Quanta Image Sensors Boost Bioluminescence Signals for Live Cell Microscopy

NEUHERBERG, Germany,— A microscope built with quanta image sensor (QIS) technology will allow researchers to visualize bioluminescence signals in living cells in detail and over long durations. Researchers at Helmholtz Munich and the Technical University of Munich (TUM) developed the QIScope instrument to overcome the constraints of bioluminescence imaging. The device uses highly sensitive camera technology that is able to detect extremely low levels of light.

Bioluminescence offers an alternative to fluorescence that is less harsh for live-cell imaging, but the use of bioluminescence is limited by its low intensity. Specialized instruments, such as electron-multiplying charge-coupled device microscopes, compensate for the faint emission in bioluminescence by sacrificing spatial resolution, field of view, and dynamic range.

The researchers harnessed the full potential of the QIS camera technology by developing an optical system that combines features of a telescope with those of a microscope. Inspired by the Keplerian telescope, the design maximizes signal detection using the QIS, while maintaining a high field of view. The design also allows for modularity, enabling multimodal imaging with epifluorescence.

The QIScope captured images of cellular bioluminescence with modestly improved signal-to-noise ratio and substantially higher spatial resolution, field of view, and dynamic range compared to electron-multiplying charge-coupled device, a state-of-the-art bioluminescence system. The capabilities exhibited by the QIScope could support challenging experiments previously not possible using bioluminescence.

“To take full advantage of the sensor’s capabilities, we took inspiration from the optical layout of telescopes,” researcher Ruyu Ma said. “By combining this approach with the QIS camera, we created a system that can reveal cellular processes with a clarity and sensitivity that was not possible with the state-of-the-art system.”

The researchers used the QIScope to track fine-scale dynamics in living cells, such as the movement of vesicles and the behavior of low-abundance proteins, over extended periods (greater than 18 h), with minimal toxicity and probe bleaching.

All the components of the QIScope were obtained commercially and can be modified and integrated with other imaging modalities.

The construction, performance, and capabilities of the QIScope could make bioluminescence an accessible, viable technique for live-cell imaging at high spatiotemporal resolution. And, by addressing key limitations of traditional bioluminescence imaging, the QIScope provides researchers with a valuable tool for studying a range of biological systems, from single cells to organoids and tissue models. Its ability to reveal subtle and long-term changes in cell behavior could support progress in diverse research areas, including cell biology, disease modeling, and drug discovery.

“It also integrates other imaging methods such as epifluorescence and, in principle, phase contrast," said researcher Jian Cui, who led the study. "This opens the door to observing living systems with much less disturbance, which is essential for understanding complex biological processes in health and disease.”


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Biophotonics in Tissue Biology

A significant feature of this field is visualizing and detecting cells and tissue. This involves the injection of fluorescent markers, into a living system, to follow dynamics of a cell and drug delivery.

Tissue biology involves the analysis of the microscopic structure of animal and human tissues. This is often performed by examining a thin tissue slice under a light or an electron microscope.

This inter-disciplinary analysis of the biology and photonics is utilized to detect, image, and govern biological components in the tissues.

Laser processing of tissue by biophotons

The mechanisms of various laser tissue interactions for removal of tissue, cutting, and coagulating are widely utilized for surgical measures in several major clinical professions such as dentistry, ophthalmology, gynecology, nose and throat surgery, surgery of ear, and urology.

This is inspired by the fact that the magnificent dominance on laser parameters permits ultra-precise surgical procedures without harming the surroundings of the regular tissue. In addition, removal and cutting of the tissue takes place at a very high temperature on laser surgery.

The blood vessels and nerve endings that have been slit during surgery get clotted and result in minimum blood loss and increased severity of pain.

The major advantage of lasers is that the transportation of radiation can be performed through flexible, thin, optical fibers to internal organs endoscopically through minor laceration.

Biophotonics application in the field of histology

Laser system with sensor control: Sensor controlled laser systems are of focus in the field of therapy. These systems have already been utilized in experimental assays with living tissues and humans.

They can also be utilized for intraluminal calculi and for destruction of tumor tissues. Most tumors are destroyed through vaporization by different laser sources and photodynamic therapy. The advancement of sensors with laser sources for treatment of malignant tissue for efficient, specific, and safe destruction of tissues is under research.

