Matthew R. Foreman

Single-molecule nucleic acid interactions monitored on a label-free microcavity biosensor platform

Biosensing relies on the detection of molecules and their specific interactions. It is therefore highly desirable to develop transducers exhibiting ultimate detection limits. Microcavities are an exemplary candidate technology for demonstrating such a capability in the optical domain and in a label-free fashion. Additional sensitivity gains, achievable by exploiting plasmon resonances, promise biosensing down to the single-molecule level. Here, we introduce a biosensing platform using optical microcavity-based sensors that exhibits single-molecule sensitivity and is selective to specific single binding events. Whispering gallery modes in glass microspheres are used to leverage plasmonic enhancements in gold nanorods for the specific detection of nucleic acid hybridization, down to single 8-mer oligonucleotides. Detection of single intercalating small molecules confirms the observation of single-molecule hybridization. Matched and mismatched strands are discriminated by their interaction kinetics. Our platform allows us to monitor specific molecular interactions transiently, hence mitigating the need for high binding affinity and avoiding permanent binding of target molecules to the receptors. Sensor lifetime is therefore increased, allowing interaction kinetics to be statistically analysed.

Whispering gallery mode sensors

We present a comprehensive overview of sensor technology exploiting optical whispering gallery mode (WGM) resonances. After a short introduction we begin by detailing the fundamental principles and theory of WGMs in optical microcavities and the transduction mechanisms frequently employed for sensing purposes. Key recent theoretical contributions to the modeling and analysis of WGM systems are highlighted. Subsequently we review the state of the art of WGM sensors by outlining efforts made to date to improve current detection limits. Proposals in this vein are numerous and range, for example, from plasmonic enhancements and active cavities to hybrid optomechanical sensors, which are already working in the shot noise limited regime. In parallel to furthering WGM sensitivity, efforts to improve the time resolution are beginning to emerge. We therefore summarize the techniques being pursued in this vein. Ultimately WGM sensors aim for real-world applications, such as measurements of force and temperature, or alternatively gas and biosensing. Each such application is thus reviewed in turn, and important achievements are discussed. Finally, we adopt a more forward-looking perspective and discuss the outlook of WGM sensors within both a physical and biological context and consider how they may yet push the detection envelope further.

Determination of the transfer function for optical surface topography measuring instruments—a review

A significant number of areal surface topography measuring instruments, largely based on optical techniques, are commercially available. However,implementation of optical instrumentation into production is currently difficult dueto the lack of understanding of the complex interaction between the light and the component surface. Studying the optical transfer function of the instrument can help address this issue. Herea review is given of techniques for the measurement of optical transfer functions. Starting from the basis of a spatially coherent, monochromatic confocal scanning imaging system, the theory of optical transfer functions in three-dimensional (3D) imaging is presented. Further generalizations are reviewed allowing the extension of the theory to the description of conventional and interferometric 3D imaging systems. Polychromatic transfer functions and surface topography measurements are also discussed. Following presentation of theoretical results, experimental methods to measure the optical transfer function of each class of system are presented, with a focus on suitable methods for the establishment of calibration standards in 3D imaging and surface topography measurements.

Optimizing detection limits in whispering gallery mode biosensing.

A theoretical analysis of detection limits in swept-frequency whispering gallery mode biosensing modalities is presented based on application of the Cramér-Rao lower bound. Measurement acuity factors are derived assuming the presence of uncoloured and 1/ f Gaussian technical noise. Frequency fluctuations, for example arising from laser jitter or thermorefractive noise, are also considered. Determination of acuity factors for arbitrary coloured noise by means of the asymptotic Fisher information matrix is highlighted. Quantification and comparison of detection sensitivity for both resonance shift and broadening sensing modalities are subsequently given. Optimal cavity and coupling geometries are furthermore identified, whereby it is found that slightly under-coupled cavities outperform critically and over coupled ones.

Spectral broadening in Brillouin imaging

Brillouin microscopy is an emerging imaging modality that provides fundamental information about mechanical properties of media in a non-contact manner. To date, low numerical aperture (NA) optics have been used, due to noticeable angular broadening of the Brillouin spectrum at higher NAs. In this work, we investigate theoretically and experimentally the dependence of spectral broadening effects in Brillouin imaging on system NA, for both 90° and 180° scattering geometries. Lineshape deformations and broadening are found to be minimised in a backscattering geometry, hence paving the way for high resolution in-vivo mechanical imaging.

