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SERS-based detection and quantification of cancer biomarkers in cells and tissue microarrays

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TitleInfo
Title
SERS-based detection and quantification of cancer biomarkers in cells and tissue microarrays
Name (type = personal)
NamePart (type = family)
Bhamidipati
NamePart (type = given)
Manjari
NamePart (type = date)
1987-
DisplayForm
Manjari Bhamidipati
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Fabris
NamePart (type = given)
Laura
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Laura Fabris
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Moghe
NamePart (type = given)
Prabhas
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Prabhas Moghe
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Pierce
NamePart (type = given)
Mark
DisplayForm
Mark Pierce
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Kim
NamePart (type = given)
Isaac
DisplayForm
Isaac Kim
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateOther (qualifier = exact); (type = degree)
2018-10
CopyrightDate (encoding = w3cdtf); (keyDate = yes)
2018
Place
PlaceTerm (type = code)
xx
DateCreated (encoding = w3cdtf)
2018
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
The need for early detection of cancer has resulted in the development of a number of molecular identification techniques that can screen for cancer biomarkers or cellular components indicative of a cancerous state. Biomarkers play a crucial role in cancer diagnosis and their identification and quantification can help monitor disease progression and therefore significantly contribute to clinical prognosis and to individualization and optimization of systemic therapy. Nanomaterial-based imaging systems provide the sensitivity, selectivity, and high multiplexing capability needed for molecular detection when leveraging the optical phenomenon of surface-enhanced Raman scattering (SERS). SERS is a vibrational spectroscopic technique that can be used to detect molecules present on or near the surface of plasmonic nanomaterials such as gold nanoparticles. The objective of this dissertation was to develop a SERS-based imaging tool for phenotype assessment of cancer cells and tissues by utilizing the optical properties of gold nanostars (i.e. gold nanoparticles (AuNPs) with a spherical core and sharp protruding spikes) together with the effective targeting ability of aptamers. It was hypothesized that gold nanostars would be able to provide excellent SERS enhancement factors that would enable the quantification of biomarker expression at the single cell level. However, toxicity of the nanoparticles is a critical issue that needs to be taken into consideration before their implementation in vitro. For this purpose, detailed multi-parametric assessment of gold nanoparticle toxicity was carried out in cancerous (glioblastoma cells, U-87) and healthy cells (human fibroblasts) where the effects of nanoparticle shape, surface chemistry, and size on cell toxicity and cellular uptake were assessed. The study demonstrated that gold nanostars can be effectively taken up by both cell types without inducing significant toxicity when capped by a suitable ligand. They were therefore considered to be less toxic when compared to other nanoparticle shapes with the same surface coating and at the same dosage. Gold nanostars were then implemented in the development of a SERS based sensing platform for the recognition of soluble and cell membrane embedded epithelial cell adhesion molecule (EpCAM) protein with high sensitivity and selectivity. EpCAM is a key epithelial biomarker that is overexpressed in several types of cancer and changes in its expression have been associated with the onset of metastasis. The developed biosensor enabled the detection and quantification of EpCAM at the single cell level in two cancer cells with varying expression levels, MCF-7 and PC-3. The highly sensitive cellular targeting with a detection limit of 10 pM was achieved by using EpCAM aptamers. The results demonstrated potential in using this approach for detecting cells that undergo phenotype variations during cancer metastasis. Finally, the gold nanostar aptamer-based SERS tags were implemented to distinguish between early and late stage prostate cancer based on the expression of the prostate specific membrane antigen (PSMA) biomarker. The SERS tags enabled sensitive detection of the PSMA biomarker in the prostate cancer cell LNCaP and in a tissue microarray containing samples from prostate cancer patients. Results showed elevated PSMA expression with progression of the disease and was found to outperform immmunofluorescence. Overall, the dissertation established the importance of cancer diagnosis and staging based on biomarker expression and demonstrated the potential of SERS based diagnostic tools for molecular detection.
Subject (authority = RUETD)
Topic
Biomedical Engineering
Subject (authority = LCSH)
Topic
Raman effect, Surface enhanced
Subject (authority = LCSH)
Topic
Cancer—Early detection
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Identifier
ETD_9137
Identifier (type = doi)
doi:10.7282/T3VH5SGQ
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xviii, 124 pages : illustrations)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Manjari Bhamidipati
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

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The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Bhamidipati
GivenName
Manjari
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2018-08-08 21:52:42
AssociatedEntity
Name
Manjari Bhamidipati
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical

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