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How Biophotonics Is Harnessing Light for Health And Science

Fifty or so years ago French physicist Pierre Aigrain coined the term photonics as a research field whose goal was to use light to perform functions that traditionally fell within the typical domain of electronics, such as telecommunications, and information processing.

Or maybe it was John Campbell who, in a letter sent to Gotthard Gunther in 1954, wrote, “Incidentally, I’ve decided to invent a new science — photonics. It bears the same relationship to Optics that electronics does to electrical engineering. Photonics, like electronics, will deal with the individual units; optics and EE deal with the group phenomena! And note that you can do things with electronics that are impossible in electrical engineering!”

Naming rights aside, the field of photonics began in earnest between 1958 and 1960 with the invention of the maser and the laser. The laser diode followed during the 1970s, optical fibers and the erbium-doped fiber amplifier after that, and, pretty soon, the telecommunications revolution was taking place and the infrastructure for the internet was forming.

Though the word biophotonics can be traced to Alexander Gurwitsch’s 1923 discovery that living organisms emit an ultra-weak light, the term itself has only been around since the mid-1980s. Since then, biophotonics – a light-based method that gathers information about biological processes at the molecular, cellular, and organismal levels – has been used in many applications including medicine, biology, physics, and engineering.

The Advantages Of Biophotonics

Today, biophotonics is used to describe any technique dealing with the interaction between biological items and photons. This refers to emissions, detection, absorption, reflection, modification, and creation of radiation from biomolecular, cells, tissues, organisms, and biomaterials. In addition to the applications noted earlier – biophotonics is used in industries such as life science, medicine, agriculture, and environmental science.

There is a difference between the use of light for therapy and surgery, where it serves the purpose of transferring energy, and its use for diagnostics. In the latter case, light is utilized to excite matter and provide information to the operator. Biophotonics is usually associated with the latter type of application.

The application of biophotonics brings with it many advantages, including a diverse spatial scale writes AIP Publishing. “The spatial dimensions of biological objects that can be probed or manipulated by light range from approximately nanometer (biological molecules) to approximately centimeter (biological tissue), spanning more than several orders of magnitude in size. For example, superresolution fluorescence microscopy can image the intracellular localization of proteins and RNA in detail while endoscopy can detect cancer tumors in vivo.”


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Biophotonics Market Projected Expansion to $133.9+ Billion Market Value by 2030 with a 10.5% CAGR During 2021-2030

Allied Market Research published a report, titled, "Biophotonics Market By End User (Medical Diagnostics, Medical Therapeutics, Tests & Components, and Nonmedical Application) and Application (See-through Imaging, Inside Imaging, Spectro Molecular, Surface Imaging, Microscopy, Light Therapy, Analytical Sensing, and Biosensors): Global Opportunity Analysis and Industry Forecast, 2021-2030." According to the report, the global biophotonics industry generated $52.17 billion in 2020, and is expected to reach $133.90 billion by 2030, witnessing a CAGR of 10.5% from 2021 to 2030.

The emergence of nanotechnology, R&D activities in the field of optics, and surge in use of biophotonic devices for medical & nonmedical purposes drive the growth of the global biophotonics market. However, high cost of equipment restrains the market growth. Contrarily, the use of biophotonics in non-medical sectors is expected to present opportunities for the market.

The Medical Diagnostics Segment to Maintain its Dominant Share during the forecast period

Based on end use, the medical diagnostics segment accounted for the highest market share in 2020, contributing to nearly three-fifths of the global biophotonics market, and is projected to maintain its dominant share in terms of revenue during the forecast period. This is due to technological advancements in the field of diagnostics, rise in incidences of chronic diseases, and surge in awareness about healthcare. However, the non-medical segment is estimated to witness the highest CAGR of 13.4% from 2021 to 2030, owing to increase in use in life science, agriculture, environmental science, and microscopy.

The Analytics Sensing Segment to continue its Lead Position Throughout the Forecast Period

Based on application, the analytics sensing segment held the highest market share in 2020, accounting for more than one-fourth of the global biophotonics market, and is projected to continue its lead position throughout the forecast period. This is attributed to the widespread usage of this application. However, the microscopy segment is estimated to register the largest CAGR of 11.5% from 2021 to 2030, owing to high-throughput techniques and the digitization of microscopes.

