Interferometric Detection of Single Gold Nanoparticles Calibrated against TEM Size Distributions.

Single nanoparticle analysis: An interferometric optical approach calibrates sizes of gold nanoparticles (AuNPs) from the interference intensities by calibrating their interferometric signals against the corresponding transmission electron microscopy measurements. This method is used to investigate whether size affects the diffusion behavior of AuNPs conjugated to supported lipid bilayer membranes and to multiplex the simultaneous detection of three different AuNP labels.

Intra-observer and inter-observer repeatability of ocular surface interferometer in measuring lipid layer thickness.

BACKGROUND: Tear lipid morphology is important for normal tear function. Recently, there have been clinical studies using interferometry to assess lipid layer thickness (LLT). The aim of the study is to examine the repeatability of a commercially available interferometer. METHODS: Two observers measured LLT in twenty Asian subjects (20 eyes) using an interferometer (LipiView® ocular surface interferometer, TearScience Inc, Morrisville, NC). Dry eye symptoms, tear break up time (TBUT) and corneal fluorescein staining were also prospectively evaluated. RESULTS: Data for 20 participants are presented for either right or left eye (randomly selected). The mean LLT ± standard deviation of these participants was 53.53 ± 14.59 nm. When a single observer repeated the imaging on the same day, the coefficient of repeatability was 16 nm and the 95% limits of agreement were between -11 nm and 18 nm. When a different observer repeated the scan, the coefficient of repeatability was 13 nm and limits of agreement were -9 nm and 16 nm. LLT was not significantly associated with TBUT, presence of any corneal staining in any corneal zones, or symptomatic status. CONCLUSION: With the repeatability of measurements being known, the significance of LLT changes measured by this interferometer may be better interpreted. In this small Asian study, the LLT was lower than previously reported studies.

Axial Length Measurement: PalmScan Versus IOLMaster.

OBJECTIVE: To compare axial length measurements taken on the handheld Micro Medical Devices (MMD) PalmScan with those taken with the Carl Zeiss Meditec IOLMaster. METHODS: Sixty subjects had IOLMaster performed by a single operator to measure axial length in both eyes. Subjects then had axial length measurements taken by a different single operator with the MMD device. Each operator was masked to the other's results. Independent statistical analysis was performed to compare results. RESULTS: Sixty subjects had both eyes measured with each device for a total of 120 eyes. Subjects were categorized into 1 of 3 groups with 20 subjects each, 40 eyes in each group. Subjects in group A were wearers of overnight corneal reshaping, group B were soft lens wearers, and group C were noncontact lens wearers. Overall, the measures of axial length from IOLMaster and MMD were highly correlated (correlation = 0.93, P < 0.001, n = 120). Similarly, measures within each group between the 2 methods were highly correlated: group A (correlation = 0.94, P < 0.0001, n = 40), group B (correlation = 0.90, P < 0.0001, n = 40), and group C (correlation = 0.98, P < 0.001, n = 40). Results were highly correlated between the two devices. Data scatter plots and Bland-Altman plots were generated, showing that although there was good agreement between the methods, the MMD almost always measured the axial length smaller than the IOLMaster (median difference = 0.21 mm, mean difference ± SD = 0.26 ± 0.42 mm). CONCLUSIONS: The MMD is a convenient, reliable, and portable device to measure axial length. It can be used to monitor axial length in patients over time.

Reproducibility of a long-range swept-source optical coherence tomography ocular biometry system and comparison with clinical biometers.

