Advanced Nanofabrication for Novel Plasmonic Biosensors

Abstract: There is an increasing interest in the development of novel biosensors in the foreseeable future. The impact on society of diseases connected to the aging of population, for example infectious diseases, cancer and Alzheimer’s disease, has the potential of increasing the running costs of welfare over a sustainable threshold already within a few years. Early diagnostics and pointof- care testing will play a fundamental role in achieving a cost-effective health-care capable of satisfying the increasing needs. This translates into a drive towards further improved diagnostic devices where miniaturization and enhanced performances enabling detection of low-abundant biomarkers is expected a key component. In this thesis work, the aim has been to translate advanced nanotechnology fabrication processes to novel biosensor platforms which could address some of the key issues just presented above. In order to achieve this, a sensing principle suitable for employment in miniaturized devices is necessary. In this work, we exploited the sensitivity of the optical properties of metal nanoparticles to changes in refractive index of the surrounding environment. Such nanoplasmonic structures enable a transduction of biorecognition events occurring within a few tens of nanometers from their surface into a detectable optical contrast, or color. The inherent flexibility of nanofabrication processing combined with the size and simple instrumentation of nanoplasmonic based transducers allows for a wide variety of potential applications. In this work, two novel biosensing platforms were developed addressing two different challenges: on the one hand, the development of a portable and simple device for point-of-care diagnostics, and on the other hand, a sensor with potential to effectively tackle the challenge of detecting low-abundant analyte in small volumes. In the first case, the sensor and detector elements were integrated into the same chip by fabricating gold nanostructures directly onto photodiodes. In this way, biorecognition events could be directly transduced into electric signals via shifts in the photocurrent generated by the detectors. The sensor was tested by detection of specific protein binding in a custom made flow cell. In the second case, steps towards the development of a biosensing platform for detection of low concentration of biomarkers in small volumes were taken by developing a fabrication process which integrates gold nanoplasmonic structures in a nanofluidic network. By locating the sensor elements directly into nanofluidic channels, target molecules can be efficiently transported from the bulk to the sensor surface. We believe that this could enable combined high capture efficiency, short detection time and low sample consumption even at low concentration of analytes.