Detection of chemical and biological agents plays a fundamental role in biomedical, forensic and environmental sciences1–4 as well as in anti bioterrorism applications.5–7 The development of highly sensitive, cost effective, miniature sensors is therefore in high demand which requires advanced technology coupled with fundamental knowledge in chemistry, biology and material sciences.8–13

In general, sensors feature two functional components: a recognition element to provide selective/specific binding with the target analytes and a transducer component for signaling the binding event. An efficient sensor relies heavily on these two essential components for the recognition process in terms of response time, signal to noise (S/N) ratio, selectivity and limits of detection (LOD).14,15 Therefore, designing sensors with higher efficacy depends on the development of novel materials to improve both the recognition and transduction processes. Nanomaterials feature unique physicochemical properties that can be of great utility in creating new recognition and transduction processes for chemical and biological sensors15–27 as well as improving the S/N ratio by miniaturization of the sensor elements.28

Gold nanoparticles (AuNPs) possess distinct physical and chemical attributes that make them excellent scaffolds for the fabrication of novel chemical and biological sensors (Figure 1).29–36 First, AuNPs can be synthesized in a straightforward manner and can be made highly stable. Second, they possess unique optoelectronic properties. Third, they provide high surface-to-volume ratio with excellent biocompatibility using appropriate ligands.30 Fourth, these properties of AuNPs can be readily tuned varying their size, shape and the surrounding chemical environment. For example, the binding event between recognition element and the analyte can alter physicochemical properties of transducer AuNPs, such as plasmon resonance absorption, conductivity, redox behavior, etc. that in turn can generate a detectable response signal. Finally, AuNPs offer a suitable platform for multi-functionalization with a wide range of organic or biological ligands for the selective binding and detection of small molecules and biological targets.30–32,36 Each of these attributes of AuNPs has allowed researchers to develop novel sensing strategies with improved sensitivity, stability and selectivity. In the last decade of research, the advent of AuNP as a sensory element provided us a broad spectrum of innovative approaches for the detection of metal ions, small molecules, proteins, nucleic acids, malignant cells, etc. in a rapid and efficient manner.37



Figure 1

Physical properties of AuNPs and schematic illustration of an AuNP-based detection system.



In this current review, we have highlighted the several synthetic routes and properties of AuNPs that make them excellent probes for different sensing strategies. Furthermore, we will discuss various sensing strategies and major advances in the last two decades of research utilizing AuNPs in the detection of variety of target analytes including metal ions, organic molecules, proteins, nucleic acids, and microorganisms.

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Gold nanoparticles in chemical and biological sensing.

5.1. Detection Formats 475 5.2. Food Quality and Safety Analysis 477 5.2.1. Pathogens 477 5.2.2. Toxins 479 5.2.3. Veterinary Drugs 479 5.2.4. Vitamins 480 5.2.5. Hormones 480 5.2.6. Diagnostic Antibodies 480 5.2.7. Allergens 481 5.2.8. Proteins 481 5.2.9. Chemical Contaminants 481 5.3. Medical Diagnostics 481 5.3.1. Cancer Markers 481 5.3.2. Antibodies against Viral Pathogens 482 5.3.3. Drugs and Drug-Induced Antibodies 483 5.3.4. Hormones 483 5.3.5. Allergy Markers 483 5.3.6. Heart Attack Markers 484 5.3.7. Other Molecular Biomarkers 484 5.4. Environmental Monitoring 484 5.4.1. Pesticides 484 5.4.2. 2,4,6-Trinitrotoluene (TNT) 485 5.4.3. Aromatic Hydrocarbons 485 5.4.4. Heavy Metals 485 5.4.5. Phenols 485 5.4.6. Polychlorinated Biphenyls 487 5.4.7. Dioxins 487 5.5. Summary 488 6. Conclusions 489 7. Abbreviations 489 8. Acknowledgment 489 9. References 489

Surface Plasmon Resonance Sensors for Detection of Chemical and Biological Species

Surface plasmon resonance (SPR) biosensors are optical sensors exploiting special electromagnetic waves—surface plasmon-polaritons—to probe interactions between an analyte in solution and a biomolecular recognition element immobilized on the SPR sensor surface. Major application areas include detection of biological analytes and analysis of biomolecular interactions where SPR biosensors provide benefits of label-free real-time analytical technology. This paper reviews fundamentals of SPR affinity biosensors and discusses recent advances in development and applications of SPR biosensors.

Present and future of surface plasmon resonance biosensors.

Sensitive optical biosensors for unlabeled targets: a review.

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Functional Nucleic Acid Sensors

Analytical applications of aptamers.

Surface plasmon resonance imaging for affinity-based biosensors

The DNA thrombin aptamer has been extensively investigated, and the coupling of this aptamer to different transduction principles has demonstrated the wide applicability of aptamers as bioreceptors in bioanalytical assays. The goal of this work was to design an aptamer-based sandwich assay with electrochemical detection for thrombin analysis in complex matrixes, using a simple target capturing step by aptamer-functionalized magnetic beads. The conditions for the aptamer immobilization and for the protein binding have been first optimized by surface plasmon resonance, and then transferred to the electrochemical-based assay performed onto screen-printed electrodes. The assay was then applied to the analysis of thrombin in buffer, spiked serum, and plasma and high sensitivity and specificity were found. Moreover, thrombin was generated in situ in plasma by the conversion of its precursor prothrombin, and the formation of thrombin was followed at different times. The concentrations detected by the electrochemical assay were in agreement with a simulation software that mimics the formation of thrombin over time (thrombogram). The proposed work demonstrates that the high specificity of aptamers together with the use of magnetic beads are the key features for aptamer-based analysis in complex matrixes, opening the possibility of a real application to diagnostics or medical investigation.

Aptamer-Based Detection of Plasma Proteins by an Electrochemical Assay Coupled to Magnetic Beads

Aptamers-based assays for diagnostics, environmental and food analysis

Aptamers are artificial nucleic acid ligands that can be generated against amino acids, drugs, proteins and other molecules. They are isolated from complex libraries of synthetic nucleic acids by an iterative process of adsorption, recovery and amplification. This review described the in vitro process to obtain aptamers (SELEX). It mentions the main characteristics of these molecules (i.e. affinity, specificity and stability). Moreover, it discusses advantages over antibodies. It reports potential applications of aptamers in analytical and diagnostic assays as biocomponents of biosensors (aptasensors) and allosteric ribozymes (aptazymes).

Maria Minunni

Papers

Analytical applications of aptamers.

Surface plasmon resonance imaging for affinity-based biosensors

Aptamer-Based Detection of Plasma Proteins by an Electrochemical Assay Coupled to Magnetic Beads

Aptamers-based assays for diagnostics, environmental and food analysis

New trends in affinity sensing: aptamers for ligand binding