A four-grating interferometer for x-ray multi-contrast imaging.

BACKGROUND: X-ray multi-contrast imaging with gratings provides a practical method to detect differential phase and dark-field contrast images in addition to the x-ray absorption image traditionally obtained in laboratory or hospital environments. Systems have been developed for preclinical applications in areas including breast imaging, lung imaging, rheumatoid arthritis hand imaging and kidney stone imaging. PURPOSE: Prevailing x-ray interferometers for multi-contrast imaging include Talbot-Lau interferometers and universal moiré effect-based phase-grating interferometers. Talbot-Lau interferometers suffer from conflict between high interferometer sensitivity and large field of view (FOV) of the object being imaged. A small period analyzer grating is necessary to simultaneously achieve high sensitivity and large FOV within a compact imaging system but is technically challenging to produce for high x-ray energies. Phase-grating interferometers suffer from an intrinsic fringe period ranging from a few micrometers to several hundred micrometers that can hardly be resolved by large area flat panel x-ray detectors. The purpose of this work is to introduce a four-grating x-ray interferometer that simultaneously allows high sensitivity and large FOV, without the need for a small period analyzer grating. METHODS: The four-grating interferometer consists of a source grating placed downstream of and close to the x-ray source, a pair of phase gratings separated by a fixed distance placed downstream of the source grating, and an analyzer grating placed upstream of and close to the x-ray detector. The object to be imaged is placed upstream of and close to the phase-grating pair. The distance between the source grating and the phase-grating pair is designed to be far larger than that between the phase-grating pair and the analyzer grating to promote simultaneously high sensitivity and large FOV. The method was evaluated by constructing a four-grating interferometer with an 8 µm period source grating, a pair of phase gratings of 2.4 µm period, and an 8 µm period analyzer grating. RESULTS: The fringe visibility of the four-grating interferometer was measured to be ≈24% at 40 kV and ≈18% at 50 kV x-ray tube operating voltage. A quartz bead of 6 mm diameter was imaged to compare the theoretical and experimental phase contrast signal with good agreement. Kidney stone specimens were imaged to demonstrate the potential of such a system for classification of kidney stones. CONCLUSIONS: The proposed four-grating interferometer geometry enables a compact x-ray multi-contrast imaging system with simultaneously high sensitivity and large FOV. Relaxation of the requirement for a small period analyzer grating makes it particularly suitable for high x-ray energy applications such as abdomen and chest imaging.

Towards non-blind optical tweezing by finding 3D refractive index changes through off-focus interferometric tracking.

In modern 3D microscopy, holding and orienting arbitrary biological objects with optical forces instead of using coverslips and gel cylinders is still a vision. Although optical trapping forces are strong enough and related photodamage is acceptable, the precise (re-) orientation of large specimen with multiple optical traps is difficult, since they grab blindly at the object and often slip off. Here, we present an approach to localize and track regions with increased refractive index using several holographic optical traps with a single camera in an off-focus position. We estimate the 3D grabbing positions around several trapping foci in parallel through analysis of the beam deformations, which are continuously measured by defocused camera images of cellular structures inside cell clusters. Although non-blind optical trapping is still a vision, this is an important step towards fully computer-controlled orientation and feature-optimized laser scanning of sub-mm sized biological specimen for future 3D light microscopy.

Quantification of HER2 in COS7 cells using quantum weak measurement.

A Mach-Zehnder interferometer system based on weak measurement was set up to determinate the concentration variation of molecule by measuring the phase difference change between the two optical paths. The spectrum of the light was recorded to monitor the concentration of trastuzumab (Herceptin), which is a humanised monoclonal antibody, targeted to human epidermal growth factor receptor 2 (HER2). The trastuzumab targeting to HER2 was real-time detected and continuously monitored, the HER2 numbers of COS7 cells on a coverslip was determined at pico-molar level. Our weak measurement enabled method proposes an alternative approach for the concentration detection of molecules, providing a promising functional tool for the quantification of HER2 in cancer cells, possibly promoting fields such as the diagnosis and treatment of cancer.

Comparison of two novel swept-source optical coherence tomography devices to a partial coherence interferometry-based biometer.

