THz Light Probes Structural Tissue Changes for Disease Diagnosis

Changes in tissue structure, such as to the boundaries of cancerous tumors, occur in many disease processes. Terahertz (THz) waves demonstrate the potential to detect these changes. The ability to identify and characterize microscopic structural changes in tissue using THz imaging could enable earlier detection of cancer, improving patient outcomes.

While polarization measurements of reflected THz waves are thought to have diagnostic value, the underlying mechanisms that create different polarization responses in tissues remain poorly understood. This gap in understanding underscores a need for computational models capable of explaining and predicting the phenomena that researchers have observed experimentally.

In a study led by professor Hassan Arbab, researchers at Stony Brook University analyzed Mie scattering of polarized THz light from cancerous tumor budding using Monte Carlo simulation. They compared the outcome of the simulation with experimental results obtained in phantom models, and performed an analysis of a polarization-sensitive THz scan of an ex vivo porcine burn injury.

The results of the Stony Brook study indicate that polarimetric imaging using THz waves has the potential to detect structural changes due to disease progression.

The team began by using Monte Carlo simulation to model how THz waves scatter from spherical particles embedded in highly absorbing biological media. Particles of varying diameters can be representative of disease-related structures like tumor clusters or hair follicles that have been destroyed due to burn injuries. The simulation revealed contrast in the Stokes vectors and Mueller Matrix elements for varying scattering particle sizes.

The researchers compared the simulation results with experimental data from four phantoms consisting of polypropylene particles of varying sizes, suspended in gelatin. The phantoms mimicked the optical properties of actual tissue.

They measured phantoms of moderately-sized tumor budding and poorly differentiated clusters. The results showed frequency-dependent patterns that clearly correlated with particle size, confirming the simulation predictions. As predicted, the larger scattering particles produced higher-intensity diffusely scattered light. The larger particles also produced distinct dips in polarization at specific frequencies. This finding could be used to assess the size of the scattering particles.

These experimental results demonstrate the potential to use THz light — specifically, the degree of polarization and intensity of diffusely scattered light — as a diagnostic marker. The team further showed that a characterization of the tissue’s relevant polarization properties can be achieved using just one polarization measurement, unlike conventional approaches that require at least four measurements.

Finally, the researchers induced a full-thickness burn injury in ex vivo porcine skin samples and compared the data captured over the burned and healthy regions of the tissue. The results showed contrast between the burned and healthy tissue regions, demonstrating the potential to use THz polarimetric imaging to distinguish between disease states in ex vivo tissue.

Most existing THz imaging techniques use the differences in water content between healthy and diseased tissue as their main source of diagnostic contrast. This approach can be overly simplistic for many disease conditions.

The ability to detect and characterize structural changes in tissue through THz polarimetric imaging could open new possibilities for timely detection of malignancies. For example, THz imaging could be used to identify tumor budding, where small clusters of cancer cells break away from the main tumor. THz polarimetric imaging offers a potentially simpler, more efficient way to detect these clusters than current methods that rely on tissue sampling and intricate staining procedures.

The research team plans to extend its study by investigating actual cancer tissue samples and expanding its THz measurement capabilities to capture even smaller tissue features. THz systems with larger bandwidth, currently in development, could enable polarimetric techniques with the potential to resolve structures as small as 10-30 μm, enabling a wider range of disease-related tissue changes to be detected with THz light.

As THz technology continues to advance, the results of the Stony Brook study could have a significant influence on the inclusion of THz imaging in routine medical diagnosis, potentially transforming the way clinicians detect and monitor disease progression.

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PhotonDelta Teams with Luminate NY for Transatlantic Growth

Netherlands-based photonic chip accelerator PhotonDelta has collaborated with Luminate NY, an accelerator for startups with optics, photonics, and imaging enabled technologies, to support the growth of early-stage photonics companies across North America and the Netherlands.

Through this collaboration, startups that are part of the PhotonDelta or Luminate can get access to the benefits from each other's accelerator programs. This will enable photonics startups to leverage these ecosystems and relationships to accelerate innovation and scaling into the global market.