North America to Maintain its Leadership Status by 2030

Based on region, North America contributed to the highest market share in terms of revenue in 2020, accounting for more than one-third of the global biophotonics market, and is expected to maintain its leadership status by 2030. This is due to increased use in the medical sector for therapy and non-medical applications. However, Asia-Pacific is projected to portray the fastest CAGR of 11.8% during the forecast period, owing to technological advancements and development of new products by leading market players in the region.



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Red light can reduce blood glucose levels, says study

In a new study appearing in the Journal of Biophotonics, researchers have found that 670 nanometers (nm) of red light stimulated energy production within mitochondria, leading to increased consumption of glucose. In particular, it led to a 27.7% reduction in blood glucose levels following glucose intake, and it reduced maximum glucose spiking by 7.5%.

While the study was conducted in healthy individuals, the non-invasive, non-pharmacological technique has the potential to have an impact on diabetes control after meals, as it can reduce damaging fluctuations of blood glucose in the body that contribute to aging.

The study also highlights the significant long-term consequences for human health, including the potential dysregulation of blood sugars posed by lengthy exposure to blue light. Given the prominence of LED lighting and the fact that LEDs emit towards the blue end of the spectrum with very little red, the authors suggest that this may be a potential public health issue.

Mitochondria provide energy for vital cellular processes, using oxygen and glucose to produce the energy-rich nucleoside adenosine triphosphate (ATP). Previous research has established that long-wavelength light between approximately 650–900 nm (spanning the visible through to the near-infrared range) can increase mitochondrial production of ATP which reduces blood glucose and also improves health/lifespan in animals.

The authors Dr. Michael Powner, Senior Lecturer in Neurobiology in the School of Health & Psychological Sciences at City, and Professor Glen Jeffery, Professor of Neuroscience in the UCL Institute of Ophthalmology, also say that this improvement in ATP production can cause signaling changes that are transmitted throughout the body.

They suggest that it may be mediating the abscopal effect, which refers to the phenomenon in cancer treatment where specific irradiation of a primary tumor can result in shrinkage of secondary tumors located in a different part of the body. Likewise, 670 nm light shone selectively onto the backs of mice in previous studies has been shown to result in improvements in ATP that improve symptoms in both a model of Parkinson's disease and a model of diabetic retinopathy.

To explore the impact of 670 nm red light on blood glucose, the researchers recruited 30 healthy participants, who were then randomized into two groups: 15 in the 670 nm red light group, and 15 in the placebo (no light) group. They had no known metabolic conditions and were not taking medication.

Participants were then asked to do an oral glucose tolerance test and record their blood glucose levels every 15 minutes over the next two hours. People who received red light exposure 45 minutes prior to drinking glucose exhibited a reduced peak blood glucose level and reduced total blood glucose during the two hours.

Dr. Powner, who was the lead author of the study, said, "It is clear that light affects the way mitochondria function and this impacts our bodies at a cellular and physiological level. Our study has shown that we can use a single, 15-minute exposure to red light to reduce blood sugar levels after eating. While this has only been done in healthy individuals in this paper, it has the potential to impact diabetes control going forward, as it could help to reduce potentially damaging glucose spikes in the body after meals."

Professor Jeffery said, "Sunlight has a balance between red and blue, but we now live in a world where blue light is dominant because although we do not see it, LED lights are dominant in blue and have almost no red in them. This reduces mitochondrial function and ATP production. Hence our internal environments are red-starved. Long-term exposure to blue light is potentially toxic without red. Blue light on its own impacts badly on physiology and can drive disrupted blood sugars that may in the long run contribute to diabetes and undermine health spans.

"Pre-1990, we all had incandescent lighting which was okay because it had the balance of blue and red similar to sunlight, but there is a potential health span time bomb in the change to LEDs in an aging population. This can partly be corrected by spending more time in sunlight."


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Laser Method Enables Fast & Precise Blood Vessels in Hydrogel

Researchers from Vienna University of Technology (TU Wien) and Keio University have found a way to create artificial blood vessels in miniature organ models in a quick and reproducible manner. The method utilizes ultrashort laser pulses in the femtosecond range to write highly 3D structures into a hydrogel.

In biomedical research, organs-on-a-chip are becoming increasingly important: By cultivating tissue structures in precisely controlled microfluidic chips, it is possible to conduct research much more accurately than in experiments involving living humans or animals.

