Duplexed aptamers and fiber optic SPR sensors to enable continuous biosensing

Promovendus/a: Annelies Dillen

Promotor(en): Prof. dr. ir. Jeroen Lammertyn, Prof. dr. ir. Wouter Saeys

Biomarkers are measurable analytes that predict specific biological conditions. As the practice of biomarker monitoring therefore enables diagnosis, intervention, and quality control, this has become standard practice in various fields such as health care, environmental analysis, biotechnology, and food and beverage production. For example, in healthcare, biomarkers are often used for the diagnosis of various diseases including cancer, autoimmune diseases, inflammation, sepsis, or infections. However, the practice of biomarker monitoring currently requires various tedious and time-consuming steps, including sampling, sample transportation, pretreatment, analysis, and data output. This limits the possibilities for rapid diagnosis and intervention, which can negatively affect the final outcome (e.g. a decreased chance at survival). This can be overcome by applying continuous biosensors, which provide real-time information about the respective biomarker concentrations, and thereby enable direct and even feedback-controlled intervention. Unfortunately, these biosensors are still in their infancy, as various requirements need to be met in order to achieve this goal.

Therefore, the aim of this dissertation was to develop a novel method for continuous biomarker monitoring, to enable rapid diagnosis and intervention in the future. To do this, optical fiber-based sensors were combined with ‘DNA switches’. More specifically, DNA cannot only be used to store genetic information, but can also be used to specifically recognize certain biomarkers, and even to convert this recognition directly into a quantifiable and reversible signal. In this work, by using these functionalities, ‘DNA switches’ were developed which induced the movement of gold nanoparticles in presence of the biomarkers of interest. This movement could be picked up by the optical fiber-based sensors, so the concentration of the biomarkers could be monitored in real-time. It was demonstrated that with this concept (i) a quantitative, amplified and reversible signal could be achieved, (ii) various target molecules could be detected with a high sensitivity, and (iii) measurements could be performed in relevant samples. Altogether, the results demonstrated that the proposed concept in which ‘DNA switches’ were combined with optical fiber-based sensors is a suitable strategy for continuous biomarker monitoring, which will enable rapid diagnosis and intervention in the future.