Abstract
Label-free optical biosensors are an intriguing option for the analyses of many analytes, as they offer several advantages such as high sensitivity, direct and real-time measurement in addition to multiplexing capabilities. However, development of label-free optical biosensors for small molecules can be challenging as most of them are not naturally chromogenic or fluorescent, and in some cases, the sensor response is related to the size of the analyte. To overcome some of the limitations associated with the analysis of biologically, pharmacologically, or environmentally relevant compounds of low molecular weight, recent advances in the field have improved the detection of these analytes using outstanding methodology, instrumentation, recognition elements, or immobilization strategies. In this review, we aim to introduce some of the latest developments in the field of label-free optical biosensors with the focus on applications with novel innovations to overcome the challenges related to small molecule detection. Optical label-free methods with different transduction schemes, including evanescent wave and optical fiber sensors, surface plasmon resonance, surface-enhanced Raman spectroscopy, and interferometry, using various biorecognition elements, such as antibodies, aptamers, enzymes, and bioinspired molecularly imprinted polymers, are reviewed.
Highlights
Label-free optical biosensors are an intriguing option for the analyses of many analytes, as they offer several advantages such as high sensitivity, direct and real-time measurement in addition to multiplexing capabilities
By surface-initiated polymerization, where the initiator is immobilized to the sensor surface prior to the polymerization, ultrathin molecularly imprinted polymer (MIP) films have been prepared, for example, for domoic acid (DA) [123], malachite green [131], acephate [132], ametryn [133], and profenofos [134] detection showing the potential of MIPs for selective and sensitive analysis of small molecules
Surface-enhanced Raman spectroscopy (SERS) is a powerful vibrational spectroscopy technique that has unique features compared to other sensor devices using various kinds of signal readouts, including colorimetry, fluorescence, surface plasmon resonance, and electrochemistry [154,155,156]
Summary
Small molecules can be defined as low molecular weight organic molecules which are typically less than 1000 Da in size This category includes a wide variety of different chemical compounds, of either natural or pharmaceutical origin, many of which are biological, pharmacologically, or environmentally relevant, which makes detection and quantification of these molecules important in many disciplines. Chlorpyrifos, a broad spectrum pesticide which belongs to the group of organophosphates and is used worldwide in a wide range of crops, presents a major concern for potential environmental contamination and overuse, improper storage or disposal of these molecules [8,9]. Some of the advantages of biosensors over classical methods for small molecule detection include real-time monitoring, high specificity, fast response times, reduced consumption of organic solvents and sample manipulation, portability, compactness, and easy operation avoiding the need of skilled personnel [23]
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