Abrupt autofocusing beam from a phase-only mask.

Airy beams have become an important beam shape for structured light beams because of their interesting self-accelerating and parabolic propagation properties. Many variants of Airy beams have been proposed, among which the Airy beam with cylindrical symmetry [also known as the circular Airy beam or abrupt autofocusing (AAF) beam] is particularly peculiar and has attracted special attention due to its shape transformation during propagation. Much effort has been devoted to understanding the properties of the AAF beam. In this work, we present simulation results for generating the AAF beam using a phase-only mask. A cubic chirp-modulated axicon phase is used to create the mask. We found an optimal value for the axiconic phase, and the cubic phase is essential for controlling the AAF beam's shape. We demonstrate that a phase-only mask is an effective and simple method for generating high contrast between the initial and AAF plane. We present the results for beam formation and propagation dynamics of the AAF beam using the control parameters of the phase mask. We also discuss the design parameters and their influence on the AAF beam shapes. Our results pave the way for a deeper understanding of the beam formation and propagation dynamics of the AAF beam.

Volume holographic illuminator for Airy light-sheet microscopy.

Airy light sheets combined with the deconvolution approach can provide multiple benefits, including large field of view (FOV), thin optical sectioning, and high axial resolution. The efficient design of an Airy light-sheet fluorescence microscope requires a compact illumination system. Here, we show that an Airy light sheet can be conveniently implemented in microscopy using a volume holographic grating (VHG). To verify the FOV and the axial resolution of the proposed VHG-based Airy light-sheet fluorescence microscope, ex-vivo fluorescently labeled Caenorhabditis elegans (C. elegans) embryos were imaged, and the Richardson-Lucy deconvolution method was used to improve the image contrast. Optimized parameters for deconvolution were compared with different methods. The experimental results show that the FOV and the axial resolution were 196 µm and 3 µm, respectively. The proposed method of using a compact VHG to replace the common spatial light modulator provides a direct solution to construct a compact light-sheet fluorescence microscope.

Multifocal confocal microscopy using a volume holographic lenslet array illuminator.

Multifocal illumination can improve image acquisition time compared to single point scanning in confocal microscopy. However, due to an increase in the system complexity, obtaining uniform multifocal illumination throughout the field of view with conventional methods is challenging. Here, we propose a volume holographic lenslet array illuminator (VHLAI) for multifocal confocal microscopy. To obtain uniform array illumination, a super Gaussian (SG) beam has been incorporated through VHLAI with an efficiency of 43%, and implemented in a confocal microscope. The design method for a photo-polymer based volume holographic beam shaper is presented and its advantages are thoroughly addressed. The proposed system can significantly improve image acquisition time without sacrificing the quality of the image. The performance of the proposed multifocal confocal microscopy was compared with wide-field images and also evaluated by measuring optically sectioned microscopic images of fluorescence beads, florescence pollen grains, and biological samples. The proposed multifocal confocal system generates images faster without any changes in scanning devices. The present method may find important applications in high-speed multifocal microscopy platforms.

A pilot study for the prediction of liver function related scores using breath biomarkers and machine learning.

Volatile organic compounds (VOCs) present in exhaled breath can help in analysing biochemical processes in the human body. Liver diseases can be traced using VOCs as biomarkers for physiological and pathophysiological conditions. In this work, we propose non-invasive and quick breath monitoring approach for early detection and progress monitoring of liver diseases using Isoprene, Limonene, and Dimethyl sulphide (DMS) as potential biomarkers. A pilot study is performed to design a dataset that includes the biomarkers concentration analysed from the breath sample before and after study subjects performed an exercise. A machine learning approach is applied for the prediction of scores for liver function diagnosis. Four regression methods are performed to predict the clinical scores using breath biomarkers data as features set by the machine learning techniques. A significant difference was observed for isoprene concentration (p < 0.01) and for DMS concentration (p < 0.0001) between liver patients and healthy subject's breath sample. The R-square value between actual clinical score and predicted clinical score is found to be 0.78, 0.82, and 0.85 for CTP score, APRI score, and MELD score, respectively. Our results have shown a promising result with significant different breath profiles between liver patients and healthy volunteers. The use of machine learning for the prediction of scores is found very promising for use of breath biomarkers for liver function diagnosis.

Male factor infertility and placental pathology in singleton live births conceived with in vitro fertilization.

