Measuring visual acuity and spherical refraction with smartphone screens emitting blue light

Introduction A periodical self-monitoring of spherical refraction using smartphones may potentially allow a quicker intervention by eye care professionals to reduce myopia progression. Unfortunately, at low levels of myopia, the far point (FP) can be located far away from the eye which can make interactions with the device difficult. To partially remedy this issue, a novel method is proposed and tested wherein the longitudinal chromatic aberration (LCA) of blue light is leveraged to optically bring the FP closer to the eye. Methods Firstly, LCA was obtained by measuring spherical refraction subjectively using blue pixels in stimuli shown on organic light-emitting diode (OLED) screens and also grey stimuli with matching luminance. Secondly, the visual acuity (VA) measured with a smartphone located at 1.0 m and 1.5 m and displaying blue optotypes was compared with that obtained clinically standard measurements. Finally, the spherical over refraction obtained in blue light with a smartphone was compared with clinical over-refraction with black and white (B&W) optotypes placed at 6 m. Results Mean LCA of blue OLED smartphone screens was −0.67 ± 0.11 D. No significant differences (p > 0.05) were found between the VA measured with blue optotypes on a smartphone screen and an eye chart. Mean difference between spherical over-refraction measured subjectively by experienced subjects with smartphones and the one obtained clinically was 0.08 ± 0.34 D. Conclusions Smartphones using blue light can be used as a tool to detect changes in visual acuity and spherical refraction and facilitate monitoring of myopia progression. (AU)

Shape- and Size-Dependent Refractive Index Sensing and SERS Performance of Gold Nanoplates.

Plasmonic sensors are promising for ultrasensitive chemical and biological analysis. Gold nanoplates (Au NPLs) show unique geometrical structures with high ratios of surface to bulk atoms, which display fascinating plasmonic properties but require optimization. This study presented a systematic investigation of the influence of different parameters (shape, aspect ratio, and resonance mode) on localized surface plasmon resonance properties, refractive index (RI, n) sensitivities, and surface-enhanced Raman scattering (SERS) enhancement ability of different types of Au NPLs through finite-difference time-domain (FDTD) simulations. As a proof of concept, triangular, circular, and hexagonal Au NPLs with varying aspect ratios were fabricated via a three-step seed-mediated growth method by the experiment. Both FDTD-simulated and measured experimental results confirm that the RI sensitivities increase with the aspect ratio. Furthermore, choosing a lower order resonance mode of Au NPLs benefits higher RI sensitivities. The SERS enhancement abilities of Au NPLs also predicted to be highly dependent on the shape and aspect ratio. The triangular Au NPLs showed the highest SERS enhancement ability, while it drastically decreased for circular Au NPLs after the rounding process. The SERS enhancement ability gradually became more intense as the hexagonal Au NPLs overgrown on circular Au NPLs with increasing volumes of HAuCl4 solution. The results are expected to help develop effective biosensors.

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.

Etched fiber Bragg grating probe using a regular CNC machine and a 3D printer.

Etched fiber Bragg gratings (EFBGs) have been widely employed for refractive index (RI) measurements that can be used to monitor sugar consumption during the fermentation of alcoholic beverages. EFBGs are obtained by removing the cladding of a fiber Bragg grating, which is traditionally performed by a chemical attack with hydrogen fluoride, an extremely hazardous corrosive substance that causes severe wounds and even death. To overcome such drawbacks, this technical note presents a simple, practical, and low cost method for the diameter reduction of single mode optical fibers by mechanical polishing, employing a small scale computer numerical control device and an ad hoc 3D-printed rod. The sensor probe obtained was tested using sucrose aqueous solutions with RIs between 1.333 and 1.394, measured in an Abbe refractometer. The results show a linear shift of the Bragg wavelength with respect to RI with a correlation of 0.928.

Integrated plasmonic biosensor on a vertical cavity surface emitting laser platform.

