Aptamer-based nanobiosensors
Introduction
For four decades, antibodies have dominated the healthcare market based on their effective capturing capacity for proteins. Then, immunoassay has become the most popular platform in clinical tests and biosensors today. Since its first report in 1990, aptamers have received extensive interests as a rival of antibody due to its several advantages compared to antibodies. One of the most important merits of using aptamers is that there are no limitations on their targets. Although antibodies- or enzyme-based assays are well established as a standard biosensor platform for the detection of various targets, they are still restricted in recognizing many of targets, such as toxic small molecules or non-immunogenic targets, and also not easy to recognize the small differences of their macromolecular targets like proteins. To date, thousands of DNA or RNA aptamers have been identified for various targets, such as proteins, peptides, amino acids, antibiotics, small chemicals, viruses, whole or part of cells, and even metal ions, with high affinity and specificity, and they have been applied in various fields, such as diagnostics, therapeutics, biosensors and bio-analytical fields. This fast enrichment of available aptamers should be mainly due to the recent advances in the systematic evolution of ligands by exponential enrichment (SELEX) process, such as the high-throughput and automated SELEX processes, including the most recent development of the immobilization-free screening of aptamers using graphene oxide (Park et al., 2012). According to the advancement on the aptamer screening and development, thousands of articles about aptamers and SELEX have been published, and numerous patents have been issued. Therefore, researchers and companies have obtained more chances to develop or commercialize various platforms of aptasensors for numerous targets, especially since it has been now found that the dual aptamers can be developed cognately (Ahmad Raston and Gu, 2015, Park et al., 2014).
Aptamer-based biosensors among various applications have exceptional merits, compared to the natural receptors, such as antibodies and enzymes. The intrinsic properties of aptamers, as nucleic acids, high flexibility of structure, and convenience in the design of their structure, enable to develop the various novel aptasensors. 1) Aptamers as even complex form with target can be amplified by polymerase chain reaction (PCR). Based on this property, a real-time PCR analysis (Fischer et al., 2008, Lee et al., 2009) and rolling-circle amplification (Cho et al., 2005, Liu et al., 2014b, Yang et al., 2007, Zhou et al., 2007) have been applied in aptasensors for signal amplification. Microarray platform is also available for aptamer-based analysis, in which the quantification of thousands of targets is possible (Kraemer et al., 2011). Besides, any other nucleic detection methods can be adopted for aptasensors by combining both capturing and detection steps. 2) Aptamers fold as well-defined 3-D structure upon binding to target and their conformation are very flexible depending on the existence of target molecules (Cho et al., 2009). 3) The formation of aptamers can be easily modulated using complementary sequences. This aptamer-complementary DNA complex can be easily destroyed by competitive interaction among aptamer, target, and complementary DNA, when the target molecules are added. The design of complementary sequences should be depending on the sequence of aptamer and their affinity with target sophisticatedly. These unique properties of aptamers on the flexible conformational change added a few novel methods in the signal generation on different formats of biosensors, such as simple binding or sandwich-type assay. These approaches are considered to be very powerful especially for the detection of the small molecular targets, since, the sandwich assay format or the mass-dependent detection methods, such as SPR or quartz crystal microbalance (QCM), are not possible due to their small molecular sizes. 4) The easy modification and labeling of dyes or functional group at the end or inter-sites of the aptamer sequence is an another merit to establish the aptamer-based assay format in terms of the signal generation and the well oriented immobilization on solid supports. From these advantages, aptasensors have now been a significantly established in life science, biomedical diagnostics, and biosensors, although they entered only about a decade ago into this bio-analytical field.
In addition, the most recent success in the cognate generation of dual aptamers, which is known to be possible due to the success of aptamer screening without target immobilization, has resulted in opening the use of a sandwich-type sensing platform (Ahmad Raston and Gu, 2015, Park et al., 2014). The advantages of using dual aptamers in aptasensors should be as follow: 1) easy and highly amplified signals can be generated from the use of the secondary signaling aptamer, 2) sandwich-type stable platforms can be definitely adopted, which has been known to be one of the weak points using an aptamer, and 3) the realization of aptasensors in markets are now very close, since stripe-type sandwich platform can be used like ELISA or any other antibody-based sandwich assays.
Recently, nanotechnology has added a prominent value to the analytical and diagnostics field, i.e. the conjugation of aptamers on various nanomaterials, which has led to highly sensitive and selective aptasensors. The unique properties of nanomaterials such as size- and shape-dependent optical property, easy tuning of surface properties, and catalytic activities are very useful not only for the signal generation but also for the signal amplification. During past few years, there have been great advances in the synthesis of numerous nanomaterials, such as metallic nanoparticles, quantum dots, silica nanoparticles, and carbon nanotubes (Burda et al., 2005), and their application into nanosensors (Baron et al., 2007, Lu and Liu, 2007, Stewart et al., 2008, Wang and Lu, 2009). The integration of aptamers and nanomaterials has been studied actively to develop novel and sensitive sensing system (Lin et al., 2009, Wang et al., 2009a). Although aptasensors are still in its infancy, compared to immunoassay and enzyme-based biosensors, aptamer-based biosensors will be eventually become a great tool by the combination with nanomaterials.
This review summarized recent prominent reports on aptasensors utilizing nanomaterials to understand the principle of aptamer-based biosensors and provide an insight for new design of aptasensing techniques. The perspective on aptasensors was also discussed in view of technology and market.
Section snippets
Gold nanoparticles
Gold nanoparticles (AuNPs) are considered as the most favorite nanomaterials for the aptasensor development due to their physical and chemical properties. In addition, the conjugation of aptamers on AuNPs by chemisorption or physical adsorption has been well accomplished (Huang et al., 2005, Li and Rothberg, 2004a, Li and Rothberg, 2004b, Mirkin et al., 1996, Pavlov et al., 2004). These features of AuNPs have contributed to conduct simple, efficient and sensitive aptamer-based biosensors. In
Surface plasmon resonance (SPR)-based aptasensors
To date, a number of aptasensors have been developed based on remarkable merits over immunoassay. Among the different available aptasensing platforms, SPR hold a great promise for the development of aptasensors, because this technology offers label-free detection and real time quantitative analysis, and provides binding constant determination. SPR is a mass-sensitive biosensor which sensitively detects mass changes associated with the change in refractive index at the surface due to the
Lateral flow strip-based aptasensors
A lateral flow strip aptasensor can be developed by two approaches, sandwich format and target induced conformational change/displacement format that were described enough in above sections. In this section, the recent examples and advances of lateral flow strip aptasensors were introduced and the strategies for the design of them were comprehended. Xu and co-workers demonstrated a lateral flow aptasensor for thrombin detection according to the conventional sandwich format (Xu et al., 2009a).
Conclusions and perspectives
In a past decade, the development of aptasensors have been remarkable and aptasensors have enough demonstrated their merits and potentials in bio-analysis field. Despite of this excellent progress, the market of aptasensors and aptamer-based diagnostics is not explored yet. For the successive penetration of aptasensors into market, a number of issues should be solved at technical and industrial aspects. At first, only a few of aptamers such as thrombin, adenosine, cocaine, ATP and PDGF binding
Acknowledgment
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MEST) (no. 2013R1A1A2021531).
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