To evaluate the repeatability and agreement of corneal and biometry measurements obtained with two swept-source optical coherence tomography (SSOCT) and a partial coherence interferometry-based device. This is a cross-sectional study. Forty-eight eyes of 48 patients had three consecutive measurements for ANTERION (Heidelberg Engineering, Germany), CASIAII (Tomey, Japan) and IOLMaster500 (Carl Zeiss Meditec, USA) on the same visit. Mean keratometry (Km), central corneal thickness (CCT), anterior chamber depth (ACD) and axial length (AL) were recorded. Corneal astigmatic measurements were converted into vector components-J0 and J45. Intra-device repeatability and agreements of measurements amongst the devices were evaluated using repeatability coefficients (RCs) and Bland-Altman plots, respectively. All devices demonstrated comparable repeatability for Km (p ≥ 0.138). ANTERION had the lowest RC for J0 amongst the devices (p ≤ 0.039). Systematic difference was found for the Km and J0 obtained with IOLMaster500 compared to either SSOCTs (p ≤ 0.010). The ACD and AL measured by IOLMaster500 showed a higher RC compared with either SSOCTs (p < 0.002). Systematic difference was found in CCT and ACD between the two SSOCTs (p < 0.001), and in AL between ANTERION and IOLMaster500 (p < 0.001), with a mean difference of 1.6 µm, 0.022 mm and 0.021 mm, respectively. Both SSOCTs demonstrated smaller test-retest variability for measuring ACD and AL compared with IOLMaster500. There were significant disagreement in keratometry and AL measurements between the SSOCTs and PCI-based device; their measurements should not be considered as interchangeable.

Tapered Mach-Zehnder interferometer based on PbS quantum dots modified by polymers for copper ion sensing.

An optical fiber interferometer coated with PbS quantum dots (QDs) was developed for copper ion (${{\rm{Cu}}^{2 +}}$) detection. The QDs were modified by a multifunctional copolymer that enabled QD surface ligation, dispersion, and coordination with ${{\rm{Cu}}^{2 +}}$. ${{\rm{Cu}}^{2 +}}$ coordination with the polymer induced changes in the surrounding refractive index of the interferometer. The sensor was highly selective for ${{\rm{Cu}}^{2 +}}$ and showed a linear detection range of 0-1000 µM with a limit of detection of 2.20 µM in both aqueous and biological solutions.

Au-NPs signal amplification ultra-sensitivity optical microfiber interferometric biosensor.

An optical microfiber interferometric biosensor for the low concentration detection of sequence-specific deoxyribonucleic acid (DNA) based on signal amplification technology via oligonucleotides linked to gold nanoparticles (Au-NPs) is proposed and experimentally analyzed. The sensor uses a "sandwich" detection strategy, in which capture probe DNA (DNA-c) is immobilized on the surface of the optical microfiber interferometer, the reporter probe DNA (DNA-r) is immobilized on the surface of Au-NPs, and the DNA-c and DNA-r are hybridized to the target probe DNA (DNA-t) in a sandwich arrangement. The dynamic detection of the DNA-t was found to range from 1.0×10-15 M to 1.0×10-8 M, and the limit of detection (LOD) concentration was 1.32 fM. This sensor exhibited not only a low LOD but also excellent selectivity against mismatched DNA-t, and it can be further developed for application in various sensing platforms.

Real-time measurement method for the skin temperature of the human arm via large lateral shearing interferometry.

This paper presents a real-time measurement method for the skin temperature of the human arm. In this method, the air temperature close to the arm skin is measured via large lateral shearing interferometry, thus avoiding the possible influences of the different physical characteristics of different people, while maintaining the advantages of optical measurement, including its noncontact, noninvasive, and rapid features. The method captures the real-time fringe patterns generated using a parallel-sided plate when a collimated laser light beam transfers through the air surrounding the arm to be measured. Additionally, the phase difference distribution caused by the temperature difference is calculated in combination with the background fringe patterns. The phase difference in the light close to the arm skin is then estimated via a linear fitting method. Accordingly, based on the size parameters of the arm cross section and the ambient temperature monitored in real time, the air temperature close to the arm skin, which is considered equal to the arm skin temperature, is determined while considering the heat conduction effect. Experimental measurements of the temperature of human arm skin were conducted using the proposed method, and the axillary temperatures of the same person before and after the experiments were also measured using an electronic thermometer and a mercury thermometer. Good agreements were found, verifying the reliability of the proposed method. Moreover, based on this method, the possibility for the construction of a real-time body temperature measurement system is also discussed.

High sensitivity X-ray phase contrast imaging by laboratory grating-based interferometry at high Talbot order geometry.