PhotonDelta and Luminate will work together to identify and vet candidates for participation in their programs and accelerator cycles. In addition, both organizations will introduce startups to their extensive networks of industry experts, investors, mentors, and production facilities. The collaboration will also provide soft-landing services as they establish a presence in both the U.S. and the Netherlands, thereby offering startups access to U.S. and European markets.

The memorandum of understanding with Luminate also underpins the importance of the strategic collaboration between the Netherlands and New York state in the field of semiconductors and integrated photonics. Earlier this month, a NY State delegation consisting of government officials and industry experts visited the Netherlands to strengthen connections and share knowledge. The trip was supported by the Dutch Ministry of Foreign Affairs and the Ministry of Economic Affairs.

The scope of the collaboration includes joint programming, beginning with a series of planned investor summits, pitch events, and webinars. This will include the Luminate 5x5 Pitches in August, Luminate Investor Summit in New York City on Sept. 12, the Luminate Finals on Oct. 22 and the PIC Summit Europe event in Eindhoven, the Netherlands on Nov. 4 and 5. Executives from both organizations will meet quarterly to exchange insights on photonics developments and identify startups with strong potential for acceleration, funding, or market entry and develop new initiatives such as the Global Photonics Engineering Contest, which recently concluded with 33 submissions from all over the world.

Luminate, created and administered by non-profit NextCorps, and funded by Empire State Development, accepts 10-12 companies from around the world annually into its cohort-based program. The accelerator now has more than 80 companies in its portfolio, representing a variety of industries, from AR/VR, quantum computing, and semiconductors to materials and metrology, autonomous vehicles, healthcare, and clean energy. These companies collectively have an estimated value of more than $700 million. Luminate is a member of the NY Photonics cluster in a region that is home to over 150 optics companies.

PhotonDelta’s ecosystem currently comprises over 75 different organizations that form a complete value chain, including design services, multiple foundries for photonic chip fabrication, packaging, assembly and testing, and an increasing number of fabless companies that use PIC technology for innovative solutions. PhotonDelta, a Dutch-based industry accelerator focused on photonic chip technology, has secured €1.1 billion ($1.3 billion) to accelerate this next-generation semiconductor technology by running R&D programs, leading international roadmapping activities, and investing in pioneering startups that apply integrated photonics technology.

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Accurate Magnetic Field Measurement Method Could Advance Quantum Sensing

 

Optically pumped magnetometers (OPMs) are used to measure magnetic fields in biosensing, contraband testing, and magnetic communications. They also aid in dark matter searches and serve as promising platforms for quantum-enhanced measurements.

Accurate vector magnetometry, however, remains a challenge for OPMs due to the OPM’s inherent scalar operation. Scalar OPMs require an external reference to extract directional information. While scalar measurements are often sufficient, robust calibration of vector OPMs is increasingly important for applications requiring high accuracy as well as precision.

Researchers at JILA, a joint research institute of the University of Colorado Boulder and the National Institute of Standards and Technology, demonstrated a vector OPM that uses Rabi oscillations driven between the manifolds of rubidium atoms to measure the direction of a magnetic field against the polarization ellipse structure of a microwave field.

The researchers exposed a cell containing roughly one hundred billion rubidium atoms, in vapor form, to a microwave signal. They hit the chamber with a magnetic field, which caused the atoms inside the chamber to shift. Using a laser, the researchers measured the shift in the atomic energy.

“Atoms can tell you a lot,” professor Cindy Regal said. “We’re data mining them to glean simultaneously whether magnetic fields are changing by extremely small amounts and what direction those fields point.”

Regal said that if an atom is hit with a microwave signal, its internal structure will “wiggle.” This “atomic dance” can tell physicists a lot.

“Ultimately, we can read out those wiggles, which tell us about the strength of the energy transitions the atoms are undergoing, which then tells us about the direction of the magnetic field,” Regal said.

In the current study, the team observed the shifts in the atomic energy — the atomic “dancing” — to pinpoint the orientation of a magnetic field to an accuracy of nearly one-hundredth of a degree.

By relying only on atomic measurements, the researchers were able to detect drift in the microwave vector reference and compensate for systematic shifts. To enable deadzone-free operation, the researchers introduced a Rabi measurement that used dressed-state resonances.