Theory of resonance shifts of whispering gallery modes by arbitrary plasmonic nanoparticles

Shifts of the resonance frequency of high Q whispering gallery modes (WGMs) in spherical dielectric microresonators by plasmonic nanoparticles can be greater than the WGM line width, such that the perturbation theory commonly used for describing resonance shifts by dielectric nanoparticles (Teraoka and Arnold 2006 J. Opt. Soc. Am. B 23 1381) is no longer applicable. This paper therefore reports on an analytic framework, based on generalized Lorenz-Mie theory, capable of describing resonance shifts by metallic nanoparticles supporting plasmon oscillations. Generalization to nanoparticles of arbitrary geometry is presented by employing the extended boundary condition method. Within this framework, hybrid resonance conditions for coupled spherical photonic and plasmonic resonators are established and shown to simplify for small plasmonic nanoparticles. Approximate analytic formulae are derived for the shift and broadening of the isolated WGM and plasmon resonances, from which either apparent resonance shifts or mode splitting are shown to follow. Tuning of plasmon resonances using, for example, core-shell nanoparticles to attain a large spectral overlap between WGM and plasmon resonances is demonstrated to significantly enhance the magnitude of resonance shifts, with a 60-fold enhancement achieved without any optimization. Hybridization of photonic-plasmonic resonances is furthermore demonstrated

Integrated plasmonic metasurfaces for spectropolarimetry

Plasmonic metasurfaces enable simultaneous control of the phase, momentum, amplitude and polarization of light and hence promise great utility in realization of compact photonic devices. In this paper, we demonstrate a novel chip-scale device suitable for simultaneous polarization and spectral measurements through use of six integrated plasmonic metasurfaces (IPMs), which diffract light with a given polarization state and spectral component into well-defined spatial domains. Full calibration and characterization of our device is presented, whereby good spectral resolution and polarization accuracy over a wavelength range of 500-700 nm is shown. Functionality of our device in a Müller matrix modality is demonstrated through determination of the polarization properties of a commercially available variable waveplate. Our proposed IPM is robust, compact and can be fabricated with a single photolithography step, promising many applications in polarization imaging, quantum communication and quantitative sensing.

Polarization-resolved second harmonic generation microscopy with a four-channel Stokes-polarimeter

We developed a four-channel photon counting based Stokes-polarimeter for spatial characterization of polarization effects in second harmonic generation (SHG). We have implemented a calibration technique allowing quantitative measurement of polarization parameters, such as the degree of polarization (DOP), degree of linear polarization (DOLP), degree of circular polarization (DOCP), as well as anisotropy from the acquired Stokes parameters. The technique is used as contrast mechanism to characterize the polarization properties from two potassium dihydrogen phosphate (KDP) micro-crystals and collagen type-I in SHG microscopy.

Inversion of the Debye-Wolf diffraction integral using an eigenfunction representation of the electric fields in the focal region

The forward problem of focusing light using a high numerical aperture lens can be described using the Debye-Wolf integral, however a solution to the inverse problem does not currently exist. In this work an inversion formula based on an eigenfunction representation is derived and presented which allows a field distribution in a plane in the focal region to be specified and the appropriate pupil plane distribution to be calculated. Various additional considerations constrain the inversion to ensure physicality and practicality of the results and these are also discussed. A number of inversion examples are given.

Computational methods in vectorial imaging

In the search for higher resolution, modern day imaging systems frequently employ objective lenses with a high numerical aperture. Propagation of light through such lenses introduces a spatial variation in the polarisation across the beam profile, whilst the inherently large propagation angles also necessitates inclusion of additional transverse and axial electric field components in modelling. A full treatment of polarisation effects including such considerations has implications at all stages in the image formation process, namely; illumination, scattering from the sample, imaging and detection. This tutorial review considers each stage in turn and details the theories required for rigorous modelling and analysis. In particular a generalisation of the well known Jones calculus and ray tracing methods are shown to conveniently and accurately allow rigorous studies of high numerical aperture confocal and conventional polarised light microscopes, imaging samples of arbitrary complexity. Generalisation of the illumination to partially coherent, partially polarised systems is also briefly given. Whilst rigorous modelling techniques can prove time consuming a number of simplifications and approximations can be adopted, allowing computational gains to be achieved. Discussion in this vein is hence also presented.