Spatial Light Modulation Gauges How Lenses Slow Progress of Myopia

Myopia, or nearsightedness, is one of the most common ocular disorders worldwide and a leading cause of visual impairment in children. Although specialized eyeglass lenses have been clinically tested to treat myopia progression, an in-depth optical characterization of the lenses has not yet been performed.

Researchers from the ZEISS Vision Science Lab at the University of Tübingen and the University of Murcia undertook a comprehensive characterization to investigate the properties of spectacle lenses designed to slow the progress of myopia. The results of their study could help increase the efficacy of future lens designs.

Myopia is typically caused when a person’s eyes become elongated, which affects how the eyes focus on faraway objects. The condition can progress in children and teens as their bodies grow.

To reproduce pupil shape and myopic ocular aberrations, researchers developed an instrument that reproduced the aberrations in myopic eyes and enabled physical simulation of the pupil. They based their instrument on spatial light modulation (SLM) technology.

“After exploring the state of the art, we didn’t find a method that could be used to characterize the optical properties of these eyeglass lenses under real viewing conditions,” said researcher Augusto Arias-Gallego. As a result, Arias-Gallego said, the researchers endeavored to build an instrument that can measure the lens’ optical response to different angles of illumination, while also reproducing the myopic eye’s pupil and refractive errors.

The team’s instrument uses an illumination source mounted on an arm that rotates around the lens. After the light passes through the lens, it is guided to an SLM by a rotating mirror. The SLM is composed of tiny liquid crystal cells that modify the propagating light, boosting its spatial resolution.

The SLM reproduces the refractive errors and pupil shape of myopic eyes, allowing the researchers to re-create myopic aberrations and to produce different aberrations depending on the angle of illumination. Using the SLM, the researchers programmed the aberrations as phase maps and induced programmed amounts of defocus to perform through-focus testing.

Tests helped the researchers determine the image quality within the proximity of a simulated retinal position, shedding light on how the special lens interacts with eye elongation signaled at the retina. “By combining the through-focus results with light-scattering measurements, we were able to accurately characterize several types of eyeglass lenses,” Arias-Gallego said. The researchers then compared measurements for each lens with their reported clinical efficacy for slowing myopia progression, he said.

The researchers quantified and compared the focusing and scattering properties of a single vision lens with two types of spectacle lenses for myopia progression management: defocus incorporated multiple segments (DIMS) and diffusion-optical technology (DOT). They calculated four optical metrics potentially related to myopia progress and quantified the scattered light from the peripheral lens zones. Scattering was quantified by implementing the optical integration method.

The characterization showed an increased contrast and sharpness of images through the DIMS lens at the peripheral retina when inducing myopic defocus, with respect to the single vision and DOT lenses. It further showed that contrast reduction by the DOT lens was dependent on the luminance at the pupil.

According to Arias-Gallego, the results both raised new questions and pointed to potential strategies that could increase the efficacy of future designs.

“Insights into the link between the optical properties of myopia progression management lenses and effectiveness in real-world scenarios will pave the way to more effective treatments,” Arias-Gallego said. “This could help millions of children and is fundamental in understanding the mechanisms by which these lenses work.”

The researchers are working to adapt the SLM instrument to include sources with varying wavelengths.

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TiHive Raises $9.3M to Advance Terahertz-AI Vision Technology

TiHive, a company focused on terahertz-AI vision systems, has raised €8 million ($9.3 million) to accelerate growth and expand internationally. The company’s technology combines industrial-grade, silicon-based terahertz imaging devices and AI to enable real-time, non-destructive, see-through quality and process control on production lines.

The company said the funding will support the commercialization of its industrial vision solutions, reinforce international deployment — particularly in hygiene, textiles, recycling, agriculture, and space industries — and accelerate R&D. The company aims to develop a new generation of terahertz chips with extended frequencies and advanced AI features.