These measurements, performed within the vapor cell platform, achieved an average vector accuracy of 0.46 milliradians and vector sensitivities down to 11 micro-radians per square root hertz, for geomagnetic field strengths near 50 micro-teslas. This performance surpassed the accuracy threshold of several existing OPM methods that use atomic vapors with an electromagnetic vector reference.

“You can think of each atom as a compass needle, and we have a billion compass needles, which could make for really precise measurement devices,” researcher Dawson Hewatt said.

In the future, the findings could be used to build quantum sensors to map brain activity, for example, or help airplanes navigate.

“What magnetic imaging allows us to do is measure sources that are buried in dense and optically opaque structures,” professor Svenja Knappe said. “They’re underwater. They’re buried under concrete. They’re inside your head, behind your skull.”

Unlike mechanical devices with internal parts that can change over time, atoms are always the same, Regal said.

The team plans to further improve the precision of its vector OPM before introducing it for practical use. The researchers hope that one day airplane pilots can use the vector OPM based on atomic vapors to navigate the plane by following local changes in Earth’s magnetic field, much like migratory birds use their innate biological magnetic sensors.

“It’s now a question of how far can we push these atomic systems,” Knappe said.


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Microlaser Bandage Measures Glucose Without Drawing Blood

A research team at Nanyang Technological University, Singapore (NTU Singapore) has developed a wearable sensor based on microlasers to measure biomarkers found in sweat. The bandage-like device could provide a way to monitor blood sugar levels noninvasively.

Human sweat contains biomarkers such as glucose, lactate, and urea that indicate various health conditions and can be collected in a noninvasive and painless manner, making it ideal for daily monitoring, the researchers said.

Diabetic patients typically use an invasive finger prick test to self-monitor blood glucose levels. A small drop is drawn from the finger and put into contact with a strip which is inserted into a portable glucose meter for reading. Alternatively, there are sensor-based monitoring devices, which can be expensive and rigid and must be attached to a patient’s skin over prolonged periods of time.

By encapsulating a microlaser in liquid crystal droplets and embedding the liquid within a soft hydrogel film, the NTU team created a compact and flexible light-based sensing device — like a bandage that can provide highly accurate biomarker readings within minutes.

“Our innovation represents a non-invasive, quick and effective way for diabetic patients to monitor their health,” said Chen Yu-Cheng, director of NTU’s Centre for Biodevices and Bioinformatics. “By combining a microlaser with a soft hydrogel film, we have demonstrated the feasibility of a wearable laser to provide a more pleasant health monitoring experience for patients.”

The NTU team created their bandage device by embedding microlasers in liquid crystal droplets. The microlasers are customized to pick up three different types of biomarkers (lactate, glucose, and urea). A different colored liquid crystal dot on the device distinguishes each biomarker.

When sweat interacts with the bandage device, the amount of light emitted by the microlasers fluctuates based on the concentration of biomarkers present. To read the biomarker levels, users shine a light source on the device, and the light emitted from the microlaser sensors is analyzed and translated using a mobile application.

In real-live experiments, the bandage device successfully picked up tiny fluctuations of glucose, lactate and urea levels in sweat down to 0.001 mm, which is 100x better than current similar technology, according to the researchers.

The NTU team believes their innovation to be the first reported wearable sensing device capable of measuring multiple biomarkers in sweat with ultra-high sensitivity and dynamic range. The sensitivity enables tracking of a dynamic range (low to high) in biomarkers levels, which provide comprehensive information on patients’ health.

“Our device is capable of detecting both the high and low range of biomarkers levels. This is particularly beneficial for diabetic patients as current similar health monitoring devices focus on tracking only high glucose levels, but not abnormal or low glucose levels, which may indicate other health complications,” said Nie Ningyuan, first author of the study and a PhD candidate at NTU. “In comparison, our device will provide a clearer picture of the users’ health condition with a variety of readings captured.”

To further develop the technology, the research team plans to fine-tune the microlaser sensors to detect a wider variety of substances, including drugs and other chemicals found in sweat.


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Photoacoustic Probes Enable Deep Brain Tissue Imaging

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Molecular engineering spearheaded by two groups at the European Molecular Biology Laboratory (EMBL) has developed an approach to create photoacoustic probes for neuroscience applications.