Plasmonic devices can modulate light beyond the diffraction limit and thus have unique advantages in realizing an ultracompact feature size. However, in most cases, external light coupling systems are needed, resulting in a prohibitively bulky footprint. In this paper, we propose an integrated plasmonic biosensor on a vertical cavity surface emitting laser (VCSEL) platform. The plasmonic resonant wavelength of the nanohole array was designed to match (detune) with the emission peak wavelength of the VCSEL before (after) binding the molecules, thus the refractive index that represents the concentration of the molecule could be measured by monitoring the light output intensity. It shows that high contrast with relative intensity difference of 98.8% can be achieved for molecular detection at conventional concentrations. The size of the device chip could be the same as a VCSEL chip with regular specification of hundreds of micrometers in length and width. These results suggest that the proposed integrated sensor device offers great potential in realistic applications.

Imaging-based spectrometer-less optofluidic biosensors based on dielectric metasurfaces for detecting extracellular vesicles.

Biosensors are indispensable tools for public, global, and personalized healthcare as they provide tests that can be used from early disease detection and treatment monitoring to preventing pandemics. We introduce single-wavelength imaging biosensors capable of reconstructing spectral shift information induced by biomarkers dynamically using an advanced data processing technique based on an optimal linear estimator. Our method achieves superior sensitivity without wavelength scanning or spectroscopy instruments. We engineered diatomic dielectric metasurfaces supporting bound states in the continuum that allows high-quality resonances with accessible near-fields by in-plane symmetry breaking. The large-area metasurface chips are configured as microarrays and integrated with microfluidics on an imaging platform for real-time detection of breast cancer extracellular vesicles encompassing exosomes. The optofluidic system has high sensing performance with nearly 70 1/RIU figure-of-merit enabling detection of on average 0.41 nanoparticle/µm2 and real-time measurements of extracellular vesicles binding from down to 204 femtomolar solutions. Our biosensors provide the robustness of spectrometric approaches while substituting complex instrumentation with a single-wavelength light source and a complementary-metal-oxide-semiconductor camera, paving the way toward miniaturized devices for point-of-care diagnostics.

Cholesteric liquid crystal mirror-based imaging Stokes polarimeter.

We have developed a cholesteric liquid crystal (CLC) mirror-based innovative model for detection and visualization of images in turbid media. Due to its unique optical-polarization properties, the CLC mirror is suggested as the basic element of the imaging Stokes polarimeter. The particular design of the proposed polarimeter, coupled with its distinguished operational simplicity, reliability, and real-time operational facilities, promises to fabricate a new generation of the imaging Stokes polarimeter, which can find applications in areas such as diagnostics, biology, astronomy, and remote sensing.

Evaluation of Brix refractometer as an on-farm tool for colostrum IgG evaluation in Italian beef and dairy cattle.

In this study it is hypothesized that there are differences between immunoglobulin G (IgG) content in colostrum from beef (Chianina, Podolica) and dairy (Holstein Friesian) cows and that variables such as breed, and parity can influence IgG content. The further objective was to determine if these factors may vary in terms of sensitivity, specificity and the cut point when data obtained with the digital Brix refractometer is compared with the gold standard radial immunodiffusion assay (RID). A total of 90 samples of first-milking colostrum were collected within 2 h after parturition. IgG concentration was determined indirectly by digital Brix refractometer and directly by RID. Results obtained by RID were compared among breed and parity. For the digital Brix refractometer, sensitivity and specificity to detect colostrum with an IgG concentration lower than 50 g/l were calculated and the optimal cut-point was selected for each breed. Samples containing less than <50 g/l IgG accounted for 15.9% of the total. Parity influenced colostral IgG concentration and beef cows had a higher mean concentration of IgG (101.1 g/l in Chianina and 90.6 g/l in Podolica) than dairy cows (71.1 g/l in Holstein Friesian) First parity Chianina cows had the highest IgG mean content (116.1 g/l). At the optimal cut-point for Brix refractometer (20%) sensitivity and specificity were 0.93 (0.84-0.97) and 0.81 (0.70-0.88), however, a breed-related cut-point could be used to reduce evaluation error. Linear regression modeling showed that refractometer data were related to RID (r = 0.78). Results obtained suggest that breed and parity can influence IgG content of colostrum and, despite the Brix refractometer being an excellent on-farm tool, a breed-based definition of optimal cut point is needed.

Biosensor based on two-dimensional gradient guided-mode resonance filter.

