Diffractive Optics Technology Research Articles

History and Application of Diffractive Optics Technology

History and Application of Diffractive Optics Technology

Computer-generated holograms for fiber optical communication with spatial-division multiplexing

We report here on applications of computer-generated holograms in fiber optical communication with mode-division multiplexing. It is shown that a pair of multichannel spatial filters matched to spatial modes provides a viable solution for transmission of several temporal signals of the same wavelength in a sole multimode fiber. Spatial filters for combining and decomposition of modes were designed, analyzed, fabricated with diffractive optics technology, and optically evaluated.

Development of a Qualitative Sequential Immunoassay for Characterizing the Intrinsic Properties of Circulating Cardiac Troponin I

With myocardial infarction (MI), cardiac troponin is released from the heart into circulation, where it can be detected with immunoassays independently quantifying cardiac troponin I (cTnI) or cTnT. There is, however, no single immunoassay that sequentially probes the posttranslational modification status of cTnI or directly characterizes whether circulating cTnI is bound to cTnC and/or cTnT. Here we describe the development of a qualitative immunoassay to directly probe the primary and ternary structure of circulating cTnI through diffractive optics technology (dotLab System, Axela). Anti-cTnI antibody 8I-7 was immobilized on a patterned sensor to capture cTnI. One or more detector antibodies were sequentially introduced to probe for amino acid sequence integrity or phosphorylation status of cTnI, or its association with cTnC and/or cTnT. Respective immunocaptures were recorded as real-time diffractive intensities (DIs), and the DI differences were analyzed. Each immunodetection was independent of the others but was done in a single sequential assay. This diffraction-based immunoassay successfully characterized cTnI. The unamplified assay determined whether cTnI was degraded at N-terminus and/or C-terminus or phosphorylated. Sequential application of multiple detector antibodies without an antibody-stripping step enables real-time interrogation of 5 different epitopes of cTnI, or direct detection of the cTn complex (cTnI-cTnC-cTnT) in a single sequential assay. Finally, this assay was optimized with amplification to directly detect circulating cTnI bound to cTnC and cTnT in serum from an MI patient. The dot Immunoassay is the first qualitative sequential immunoassay to address the direct interactions of the troponin subunits and various modified forms of cTnI.

Degradable Thermoresponsive Core Cross-Linked Micelles: Fabrication, Surface Functionalization, and Biorecognition

We report on the fabrication of core cross-linked (CCL) micelles possessing thermoresponsive and degradable cores and biocompatible coronas cofunctionalized with carbohydrate and biotin moieties. Well-defined poly(2-aminoethylmethacrylamide) (PAEMA) homopolymer was first synthesized in a controlled fashion via the reversible addition-fragmentation chain transfer (RAFT) process. CCL micelles comprising of well-solvated PAEMA coronas and thermoresponsive cores were then obtained in a one-pot manner via RAFT copolymerization of N-isopropylacrylamide (NIPAM) and bis(2-methacryloyloxyethyl) disulfide (DSDMA) difunctional monomers by employing PAEMA as the macro-RAFT agent. In the presence of dithiothreitol (DTT), the obtained CCL micelles can be disintegrated into unimers due to the cleavage of disulfide cross-linkers, whereas deswelling of micellar cores can be achieved via heating above the phase transition temperature of PNIPAM. Thus, the release profiles of this type of nanocarriers are expected to be triggered by temperature and thiols or a combination of both. Furthermore, primary amine residues located within coronas of CCL micelles have been further exploited for surface functionalization with biotin and carbohydrate moieties, rendering them biocompatible and bioactive. The availability of biotin within the coronas of CCL micelles was confirmed by HABA/avidin binding assay and Diffractive Optics Technology (DOT) biosensing instrument. After the micelles were immobilized on the surface of avidin-sensor chip, specific biorecognition of the available biotins and carbohydrate moieties on the CCL micelles was further confirmed. We expect that this novel type of bioactive and potentially biocompatible CCL micelles can be employed as smart nanocarriers for targeted drug delivery and controlled release.

A Novel Approach to Label-Free Sensing: Diffractive Optics Technology (dot®)

Label-free detection methods have played a very significant role in drug design and refinement. They have been used primarily during secondary screening and for in-depth characterization of biomolecular interactions. Misconceptions about the accessibility of these platforms, since they often require specialized training, throughput and robustness in complex media have hampered their adoption in the earliest phases of discovery not to mention their significant and unrealized potential in qualifying reagents for high throughput screening or during novel assay development. A new wave of more cost effective, robust and accessible platforms has made significant inroads, demonstrating that significant information can be derived from these methods all along the drug discovery research continuum. One of these recent entrants, the dotLab System uses diffractive optics technology (dot) to detect biomolecular interactions and can be used for a wide variety of applications in the study of a broad spectrum of biological analytes including proteins, DNA and even microorganisms.

