I’m currently conducting an experiment in which I capture amplified genomic DNA on nanoparticle surface at electrode surface, then load ruthenium solution onto the electrode to measure the DPV signal. Theoretically, if there is more gDNA, more ruthenium complexes should bind, resulting in a higher current signal.

However, in my experiments, the DPV current from the gDNA@AuNP samples is consistently lower than that of the Primer@AuNP control.

I’ve tried various approaches—such as using different DNA concentrations, adjusting nanoparticle sizes, etc.—but the signal difference remains minimal. Interestingly, when I replace gDNA with a shorter cDNA fragment (e.g., a COVID gene), the signal behaves as expected and is higher than the control.

I suspect the issue might be due to the length of the gDNA—possibly causing spatial or electrostatic hindrance that prevents the ruthenium from effectively reaching or intercalating with the DNA near the electrode. However, I’m not entirely sure. For reference, the nanoparticles are captured on the electrode surface, and the measurement is then taken via DPV.

My questions are:

Any suggestions or insights would be greatly appreciated. Thank you!