M.Sc Thesis


M.Sc StudentShapira Nofar
SubjectEvaluation of Ionic Liquids for Improved Single-Molecule
DNA Detection in Solid-State Nanopores
DepartmentDepartment of Biomedical Engineering
Supervisor PROF. Amit Meller
Full Thesis textFull thesis text - English Version


Abstract

In the past few decades, solid-state nanopores (ssNPs) have been the subject of intense study of many research and industrial groups around the world, owing to their fast and cost-effective single-molecule detection capability. Specifically, this capability makes them ideal candidates for medical applications requiring biomolecular characterization, detection of epigenetic markers, genotyping and sequencing. The performance of ssNPs is particularly influenced by two parameters: the translocation time and ionic current drop during the passage of a biomolecule through the ssNP, which affect the temporal resolution and SNR of the system, respectively. These two parameters are in turn influenced by the conductivity and viscosity of the electrolyte solution in which the NP is immersed. However, while high viscosity increases the translocation time hence improving the temporal resolution, it also decreases the mobility of the ions in the nanopore, reducing the solution conductivity, and reducing the current drop. This trade- off is a fundamental limitation of ssNPs sensors that use conventional electrolytes such as potassium chloride (KCl) or sodium chloride (NaCl). Here, we propose to replace these electrolytes with highly conductive and highly viscous ionic liquids (ILs) to

significantly increase the translocation time without severely compromising the SNR.

Here, we propose a novel hybrid configuration composed of a conventional electrolyte in the negatively biased chamber (cis) and an IL in the positively biased chamber (trans) and investigate its performance, comparing to the performance of conventional ionic solutions, by using numerical simulations and experiments. We present a new generic numerical model developed to evaluate ion concentration profiles, relying on the physiochemical properties of the two electrolytes. Subsequently, the model calculates the parameters of the system using well-known analytical equations that describe the behavior of ssNPs. The model was validated in a series of experiments performed with Tetrakis(hydroxymethyl)phosphonium chloride (THPC) and a conventional electrolyte (KCl). Overall, we predict an improvement of one order of magnitude in the translocation time when using our proposed hybrid configuration. These results suggest that ILs are beneficial and perhaps even essential for ssNP applications that have demanding requirements on temporal resolution.