OBJECTIVE: To demonstrate a novel swept source optical coherence tomography (SS-OCT) imaging device using a vertical cavity surface-emitting laser (VCSEL) capable of imaging the full eye length and to introduce a method using this device for noncontact ocular biometry. To compare the measurements of intraocular distances using this SS-OCT instrument with commercially available optical and ultrasound biometers. To evaluate the intersession reproducibility of measurements of intraocular distances using SS-OCT. DESIGN: Evaluation of technology. PARTICIPANTS: Twenty eyes of 10 healthy subjects imaged at the New England Eye Center at Tufts Medical Center and Massachusetts Institute of Technology between May and September 2012. METHODS: Averaged central depth profiles were extracted from volumetric SS-OCT datasets. The intraocular distances, such as central corneal thickness (CCT), aqueous depth (AD), anterior chamber depth (ACD), crystalline lens thickness (LT), vitreous depth (VD), and axial length (AL), were measured and compared with a partial coherence interferometry device (IOLMaster; Carl Zeiss Meditec, Inc., Dublin, CA) and an immersion ultrasound (IUS) A-scan biometer (Axis-II PR; Quantel Medical, Inc., Cournon d'Auvergne Cedex, France). MAIN OUTCOME MEASURES: Reproducibility of the measurements of intraocular distances, correlation coefficients, and intraclass correlation coefficients. RESULTS: The standard deviations of the repeated measurements of intraocular distances using SS-OCT were 6 µm (CCT), 16 µm (ACD), 14 µm (AD), 13 µm (LT), 14 µm (VD), and 16 µm (AL). Strong correlations among all 3 biometric instruments were found for AL (r > 0.98). The AL measurement using SS-OCT correlates better with the IOLMaster (r=0.998) than with IUS (r=0.984). The SS-OCT and IOLMaster measured higher AL values than ultrasound (175 and 139 µm, respectively). No statistically significant difference in ACD between the optical (SS-OCT or IOLMaster) and ultrasound methods was detected. High intersession reproducibility of SS-OCT measurements of all intraocular distances was observed with intraclass correlation coefficients >0.99. CONCLUSIONS: The SS-OCT using VCSEL technology enables full eye length imaging and high-precision, noncontact ocular biometry. The measurements with the prototype SS-OCT instrument correlate well with commercial biometers. The SS-OCT biometry has the potential to provide clinically useful comprehensive biometric parameters for pre- and postoperative eye evaluation.

Active angular alignment of gauge blocks in double-ended interferometers.

This paper presents a method implemented in a system for automatic contactless calibration of gauge blocks designed at ISI ASCR. The system combines low-coherence interferometry and laser interferometry, where the first identifies the gauge block sides position and the second one measures the gauge block length itself. A crucial part of the system is the algorithm for gauge block alignment to the measuring beam which is able to compensate the gauge block lateral and longitudinal tilt up to 0.141 mrad. The algorithm is also important for the gauge block position monitoring during its length measurement.

Verification of polarising optics for the LISA optical bench.

The Laser Interferometer Space Antenna (LISA) is a space-based interferometric gravitational wave detector. In the current baseline design for the optical bench, the use of polarising optics is foreseen to separate optical beams. Therefore it is important to investigate the influence of polarising components on the interferometer sensitivity and validate that the required picometre stability in the low-frequency band (1 mHz - 1 Hz) is achievable. This paper discusses the design of the experiment and the implemented stabilisation loops. A displacement readout fulfilling the requirement in the whole frequency band is presented. Alternatively, we demonstrate improvement of the noise performance by implementing various algorithms in data post-processing, which leads to an additional robustness for the LISA mission.

Displacement interferometry with stabilization of wavelength in air.

We present a concept of suppression of the influence of variations of the refractive index of air in displacement measuring interferometry. The principle is based on referencing of wavelength of the coherent laser source in atmospheric conditions instead of traditional stabilization of the optical frequency and indirect evaluation of the refractive index of air. The key advantage is in identical beam paths of the position measuring interferometers and the interferometer used for the wavelength stabilization. Design of the optical arrangement presented here to verify the concept is suitable for real interferometric position sensing in technical practice especially where a high resolution measurement within some limited range in atmospheric conditions is needed, e.g. in nanometrology.

Future directions in non-invasive measurements of tear film surface kinetics.

PURPOSE: To review the methods for dynamic, non-invasive, and objective assessment of tear film surface quality and to outline their current state-of-the-art and their future potential. METHODS: Among the methods available, high-speed videokeratoscopy, lateral shearing interferometry, and dynamic wavefront sensing are being considered. RESULTS: The principles of operations, their advantages and disadvantages, and limitations of each method are being outlined. The possible future directions of each method are also discussed. CONCLUSIONS: To gain a better understanding of tear film, its structure and function, it is essential to combine macroimaging technologies with those focusing on tear film microstructure. In this way, one can envisage a clinical device that could help, in future, early diagnosis of dry eye syndrome and development of better materials for contact lenses and eye lubricants.

