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Biosensing Based on Tethered Particle Motion Biosensing based on tethered particle motion Citation for published version (APA): Visser, E. W. A. (2017). Biosensing based on tethered particle motion. Technische Universiteit Eindhoven. Document status and date: Published: 19/04/2017 Document Version: Publisher’s PDF, also known as Version of Record (includes final page, issue and volume numbers) Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license above, please follow below link for the End User Agreement: www.tue.nl/taverne Take down policy If you believe that this document breaches copyright please contact us at: [email protected] providing details and we will investigate your claim. Download date: 09. Oct. 2021 Biosensing Based on Tethered Particle Motion PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Technische Universiteit Eindhoven, op gezag van de rector magnificus prof.dr.ir. F.P.T. Baaijens, voor een commissie aangewezen door het College voor Promoties, in het openbaar te verdedigen op woensdag 19 april 2016 om 16:00 uur door Emilius Willem Adriaan Visser geboren te Veghel Dit proefschrift is goedgekeurd door de promotoren en de samenstelling van de promotiecommissie is als volgt: voorzitter: prof.dr.ir. G.M.W. Kroesen 1e promotor: prof.dr.ir. M.W.J. Prins copromotor(en): dr. L.J. van IJzendoorn leden: prof.dr.ir. G.J.L. Wuite (Vrije Universiteit Amsterdam) dr. L. Salomé (Institute of Pharmacology and Structural Biology, Toulouse) prof.dr. M. Merkx adviseur(s): dr.ir. J.B.A. van Zon (Philips Research) Het onderzoek of ontwerp dat in dit proefschrift wordt beschreven is uitgevoerd in overeenstemming met de TU/e Gedragscode Wetenschapsbeoefening. A catalogue record is available from the Eindhoven University of Technology Library ISBN: 978-90-386-4245-1 Druk: Ipskamp Printing Illustratie op de cover: ICMS Animation Studio Omslag ontwerp: Markéta Kurfürstová © Emiel Visser 2017 This work was partially conducted in the framework of the project NextDx, funded within the European Commission FP7 program Contents Contents Chapter 1. Introduction...................................................................................................... 1 1.1 History, development, and current state of tethered particle motion ................ 2 1.1.1. The origin of Tethered Particle Motion .................................................................. 2 1.1.2. Progress in methods, theory and analysis of TPM data .................................. 4 1.1.3. Application of TPM in molecular research ............................................................ 8 1.2 Challenges in single molecule research and diagnostics .......................................... 9 1.2.1. TPM for point-of-care biosensing applications ................................................... 9 1.2.2. Molecular patient monitoring .................................................................................. 13 1.3 Outline of the thesis ............................................................................................................... 15 Chapter 2. Theory and basics of TPM .......................................................................... 17 2.1 Tracking the motion of particles ...................................................................................... 17 2.1.1. Observation of the particles ..................................................................................... 17 2.1.2. Particle localization from microscope images .................................................. 20 2.1.3. Imaging techniques ...................................................................................................... 22 2.2 Motion and motion patterns of tethered particles ................................................... 25 2.2.1. Quantification of motion pattern shape .............................................................. 25 2.2.2. Radial confinement parameter................................................................................ 27 2.2.3. Motion distribution plot ............................................................................................. 28 2.3 DNA as nature's information carrier and tether ....................................................... 30 2.3.1. Chemical structure of DNA ........................................................................................ 30 2.3.2. Physical properties of DNA ....................................................................................... 32 2.3.3. DNA flexibility and persistence length ................................................................ 33 2.4 Modeling flexible molecules ............................................................................................... 34 2.4.1. Ideal chain or the freely jointed chain ................................................................. 35 2.4.2. Kratky-Porod and the worm-like chain model................................................. 37 2.4.3. Extension of the worm like chain ........................................................................... 39 2.5 Simulation of motion patterns .......................................................................................... 40 2.5.1. Monte Carlo simulation of TPM .............................................................................. 40 2.5.2. Extension of the simulation method to more complex systems ............... 43 Chapter 3. Particle Motion Analysis Reveals Nanoscale Bond Characteristics and Enhances Dynamic Range for Biosensing ............................................................... 47 3.1 Abstract ....................................................................................................................................... 47 3.2 Introduction ............................................................................................................................... 48 3.3 Methods ....................................................................................................................................... 50 3.3.1. Sample preparation ...................................................................................................... 50 3.3.2. Particle Imaging and Tracking Algorithm .......................................................... 51 3.3.3. Monte Carlo Based TPM Simulations. .................................................................. 51 3.4 Results and discussion .......................................................................................................... 53 i Contents 3.5 Observed motion patterns .................................................................................................. 54 3.5.1. Circular symmetric motion patterns .................................................................... 55 3.5.2. Non-circular symmetric motion patterns ........................................................... 58 3.5.3. Application for target molecule quantification in diagnostic assays...... 60 3.6 Conclusion .................................................................................................................................. 65 Appendix .................................................................................................................................................... 66 A. Particle position tracking accuracy ................................................................................. 66 B. Quantification of DNA binding efficiency on the particles .................................... 67 C. Antibody and dsDNA concentration series .................................................................. 68 D. Dependence of motion distribution on DNA tether concentration ................... 70 E. Friction experienced by particles pinned to the surface by molecular bonds .. ......................................................................................................................................................... 72 F. Additional simulations of particle roughness ............................................................ 72 G. Model describing the tethering of particles to the surface by target molecules .............................................................................................................................................
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