PURPOSE: We sought to determine whether pregnancies conceived in those with male factor infertility have unique placental pathology profiles compared to those undergoing infertility treatments for other indications. METHODS: This was a retrospective cohort study of placental pathology from 464 live births conceived from autologous fresh IVF cycles at an academic fertility center from 2004 to 2017. Placental pathology was compared between live births arising from patients with male factor infertility alone and those with another infertility diagnosis. Placental outcomes were compared with parametric or non-parametric tests; logistic regression was performed to account for potential confounders. RESULTS: Compared to cycles performed for a non-male factor diagnosis, male factor infertility cycles had a higher mean paternal age (38.2 years vs. 36.5 years, p < 0.001), a higher female mean BMI (24.3 vs. 23.3 kg/m2, p = 0.01), and a lower day 3 follicle stimulating hormone (FSH) level (6.8 vs. 7.3 IU/mL, p = 0.02). The mean numbers of embryos transferred, and day of transfer were similar between groups, and more cycles used ICSI in the male factor infertility group (90.6% vs. 22.5%, p < 0.001). Placental pathology in our adjusted model was similar between the male factor and non-male factor groups. In our unadjusted subgroup analysis, cycles for male factor using ICSI appeared to lead to more small placentas by weight compared to cycles performed with conventional insemination (45.8% < 10th percentile vs. 18.8%, p = 0.04). CONCLUSION: Male factor infertility is not associated with significantly different placental pathology compared to other infertility diagnoses.

Multi-plane confocal microscopy with multiplexed volume holographic gratings [Invited].

A volume holographic (VHG) grating-based multi-plane differential confocal microscopy (DCM) is proposed for axial scan-free imaging. Also, we briefly reviewed our previous works on volume holographic-based confocal imaging. We show that without degrading imaging performance, it is possible to simultaneously obtain two depth-resolved optically sectioned images with improved axial resolution using multi-plane DCM. The performance of our multi-plane DCM was evaluated by measuring the surface profile of a silicon micro-hole array with depths separation around 10 µm. The axial sensitivity of the system is around 25 nm. Our system has the advantages of multi-plane imaging with high axial sensitivity and high optical sectioning ability. Our method can be used for reflective surface profiling and multi-plane fluorescence imaging. The present methods may find important applications in surface metrology for label-free biological samples, as well as industrial applications.

Surface Wettability and Electrical Resistance Analysis of Droplets on Indium-Tin-Oxide Glass Fabricated Using an Ultraviolet Laser System.

Indium tin oxide (ITO) is widely used as a substrate for fabricating chips because of its optical transparency, favorable chemical stability, and high electrical conductivity. However, the wettability of ITO surface is neutral (the contact angle was approximately 90°) or hydrophilic. For reagent transporting and manipulation in biochip application, the surface wettability of ITO-based chips was modified to the hydrophobic or nearly hydrophobic surface to enable their use with droplets. Due to the above demand, this study used a 355-nm ultraviolet laser to fabricate a comb microstructure on ITO glass to modify the surface wettability characteristics. All of the fabrication patterns with various line width and pitch, depth, and surface roughness were employed. Subsequently, the contact angle (CA) of droplets on the ITO glass was analyzed to examine wettability and electrical performance by using the different voltages applied to the electrode. The proposed approach can succeed in the fabrication of a biochip with suitable comb-microstructure by using the optimal operating voltage and time functions for the catch droplets on ITO glass for precision medicine application. The experiment results indicated that the CA of droplets under a volume of 20 µL on flat ITO substrate was approximately 92° ± 2°; furthermore, due to its lowest surface roughness, the pattern line width and pitch of 110 µm exhibited a smaller CA variation and more favorable spherical droplet morphology, with a side and front view CA of 83° ± 1° and 78.5° ± 2.5°, respectively, while a laser scanning speed of 750 mm/s was employed. Other line width and pitch, as well as scanning speed parameters, increased the surface roughness and resulted in the surface becoming hydrophilic. In addition, to prevent droplet morphology collapse, the droplet's electric operation voltage and driving time did not exceed 5 V and 20 s, respectively. With this method, the surface modification process can be employed to control the droplet's CA by adjusting the line width and pitch and the laser scanning speed, especially in the neutral or nearly hydrophobic surface for droplet transporting. This enables the production of a microfluidic chip with a surface that is both light transmittance and has favorable electrical conductivity. In addition, the shape of the microfluidic chip can be directly designed and fabricated using a laser direct writing system on ITO glass, obviating the use of a mask and complicated production processes in biosensing and biomanipulation applications.

Telecentric design for digital-scanning-based HiLo optical sectioning endomicroscopy with an electrically tunable lens.

