Recent advances have suggested that the ‘nature’ and ‘extent’ of affinity interaction between bare metal surface (i.e., gold, platinum, etc) and biological molecules (e.g., DNA, RNA, proteins) depends on the molecular structures and three-dimensional (3D) conformations of the adsorbents, and follows conventional physisorption and chemisorption mechanisms. Thus, this affinity interaction can be used to distinguish two structurally or conformationally different biomarkers. This is the basis of the ‘interfacial nanobiosensing’- a method by which one could directly detect two structurally or conformationally different biomolecules. For example, during disease progression, genomes usually undergo considerable changes in their structure and 3D conformation as compared to their normal (i.e., healthy) stage. The adsorption (affinity) of these two genomes towards a bare-gold electrode is significantly different. Via accurate detection of this adsorption, one can easily detect the disease.
Our 2014’s ‘eMethylsorb’ work was the first report based on this concept, where we used the affinity interaction of epigenetically different two DNA sequences towards gold electrode to quantify the level of DNA methylation. More recently, we used this novel concept to develop a unique method for detecting a universal cancer biomarker referred to as ‘MethylScape’. This sensing concept gave a completely new dimension to the field, and attracted massive interest to the biosensing community as it can overcome all major technological drawbacks in current biosensing approaches. It uses direct adsorption of target biomarkers on a bare gold electrode/surface rather than the conventional approach of using recognition and transduction layers in hybridisation or immunoassays based biosensors. This is a substantial invention because it substantially simplifies the method by avoiding the complicated chemistries underlying each step of the sensor fabrication thereby significantly reduce the analysis time and assay cost.
The ‘interfacial nanobiosensing’ approach now serves as the foundation for a research program in Shiddiky Laboratory, where they used the affinity interaction between the bare metal electrode and disease-specific biomolecules as a tool for analysing a range of genetic, epigenetic, and proteomic biomarkers in cancer and other diseases.