Quad-Band Terahertz Metasurface Flexible Biosensor for HCC Biomarker Detection Using a Multipeak Data Fusion Strategy.

Terahertz technology, with its label-free, nondestructive nature and unique fingerprint spectral characteristics for biomolecules, holds great promise for high-sensitivity detection of cancer biomarkers. However, conventional terahertz biosensors typically achieve sensing based on a single resonant peak, which inherently limits the sensitivity and detection precision. In this article, a flexible quad-band terahertz metasurface biosensor is proposed. The biosensor employs a mirrored double-F-shaped metallic unit cell, which generates four resonant peaks at 1.02, 2.27, 2.60, and 2.95 THz. Moreover, a multipeak data fusion strategy is proposed to jointly analyze the frequency shifts of the four resonant peaks, which can enhance the sensitivity and precision simultaneously. For verification, a biosensor prototype is fabricated on a polyethylene terephthalate substrate. Two kinds of cancer biomarkers alpha-fetoprotein and carcinoembryonic antigen related to hepatocellular carcinoma (HCC) are used as experimental samples. The results show that the detection sensitivities (35.4 and 31.1 GHz/lg (ng/mL)) obtained using the multipeak data fusion strategy based on cumulative frequency shifts are both higher than those measured from the four single peaks under the same concentration. The biosensor achieves a limit of detection as low as 1.00 ng/mL for both biomarkers. Furthermore, by fusing multipeak data through average frequency shift analysis, random noise is effectively suppressed, thereby reducing the relative standard deviation to less than 3% and significantly improving the linearity (R2 > 0.99). In comparison with conventional approaches, the proposed method exhibits heightened sensitivity and precision. Consequently, this research offers an effective solution for the early clinical diagnosis of cancer.