Confocal endoscopy has been widely used to obtain fine optically sectioned images. However, confocal endomicroscopic images are formed by point-by-point scanning in both lateral and axial directions, which results in long image acquisition time. Here, an endomicroscope with telecentric configuration is presented to achieve nonmechanical and rapid axial scanning for volumetric fluorescence imaging. In our system, optical sectioning in wide-field fashion is obtained through HiLo imaging with a digital micromirror device. Axial scanning, without mechanical moving parts, is conducted by digital focus adjustment using an electrically tunable lens, offering constant magnification and contrast. We demonstrate imaging performance of our system with optically sectioned images using fluorescently labeled beads, as well as ex vivo mice cardiac tissue samples. Our system provides multiple advantages, in terms of improved scanning range, and reduced image acquisition time, which shows great potentials for three-dimensional biopsies of volumetric biological samples.

Simultaneous multi-color optical sectioning fluorescence microscopy with wavelength-coded volume holographic gratings.

Optical sectioning fluorescence microscopy provides high contrast images of volumetric samples and has been widely used for many biological applications. However, simultaneously acquiring multi-color fluorescence images require additional optical elements and devices, which are bulky, wavelength specific, and not cost-effective. In this paper, wavelength-coded volume holographic gratings (WC-VHGs) based optical sectioning fluorescence microscopy is proposed to simultaneously offer multi-color fluorescence images with fine out-of-focus background rejection. Due to wavelength degeneracy, multiplexed WC-VHGs are capable of acquiring multi-wavelength fluorescence images in a single shot, and displaying the laterally separated multi-wavelength images onto CCD. In our system optical sectioning capability is achieved through speckle illumination and HiLo imaging method. To demonstrate imaging characteristics of our system, dual-wavelength fluorescence images of both standard fluorescent microspheres and ex vivo mT/mG mice cardiac tissue are presented. Current results may find important applications in hyperspectral imaging for biomedical research.

Two-photon fluorescence imaging of subsurface tissue structures with volume holographic microscopy.

SIGNIFICANCE: Two-photon (2P) fluorescence imaging can provide background-free high-contrast images from the scattering tissues. However, obtaining a multiplane image is not straightforward. We present a two-photon volume holographic imaging (2P-VHI) system for multiplane imaging. AIM: Our goal was to design and implement a 2P-VHI system that can provide the high-contrast optically sectioned images at multiple planes. APPROACH: A 2P-VHI system is presented that incorporates angularly multiplexed volume holographic gratings and a femtosecond laser source for fluorescence excitation for multiplane imaging. A volume hologram with multiplexed gratings provides multifocal observation, whereas nonlinear excitation using a femtosecond laser helps in significantly enhancing both depth resolution and contrast of images. RESULTS: Standard fluorescent beads are used to demonstrate the imaging performance of the 2P-VHI system. Two-depth resolved optical-sectioning images of fluorescently labeled thick mice intestine samples were obtained. In addition, the optical sectioning capability of our system is measured and compared with that of a conventional VHI system. CONCLUSIONS: Results demonstrated that 2P excitation in VHI systems provided the optical sectioning ability that helps in reducing background noise in the images. Integration of nonlinear fluorescence excitation in the VHI provides some unique advantages to the system and has potential to design multidepth optical sectioned spatial-spectral imaging systems.

Multiplane differential phase contrast imaging using asymmetric illumination in volume holographic microscopy.

SIGNIFICANCE: Differential phase contrast (DPC) is a well-known imaging technique for phase imaging. However, simultaneously acquiring multidepth DPC images is a non-trivial task. We propose simultaneous multiplane DPC imaging using volume holographic microscopy (VHM). AIM: To design and implement a new configuration of DPC-VHM for multiplane imaging. APPROACH: The angularly multiplexed volume holographic gratings (AMVHGs) and the wavelength-coded volume holographic gratings (WC-VHGs) are used for this purpose. To obtain asymmetric illumination for DPC images, a dynamic illumination system is designed by modifying the regular Köhler illumination using a thin film transistor panel (TFT-panel). RESULTS: Multidepth DPC images of standard resolution chart and biosamples were used to compare imaging performance with the corresponding bright-field images. An average contrast enhancement of around three times is observed for target resolution chart by DPC-VHM. Imaging performance of our system is studied by modulation transfer function analysis, which suggests that DPC-VHM not only suppresses the DC component but also enhances high-frequency information. CONCLUSIONS: Proposed DPC-VHM can acquire multidepth-resolved DPC images without axial scanning. The illumination part of the system is adjustable so that the system can be adapted to bright-field mode, phase contrast mode, and DPC mode by controlling the pattern on the TFT-panel.

Contemporary endovascular management of splenic vascular pathologies.

The spleen is a commonly injured organ and the splenic vasculature is also susceptible to inflammation and trauma, often resulting in aneurysm formation. Splenic artery aneurysms carry a high risk of rupture and are associated with high mortality and morbidity. Due to the advances in endovascular techniques and devices, endovascular management of splenic vascular pathologies is now considered a first-line strategy. Endovascular embolisation and advance techniques including balloon- or stent-assisted coil embolisation enables minimally invasive management option while preserving splenic function.

