The term photonic crystals appears because of the analogy between electron waves in crystals and the light waves in artificial periodic dielectric structures. During the recent years the investigation of one-, two-and three-dimensional periodic structures has attracted a widespread attention of the world optics community because of great potentiality of such structures in advanced applied optical fields. The interest in periodic structures has been stimulated by the fast development of semiconductor technology that now allows the fabrication of artificial structures, whose period is comparable with the wavelength of light in the visible and infrared ranges.

http://ieeexplore.ieee.org/iel5/6354/16969/00781867.pdf

Photonic crystals

High-throughput screening (HTS) assays enable the testing of large numbers of chemical substances for activity in diverse areas of biology. The biological responses measured in HTS assays span isolated biochemical systems containing purified receptors or enzymes to signal transduction pathways and complex networks functioning in cellular environments. This Review addresses factors that need to be considered when implementing assays for HTS and is aimed particularly at investigators new to this field. We discuss assay design strategies, the major detection technologies and examples of HTS assays for common target classes, cellular pathways and simple cellular phenotypes. We conclude with special considerations for configuring sensitive, robust, informative and economically feasible HTS assays.

High-throughput screening assays for the identification of chemical probes

It is useful to consider seven transmembrane receptors (7TMRs) as disordered proteins able to allosterically respond to a number of binding partners. Considering 7TMRs as allosteric systems, affinity and efficacy can be thought of in terms of energy flow between a modulator, conduit (the receptor protein), and a number of guests. These guests can be other molecules, receptors, membrane-bound proteins, or signaling proteins in the cytosol. These vectorial flows of energy can yield standard canonical guest allostery (allosteric modification of drug effect), effects along the plane of the cell membrane (receptor oligomerization), or effects directed into the cytosol (differential signaling as functional selectivity). This review discusses these apparently diverse pharmacological effects in terms of molecular dynamics and protein ensemble theory, which tends to unify 7TMR behavior toward cells. Special consideration will be given to functional selectivity (biased agonism and biased antagonism) in terms of mechanism of action and potential therapeutic application. The explosion of technology that has enabled observation of diverse 7TMR behavior has also shown how drugs can have multiple (pluridimensional) efficacies and how this can cause paradoxical drug classification and nomenclatures.

https://cdr.lib.unc.edu/downloads/hm50tt91t

Seven Transmembrane Receptors as Shapeshifting Proteins: The Impact of Allosteric Modulation and Functional Selectivity on New Drug Discovery

The application of portable, easy-to-use and highly sensitive lab-on-a-chip biosensing devices for real-time diagnosis could offer significant advantages over current analytical methods. Integrated optics-based biosensors have become the most suitable technology for lab-on-chip integration due to their ability for miniaturization, their extreme sensitivity, robustness, reliability, and their potential for multiplexing and mass production at low cost. This review provides an extended overview of the state-of-the-art in integrated photonic biosensors technology including interferometers, grating couplers, microring resonators, photonic crystals and other novel nanophotonic transducers. Particular emphasis has been placed on describing their real biosensing applications and wherever possible a comparison of the sensing performances between each type of device is included. The way towards achieving operative lab-on-a-chip platform incorporating the photonic biosensors is also reviewed. Concluding remarks regarding the future prospects and potential impact of this technology are also provided.

/pdf/integrated-optical-devices-for-lab-on-a-chip-biosensing-4dvxngj3uf.pdf

Integrated optical devices for lab-on-a-chip biosensing applications

Semiconductor quantum dots (QDs) are brightly luminescent nanoparticles that have found numerous applications in bioanalysis and bioimaging. In this review, we highlight recent developments in these areas in the context of specific methods for fluorescence spectroscopy and imaging. Following a primer on the structure, properties, and biofunctionalization of QDs, we describe select examples of how QDs have been used in combination with steady-state or time-resolved spectroscopic techniques to develop a variety of assays, bioprobes, and biosensors that function via changes in QD photoluminescence intensity, polarization, or lifetime. Some special attention is paid to the use of Forster resonance energy transfer-type methods in bioanalysis, including those based on bioluminescence and chemiluminescence. Direct chemiluminescence, electrochemiluminescence, and charge transfer quenching are similarly discussed. We further describe the combination of QDs and flow cytometry, including traditional cellular analyses and spectrally encoded barcode-based assay technologies, before turning our attention to enhanced fluorescence techniques based on photonic crystals or plasmon coupling. Finally, we survey the use of QDs across different platforms for biological fluorescence imaging, including epifluorescence, confocal, and two-photon excitation microscopy; single particle tracking and fluorescence correlation spectroscopy; super-resolution imaging; near-field scanning optical microscopy; and fluorescence lifetime imaging microscopy. In each of the above-mentioned platforms, QDs provide the brightness needed for highly sensitive detection, the photostability needed for tracking dynamic processes, or the multiplexing capacity needed to elucidate complex systems. There is a clear synergy between advances in QD materials and spectroscopy and imaging techniques, as both must be applied in concert to achieve their full potential.

https://journals.sagepub.com/doi/pdf/10.1366/12-06948

Quantum Dots in Bioanalysis: A Review of Applications across Various Platforms for Fluorescence Spectroscopy and Imaging