Assessing tear film on soft contact lenses with lateral shearing interferometry.

OBJECTIVES: Evaluating precorneal tear film is one of important clinical measurements for assessing health of anterior eye. Contact lens wear is known to influence the quality of tear film. The aim was to evaluate the applicability of lateral shearing interferometry technique in the noninvasive assessment of the effects of contact lens replacement modality and its water content on tear film stability. METHODS: Sixteen regular soft contact lens wearers took place in the study. Lateral shearing interferometry measurements, in suppressed blinking conditions, were taken in the mornings and afternoons, after a minimum of 5 hours of lens wear for the daily lenses, and after 2 weeks and 1 month for the fortnightly and monthly lens replacement modalities, respectively. RESULTS: Significant differences (paired bootstrap-based Behrens-Fisher test, P < 0.05) in the tear film surface quality were found between all considered pairs of replacement modalities except for the daily and fortnightly lenses measured in the afternoon of the first day of wear. Significant worsening (paired bootstrap-based Behrens-Fisher test, P < 0.001) of tear film quality was found for the low water content materials. CONCLUSIONS: Lateral shearing interferometry is a powerful method for the noninvasive assessment of tear film surface quality on soft contact lenses that may find, in future, its use in the clinical assessment of anterior eye's health.

Simultaneous calibration of optical tweezers spring constant and position detector response.

We demonstrate a fast and direct calibration method for systems using a single laser for optical tweezers and particle position detection. The method takes direct advantage of back-focal-plane interferometry measuring not an absolute but a differential position, i.e. the position of the trapped particle relative to the center of the optical tweezers. Therefore, a fast step-wise motion of the optical tweezers yields the impulse response of the trapped particle. Calibration parameters such as the detector's spatial and temporal response and the spring constant of the optical tweezers then follow readily from fitting the measured impulse response.

Error-free demodulation of pixelated carrier frequency interferograms.

Recently, pixelated spatial carrier interferograms have been used in optical metrology and are an industry standard nowadays. The main feature of these interferometers is that each pixel over the video camera may be phase-modulated by any (however fixed) desired angle within [0,2pi] radians. The phase at each pixel is shifted without cross-talking from their immediate neighborhoods. This has opened new possibilities for experimental spatial wavefront modulation not dreamed before, because we are no longer constrained to introduce a spatial-carrier using a tilted plane. Any useful mathematical model to phase-modulate the testing wavefront in a pixel-wise basis can be used. However we are nowadays faced with the problem that these pixelated interferograms have not been correctly demodulated to obtain an error-free (exact) wavefront estimation. The purpose of this paper is to offer the general theory that allows one to demodulate, in an exact way, pixelated spatial-carrier interferograms modulated by any thinkable two-dimensional phase carrier.

Design optimization of a periodic microstructured array anode for hard x-ray grating interferometry.

Talbot-Lau grating interferometer (TLGI) has great advantages in x-ray imaging contrasts, especially for low-Z materials, over conventional absorption contrast. A microstructured array anode target (MAAT) source offers significantly higher imaging throughput than the combination of an extended x-ray source paired with an absorption grating (also known as source grating). The performance of the MAAT source can be optimized with respect to the areal density, dimensions, and choice of material for the microstructured metal inserts (MMI) and the substrate in which they are embedded. In this paper, we analyze the x-ray generation efficiency per incident electron, relative fraction of x-rays generated by MMI and substrate, x-ray spectrum, and angular distribution via Monte Carlo simulation. Based on the simulation results, the optimal parameters are obtained for a MAAT with incident electron energies from 30 keV to 120 keV. The corresponding temperature distribution within the MAAT is also simulated for the optimal set of the parameters via finite element analysis. As demonstrated by the thermal analysis data, the maximum allowable electron-beam power loading was derived that allows a stable operation of the transmission MAAT.