Scientists can learn more about biological processes by tracking certain chemicals, such as ions or biomolecules. Photoacoustic probes can act as ‘reporters’ for hard-to-detect chemicals by binding to them specifically. The probes can then absorb light when excited by lasers and emit sound waves that can be detected by specialized imaging equipment. For neuroscience applications, however, researchers have so far been unable to engineer targeted reporters that can visualize brain functions tailored for photoacoustics.

“Photoacoustics offer a way to capture imagery of an entire mouse brain, but we just lacked the right probes to visualize a neuron’s activity,” said Robert Prevedel, an EMBL group leader and a senior author on the paper.

To overcome this challenge, Prevedel enlisted the help of fellow EMBL group leader Claire Deo, also a senior author on the paper. She and her team specialize in chemical engineering.

“We have been able to show that we can actually label neurons in specific brain areas with probes bright enough to be detected by our customized photoacoustic microscope,” Prevedel said.

While researchers have experimented with using synthetic dyes as photoacoustic reporters of neuronal activity, controlling where the dye goes and what might be labelled has been challenging. Proteins have been particularly useful as probes for tagging specific molecules, but have not yet led to effective photoacoustic probes to monitor neural activity across the entire brain.

“In our case, we took the best of both of these sensors, combining a protein with a rationally designed synthetic dye, and we can now label and visualize neurons in specific regions of interest,” said Alexander Cook, first author of the study and a predoctoral fellow in the Deo group. In rational design approaches, researchers use existing knowledge and principles to build molecules with the desired properties, instead of blindly making and testing random compounds. The probe not only gave a static observation, Cook said, but showed a reversible, dynamic response to calcium, which is a marker of neuron activity.

According to Deo, an important challenge stood in the way of this technological development. Because photoacoustic probes have not been extensively studied, the researchers lacked a way to evaluate the probes they were building.

Consequently, the project began with Nikita Kaydanov, co-author of the study and predoctoral fellow in the Prevedel Group, who custom-made a spectroscopy setup.

“There is no commercial setup that can measure photoacoustic signals of a probe in test tubes or cuvettes, so we had to build one,” Kaydanov said. “We created our own photoacoustic spectrometer to assess and optimize the probes.”

“This allowed us to evaluate and characterize the different probes we made to assess a few things,” Deo said. “Did they produce a detectable photoacoustic signal? Are they sensitive enough? That’s how we inferred the next steps.”

Having proved that the probes could work in vial, the team took the work further by devising a way to deliver the probes into a mouse brain where they successfully detected photoacoustic signals from neurons inside the targeted brain regions.

“While we are excited about the progress, we need to be clear that this is just the first generation of these probes,” Deo said. “While they offer a very promising approach, we have a lot more work to do, but it’s a good first demonstration of what this system can enable and the potential it has in better understanding brain function.”

The researchers plan to continue development of the technology by improving the dye delivery system and confirming the ability to use them for dynamic imaging inside cells.

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Light Source Aims to Build on Nobel Prize-winning Technology

A team at Heriot-Watt University, led by professor Christian Brahms, is developing a light source for extremely fast laser pulses that will enable scientists to observe some of the fastest processes in the natural world as they occur. The new laser light source will capture natural processes like light absorption in photosynthesis in attoseconds.

The project, which is called FASTER — short for Flexible Attosecond Soliton Transients for Extreme Resolution — will build on the EUV attosecond technology that received the Nobel Prize in Physics in 2023.

Brahms and his team will design and build a laser light source that mimics natural sunlight, but in extremely short flashes. “My aim is to create laser pulses with similar extremely short duration to conventional attosecond science sources, but at the same ultraviolet and visible wavelengths as we get from the sun,” he said.

FASTER will bring attosecond time resolution to ultrafast spectroscopy experiments in the UV, visible, and IR regions of the electromagnetic spectrum. This will enable scientists to study ultrafast dynamics entirely with non-ionizing radiation and without the need for strong-field excitation or probing.

Ultrabroadband optical attosecond spectroscopy will be enabled by soliton self-compression. The researchers will create the optical attosecond pulses required for the new laser light source by building on the results of the recent High-energy soliton (HISOL) project.

