Colloidal nanoparticles as advanced biological sensors

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Science  03 Oct 2014:
Vol. 346, Issue 6205, 1247390
DOI: 10.1126/science.1247390

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Structured Abstract


Nanoparticle biosensors have the potential to enhance or supersede current analytical techniques, and their introduction could have a great impact in research and clinical practice. The unique optical properties of many nanomaterials make them ideal for biosensing. Colloidal fluorescent and plasmonic nanoparticles are particularly interesting, as they produce intense responses to incident light, and linking this response to the presence of a target analyte yields extremely sensitive detection in solution.

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Optimization of nanoparticle biosensors by considering the nanoparticle core, surface, and sensing properties, with an eye toward their application in research and as clinical tools. This translational process relies on the availability of high-quality nanoparticles with precisely engineered surfaces and biosensing mechanisms that allow detection with high sensitivity and specificity.


Much research has centered on fluorescent quantum dots (QDs) and plasmonic gold nanoparticles (AuNPs) and has expanded to include carbon dots, silicon dots, upconverting nanoparticles, alloyed plasmonic nanoparticles, and gold and silver nanoclusters, among a constantly growing repertoire. New tools for probing the nucleation and growth of nanoparticles, such as in situ synchrotron x-ray irradiation, liquid cell transmission electron microscopy, and computer simulation, are revealing ever more about fundamental processes—for example, the importance of particle coalescence and surface ligand conformation during particle growth. Precision engineering of particle surfaces is required to construct advanced nanoparticle biosensors, and this is being facilitated by a new generation of modular small-molecule and polymeric capping agents, the incorporation of new high-yield bio-orthogonal “click”-like functional groups, and advanced engineering of biomolecular sensing constructs (e.g., by recombinant protein engineering). Notable successes in the field include the precision synthesis of nanoparticles in microfluidic systems; ultrasensitive detection of cancer biomarkers in human serum with time-gated QD fluorescence; multiplexed intracellular sensing of mRNA using superquenching AuNPs; multiplexed detection of analytes with simple technologies such as smartphones; in vivo sensing of reactive oxygen species and methyl mercury; and the integration of nanoparticle biosensors with advanced DNA/RNA target amplification protocols.


Many advanced applications are anticipated for nanoparticle biosensors, including as research analytical tools, intracellular sensors, and in vivo sensors for real-time detection and visualization of analytes and structures inside the body. There has been great success in synthesizing nanoparticles with excellent physical and chemical properties and in demonstrating their applications as biosensors. Looking toward high-impact applications, the main challenges are to develop techniques to synthesize reproducible high-quality nanoparticle biosensors on a mass scale and to maximize performance in physiological conditions. By drawing on many fields, including molecular biology, bioinformatics, computer modeling, bioengineering, and applied physics, we can compile the diverse toolset required to overcome these challenges and move toward high-impact applications of nanoparticle biosensors.

Biological sensing using nanoparticles

Colloidal fluorescent and plasmonic nanoparticles yield intense responses to incident light, making them useful as sensors or probes for sensitive detection in solution. Howes et al. review the potential uses of nanoparticle biosensors in research and diagnostics. A range of methods allow for the chemical modification of the particle surfaces so that they can be tuned for specific analytes and give optical signals for a range of biological conditions of interest. Signals can be detected in complex media or in vivo making the particles of interest for both laboratory research and in clinical settings.

Science, this issue 10.1126/science.1247390


Colloidal nanoparticle biosensors have received intense scientific attention and offer promising applications in both research and medicine. We review the state of the art in nanoparticle development, surface chemistry, and biosensing mechanisms, discussing how a range of technologies are contributing toward commercial and clinical translation. Recent examples of success include the ultrasensitive detection of cancer biomarkers in human serum and in vivo sensing of methyl mercury. We identify five key materials challenges, including the development of robust mass-scale nanoparticle synthesis methods, and five broader challenges, including the use of simulations and bioinformatics-driven experimental approaches for predictive modeling of biosensor performance. The resultant generation of nanoparticle biosensors will form the basis of high-performance analytical assays, effective multiplexed intracellular sensors, and sophisticated in vivo probes.

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