Multi-wavelength quantitative differential phase contrast imaging by radially asymmetric illumination.

A new approach for achieving isotropic differential phase contrast imaging by applying multi-wavelength asymmetric illumination is demonstrated. Multi-wavelength isotropic differential phase contrast scheme (MW-iDPC) can be implemented using an add-on module in any commercial inverted microscope. Isotropy of intensity transfer function is achieved using three axis measurements. The expression for MW-iDPC imaging is presented, and detailed mathematical analysis is performed for transfer function. By applying color leakage correction, image sensor responses can be calibrated. Asymmetric illumination masks are designed, and simulation studies for intensity of the transfer function are performed. We utilize the MW-iDPC system to reconstruct quantitative phase images of standard microspheres and live breast cancer cells. The optical thickness of cells can be measured with high accuracy and image acquisition time is reduced significantly.

Indium Nitrite (InN)-Based Ultrasensitive and Selective Ammonia Sensor Using an External Silicone Oil Filter for Medical Application.

Ammonia is an essential biomarker for noninvasive diagnosis of liver malfunction. Therefore, selective detection of ammonia is essential for medical application. Here, we demonstrate a portable device to selectively detect sub-ppm ammonia gas. The presented gas sensor is composed of a Pt coating on top of an ultrathin Indium nitrite (InN) epilayer with a lower detection limit of 0.2 ppm, at operating temperature of 200 °C, and detection time of 1 min. The sensor connected with the external filter of nonpolar 500 CS silicone oil to diagnose liver malfunction. The absorption of 0.7 ppm acetone and 0.4 ppm ammonia gas in 10 cc silicone oil is 80% (0.56 ppm) and 21.11% (0.084 ppm), respectively, with a flow rate of 10 cc/min at 25 °C. The absorption of acetone gas is 6.66-fold higher as compared to ammonia gas. The percentage variation in response for 0.7 ppm ammonia and 0.7 ppm acetone with and without silicone oil on InN sensor is 17.5% and 4%, and 22.5%, and 14% respectively. Furthermore, the percentage variation in response for 0.7 ppm ammonia gas with silicone oil on InN sensor is 4.3-fold higher than that of 0.7 ppm acetone. The results show that the InN sensor is suitable for diagnosis of liver malfunction.

A Simple Imaging Device for Fluorescence-Relevant Applications.

This article unveiled the development of an inexpensive, lightweight, easy-to-use, and portable fluorescence imaging device for paper-based analytical applications. We used commercial fluorescent dyes, as proof of concept, to verify the feasibility of our fluorescence imaging device for bioanalysis. This approach may provide an alternative method for nucleotide detection and semen analysis, using a miniaturized fluorescence reader that is more compact and portable than conventional analytical equipment.

Multiplexed holographic non-axial-scanning slit confocal fluorescence microscopy.

A non-axial-scanning multi-plane microscopic system incorporating multiplexed volume holographic gratings and slit array detection to simultaneously acquire optically sectioned images from different depths is presented. The proposed microscopic system is configured such that multiplexed volume holographic gratings are utilized to selectively produce axial focal points in two or more planes inside the sample, and then to use confocal slit apertures to simultaneously image these multiple planes onto corresponding detection areas of a CCD. We describe the design, implementation, and experimental data demonstrating this microscopic system's ability to obtain optically sectioned multi-plane images of fluorescently labeled standard micro-spheres and tissue samples without scanning in axial directions.

Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer's disease therapy.

Here, we report a novel target of the drug memantine, ATP-sensitive K+ (KATP) channels, potentially relevant to memory improvement. We confirmed that memantine antagonizes memory impairment in Alzheimer's model APP23 mice. Memantine increased CaMKII activity in the APP23 mouse hippocampus, and memantine-induced enhancement of hippocampal long-term potentiation (LTP) and CaMKII activity was totally abolished by treatment with pinacidil, a specific opener of KATP channels. Memantine also inhibited Kir6.1 and Kir6.2 KATP channels and elevated intracellular Ca2+ concentrations in neuro2A cells overexpressing Kir6.1 or Kir6.2. Kir6.2 was preferentially expressed at postsynaptic regions of hippocampal neurons, whereas Kir6.1 was predominant in dendrites and cell bodies of pyramidal neurons. Finally, we confirmed that Kir6.2 mutant mice exhibit severe memory deficits and impaired hippocampal LTP, impairments that cannot be rescued by memantine administration. Altogether, our studies show that memantine modulates Kir6.2 activity, and that the Kir6.2 channel is a novel target for therapeutics to improve memory impairment in Alzheimer disease patients.