Miniature multi-channel SPR instrument for methotrexate monitoring in clinical samples

A multi-channel fully integrated SPR biosensor was applied for the analysis of an anti-cancer drug, methotrexate (MTX) as a potential analytical tool used in clinical chemistry laboratories for therapeutic drug monitoring (TDM). MTX concentrations in a patient's serum undergoing chemotherapy tr...

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Published inBiosensors & bioelectronics Vol. 64; pp. 664 - 670
Main Authors Zhao, Sandy Shuo, Bukar, Natalia, Toulouse, Jacynthe L., Pelechacz, Daniel, Robitaille, Robert, Pelletier, Joelle N., Masson, Jean-François
Format Journal Article
LanguageEnglish
Published England Elsevier B.V 15.02.2015
Subjects
Antimetabolites, Antineoplastic - blood
Antimetabolites, Antineoplastic - chemistry
Biosensors
Calibration
Complex Mixtures - analysis
Complex Mixtures - chemistry
Drug Monitoring - instrumentation
Dynamic range
Dynamical systems
Equipment Design
Equipment Failure Analysis
Gold nanoparticles
Hospitals
Lighting - instrumentation
Localized surface plasmon resonance
Methotrexate
Methotrexate - blood
Methotrexate - chemistry
Miniaturization
Monitoring
Sensors
Surface plasmon resonance
Surface Plasmon Resonance - instrumentation
Therapeutic drug monitoring
Therapeutic drug monitoring
Surface plasmon resonance
Biosensors
Localized surface plasmon resonance
Methotrexate
Gold nanoparticles
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Abstract A multi-channel fully integrated SPR biosensor was applied for the analysis of an anti-cancer drug, methotrexate (MTX) as a potential analytical tool used in clinical chemistry laboratories for therapeutic drug monitoring (TDM). MTX concentrations in a patient's serum undergoing chemotherapy treatments can be determined by surface plasmon resonance (SPR) sensing using folic acid-functionalized gold nanoparticles (FA-AuNP) in competition with MTX for the bioreceptor, human dihydrofolate reductase (hDHFR) immobilized on the SPR sensor chip. To validate this biosensor, 13nm FA-AuNP were shown to interact with immobilized hDHFR in the absence of MTX and this interaction was inhibited in the presence of MTX. The sensor was calibrated for MTX in phosphate buffer at different dynamic range by varying nanoparticle sizes (5, 13, 23nm) and by modifying the Kd of the bioreceptor using wild-type and mutant hDHFR. Furthermore, initial binding rate data analyzes demonstrated quantitative and fast sensor response under 60s. This MTX assay was subsequently adapted to a fully integrated multi-channel SPR system built in-house and calibrated in human serum with a dynamic range of 28–500nM. The SPR system was applied to analyzes of actual clinical samples and the results are in good agreement with fluorescence polarization immunoassay (FPIA) and LC–MS/MS. Finally, the prototype system was tested by potential clinical users in a hospital setting at the biochemistry laboratory of a Montreal hospital (Hôpital Maisonneuve-Rosemont). •Portable four channel SPR instrument powered by USB from small laptop computer.•SPR sensor for MTX in serum sample of patients undergoing chemotherapy.•Optimization of AuNP and hDHFR receptor for low detection limit.•Comparative study with FPIA and LC–MS/MS.
AbstractList A multi-channel fully integrated SPR biosensor was applied for the analysis of an anti-cancer drug, methotrexate (MTX) as a potential analytical tool used in clinical chemistry laboratories for therapeutic drug monitoring (TDM). MTX concentrations in a patient's serum undergoing chemotherapy treatments can be determined by surface plasmon resonance (SPR) sensing using folic acid-functionalized gold nanoparticles (FA-AuNP) in competition with MTX for the bioreceptor, human dihydrofolate reductase (hDHFR) immobilized on the SPR sensor chip. To validate this biosensor, 13 nm FA-AuNP were shown to interact with immobilized hDHFR in the absence of MTX and this interaction was inhibited in the presence of MTX. The sensor was calibrated for MTX in phosphate buffer at different dynamic range by varying nanoparticle sizes (5, 13, 23 nm) and by modifying the Kd of the bioreceptor using wild-type and mutant hDHFR. Furthermore, initial binding rate data analyzes demonstrated quantitative and fast sensor response under 60s. This MTX assay was subsequently adapted to a fully integrated multi-channel SPR system built in-house and calibrated in human serum with a dynamic range of 28-500 nM. The SPR system was applied to analyzes of actual clinical samples and the results are in good agreement with fluorescence polarization immunoassay (FPIA) and LC-MS/MS. Finally, the prototype system was tested by potential clinical users in a hospital setting at the biochemistry laboratory of a Montreal hospital (Hôpital Maisonneuve-Rosemont).
A multi-channel fully integrated SPR biosensor was applied for the analysis of an anti-cancer drug, methotrexate (MTX) as a potential analytical tool used in clinical chemistry laboratories for therapeutic drug monitoring (TDM). MTX concentrations in a patient's serum undergoing chemotherapy treatments can be determined by surface plasmon resonance (SPR) sensing using folic acid-functionalized gold nanoparticles (FA-AuNP) in competition with MTX for the bioreceptor, human dihydrofolate reductase (hDHFR) immobilized on the SPR sensor chip. To validate this biosensor, 13nm FA-AuNP were shown to interact with immobilized hDHFR in the absence of MTX and this interaction was inhibited in the presence of MTX. The sensor was calibrated for MTX in phosphate buffer at different dynamic range by varying nanoparticle sizes (5, 13, 23nm) and by modifying the K d of the bioreceptor using wild-type and mutant hDHFR. Furthermore, initial binding rate data analyzes demonstrated quantitative and fast sensor response under 60s. This MTX assay was subsequently adapted to a fully integrated multi-channel SPR system built in-house and calibrated in human serum with a dynamic range of 28-500nM. The SPR system was applied to analyzes of actual clinical samples and the results are in good agreement with fluorescence polarization immunoassay (FPIA) and LC-MS/MS. Finally, the prototype system was tested by potential clinical users in a hospital setting at the biochemistry laboratory of a Montreal hospital (Hopital Maisonneuve-Rosemont).
