Thesis assignments

Nanomechanical sensing of circulating tumor DNA

Nanomechanical biosensors are promising candidates for the early detection of several types of cancer in bodily fluids such as blood, urine or other bodily fluids. Hypermethylated DNA in urine has been shown to have a 100% diagnostic sensitivity for bladder cancer. Inorganic Materials Science (IMS, prof. Rijnders) has developed a sensing platform based on piezoelectric nanomechanical resonators for DNA. Currently IMS cooperating with Molecular Nano Fabrication (prof. Huskens) within the Nanopil 2.0 project to develop the chemical functionalization using self-assembled monolayers (SAMs).

Recent experiments to functionalize the sensor have generated mixed results, such as unrealistic magnitude, varying response of parallel experiments and from experiment to experiment. A range of effects are expected to play a role, such as humidity of environment, concentration of the analyte, sensor geometry, functionalization geometry, non-specific interactions such as the deactivation of the SAM by the non-complementary DNA control step. We designed a set of experiments that could shed more light on the involved interactions influencing the sensing process.

Nanopill detecting DNA in the in the GI tract

In this project, investigate the functionalization sequence: 1) thiol single-strand DNA on gold surface, 2) hybridization using a complementary single strand DNA. A anti-fouling will be added before or after the functionalization sequence. We use the fluorescently labeled self-assembled monolayers to verify the areal density of the SAMs and using non-complementary DNA control. Also different temperature will be used to minimize the non-specific hybridization at elevated temperatures (~70 degrees C). By studying frequency shift of the sensor, the stiffness and mass of the SAM can be studied individually, using the fact that the tip of the nanomechanical cantilever is expected to be more mass responsive while on the base they are more stress responsive. The project will be directed as the insight progresses.

Ruud Steenwelle,