Novel Methods in Optical and Mechanical Biosensors

The commercialization of biosensing is driven by application. Toward this goal, many interesting physical phenomena inherent in biosensing platforms are de-emphasized in favor of a quantitative and repeatable assay. Such phenomena are often treated as a source of noise to be overcome, and, as the engineering of a platform is perfected towards a specific biodetection goal, the principles of these phenomena become obscured to those who employ it solely as a tool in pursuit of other matters. This is a ubiquitous pattern in science, perhaps the best examples of which are two most ubiquitous biotransducers: the optical surface plasmon resonance (SPR), and the mechan- ical piezoelectric quartz crystal microbalance (QCM). These two devices, the subject of the present work, both possess novel modes of operation which extend their versatility to other bio-relevant sensing applications. In the optical regime surface plasmon polaritons (SPPs) excited evanescently by light are by far the most popular label-free affinity biotransducer for monitoring bulk refrac- tive index changes. The sensitivity of SPR is primarily due to the field enhancement by SPPs on the sensor surface, however SPPs themselves also possess high spatial res- olution beyond the diffraction limit; a property typically absent as specific feature of the SPR sensorgram. In this work, it is shown that by considering optical speckle from single and multiply scattered SPPs inherent in the SPR signal itself, an entirely new set of information can be obtained descriptive of the underlying scattering microstructure. Furthermore, it is demonstrated that the motion and addition of single nanoparticles can be resolved in an unmodified SPR setup, whereby the breadth of SPR experiments may be extended to encompass both bulk sensing and discrete events on the nanoscale. Moving into the mechanical regime, the sensitivity, low cost, ease of use, and integrability have made the piezoelectric quartz crystal microbalance an ideal biotransducer for real time monitoring properties such as viscoelasticity, as well as an affinity sensor for mass adsorption. Naturally, these desirable features do not come without disadvantages: the underlying mechanical properties of the sample are often not revealed by the relative and stepwise changes in the QCM sensorgram, an issue complicated by choice of theoretical model. Here it is shown that application of controlled centrifugal forces in a QCM assay has a profound utility in revealing the underlying biomechanical properties of a sample. This centrifugal force quartz crystal microbalance concept works by modifying the QCM- sample coupling mechanism. Centrifugal force is demonstrated to be useful in not only to enhancing the sensitivity of a traditional QCM measurement, but also in obtaining the sample’s complex biomechanical properties repeatedly in situ and in real time.