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Towards the development of a continuous-flow, smart micro-electroporation technology to advance cell therapy

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TitleInfo
Title
Towards the development of a continuous-flow, smart micro-electroporation technology to advance cell therapy
Name (type = personal)
NamePart (type = family)
Sherba
NamePart (type = given)
Joseph J.
NamePart (type = date)
1991-
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Joseph J. Sherba, Jr.
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author
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Jr.
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Zahn
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Jeffrey D
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Jeffrey D Zahn
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Advisory Committee
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chair
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Shreiber
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David I
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David I Shreiber
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Advisory Committee
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internal member
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Sy
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Jay
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Jay Sy
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Advisory Committee
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internal member
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Lin
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Hao
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Hao Lin
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Advisory Committee
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outside member
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Shan
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Jerry W
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Jerry W Shan
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Advisory Committee
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outside member
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Roberts
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Christine
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Christine Roberts
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Advisory Committee
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outside member
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Maslow
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Joel
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Joel Maslow
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Advisory Committee
Role
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outside member
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Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
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NamePart
School of Graduate Studies
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school
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Text
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theses
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2020
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2020-05
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2020
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
Abstract (type = abstract)
FDA approved patient-derived cellular therapies are a groundbreaking biomedical/clinical accomplishment in recent years. This therapy involves the intricate process of removing cells from the patient, genetically modifying them ex vivo, and then returning the cells to the patient to combat disease. Though this field is very promising for treatment of otherwise untreatable cancers and other genetic/auto-immune disorders, current manufacturing costs may make this life-saving therapy unaffordable to the general population. Of the manufacturing steps, the use of viral vectors for gene delivery remains the ‘rate-limiting’ step from an economic point of view. Electroporation is an alternative to viral-mediated gene delivery. Electroporation is an electro-physical, non-viral approach to perform DNA, RNA, and protein transfections of cells. Upon application of an electric field, the cell membrane is compromised, allowing the delivery of exogenous materials into cells. This dissertation focuses on advancing a novel, micro-electroporation technology capable of electrically monitoring the degree of cell membrane permeabilization throughout the process. Technological advancements are made from a biochemical standpoint, through optimization of the electroporation buffer that cells are suspended in during the electroporation process, as well as microfluidic/hardware/software design. Highly desirable biomedical and clinical applications, such as DNA plasmid delivery and gene editing with CRISPR-Cas9, are demonstrated using this micro-electroporation technology. Furthermore, ideas to enhance the overall throughput of the technology are introduced, such single-cell level feedback control, population-based feedback control, and microfluidic device parallelization. Ultimately with further technological advancement, this continuous-flow, micro-electroporation system may shift the existing cell therapy manufacturing paradigm, with hopes of eliminating the need for viral-mediated gene delivery.
Subject (authority = LCSH)
Topic
Electroporation
Subject (authority = RUETD)
Topic
Biomedical Engineering
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
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ETD_10920
PhysicalDescription
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application/pdf
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text/xml
Extent
1 online resource (xxviii, 170 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
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Title
School of Graduate Studies Electronic Theses and Dissertations
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rucore10001600001
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NjNbRU
Identifier (type = doi)
doi:10.7282/t3-17xs-qm76
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Sherba
GivenName
Joseph
Role
Copyright Holder
RightsEvent
Type
Permission or license
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2020-05-01 14:49:50
AssociatedEntity
Name
Joseph Sherba
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
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License
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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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2020-05-04T14:58:51
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2020-05-04T14:58:51
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