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Biomarker detection via lab-on-a-chip integrated immunoaffinity approach for fluorescence and mass spectrometry readout

Författare:
Publiceringsår: 2011
Språk: Engelska
Sidor: 160
Dokumenttyp: Doktorsavhandling

Sammanfattning

The blood/plasma protein biomarker profile represents the pathological and physiological changes relating
to human diseases. However, the plasma proteome reflects a high degree of complexity that results in a
challenge for most analytical methods in clinical diagnostics.
The focus in this thesis is the development and application of several integrated platforms to detect already
established protein/peptide biomarkers from blood and plasma (Prostate Specific Antigen, PSA and
Angiotensin I, Ang I). The integrated platforms that are described in the papers included in this thesis
utilize protein/peptide immunoaffinity-capturing since it offers insights into dealing with the challenges of
the plasma proteome analysis by reducing complexity and enriching the proteins/peptides of interest.
Several integrated platforms were developed with the overall main aim of detecting biomarkers from
complex biological samples:
• porous silicon antibody microarray with signal amplification step (Paper I)
• microfluidic whole blood immunoassay (Paper II and III)
• integrated protein immunoaffinity capturing with microfabricated proteomic sample processing
platform (ISET) enabling a direct interface to MALDI MS/MS analysis (Paper IV)
• integrated peptide immunoaffinity capturing via porous silicon array-based immuno-MALDI
(Paper V) enabling a direct interface to MALDI MS/MS analysis
Ultimately, these platforms target future use in point-of-care settings (Paper I-III) and immuno-MALDI
mass spectrometry immunoassays for identification and quantitative measurements of biomarkers using
isotope labelled standards (Paper V) as well as outlook for use in the development of SRM/MRM assays
(Paper IV).

Disputation

2011-12-16
10:00
E:1406, E-huset, Ole Römers väg 3, Lund University, Faculty of Engineering
  • Fred Regnier (Prof.)

Nyckelord

  • Biology and Life Sciences
  • immunoaffinity
  • affinity prefractionation
  • immunoMALDI
  • solid-phase extraction
  • protein digestion
  • ISET
  • antibody microarray
  • signal amplification
  • fluorescence
  • microfluidics
  • lab on a chip
  • separation
  • acoustophoresis
  • ultrasound
  • acoustic radiation force
  • plasma
  • proteomics
  • MALDI mass spectrometry
  • immunoassay
  • porous silicon.

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