Self Calibrating Interferometric Sensor
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.
| Original language | English |
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| Publication date | Jun 2006 |
| Place of publication | Kgs. Lyngby, Denmark |
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| Publisher | Technical University of Denmark (DTU) |
| Number of pages | 176 |
| ISBN (print) | 87-550-3495-0 |
| State | Published |
| Name | Risø-PhD-19(EN) |
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