Ultrasensitive marker-free biomolecular THz-detection for tumor related analytics: PCR-free sensitivity, biomolecular extension and biological relevance

Genomics and proteomics hold promise to revolutionize future health care, targeting profound novel visions like predictive, preventive and personalized medicine. The enormous advance in these fields is closely coupled to the development of powerful, reliable and efficient methods to detect, identify and analyze biomolecules and their complex interaction networks. In the last decades techniques have continuously improved, providing a plethora of information for biomolecular function. The current progress changes from “observing” dependencies, towards “understanding” mechanisms in their full interaction network. This clearly shows that new analytic tools with enhanced capabilities still need to be developed.

THz technologies have demonstrated a huge potential to investigate and detect biomolecular systems, as macromolecular modes and biomolecular interactions are resonant in this frequency range. This is paving the path to label-free bioanalytic sensing. The goal of this project is the fundamental expansion of biomolecular sensing with electromagnetic (EM) radiation in the THz frequency range. Herein, three aspects are of primary interest:

  • Sensitivity enhancement by 2 to 3 orders of magnitude towards PCR-free direct detection,
  • Extension of the label-free sensing application from DNA sensing towards further molecular systems,
  • Detailed evaluation of the quantification capability and biological relevance of such analyses.

This activity sets upon previous label-free THz DNA activities which have already enhanced sensitivity by 8 orders of magnitude down to an unsurpassed sub-femtomol detection level.

In order to focus this research activity and validate the application relevance of these developments, all analysis will concentrate on tumor related biomolecular sensing applications. Especially in this field, it is becoming increasingly clear, that the traditional scientific approach attempting to reduce cellular function to individual components (e.g. biomarkers) and signal transduction pathways is insufficient. It is nowadays increasingly evident that the behavior of biological systems, especially those affecting tumors, cannot be attributed to a single molecule or pathway, as they emerge as a result of interactions at multiple levels. In this project it will be analyzed and validated quantitatively if THz sensors based on frequency selective surfaces can provide such a multilevel biomolecular detection capability.

The project is part of the DFG (German Research Foundation) founded SPP 1857 ESSENCE (Electromagnetic sensors for life sciences). Further information is available on the project website.

Electronic measurement setup operating at 280GHz for detection of DNA-DNA interactions.
Partial loading of the sensor surface with the probe material.