Interferometric Reflectance Imaging Sensor (IRIS) for Molecular Kinetics with a Low-Cost, Disposable Fluidic Cartridge.

The determination of kinetic information and appropriate binding pairs is fundamental to the proper optimization and selection of ligands used in immunoassays, diagnostics, and therapeutics. However, the ability to estimate such parameters in a multiplexed and inexpensive format remains difficult and modification of the ligand is often necessary. Here, we detail the methods and materials necessary to evaluate hundreds of unlabeled ligands simultaneously using the interferometric reflectance imaging sensor (IRIS). The incorporation of a low-cost fluidic cartridge that integrates on the top of the sensor simplifies reagent handling considerably.

Ultrafast Multiplexed-Allergen Detection through Advanced Fluidic Design and Monolithic Interferometric Silicon Chips.

A silicon-based miniaturized sensor chip combined with an advanced microfluidic module for the simultaneous, label-free immunochemical determination of four allergens, bovine milk protein, peanut protein, soy protein, and gliadin, is presented. The sensor chip consists of an array of 10 broad-band Mach-Zehnder interferometers (BB-MZIs) monolithically integrated on silicon, along with their respective broad-band light sources. The BB-MZIs were biofunctionalized with the targeted allergens and their responses during immunoreaction were monitored by multiplexing their transmission spectra through an external miniaturized spectrometer. The assay is performed by running mixtures of calibrators or samples with the antibodies against the four allergens followed by an antispecies specific antibodies solution. Employing a fluidic module of nearly one-dimensional geometry, that provided for uniform delivery of the reagents, CV values <6% were achieved for the responses of the 10 BB-MZIs, allowing for reliable multianalyte determinations. The analysis is completed in 6.5 min, and the detection limits were 0.04 µg/mL for bovine k-casein, 1.0 µg/mL for peanut protein, 0.80 µg/mL for soy protein, and 0.10 µg/mL for gliadin. The assays were accurate (recoveries 88-118%) and repeatable (intra- and interassay CVs <7% for all four allergens). Finally, the sensor was evaluated by analyzing samples from a cleaning in place system (CIP) of a dairy industry and the results obtained were in good agreement with those received by the respective ELISAs. The analytical characteristics of the sensor combined with the short analysis time and the small chip size make the proposed system an ideal tool for on-site multianalyte determinations.

A biolayer interferometry-based enzyme-linked aptamer sorbent assay for real-time and highly sensitive detection of PDGF-BB.

Accurate, fast and sensitive detection of disease-specific protein biomarkers, especially in blood, urine, or other bodily fluids, is an important approach to achieve early disease diagnosis. Platelet-derived growth factor-BB (PDGF-BB), a widely used biomarker, is involved in a substantial number of serious diseases, such as hepatic fibrosis, atherosclerosis, age-related macular degeneration and diabetic eye disease and is often over-expressed in human malignant tumors. Therefore, the development of sensitive and specific detection methods for PDGF-BB is of great importance for the early diagnosis of disease and assessments of patient recovery. In the current study, a biolayer interferometry-based enzyme-linked aptamer sorbent assay (BLI-ELASA) was successfully established for rapid (20-25min), high-throughput (8 or 16 samples) and real-time monitoring of PDGF-BB in clinical samples. The method exhibited a broad detection range from 0.5 to 1000ng/mL of PDGF-BB (good linear range from 0.5 to 10ng/mL), with a low detection limit of 0.08ng/mL. Moreover, BLI-ELASA was applied to the detection of PDGF-BB in spiked serum and urine samples and showed a high degree of selectivity for PDGF-BB, good reproducibility, and stability. We believe that the methodology in this work can be easily adapted to detect other biomolecules in clinical samples, including viruses, pathogens and toxins, in a rapid, sensitive, high-throughput and real-time manner.

Design of a birefringent Michelson interferometer-based interleaver with ultra-low dispersion and low cost.

We design and demonstrate a birefringent Michelson interferometer based interleaver with ultra-low dispersion and low cost. The interleaver consists of polarizing beam splitters (PBS's) and quarter-wave plates and half-wave plates. The PBS's based Michelson interferometers provide the optical path difference for interference between the two orthogonal polarization components and the half-wave plates provide the birefringent needed to minimize ripple of output. The designed interleaver with two-stage interferometer in a 50 GHz channel spacing application exhibits a 0.5 dB passband and a 25 dB stopband both 27 GHz; a channel isolation higher than 35 dB and chromatic dispersion less than ±5 ps/nm within 0.5 dB passband; 1.3 dB insertion loss and 0.3 dB PDL; 0.04 GHz/°C thermal stability. Since all of the optical components can be optically bonded together, the device is robust and easy to be aligned, which reduces labor cost.

An improved heterodyne laser interferometer for use in studies of cochlear mechanics.

A displacement-sensitive heterodyne laser interferometer is described which is suitable to measure the sound-evoked motion of various structures in the intact, living cochlea. Data are included to demonstrate the interferometer's low noise-floor ( < 1 pm Hz (-0.5)), wide bandwidth (from d.c. to 63 kHz) and linear dynamic range ( > 300 microm). The interferometer's optical sensitivity is sufficient to detect the motion of the basilar membrane and various components of the organ of Corti without the use of artificial reflectors: the reflectivity needed to achieve a 10 pm Hz(-0.5) noise-floor is approximately 0.0001%, and the optical sectioning depth is approximately 23 microm. These features make the interferometer ideally suited to measure acoustic vibrations in the living inner ear, but there may also be applications in other fields of neuroscience.