Small molecule detection in solution via the size contraction response of aptamer functionalized nanoparticles

We demonstrate a simple new sensor design that exploits aptamer functionalized nanoparticles (NPs) to transduce the signal of aptamer receptors binding to target small molecules. An aptamer capable of binding to our target 17β-estradiol (E2) was isolated by SELEX with dissociation constant of 50 nM and tethered to the surface of carboxylated polystyrene NPs. Upon exposing the aptamer functionalized NPs to E2 in buffered water, we use dynamic light scattering (DLS) and resistive pulse sensing (TRPS) to observe a distinct reduction of the conjugated particle size and a less negative zeta potential, which can be correlated to the E2 concentration in the lower nanomolar range. The sensor showed similar affinity towards other hormones of the E2 steroidal family and excellent discrimination against potential non-steroidal interfering agents. The simplicity of the sensing scheme makes it readily applicable to other low molecular weight targets, as we further demonstrate using a known adenosine aptamer. In addition to sensing, our method shows potential to guide the synthetic evolution of aptamers with better binding affinity and specificity.