Cancer in-vitro diagnostics using upconversion nanoprobe

He, Hao

Cancer in-vitro diagnostics using upconversion nanoprobe

He, Hao

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Publication Type:: Thesis
Issue Date:: 2019

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Field	Value	Language
dc.contributor.author	He, Hao
dc.date.accessioned	2019-12-02T03:53:57Z
dc.date.available	2019-12-02T03:53:57Z
dc.date.issued	2019
dc.identifier.uri	http://hdl.handle.net/10453/137109
dc.description	University of Technology Sydney. Faculty of Science.	en_AU
dc.description.abstract	Developing sensitive, specific and fast assays to detect and quantify cancer biomarkers at low concentration permit early stage diagnosis of cancer and to improve the survival rate. Many kinds of nanomaterials have been applied to break the limitations of conventional bioassays so as to offer high sensitivity, simplicity and at lower cost. The current development of nanoparticle based in-vitro diagnostics tests, such as paper-based testing strips using gold nanoparticles, remain as being indicative rather than being quantitative. To fill the gap between lab based quantitative assays and techniques for point of care testing, smartphones will play an essential role. This takes the advantage of build-in optics and electronics suitable for data acquisition, quantification and communication. But this still requires the biochemistry methods to be more stable, selective and quantitative, particularly suitable for small volume of samples after minimum level of preparations. This thesis explores a new class of fluorescent probes and detection methods to bridge this gap. The new probes are rare earth doped upconversion nanoparticles (UCNPs) with high fluorescent intensity and negligible background noise. To improve the stability and selectivity of UCNPs, two techniques have been explored. Phage display has been employed to select antibodies that can bind to UCNPs surface forming more stable and biocompatible upconversion nanoprobe; bispecific antibodies are used to avoid chemical reaction in the bioconjugation step and deactivation of antibody bioconjugated to UCNPs so that the upconversion nanoprobes can have higher binding efficiency to the cancer biomarker. To meet the requirements of simple and quantitative point of care testing, highly rare earth doped UCNPs with hundreds to thousands of emitters have been introduced to essentially amplify the signal strength so that smartphone can read and quantify the prostate cancer biomarkers resulted in a paper based strip sensor; single nanoparticle image system has been applied to reach a single molecule level sensitivity for detecting prostate cancer biomarkers in sub-microliter samples.	en_AU
dc.format	Thesis (PhD)
dc.language.iso	en_AU	en_AU
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/137109/2/02whole.pdf
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	au.edu.uts.lib/ppc
dc.subject	Cancer.
dc.subject	Prostate cancer.
dc.subject	In vitro diagnostics.
dc.subject	Medical tests.
dc.subject	Upconverting nanoparticles.
dc.subject	Cancer biomarker.
dc.subject	Assay.
dc.subject	Nanotechnology.
dc.subject	Smartphone.
dc.subject	Antibody.
dc.subject	Bioconjugation.
dc.title	Cancer in-vitro diagnostics using upconversion nanoprobe	en_AU
dc.type	Thesis	en_AU
utslib.copyright.status	open_access

Abstract:

Developing sensitive, specific and fast assays to detect and quantify cancer biomarkers at low concentration permit early stage diagnosis of cancer and to improve the survival rate. Many kinds of nanomaterials have been applied to break the limitations of conventional bioassays so as to offer high sensitivity, simplicity and at lower cost. The current development of nanoparticle based in-vitro diagnostics tests, such as paper-based testing strips using gold nanoparticles, remain as being indicative rather than being quantitative. To fill the gap between lab based quantitative assays and techniques for point of care testing, smartphones will play an essential role. This takes the advantage of build-in optics and electronics suitable for data acquisition, quantification and communication. But this still requires the biochemistry methods to be more stable, selective and quantitative, particularly suitable for small volume of samples after minimum level of preparations. This thesis explores a new class of fluorescent probes and detection methods to bridge this gap. The new probes are rare earth doped upconversion nanoparticles (UCNPs) with high fluorescent intensity and negligible background noise. To improve the stability and selectivity of UCNPs, two techniques have been explored. Phage display has been employed to select antibodies that can bind to UCNPs surface forming more stable and biocompatible upconversion nanoprobe; bispecific antibodies are used to avoid chemical reaction in the bioconjugation step and deactivation of antibody bioconjugated to UCNPs so that the upconversion nanoprobes can have higher binding efficiency to the cancer biomarker. To meet the requirements of simple and quantitative point of care testing, highly rare earth doped UCNPs with hundreds to thousands of emitters have been introduced to essentially amplify the signal strength so that smartphone can read and quantify the prostate cancer biomarkers resulted in a paper based strip sensor; single nanoparticle image system has been applied to reach a single molecule level sensitivity for detecting prostate cancer biomarkers in sub-microliter samples.

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http://hdl.handle.net/10453/137109