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THz technologies are a powerful tool for label-free detection of biomolecules. However, significant reduction of the lower detection limit is required to apply THz-sensors in biomedical diagnosis. This paper reports an ultrasensitive THz-biosensor based on asymmetric double split ring resonators (aDSRR) for the direct label-and PCR-free detection of DNA at physiologically relevant concentrations. We introduce selective functionalization and localized electric field concentration to enhance aDSRR sensitivity and specificity. The sensor characteristics are demonstrated using the human tumor marker MIA in cDNA samples produced from total RNA without PCR-amplification. Measurements of DNA samples with concentrations as low as 1.55 × 10 −12 mol/l are presented.

Bioanalytical THz sensing techniques have proven to be an interesting and viable tool for the label-free detection and analysis of biomolecules. However, a major challenge for THz bioanalytics is to perform investigations in the native aqueous environments of the analytes. This review recapitulates the status and future requirements for establishing THz biosensing as a complementary toolbox in the repertoire of standard bioanalytic methods. The potential use in medical research and clinical diagnosis is discussed. Under these considerations, this article presents a comprehensive categorization of biochemically relevant analytes that have been investigated by THz sensing techniques in aqueous media. The detectable concentration levels of ions, carbohydrates, (poly-)nucleotides, active agents, proteins and different biomacromolecules from THz experiments are compared to characteristic physiological concentrations and lower detection limits of state-of-the-art bioanalytical methods. Finally, recent experimental developments and achievements are discussed, which potentially pave the way for THz analysis of biomolecules under clinically relevant conditions.

Metamaterials can be utilized for a variety of applications and have emerged as a valuable tool in THz technologies. Used as THz biosensors, metasurfaces can significantly improve the sensitivity in the detection of biomolecules, but the high THz absorption of water represents a major challenge for the realization of a sensor for measurements in liquids. In this article, we propose an approach where the resonance feature of complementary asymmetric split ring resonators (CASRR) is maintained even for measurements in water, allowing highly sensitive detection of biomolecules in strongly absorbing liquids. This is enabled by the introduction of substrate-integrated microfluidics, which are shown to have a minimal effect on the transmission properties of the metamaterial. Due to this approach, the metamaterial structure design is independent from the microfluidic channels. Our simulations also show that the sensitivity of CASRR changes only marginally for lossless and highly absorbing materials. At the same time, the presented concept is easy to fabricate by standard lithography methods and can be applied to other metamaterial structures as well.