A novel biosensor based on a two-dimensional gradient (TDG) guided-mode resonance (GMR) filter was introduced in this study. The TDG-GMR is demarcated in terms of the gradient grating period (GGP) in one dimension and gradient waveguide thickness (GWT) in the other dimension. A single compact sensor can combine these two features to simultaneously provide a broad detection range through GGP and high resolution through GWT. A detection range of 0.109 RIU (0%-60% sucrose content) with a limit of detection of 5.62 × 10-4 was demonstrated in this study by using a TDG-GMR with a size of 140.8 × 125.4 µm2. This value cannot be achieved using one dimensional gradient GMR sensor. Label-free (LF) biomolecule detection through TDG-GMR was also experimentally demonstrated in a model assay of albumin. The result confirms that the GWT-GMR provides a better resolution, whereas the GGP-GMR provides a broader detection range. A device for multiplex measurement could be easily implemented with a compact sensor chip and a simple readout directly from a charge-coupled device. This system would require a narrow-band source such as a light emitting diode or a laser diode, in addition to a limited number of other components such as a polarizer and a collimator. The proposed TDG-GMR could easily be integrated with smartphones and portable devices.

Chemotherapy readiness in pediatric oncology: Assessing an automated method to measure urine specific gravity.

As part of the evaluation for chemotherapy readiness, urine specific gravity is measured to assess the patient's overall hydration status. Depending on the accuracy of the methods used, patients may be adversely affected by having their chemotherapy delayed or prematurely started. To evaluate the diagnostic accuracy of a new automated urine dipstick readout device (Clinitek), we tested 196 consecutive urine samples for urine specific gravity and compared them with the practical gold standard, a urine refractometer. We found a high correlation between both tools among clean urine samples, but a poor correlation among the pathological urine samples.

Multi-diffractive grating for surface plasmon biosensors with direct back-side excitation.

A multi-diffractive nanostructure is reported for the resonant excitation of surface plasmons that are cross-coupled through a thin metallic film. It consists of two superimposed periodic corrugations that allow diffraction excitation of surface plasmons on the inner side of a thin metal film and their subsequent phase matching with counterpropagating surface plasmons travelling to the opposite direction on its other side. This interaction leads to establishing of a set of cross-coupled Bragg-scattered surface plasmon modes that exhibit an electromagnetic field localized on both metal film interfaces. The reported structure is attractive for surface plasmon resonance biosensor applications, where direct optical probing can be done through the substrate without the need of optical matching to a high refractive index prism. In addition, it can be prepared by mass production - compatible means with UV-nanoimprint lithography and its biosensing performance characteristics are demonstrated by refractometric and biomolecular affinity binding studies.

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.

Performance limitations of resonant refractive index sensors with low-cost components.

Resonant biosensors are attractive for diagnostics because they can detect clinically relevant biomarkers with high sensitivity and in a label-free fashion. Most of the current solutions determine their detection limits in a highly stabilised laboratory environment, which does, however, not apply to real point-of-care applications. Here, we consider the more realistic scenario of low-cost components and an unstabilised environment and consider the related design implications. We find that sensors with lower quality-factor resonances are more fault tolerant, that a filtered LED lightsource is advantageous compared to a diode laser, and that a CMOS camera is preferable to a CCD camera for detection. We exemplify these findings with a guided mode resonance sensor and experimentally determine a limit of detection of 5.8 ± 1.7×10-5 refractive index units (RIU), which is backed up by a model identifying the various noise sources. Our findings will inform the design of high performance, low cost biosensors capable of operating in a real-world environment.

Single nanosecond-pulse production of polymeric fiber Bragg gratings for biomedical applications.

In this study, we present first-time fabrication of FBGs in all ZEONEX-based SMPOFs with a single 25 ns pulse of 248 nm UV irradiation over a 12-month period, which opens up new frontiers in optics and photonics for the effective fabrication of polymer optical fiber Bragg gratings (POFBGs), permitting mass producibility of them. POFBGs were characterized by subjecting them to various physical parameters including temperature and tensile strain. Strain responses of FBGs with similar grating strengths fabricated with 248 nm and 325 nm He-Cd laser irradiations were explored over a year to demonstrate their long-term stability and applicability. Owing to the unique features of the proposed sensing device fabricated by embedding POFBGs in silicone rubber, a good performance in the detection of human heart rate with an amplitude of 4 pm, which is 4 times higher compared to that of silica single mode fiber (SMF) was demonstrated. The response of the sensing device during a human respiration process was also explored where exhalation and inhalation were monitored and distinguished while the breath was held. These revelations signify the importance of ZEONEX-based POFBGs, which allow consistent and effective grating fabrication and are highly promising in the foreseeable future for biomedical applications.