HISOL combines the high damage threshold and far UV (FUV) transparency of gas media, the long interaction lengths enabled by waveguides, the guidance of high-energy laser pulses in large-core hollow capillary fibers, and the nonlinear evolution of ultrafast laser pulses in the higher-order-soliton regime. This combination allows IR laser pulses to be converted to wavelength-tunable FUV pulses with a few-femtosecond duration and near-perfect beam properties.

Using tailored soliton dynamics in hollow-core waveguides, the FASTER team will convert femtosecond pulses to attosecond pulses. The resulting attosecond pulses will be used on various samples to perform ultrabroadband optical attosecond pump probe and 2D spectroscopy experiments, starting with condensed-matter targets.

While current attosecond technology, including the 2023 Nobel Prize-winning breakthrough, can create extremely short pulses of light at UV or X-ray wavelengths, it is limited when it comes to natural phenomena, because natural processes involve sunlight, not the wavelengths used in laboratory experiments.

FASTER will allow scientists to take “freeze-frame” images of exceptionally fast microscopic processes in molecules and materials. “This will fill in attosecond technology’s blind spots and directly relate our knowledge of ultrafast processes to other areas, like photochemistry or materials science,” Brahms said.

“Many of the most important breakthroughs in the history of science have been enabled by observing nature at scales far beyond the limits of human perception,” he said. “That’s exactly what we’ll be working on — pushing far beyond the limits of conventional laser sources to bring fundamental science into focus.”

The FASTER project to achieve a very fast laser light source for natural phenomena will take place over a five-year period and is scheduled to officially begin in the summer of 2025. It is one of 50 research projects in the UK to receive the European Research Council’s (ERC’s) Starting Grant in 2024. Brahms and his team will receive £2.5 million ($3.3 million) in ERC funding.

ERC funding supports research in a range of fields. “The new ERC Starting Grants winners aim to deepen our understanding of the world,” Iliana Ivanova, European Commissioner for Innovation, Research, Culture, Education, and Youth, said. “Their creativity is vital to finding solutions to some of the most pressing societal challenges.”

“Empowering researchers early on in their careers is at the heart of the mission of the ERC,” Maria Leptin, ERC president, said.

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Doublet Design Overcomes a Metalens Bottleneck in Microscopy

A research team from Nanjing University has developed a solution that improves metalens performance in and for microscopy applications. The researchers’ metalens-based microscope achieves both a wide field of view (FOV) and high-resolution imaging, addressing the inherent trade-off between these two critical parameters that, according to the researchers, has prevented metalenses to date from achieving performance comparable to conventional microscopes.

Metalenses face significant challenges in practical microscopy applications. Off-axis aberrations, which severely restrict metalens FOV and resolution capabilities, are the primary limitations to the use of metalenses in practical microscopy.

In their system architecture, the researchers used a doublet configuration of two metalenses on opposite sides of a transparent silica substrate combined with annular illumination. The two metalenses consist of silicon nitride nano-fins, crafted as high-aspect-ratio squares with precise dimensions and arranged at carefully calculated intervals. This design approach mitigates off-axis aberrations and increases resolution capabilities, thereby optimizing imaging performance.

The researchers’ prototype had a 1-mm FOV with a half-pitch resolution of 620 nm. Additionally, the prototype is compact, with a measurement of 4 cm × 4 cm × 5 cm. The researchers used their meta-microscope prototype to image cervical cancer cells. The system captured images of various stages of cancer development within the same FOV, revealing important cellular details such as nuclear enlargement, deformation, and division.

“Our experimental results demonstrate high-quality microscopic bioimages that are comparable to those obtained from traditional microscopes within a compact prototype, highlighting its potential applications in portable and convenient settings,” said Li.

According to the researchers, the technology could be used for research scenarios where traditional microscopes would be impractical. Further, it could be integrated into microelectronic devices and systems for clinical or biomedical automation.

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Raman Spectroscopy Undergoes Major Speed Upgrade

Researchers at the University of Tokyo have increased the measurement rate of Raman spectroscopy by 100-fold. Since the measurement rate of the technique has been a major limitation, the improvement is expected to aid advancements in multiple fields relying on the identification of molecules and cells, such as biomedical diagnostics and material analytics.

As a mode of identification for cells and molecules, Raman spectroscopy is widely used, but it’s limited in its ability to keep up with the speed of changes in certain chemical and physical reactions due to the low scattering cross section.

