Biomarker detection via lab-on-a-chip integrated immunoaffinity approach for fluorescence and mass spectrometry readout
Author
Summary, in English
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).
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).
Department/s
Publishing year
2011
Language
English
Full text
Document type
Dissertation
Topic
- Medical Engineering
Keywords
- 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.
Status
Published
Supervisor
ISBN/ISSN/Other
- ISBN: 978-91-7473-217-7
Defence date
16 December 2011
Defence time
10:00
Defence place
E:1406, E-huset, Ole Römers väg 3, Lund University, Faculty of Engineering
Opponent
- Fred Regnier (Prof.)