Nanoplasmonic Biosensing - Exploring Unique Possibilities

Doctoral thesis, 2010

Bioanalytical sensors are indispensible tools in medical diagnostics and drug discovery as well as for life science research, environmental monitoring and food safety. In essence, they are used to detect and determine the concentrations of specific biomolecules in complex mixtures. In this work, challenges of current technologies are addressed using biosensors based on the peculiar optical properties of metal nanostructures and in particular, the sensitivity of these nanoplasmonic properties to changes in the refractive index of the surrounding environment. The main focus has been to explore unique possibilities provided by nanoplasmonic sensors. This includes utilizing the tight confinement of the sensitivity to the surface to investigate structural biomolecular changes. Nanoplasmonic structural sensing was further investigated using combined nanoplasmonic and quartz crystal microbalance (QCM) measurements. This was conducted using a thin gold film perforated with nanoholes, which served as both the nanoplasmonic sensor and one of the electrodes of the QCM sensor. Even with the most sensitive surface-based sensor, molecules can only be detected if they reach the surface and bind. In fact, the transport of molecules to the sensor surface can be a limiting factor for the performance of a biosensor. Ways of improving mass transport were investigated by (i) flow-through sensing using nanoplasmonic pores and (ii) directed binding to high-sensitivity nanoscale regions using materials-specific surface modifications. Both concepts were shown to enable a reduction in the sensor response time of more than one order of magnitude compared with conventional diffusion-limited binding. Finally, one reason for the potential of nanoplasmonic sensors stems from their competitive performance combined with relatively simple instrumentation and the possibility for scalable and low-cost fabrication. Steps towards a portable nanoplasmonic sensor device, for example to be used for medical diagnostics at point-of-care, were taken by integrating the opto-electrical conversion directly on the sensor chip. This was achieved by designing the nanoplasmonic sensor structure on an array of photoactive diodes. By simple means, specific protein binding could be detected in a label-free and real-time format through changes in the photocurrent output.