Monolithic CMOS photoluminescence lifetime microsensors for oxygen concentration measurement

The oxygen partial pressure within a cancer tumour is a key factor which determines the prognosis and the effectiveness of cancer treatments; particularly radiotherapy. Due to the unregulated growth of cancer cells, the supporting vasculature is incapable of supplying the entire tumour. This leads to inhomogeneities that vary both spatially, as some parts of the tumour are not serviced by the blood supply; and temporally as the vasculature formed can be temporary and disappear and reform due to a number of factors. The lack of oxygen within a tumour is known as hypoxia wherein a cell - or in the case of a cancer tumour, a grouping of cells - is devoid of oxygen due to a lack of blood supply. The ability to measure and monitor the levels of hypoxia within a cancer tumour is thus important to ensure that cancer treatments are given at periods of maximum efficacy wherein hypoxia is least present. Measurement of tumour hypoxia is currently typically achieved through the use of one-off imaging methods such as PET or MRI scans and thus cannot be used for continuous monitoring. The Implantable Microsystems for Personalised Anti-Cancer Therapy (IMPACT) project aims to allow continuous monitoring of the tumour microenvironment via miniaturised oxygen sensors, with the main focus being the use of electrochemical sensors. As driven by the main goal of the IMPACT project, this PhD work presents the development of a novel microsensor integrable and manufactured with standard CMOS fabrication technologies capable of monitoring of oxygen concentrations via measurement of the photoluminescence (PL) emission lifetime of oxygen-sensitive luminophores. Three iterations of CMOS microchips were developed in the High-Voltage austriamicrosystems 0.35 µm technology node over the course of the PhD to reach a functioning photoluminescence lifetime microsensor (PLµS); with each chip contributing to a better understanding of the overall PLµS design. The developed PLµS chip is the first-of-its-kind monolithic photoluminescence microsensor. It consists of silicon light emitting diodes (SiLED) for PL excitation, silicon photon avalanche diodes (SPAD) for detection of the emission, and the associated switching and driving circuitry required for PL lifetime measurement. This developed PLµS pixel is 125×125µm2 and can be modularly added to other CMOS microsystems in the same process. To functionalise the PLµS for oxygen concentration measurements, platinum octaethylporphyrin (PtOEP) is immobilised in polystyrene to form an oxygen sensitive PL material which is deposited directly onto the PLµS. This work demonstrates the capability of the PLµS to measure the photoluminescence lifetimes of the PtOEP-PS film when exposed to gaseous oxygen concentrations of 0% to 21%. While all PLµS measurements were done ex-vivo, the tested concentration ranges cover all possible physiologic oxygen concentrations including those associated with tumour hypoxia. Continuation of this work would be the use of the PLµS for testing of biological samples, and the extension of the capabilities of the PLµS pixel itself for the measurement of other optical biomarkers.