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Development and evaluation of luminescent nanoparticles for immunolabeling and imaging via microscopy and smartphone-based devices

University of British Columbia

Fluorescent nanomaterials are of interest for applications in bioanalysis and imaging due to their potential for high brightness, robust photostability, diverse surface functionalization, and special size-dependent properties. Cellular immunolabeling with antigen-targeting biomolecules (e.g. antibodies, aptamers) is one such application, and has numerous applications in biomedical research and for laboratory-based or point-of-care molecular diagnostics for health care. For example, immunolabeling is a commonly used technique for the diagnostic screening of cancerous cells and relies on the detection of antigens that are specific to malignant cells. However, integrating fluorescent nanomaterials within molecular diagnostic assays can be challenging— optimization to the physicochemical properties of a nanomaterial and its surface chemistry is necessary. When optimized, fluorescent nanoparticles have the ability to address key challenges in bioanalysis and imaging, including enhanced sensitivity and enabling the use of mass-produced consumer technologies, such as smartphones, as a platform for point-of-care diagnostics. This thesis presents key contributions towards the development of fluorescent nanoparticles for applications in bioanalysis and imaging, and particularly immunofluorescent labeling of cells. These materials include quantum dots (QDs), single-chain polymer nanoparticles (SCPNs), polymer dots (Pdots), and composite supra-nanoparticles that comprise iron oxide nanoparticles/QDs and silica nanoparticle/QDs. Breast cancer cells were labeled and imaged using various antibody conjugates of these nanoparticles. With several of the materials, dextran is demonstrated to be an ideal surface coating. Benefits include improved colloidal stability, reduced non-specific binding, and utility as a biochemical handle for the assembly of tetrameric antibody complexes (TACs) for specific cellular immunolabeling. Despite several advantages, TACs had not been used with fluorescent nanoparticles prior to this thesis. In addition, the exceptional brightness of the supra-nanoparticles enabled their utilization for smartphone-based imaging of immunolabeled cells. This imaging is done with a device manufactured by 3-D printing, which, in conjugation with the brightness of the materials, avoids the typical trade-off between optimal sensitivity and portability, simplicity, and low cost. Overall, this thesis enriches the science of cellular immunolabeling and imaging via novel materials, novel immunoconjugation methods, and novel devices.

Text

2020-12-15

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/76807

Chemistry

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/