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Micromechanical Mass Correlation Spectroscopy for the Characterization of Nanoparticles and Biomolecular Complexes in Fluid

dc.contributor.advisorBurg, Thomas Dr.
dc.contributor.authorModena, Mario Matteo
dc.date.accessioned2016-03-15T09:45:49Z
dc.date.available2016-03-15T09:45:49Z
dc.date.issued2016-03-15
dc.identifier.urihttp://hdl.handle.net/11858/00-1735-0000-0028-86FC-8
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-5563
dc.language.isoengde
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc571.4de
dc.titleMicromechanical Mass Correlation Spectroscopy for the Characterization of Nanoparticles and Biomolecular Complexes in Fluidde
dc.typedoctoralThesisde
dc.contributor.refereeEnderlein, Jörg Prof. Dr.
dc.date.examination2015-09-14
dc.description.abstractengDespite the wide range of techniques for the analysis of sub-micrometer objects, label- free characterization of nanoparticles in solution still remains a challenge. Microme- chanical resonators with embedded fluidic channels have recently emerged as an en- abling new technology for the mass characterization of suspended particles. However, technological limitations have prevented their application to particles and biomolecular complexes less than ∼1 attogram (0.6 MDa) in mass. In this thesis, correlation analysis of the time-domain mass signal is introduced as a novel method to extend the application of microfluidic resonators to samples in sub-MDa mass range. This method, called mass correlation spectroscopy (MCS), al- lows the detection of suspended particles even when their signatures in the time-trace cannot be individually recognized. The analysis is formally derived and the limits of detection for resonators of different dimensions are discussed. It is shown that the resolution of the analysis is not limited by the measurement noise, and the signal-to-noise ratio can be improved by increasing particle concentration and acquisition time. Measurements on validated samples prove that resolution enhancement of over five orders of magnitude can be obtained in usual experimental conditions. After derivation of an approximate model for the transport of particles in the embed- ded channel, particle size is inferred from the shape of the correlation curve, enabling the microfluidic resonators to detect mass, size and density of particles in solution in a single experiment. Limitations on the detection of samples composed of a heteroge- neous population of particles are discussed. Proof-of-principle application of the MCS method for the mass characterization of samples of biological interest is presented. The time course of amyloid formation is monitored from the early state of amorphous aggregates to mature fibrils by detecting the increase in average mass of the complexes in solution. As another application, the quantification of surface coatings of nanoparticles is discussed; the detection method is validated by measuring the adsorption of a protein monolayer on the surface of 400 nm polystyrene beads. Finally, proof-of-concept measurements of ribosomes are presented, proving that correlation analysis might find wide application in the characterization of biomolecular complexes in solution.de
dc.contributor.coRefereeGroot, Bert de Prof. Dr.
dc.subject.engNanoparticle characterizationde
dc.subject.engMass detectionde
dc.subject.engLabel-free detectionde
dc.subject.engResonatorsde
dc.subject.engNanotechnologyde
dc.identifier.urnurn:nbn:de:gbv:7-11858/00-1735-0000-0028-86FC-8-7
dc.affiliation.instituteGöttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)de
dc.subject.gokfullBiologie (PPN619462639)de
dc.identifier.ppn85214184X


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