Over the last decade, various broadband-coherent Raman scattering spectroscopy techniques have been developed to address the limitation, achieving a measurement of 500 kSpectra/s (kilospectra per second).

In order to further improve the measurement rate, the team built a system from scratch, leveraging a mode-locked ytterbium laser system developed by Takuro Ideguchi and his team at the Institute for Photon Science and Technology at the University of Tokyo.

In building the system, the team combined coherent Raman spectroscopy — a version of Raman spectroscopy that produces stronger signals than the conventional, spontaneous Raman spectroscopy— with their previously developed specifically designed ultrashort pulse laser and time-stretch technology using optical fibers.

The developed system provides a 50 MSpectra/s (megaspectra per second) measurement rate, a 100-fold increase compared to the previous fastest rate of 500 kSpectra/s. The system enables highly efficient Raman scattering with an ultrashort femtosecond pulse and sensitive time-stretch detection with picosecond probe pulse at a high repetition of the laser.

As a proof-of-concept, the team measured broadband coherent Stokes Raman scattering spectra of organic compounds covering the molecular fingerprint region from 200 to 1200 cm-1.

“We aim to apply our spectrometer to microscopy, enabling the capture of 2D or 3D images with Raman scattering spectra,” Ideguchi said. “Additionally, we envision its use in flow cytometry by combining this technology with microfluidics. These systems will enable high-throughput, label-free chemical imaging and spectroscopy of biomolecules in cells or tissues.”

According to the researchers, the high-speed broadband vibrational spectroscopy technique holds promise for unprecedented measurements of sub-microsecond dynamics of irreversible phenomena and extremely high throughput measurements.

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Light-Based Control of Bacteria Aims to Quell Antibiotic Resistance

Bacterial resistance to antibiotics is a growing challenge for the healthcare and environmental sectors. Bacterial persistence is usually the first step leading to resistance, which involves a change in an organism’s genome.

In the future, it may be possible to address antibiotic persistence and resistance by using light to regulate bacterial response to antibiotics. A technique developed at the Polytechnic University of Milan (Politecnico di Milano), by a team participating in the Engineering of Bacteria to See Light (EOS) project, allows bacteria to sense light and convert light energy into electrical signals across the bacterial membrane, without the need for genetic modification.

To demonstrate photocontrol of bacterial membrane potential, the researchers attached phototransducing molecules to bacterial surfaces to make the bacteria light-responsive. When the researchers exposed the phototransducers to light, the electrical potential of the bacterial membrane changed.

The researchers used Ziapin2, a photoswitchable chemical compound, with two broad-spectrum antibiotics, Kanamycin and Ampicillin. These antibiotics have different modes of activation. Kanamycin requires cytosolic uptake to inhibit protein synthesis, while Ampicillin targets cell wall polymerization at the cell envelope.

When the researchers exposed B. subtilis to Kanamycin and Ziapin2 through photoactivation with 470-nm light, the previously lethal effects of Kanamycin were markedly reduced. In contrast, Ampicillin-treated samples remained largely unaffected by light-induced membrane modulation.

“This interplay between light and electrical signaling allows us to control key biological processes such as movement, biofilm formation, and antibiotic sensitivity,” professor Giuseppe Maria Paternò said. “By manipulating the membrane potential on demand, we can influence antibiotic uptake and restore or even enhance the effectiveness of treatments against resistant strains.”

Possible applications for the technique include developing next-generation antimicrobial platforms that use light to target resistant pathogens, and biocompatible, light-guided “bacterial robots” capable of delivering drugs to specific areas of the body — even the areas that are hard to reach, such as the gastrointestinal tract.

More broadly, the potential to modulate and control the interaction between bacterial cells and antibiotics using light and synthetic photoswitches, without genetic engineering, in real time, represents a first step in developing a new approach to combating antibiotic resistance.

In the future, photoswitchable chemical compounds could be membrane-targeted and tailored to work with different classes of antibiotics, advancing bacterial bioelectric regulation and its applications in antimicrobial therapies.