Screening of biochemical interactions becomes simpler, less expensive, and more accurate when labels, such as fluorescent dyes, radioactive markers, and colorimetric reactions, are not required to quantify detected material. SRU Biosystems has developed a biosensor technology that is manufactured on continuous sheets of plastic film and incorporated into standard microplates and microarray slides to enable label-free assays to be performed with high throughput, high sensitivity, and low cost per assay. The biosensor incorporates a narrowband guided-mode resonance reflectance filter, in which the reflected color is modulated by the attachment/detachment of biochemical material to the surface. The technology offers 4 orders of linear dynamic range and uniformity within a plate, with a coefficient of variation of 2.5%. Using conventional biochemical immobilization surface chemistries, a wide range of assay applications are enabled. Small molecule screening, cell proliferation/ cytotoxicity, enzyme activity screening, protein-protein interaction, and cell membrane receptor expression are among the applications demonstrated. (Journal of Biomolecular Screening 2004:481-490)

Label-free assays on the BIND system.

A Photonic Crystal (PC) surface fabricated upon a quartz substrate using nanoimprint lithography has been demonstrated to enhance light emission from fluorescent molecules in close proximity to the PC surface. Quartz was selected for its low autofluorescence characteristics compared to polymer-based PCs, improving the detection sensitivity and signal-to-noise ratio (SNR) of PC Enhanced Fluorescence (PCEF). Nanoimprint lithography enables economical fabrication of the subwavelength PCEF surface structure over entire 1x3 in2 quartz slides. The demonstrated PCEF surface supports a transverse magnetic (TM) resonant mode at a wavelength of λ = 632.8 nm and an incident angle of θ = 11°, which amplifies the electric field magnitude experienced by surface-bound fluorophores. Meanwhile, another TM mode at a wavelength of λ = 690 nm and incident angle of θ = 0° efficiently directs the fluorescent emission toward the detection optics. An enhancement factor as high as 7500 × was achieved for the detection of LD-700 dye spin-coated upon the PC, compared to detecting the same material on an unpatterned glass surface. The detection of spotted Alexa-647 labeled polypeptide on the PC exhibits a 330 × SNR improvement. Using dose-response characterization of deposited fluorophore-tagged protein spots, the PCEF surface demonstrated a 140 × lower limit of detection compared to a conventional glass substrate.

Photonic crystal enhanced fluorescence using a quartz substrate to reduce limits of detection.

A grating-based sensor is disclosed that has a grating structure constructed and designed for both evanescent resonance (ER) fluorescence detection and label-free detection applications. Some embodiments are disclosed which are optimized for ER detection in an air mode, in which the sample is dry. Other embodiments are optimized for ER detection in liquid mode, in which the sample is suspended in liquid medium such as water. One and two-dimensional gratings are also disclosed, including gratings characterized by unit cells with central posts, central holes, and two-level, two-dimensional gratings. A readout system for such sensors is also disclosed. One embodiment includes a first light source optimized for collecting label-free detection data, a second light source optimized for collecting ER fluorescence amplification data, and at least one detector. In one embodiment, the detector is an imaging system and includes a CCD camera for collecting both ER and label-free data. In other embodiments, the at least one detector takes the form of a spectrometer for collection of label-free data and a photomultiplier for collecting ER data. In other embodiments, a single light source such as a tunable laser or broad band light source is used.

Grating-based sensor combining label-free binding detection and fluorescence amplification and readout system for sensor

A photonic crystal substrate exhibiting resonant enhancement of multiple fluorophores has been demonstrated. The device, fabricated uniformly from plastic materials over a ∼3×5 in.2 surface area by nanoreplica molding, utilizes two distinct resonant modes to enhance electric field stimulation of a dye excited by a λ=632.8 nm laser (cyanine-5) and a dye excited by a λ=532 nm laser (cyanine-3). Resonant coupling of the laser excitation to the photonic crystal surface is obtained for each wavelength at a distinct incident angle. Compared to detection of a dye-labeled protein on an ordinary glass surface, the photonic crystal surface exhibited a 32× increase in fluorescent signal intensity for cyanine-5 conjugated streptavidin labeling, while a 25× increase was obtained for cyanine-3 conjugated streptavidin labeling. The photonic crystal is capable of amplifying the output of any fluorescent dye with an excitation wavelength in the 532 nm<λ<633 nm range by selection of an appropriate incident angle. The devic...

Multicolor fluorescence enhancement from a photonics crystal surface.

Calibration and normalization methods for a grating-based sensor design are disclosed. The sensor may be constructed in a manner optimized for both label-free and luminescence, e.g. fluorescence, amplification detection in a single device. Such a sensor, based on grating or another periodical structure with appropriate coating, dramatically increases the diversity of applications and allows realizing novel concepts that provide qualitative and quantitative information/data for each location or capture element in the sensor surface. The invention takes advantage of these different modes to carry out a quality control (QC) step and a calibration of each individual location of the sensor. Thus, the assay data can be flagged according to their quality and local density variations, batch variations and variations in the printed deposition of probes or the materials to the surface can be compensated.

Stephen C. Schulz

Papers

Label-free assays on the BIND system.

Photonic crystal enhanced fluorescence using a quartz substrate to reduce limits of detection.

Grating-based sensor combining label-free binding detection and fluorescence amplification and readout system for sensor

Multicolor fluorescence enhancement from a photonics crystal surface.

Calibration and normalization method for biosensors