Advanced nanomaterial-empowered optical molecular biosensing platforms: towards detection of biomolecular profiles in complex biological matrices
File(s)
Author(s)
Kim, Nayoung
Type
Thesis
Abstract
To successfully monitor disease, accurate detection is essential. Tools that can better enable sensitive and reliable monitoring of a changing biomolecular landscape composed of DNA and proteins through to small molecules such as metabolites, in complex environments hold great value in the area of cancer diagnostics in particular. The use of nanostructures in diagnostics has been promoted as a next-generation diagnostic paradigm opening up a huge variety of new approaches to tackle these challenges. Optically sensitive nanoscale architectures are well suited to probe biological phenomena where their response can often be influenced by a single molecular interaction. While this is useful for sensitivity, it also creates challenges where competing biomolecules can contribute significantly or even dominate responses. Creating approaches to reduce the impact of this while providing the opportunity to generate information about multiple endogenous biomarkers through the optical properties of nanomaterials is the focus of this work. The platform technologies proposed in the thesis aim to establish nanomaterial-empowered strategic molecular biosensing that accurately identifies and detects the dysregulation of biomolecular profiles within complex biological matrices such as (undiluted) biologically derived fluids and cellular environments. The rational designs of nanoscale architectures; strategic sensing principles; and elegant data processing and interpretation strategies are highlighted. Several practical challenges that have previously limited the accuracy of optical nanobiosensors in complex biological matrices, mainly associated with signal overlaps from competing biomolecules and background interference, are effectively circumvented in the presented works in both label-free and labelled approaches.
This thesis presents two strategic designs for optical nanobiosensing platforms towards in vitro and intracellular molecular diagnostics by employing surface-enhanced Raman scattering (SERS) and Förster resonance energy transfer (FRET) as the core means of signal transducing. The first research focus demonstrates an artificial-nose-empowered platform for in vitro diagnostics based on an array of plasmonic SERS substrates fabricated by lithographic techniques, whereby the increased amount of information enables to accurately identify biological samples in a label-free, wash-free, and targeting-free regime. The second research focus presents a highly programmable aptasensor nanoprobe, formulated by enzymatic amplification-driven self-assembly of DNA-inorganic hybrid nanocomposites. Leveraging the sequence-encoded multifunctionalities, the designer probe is capable of being selectively internalised into target cells and performing FRET-based ratiometric detection of intracellular endogenous biomolecules. The designs presented in this thesis, demonstrated in proof of principle, propose elegant approaches of optical nanobiosensing both in label-free and labelled formats towards in vitro biological sample identification and direct monitoring of the dysregulated biology within intracellular environments at the site of disease. It is envisioned these strategies will open up a wide-ranging potential of molecular nanodiagnostics for the breadth of diseases that enables simple yet accurate detection and monitoring of the diseased biological systems.
This thesis presents two strategic designs for optical nanobiosensing platforms towards in vitro and intracellular molecular diagnostics by employing surface-enhanced Raman scattering (SERS) and Förster resonance energy transfer (FRET) as the core means of signal transducing. The first research focus demonstrates an artificial-nose-empowered platform for in vitro diagnostics based on an array of plasmonic SERS substrates fabricated by lithographic techniques, whereby the increased amount of information enables to accurately identify biological samples in a label-free, wash-free, and targeting-free regime. The second research focus presents a highly programmable aptasensor nanoprobe, formulated by enzymatic amplification-driven self-assembly of DNA-inorganic hybrid nanocomposites. Leveraging the sequence-encoded multifunctionalities, the designer probe is capable of being selectively internalised into target cells and performing FRET-based ratiometric detection of intracellular endogenous biomolecules. The designs presented in this thesis, demonstrated in proof of principle, propose elegant approaches of optical nanobiosensing both in label-free and labelled formats towards in vitro biological sample identification and direct monitoring of the dysregulated biology within intracellular environments at the site of disease. It is envisioned these strategies will open up a wide-ranging potential of molecular nanodiagnostics for the breadth of diseases that enables simple yet accurate detection and monitoring of the diseased biological systems.
Version
Open Access
Date Issued
2020-10-16
Date Awarded
01/03/2021
License URL
Advisor
Stevens, Molly
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)