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Advanced OCT System Integral to Eye Transplantation

An adaptation of OCT put into use at Northwestern University, visible OCT (vis-OCT), will be a key component in an Advanced Research Projects Agency for Health (ARPA-H)-funded project that aims to conduct successful eye transplants in the next several years. The technology will be used to examine the structural integrity of eyes in donors, such as the health of retinal layers and the flow of blood as well as monitoring their continued viability throughout the process.

This work will be supported by over $50 million in ARPA-H funds to multiple institutions, earmarked for viability, imaging, surgical, immunomodulation, ocular preservation, and neuroregeneration strategies within the Transplantation of Human Eye Allografts (THEA) project. The Northwestern team, led by Hao Zhang, a professor of biomedical engineering, and Cheng Sun, a professor of mechanical engineering, will be part of group directed by Jeffrey Goldberg, professor and chair of ophthalmology at the Byers Eye Institute at Stanford University.

Opticent Health, a spinoff company of Zhang’s lab at Northwestern, created the Halo 375 for animal research and the Aurora X4 for human research. These center on a vis-OCT system that includes a supercontinuum white light laser based on photonic crystals, fundus camera for fast imaging, an adjustable field of view, and software to analyze the generated data. It has not yet been approved by the FDA, but is in use for clinical research.

“At this point, we have created the system, it is about overcoming logistical issues associated with this project,” Zhang said. “We have to adapt it for a robotic arm and account for multiple instruments at the bedside. A traditional OCT instrument is used with a chin rest when the patient is sitting, but obviously that wouldn’t work for something like this.”

He said the ARPA-H funding includes expectations of meeting certain guidelines, such as a system ready for use in a medical setting within the next two years, and a clinical protocol within the next three years.

Eye transplants are not new, as more than 70,000 people in the U.S. donate their eyes each year when they die. But these historically have involved corneal transplants, whereas the most common forms of vision loss are caused by retinal degeneration. That is where the whole-eye transplants fit into global eye health. And Zhang acknowledged the questions that need to be answered go beyond the imaging itself.

“With a whole-eye transplant you would need to look at how the muscles attach and whether the blood will flow as it should,” he said. “Then there’s the question of attaching and regenerating the nerves. But I know there are lots of people working on that part of the problem, too.”


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Microscopy Method Doubles the Depth Limit for Live Tissue Imaging

Label-free imaging using two-photon autofluorescence of reduced form nicotinamide adenine dinucleotide phosphate, or NAD(P)H, provides nondestructive, high-resolution, 3D visualization of cellular activities in living systems. Due to light scattering, however, this imaging technique typically can only penetrate as far as 300 μm into living tissues.

To enable deep imaging of thick tissues, researchers at MIT implemented multimode fiber-based, three-photon excitation of NAD(P)H with a low repetition rate and high peak power. They used living, engineered, human multicellular microtissues as test samples.

With this approach, the researchers more than doubled the standard depth limit of NAD(P)H imaging, extending it beyond 700 μm. They achieved deep and dynamic simultaneous localization and mapping (dSLAM) microscopy for structural and metabolic imaging of intact, living biosystems.

The dSLAM microscopy technique attained a high peak power exceeding 0.5 megawatts (MW) at a band of 1100 nm, plus or minus 25 nm. This was achieved by adaptively modulating multimodal, nonlinear pulse propagation with a compact fiber shaper.

The new, noninvasive imaging technique could help biomedical researchers study the body’s immune responses in living tissue and develop new medicines.

The ability to capture the metabolic dynamics of living biosystems is essential for basic biomedical research and laboratory testing. The enhanced depth provided by dSLAM microscopy, combined with the improved imaging speed, could help fuel new investigations into complex cellular interactions.

The flexibility provided by the modular design — a step-index multimode fiber with a slip-on fiber shaper — makes this imaging methodology suitable for demanding in vivo and in vitro imaging applications, including cancer research, immune responses, and tissue engineering.

Advanced microscopy technologies have led to a better understanding of biology, with each technique offering unique advantages for specific applications. With its noninvasive, deep tissue imaging capabilities, dSLAM microscopy could serve as a complementary tool to other imaging techniques for studying cellular dynamics in living tissues. It requires minimal sample preparation and no exogenous labels.

Continued advancements in beam optimization, system design, and streamlined data analysis could make dSLAM microscopy increasingly accessible to biomedical researchers, as a valuable addition to the existing arsenal of microscopy techniques for investigating living tissues.

