prevention and control but also has important scientific research value. Seize the strategic opportunity offered by THz chiral spectroscopy: it is suggested to improve and develop the theoretical system of THz chiral spectrum characterization and sensing detection technology around the new mechanism and effect of THz chiral light field excitation, manipulation, and enhancement, develop key devices and detection systems with independent intellectual property rights, and realize the detection of biochemical substances with high specificity, high sensitivity, and high precision, thus promote the rapid development of THz biochemical detection technology.