Nanoparticles for bioanalysis

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Abstract

This review covers the emerging field of nanobiotechnology, in which nanoparticles are applied to the analysis of biomolecules. Nanoparticles can be used in a variety of bioanalytical formats, and this review discusses four classes of use. First, nanoparticles as quantitation tags, such as the optical detection of quantum dots and the electrochemical detection of metallic nanoparticles. Second, encoded nanoparticles as substrates for multiplexed bioassays, such as striped metallic nanoparticles. Third, nanoparticles that leverage signal transduction, for example in colloidal gold-based aggregation assays. Fourth, functional nanoparticles that exploit specific physical or chemical properties of nanoparticles to carry out novel functions, such as the catalysis of a biological reaction. In addition, the review discusses the next generation of nanoparticles that will be utilized in the life sciences, such as nanodots and carbon nanotubes.

Introduction

Nanobiotechnology — a new word — describes the use of nanotechnology in biological systems. Although still in its infancy, nanotechnology is already having an impact in bioanalysis, where nanoparticles of a variety of shapes, sizes and compositions are poised to fundamentally change the bioanalytical measurement landscape. For example, it now appears clear that nanoparticles will overcome many of the significant chemical and spectral limitations of molecular fluorophores. Equally important, methods for preparation and handling of nanoparticle–biomolecule conjugates are proliferating, and such bioconjugation-ready nanoparticles are becoming commercially available. Thus, it seems appropriate to provide a critical assessment of the state-of-the art, as well as an indication of future directions.

This review focuses on nanoparticles for bioanalysis, covering peer-reviewed publications from 2001–2003. Accordingly, several of the groundbreaking papers from the late 1990s that had a catalytic effect on the field 1., 2., 3., 4., 5., 6., fall outside the period under review. Moreover, the earliest work in nanoparticles for bioanalysis, namely the use of 5–50 nm diameter colloidal gold as electron-dense, and immunocytochemical probes for electron microscopy, dates back to the 1970s, and was reviewed extensively in a three-volume series [7].

A further narrowing of the scope comes from our decision to focus on nanoparticles that are initially in suspension (and thus, equivalent, in some sense, to traditional biological reagents). Thus, while immobilized nanoparticles have tremendous potential in a variety of bioanalytical detection schemes (see, for example, Van Duyne’s recent work on nanoparticle-based sensing of glucose [8]), this field is not discussed herein. In addition, because of space limitations, we are unable to cover the entire landscape of excellent work in the nanoparticles arena, and therefore have instead tried to give the reader a taste of the scope of the work being carried out in the field.

Nanoparticles can be used in a variety of bioanalytical formats, and the review is divided accordingly (Figure 1). When nanoparticles are used as quantitation tags, either the particles themselves or a measurable parameter emanating from the particles (e.g. photons) are quantified. Encoded nanoparticles used as substrates rely on one or more identifiable characteristics to allow them to serve as encoded physical hosts for multiplexed bioassays. This is analogous to the positional encoding of assays on microarrays, but in solution. Nanoparticles that leverage signal transduction involve a change either in the location of nanoparticles relative to one another, or a perturbation in the biological system caused by the nanoparticle — both of which, in turn, lead to a change in a measurable signal. Functional nanoparticles exploit specific physical or chemical properties of nanoparticles to carry out novel functions, such as catalysis of a biological reaction. For certain particles and/or applications, these divisions can be blurred, but they nonetheless serve as a general classification method.

Section snippets

Nanoparticles as quantitation tags in biological assays

The driving force behind the use of nanoparticles as tags in biological assays is to eliminate the need for either organic fluorophores or radioactive labeling, both of which have shortcomings. The majority of the work has been focused in two areas, quantum dots and metallic-nanoparticles, with some development of novel reporters as well.

Quantum dots take advantage of the quantum confinement effect, giving the nanoparticles unique optical and electronic properties. Quantum dots offer advantages

Nanoparticles as substrates

Encoded nanoparticles can serve as substrates for multiplexed biological assays in solution. Compared with microarray-based methods, these ‘suspension arrays’ offer, in principle, greater flexibility (via the ability to easily incorporate a new assay via addition of a new bead type), more rapid assay times (radial versus planar diffusion), greater reproducibility (10 s to 100 000 s of replicates for each assay), and can potentially use less sample and reagent. Typically, analyte quantitation

Nanoparticles that leverage signal transduction

Nanoparticles that act as signal transducers show the most promise in diagnostic assays, due to the elimination of the need to tag a biological sample. With the sample preparation steps reduced or eliminated, the diagnostic test will become more robust and less expensive. As previously stated, we define signal transduction as a system in which a change occurs either to the location of nanoparticles relative to one another, or as a perturbation to the biological component of the assay — both of

Functional nanoparticles

One of the most exciting areas of nanobiotechnology is the use of nanomaterials to carry out particle-specific functions. In other words, intrinsic physical or chemical properties of the particles effect analytically relevant transformations. Three leading edge studies have been recently published that demonstrate this concept. Hamad-Schifferil et al. [52] used a radio-frequency magnetic field to inductively heat a gold nanoparticle attached to a DNA duplex to promote dehybridization. They

The next generation of nanoparticles

There are several nanoparticles currently being developed that show promise for bioassays, but have not yet been exploited to their full potential. A key advance has been the ability to control the shape of metallic nanoparticles, such as the Xia group’s [58] ‘nanocubes’. The same group has also synthesized hollow nanoparticles, which may be important in simultaneous bioanalysis and drug delivery regimes [59], particularly in light of their interesting optical properties [60]. Carbon nanotubes

Summary

While there can be no denying that instrumentation has had a major role in accelerating the pace of biological knowledge generation, the fundamental reality is that life science research is reagent driven. Indeed, even the most important instrumentation (e.g. DNA sequencing) incorporates reagent-intensive processes. The focus of this review has been to highlight advances in nanoparticles for bioanalysis, and in particular, nanoparticles that are used, or could eventually be used, as reagents.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • of special interest

  • ••

    of outstanding interest

Acknowledgements

The authors would like to acknowledge the Advanced Technology Program of the National Institute of Standards and Technology for funding (grant # 70NANB1H3028).

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