X-ray phase contrast imaging is a powerful analysis technique for materials science and biomedicine. Here, we report on laboratory grating-based X-ray interferometry employing a microfocus X-ray source and a high Talbot order (35th) asymmetric geometry to achieve high angular sensitivity and high spatial resolution X-ray phase contrast imaging in a compact system (total length <1 m). The detection of very small refractive angles (∼50 nrad) at an interferometer design energy of 19 keV was enabled by combining small period X-ray gratings (1.0, 1.5 and 3.0 µm) and a single-photon counting X-ray detector (75 µm pixel size). The performance of the X-ray interferometer was fully characterized in terms of angular sensitivity and spatial resolution. Finally, the potential of laboratory X-ray phase contrast for biomedical imaging is demonstrated by obtaining high resolution X-ray phase tomographies of a mouse embryo embedded in solid paraffin and a formalin-fixed full-thickness sample of human left ventricle in water with a spatial resolution of 21.5 µm.

1/f-noise-free optical sensing with an integrated heterodyne interferometer.

Optical evanescent sensors can non-invasively detect unlabeled nanoscale objects in real time with unprecedented sensitivity, enabling a variety of advances in fundamental physics and biological applications. However, the intrinsic low-frequency noise therein with an approximately 1/f-shaped spectral density imposes an ultimate detection limit for monitoring many paramount processes, such as antigen-antibody reactions, cell motions and DNA hybridizations. Here, we propose and demonstrate a 1/f-noise-free optical sensor through an up-converted detection system. Experimentally, in a CMOS-compatible heterodyne interferometer, the sampling noise amplitude is suppressed by two orders of magnitude. It pushes the label-free single-nanoparticle detection limit down to the attogram level without exploiting cavity resonances, plasmonic effects, or surface charges on the analytes. Single polystyrene nanobeads and HIV-1 virus-like particles are detected as a proof-of-concept demonstration for airborne biosensing. Based on integrated waveguide arrays, our devices hold great potentials for multiplexed and rapid sensing of diverse viruses or molecules.

Contactless analysis of heart rate variability during cold pressor test using radar interferometry and bidirectional LSTM networks.

Contactless measurement of heart rate variability (HRV), which reflects changes of the autonomic nervous system (ANS) and provides crucial information on the health status of a person, would provide great benefits for both patients and doctors during prevention and aftercare. However, gold standard devices to record the HRV, such as the electrocardiograph, have the common disadvantage that they need permanent skin contact with the patient. Being connected to a monitoring device by cable reduces the mobility, comfort, and compliance by patients. Here, we present a contactless approach using a 24 GHz Six-Port-based radar system and an LSTM network for radar heart sound segmentation. The best scores are obtained using a two-layer bidirectional LSTM architecture. To verify the performance of the proposed system not only in a static measurement scenario but also during a dynamic change of HRV parameters, a stimulation of the ANS through a cold pressor test is integrated in the study design. A total of 638 minutes of data is gathered from 25 test subjects and is analysed extensively. High F-scores of over 95% are achieved for heartbeat detection. HRV indices such as HF norm are extracted with relative errors around 5%. Our proposed approach is capable to perform contactless and convenient HRV monitoring and is therefore suitable for long-term recordings in clinical environments and home-care scenarios.

Mid-IR refractive index sensor for detecting proteins employing an external cavity quantum cascade laser-based Mach-Zehnder interferometer.

Novel laser light sources in the mid-infrared region enable new spectroscopy schemes beyond classical absorption spectroscopy. Herein, we introduce a refractive index sensor based on a Mach-Zehnder interferometer and an external-cavity quantum cascade laser that allows rapid acquisition of high-resolution spectra of liquid-phase samples, sensitive to relative refractive index changes down to 10-7. Dispersion spectra of three model proteins in deuterated solution were recorded at concentrations as low as 0.25 mg mL-1. Comparison with Kramers-Kronig-transformed Fourier transform infrared absorbance spectra revealed high conformance, and obtained figures of merit compare well with conventional high-end FTIR spectroscopy. Finally, we performed partial least squares-based multivariate analysis of a complex ternary protein mixture to showcase the potential of dispersion spectroscopy utilizing the developed sensor to tackle complex analytical problems. The results indicate that laser-based dispersion sensing can be successfully used for qualitative and quantitative analysis of proteins.

Coherent silicon photonic interferometric biosensor with an inexpensive laser source for sensitive label-free immunoassays.

Over the past two decades, integrated photonic sensors have been of major interest to the optical biosensor community due to their capability to detect low concentrations of molecules with label-free operation. Among these, interferometric sensors can be read-out with simple, fixed-wavelength laser sources and offer excellent detection limits but can suffer from sensitivity fading when not tuned to their quadrature point. Recently, coherently detected sensors were demonstrated as an attractive alternative to overcome this limitation. Here we show, for the first time, to the best of our knowledge, that this coherent scheme provides sub-nanogram per milliliter limits of detection in C-reactive protein immunoassays and that quasi-balanced optical arm lengths enable operation with inexpensive Fabry-Perot-type lasers sources at telecom wavelengths.