“It opens new avenues for studying and exploring metabolic dynamics deep in living biosystems,” professor Sixian You said.


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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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Leica Microsystems Acquires ATTO-TEC

Leica Microsystems has acquired ATTO-TEC GmbH, a specialty supplier of fluorescent dyes and reagents. The addition of dyes and reagents for sample preparation complements the Leica portfolio of microscopy imaging platforms and advanced AI-based analysis software.

TTO-TEC’s dyes, antibody labeling kits, labeled phospholipids, and other reagents are used in fluorescence microscopy imaging and can be a key advantage for reliable results, such as in high-plex 3D experiments in cancer research, according to Annette Rinck, president of Leica Microsystems.

The acquisition is expected to provide ATTO-TEC with additional resources to aid in future developments of the product portfolio. “Direct access to knowledge of subsequent imaging and analysis steps leads to new approaches in developing assays, kits, and dyes optimized for the entire workflow,” said Jörg Reichwein, CEO of ATTO-TEC.

According to a press release from Leica Microsystems, ATTO-TEC products will remain available through its existing online store and commercial partners.
 
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Chip-size Amplifier Increases Data Transmission Tenfold

A research team from Chalmers University of Technology has introduced a new amplifier that allows the transmission of ten times more data per second than those in current fiber optic systems. The amplifier, which fits on a small chip, holds potential for various critical laser systems, including those used in medical diagnostics and treatment.

To ensure that information maintains a high quality and is not overwhelmed by noise, optical amplifiers are essential. The data transmission capacity of an optical communication system is largely determined by the amplifier's bandwidth, which refers to the range of light wavelengths it can handle.

“The amplifiers currently used in optical communication systems have a bandwidth of approximately 30 nanometers. Our amplifier, however, boasts a bandwidth of 300 nanometers, enabling it to transmit ten times more data per second than those of existing systems,” said lead author and professor of photonics Peter Andrekson.

The new amplifier, made of silicon nitride, features several small, spiral-shaped, interconnected waveguides that efficiently direct light with minimal loss. By combining this material with an optimized geometric design, several technical advantages have been achieved.

“The key innovation of this amplifier is its ability to increase bandwidth tenfold while reducing noise more effectively than any other type of amplifier. This capability allows it to amplify very weak signals, such as those used in space communication,” said Andrekson.

Additionally, the researchers have successfully miniaturized the system to fit on a chip just a few centimeters in size.

“While building amplifiers on small chips is not a new concept, this is the first instance of achieving such a large bandwidth,” said Andrekson.

The researchers have integrated multiple amplifiers onto the chip, allowing the concept to be easily scaled up as needed. Since optical amplifiers are crucial components in all lasers, the Chalmers researchers’ design can be used to develop laser systems capable of rapidly changing wavelengths over a wide range. According to the researchers, the innovation opens up numerous applications in society.

“Minor adjustments to the design would enable the amplification of visible and infrared light as well. This means the amplifier could be utilized in laser systems for medical diagnostics, analysis, and treatment. A large bandwidth allows for more precise analyses and imaging of tissues and organs, facilitating earlier detection of diseases,” said Andrekson.

In addition to its broad application potential, the amplifier can also help make laser systems smaller and more affordable.

“This amplifier offers a scalable solution for lasers, enabling them to operate at various wavelengths while being more cost-effective, compact, and energy efficient. Consequently, a single laser system based on this amplifier could be utilized across multiple fields. Beyond medical research, diagnostics, and treatment, it could also be applied in imaging, holography, spectroscopy, microscopy, and material and component characterization at entirely different wavelengths,” said Andrekson.

Light at different wavelengths serves various applications. The researchers have demonstrated that the amplifier functions effectively within the optical communication spectrum, ranging from 1400 to 1700 nm. With its extensive bandwidth of 300 nm, the amplifier can potentially be adapted for use at other wavelengths.

By modifying the waveguide design, it is possible to amplify signals in other ranges, such as visible light (400 to 700 nm) and infrared light (2000 to 4000 nm). Consequently, in the long term, the amplifier could be used in fields where visible or IR light is essential, such as disease diagnosis, treatments, visualization of internal organs and tissues, and surgical operations.


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