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Biomolecular sensing and imaging usi...

University of California, Berkeley.

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Biomolecular sensing and imaging using hyperpolarized xenon-129 magnetic resonance.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Biomolecular sensing and imaging using hyperpolarized xenon-129 magnetic resonance./
Author:	Lowery, Thomas J.
Description:	229 p.
Notes:	Adviser: David E. Wemmer.
Contained By:	Dissertation Abstracts International68-08B.
Subject:	Chemistry, Analytical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3275499
ISBN:	9780549169185

Biomolecular sensing and imaging using hyperpolarized xenon-129 magnetic resonance.
Lowery, Thomas J.

Biomolecular sensing and imaging using hyperpolarized xenon-129 magnetic resonance. - 229 p.

Adviser: David E. Wemmer.

Thesis (Ph.D.)--University of California, Berkeley, 2007.

The high signal-to-noise afforded by optical pumping and the remarkable chemical shift sensitivity of xenon to its local environment make hyperpolarized xenon magnetic resonance an attractive means to probe biomolecular samples. Two general approaches are presented in this dissertation to sense and image biomolecular events with hyperpolarized xenon. The first approach used weak interactions between the xenon atom and hydrophobic, conformation-sensitive protein cavities. Such cavities can occur naturally in proteins or can be introduced with protein engineering methods. Protein-cavity based sensing allowed for detection of protein activation, ligand binding, and peptide binding at concentrations as low as hundreds of micromolar. The second approach used a water-soluble, biotinylated, xenon biosensor. The biosensor-associated xenon signals changed upon the addition of avidin, reporting the biotin-avidin binding event. The molecular composition of the xenon biosensor required for optimal sensing of binding events was determined to facilitate the development of more sophisticated biosensor constructs. Three such constructs are presented: an antibody-targeted construct for molecular imaging, a biosensor-functionalized quantum dot for dual-modality affinity-tag imaging, and an engineered maltose binding protein for metabolite sensing. Xenon biosensor solutions at concentrations as low as hundreds of nanomolar were detected by means of a bubble-delivery apparatus in combination with various signal amplification methods. Development of a liquid-flow apparatus enabled the first demonstration of xenon-based molecular imaging using the xenon biosensor as an in vitro affinity tag in a polymer bead phantom. These initial images were subsequently improved upon with a signal amplification technique called HYPER-CEST, which allowed for biosensor concentrations as low as single micromolar to be rapidly imaged. The new xenon biosensor methodologies and constructs presented in this dissertation motivate further efforts to develop more practical xenon-based sensors and imaging agents.

ISBN: 9780549169185Subjects--Topical Terms:

586156
Chemistry, Analytical.

Biomolecular sensing and imaging using hyperpolarized xenon-129 magnetic resonance.
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100 1 $a Lowery, Thomas J. $3 1269495
245 1 0 $a Biomolecular sensing and imaging using hyperpolarized xenon-129 magnetic resonance.
300 $a 229 p.
500 $a Adviser: David E. Wemmer.
500 $a Source: Dissertation Abstracts International, Volume: 68-08, Section: B, page: 5192.
502 $a Thesis (Ph.D.)--University of California, Berkeley, 2007.
520 $a The high signal-to-noise afforded by optical pumping and the remarkable chemical shift sensitivity of xenon to its local environment make hyperpolarized xenon magnetic resonance an attractive means to probe biomolecular samples. Two general approaches are presented in this dissertation to sense and image biomolecular events with hyperpolarized xenon. The first approach used weak interactions between the xenon atom and hydrophobic, conformation-sensitive protein cavities. Such cavities can occur naturally in proteins or can be introduced with protein engineering methods. Protein-cavity based sensing allowed for detection of protein activation, ligand binding, and peptide binding at concentrations as low as hundreds of micromolar. The second approach used a water-soluble, biotinylated, xenon biosensor. The biosensor-associated xenon signals changed upon the addition of avidin, reporting the biotin-avidin binding event. The molecular composition of the xenon biosensor required for optimal sensing of binding events was determined to facilitate the development of more sophisticated biosensor constructs. Three such constructs are presented: an antibody-targeted construct for molecular imaging, a biosensor-functionalized quantum dot for dual-modality affinity-tag imaging, and an engineered maltose binding protein for metabolite sensing. Xenon biosensor solutions at concentrations as low as hundreds of nanomolar were detected by means of a bubble-delivery apparatus in combination with various signal amplification methods. Development of a liquid-flow apparatus enabled the first demonstration of xenon-based molecular imaging using the xenon biosensor as an in vitro affinity tag in a polymer bead phantom. These initial images were subsequently improved upon with a signal amplification technique called HYPER-CEST, which allowed for biosensor concentrations as low as single micromolar to be rapidly imaged. The new xenon biosensor methodologies and constructs presented in this dissertation motivate further efforts to develop more practical xenon-based sensors and imaging agents.
590 $a School code: 0028.
650 4 $a Chemistry, Analytical. $3 586156
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