Chiral colorimetric sensing of cardiovascular biomarker with smart plasmonic DNA nanoswitches

Abstract

Rapid and sensitive detection of biomarkers is crucial in diagnostics, especially for diseases that require early diagnosis and management, such as cardiovascular diseases (CVDs). This thesis aims to demonstrate a novel biosensing approach using reconfigurable chiral plasmonic nanoswitches for chiral colorimetric sensing of the common biomarker for myocardial infarction, cardiac troponin I (cTnI). Furthermore, the universality of the nanoswitch and the potential for multiplex sensing is illustrated. Nanoswitches are engineered to undergo a configurational change in the presence of the target analyte, leading to a change in chirality and thus chiroptical properties. The change is both measurable with CD spectrometry and visible as the color and intensity change of the solutions containing the nanoswitches.

The methods of this thesis include the fabrication of the nanoswitches as well as the incorporation of biorecognition elements. The nanoswitches were fabricated using scaffolded DNA origami as a template for the assembly of two gold nanorods into chiral plasmonic nanostructures. The biorecognition elements were incorporated into the DNA origami structure. Both single-stranded DNA aptamers and antibody fragments were evaluated as biorecognition elements to target cTnI proteins. Furthermore, multiplex sensing was demonstrated with well-defined neutravidin-biotin and digoxigenin–anti–digoxigenin interactions.

The results suggest further work with the development and characterization of cTnI detection. However, the biosensing platform showed great potential for biosensing due to its universality and potential for multiplex sensing. In conclusion, the sensing methodology with chiral plasmonic nanoswitches reveals a new potential biosensing platform for rapid point-of-care testing.