Thursday, October 9, 2025

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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Tuesday, October 7, 2025

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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Monday, October 6, 2025

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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Friday, October 3, 2025

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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Tuesday, September 30, 2025

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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Monday, September 29, 2025

Expansion Microscopy Technique Enables 20-nm Resolution






A new expansion microscopy (ExM) technique from MIT makes it possible to use a conventional light microscope to generate high-resolution images at the nanoscale, by expanding specimens 20-fold before imaging them.

Historically, nanoscale structures in cells and tissues have been imaged with high-powered, expensive, superresolution microscopes. The new ExM protocol, which achieves 20-fold expansion in just one step, provides a simple, inexpensive method that can be used by most biology labs to perform imaging at a resolution of about 20 nm.

“What this new technique allows you to do is see things that you couldn’t normally see with standard microscopes,” professor Laura Kiessling said. “It drives down the cost of imaging because you can see nanoscale things without the need for a specialized facility.”

The original version of the ExM technique, developed by professor Edward Boyden and his team in 2015, expanded tissue about 4-fold and provided images with a resolution of around 70 nm. In 2017, Boyden’s lab modified the process to include a second expansion step, achieving an overall 20-fold expansion.

“We’ve developed several 20-fold expansion technologies in the past, but they require multiple expansion steps,” Boyden said. “If you could do that amount of expansion in a single step, that could simplify things quite a bit.”

The new method reaches the same level of performance possible with iterative expansion methods, but with the simplicity of a single-shot protocol.

To implement ExM, the researchers embed the tissue specimen in an absorbent polymer and added water, creating a hydrogel that expands the polymer and pulls the biomolecules in the specimen apart. For one-step, 20-fold expansion, the researchers use gel that is extremely absorbent and mechanically stable to ensure that the gel does not fall apart when the specimen is expanded by 20x.

To further stabilize the gel and enhance its reproducibility, the researchers remove oxygen from the polymer solution prior to gelation, preventing side reactions that could interfere with crosslinking. Unlike previous expansion gels that require another molecule to be added to form crosslinks between the polymer strands, the gel used for the single-shot, 20-fold ExM technique forms crosslinks spontaneously.

Once the gel is formed, select bonds in the proteins that hold the tissue together are broken and water is added to make the gel expand. After the gel expands, target proteins in the tissue can be labeled and imaged. The new technique supports post-expansion staining for brain tissue to facilitate biomolecular labeling.

“This approach may require more sample preparation compared to other superresolution techniques, but it’s much simpler when it comes to the actual imaging process, especially for 3D imaging,” researcher Tay Won Shin said.

In one round of expansion, the new ExM technique, which the team calls 20ExM, enabled the researchers to image hollow microtubule structures in cultured cells and synaptic nanocolumns in the mouse somatosensory cortex on a conventional confocal microscope. The team could also visualize mitochondria and the organization of individual nuclear pore complexes in the cells.

The new ExM technique could be used for a variety of experiments where high resolution and single-step simplicity are desired. The researchers are currently using the technique to image glycans — carbohydrates, found on the surface of a cell that help control how the cell interacts with its environment.

20ExM could also be used to image tumor cells, providing insight into how proteins are organized within these cells. In principle, the new ExM technique could be used to simplify or enhance the resolution of other expansion-based technologies, such as in situ RNA detection and sequencing and genome imaging.

The single-shot, 20-fold expansion microscopy method provides a robust, simple, affordable solution to nanoscale-resolution imaging of preserved cells and tissues using conventional microscopes. The researchers believe that any biology lab could use the technique at a low cost, because it relies on standard, off-the-shelf chemicals and equipment that most labs already have or can easily access.

“Our hope is that with this new technology, any conventional biology lab can use this protocol with their existing microscopes, allowing them to approach resolution that can only be achieved with very specialized and costly state-of-the-art microscopes,” researcher Shiwei Wang said.

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Friday, September 26, 2025

Optogenetic Light Source Transmits Information Between Neurons




Researchers at The Institute of Photonic Sciences (ICFO) demonstrated that photons, acting as neurotransmitters, can enable communication between neurons. The researchers developed an all-optogenetic, synaptic transmission system that enabled synthetic signaling between unconnected neurons and the generation of synaptic circuits.

The team’s findings could lead to therapies that use light instead of chemicals or drugs to restore communication between nerve cells in the treatment of diseases such as Alzheimer’s and Parkinson’s. In addition to treating neurological disorders, the team’s approach could potentially be used to rewire damaged neural circuits and improve learning.

The Photons as Synaptic Transmitters (PhAST) system connects two neurons by using light-emitting enzymes and light-sensitive ion channels. The researchers tested the PhAST system on the roundworm model C. elegans and showed that photon-based synaptic transmission can facilitate the modification of animal behavior.

After genetically modifying the roundworms to have faulty neurotransmitters, which made the worms insensitive to mechanical stimuli, the researchers engineered a luciferase enzyme to generate light inside the worms and a specially designed microscope for viewing the light being emitted by the worms. They also selected ion channels for the postsynaptic cells. The channels are highly sensitive, so that very little light is needed to open them.

The genetically engineered enzyme introduced into the worms as a light source requires calcium and the binding of a co-factor to emit light. The calcium increase occurs when the presynaptic cell activates, so the light is only on when the presynaptic neuron is on as well. When the light source and the presynaptic cell are activated, blue light is emitted from the presynaptic cell. The ion channel in the postsynaptic cell senses the blue light and activates the postsynaptic cell, which then transmits the information to the downstream pathway.

To follow the information flow, the researchers developed a device that delivered mechanical stresses to the animals’ noses, while at the same time measuring the calcium activity in the sensory neurons. To acquire the dim light signals coming from the neurons, they built a microscope with a sensor that is strong enough to detect a faint signal from just a few photons. The researchers then took a default model of an existing microscope and removed the optical elements that were not needed for bioluminescence and that could interfere with imaging. The researchers also used artificial intelligence to enhance the bioluminescence imaging capabilities of the microscope.

In experiments, the researchers established a new transmission between two unconnected cells, restoring neuronal communication in a defective circuit. They also suppressed the worms’ response to a painful stimulus, and they switched the worms’ response to an olfactory stimulus from attractive to aversive behavior. The researchers also used PhAST to study the calcium dynamics of the temporal pattern generator in a motor circuit for ovipositioning. The experimental results showed that the PhAST system can facilitate the modification of animal behavior.

Further, the PhAST system could help researchers better understand the underlying mechanisms of brain function and complex behaviors, and how different brain regions communicate with each other. It could lead to new ways to image and map brain activity with higher spatiotemporal resolution.

Limitations to the widespread use of the technology remain. Further improvements in the engineering of the bioluminescent enzymes and the ion channels and in the targeting of molecules would allow greater optical control of the neuronal function, with higher specificity and precision. However, the ICFO study demonstrated that chemical neurotransmitters can be replaced with light to overcome malfunctioning in neural circuits and help neurons communicate again. Now that the technology has been shown to work in vivo in worms, a potential next step could be use of the PhAST system for the study of more complex neural circuits.


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24th Edition of World Biophotonics Research Awards 2026 | International Scientific Awards in Kuala Lumpur, Malaysia

  24th World Biophotonics Research Awards 2026: A Global Platform for Scientific Excellence and Innovation Science has always been the drivi...