Light Activation Tool Could Help Target Drug Delivery

Light can be a powerful tool for manipulating molecular events. It is noninvasive, relatively straightforward to use, and can provide excellent spatial and temporal control.

A light activation tool has been developed at the University of Geneva that can control both the activity and localization of various types of molecules in vivo. The tool could enable researchers to control a molecule at a specific location in a living organism without affecting the surrounding cells. It could be used for both research and medical treatments such as those for skin cancer.

The researchers initially set out to modify a well-characterized inhibitor of Polo-like kinase 1 (Plk1). Their aim was to develop a way to control the activation and inactivation of a protein at a specific location within the organism, to better understand its functions.

“Everything started from this methodological question,” professor Monica Gotta said. “We were looking for a way to inhibit a protein involved in cell division, the Plk1 protein, when and where we wanted, to better understand its function in the development of an organism.”

The researchers attached the same coumarin photolabile protecting group (PPG) at two different positions of the PLk1 inhibitor. One photocage was attached at a position important for the binding to and inhibition of Plk1, enabling temporal control of the protein. The other coumarin photocage masked an added carboxylic acid, which, once unmasked, would lead to cellular retention.

“After a complex process, we were able to block the active site of our inhibitor with a coumarin derivative, a compound naturally present in certain plants. This coumarin could then be removed with a simple light pulse,” researcher Victoria von Glasenapp said.

The team developed a way to anchor the inhibitor at the exact point in the organism where activation was desired. Exposure to light resulted in the removal of both PPGs, leading to the activation of the inhibitor and its trapping inside cells.

“We thus modified the inhibitor so that it becomes trapped in the targeted cell by adding a molecular anchor that is released only by light,” professor Nicolas Winssinger said. “This enabled us to activate and anchor the inhibitor with the same light pulse, thereby inactivating Plk1 and stopping cell division at the precise desired location.”

The researchers demonstrated the efficacy of the caged inhibitor in 3D spheroid cultures. By uncaging it with a single light pulse, they were able to inhibit Plk1 and arrest cell division, a highly dynamic process, with a high degree of spatiotemporal control.

The approach could be extended to other small molecules where spatial and temporal regulation of molecular activity is required, opening new routes for controlled drug targeting in more complex systems and improving the precision of drug delivery.

In the future, a laser could be used to activate a treatment exactly where it was needed, while sparing the surrounding healthy tissue, thereby limiting undesirable side effects. “We hope that our tool will be widely used, leading to a better understanding of how living organisms function and, in the long term, to the development of location-specific treatments,” Gotta said.

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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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