Review
Gold nanorod-based localized surface plasmon resonance biosensors: A review

https://doi.org/10.1016/j.snb.2014.01.056Get rights and content

Abstract

Noble metal nanoparticle-based localized surface plasmon resonance (LSPR) is an advanced and powerful label-free biosensing technique which is well-known for its high sensitivity to the surrounding refractive index change in the local environment caused by the biomolecular interactions around the sensing area. The characteristics of the LSPR effect in such sensors are highly dependent on the size, shape and nature of the material properties of the metallic nanoparticles considered. Among the various types of metallic nanoparticles used in studies employing the LSPR technique, the use of gold nanorods (GNRs) has attracted particular attention for the development of sensitive LSPR biosensors, this arising from the unique and intriguing optical properties of the material. This paper provides a detailed review of the key underpinning science for such systems and of recent progress in the development of a number of LSPR-based biosensors which use GNR as the active element, including an overview of the sensing principle, the synthesis of GNRs, the fabrication of a number of biosensors, techniques for surface modification of GNRs and finally their performance in several biosensing applications. The review ends with a consideration of key advances in GNR-based LSPR sensing and prospects for future research and advances for the development of the GNR-based LSPR biosensors.

Introduction

Biosensors have been continuing to play an important role in many scientific fields including clinical diagnostics, medical developments, illicit drug detection, food quality and safety, and environmental monitoring [1]. Their importance is seen in that each is a multi-billion dollar areas of activity and vitally important for the well-being of people the world over. A biosensor can be defined as an analytical device which comprises two basic components: a recognition unit used to capture the specific target, and a transducer that can convert the subtle biomolecular interactions into the quantifiable signal [2], which is usually electrical in nature. However, recent developments have seen an enormous growth in biosensors based on optical transducer principles, such as those using techniques such as fluorescence [3], [4], [5], surface plasmon resonance (SPR) [6], [7], [8] and chemiluminescence [9], [10], which have been developed for a wide range of applications. Among the various optical biosensors reported in the literature, SPR-based biosensors show a number of significant advantages over conventional sensors, including ultra-high refractive index sensitivity, fast sensor response, real-time detection, and a label-free technique. In addition, the advanced nature of SPR imaging (SPRi) technology not only retains these advantages of classical SPR sensing, but also allows the detection of target molecules on a biosensor chip to be visualized in real-time by using a CCD camera [11]. Thus SPR biosensors have been studied extensively and developed and commercialized in the past three decades in particular. SPR is an optical phenomenon where the surface conductive electrons of bulk metal oscillate collectively at their resonant frequency, and the electron oscillations propagate along the metal-dielectric interface and decay exponentially into both media [12]. However, in order to fabricate a SPR sensor chip, sophisticated instrumentation such as a sputter coater or vacuum evaporator is normally required to coat the noble metal film on the surface of an optical substrate, such as a prism and an optical fiber, to excite SPR. In addition, most commercial SPR instruments, such as the well-known Biacore™ series, are normally expensive and bulky, which limits the extent of their applications.

In recent years, biosensors based on localized surface plasmon resonance (LSPR), which is also a SPR phenomenon but exists in metallic nanoparticles (MNPs) rather than bulk metal, has attracted more and more attention. The physical properties of the noble metals change enormously from what is usually familiar when the size of these metal particles is on the nanoscale level and smaller than the wavelength of the light used to illuminate them [13], [14]. A particularly striking example is that the color of gold in the nanoworld is no longer the familiar ‘gold color’ but it can be as colorful as a rainbow, as shown in Fig. 1. Here gold nanorods (GNRs), with various aspect ratios and suspended in aqueous solutions, display a range of different colors. The SPR phenomenon also changed from SPR to LSPR when the bulk metal film was replaced by MNPs to excite SPR. Here the properties of LSPR are highly dependent on the material used and the size and shape of the metallic nanoparticles involved [14]. By manipulating these parameters, the LSPR wavelength can conveniently be tuned throughout the visible, near-infrared, and into the infrared region, allowing the LSPR sensor to be constructed for particular applications where a specific wavelength is desired. Compared to SPR sensors, LSPR sensors are of more flexible design and lower cost in terms of sensor fabrication, arising from the fact that LSPR can be excited when the light directly interacts with the MNPs and free from the need for prisms or other optical components. For instance, LSPR sensors can either be fabricated by immobilizing MNPs on a substrate, such as glass slide [15] or an optical fiber [16], or by simply suspending MNPs in solution to form a solution-phase based LSPR sensor [17]. In addition, as LSPR is highly localized at each individual MNPs, LSPR sensors can even be fabricated based on single nanoparticle [18]. Moreover, some LSPR biosensors have demonstrated superior sensitivity in comparison with the traditional bulk metal film based SPR biosensors [19], making them particularly attractive to use. These advantages of LSPR biosensors have prompted significant effort to be devoted to the development of sensitive LSPR biosensors and numerous promising LSPR biosensor designs continue to be reported in the literature, as this review emphasizes.

