Self-propagating amplification reactions for molecular detection and signal amplification: Advantages, pitfalls, and challenges

Self-propagating cascade reactions are a recent development for chemosensing protocols. These cascade reactions, in principle, offer low limits of detection by virtue of exponential signal amplification and are initiated by a specific, preplanned molecular detection event. This combination of selectivity for a detection event followed by in situ signal amplification is achieved by exploitation of mechanistic organic chemistry and thus has resulted in various chemosensing protocols that use one or more reagents to achieve the desired selectivity and sensitivity for an assay. Species such as hydrogen peroxide, thiols, and fluoride have been used as active reagents to initiate the first examples of self-propagating signal amplification reactions, although many other active reagents should be compatible with the approaches. A common feature of the reagents that support the self-propagating signal amplification reactions is the involvement of quinone methide intermediates resulting from elimination of optical reporters and/or active reagents, where the latter propagates the signal amplification reaction. The early examples of these amplification sequences, however, are slow to reach full signal, thus leaving time for background reactions to generate nonspecific signals. This issue of background has limited practical applications of these self-propagating signal amplification reactions, as has challenging synthetic routes to the reagents, as well as the potential for other chemical species to interfere with the detection and signal amplification processes. Thus, the goal of this review is to summarize the progress of self-propagating signal amplification technology, to identify the pitfalls of current designs, and by doing so, to stimulate future studies in this growing and promising research area.