However, there has been a major obstacle: such mini-organs are incomplete without blood vessels. To facilitate systematic studies and ensure meaningful comparisons with living organisms, a network of perfusable blood vessels and capillaries must be created — in a way that is precisely controllable and reproducible.

“We can create channels spaced only a hundred micrometers apart. That’s essential when you would like to replicate the natural density of blood vessels in specific organs,” said Aleksandr Ovsianikov.

It’s not just about precision: The artificial blood vessels have to be formed quickly and remain structurally stable once they are populated with living cells. “We know that cells actively remodel their environment. That can lead to deformations or even to the collapse of vessels,” Salvadori said. “That’s why we also improved the material preparation process.”

Instead of using the standard single-step gelation method, the team used a two-step thermal curing process, in which the hydrogel is warmed in two phases, using different temperatures, rather than just one. This alters its network structure, producing a more stable material. The vessels formed within such material remain open and maintain their shape over time.

“We have not only shown that we can produce artificial blood vessels that can actually be perfused. The even more important thing is: We have developed a scalable technology that can be used on an industrial scale,” said Aleksanr Ovsianikov. “It takes only 10 minutes to pattern 30 channels, which is at least 60 times faster than other techniques.”

If biological processes are to be realistically modeled on a chip, the artificial tissues must behave like their natural counterparts.

“We showed that these artificial blood vessels are colonized by endothelial cells that respond just like real ones in the body,” Salvadori said. “For example, they react to inflammation in the same way – becoming more permeable, just like real blood vessels.”

According to the researchers, this marks an important step toward establishing lab-on-a-chip technology as an industrial standard in many fields of medical research.

“Replicating the liver’s dense and intricate microvasculature has long been a challenge in organ-on-chip research. By building multiple layers of microvessels spanning the entire tissue volume, we were able to ensure adequate nutrient and oxygen supply — which, in turn, led to improved metabolic activity in the liver model. We believe that these advancements bring us a step closer to integrating organ-on-a-chip technology into preclinical drug discovery,” said Masafumi Watanabe of Keio University.


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Photonic Crystal Sensor Measures Key Parameters Simultaneously

Twisted moiré photonic crystals — an advanced type of optical metamaterial — have shown enormous potential in the race to engineer smaller, more capable, and more powerful optical systems.

In twisted moiré photonic crystals, how the layers twist and overlap can change how the material interacts with light. By changing the twist angle and the spacing between layers, these materials can be fine-tuned to control and manipulate different aspects of light simultaneously — meaning the multiple optical components typically needed to simultaneous measure light’s phase, polarization, and wavelength could be replaced with one device.

However, researchers have been unable to integrate twisted moiré photonic crystals into devices that can actively control the twist and distance between layers in real time, severely limiting their application.

Now, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), in collaboration with Stanford University and the University of California, Berkeley, have developed an on-chip twisted moiré photonic crystal sensor that uses MEMS technology to control the gap and angle between the crystal layers in real time. The sensor can detect and collect detailed polarization and wavelength information simultaneously.

“Twisted moiré photonic crystals are promising for engineering smaller, more powerful optical systems because they offer highly tunable optical properties, precise light control, compact and scalable design, and broad application potential across various advanced photonic technologies,” said Eric Mazur, the Balkanski Professor of Physics and Applied Physics at SEAS and senior author of the paper.

“Our research demonstrates how powerful these materials can be when we have precise control and establishes a scalable path towards creating comprehensive flat-optics devices suitable for versatile light manipulation and information processing tasks,” said Haoning Tang, a postdoctoral fellow at SEAS and first author of the paper.

In the researchers’ device, the layers of photonic crystals sit on vertical and rotary actuators connected to an electrode. The whole device is only a few millimeters in scale and can be fabricated using CMOS-compatible processes.

The researchers demonstrated that by using the actuators to change the distance and rotational position of the layers of photonic crystals, they could perform simultaneous hyperspectral and hyperpolarimetric imaging — meaning every pixel captured by the sensor contained information from across the electromagnetic spectrum and detailed information about the polarization state. According to the researchers, it is the first device with active tuning to demonstrate such detailed information about multiple properties of light.

“These devices could be used for a range of applications including quantum computing, data communications, satellites, or medical scans, where getting a clear image and detailed information about light and color is really important,” said Tang.

In the future, these devices would be made with even more complex tuning capabilities, including actuators with even more degrees of freedom.


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