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Expanding the Capabilities of Biosensors with Novel Molecular Switches
Expanding the Capabilities of Biosensors with Novel Molecular Switches
Expanding the Capabilities of Biosensors with Novel Molecular Switches

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자료유형  
 학위논문 서양
최종처리일시  
20260202104738
ISBN  
9798290649962
DDC  
612
저자명  
Thompson, Ian Andrew Paul.
서명/저자  
Expanding the Capabilities of Biosensors with Novel Molecular Switches
발행사항  
[Sl] : Stanford University, 2023
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2023
형태사항  
186 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-01, Section: B.
주기사항  
Advisor: Soh, H. Tom.
학위논문주기  
Thesis (Ph.D.)--Stanford University, 2023.
초록/해제  
요약Biosensors capable of tracking the body's molecular state have tremendous potential to improve lives by making healthcare more accessible, personalized, and preventative. At the same time, developing biosensors that are both compatible with point-of-care or continuous monitoring and can accurately track a wide range of clinically important biomarkers poses a tremendous technical challenge. These sensors must operate without the sample processing employed by conventional laboratory diagnostic assays and must measure targets rapidly with molecular sensitivity and specificity within complex biofluid samples. These demands may be met by biosensors based on "molecular switches" -- engineered receptors that bind molecular targets with high specificity and undergo a binding-induced conformational change that produces measurable optical or electronic signals. However, to date these molecular switch biosensors have remained limited to sensing only a handful of molecules. It remains an outstanding challenge to develop generalizable strategies to methods for engineering molecular switches to sense the complete range of health biomarkers.In this dissertation, I begin by considering how we can develop sensors that are compatible with real world, day-to-day use. I analyze the diagnostic value of biosensing in dermal interstitial fluid, a biofluid with emerging interest for use with minimally invasive and continuous wearable sensors. The remainder of the dissertation focuses on three projects where I expand the generalizability molecular switches, enabling more rapid development of biosensors for new biomarker targets. In the first project, I introduce an approach for engineering off-the-shelf antibodies into antibody-based molecular switches that achieve continuous optical biosensing by augmenting them with a rationally designed DNA-linked competitor molecule. In the second project, I develop a universal protein-based competitor molecule that provides an even more universal method for our antibody-based molecular switch design to be applied to sensing new targets. In the third project, I develop a rational design approach for engineering DNA-based molecular switches that have pH-dependent properties which can be tailored to improve biosensor performance, and for potential drug delivery applications. Taken together, these advances in molecular switch design offer a toolkit of generalizable strategies that can be used to develop next-generation biosensors which sense a wide range of biomarkers for addressing a wide range of clinical needs.
일반주제명  
Physiology
일반주제명  
Diabetes
일반주제명  
Hormones
일반주제명  
Antibodies
일반주제명  
Extracellular matrix
일반주제명  
Oxygen saturation
일반주제명  
Drug dosages
일반주제명  
Hemoglobin
일반주제명  
Fibroblasts
일반주제명  
Pulse oximetry
일반주제명  
Immune system
일반주제명  
Glucose
일반주제명  
Biomarkers
일반주제명  
Design
일반주제명  
Engineering
일반주제명  
Biosensors
일반주제명  
Antigens
기타저자  
Stanford University.
기본자료저록  
Dissertations Abstracts International. 87-01B.
전자적 위치 및 접속  
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MARC

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■1001  ▼aThompson,  Ian  Andrew  Paul.
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■260    ▼a[Sl]▼bStanford  University▼c2023
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2023
■300    ▼a186  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-01,  Section:  B.
■500    ▼aAdvisor:  Soh,  H.  Tom.
■5021  ▼aThesis  (Ph.D.)--Stanford  University,  2023.
■520    ▼aBiosensors  capable  of  tracking  the  body's  molecular  state  have  tremendous  potential  to  improve  lives  by  making  healthcare  more  accessible,  personalized,  and  preventative.  At  the  same  time,  developing  biosensors  that  are  both  compatible  with  point-of-care  or  continuous  monitoring  and  can  accurately  track  a  wide  range  of  clinically  important  biomarkers  poses  a  tremendous  technical  challenge.  These  sensors  must  operate  without  the  sample  processing  employed  by  conventional  laboratory  diagnostic  assays  and  must  measure  targets  rapidly  with  molecular  sensitivity  and  specificity  within  complex  biofluid  samples.  These  demands  may  be  met  by  biosensors  based  on  "molecular  switches"  --  engineered  receptors  that  bind  molecular  targets  with  high  specificity  and  undergo  a  binding-induced  conformational  change  that  produces  measurable  optical  or  electronic  signals.  However,  to  date  these  molecular  switch  biosensors  have  remained  limited  to  sensing  only  a  handful  of  molecules.  It  remains  an  outstanding  challenge  to  develop  generalizable  strategies  to  methods  for  engineering  molecular  switches  to  sense  the  complete  range  of  health  biomarkers.In  this  dissertation,  I  begin  by  considering  how  we  can  develop  sensors  that  are  compatible  with  real  world,  day-to-day  use.  I  analyze  the  diagnostic  value  of  biosensing  in  dermal  interstitial  fluid,  a  biofluid  with  emerging  interest  for  use  with  minimally  invasive  and  continuous  wearable  sensors.  The  remainder  of  the  dissertation  focuses  on  three  projects  where  I  expand  the  generalizability  molecular  switches,  enabling  more  rapid  development  of  biosensors  for  new  biomarker  targets.  In  the  first  project,  I  introduce  an  approach  for  engineering  off-the-shelf  antibodies  into  antibody-based  molecular  switches  that  achieve  continuous  optical  biosensing  by  augmenting  them  with  a  rationally  designed  DNA-linked  competitor  molecule.  In  the  second  project,  I  develop  a  universal  protein-based  competitor  molecule  that  provides  an  even  more  universal  method  for  our  antibody-based  molecular  switch  design  to  be  applied  to  sensing  new  targets.  In  the  third  project,  I  develop  a  rational  design  approach  for  engineering  DNA-based  molecular  switches  that  have  pH-dependent  properties  which  can  be  tailored  to  improve  biosensor  performance,  and  for  potential  drug  delivery  applications.  Taken  together,  these  advances  in  molecular  switch  design  offer  a  toolkit  of  generalizable  strategies  that  can  be  used  to  develop  next-generation  biosensors  which  sense  a  wide  range  of  biomarkers  for  addressing  a  wide  range  of  clinical  needs.
■590    ▼aSchool  code:  0212.
■650  4▼aPhysiology
■650  4▼aDiabetes
■650  4▼aHormones
■650  4▼aAntibodies
■650  4▼aExtracellular  matrix
■650  4▼aOxygen  saturation
■650  4▼aDrug  dosages
■650  4▼aHemoglobin
■650  4▼aFibroblasts
■650  4▼aPulse  oximetry
■650  4▼aImmune  system
■650  4▼aGlucose
■650  4▼aBiomarkers
■650  4▼aDesign
■650  4▼aEngineering
■650  4▼aBiosensors
■650  4▼aAntigens
■690    ▼a0389
■690    ▼a0537
■690    ▼a0719
■71020▼aStanford  University.
■7730  ▼tDissertations  Abstracts  International▼g87-01B.
■790    ▼a0212
■791    ▼aPh.D.
■792    ▼a2023
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17358695▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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