Terahertz-Biosensorik: Metamaterial-basierte THz-Sensoren für biomedizinische Anwendungen

The COVID-19 pandemic has shown that rapid and sensitive test methods for the detection of viruses and biomolecules are important tools in medical laboratory diagnostics. With the dynamic development of the infectious event and great efforts in research and development, enormous progress has been made in the field of mRNA vaccine development and in the introduction of personalized testing methods, from which classical analytical methods could also benefit. However, it has become impressively clear that conventionally used laboratory-based diagnostic methods are complex and time-consuming processes that constitute a major challenge for medical care in the dynamic environment of a pandemic. Thus, it is becoming increasingly apparent that new analytical tools with increased analytical speeds and expanded application ranges need to be developed to advance future understanding of disease mechanisms or drug action. Due to the existence of biomolecular resonances in the terahertz (THz) frequency range, there has been a great interest in studying biomolecules using THz technologies since the 2000s. The use of field-enhancing structures such as metamaterials can significantly increase their sensitivity, giving THz biosensors the potential to reach physiologically relevant concentration ranges and thus making them promising candidates for the development of new testing methods.
This work presents a THz sensor based on metamaterials in the form of a complementary split ring resonator (CSRR) developed for biomedical applications. The CSRR produce a sharp resonance in the transmission spectrum, which is shifted to a lower resonance frequency in the presence of a dielectric loading. This mechanism can combine the advantages of existing classical THz analyses, such as label-free and rapid detection of biomolecules, with a significant increase in sensitivity and selectivity. In addition, the biosensor can be specifically adapted for the detection of a biomolecule by scaling the geometric dimensions. The polarization properties of the biosensor also allow the additional integration of microfluidic structures for measurements in liquid environments. These are fundamentally challenging for THz analyses due to the high absorption in water, requiring the use of thin liquid films or microfluidic structures.
In this work, an extremely high sensitivity of the THz biosensor in the detection of complementary DNA (cDNA) samples obtained from the human melanoma cell line MIA is demonstrated compared to previously published results, but without performing a usually required amplification of the DNA (polymerase chain reaction, PCR). Further experiments also demonstrate that the shift in resonance frequency differs for single- and double-stranded DNA and is also dependent on the resonance frequency of the sensor. A detailed review of biomolecular THz analyses in liquid environments is provided, and a conceptual development and analysis for studies using metamaterial-based THz biosensors with analytes in liquid environments is presented, describing the introduction of a microfluidic structure integrated into the substrate. In addition, the development of measurement technology and design concepts necessary for the realization of THz biosensors is described in detail. Finally, the potential for the development of metamaterial-based THz biosensors is discussed and an outlook for possible future developments is given.