ReviewNanoparticles-based strategies for DNA, protein and cell sensors
Introduction
Bottom–up nanotechnology approaches are offering a large series of nanoparticles (NPs) with special interest for biosensing systems. Investigations of these materials are gaining interest due to the size and shape-dependent physical, chemical and electrochemical properties which make them extremely useful in sensing and biosensing applications (Rosi and Mirkin, 2005) The size and composition sometimes make NPs even more attractive than the corresponding bulk structure. A target binding event (i.e. DNA hybridization or immunoreaction) occurring onto NPs surface may have a significant effect on its optical (change of the light absorption/emission) or electrochemical properties (oxidation/reduction current onto a transducing platform) offering novel alternatives for bioanalysis. For example of a special interest are metal nanoparticles of group II–VI compound semiconductors like CdSe, ZnSe, CdTe, etc. called also quantum dots (QDs) (Murphy, 2002) as well as gold nanoparticles (AuNPs). QDs are highly fluorescent and in comparison with organic dyes such as rhodamine are 20 times as bright, 100 times as stable against photobleaching, and one-third as wide in spectral line width (Chan and Nie, 1998). Another intrinsic benefit of NPs is the increased surface area available with special interest for bioapplications between others.
The application of NPs in biosensors is strongly related to their properties that depend in certain mode from the synthesis (quality of nanoparticles) and posterior modifications (chemical and biological). The NPs preparation procedures, either in colloidal solutions or grown on solid substrates, have been extensively reviewed (Parak et al., 2003). Along with synthetic advances for varying the size, shape, and composition of nanostructured materials has come the ability to tailor their binding affinities for various biomolecules through surface modification and engineering.
Many types of NPs of different sizes and compositions are now available, which facilitate their optical (Rosi and Mirkin, 2005, Merkoçi, 2007a, Merkoçi, 2007b) and electrochemical (Wang, 2003, Merkoçi et al., 2005a, Merkoçi et al., 2005b) related application in enzyme-based sensors, immunosensors and DNA sensors. Nevertheless biological or molecular coating which will act as a bioactive and selective interface is necessary to be attached to the nanoparticles prior to their application in biosensing systems. The functionalization of inorganic nanoparticles by means of evolutionary optimized biological components concerns an important point. Adsorption, linkage via thiol groups, electrostatic interaction, covalent linkage eyc. are the various reported strategies. Since the nanoparticles and biomolecules typically meet at the same nanometer length scale, this interdisciplinary approach is even contributing to the establishment of the novel field, descriptively termed biomolecular nanotechnology or nanobiotechnology (Niemeyer, 2001).
In addition to the chemical and biological modification (including coatings with antibodies, DNA, cells etc.) the NP characterisation and quantification play a crucial role for the final biosensing application. The optical and electrochemical properties of NPs offer various signal transduction modes, including simultaneous approaches (optical and electrochemical) not available with other materials (Ambrosi et al., 2007, Merkoçi, 2007a, Merkoçi, 2007b,).
The range of the used NPs is as large as the range of potential applications in biosensors and depends strongly from the applications, the biomolecules to detect as well as the type of the sample to be analysed. This review will discuss some typical examples of NPs application for DNA, protein and cell analysis using optical and electrical biosensing systems. (see Fig. 1). As some of the detection principles, i.e. optical (Rosi and Mirkin, 2005) or electrical (Merkoçi et al., 2005a, Merkoçi et al., 2005b) detections only along with the corresponding biosensing application, are previously revised the objective now of this review is to give readers in a single source the whole range of the NP detection possibilities offered and discuss novel opportunities for future applications in bioanalysis. Detailed aspects related to the (bio)chemistry of nanoparticles (Niemeyer, 2001) including their modifications and the detection principle are not included as these have been extensively revised in the mentioned earlier reviews.
Section snippets
Light absorption
Conventional methods that use radioactive labeled nucleic acid probes or the polymerase chain reaction (PCR) coupled with molecular fluorophore assays offer high sensitivity of detection, but they suffer from several drawbacks that include complex handling procedures, easy contamination, high cost, and lack of portability (Xu et al., 2009a, Xu et al., 2009b). In this context the use of NPs along with simple detection alternatives such as those based on light absorption measurement is very
Electro-mechanical, electrical and electrochemical detection alternatives
In this section several strategies based on electro-mechanical (i.e. quartz crystal microbalance), electrical (measurements of changes in the ohmic response of a circuit) and
electrochemical methods will be discussed. In the last one the current that indicates the presence of a target is faradaic in origin. It arises as a result of the oxidation or reduction of either a redox probe in the detection medium or the redox activity of a conjugated electroactive nanoparticle approaches. This will
Magnetic sensors
Surface-functionalized paramagnetic particles are widely employed in various protein and DNA detection systems as immobilization platform with interest for purification/incubation processes. Although they are originally designed to enhance and simplify the protein/DNA isolation and purification process, their field of application has significantly widened.
Sensing based on the combination of giant magnetoresistive (GMR) sensors and magnetic nanoparticles has attracted much attention as a
Concluding remarks
Recent advances in nanoscience and nanotechnology have enabled a paradigm shift in biosensing technology. In this review an attempt to give a broad overview on the use of nanoparticles for DNA, protein and cell analysis is made. Nanoparticles are leading to the development of various biosensing devices with interest for applications in several fields. Optical detection alternatives based on light absorption and scattering induced by nanoparticles used as labels are being extended not only to
Acknowledgments
We acknowledge funding from the MEC (Madrid) for the projects MAT2008-03079/NAN, CSD2006-00012 “NANOBIOMED” (Consolider-Ingenio 2010).
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