Graduation Semester and Year

Summer 2024

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering

Department

Bioengineering

First Advisor

George Alexandrakis

Abstract

In this dissertation I have studied a novel single-molecule nanosensor that integrates a Solid-State Nanopore (SSNP), milled in silicon nitride with a Double Nanohole (DNH) nanoaperture, milled in gold. This device leverages Self-Induced Back-Action (SIBA) for optical trapping with ssNP electrical sensing and is called the SIBA-Actuated Nanopore Electrophoresis (SANE) sensor. My lab has previously shown that simultaneous acquisition of bimodal optical and direct current (DC) electrical signatures enables more detailed characterization of nanoscopic analytes compared to using electrical data alone, which are typically collected by ssNP sensors. In this work I have first studied by COMSOL Multiphysics simulations the interplay between optically and electrically driven forces acting on 20 nm silica nanoparticle trapped by the SANE sensor, with the aim of understanding the range of experimental conditions leading to nanoparticle trapping and generating the observed optical and electrical signals. Subsequently, I have used COMSOL Multiphysics simulations to study the feasibility of extending SANE sensing capabilities by adding AC signal modulation on top of the baseline DC voltage. The AC simulations explored the relative contributions of plasmonic and electrical fields to the observed electrical conductance changes and phase shifts induced by the optical trapping of a 20 nm silica nanoparticle at the SANE sensor. Experimental data were analyzed for 20 nm silica nanoparticles under both DC and AC SANE sensing conditions and were matched to the COMSOL Multiphysics computational parameters as closely as possible. Computational predictions for both DC and AC conditions aligned well with the observed experimental data trends. Importantly, the AC sensing approach indicated the feasibility of identifying an optimal frequency that allows a significant amount of current to travel through, and hence probe, the interior of a nanoparticle. This pilot work highlights the future utility of AC SANE sensing as an ultrasensitive means of probing the interior of nanoparticles loaded with drug or gene therapeutics, enabling ultra-sensitive quality control of nanomedicines.

Keywords

Single-Molecule, Nanosensor, Simulations, Optical and Electrical Sensing, Fabrication, COMSOL, Electric Field, Electroosmotic Force, Electrophoretic Forces, Resultant Forces, Skin Effect

Disciplines

Bioimaging and Biomedical Optics | Biomedical Devices and Instrumentation

License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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Available for download on Monday, June 16, 2025

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