Structural identifiability of surface binding reactions involving heterogeneous analyte: Application to surface plasmon resonance experiments

  • Authors:

  • N. D. Evans;H. A. J. Moyse;D. Lowe;D. Briggs;R. Higgins;D. Mitchell;D. Zehnder;M. J. Chappell

  • Affiliations:

  • School of Engineering, University of Warwick, Coventry CV4 7AL, UK;MOAC Doctoral Training Center, University of Warwick, Coventry CV4 7AL, UK;Clinical Sciences Research Laboratory, University of Warwick, Clifford Bridge Road, Coventry CV2 2DX, UK and Histocompatibility Laboratory, NHS Blood and Transplant, Birmingham B15 2SG, UK;Histocompatibility Laboratory, NHS Blood and Transplant, Birmingham B15 2SG, UK;Transplant Unit, University Hospitals Coventry and Warwickshire NHS Trust, Clifford Bridge Road, Coventry CV2 2DX, UK;Clinical Sciences Research Laboratory, University of Warwick, Clifford Bridge Road, Coventry CV2 2DX, UK;Clinical Sciences Research Laboratory, University of Warwick, Clifford Bridge Road, Coventry CV2 2DX, UK and Transplant Unit, University Hospitals Coventry and Warwickshire NHS Trust, Clifford Bri ...;School of Engineering, University of Warwick, Coventry CV4 7AL, UK

  • Venue:
  • Automatica (Journal of IFAC)
  • Year:
  • 2013

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Abstract

Binding affinities are useful measures of target interaction and have an important role in understanding biochemical reactions that involve binding mechanisms. Surface plasmon resonance (SPR) provides convenient real-time measurement of the reaction that enables subsequent estimation of the reaction constants necessary to determine binding affinity. Three models are considered for application to SPR experiments-the well-mixed Langmuir model and two models that represent the binding reaction in the presence of transport effects. One of these models, the effective rate constant approximation, can be derived from the other by applying a quasi-steady state assumption. Uniqueness of the reaction constants with respect to SPR measurements is considered via a structural identifiability analysis. It is shown that the models are structurally unidentifiable unless the sample concentration is known. The models are also considered for analytes with heterogeneity in the binding kinetics. This heterogeneity further confounds the identifiability of key parameters necessary for reliable estimation of the binding affinity.