Publication: Research › Ph.d. thesis – Annual report year: 2006
This thesis deals with the development of an optical sensor based on micro interferometric backscatter detection (MIBD). A price effective, highly sensitive and ready for mass production platform is the goal of this project. The thesis covers three areas. The first part of the thesis deals with theoretical models for describing the optical phenomena utilized in this technique. A model based on ray–tracing has been developed and shown to be a valuable tool for describing certain features in the fringe pattern. The MIBD measurement technique has been expanded to do absolute determination of the refractive index, with an experimental precision of 2.5 · 10−4, using this newly discovered feature. As the MIBD has been used as a biosensor for detecting molecular scaled species, a model valid for changes in system sizes below the geometrical optics regime has been developed. Modeling based on solutions to Maxwell’s equations has with high accuracy described the optical effects when binding events occurs on the inside of a capillary. It is of paramount importance to find a practical stop criteria for the else infinite summation used to find the scattering constants, which is the basis for the model. Different geometries have been modeled, including semicircular, circular and rectangular flowchannels. Theoretical work has shown that the sensitivity of the rectangular geometry is caused by diffraction off the corners. The second part of the thesis deals with the fabrication of injection molded polymer microflow chips. The MIBD technology has been transferred to a chip based platform with a close–to–capillary like geometry. These assembled chips has in the MIBD setup shown detection limits of Δn = 4 · 10−6. The fabrication has been done by isotropic etching in silicon through a silicon nitride sacrificial mask. The fabricated micro structures have been electroplated for later injection molding, showing the potential of the MIBD sensor to be mass produced with high reproducibility and sensitivity. In part three MIBD experiments on vital biological systems are described. Label–free binding studies of bio molecules have been performed in easy to fabricate micro flow channels in elastomer material (PDMS), both surface bound and in free solution. Thermodynamic binding constants for protein–protein interactions has been found and validated by other techniques. The detection limit obtained from these experiments were 9 attomole Human IgG in a 495 pL measurement volume. The free solution protein binding experiments and results places MIBD in a unique position with comparable thermodynamic capabilities with the golden standard ITC, but orders of magnitude faster and less analyte sample consuming. The completion of a Lab–on–a–chip device making a complete blood analysis will be a paradigm shift moving the analysis from the laboratories closer to the bedside.
|Publication date||Jun 2006|
|Place of publication||Kgs. Lyngby, Denmark|
|Publisher||Technical University of Denmark (DTU)|
|Number of pages||176|
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