The advances seen in the fabrication of MNPs have led to considerable progress in the development of a range of LSPR biosensors in the past decade. Early research on the development of LSPR biosensor had mainly been focused on the use of spherical gold nanoparticles, due to their ease of synthesis. However recent developments have allowed a number of LSPR sensors, based on noble MNPs and of various shapes, to be developed and these have shown both higher sensitivities and other important advantages, in comparison to using gold nanosphere-based (GNS) LSPR sensors. Among these MNPs recently reported, GNRs have demonstrated unique optical properties, such as higher refractive index sensitivity and a tuneable longitudinal plasmon band, achieved by adjusting their aspect ratio [20], [21] and thus allowing them to show excellent characteristics as LSPR biosensors. In addition to LSPR sensing, GNRs have also been applied in many other fields such as SERS sensing [22], chemical imaging [23] and in cancer therapy [24].

Despite the fact that several excellent and well cited reviews on the general LSPR biosensors have been reported previously, these past reviews have not focused particularly on LSPR biosensors based on GNRs, to the best of our knowledge. This aspect is addressed directly in this paper which is designed to supplement the body of knowledge in this area by reviewing both key fundamental aspects and recent progress on the development of GNR-based LSPR biosensors. The paper thus deals with an overview of the underpinning sensing principles, the synthesis of GNRs, the surface modification of GNRs, the fabrication of a number of different biosensors and a range of biosensing applications, followed by a discussion of advances in GNR-based LSPR sensing. The paper ends with a view of future potential directions in research in this field.

Section snippets

Principles of LSPR

MNPs have particular optical properties which are significantly different from those observed in the bulk metal. When incident light interacts with MNPs, the electromagnetic field of the light induces a collective coherent oscillation of the surface conduction electrons of the MNPs in resonance with the frequency of light, in a phenomenon known as LSPR [14], [25]. The electric field of the light interacts with the free electrons in the nanoparticles, leading to a charge separation between the

Synthesis of GNRs

The successful development of LSPR sensors using GNRs depends on the reliable and accurate synthesis of GNRs that can then be applied to create consistent and reproducible sensors. The history of synthesis of spherical gold nanoparticles dates back more than a century. The most commonly used method for producing GNSs is citrate reduction, where the GNSs are synthesized by the addition into the boiling gold salt (HAuCl4) solution of a known amount of citrate solution, allowing the size of GNSs

Surface modification of the CTAB-capped GNRs

For GNRs synthesized in the presence of a CTAB surfactant using the wet-chemical methods, such as the seed-mediated growth method and electrochemical method, the surface of these GNRs is covered by a bilayer of positively charged CTAB molecules, as illustrated in Fig. 12. The CTAB surfactant is important to the synthesis of GNRs, because it not only works as a “structure-directing agent” to control the final particle shape, but also acts as a stabilizer to protect the as-synthesized GNRs

GNR-based LSPR biosensors

As LSPR can be excited when light directly interacts with metallic nanoparticles, the design of LSPR sensors is more flexible than that of SPR sensors. Both the GNS-based and the GNR-based LSPR sensors can share the same sensor configuration, in which the sensors can be configured by either immobilizing gold nanoparticles on a transparent substrate such as a glass slide or just simply leaving functionalized nanoparticles suspended in the solution in a cuvette where the detection will take place

Advances in LSPR biosensing

Advances in two specific fields, multiplexing of biosensors and single-nanoparticle based LSPR biosensing are highlighted below.

Conclusion and future outlook

In this review it can be seen that compared to other metallic nanoparticles, GNRs have shown both exceptional and highly desirable optical properties in LSPR-based biosensing applications, taking advantage of the high refractive index sensitivity and the potential for multiplexed sensing, all of which have attracted considerable attention from researchers focused on the development of GNR-based sensitive LSPR biosensors. Nevertheless, important challenges still remain in the practical

Acknowledgements

The authors would like to thank the Engineering and Physical Sciences Research Council (EPSRC) in the UK for the funding support via various schemes. The support of the George Daniels Educational Trust is also greatly appreciated.

