The Evolving Landscape of Terahertz Biosensing: From Sensitivity to Precision

Clinical Snapshot

Key Findings

• P Value: Not reported at the review level

• Effect Size: Not applicable — no meta-analytic effect size calculated; individual study performance metrics are described narratively without aggregation

• Primary Outcome: Narrative summary of THz biosensing platform capabilities for biomacromolecule detection, including refractive index sensing and molecular fingerprint recognition; no pooled primary outcome reported

• Nnt Or Sensitivity: No pooled sensitivity, specificity, or diagnostic accuracy metrics reported; individual studies within the review may report detection limits and sensitivity values for specific analytes, but these are not synthesised

• Confidence Interval: Not reported at the review level

Clinical Application

Clinical feasibility remains low at present. THz biosensing requires specialised equipment (THz time-domain spectrometers, quantum cascade lasers, metamaterial substrates) that is expensive, technically demanding, and not yet miniaturised for point-of-care use. Integration into clinical laboratory workflows would require substantial regulatory approval, standardisation, and health technology assessment. The review acknowledges the need for a standardised workflow but does not provide implementation evidence. No THz-based diagnostic devices are currently listed on the Australian Register of Therapeutic Goods (ARTG) or approved by the Therapeutic Goods Administration (TGA) for clinical use. The technology is not referenced in current RACGP clinical guidelines or MBS item descriptors. PBS listing is not applicable at this stage. Australian research institutions (e.g., CSIRO, university physics departments) are active in THz research, but clinical translation remains distant. Australian clinicians should regard THz biosensing as an emerging research technology requiring prospective clinical validation before any practice integration is considered. Currently applicable only in research laboratory settings for proof-of-concept biomacromolecule detection. Potential future populations include patients requiring label-free, non-destructive molecular diagnostics (e.g., cancer biomarker detection, pathogen identification, protein conformational analysis). No validated clinical population has been defined in this review.

Abstract

Terahertz (THz) spectroscopy has recently gained significant attention as a powerful tool for biomacromolecule detection due to its exceptional sensitivity in capturing molecular fingerprints, attributed to its unique wavelength range. THz biosensing platforms offer distinct advantages in identifying molecular rotational and vibrational states, making them effective for high-sensitivity, high-precision biomacromolecule analysis. This review highlights recent advancements in THz biosensing platforms, focusing on their spectroscopy interpretation and practical applications. We begin by introducing commonly used THz equipment and various metamaterials, followed by an overview of the key spectroscopy interpretation strategies for THz spectral analysis, including refractive index sensing and molecular fingerprint recognition. We also summarize the machine learning (ML) methods applied to enhance spectral analysis in THz biosensing platforms. Lastly, we provide an integrated perspective on the spectroscopy interpretation, clinical applications, and recent technological advancements in THz biosensing platforms, with an emphasis on how to construct a standardized THz-based biosensing workflow. We believe THz biosensing platforms hold immense potential to revolutionize molecular detection by enabling precise, label-free, and highly sensitive analysis of biomacromolecule interactions, paving the way for breakthroughs in medical diagnostics, environmental monitoring, and biochemical research.

References

1. 1.Xu, C., Yang, T., Li, X., Zhang, Z., Yang, H., Zhan, H., Lou, J., Sun, L., Yang, R., & Min, L. (2026). The evolving landscape of terahertz biosensing: From sensitivity to precision. ACS Applied Materials & Interfaces. https://doi.org/10.1021/acsami.6c08153