This version is available at https://strathprints.strath.ac.uk/7337/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output.Parameter estimation in kinetic reaction models using nonlinear observers is facilitated by model extensions ⋆ Abstract: An essential part of mathematical modeling is the accurate and reliable estimation of the model parameters. In biology, the required parameters are particularly difficult to measure because of either shortcomings of the measurement technology or a lack of direct measurements. In both cases, parameters must be estimated from indirect measurements, usually in the form of time-series data. Here, we present a novel approach for parameter estimation that is particularly tailored to biological models consisting of nonlinear ordinary differential equations. By assuming specific types of nonlinearities common in biology, such as generalized mass action, Hill kinetics and products thereof, we can take a three step approach: (1) transform the identification into an observer problem using a suitable model extension that decouples the estimation of non-measured states from the parameters; (2) reconstruct all extended states using nonlinear observers; (3) estimate the parameters using the reconstructed states. The actual estimation of the parameters is based on the intrinsic dependencies of the extended states arising from the definitions of the extended variables, and solved via least squares approximation. An important advantage of the proposed method is that it allows us to identify suitable measurements and/or model structures for which the parameters can be estimated. In addition, the proposed identification approach is generally applicable to models of metabolic networks, signal transduction and gene regulation.