# Surface-Modified Compounds Improve the Detection Sensitivity of Terahertz Metasurface Biosensors
## 1 Introduction  
Proteins are a class of macromolecules with important biological functions, including replicating genomic information, regulating transcription, signaling, providing structure, catalyzing reactions, and transporting molecules [1; 2]. When proteins are misfolded, truncated, or mutated, as well as overexpressed or underexpressed proteins, they are often associated with many diseases. Therefore, proteins are usually used as biomarkers, which are closely related to the physiological state of the human body, and have different metabolic, structural and regulatory functions in different diseases [3; 4]. By trackingthe concentration of protein, it can reveal the health or disease of the human body. For example, cancer-related proteins include CEA, NSE, and SCC, etc. [5; 6; 7], and the changes in the concentration of these protein in human serum can assist in the analysis of cancer. In addition, some research have introduced the use of cancer stem cell (CSC) biomarkers for prognostic analysis, among which 8 types CSC biomarkers CD133, CD44, CD90, ALDH1A1, EPCAM, SOX2, SOX9, and LGR5 have significant prognostic value in digestive system tumors (including pancreas, colon, liver, stomach, and esophagus) [8]. Therefore, the detection of protein in human body is of great significance for monitoring human health status, recovery after exercise, disease diagnosis and prognosis analysis. At present, there are many detection methods applied to protein detection, including enzyme-linked immunosorbent assay(ELISA) [9], chemiluminescence Immunoassay(CLIA) [10], electrochemical method [11], biological mass spectrometry [12], etc. However, these methods are often limited by sensitivity, operational difficulty, and high costs. Therefore, there is an urgent need to develop fast, convenient, and highly sensitive protein detection methods. THz wave is between infrared and microwave, which has the following characteristics. The electron energy is very low and will not cause harmful ionization to biological samples. The detection of THz wave belongs to coherence detection, and physical parameters such as refractive index and absorption coefficient can be obtained through calculation. Most importantly, the vibrational and rotational energy levels of many biomolecules and organic molecules are in the THz frequency band [13; 14; 15]. Therefore, THz technology has broad application prospects in food safety, biomedicine, human health and other fields [16; 17; 18]. Metassurface is a kind of artificially designed periodic structure, which have unique electromagnetic characteristics such as negative refractive index and negative conductivity. Its resonance frequency can be drastically changed by the change of local electric field on the surface. Based on these characteristics, sensors for sensing detection can be designed [19; 20; 21]. However, THz metasurface sensor is a kind of sensor with special electromagnetic characteristics designed by humans in the THz range [22; 23]. However, because the change of dielectric environment caused by the trace amounts of biological samples is not obvious, the direct use of THz metasurface sensor detection cannot produce better detection results. Therefore, a new method to improve the detection sensitivity of metasurface sensors need is to explored. In recent years, metasurface structures working in the terahertz frequency band are a hot research direction, and researchers have carried out a lot of work on them. [PERSON] et al. [24] proposed a folded metamaterial sensor with high aspect ratio nano profile SRRs. The resonant transmittance of the sensor is far lower than that of ordinary Metamaterial, reaching \(-\)49 dB. The Q factor pf sensor reaches 37.0. The sensitivity of the sensor to the refractive index is up to 647 GHz/RIU. In the same year, [PERSON] et al. [25] revealed the unprecedented optical phonon response of CaMg(CO\({}_{3}\))\({}_{2}\)(dolomite) thin films in planar ultra-narrow band mid-infrared (MIR) thermal emitter designs.