Metabolic activity interferometer: description and calibration of an interferometric method to measure growth of mycobacteria.

An interferometer that measures the refractive index changes due to bacterial metabolism is described. The apparatus permits simultaneous and real time measurement of bacterial growth in several samples of slowly growing mycobacteria. The error sources are discussed and the sensitivity of the apparatus is tested. For the species Mycobacterium bovis BCG and M. smegmatis, a relation between refractive index change and bacterial concentration is determined experimentally and the time constant of bacterial growth is measured.

Influence of the signal-to-noise ratio on the accuracy of IOLMaster measurements.

PURPOSE: To evaluate the relationship between the sound-to-noise ratio (SNR) and the reliability of axial length (AL) measurements obtained with the IOLMaster (Carl Zeiss Meditec AG). SETTING: Department of Ophthalmology, Saiseikai Kurihashi Hospital, Saitama, Japan. METHODS: In a clinical prospective study, 216 consecutive eyes of 144 patients scheduled for cataract surgery were evaluated for the type and severity of cataract using the Lens Opacities Classification System III. Preoperative and postoperative AL measurements were performed with the IOLMaster. The preoperative SNR values were used to divide the eyes into 5 groups. The following were compared between the groups: preoperative logMAR best spectacle-corrected visual acuity (BSCVA), difference in AL between preoperatively and postoperatively, error in the postoperative predicted refraction, and type and severity of cataract. RESULTS: The preoperative logMAR BSCVA was significantly worse in eyes with an SNR <2 (P<.05). The AL was longer preoperatively than postoperatively in all groups, and there was a significant difference in the <2 SNR group and the 2 to <5 group (P<.05). There were no significant differences in the error in postoperative predicted refraction. The percentage of patients with P4 or worse posterior subcapsular cataract (PSC) increased significantly with a decrease in the SNR (P<.01). However, there was no correlation between nuclear color grade and the SNR. CONCLUSION: The SNR value was useful in confirming the good quality of AL readings taken with the IOLMaster, even though the SNR value correlated significantly with the preoperative logMAR BSCVA and PSC severity.

The clinical value of Moiré topography in the management of scoliosis.

An analysis of the diagnostic reliability and the clinical value of moiré topography is presented. Moiré topography was used as an adjunct to clinical assessment and roentgenographic examination in a consecutive series of 139 scoliosis observations. In 17%, the moiré pattern lateral to the scapulae was impossible to analyze. One false negative finding and 23 false positive findings were observed. There was no correlation between the moiré asymmetry and the Cobb angle. An asymmetry of one contour line implied a curve less than 25 degrees. (The location of the maximal moiré asymmetry did not necessarily coincide with the apex of the scoliosis.) It is concluded that moiré topography is loaded with pitfalls that must be considered. However, used in a designed way, the method is of clinical value, complementing physical examination in screening and longitudinal observation of scoliosis.

Fiber optic pressure sensor for biomedical applications.

In vivo measurement of blood pressure is critical in many settings, including patient care, medical research, and control of cardiovascular assist and replacement devices. This article describes a pressure sensor based on fiber optic, white light interferometry. An optical interference filter formed between the end face of an optical fiber and the sensing diaphragm selectively reflects a wavelength component. A low cost, thin film optical wedge interferometer placed at the output end detects the wavelength of the reflected signal, which represents a unique cavity length of the interference filter directly related to the diaphragm deflection and, therefore, pressure. Several key features of this sensing scheme include low drift, high accuracy, and insensitivity to light loss factors along the length of the optical fiber. This fiber optic pressure sensor promises significant advances as a medical monitoring tool, a research instrument, and a component of cardiovascular assist and replacement devices. A prototype pressure gauge has been built, and the feasibility of the optical approach verified. Experimental results of the prototype gauge for resolution, repeatability, and drift and a preliminary design for a high resolution, low drift, miniature fiber optic pressure probe are presented herein.

Calibration of high-frequency hydrophone up to 40 MHz by heterodyne interferometer.