Jie Cao received the B.E. degree in Electrical and Electronic Engineering from Harbin University of Science and Technology, Harbin, China, in 2004 and the M.E. degree in Mechatronic Engineering from Harbin Institute of Technology, Harbin, China, in 2007. He recently received the Ph.D. degree in Measurement and Instrumentation from City University London, London, UK. His research is focused on the design and fabrication of the SPR and LSPR based optical fiber sensors, and their biosensing

References (129)

  • E. Petryayeva et al.

    Localized surface plasmon resonance: nanostructures, bioassays and biosensing – a review

    Analytica Chimica Acta

    (2011)
  • J. Perez-Juste et al.

    Gold nanorods: synthesis, characterization and applications

    Coordination Chemistry Reviews

    (2005)
  • V.V.R. Sai et al.

    Novel U-bent fiber optic probe for localized surface plasmon resonance based biosensor

    Biosensors & Bioelectronics

    (2009)
  • X.C. Jiang et al.

    Gold nanorods: influence of various parameters as seeds, solvent, surfactant on shape control

    Colloids and Surfaces A – Physicochemical and Engineering Aspects

    (2007)
  • L. Billot et al.

    Surface enhanced Raman scattering on gold nanowire arrays: evidence of strong multipolar surface plasmon resonance enhancement

    Chemical Physics Letters

    (2006)
  • Y.J. Kim et al.

    Synthesis of size and shape-selective Au nanocrystals via proton beam irradiation

    Nuclear Instruments & Methods in Physics Research Section B – Beam Interactions with Materials and Atoms

    (2006)
  • C.J. Murphy et al.

    Gold nanorod crystal growth: from seed-mediated synthesis to nanoscale sculpting

    Current Opinion in Colloid & Interface Science

    (2011)
  • X. Li et al.

    Localized surface plasmon resonance (LSPR) of polyelectrolyte-functionalized gold-nanoparticles for bio-sensing

    Colloids and Surfaces A: Physicochemical and Engineering Aspects

    (2009)
  • J. Perez-Juste et al.

    Silica gels with tailored, gold nanorod-driven optical functionalities

    Applied Surface Science

    (2004)
  • T. Niidome et al.

    PEG-modified gold nanorods with a stealth character for in vivo applications

    Journal of Controlled Release

    (2006)
  • J. Cao et al.

    Effective surface modification of gold nanorods for localized surface plasmon resonance-based biosensors

    Sensors and Actuators B: Chemical

    (2012)
  • H.W. Huang et al.

    Label-free optical biosensor based on localized surface plasmon resonance of immobilized gold nanorods

    Colloids and Surfaces B – Biointerfaces

    (2009)
  • S.M. Borisov et al.

    Optical biosensors

    Chemical Reviews

    (2008)
  • L.Y. Wang et al.

    Fluorescence resonant energy transfer biosensor based on upconversion-luminescent nanoparticles

    Angewandte Chemie International Edition

    (2005)
  • J. Homola

    Present and future of surface plasmon resonance biosensors

    Analytical and Bioanalytical Chemistry

    (2003)
  • J. Homola

    Surface plasmon resonance sensors for detection of chemical and biological species

    Chemical Reviews

    (2008)
  • J. Zhang et al.

    Electrogenerated chemiluminescence DNA biosensor based on hairpin DNA probe labeled with ruthenium complex

    Analytical Chemistry

    (2008)
  • S. Eustis et al.

    Why gold nanoparticles are more precious than pretty gold: noble metal surface plasmon resonance and its enhancement of the radiative and nonradiative properties of nanocrystals of different shapes

    Chemical Society Reviews

    (2006)
  • K.A. Willets et al.

    Localized surface plasmon resonance spectroscopy and sensing

    Annual Review of Physical Chemistry, Annual Reviews, Palo Alto

    (2007)
  • S.M. Marinakos et al.

    Plasmonic detection of a model analyte in serum by a gold nanorod sensor

    Analytical Chemistry

    (2007)
  • K. Kajikawa et al.

    Optical fiber biosensor based on localized surface plasmon resonance in gold nanoparticles

  • M. Potara et al.

