Advancing Terahertz Biochemical Sensing: From Spectral Fingerprinting to Intelligent Detection

Biochemical detection is fundamental to various scientific disciplines, yet conventional methods still face inherent bottlenecks in achieving rapid, ultrasensitive, and simultaneous multi-target analysis. Terahertz (THz) waves, characterized by their unique spectral fingerprinting capabilities and non-destructive properties, have emerged as a compelling platform for advanced biochemical sensing. This review outlines the evolution of THz biochemical sensing over the past two decades, tracing its progression from passive identification toward intelligent perception. We structure this technological trajectory around four core themes: sensitivity enhancement, specific recognition, multi-target visualization, and system intelligence. We first evaluate the fundamental limitations of direct detection techniques, such as THz time-domain spectroscopy (THz-TDS). Building on this, we examine how metamaterial-assisted architectures utilize high-quality-factor resonances to achieve trace-level detection, pushing the limits of detection (LOD) down to the ng/mL or even pg/mL scale, and how surface chemical functionalization provides a molecular lock mechanism for selective targeting in complex samples. Furthermore, we highlight the paradigm shift from single-point spectral measurements to spatially resolved multi-target imaging using pixelated metasurfaces. Finally, the review addresses emerging directions, including dynamically tunable intelligent metasurfaces, multimodal on-chip integration platforms, and the growing integration of artificial intelligence (AI) in inverse design and data interpretation, which achieves classification accuracies exceeding 95% even in complex matrices. By synthesizing these developments, this review provides a comprehensive perspective on the future trajectory of THz sensing technologies.