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.

/pdf/gold-nanoparticles-in-chemical-and-biological-sensing-5e2qojkdzn.pdf

Gold nanoparticles in chemical and biological sensing.

The field of chemical sensing is becoming ever more dependent upon novel materials. Polymers, crystals, glasses, particles, and nanostructures have made a profound impact and have endowed modern sensory systems with superior performance. Electronic polymers have emerged as one of the most important classes of transduction materials; they readily transform a chemical signal into an easily measured electrical or optical event. Although our group reviewed this field in 2000,1 the high levels of activity and the impact of these methods now justify a subsequent review as part of this special issue. In this review we restrict our discussions to purely fluorescence-based methods using conjugated polymers (CPs). We further confine our detailed coverage to articles published since our previous review and will only detail earlier research in this Introduction to illustrate fundamental concepts and terminology that underpin the recent literature.

Chemical sensors based on amplifying fluorescent conjugated polymers.

This critical review provides an overall survey of the basic concepts and up-to-date literature results concerning the very promising use of gold nanoparticles (AuNPs) for medicinal applications. It includes AuNP synthesis, assembly and conjugation with biological and biocompatible ligands, plasmon-based labeling and imaging, optical and electrochemical sensing, diagnostics, therapy (drug vectorization and DNA/gene delivery) for various diseases, in particular cancer (also Alzheimer, HIV, hepatitis, tuberculosis, arthritis, diabetes) and the essential in vitro and in vivo toxicity. It will interest the medicine, chemistry, spectroscopy, biochemistry, biophysics and nanoscience communities (211 references).

Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity

9.2. Protein-Based Hg(II) Detectors 3467 9.3. Oligonucleotide-Based Hg(II) Detector 3467 9.4. DNAzyme-Based Hg(II) Detectors 3469 9.5. Antibody-Based Hg(II) Detector 3469 10. Mercury Detectors Based on Materials 3469 10.1. Soluble and Fluorescent Polymers 3469 10.2. Membranes, Films, and Fibers 3471 10.3. Micelles 3473 10.4. Nanoparticles 3473 11. Perspectives 3474 12. Addendum 3475 12.1. Small Molecules 3475 12.2. Biomolecules 3477 12.3. Materials 3477 13. List of Abbreviations 3477 14. Acknowledgments 3478 15. References 3478

Tools and tactics for the optical detection of mercuric ion.

Exposure to even very low levels of lead, cadmium, and mercury ions is known to cause neurological, reproductive, cardiovascular, and developmental disorders, which are more serious problems for children particularly. Accordingly, great efforts have been devoted to the development of fluorescent and colorimetric sensors, which can selectively detect lead, cadmium, and mercury ions. In this critical review, the fluorescent and colorimetric sensors are classified according to their receptors into several categories, including small molecule based sensors, calixarene based chemosensors, BODIPY based chemosensors, polymer based chemosensors, DNA functionalized sensing systems, protein based sensing systems and nanoparticle based sensing systems (197 references).

Fluorescent and colorimetric sensors for detection of lead, cadmium, and mercury ions

A sensor array containing six non-covalent gold nanoparticle-fluorescent polymer conjugates has been created to detect, identify and quantify protein targets. The polymer fluorescence is quenched by gold nanoparticles; the presence of proteins disrupts the nanoparticle-polymer interaction, producing distinct fluorescence response patterns. These patterns are highly repeatable and are characteristic for individual proteins at nanomolar concentrations, and can be quantitatively differentiated by linear discriminant analysis (LDA). Based on a training matrix generated at protein concentrations of an identical ultraviolet absorbance at 280 nm (A280 = 0.005), LDA, combined with ultraviolet measurements, has been successfully used to identify 52 unknown protein samples (seven different proteins) with an accuracy of 94.2%. This work demonstrates the construction of novel nanomaterial-based protein detector arrays with potential applications in medical diagnostics.

Detection and identification of proteins using nanoparticle-fluorescent polymer 'chemical nose' sensors.

The complexes of a carboxylate-substituted poly(para-phenyleneethynylene) (PPE) with histone, bovine serum albumin, and papain were investigated. At higher concentrations, the proteins have a significant effect on the emission characteristics of the PPE. The electrostatic complexes formed from the PPE, and the proteins are agglutinated by different metal cations. The observed selectivities and sensitivities of these simple systems are most unusual; combination of the carboxylate-PPE and commercially available papain forms an electrostatic complex that is precipitated by mercury ions at concentrations above 10-5 mol L-1.

Modulating the sensory response of a conjugated polymer by proteins: an agglutination assay for mercury ions in water.

Rapid and effective differentiation between normal and cancer cells is an important challenge for the diagnosis and treatment of tumors. Here, we describe an array-based system for identification of normal and cancer cells based on a “chemical nose/tongue” approach that exploits subtle changes in the physicochemical nature of different cell surfaces. Their differential interactions with functionalized nanoparticles are transduced through displacement of a multivalent polymer fluorophore that is quenched when bound to the particle and fluorescent after release. Using this sensing strategy we can rapidly (minutes/seconds) and effectively distinguish (i) different cell types; (ii) normal, cancerous and metastatic human breast cells; and (iii) isogenic normal, cancerous and metastatic murine epithelial cell lines.

https://www.pnas.org/content/pnas/106/27/10912.full.pdf

Detection and differentiation of normal, cancerous, and metastatic cells using nanoparticle-polymer sensor arrays

A sensor array comprising six functionalized poly(p-phenyleneethynylene) polymers was constructed and used to detect and identify protein analytes. The presence of proteins alters the fluorescence properties of the polymers, generating a distinct fluorescence response pattern for a given protein. Linear discriminant analyses accurately differentiate the patterns of 17 proteins at nano- to micromolar concentrations. An identification accuracy of 97% was obtained on the basis of the tests with 68 unknown protein samples from the training set.

/pdf/array-based-sensing-of-proteins-using-conjugated-polymers-3ndlzg7z51.pdf

Ik-Bum Kim

Papers

Detection and identification of proteins using nanoparticle-fluorescent polymer 'chemical nose' sensors.

Modulating the sensory response of a conjugated polymer by proteins: an agglutination assay for mercury ions in water.

Detection and differentiation of normal, cancerous, and metastatic cells using nanoparticle-polymer sensor arrays

Array-Based Sensing of Proteins Using Conjugated Polymers

Sensing of Lead Ions by a Carboxylate-Substituted PPE: Multivalency Effects