Open-channel-based dual-core D-shaped photonic crystal fiber plasmonic biosensor.

A simple dual-core D-shaped plasmonic refractive index (RI) sensor with an open-arch channel is introduced in this paper. A thin plasmonic gold layer is inserted on the slotted portion, which makes the sensor cost effective. By introducing a ring in the flat surface of the D-shaped structure, the coupling effect is increased, which enhances sensor performance. The commonly used finite element method is applied to characterize sensor performance. Numerical investigation under the wavelength interrogation method shows maximum spectral sensitivities of 16,000 nm/RIU and 17,000 nm/RIU along with corresponding resolutions of 6.25×10-6RIU and 5.88×10-6RIU for x and y polarizations, respectively. In tandem with this, maximum amplitude sensitivities governed by the amplitude interrogation method are calculated at about 2,603.7000RIU-1 and 3,432.1929RIU-1 for x and y polarizations, respectively. The proposed sensor exhibits high figures of merit of 320RIU-1 and 283.33RIU-1 for x and y polarizations, respectively, in the RI detection range of 1.33 to 1.44. Moreover, the impact on sensitivity with the overall sensor behavior is analyzed by altering geometrical parameters such as pitch, air hole diameter, and gold layer thickness. So, with an eye toward sensor performance and economic viability, this sensor is assignable to bio-sensing applications.

Validation of Brix refractometers and a hydrometer for measuring the quality of caprine colostrum.

On-farm assessment of caprine colostrum quality is important for goat farmers; the ability to quickly recognize whether colostrum is suitable to feed to kids helps achieve successful passive transfer of immunity. The study compared the use of optical and digital Brix refractometers and a hydrometer against the international gold standard radial immunodiffusion (RID), using both fresh and frozen samples. A locally available ELISA methodology was included for comparison. A total of 300 samples were collected from 2 farms (farm 1: n = 157, collected by research staff within 24 h of parturition; farm 2: n = 143, collected by the farmer within 12 h of parturition). Farm 1 provided doe age for a subset of samples (n = 86). Samples were tested fresh and then frozen for shipment and repeated testing. Specific gravity was measured using a hydrometer in a subset of samples (n = 22) from farm 2. Because no gold standard thresholds are currently available for caprine colostrum, RID-derived values of 30, 40, and 50 g/L IgG were used as potential "good quality" thresholds. Pearson (ρ) and Lin's concordance correlation coefficients (CCC) were calculated for comparison of methods. Optimum thresholds were established maximizing the Youden index and minimizing the "distance closest to the top left corner" of the receiver operator characteristic curves. Brix values were correlated with RID (optical Brix, fresh: ρ = 0.73; digital Brix, fresh: ρ = 0.71; digital Brix, frozen: ρ = 0.76) and with each other (range: ρ = 0.93 to 0.99; CCC = 0.91 to 0.99). Specific gravity measured by the hydrometer yielded a strong relationship with RID (ρ = 0.83) and with Brix values (range: ρ = 0.88 to 0.90). The ELISA method was not correlated with Brix methods (range: ρ = 0.02 to 0.09) or RID (ρ = 0.20). Depending on the colostrum IgG threshold, the hydrometer yielded high Youden indices (range: 0.78 to 0.93) and low distance closest to the top left corner criteria (0 to 0.05) at a threshold of 1.047 specific gravity. For all RID IgG thresholds, the best Brix threshold (regardless of type or whether the sample was fresh or frozen) was 18 or 19%, with the highest Youden indices (range: 0.47 to 0.61) and lowest distance to the top left corner criteria (range: 0.09 to 0.16); however, we recommend 19%, because this reduces the potential of feeding poor-quality colostrum. The ELISA method was the poorest predictor of colostrum concentration. Age was not found to affect colostrum quality; however, the sample size of this subset was small. Hydrometers are inexpensive and easy to use, whereas Brix methods use only a small amount of colostrum; we suggest that either method could be used on-farm.

