Specific Versus Non‐specific Response in Exponential Molecular Amplification from Cross‐Catalysis: Modeling the Influence of Background Amplifications on the Analytical Performances

• Published in: Chemphyschem 2021-08, Vol.22 (15), p.1611-1621
• Main Authors: Branca, Mathieu, Calvet, Corentin, Limoges, Benoît, Mavré, François
• Format: Article
• Language: English
• Subjects: Amplification; Analytical chemistry; autocatalysis; background amplification; Catalysis; Chemical Sciences; cross-catalysis; Design optimization; detection limit; molecular amplification; Signal processing; Stability analysis
• ISSN: 1439-4235; 1439-7641
• DOI: 10.1002/cphc.202100342

Molecule based signal amplifications relying on an autocatalytic process may represent an ideal strategy for the development of ultrasensitive analytical or bioanalytical assays, the main reason being the exponential nature of the amplification. However, to take full advantage of such amplification rates, high stability of the starting co‐reactants is required in order to avoid any undesirable background amplification. Here, on the basis of a simple kinetic model of cross‐catalysis including a certain degree of intrinsic instability of co‐reactants, we highlight the key parameters governing the analytical response of the system and discuss the analytical performances that are expected from a given kinetic set. In particular, we show how the detection limit is directly related to the relative instability of reactants within each catalytic loop. The model is validated with an experimental dataset and is intended to serve as a guide in the design and optimization of autocatalytic molecular‐based amplification systems with improved analytical performances. Towards developing ultrasensitive assays: A simple model to demonstrate the analytical potentialities associated with autocatalytic molecular‐based signal amplification is developed. The key parameters governing the response of the system is underlined and the analytical performance that can be expected from a given set of kinetic parameters is discussed. The detection limit is demonstrated to be directly related to the relative instability within each catalytic loop and to the kinetic symmetry factor.