ReviewSurface plasmon resonance sensing of nucleic acids: A review
Graphical abstract
Highlights
► Advances of nucleic acid (NA) surface plasmon resonance (SPR) sensors are presented. ► Bioanalytical applications of NA SPR biosensors are reviewed. ► Applications for study of molecular interactions involving NAs are also discussed.
Introduction
Nucleic acids (NAs) are biomolecules that play vital role in numerous processes in cells—from the storage, transmission and expression of genetic information to regulatory roles [1], [2]. Human genome sequencing has helped elucidate the links between abnormalities in an individual's DNA and genetic disorders. In addition, new families of nucleic acids (e.g. siRNA, miRNA) have been discovered and some of them were identified as prospective biomarkers of various diseases and health conditions [3], [4].
An optical nucleic acid biosensor consists of specific nucleic acid (probe) and an optical transducer which serves to translate the binding of a target biomolecule to the probe into an output signal. Optical transduction methods either employ labels (e.g. fluorescent labels) or measure the binding directly. The latter are referred to as label-free optical biosensors and are typically based on absorption or Raman spectroscopy, interferometry, or spectroscopy of guided modes pertaining to dielectric and metallic waveguides [5], [6]. Surface plasmon resonance (SPR) biosensors exploit a special mode of the metal-dielectric waveguide – a surface plasmon – to measure changes in the refractive index caused by the biomolecular interaction occurring at the surface of the SPR sensor. SPR biosensors represent the most advanced and mature label-free optical biosensor technology. The ability to measure biomolecular interactions directly, in real time and without the use of labels makes SPR biosensors a powerful tool for the investigation of kinetic properties of biomolecular interactions [7], [8], [9], [10], [11], [12]. Various kinds of nucleic acids have been targeted by SPR biosensors [13], [14]. These range from short oligonucleotides such as miRNA [14], [15], through polymerase chain reaction (PCR) products [16], [17], to large molecules such as cDNA [18] and 16S ribosomal RNA, which is genetic marker of specific bacteria [19].
This paper presents a review of the state of the art of NA SPR biosensing and its applications in the research of molecular interactions and bioanalytics.
Section snippets
Principles of SPR sensors
Surface plasmons are special electromagnetic modes which may exist at the surface of a metal. Surface plasmon resonance (bio)sensors employ surface plasmons propagating on a planar metal-dielectric interface, which are sometimes referred to as propagating surface plasmons (PSPs) [20]. The electromagnetic field of the PSP reaches its maximum at the metal-dielectric interface and decays exponentially into both media. The penetration depth of the PSP at the boundary of gold and a dielectric (in
SPR sensors for the investigation of nucleic acids and their interactions
One of the major areas of applications for SPR biosensors is the investigation of biomolecules as well as their interactions, including the interactions of NAs with NAs, DNA/RNA-binding proteins, enzymes, and small molecules.
SPR sensors for the quantification of nucleic acids
Although there is a growing interest in applying SPR biosensors for bioanalytical tasks, the number of publications documenting applications of SPR biosensors for the detection of NAs in complex real-world samples is still rather limited. As the analytical performance of NA SPR sensors depends on a large number of factors (sensor platform, probes, functionalization method, sample composition, detection methodology, etc.), it is difficult to draw conclusions about the bioanalytical capabilities
Conclusions
Over the last decade, surface plasmon resonance biosensors have become an invaluable tool for the investigation of molecular interactions. The interactions of nucleic acids, such as NA–NA, NA–protein, NA–small molecule interactions, have been studied with SPR biosensors to deepen the understanding of complex biological processes in cells and enable the development of new drugs and therapies. The major asset of the SPR biosensors in this perspective is their ability to provide real-time
Acknowledgments
This research was supported by Praemium Academiae of the Academy of Sciences of the Czech Republic, by the Czech Science Foundation (contracts P205/12/G118, 202/09/0193, and P305/12/1801), and by the Ministry of Education, Youth and Sports (contract LH11102).
Hana Šípová is a graduate student under the supervision of Prof Jiří Homola in the Department of Optical Sensors of the Institute of Photonics and Electronics AS CR in Prague. Her research interests include optical biosensors and bioassays for sensitive and specific detection of biomolecules and the use of label-free biosensors for investigation of biomolecular interactions with a focus on interactions of nucleic acids.
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Hana Šípová is a graduate student under the supervision of Prof Jiří Homola in the Department of Optical Sensors of the Institute of Photonics and Electronics AS CR in Prague. Her research interests include optical biosensors and bioassays for sensitive and specific detection of biomolecules and the use of label-free biosensors for investigation of biomolecular interactions with a focus on interactions of nucleic acids.
Jiří Homola (PhD 1993, DSc 2009) is head of Photonics Division and Chairman of Department of Optical Sensors at the Institute of Photonics and Electronics (Czech Republic). He also is affiliate professor at the University of Washington, Seattle (USA), adjunct professor at the University of Oulu (Finland), and associate professor at Charles University in Prague (Czech Republic). His research interests are in photonics and biophotonics, in particular in optical sensors and biosensors. He is a member of International Advisory Board of Analytical and Bioanalytical Chemistry and a member of Editorial Boards of Sensors and Actuators B and Journal of Sensors.