Predicting fringe visibility in dual-phase grating interferometry with polychromatic X-ray sources.

Dual phase grating X-ray interferometry is radiation dose-efficient as compared to common Talbot-Lau grating interferometry. The authors developed a general quantitative theory to predict the fringe visibility in dual-phase grating X-ray interferometry with polychromatic X-ray sources. The derived formulas are applicable to setups with phase gratings of any phase modulation and with either monochromatic or polychromatic X-rays. Numerical simulations are presented to validate the derived formulas. The theory provides useful tools for design optimization of dual-phase grating X-ray interferometers.

Research on multi-parameter characteristics of a PCF sensor modified by GO composite films.

We propose a photonic crystal fiber (PCF) sensor based on graphene oxide (GO) composite film modification to simultaneously measure the multi-parameter sensing characteristics of humidity, temperature, and glucose concentration. The GO-polyvinyl alcohol (PVA) composite film is used to measure the humidity-sensing characteristics of the sensor, and the glucose oxidase composite film is used to measure the sensing characteristics of the glucose concentration, respectively. Experiment results show that the sensitivities of the temperature of the GO-PVA coating structure are 0.037 nm/°C, 0.047 nm/°C, and 0.031 nm/°C; the sensitivities of humidity are 0.059 nm/%RH, 0.121 nm/%RH, and 0.047 nm/%RH; and the sensitivities of the glucose concentration of the GO-GOD coating structure are 0.028 nm/(g/L), 0.049 nm/(g/L), and 0.010 nm/(g/L) for three interference dips, respectively. The structure is simple to manufacture and can be used as a sensor for detecting multiple parameters. It can be widely used in biomedicine, environmental monitoring, and other fields.

Surface-enhanced Raman scattering holography.

Nanometric probes based on surface-enhanced Raman scattering (SERS) are promising candidates for all-optical environmental, biological and technological sensing applications with intrinsic quantitative molecular specificity. However, the effectiveness of SERS probes depends on a delicate trade-off between particle size, stability and brightness that has so far hindered their wide application in SERS imaging methodologies. In this Article, we introduce holographic Raman microscopy, which allows single-shot three-dimensional single-particle localization. We validate our approach by simultaneously performing Fourier transform Raman spectroscopy of individual SERS nanoparticles and Raman holography, using shearing interferometry to extract both the phase and the amplitude of wide-field Raman images and ultimately localize and track single SERS nanoparticles inside living cells in three dimensions. Our results represent a step towards multiplexed single-shot three-dimensional concentration mapping in many different scenarios, including live cell and tissue interrogation and complex anti-counterfeiting applications.

Detection of Collagen-IV Using Highly Reflective Metal Nanoparticles-Immobilized Photosensitive Optical Fiber-Based MZI Structure.

In this work, a photosensitive (PS) optical fiber-based Mach-Zehnder interferometer (MZI) structure is developed to diagnose the presence of collagen-IV in human bodies. The MZI is fabricated by sequentially splicing the single mode-multimode-photosensitive-multimode-single mode (SMPMS) fiber segments. The sensing region in MZI structure is created by partially removing the cladding of photosensitive fiber by using 40% hydrofluoric (HF) acid and depositing the layers of highly reflective metal nanoparticles (NPs) over it. The used NPs are polyvinyl alcohol stabilized silver nanoparticles (PVA-AgNPs), gold nanoparticles (AuNPs), and zinc oxide nanoparticles (ZnO-NPs). The size of AuNPs, PVA-AgNPs, and ZnO-NPs are 10 ± 0.2 nm,  âˆ¼  4 -5 nm, and < 50 nm, respectively. In order to avoid the interference of other biomolecules in the detection of collagen-IV, the sensing region is functionalized with a collagenase enzyme. The sensing ability of the probe is ascertained by sensing a wide concentration of collagen solution ranging from 0 ng/ml to [Formula: see text]/ml. It is observed that sensing performance of probe is much better on immobilizing it with PVA-AgNPs and ZnO-NPs.

Design and development of volume phase holographic grating based digital holographic interferometer for label-free quantitative cell imaging.

In this paper, a volume phase holographic optical element based digital holographic interferometer is designed and used for quantitative phase imaging of biological cells [white blood cells, red blood cells, platelets, and Staphylococcus aureus (S. aureus) bacteria cells]. The experimental results reveal that sharp images of the S. aureus bacteria cells of the order of ${\sim}{1}\;{\unicode{x00B5}{\rm m}}$∼1µm can be clearly seen. The volume phase holographic grating will remove the stray light from the system reaching toward the grating and will minimize the coherent noise (speckle noise). This will improve the sharpness in the image reconstructed from the recorded digital hologram.

