Singular-phase nanooptics: towards label-free single molecule detection

Non-trivial topology of phase is crucial for many important physics phenomena such as, for example, the Aharonov-Bohm effect 1 and the Berry phase 2. Light phase allows one to create "twisted" photons 3, 4 , vortex knots 5, dislocations 6 which has led to an emerging field of singular optics relying on abrupt phase changes 7. Here we demonstrate the feasibility of singular visible-light nanooptics which exploits the benefits of both plasmonic field enhancement and non-trivial topology of light phase. We show that properly designed plasmonic nanomaterials exhibit topologically protected singular phase behaviour which can be employed to radically improve sensitivity of detectors based on plasmon resonances. By using reversible hydrogenation of graphene 8 and a streptavidin-biotin test 9, we demonstrate areal mass sensitivity at a level of femto-grams per mm2 and detection of individual biomolecules, respectively. Our proof-of-concept results offer a way towards simple and scalable single-molecular label-free biosensing technologies.Comment: 19 pages, 4 figure

Layered material platform for surface plasmon resonance biosensing

Plasmonic biosensing has emerged as the most sensitive label-free technique to detect various molecular species in solutions and has already proved crucial in drug discovery, food safety and studies of bio-reactions. This technique relies on surface plasmon resonances in ~50 nm metallic films and the possibility to functionalize the surface of the metal in order to achieve selectivity. At the same time, most metals corrode in bio-solutions, which reduces the quality factor and darkness of plasmonic resonances and thus the sensitivity. Furthermore, functionalization itself might have a detrimental effect on the quality of the surface, also reducing sensitivity. Here we demonstrate that the use of graphene and other layered materials for passivation and functionalization broadens the range of metals which can be used for plasmonic biosensing and increases the sensitivity by 3-4 orders of magnitude, as it guarantees stability of a metal in liquid and preserves the plasmonic resonances under biofunctionalization. We use this approach to detect low molecular weight HT-2 toxins (crucial for food safety), achieving phase sensitivity~0.5 fg/mL, three orders of magnitude higher than previously reported. This proves that layered materials provide a new platform for surface plasmon resonance biosensing, paving the way for compact biosensors for point of care testing

Surface Plasmon Resonance kinetic analysis of the interaction between G-quadruplex nucleic acids and an anti-G-quadruplex monoclonal antibody

Background G-quadruplexes (G4s) are nucleic acids secondary structures formed in guanine-rich sequences. Anti-G4 antibodies represent a tool for the direct investigation of G4s in cells. Surface Plasmon Resonance (SPR) is a highly sensitive technology, suitable for assessing the affinity between biomolecules. We here aimed at improving the orientation of an anti-G4 antibody on the SPR sensor chip to optimize detection of binding antigens. Methods SPR was employed to characterize the anti-G4 antibody interaction with G4 and non-G4 oligonucleotides. Dextran-functionalized sensor chips were used both in covalent coupling and capturing procedures. Results The use of two leading molecule for orienting the antibody of interest allowed to improve its activity from completely non-functional to 65% active. The specificity of the anti-G4 antobody for G4 structures could thus be assessed with high sensitivity and reliability. Conclusions Optimization of the immobilization protocol for SPR biosensing, allowed us to determine the anti-G4 antibody affinity and specificity for G4 antigens with higher sensitivity with respect to other in vitro assays such as ELISA. Anti-G4 antibody specificity is a fundamental assumption for the future utilization of this kind of antibodies for monitoring G4s directly in cells. General significance The heterogeneous orientation of amine-coupling immobilized ligands is a general problem that often leads to partial or complete inactivation of the molecules. Here we describe a new strategy for improving ligand orientation: driving it from two sides. This principle can be virtually applied to every molecule that loses its activity or is poorly immobilized after standard coupling to the SPR chip surface

Modeling and Simulation of a high sensitivity biosensor in a periodic array of metal nanorod pair by using the finite element method

We numerically investigated the surface plasmon resonances (SPRs) in a periodic array of solid-silver/silver-shell nanorod pair structures for sensing applications by employing a finite-element method. The proposed periodic array of silver-shell nanorod pair structure is composed of a pair of metallic nanorod with a dielectric hole (DH) that interact with a transverse magnetic mode incident plane wave, which includes the investigation of particle particle interaction. We demonstrate that near-field coupling of the periodic array of solid-silver/silver-shell ranorod pair structures result in a periodic lattice of SPR modes with enhanced field intensities and transmittance dips. The influences of different illumination wavelengths, periods, transmittance spectra, energy flows and electric stream lines, DHs, electric field component distributions and total field intensities, charge density distribution, and the model of the induced local field of the periodic array of solid-silver/silver-shell nanorod pair on "bonding"modes are discussed in our simulations. The proposed structure exhibits a redshifted localized SPR that can be modified over an extended wavelength range of peak resonances and transmittance dips by varying the relative permittivities in DHs and the period of the periodic nanostructure. Simulation results show that the SPR modes are very sensitive to the relative permittivities change in the surrounding materials,  which could be used as highly sensitive sensors

