Nanoconjugated materials as sensors in point-of-care diagnostic tools: Detection of small molecules and viruses

Recent Advances in Real-Time Label-Free Detection of Small Molecules

“…Although reviews of label-free biosensing technologies are readily available [21][22][23], we offer a perspective on challenges and advancements that specifically target the detection of small molecules under 1 kDa. Recent reviews on small-molecule detection have been focused on advancements of particular transducers or particular small molecules of interest [2,[4][5][6][7]16]. Therefore, this review offers a comprehensive introduction to the recent advancement in label-free and real-time small-molecule detections since the last comprehensive review to our knowledge [1].…”

“…Optical transductions can measure a variety of signals related to the presence of small molecules, such as absorption, scattering, luminescence, or refractive index [2]. Optical biosensors typically offer fast results with high temporal resolution for real-time monitoring of binding, making them ideal for diagnostics and point-of-care devices [7]. However, the signal of optical transducers generally scales with the size and/or mass of the analyte of interest, especially when avoiding the use of fluorescent labels [2,7,24].…”

“…Optical biosensors typically offer fast results with high temporal resolution for real-time monitoring of binding, making them ideal for diagnostics and point-of-care devices [7]. However, the signal of optical transducers generally scales with the size and/or mass of the analyte of interest, especially when avoiding the use of fluorescent labels [2,7,24]. For example, one of the commonly used label-free optical detection techniques, surface plasmon resonance, has been lauded as the gold standard for molecular binding kinetic measurement, being used for analytes such as proteins, DNA, RNA, peptides, and other biological macromolecules, but attempts to utilize SPR for the detection of small molecules required advanced instrumentation or significant enhancement of receptor surface [15,25].…”

“…These properties have great appeal in the pharmaceutical industry, with 15 of the 37 drugs approved by the FDA in 2022 being small molecules [3]. On the other hand, the properties that make small molecules appealing for drug development also make them effective toxins, carcinogens, mutagens, and endocrine disruptors both natural, such as several secondary metabolites of fungi, cyanobacteria, plants, and other organisms; and artificial, such as chemical warfare agents [1,2,[4][5][6][7]. Furthermore, biological systems themselves utilize small molecules such as amino acids, steroids, sugars, or metabolites for many of the processes essential for life [1,2,7].…”

“…Biosensors are generally composed of a receptor that captures an analyte and a transducer that changes in property upon the binding between the analyte and the receptor to produce a recordable signal [2]. Unfortunately, due to the low abundance and mass of small molecules, many techniques, especially those where the transducer's signal strength scales with analyte mass, are challenging to achieve the sensitivity necessary for the effective detection of small molecules under biologically relevant conditions [7,8]. In addition, label-free techniques are greatly preferred for small molecules, even more so compared to larger analytes like proteins.…”