Extended fed-batch fermentation of a C5/C6 optimised yeast strain on wheat straw hydrolysate using an online refractive index sensor to measure the relative fermentation rate.

In the production of 2nd generation ethanol, using Saccharomyces cerevisiae, the highest productivity obtained using C5/C6 fermenting yeast is in the co-fermentation phase, in which xylose and glucose are fermented simultaneously. Extending this phase in a fed-batch process increases the yield, rate and additionally reduces needed yeast amount for pitching. Extending this phase, as long as possible, would further enhance yield and economy of the process. To realise the concept a fermentation monitoring technique was developed and applied. Based on online measured refractive index an optimal residual sugar concentration could be maintained in the primary fermentor during the feed phase, requiring little knowledge of the nature of the substrate. The system was able to run stably for at least five fermentor volumes giving an ethanol yield >90% throughout the run. This was achieved with addition of only urea to the wheat straw hydrolysate and with an initial yeast pitch of 0.2 g/L total of finished broth. It has the potential to improve the fermentation technology used in fuel ethanol plants, which could help to meet the growing demand for more sustainable fuels.

Critical assessment of relevant methods in the field of biosensors with direct optical detection based on fibers and waveguides using plasmonic, resonance, and interference effects.

Direct optical detection has proven to be a highly interesting tool in biomolecular interaction analysis to be used in drug discovery, ligand/receptor interactions, environmental analysis, clinical diagnostics, screening of large data volumes in immunology, cancer therapy, or personalized medicine. In this review, the fundamental optical principles and applications are reviewed. Devices are based on concepts such as refractometry, evanescent field, waveguides modes, reflectometry, resonance and/or interference. They are realized in ring resonators; prism couplers; surface plasmon resonance; resonant mirror; Bragg grating; grating couplers; photonic crystals, Mach-Zehnder, Young, Hartman interferometers; backscattering; ellipsometry; or reflectance interferometry. The physical theories of various optical principles have already been reviewed in detail elsewhere and are therefore only cited. This review provides an overall survey on the application of these methods in direct optical biosensing. The "historical" development of the main principles is given to understand the various, and sometimes only slightly modified variations published as "new" methods or the use of a new acronym and commercialization by different companies. Improvement of optics is only one way to increase the quality of biosensors. Additional essential aspects are the surface modification of transducers, immobilization strategies, selection of recognition elements, the influence of non-specific interaction, selectivity, and sensitivity. Furthermore, papers use for reporting minimal amounts of detectable analyte terms such as value of mass, moles, grams, or mol/L which are difficult to compare. Both these essential aspects (i.e., biochemistry and the presentation of LOD values) can be discussed only in brief (but references are provided) in order to prevent the paper from becoming too long. The review will concentrate on a comparison of the optical methods, their application, and the resulting bioanalytical quality.

Combining whispering gallery mode optofluidic microbubble resonator sensor with GR-5 DNAzyme for ultra-sensitive lead ion detection.

Lead ions are deleterious pollutants that often reach drinking water, and can cause significant harm to humans (particularly children). An ultra-sensitive lead ion detection method using a whispering gallery mode (WGM) optofluidic microbubble resonator and the classic GR-5 DNAzyme is proposed in this paper. With the auxiliary piranha and Ploy-l-lysine solution, GR-5 DNAzyme was successfully modified on the inner wall of a microbubble. The mode field distribution of the microbubble was analysed, and the optofluidic sensor with thin wall exhibited a maximum bulk refractive index sensitivity of 265.2 nm/RIU. Lead ions at concentrations ranging from 0.1 pM to 100 pM were tested using the proposed WGM optofluidic sensor. The noise was decreased to 2.43 fM using the self-referenced differential method. Thus, a limit of approximately 15 fM was obtained for the detection of lead ions using the WGM optofluidic biosensor. Eight competing metal ions were also used to evaluate the selectivity of the proposed sensor, with results indicating that it has high selectivity for lead ions. Finally, the sensor performance is verified using real samples.