Application of speckle interferometry to the mechanical characterization of a biopolymer sample.

In this work, we present an optical and mechanical characterization of the behavior of an inhomogeneous biopolymer sample through the use of an in-plane electronic speckle pattern interferometer with a pulling system along the $y$y direction. The characterization of the sample subjected to stress comprised the acquisition of speckle patterns for 1360 states. Displacement maps and their corresponding strain maps were computed for every state. Since the information of the maps changes with size due to the sample being pulled at the upper end while it is clamped at the lower end, a scaling method to relate the maps to each other, point-to-point, is presented. The method allows the correct evaluation of sequential strain maps, which depicts the mechanical evolution of the material. Upon managing to relate the strain maps, it is possible to extract strain values for zones of interest from every map in order to build the respective stress-strain curves. Three stress-strain curves associated with three zones in the sample (upper, middle, and bottom) are constructed. When sequential displacement and deformation maps are optically obtained by the interferometer, we present a full-field characterization, along with the obtention stress-strain curves associated with the three zones of strain maps. The curves represent the inhomogeneous performance of the sample. Three different elastic moduli (${E_u} = 2.59\;{\rm MPa}$Eu=2.59MPa, ${E_m} = 1.97\;{\rm MPa}$Em=1.97MPa, and ${E_{b}} = 1.67\;{\rm MPa}$Eb=1.67MPa), associated with three respective zones, were obtained. The experimental results for a biopolymer sample here presented show that the technique, in conjunction with the scaling method, is a novel proposal to characterize inhomogeneous materials.

Highly sensitive and label-free digital detection of whole cell E. coli with Interferometric Reflectance Imaging.

Bacterial infectious diseases are a major threat to human health. Timely and sensitive pathogenic bacteria detection is crucial in bacterial contaminations identification and preventing the spread of infectious diseases. Due to limitations of conventional bacteria detection techniques there have been concerted research efforts towards developing new biosensors. Biosensors offering label-free, whole bacteria detection are highly desirable over those relying on label-based or pathogenic molecular components detection. The major advantage is eliminating the additional time and cost required for labeling or extracting the desired bacterial components. Here, we demonstrate rapid, sensitive and label-free Escherichia coli (E. coli) detection utilizing interferometric reflectance imaging enhancement allowing visualizing individual pathogens captured on the surface. Enabled by our ability to count individual bacteria on a large sensor surface, we demonstrate an extrapolated limit of detection of 2.2 CFU/ml from experimental data in buffer solution with no sample preparation. To the best of our knowledge, this level of sensitivity for whole E. coli detection is unprecedented in label-free biosensing. The specificity of our biosensor is validated by comparing the response to target bacteria E. coli and non-target bacteria S. aureus, K. pneumonia and P. aeruginosa. The biosensor's performance in tap water proves that its detection capability is unaffected by the sample complexity. Furthermore, our sensor platform provides high optical magnification imaging and thus validation of recorded detection events as the target bacteria based on morphological characterization. Therefore, our sensitive and label-free detection method offers new perspectives for direct bacterial detection in real matrices and clinical samples.

Characterisation of the static offset in the travelling wave in the cochlear basal turn.

In mammals, audition is triggered by travelling waves that are evoked by acoustic stimuli in the cochlear partition, a structure containing sensory hair cells and a basilar membrane. When the cochlea is stimulated by a pure tone of low frequency, a static offset occurs in the vibration in the apical turn. In the high-frequency region at the cochlear base, multi-tone stimuli induce a quadratic distortion product in the vibrations that suggests the presence of an offset. However, vibrations below 100 Hz, including a static offset, have not been directly measured there. We therefore constructed an interferometer for detecting motion at low frequencies including 0 Hz. We applied the interferometer to record vibrations from the cochlear base of guinea pigs in response to pure tones. When the animals were exposed to sound at an intensity of 70 dB or higher, we recorded a static offset of the sinusoidally vibrating cochlear partition by more than 1 nm towards the scala vestibuli. The offset's magnitude grew monotonically as the stimuli intensified. When stimulus frequency was varied, the response peaked around the best frequency, the frequency that maximised the vibration amplitude at threshold sound pressure. These characteristics are consistent with those found in the low-frequency region and are therefore likely common across the cochlea. The offset diminished markedly when the somatic motility of mechanosensitive outer hair cells, the force-generating machinery that amplifies the sinusoidal vibrations, was pharmacologically blocked. Therefore, the partition offset appears to be linked to the electromotile contraction of outer hair cells.