Sensing voltage dynamics with differential intensity surface plasmon resonance system

The voltage sensitivity of surface plasmon resonance is investigated as a potential method for label-free detection of the dynamics of the transmembrane potential of excitable cells. Development of such a method for reliable detection of these signals is one of the modern challenges in biomedical research. Since they are key physiological signals that control a number of vital functions, they report the system's behaviour in health and disease. Labelling methods are currently used to detect these signals, often with subcellular resolution, but fluorescent labels (i) have a short lifetime, which limits the timescale of the experiments and (ii) they can be toxic to cells. Surface plasmon resonance (SPR) is sensitive to perturbation of the potential at the metal-electrolyte interface. This perturbation alters the charge density of the interface, which is characterised by the well-known theory of the double-layer capacitance. Charge density on the electrolyte side is mirrored by an excess or deficiency of electrons at the metal surface. The latter shifts the resonance conditions of surface plasmons. To assess SPR capacity in the detection of the electrical signals from excitable cells, the limit of voltage detection of the SPR has to be well-characterised. First, theoretical approaches were used to estimate the voltage detection limit of surface plasmon resonance. Since different SPR systems are characterised by their refractive index sensitivity, voltage sensitivity was estimated relative to the equivalent refractive index change. This approach enables the generalisation of the outputs of this research regardless of the SPR system. A one-dimensional multilayer model was used combining the electrical properties of the metal-electrolyte interface to the optical properties of the layers. The model was used to calculate the voltage-induced changes to the optical properties of the metal surface. Then, light reflectivity from the model structure was calculated using the transfer matrix of the structure and Fresnel equations to produce SPR curves (reflectance versus angle of incidence) for a series of voltages in the double-layer charging range (_200mV). Second, to test the theoretical estimates of the voltage sensitivity of surface plasmon resonance, a differential-intensity surface plasmon resonance (DI-SPR) system was constructed and combined with an electrochemical system to control the potential at the metal-electrolyte interface. The detection limit of the system is in the range of 3 _ 1