Topological Darkness: How to Design a Metamaterial for Optical Biosensing with Virtually Unlimited Sensitivity

Due to the absence of labels and fast analyses, optical biosensors promise major advances in biomedical diagnostics, security, environmental and food safety applications. However, sensitivity of the most advanced plasmonic biosensor implementations has a fundamental limitation caused by losses in the system and or geometry of biochips. Here, we report a scissor effect in topologically dark metamaterials which is capable of providing virtually unlimited bona fide sensitivity to biosensing thus solving the bottleneck sensitivity limitation problem. We explain how the scissor effect can be realized via a proper design of topologically dark metamaterials and describe strategies for their fabrication. To validate the applicability of this effect in biosensing, we demonstrate the detection of folic acid (vitamin important for human health) in the wide 3-log linear dynamic range with the limit of detection of 0.125 nM, which is orders of magnitude better than previously reported for all optical counterparts. Our work opens possibilities for designing and realising plasmonic, semiconductor and dielectric metamaterials with ultra-sensitivity to binding events.Comment: 22 pages, 4 figure

Plasmonic Optical Sensors: Performance Analysis and Engineering Towards Biosensing

Surface plasmon resonance (SPR) sensing for quantitative analysis of chemical reactions and biological interactions has become one of the most promising applications of plasmonics. This thesis focuses on performance analysis for plasmonic sensors and implementation of plamonic optical sensors with novel nanofabrication techniques. A universal performance analysis model is established for general two-dimensional plasmonic sensors. This model is based on the fundamental facts of surface plasmon theory. The sensitivity only depends on excitation light wavelength as well as dielectric properties of metal and dielectrics. The expression involves no structure-specified parameters, which validates this formula in broad cases of periodic, quasiperiodic and aperiodic nanostructures. Further analysis reveals the intrinsic relationship between plamonic sensor performance and essential physics of surface plasmon. The analytical results are compared to the sensitivities of previously reported plasmonic sensors in the field. This universal model is a promising qualification criterion for plasmonic sensors. Plasmonic optical sensors are engineered into high-performance on-chip sensors, plasmonic optical fibers and freestanding nanomembranes. (1) Periodic nanohole arrays are patterned on chip by a simple and robust template-transfer approach. A spectral analysis approach is also developed for improving the sensor performance. This sensor is applied to demonstrate the on-chip detection of cardiac troponin-I. (2) Plasmonic optical fibers are constructed by transferring periodic metal nanostructures from patterned templates onto endfaces of optical fibers using an epoxy adhesive. Patterned metal structures are generally extended from nanohole arrays to nanoslit arrays. A special plasmonic fiber is designed to simultaneously implement multimode refractive index sensing with remarkably narrow linewidth and high figure of merit. A real-time immunoassay relying on plasmonic fiber is demonstrated. Plasmonic optical fibers also take advantages of consistent optical responses, excellent stability during fiber bending and capability of spectrum filtering. (3) Large-area freestanding metal nanomembranes are implemented using a novel fabrication approach. The formed transferrable membranes feature high-quality and uniform periodic nanohole arrays. The freestanding nanomembranes exhibit remarkably higher transmission intensity in comparison to the nanohole arrays with same features on the substrate. These three modalities of plasmonic sensors possess different applicability to fulfill various plasmonic sensing tasks in respective scenarios

Trends of biosensing: plasmonics through miniaturization and quantum sensing

Despite being extremely old concepts, plasmonics and surface plasmon resonance-based biosensors have been increasingly popular in the recent two decades due to the growing interest in nanooptics and are now of relevant significance in regards to applications associated with human health. Plasmonics integration into point-of-care devices for health surveillance has enabled significant levels of sensitivity and limit of detection to be achieved and has encouraged the expansion of the fields of study and market niches devoted to the creation of quick and incredibly sensitive label-free detection. The trend reflects in wearable plasmonic sensor development as well as point-of-care applications for widespread applications, demonstrating the potential impact of the new generation of plasmonic biosensors on human well-being through the concepts of personalized medicine and global health. In this context, the aim here is to discuss the potential, limitations, and opportunities for improvement that have arisen as a result of the integration of plasmonics into microsystems and lab-on-chip over the past five years. Recent applications of plasmonic biosensors in microsystems and sensor performance are analyzed. The final analysis focuses on the integration of microfluidics and lab-on-a-chip with quantum plasmonics technology prospecting it as a promising solution for chemical and biological sensing. Here it is underlined how the research in the field of quantum plasmonic sensing for biological applications has flourished over the past decade with the aim to overcome the limits given by quantum fluctuations and noise. The significant advances in nanophotonics, plasmonics and microsystems used to create increasingly effective biosensors would continue to benefit this field if harnessed properly