TiHive’s systems are integrated directly on production lines and connected to the machines and to the cloud, measuring the quality and the process stability of thousands of products every minute. The technology platform uses CMOS technology, paired with advanced THz optics and an AI-powered software platform. By integrating terahertz technology on CMOS chips, TiHive’s approach enables miniaturization, scalable mass production, low energy consumption, and high-speed performance.

Founded in 2017 and currently employing 14 people, TiHive is backed by support from the EIC Accelerator and Bpifrance. Karista, a deep-tech hardware specialist, and Wind, a deep-tech venture capital fund, participated in the funding.

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Cell Manipulation Technique Enters into Commercial Market

In cell biology and medical imaging, the targeted manipulation of cells under controlled conditions is a major challenge in understanding processes and causal relationships. Researchers are dependent on tools that enable them to manipulate individual components of a cell in order to explore their effects on intracellular mechanisms and interactions. However, a common problem with conventional methods of cell manipulation is that the sample is disturbed by the manipulation and the results are therefore compromised.

A laser technology developed by researchers at the Max Planck Institute of Molecular Cell Biology and Genetics makes it possible to influence and specifically control movements within living cells and embryos. The technology, called Focused Light-Induced Cytoplasmic Streaming (FLUCS), can be used to help better understand embryonic developmental disorders.

Further, the FLUCS method allows noninvasive manipulation of cells — for example, in developmental biology. As an additional module for high-resolution microscopes, FLUCS will improve cell biological and medical research, as well as open possibilities in microfluidics.

The technology has been licensed by Rapp OptoElectronic, a photomanipulation and illumination systems developer.

FLUCS is a method of photomanipulation that makes it possible to specifically influence and control movements within cells and embryos with the help of laser beams. The beam selectively induces a thermal field in the cytoplasm, which locally changes the density and viscosity of the liquid medium and causes a flow due to the rapidly moving laser point. In contrast to conventional methods such as optical tweezers, the biomolecules floating in the cytoplasm are set in motion directly without the need for modification of the sample. They can still interact freely with their environment.

Using the method, researchers from Max Planck Institute generated controlled currents in living worm embryos and transported biomolecules to different parts of the growing embryo. Through targeted redistribution, they reported successful examination of the importance of the movement of the cytoplasm for the polarization of oocytes — and thus the question of which molecule has to go where exactly during development.

Based on successful joint development as well as the license agreement of the FLUCS technology from the Max Planck Institute to Rapp OptoElectronic, Rapp now offers FLUCS as a market-ready product to researchers and industrial users worldwide. A pilot system is located in the Light Microscope Facility of the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden. Here, FLUCS is available to interested scientists from inside and outside the Max Planck Society for their research. The device is integrated as an add-on module to high-resolution microscopes via standard interfaces.

“FLUCS fills a gap in the previously available micro-manipulation techniques to study the causes and consequences of intracellular movement,” said Sven Warnck, managing director of Rapp OptoElectronic. “Directed liquid flows are induced by moderately warming up the sample with a laser spot. Their path can be easily specified individually using the user-friendly software, for example as a line, circle, or free form. In this way, cell components such as organelles, PAR proteins, and even chromatin can be moved freely in the cell nucleus without having to hold or fix them.”

The technology has a broad range of potential applications. In cell biology, artificially generated cytoplasmic currents can be used, for example, to invert PAR proteins and thus influence embryonic development. In medical research, molecular mechanisms and signaling pathways in cells can be better researched and the development of drugs can be supported. In microfluidics, the behavior of liquid quantities in the micro- or picoliter range can be examined in more detail with the help of FLUCS, thus supporting new methods of laboratory measurement technology, quality control, or food safety.

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Scalable 3D Micro-Printed Sensors Promise Optofluidic Disease Detection

Early-stage disease diagnosis relies on the highly sensitive detection of biomarkers, such as optical whispering-gallery-mode (WGM) microcavity sensors; such devices provide precise, label-free biosensing. However, scaling and integrating large-scale arrayed WGM microcavity sensors is challenging. Bottlenecks in sensor design can lead to these bottlenecks.