A calibration technique for high-frequency hydrophone utilizing a heterodyne interferometer is presented in this article. The calibration system is mainly composed of optical and signal processing modules. In the displacement measurement, a pellicle is mounted at the surface of water to avoid acousto-optical interaction. The phase modulated carrier signal is digitized and transferred to the computer, then processed by digital phase demodulation. A phase unwrapping algorithm is employed to remove ambiguity of the arctangent function and has proven effective in large displacement measurements. Pellicle displacement and voltage output of the hydrophone in focused ultrasonic field are processed by DFT to determine the amplitudes of the fundamental and harmonic components. Experiments show that the heterodyne technique can provide hydrophone calibration up to 40 MHz, with a slightly smaller sensitivity compared with the National Physical Laboratory (NPL) calibration results for most frequency ranges. Since the heterodyne technique is independent on assumptions about the geometry of the ultrasonic field and the performance of the transducer, it can be easily extended to high frequency and high power ultrasound measurement applications.

Comparison of the new biometer OA-1000 with IOLMaster and Tomey AL-3000.

BACKGROUND: The OA-1000 (Tomey, Japan) is a new optical biometer, which allows measurements of axial length (AL), anterior chamber depth (ACD) and corneal thickness (CT) due to partial coherence interferometry (PCI) technology. The aim of this study was to compare the OA-1000 results with those obtained with the IOLMaster and contact applanation A-scan ultrasonography. METHODS: We examined 133 eyes of 75 patients with age related cataract. Mean age was 72.0 ± 9.5 years. Biometry measurements of AL and ACD were performed with the Tomey OA-1000 based on PCI, the IOLMaster based on PCI (AL) and slit projection (ACD), and the Tomey AL-3000 based on contact applanation A-scan ultrasonography. RESULTS: Mean AL using the IOLMaster was 23.21 ± 1.08 mm, using the AL-3000 was 22.79 ± 1.04 mm, using the OA-1000 it was 22.97 ± 1.1 mm. Mean ACD using the IOLMaster was 2.99 ± 0.41 mm, using the OA-1000 3.40 ± 0.46 mm, using the Tomey AL-3000 it was 2.93 ± 0.43 mm. Mean difference between the AL and ACD measured with the OA-1000 and the IOLMaster was 0.22 ± 0.047 mm and 0.40 ± 0.33 mm, between OA-1000 and the AL-3000 it was 0.19 ± 0.23 mm and 0.47 ± 0.33 mm, and between IOLMaster and AL-3000 it was 0.42 ± 0.23 and 0.09 ± 0.36 mm. For AL the correlation coefficient R between IOLMaster and OA-1000 was 0.999, between IOLMaster and AL-3000 it was 0.976, between AL-3000 and OA-1000 it was 0.977. For ACD R between IOLMaster and OA-1000 was 0.735, between IOLMaster and AL-3000 it was 0.822, between AL-3000 and OA-1000 it was 0.716 (all p < 0.001). CONCLUSIONS: Compared with other used clinical instruments the OA-1000 generates accurate results. Although differences were found, the OA-1000 provided results that correlated well with the values of IOLMaster and AL-3000.

ABRF-MIRG benchmark study: molecular interactions in a three-component system.

Protein-protein interactions identified through high-throughput proteomics efforts continue to advance our understanding of the protein interactome. In addition to highly specific protein-protein interactions, it is becoming increasingly more common for yeast two-hybrid, pull-down assays, and other proteomics techniques to identify multiple protein ligands that bind to the same target protein. A resulting challenge is to accurately characterize the assembly of these multiprotein complexes and the competition among multiple protein ligands for a given target. The Association of Biomolecular Resource Facilities-Molecular Interactions Research Group recently conducted a benchmark study to assess participants' ability to correctly describe the interactions between two protein ligands and their target protein using primarily biosensor technologies, such as surface plasmon resonance. Participants were provided with microgram quantities of three proteins (A, B, and C) and asked to determine if a ternary A-B-C complex can form or if protein-B and protein-C bind competitively to protein-A. This article will summarize the experimental approaches taken by participants to characterize the molecular interactions, the interpretation of the data, and the results obtained using different biosensor instruments.