Indicator Displacement Assays (IDAs): An Innovative Molecular Sensing Approach

Taking a step forward from the indicator spacer receptor (ISR) method comprising covalent linkages between receptors and indicators via a spacer, the indicator displacement assay (IDA) offers an innovative and powerful sensing approach for various target analytes in the realm of host-guest chemistry. In this chapter, we have assembled the background and conceptual details in order to give essence to the readers about this innovative sensing approach. The photophysical phenomenon and diverse non-covalent interactions involved in the sensing mechanism have been detailed. We have elucidated the need and urgency to replace the ISR approach with IDA, one having numerous advantages. The evolutionary extension of IDA for enzymatic conversion known as supramolecular tandem assays has also been described in this chapter. We believe that the present introductory chapter will give a better understanding to readers who are new to this field. 

Owing to the unique advantages of naked eye color detection in the sensing of various important analytes, colorimetric indicator displacement assay (C-IDA) has received its recognition as the principal evolutionary extension of IDA. This chapter, besides dealing with all conceptual details of C-IDA, also offers basic criteria for the development and classification of chromogenic sensing ensembles. A plethora of examples in order to elucidate the C-IDA sensing mechanism for the detection of anionic, cationic, and neutral analytes via prominent UV-vis spectral changes have been revealed. Besides, the recognition of several biologically essential analytes viz. phosphate and saccharides have also been discussed in detail through numerous examples. The authors believe that this chapter on C-IDA will offer new dimensions to the design and fabrication of IDA-based colorimetric sensors.

Owing to the ease in their usage and versatility, fluorescent chemosensors have attracted the remarkable attention of researchers across the globe. In fact, the dawn of supramolecular chemistry has begun a new journey in the design, construction, and development of diverse fluorescent chemosensors. Fluorescent indicator displacement assays (F-IDAs) in principle utilize fluorescent indicators and emission phenomenon for the construction of various IDA-based Turn-ON/OFF fluorescent sensors. Particularly, F-IDAs have been found valuable in pattern-based recognition, where slightly different multiple sensors are constructed from diverse receptors simply by swapping fluorescent indicators in and out of receptors or even varying the concentration ratio. These F-IDAs offer huge potential to develop proficient optical sensors from numerous supramolecular receptors and imply the effective molecular recognition event via competitive assay of receptors with an indicator and an analyte. Besides conceptual and mechanistic details, authors have ensured the significance of FIDAs in the recognition of biologically and environmentally essential cationic, anionic, and neutral analytes through various examples.

As a sub-class of colorimetric indicator displacement assays (C-IDAs) as well as fluorimetric indicator displacement assays (F-IDAs), metal indicator displacement assays (M-IDAs) involve primarily the coordination of metal ions with a target receptor and subsequent coordination of colorimetric or fluorimetric indicator with complexed metal ions and also with the target receptor. The chronological addition of an interested analyte brings the displacement of the colorimetric or fluorimetric indicator from the metal ion and the receptor, which in turn illustrates the binding affair either through colorimetric or fluorescence Turn-ON/OFF response. The authors have illustrated the role of M-IDAs in the detection of various indispensable analytes through a vast number of examples and deduced their need in various domains from future perspectives. The authors are of the opinion that this chapter will bring new dimensions to metal coordination chemistry in general and sensor development in particular.

With the advancement of supramolecular chemistry in the realm of sensing, researchers across the globe have developed various evolutionary extensions of IDAs from time to time. These comprise enantioselective indicator displacement assays (eIDAs), intramolecular indicator displacement assays (I-IDAs), indicator catalyst displacement assays (ICDA), reaction-based indicator displacement assays (R-IDAs), mechanically controlled indicator displacement assays (MC-IDAs), allosteric indicator displacement assays (A-IDAs), catalytic chemosensing assay (CCA), dimer dye assembly assay (DDA), and quencher displacement assay (QDA). All these evolutionary extensions of IDAs have been discussed in detail from concept to applications along with the possible future outcomes. The authors are of the viewpoint that this chapter will develop a better understanding of the researchers worldwide in the context of the advancement of IDAs. 

For the pattern-based recognition of various metal species and bioanalytes, nature has stimulated an emergent supramolecular domain of synthetic receptor arrays and assays. It is not always necessary for a synthetic receptor to be selective for a particular analyte in a differential receptor array, but the inclusive signal response from a typical sensory array must be diagnostic for the target analyte. This new category of molecular recognition is rapidly advancing with various groups constructing novel array platforms as well as receptors. Owing to easy operation and better selectivity, the sensory array has gained significant attention in the realm of complex system analysis. Besides the conceptual background, the authors have elaborated on the applications of various differential arrays through numerous examples. The authors believe that this chapter devoted to IDA-based differential sensory arrays and assays will bring a new episode of IDA-based chemosensors for target analytes. 

Owing to the low cost, fast response, easy miniaturization, portable instrumentation, and multiple analyte detection capabilities, electrochemical sensors stand out in the realm of sensing and thus occupy a prominent place in analytical supramolecular chemistry. Over the past several decades, the recognition of biologically and environmentally vital analytes via electrochemical responses (increase or decrease in current density), has attracted much attention from supramolecular chemists. The fabrication of electrochemical sensors through a competitive sensing phenomenon known as indicator displacement assay (IDA) has made them more realistic for target analyte detection. In this chapter, besides discussing various types and techniques of electrochemical sensors, we envisioned discussing diverse IDAbased electrochemical sensors for saccharides, biomarkers, neurotransmitters, and various other analytes. The authors are of the viewpoint that this chapter will meet the needs of the researchers working on the design, fabrication, and application of IDAbased electrochemical sensors.