Introduction
Biomolecular sensing is an extremely attractive area for terahertz technology, since many characteristic spectral features of biomolecules can be found in the THz frequency range which offer the fundamental possibility of label-free biomolecule detection. However, the large amount of (identical) sample material which is needed for a sufficient contrast - if usual diffraction-limited (far-field) spectroscopy approaches are used - has been identified as a major problem very early [Brucherseifer et al. 2000].
A first demonstration to drastically reduce the required amount of biomolecules succeeded in 2002 using the near-field environment of a single waveguide-embedded THz resonator for the detection of short DNA strands [Nagel et al. 2002]. A natural next step has then been the multiplication of sensor elements in form of resonator arrays in order to inrease the number of molecules which could be detected on one sensor chip [Janke et al. 2005]. The simplicity of using THz radiation to excite and read-out resonator arrays [Debus et al. 2007] instead of using guided modes on multichannel on-chip spectroscopy structures has then triggered a lot of research into this direction. However, sensitivity has been lost again because of the restrictions of far-field detection requiring sensor ensemble instead of single-resonator read-out. Nevertheless, tremendous progress has been made on the resonator side by e.g. increasing quality-factors [Yan et al. 2021] or local field-enhancement behavior [Xie et al. 2015] to re-increase the sensitivity again to some extend.
Latest advances
Now a consortium of researchers from Sungkyunkwan University, the MIT and the University of Minnesota have successfully demonstrated in a joint initial work the spectrally selective detection of some exemplary biomolecules at dramatically improved sensitivity into the sub-picogram range (meaning an increase of "10 orders of magnitude compared to far-field THz measurements with pelletized samples"). This breakthrough in sensitivity enhancement has become possible by combining dedicated field-enhancing structures and THz sub-wavelength imaging employing a TeraCube imaging system. While still using simple far-field excitation the response of a single resonator loaded with biomolecules can be monitored with this method instead of only large ensembles as before. The obtained sensor response from this approach called STRING in the original article ("Subwavelength Terahertz Resonance Imaging") not only includes spectral but also spatial information of the generated resonance modes under molecular influence which may be helpfull to increase the selectivity further in the future.
Reference to Journal article in Nano Letters: https://doi.org/10.1021/acs.nanolett.2c04610
Reference to SKKU (CINAP) Institute homepage: https://www.ibs.re.kr/cinap/