In response, researchers at Hong Kong Polytechnic University developed a 3D micro-printed WGM micro-laser sensor for sensitive on-chip biosensing. The developed sensor, a limacon-shaped WGM micro-laser sensor, was created using flexible micro-printing technology with the optical advantages of WGM micro-lasers.

In the device, optical WGM micro-laser sensors circulate light resonantly within tiny microcavities. Experimental results highlighted the potential of the device for ultralow-limit detection of biomarkers in early disease diagnosis. When target molecules bind to the cavity’s surface, they induce slight changes in the laser’s wavelength, enabling highly sensitive detection of biological substances.

“In the future, these WGM micro-laser sensors could be integrated into a microfluidic chip to enable a new generation of lab-on-a-chip devices for ultrasensitive, quantitative detection of multiple biomarkers," said research lead A. Ping Zhang. "This technology could be used for the early diagnosis of diseases such as cancers and Alzheimer's disease, or for fighting major health crises such as the COVID-19 pandemic.”

The challenge in scaling these sensors is the need to couple light entering and leaving them, which typically requires a tapered optical fiber with a diameter <2 μm, a comparatively small size that makes them difficult to align. Using the light emitted directly from the micro-laser sensor offers a promising alternative to using tapered optical fibers for light coupling. However, the circular microcavities of conventional WGM micro-lasers make efficient far-field light collection difficult, thereby limiting the readability of the sensor’s weak signal.

The sensor, using resonance and a narrow linewidth of lasing peaks, can detect immunoglobulin G, an extremely small but common antibody found in blood and other body fluids. Experimental results showed that the sensor can detect this antibody at a detection limit of ~70 ag/mL.

Integrating the micro-laser sensors into a microfluidic chip could lead to the eventually development of optofluidic biochips for rapid, quantitative, and simultaneous detection of multiple disease biomarkers.

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Multi-Camera Microscope Produces Sharp Images of Large, Curved Samples

 

Microscopy samples are seldom completely flat across a centimeter-scale field of view. Mechanical scanning can keep all the parts of a large sample in focus, but scanning reduces throughput, slowing the imaging process.

To help large-area microscopy systems resolve trade-offs between field of view, resolution, and imaging speed, a team at Duke University developed a single-shot, re-imaging microscope that achieves seamless, gigapixel imaging over a 16.3 x 18.8 square millimeter (mm2) field of view, at 0.84-µm half-pitch resolution, without mechanical scanning.

The microscope, which the researchers call PANORAMA, could enhance imaging applications for biological research and medical diagnostics, as well for industrial inspection and quality control.

“This tool can be used wherever large-area, detailed imaging is needed,” researcher Haitao Chen said. “For instance, in medical pathology, it could scan entire tissue slides, such as those from a biopsy, at cellular resolution almost instantly. In materials science or industrial inspection, it could quickly inspect large surfaces, such as a chip wafer, at high detail.”

PANORAMA uses a telecentric photolithography lens, a large-aperture tube lens, and a flat micro-camera array with adaptive, per-camera focus control to provide sub-µm focus across flat, curved, and uneven samples that span cm.

The telecentric lens, originally developed for chip-making, is combined with a large tube lens that projects an image of the sample onto a flat array of 48 small cameras. Each camera images a portion of the scene or sample. The multi-camera configuration works like a single microscope, capturing high-resolution, gigapixel images of large and non-flat objects in a single snapshot. Each camera can be independently focused to match the sample surface, ensuring that the entire field of view stays sharp even if the sample is curved.

Additionally, the multi-camera, curvature-adaptive microscope also eliminates the need for scanning, which can take up to an hour. In a process that takes about 5-10 min, PANORAMA uses software to automatically stitch the images from each camera together into one continuous picture.

“The telecentric lens makes it possible to image a very wide field without distortion, while the multi-camera approach overcomes the usual size-and-resolution limit of a single sensor,” Chen said. “This combination lets us acquire a seamless, gigapixel image in a single snapshot, flattening out any curvature adaptively.” The detailed, gigapixel-scale images have 10-50x more pixels than the average smartphone camera image.

