New methods for sensitive analysis with nanoelectrospray ionization mass spectrometry
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
In this thesis, new methods that address some current limitations in nanoelectrospray mass spectrometry (nESI-MS) analysis are presented. One of the major objectives is the potential gain in sensitivity that can be obtained when employing the proposed techniques.
In the first part of this thesis, a new emitter, based on the generation of electrospray from a spray orifice with variable size, is presented. Electrospray is generated from an open gap between the edges of two individually mounted, pointed tips. The fabrication and evaluation of two different types of such emitters is presented; an ESI emitter fabricated from polyethylene terephtalate (Paper I), and a high-precision silicon device (Paper II). Both emitters were surface-treated in a selective way for an improved wetting of the gap and to confine the sample solution into the gap.
In the second part of this thesis, different methods for improved sensitivity of nESI-MS analysis have been developed. In Paper III, a method for nESI-MS analysis from discrete sample volumes down to 1.5 nL is presented, using commercially available nESI needles. When analyzing attomole amounts of analyte in such a small volume of sample, an increased sensitivity was obtained, compared to when analyzing equal amounts in conventional nESI-MS analysis. To be able to analyze smaller sample volumes, needles with a narrower orifice and a higher flow resistance were needed. This triggered the development of a new method for fabrication of fused silica nESI needles (Paper IV). The fabrication is based on melting of a fused silica capillary by means of a rotating plasma, prior to pulling the capillary into a fine tip. Using the described technique, needles with sub-micrometer orifices could be fabricated. Such needles enabled the analysis of sample volumes down to 275 pL, and a further improvement of the sensitivity was obtained. In a final project (Paper V), nESI-MS was used to study the aggregation behavior of Aβ peptides, related to Alzheimer’s disease. An immunoprecipitation followed by nESI-MS was employed. This technique was also utilized to study the selectivity of the antibodies utilized.
Place, publisher, year, edition, pages
Stockholm: KTH , 2010. , vii, 70 p.
Trita-CHE-Report, ISSN 1654-1081 ; 2010:41
mass spectrometry, electrospray ionization, nanoelectrospray ionization, adjustable gap, emitter, miniaturization, improved sensitivity, nanoliter/picoliter sample volumes, Alzheimer’s disease, amyloid-beta (Aβ)
IdentifiersURN: urn:nbn:se:kth:diva-25917ISBN: 978-91-7415-751-2OAI: oai:DiVA.org:kth-25917DiVA: diva2:360781
2010-11-26, K1, Teknikringen 56, Stockholm, 10:00 (English)
Bruins, Andries P., Professor
Roeraade, Johan, ProfessorEmmer, Åsa, Docent
QC 201011122010-11-122010-11-042010-11-12Bibliographically approved
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