High-Q optical sensors for chemical and biological analysis.

Optical sensors represent a vitally important class of analytical tools that have been used to provide chemical information ranging from analyte concentration and binding kinetics to microscopic imaging and molecular structure. Optical sensors utilize a variety of signal transduction pathways based on photonic attributes that include absorbance, transmission, fluorescence intensity, refractive index, polarization, and reflectivity. Within the broad classification of optical sensors, refractive index (RI) sensors, which include devices such as surface plasmon resonance instruments, interferometers, diffraction gratings, optical fibers, photonic crystals, and resonant microcavities, have emerged as promising technologies over the past two decades. These optical sensors based on the change in RI associated with analyte binding involve an impressive array of instrumentation that allows for label-free1 molecular sensing without the added complexity of fluorescent or enzymatic tags. By removing the requirement for labels, RI-based sensing allows for real-time and direct detection of molecular interactions at a dielectric interface. Though many manifestations of RI-based sensors have been proposed and demonstrated, high-quality factor (high-Q) optical sensors based on multi-pass photonic microstructures have recently emerged as an extremely promising, and perhaps the most sensitive, class of label-free sensors. Major advantages of many high-Q sensors include multiple-pass interactions between the propagating electromagnetic radiation and the respective analyte binding event, as well as the intrinsic chip-integration and wafer-scale fabrication that accompany many semiconductor-based sensing modalities. High-Q optical sensors involve microstructures that confine light due to differences in RI between a micropatterned material and its surrounding. This confinement supports multi-pass light interactions based on either multiple reflections or many circumnavigations. In both cases, this results in an increased effective optical path length that improves the sensitivity of the device. The Q factor of a given device is a measure of the resonant photon lifetime within a microstructure (higher Q factor = longer lifetime), and therefore Q is directly correlated to the number of times a photon is recirculated and allowed to interact with the analyte.2 Light is confined by either total internal reflection at a core/cladding interface (microcavities) or by the spatially periodic modulation of materials with different RI properties (photonic crystals), and resultant high-Q sensors interact with their local environments via an evanescent optical field that extends from the sensor surface and decays exponentially with distance.3, 4 A more detailed treatment of microcavity technology involving whispering gallery mode (WGM) sensing will be presented in the following section. High-Q optical sensors, whether based on guided-mode optics or photonic crystal (PC) structures, support resonances at very specific wavelengths, and these resonances are responsive to changes in the effective RI at the device surface. For most microcavity sensors, the wavelengths of light transmitted between an adjacent waveguide or optical fiber and the cavity is attenuated at narrow resonant wavelengths that are a function of the RI at the microcavity surface; for most PC sensors, light is back-reflected only at precise resonance wavelengths. As the Q factor of a device increases, the photon lifetime increases, and the resonance wavelength peak becomes narrower. For both microcavity and PC sensors, the relative shift in resonance wavelengths is directly proportional to the effective RI sampled by the confined optical mode, which samples the dielectric interface via the evanescent wave extending from the sensor surface. Since most analytes, such as organic (bio)molecules in water or gases in air, have a greater dielectric permittivity (and thus higher RI) than the surrounding medium, their binding or association with the sensor surface leads to an increase in effective RI sampled by the optical mode.4 Though factors such as biological and spectroscopic noise often set the practical limit of detection for any sensor system, the narrow resonance wavelengths associated with high-Q cavities provide an opportunity to resolve tiny spectral shifts that accompany a very small number of analyte binding interactions. The impressive sensitivity of microcavity and PC devices to minute changes in the effective RI at the sensor surface is the basis for most of the recent applications of high-Q optical sensors. The development of high-Q photonic devices has been tremendously enabled by recent advances in micro- and nanofabrication methods, and the application of these devices for chemical and biomolecular analysis has only come to fruition within the past decade. This review focuses on the most exciting research in this area over the period of 2009–2011, although enabling findings and developments that precede this range are also covered. Recent reviews have summarized advances that may include some treatment of high-Q sensors, but these reviews have been broadly focused on advances in label-free sensors in general,5–8 on applications of silicon photonics that include sensing among many others,9 or on a general treatment of optical devices for sensing that includes the devices of interest.10–13 Other excellent reviews are more narrowly focused and cover different aspects of high-Q technology, focusing specifically on ring resonator technology,14, 15 microsphere resonators,16 photonic crystals,4, 17 microfluidic integration with optical sensors,18, 19 and high-Q mechanical sensors.20 This review considers recent advances in high-Q and ultra-high-Q optical sensors for addressing fundamental challenges in measurement science, giving special attention to those techniques that demonstrate useful chemical or biomolecular measurement capabilities within relevant real-world matrices. Although not rigorously fitting within some strict definitions of high-Q devices, photonic crystal sensors are covered as they represent an exciting complementary technology that, in many ways, is more advanced at present than many high-Q microcavity sensor configurations. As this review is intended to target the broad community of practicing analytical chemists, particular focus is given to signal transduction mechanisms, surface chemistry, assay methodologies, and interesting new measurement applications, leaving detailed explanations of device optics and engineering to other, more topical reviews21, 22 and the collection of articles from the optics community cited herein. Specifically, this review will briefly discuss the theoretical basis of high-Q optical sensing, including the multitude of sensor geometries within the category of multi-pass optical sensors. Recent advances in high-Q sensor surface chemistry, capture agent immobilization, assay design, and amplification techniques are covered, as well as interesting demonstrations of these technologies in impact areas such as quantitative detection, affinity profiling, multiplexed sensing, nanoparticle analysis, light manipulation, lasers, thermal sensing, and integrated detection techniques. Finally, we provide our own critical analysis of the field in general, offering thoughts on areas in which improvements are most needed to inform the future outlook and reach the goals of high-Q optical sensing.