ISBN 9783843955713

978-3-8439-5571-3, Reihe Mikrosystemtechnik

Nathan Bentley
Tailor-Made Porous Materials for the Capturing of Biomolecules and Cells

224 Seiten, Dissertation Albert-Ludwigs-Universität Freiburg im Breisgau (2024), Softcover, B5

Zusammenfassung / Abstract

Porous materials are an extremely technologically attractive and unique class of materials for interaction with low abundance biomarkers due to their highly specific surfaces. When the high porosity of a material is coupled with functionalization for specific interaction with molecules in a penetrating fluid, porous materials can present a powerful tool for many applications in bioanalytics. In this work, two design philosophies were combined and utilized for the development of porous materials: precise pore definition and high surface-to-volume ratio. In the former case, nickel bioaffinity membranes fabricated via a combination of photolithography and electrochemistry with specified pore sizes and locations were developed for CTC isolation. The membranes were primed with a phosphonic acid to add C,H groups for surface attachment of a polystyrene layer via the C,H insertion crosslinking (CHic) reaction with a thermal crosslinker (PS-co-MAz) followed by a layer of PDMAA-co-MABP. EpCAM antibodies were added via streptavidin-biotin bridges for specific interaction with CTCs. Demonstration of the CTC isolation capabilities at very low cell counts (< 10 cells) of MCF-7 cells (as model CTCs) in 7.5 ml and 50 ml of whole blood indicated nearly perfect capture efficiencies. In the second scenario, paper-like fiber mats were fabricated via electrospinning, producing core-sheath fibers with non-swelling cores from PMMA-co-MABP and hydrogel sheaths from PDMAA-co-MABP. The polymers utilized included CHic crosslinker groups (MABP), allowing for improvements to the fiber thermal and solvent stability, and wetting properties. This material was then used in a lateral flow assay for borreliosis with OspC and Bb VlsE1 as the biomarkers, and fluorescence as the readout. Signal-to-background ratios of 4:1 could be achieved. This material was then adapted for a CTC capture by functionalizing with anti-EpCAM, exhibiting high potential as an isolation membrane.