A multi-channel fully integrated SPR biosensor was applied for the analysis of an anti-cancer drug, methotrexate (MTX) as a potential analytical tool used in clinical chemistry laboratories for therapeutic drug monitoring (TDM). MTX concentrations in a patient's serum undergoing chemotherapy treatments can be determined by surface plasmon resonance (SPR) sensing using folic acid-functionalized gold nanoparticles (FA-AuNP) in competition with MTX for the bioreceptor, human dihydrofolate reductase (hDHFR) immobilized on the SPR sensor chip. To validate this biosensor, 13nm FA-AuNP were shown to interact with immobilized hDHFR in the absence of MTX and this interaction was inhibited in the presence of MTX. The sensor was calibrated for MTX in phosphate buffer at different dynamic range by varying nanoparticle sizes (5, 13, 23nm) and by modifying the Kd of the bioreceptor using wild-type and mutant hDHFR. Furthermore, initial binding rate data analyzes demonstrated quantitative and fast sensor response under 60s. This MTX assay was subsequently adapted to a fully integrated multi-channel SPR system built in-house and calibrated in human serum with a dynamic range of 28–500nM. The SPR system was applied to analyzes of actual clinical samples and the results are in good agreement with fluorescence polarization immunoassay (FPIA) and LC–MS/MS. Finally, the prototype system was tested by potential clinical users in a hospital setting at the biochemistry laboratory of a Montreal hospital (Hôpital Maisonneuve-Rosemont). •Portable four channel SPR instrument powered by USB from small laptop computer.•SPR sensor for MTX in serum sample of patients undergoing chemotherapy.•Optimization of AuNP and hDHFR receptor for low detection limit.•Comparative study with FPIA and LC–MS/MS.
Author Robitaille, Robert
Pelletier, Joelle N.
Bukar, Natalia
Toulouse, Jacynthe L.
Pelechacz, Daniel
Zhao, Sandy Shuo
Masson, Jean-François
Author_xml – sequence: 1
  givenname: Sandy Shuo
  surname: Zhao
  fullname: Zhao, Sandy Shuo
  organization: Département de Chimie, Université de Montréal, C.P. 6128 Succ. Centre-Ville, Montréal, QC, Canada H3C 3J7
– sequence: 2
  givenname: Natalia
  surname: Bukar
  fullname: Bukar, Natalia
  organization: Département de Chimie, Université de Montréal, C.P. 6128 Succ. Centre-Ville, Montréal, QC, Canada H3C 3J7
– sequence: 3
  givenname: Jacynthe L.
  surname: Toulouse
  fullname: Toulouse, Jacynthe L.
  organization: Département de Chimie, Université de Montréal, C.P. 6128 Succ. Centre-Ville, Montréal, QC, Canada H3C 3J7
– sequence: 4
  givenname: Daniel
  surname: Pelechacz
  fullname: Pelechacz, Daniel
  organization: Département de Chimie, Université de Montréal, C.P. 6128 Succ. Centre-Ville, Montréal, QC, Canada H3C 3J7
– sequence: 5
  givenname: Robert
  surname: Robitaille
  fullname: Robitaille, Robert
  organization: Département de Biochimie, Centre de Recherche, Hôpital Maisonneuve-Rosemont, 5415 Boulevard de l'Assomption, Montréal, QC, Canada H1T 2M4
– sequence: 6
  givenname: Joelle N.
  surname: Pelletier
  fullname: Pelletier, Joelle N.
  organization: Département de Chimie, Université de Montréal, C.P. 6128 Succ. Centre-Ville, Montréal, QC, Canada H3C 3J7
– sequence: 7
  givenname: Jean-François
  surname: Masson
  fullname: Masson, Jean-François
  email: jf.masson@umontreal.ca
  organization: Département de Chimie, Université de Montréal, C.P. 6128 Succ. Centre-Ville, Montréal, QC, Canada H3C 3J7
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Keywords Therapeutic drug monitoring
Surface plasmon resonance
Biosensors
Localized surface plasmon resonance
Methotrexate
Gold nanoparticles
Language English
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Snippet A multi-channel fully integrated SPR biosensor was applied for the analysis of an anti-cancer drug, methotrexate (MTX) as a potential analytical tool used in...
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SubjectTerms Antimetabolites, Antineoplastic - blood
Antimetabolites, Antineoplastic - chemistry
Biosensors
Calibration
Complex Mixtures - analysis
Complex Mixtures - chemistry
Drug Monitoring - instrumentation
Dynamic range
Dynamical systems
Equipment Design
Equipment Failure Analysis
Gold nanoparticles
Hospitals
Lighting - instrumentation
Localized surface plasmon resonance
Methotrexate
Methotrexate - blood
Methotrexate - chemistry
Miniaturization
Monitoring
Sensors
Surface plasmon resonance
Surface Plasmon Resonance - instrumentation
Therapeutic drug monitoring
Title Miniature multi-channel SPR instrument for methotrexate monitoring in clinical samples
URI https://dx.doi.org/10.1016/j.bios.2014.09.082
https://www.ncbi.nlm.nih.gov/pubmed/25441416
https://search.proquest.com/docview/1629963564
https://search.proquest.com/docview/1647003458
https://search.proquest.com/docview/1660055733
Volume 64
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