Real-Time Analysis of Molecular Conformation Using Silicon Electrophotonic Biosensors

Silicon microring resonators are widely used as optical biosensors because of their high sensitivity and promise of low-cost mass-manufacturing. Typically, they only measure the adsorbed molecular mass via the refractive index change they detect. Here, we propose and demonstrate a silicon microring biosensor that can measure molecular thickness and density as well as electrochemical activity simultaneously, thereby enabling quantification of the conformation of surface-immobilized biological and molecular layers in real time. Insight into the molecular conformation is obtained by recording the resonance shift from two geometrically distinct ring-resonators connected to a single access waveguide. The resonant cavities both support a single TE polarized optical mode but have different widths (480 and 580 nm); the extent of their evanescent fields is thus very different, providing different depth-resolution of the interaction with a molecular layer on the sensor surface. By combining the optical shift from these two measurements, we demonstrate unambiguous quantification of the thickness and the refractive index of a molecular layer assembled on the waveguide. The precision of the technique is 0.05 nm and 0.005 RIU in the molecular layer thickness and refractive index, respectively. We demonstrate the cascaded electrophotonic ring resonator system using two exemplar systems, namely, (a) physisorption of a bovine serum albumin monolayer and (b) an electroactive DNA oligonucleotide hairpin, where we uniquely show the ability to monitor electrochemical activity and conformational change with the same device. This novel sensor geometry provides a new approach for monitoring the conformation and conformational changes in an inexpensive and miniaturized platform that is amenable to multiplexed, high-throughput measurements.