Label-free and amplified quantitation of proteins in complex mixtures using diffractive optics technology

Immunoaffinity approaches remain invaluable tools for characterization and quantitation of biopolymers. Their application in separation science is often limited due to the challenges of immunoassay development. Typical end-point immunoassays require time consuming and labor-intensive approaches for optimization. Real-time label-free analysis using diffractive optics technology (dot ®) helps guide a very effective iterative process for rapid immunoassay development. Both label-free and amplified approaches can be used throughout feasibility testing and ultimately in the final assay, providing a robust platform for biopolymer analysis over a very broad dynamic range. We demonstrate the use of dot in rapidly developing assays for quantitating (1) human IgG in complex media, (2) a fusion protein in production media and (3) protein A contamination in purified immunoglobulin preparations.

Novel method for the fabrication of spatially variant structures

Spatially varying grating structures formed at the subwavelength scale behave as a layer with an artificial effective refractive index that is dependent on the local fill fraction. We describe a novel technique to pattern gratings with a spatially varying fill fraction using a simple two-step exposure process. The first exposure forms a partial latent image of a grating in the photoresist. The resist is then saturated by overlaying an exposure with an analog spatially varying intensity, generated by using a phase-only masking technique. The cumulative exposure dose from the two steps was designed so that the point of minimum intensity will still develop the photoresist through, in all the spaces in the grating. By varying the exposure window around the saturation dose, the fill fraction of the patterned gratings was modulated; thus, the size of the space cleared at any location in the grating is a scalable function of the local cumulative dose delivered. Constant feature height is achieved across the patterned area by keeping the second exposure dose below the resist threshold exposure value. The exposure process was modeled numerically to predict the relationship between the local dose and patterned fill fraction. This technique enables rapid, low-cost fabrication of apodized grating structures for applications in diffractive optics technology.

Solving the multiplexing–dynamic range conundrum with Diffractive Optics Technology (dot™)

The ability of the dotLab™ System to concurrently perform monitoring of protein-protein interactions in real-time, while using different assay formats, overcomes the traditional limitations of multiplexed end-point assays.

Diffractive Optics Technology: A Novel Detection Technology for Immunoassays

There is an increasing need for high-sensitivity immunoassays that can be used in point-of-care patient testing of complex media. For example, analytes such as the natriuretic peptides and recently discovered sepsis markers are found in blood in very low picomolar concentrations (1)(2). Although advances have been made in the use of fluorescent, chemiluminescent, and other labels to measure markers at lower detection limits, background interference from biological samples and detection instrumentation remains problematic. Optical biosensors offer the promise of label-free real-time measurements, but their application to quantification of analytes in complex media is impaired by higher detection limits and is susceptible to changes in refractive indices or nonspecific surface binding. Moreover, the costliness of these devices has largely prohibited bedside implementation. In this report, we detail the use of a novel diffractive optics technology (dot™) that takes advantage of the inherent properties of diffractive optics to deliver a cost-effective, portable, robust, optical biosensor that detects analytes at picomolar concentrations in complex media. In the dotLab™ System, coherent light striking a nonrandom pattern of capture molecules on the dotLab Sensor creates constructive and destructive interferences that produce a well-defined diffraction image. As molecules bind to the capture molecules, the height of the diffraction pattern is increased, which in turn increases the diffraction efficiency and the diffractive order intensity. A photodiode monitors the intensity of the diffractive order, which is correlated to analyte concentrations. Because diffraction is inherently self-referencing, the transduction of binding events is dependent on the initial pattern, and an increase in diffractive order intensity will occur only if molecules bind exclusively to the patterned capture reagents. Therefore, nonspecific binding to both the patterned and nonpatterned regions will not affect the signal, a characteristic that offers an important advantage over other …

Laser Beam Splitting by Diffractive Optics

Recent advances in diffractive optics theory and technology have made it possible to design programmable, multichannel optical systems based on diffraction gratings, lenslet arrays and digital holography algorithms. Spot array generation, multiple and multifocal imaging, matched filtering, laser beam mode selection and simultaneous contour shaping are among the most promising applications of diffractive beam splitting.

Diffractive superresolution elements

Superresolution phase-only pupil filters designed to utilize the degrees of freedom made available by diffractive optics technology are investigated theoretically. These so-called diffractive superresolution elements improve the quality of the superresolved diffraction pattern from the point of view of Strehl ratio, reduction of the spot size, control of the sidelobe effects, optimization procedures, and fabrication tolerances. The performance of these elements is studied, and the nature of the solutions obtainable with binary and multiple-phase structures is analyzed. Design considerations and solutions for applications such as confocal scanning microscopy and optical data storage are presented. Optimization of the degrees of freedom to satisfy desired constraints is discussed and compared with other methods.

Binary optics: An emerging diffractive optics technology

Binary optics: An emerging diffractive optics technology