    Solution-phase, dual LSPR-SERS plasmonic sensors of high sensitivity and stability based on chitosan-coated anisotropic silver nanoparticles

    Journal of Materials Chemistry

    (2011)
  • A.D. McFarland et al.

    Single silver nanoparticles as real-time optical sensors with zeptomole sensitivity

    Nano Letters

    (2003)
  • A.V. Kabashin et al.

    Plasmonic nanorod metamaterials for biosensing

    Nature Materials

    (2009)
  • X. Huang et al.

    Gold nanorods: from synthesis and properties to biological and biomedical applications

    Advanced Materials

    (2009)
  • L. Vigderman et al.

    Functional gold nanorods: synthesis, self-assembly, and sensing applications

    Advanced Materials

    (2012)
  • C.J. Murphy et al.

    Chemical sensing and imaging with metallic nanorods

    Chemical Communications

    (2008)
  • X. Huang et al.

    Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods

    Journal of the American Chemical Society

    (2006)
  • J.N. Anker et al.

    Biosensing with plasmonic nanosensors

    Nature Materials

    (2008)
  • E. Hutter et al.

    Exploitation of localized surface plasmon resonance

    Advanced Materials

    (2004)
  • S. Link et al.

    Shape and size dependence of radiative, non-radiative and photothermal properties of gold nanocrystals

    International Reviews in Physical Chemistry

    (2000)
  • S. Link et al.

    Optical properties and ultrafast dynamics of metallic nanocrystals

    Annual Review of Physical Chemistry

    (2003)
  • K.M. Mayer et al.

    A label-free immunoassay based upon localized surface plasmon resonance of gold nanorods

    ACS Nano

    (2008)
  • K.M. Mayer et al.

    Localized surface plasmon resonance sensors

    Chemical Reviews

    (2011)
  • P.N. Njoki et al.

    Size correlation of optical and spectroscopic properties for gold nanoparticles

    Journal of Physical Chemistry C

    (2007)
  • R. Gans

    Über die form ultramikroskopischer goldteilchen

    Annalen der Physik

    (1912)
  • C.A. Foss et al.

    Template-synthesized nanoscopic gold particles – optical-spectra and the effects of particle-size and shape

    Journal of Physical Chemistry

    (1994)
  • S. Link et al.

    Simulation of the optical absorption spectra of gold nanorods as a function of their aspect ratio and the effect of the medium dielectric constant

    Journal of Physical Chemistry B

    (1999)
  • M. Hu et al.

    Gold nanostructures: engineering their plasmonic properties for biomedical applications

    Chemical Society Reviews

    (2006)
  • L.S. Jung et al.

    Quantitative interpretation of the response of surface plasmon resonance sensors to adsorbed films

    Langmuir: The ACS Journal of Surfaces and Colloids

    (1998)
  • Cited by (0)

    Jie Cao received the B.E. degree in Electrical and Electronic Engineering from Harbin University of Science and Technology, Harbin, China, in 2004 and the M.E. degree in Mechatronic Engineering from Harbin Institute of Technology, Harbin, China, in 2007. He recently received the Ph.D. degree in Measurement and Instrumentation from City University London, London, UK. His research is focused on the design and fabrication of the SPR and LSPR based optical fiber sensors, and their biosensing applications.

    Tong Sun received the received the B.E., M.E., and Dr. Eng. degrees in mechanical engineering from the Department of Precision Instrumentation, Harbin Institute of Technology, Harbin, China, in 1990, 1993, and 1998, respectively, and the Ph.D. degree in applied physics from the City University London, London, UK, in 1999. She is a Professor at the City University London, a member of the Institute of Physics and of the Institution of Engineering and Technology, and a Chartered Physicist and a Chartered Engineer in the UK.

    Kenneth T.V. Grattan received the B.Sc. degree in physics from the Queen's University Belfast, Belfast, UK, in 1974, the Ph.D. degree in laser physics in 1979, and the D.Sc. degree from the City University London, London, UK, in 1992. He is a Professor at City University London, and the Dean of the City Graduate School, having formerly been Dean of the Schools of Engineering and Mathematical and Informatics. Prof. Grattan is a member of the Editorial Board of several major journals. He was awarded the Calendar Medal of the Institute of Measurement and Control in 1992, and the Honeywell Prize for work published in the Institute's journal as well as the Hartley Medal in 2012. He is a Fellow of the Royal Academy of Engineering, the UK National Academy for the field.

    View full text