Imaging a prepared slide of rat brain tissue under brightfield illumination, which uses white light to reveal tissue structure, enabled the researchers to demonstrate the efficacy of the instrument and technique. The 48-camera array captured the entire 630-megapixel (MP) image in one snapshot, with no scanning required. The resulting image showed cellular structures as small as 0.84?µm, as well as neurons and dendrites across the sample.

The researchers also used PANORAMA to simultaneously acquire brightfield and fluorescence images of onion skin placed over a curved surface. By focusing each camera on the local curvature, they were able to obtain sharp images of the entire onion skin over the curved surface. The brightfield images revealed crisp cell walls, while the fluorescence images clearly showed stained nuclei.

“In practical terms, we saw a huge jump in throughput and flexibility — no more moving parts, no tedious focus-stacking, and no blind spots between cameras,” professor Roarke Horstmeyer, who led the research, said. “Compared to older multi-camera microscopes that needed scanning to fill gaps and maintain focus, our approach gives continuous full coverage at sub-micron resolution.”

The researchers are investigating how to improve the microscope by adding more cameras or larger sensors to capture an even bigger field, such as an entire petri dish, in a single shot. They are also developing an automated focus system, which will eliminate the need to adjust each camera manually for every sample. Future computational advances could make it possible for PANORAMA to perform 3D image reconstruction, provide depth maps in real time, and provide live videos of microscopic processes.

“Although traditional microscopes assume the sample is perfectly flat, real-life samples such as tissue sections, plant samples, or flexible materials may be curved, tilted, or uneven,” Horstmeyer said. “With our approach, it’s possible to adjust the focus across the sample, so that everything remains in focus even if the sample surface isn’t flat, while avoiding slow scanning or expensive special lenses.”

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LED Hyperspectral Imaging Device Promises Faster Gastrointestinal Cancer Diagnoses

Gastrointestinal (GI) cancer screening by endoscopy has improved localized cancer prognosis and diagnosis rate. Still, conventional GI endoscopy misses about 8-11% of tumors, due to lack of visibility during upper GI endoscopic exams.

One possible way to increase the sensitivity of endoscopic examinations is by using hyperspectral imaging techniques. Hyperspectral imaging captures images across discrete, narrowband wavelength channels, including wavelengths beyond the visible. By analyzing how cells reflect and absorb light across the electromagnetic spectrum, the technique enable users to acquire a unique spectral fingerprint of each cell in a tissue sample.

To improve endoscopic imaging and detect cancers at an earlier stage, a team led by professor Baowei Fei at the University of Texas at Dallas (UTD) developed an LED-based, real-time hyperspectral imaging device for endoscopes. The researchers designed a prototype based on a monochrome, micro-digital camera and a multiwavelength LED array comprising 18 LEDs in 18 different wavelengths ranging from 405-910 nm. The team aimed to achieve an image capturing rate of over 10 hypercubes per second (hps) without compromising spatial resolution.

The researchers used micro-LEDs with footprints smaller than 400 μm × 400 μm to miniaturize the device. This enabled the team to build an imaging device that could accommodate tens of LEDs at the tip of a clinical endoscopic catheter, and create a hyperspectral imaging system with an in situ light source.

By using an in situ hyperspectral light source, the researchers avoided the need for fiber optics, increasing the mobility of the endoscope catheter and lessening the complexity of the mechanical design.

The LED-based approach to wavelength scanning makes the device low-power, and allows illumination intensities to be adjusted dynamically based on the distance between the device and the target.

To evaluate the feasibility of using an LED-based illumination source for endoscopic imaging, the researchers studied their system’s performance on different normal and cancerous ex vivo tissues. They found that the hyperspectral signatures of different imaging targets acquired using the prototype hyperspectral imaging device were found to be comparable to the data obtained with the reference system.

