Performance of an aptamer-based neuropeptide Y potentiometric sensor: dependence on spacer molecule selection

Neuropeptide Y (NPY) plays a central role in a variety of emotional and physiological functions in humans, such as forming a part of the body′s response to stress and anxiety. This work compares the impact of MCH and PEG spacer molecules on the performance of a potentiometric NPY sensor. An NPY-specific DNA aptamer with thiol termination was immobilized onto a gold electrode surface. The performance of the sensor is compared when either an MCH- or PEG-based self-assembled monolayer is formed following aptamer immobilization. Backfilling the surface with alkanethiol spacer molecules like these is key for proper conformational folding of aptamer-target binding. Non-specific adhesion of NPY to the MCH-based sensor surface was observed via surface plasmon resonance (SPR), and then confirmed via potentiometry. It is then shown that PEG improves the sensor′s sensitivity to NPY compared to the surfaces with an MCH-based SAM. We achieve the detection of picomolar range NPY levels in buffer with a sensitivity of 36.1 mV/decade for the aptamer and PEG-based sensor surface, thus demonstrating the promise of potentiometric sensing of NPY for future wearable deployment. The sensor′s selectivity was also studied via exposure to cortisol, a different stress marker, resulting in a 13x smaller differential voltage (aptamer-specific) response compared to that of NPY.