SERS substrates for sensing in pathology and physiology

Abstract

Monitoring physiological parameters such as pH at the site of a disease are important in determining the health status in patients. Current approaches are based on the analysis of arterial blood to measure systemic blood pH along with other parameters such as PO2 and PCO2, to allow assessment of gaseous exchange and ventilation efficiency. There has been a drive to develop improved sensors capable of continuous and dynamic monitoring of these aspects.

Optical sensing devices have gained popularity as they can be designed to incorporate inexpensive optical fibres and miniaturised and mass-produced detectors and LED-based light sources. In addition to monitoring pH in a clinical situation, the development of physiological sensing tools for use at a cellular level has been critical in being able to non-invasively assess cellular response to a host of insults be it drug treatment or other cellular modulation strategies. The move towards three-dimensional (3D) cell culture has become increasingly attractive as a mimic of the 3D architecture and gradients found in vivo. The development of spatially selective sensors capable of measuring these physiological features could provide a tool in understanding cell-drug responses.

In this thesis, multiple approaches were developed to enable SERS pH sensing based on both an optical fibre as well macroscopically entrapped SERS sensors applied as a means of observing extracellular pH within a 3D cell culture system. This included the use of pH responsive reporter molecules on nanoparticles (Chapter 2), their entrapment within macro-scale supports such as polymer beads and (Chapter 3), and paper (Chapter 4).