The use of LEDs for hyperspectral imaging could enable numerous applications in endoscopic, laparoscopic, and handheld HSI devices for detecting disease, according to the researchers.

Ultimately, Fei aims to develop hyperspectral technology that can be used to track many different types of cancers, and that is small enough to be placed in handheld, affordable personal devices, such as a smartphone or pen that could be used to scan the skin or mouth, for example.

“Basically, you could complete the scan, and the information would be wirelessly transferred to the cloud," Fei said. "Then, AI may determine the lesion is suspicious and refer the person to a medical center for follow-up.

"Our goal is to produce imaging systems that are really affordable as well as cost-effective, meaning they could find cancers at earlier stages and reduce the need for unnecessary tissue removal and testing.”

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Caltech Research Enables Coherent Spectral Broadening On-Chip

Broadband, coherent light sources are highly valued in R&D. But until now, they have been difficult to achieve without bulky, inefficient tabletop devices.

A Caltech team led by professor Alireza Marandi developed an efficient solution to integrating a broad spectrum of frequencies on a microchip. Using an optical parametric oscillator (OPO), the team demonstrated multi-octave frequency comb generation on a nanophotonic device with a threshold of only femtojoules (fJ) of pump energy.

The nanophotonic device has the potential to provide ultrabroadband (visible to MIR), on-chip light sources for applications in areas ranging from communications and imaging to spectroscopy.

To generate a frequency comb on a chip, the researchers engineered an OPO in lithium niobate (LiNbO3) and used dispersion engineering to shape the way that different wavelengths traveled through the device. An OPO is essentially a resonator that traps incoming laser light at one input frequency and uses a nonlinear crystal to generate light at different output frequencies. Typically, OPOs serve as laser-like light sources with tunable output frequencies. But. by using dispersion engineering in the work, the researchers ensured that the wavelengths remained together instead of spreading out.

The device demonstrated highly efficient, highly stable coherent spectral broadening with the OPO — a result that the team initially did not expect. “We turned it on and cranked up the power, and when we looked at the spectrum, we saw that it was extremely broad,” Marandi said. “We were particularly surprised that the super-broad spectrum was actually coherent. This was against the textbook descriptions of how OPOs work.”

In subsequent simulations, the researchers found that raising the incoming light energy above the threshold caused the spectrum to become incoherent — and therefore unable to generate a frequency comb. However, in the lab, the spectrum continued to remain coherent even when the device operated far above the threshold.

By leveraging an ultralow threshold and dispersion engineering, the researchers had accessed a previously unexplored OPO regime that enables coherent spectral broadening.

“It took us maybe six months to discover that there is this new regime of OPO operation in which the OPO is far above its threshold and the coherence is reestablished,” Marandi said. “Because the threshold of this OPO is orders of magnitude lower than previous OPOs, and the dispersion and the resonator are engineered unlike the previous realization of OPOs, we could observe this phenomenal spectral broadening, which is orders of magnitude more energy-efficient than other spectral broadening schemes.”

Creating a multi-octave frequency comb from an OPO could enable ultrabroadband, on-chip, nonlinear photonic capabilities for numerous applications.

One of the primary techniques used to make stable frequency combs requires significant broadening of the comb’s spectrum. The energy demands of this spectral broadening have, so far, created a bottleneck that has impeded the integration of frequency comb technologies on-chip. The team’s approach to building frequency combs could reshape how frequency comb-based technologies, currently found in table-top setups, could transition to integrated photonic devices.

Moreover, most of the advanced lasers and detectors used for measuring molecules operate in the NIR or visible range. OPOs that are launched from NIR lasers as the input frequency, and are then able to efficiently convert the light, outputting coherent light in the MIR range, could allow researchers, for example those working with spectroscopy, to access relevant information at lower frequencies.

“There have been two main challenges with frequency combs,” Marandi said. “One is that the sources are too big, and the second is that it’s challenging to make them in different desired spectral windows. Our work offers a path toward solving both of these problems.”

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