FPGA-Based Data Compression Drives Brain Imaging Performance Gains

To help broaden the use of single-photon avalanche diode (SPAD) cameras for multispeckle diffuse correlation spectroscopy (DCS), researchers at the University of Edinburgh developed a data compression scheme for a large-pixel-count SPAD camera using a field-programmable gate array (FPGA).

The camera system’s large sensor array enabled a substantial signal-to-noise ratio (SNR) gain over a single-pixel system: The researchers demonstrated an SNR gain of 110, with respect to single-pixel multispeckle DCS, using half of the 192 × 128 SPAD array. The pixel active fill factor was 13% — an order-of-magnitude-larger pixel count than in prior works, according to the team.

FPGA compression for large-array multispeckle DCS could democratize the use of SPAD cameras in the biomedical research community, the researchers believe, extending the benefits of multispeckle DCS across many areas of biomedical research.

DCS quantifies cerebral blood flow — an important indicator of brain health — by measuring the autocorrection function of diffused light introduced through the scalp. The light scatters through the deep tissue and returns a speckle pattern at the detector. The pattern fluctuates in intensity in response to the movement of the tissue and the blood circulating within it.

SPAD cameras have made it possible to capture many independent speckles at the same time, leading to multispeckle DCS instruments with high sensitivity. However, multispeckle DCS systems are hampered by the small number of pixels in a SPAD array and by a lack of camera-embedded processing capabilities. The extremely high data rates of SPAD cameras, which exceed the maximum data transfer rates of commonly used communication protocols, require large computing resources and limit the scalability of SPAD cameras to the higher pixel resolutions.

To enable practical use of SPAD cameras for multispeckle DCS, the researchers, led by professor Robert K. Henderson, connected a SPAD sensor array composed of 192 × 128 pixels to a commercial FPGA. They embedded an autocorrelation algorithm in the FPGA to make data compression scalable to large SPAD arrays. The algorithm can perform most of the calculations needed for DCS, and the system demonstrated the ability to calculate 12,288 autocorrelations in real time from the SPAD array output.

Shifting the computational burden from a host computing system to the hardware directly connected to the SPAD sensors alleviated the need for high-powered computing resources and extremely fast data transfer rates. The researchers ran the multispeckle DCS measurements in real time using a standard PC.

“Our proposed system achieved a significant gain in the signal-to-noise ratio, which is 110 times higher than that possible on a single-speckle DCS implementation and 3× higher than other state-of-the-art multispeckle DCS systems,” Henderson said.

Although the focus of the work is on FPGA-embedded processing for multispeckle DCS, the system can also operate in multispeckle time-domain DCS with a precision of 33-ps time-of-flight resolution, the researchers said.

In the future, the FPGA-based design for data compression could enable SPAD arrays for multispeckle DCS that provide high pixel resolution without requiring specialized, high-performance computing to calculate autocorrelators for real-time measurements.


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Skin-Like Microfiber Grating Gauges Cardiovascular Wellness

According to the World Health Organization, 17.9 million people die annually due to cardiovascular diseases. Soft wearable devices are well suited for monitoring physiological signals from electrocardiogram, phonocardiogram, and pulse wave. Advantages of these types of devices include real-time operation capability, skin-like mechanical properties, and high signal-to-noise sensing capability.

However, monolithic hemodynamic parameters achieved by current wearable devices cannot adequately and precisely reflect the health status of regional vasculature. Spatiotemporal hemodynamic monitoring techniques are needed to satisfy growing demand for clinical treatment and daily health management of the cardiovascular system.

Researchers from Nanjing University have developed a hemodynamics monitoring technique that relies on a configurable, skin-like microfiber Bragg grating group to deliver information on the real dynamics of the systemic cardiovascular system, such as heartbeat, angiectasis, and pulse wave propagation. The system overcomes common bottlenecks to biophotonic sensing mechanisms that use commercial fiber Bragg grating (FBG) devices.

Although the conventional DOF sensing technique represented by the fiber Bragg grating FBG is well suited for spatiotemporal hemodynamic monitoring, the researchers said, the traditional optical fiber commonly used in the method has a large distinct mechanical property with the skin and a low response on physiological signals. This makes it difficult to be worn on the body stably and comfortably. And, while flexible packaging technology has been used to address the mechanical mismatch, thick encapsulation and the low sensitivity of commercial FBG devices pose an obstacle in detecting subtle physiological signals, thereby limiting their potential applications in wearable devices.

Similarly, optical microfibers have been proven to have excellent flexibility, configurability, and large evanescent fields for high-sensitivity sensing. However, existing devices based on optical microfiber are difficult to achieve spatially distributed, time-synchronized, and multiparameter sensing capabilities without a wavelength encoding strategy.

The researchers’ skin-like microfiber grating group combines ultrathin flexible packaging technology with microfiber to produce skin-like fiber patches. The researchers used femtosecond laser direct writing technology to noninvasively inscribe the Bragg gratings into the interior of the microfiber. This provided different wavelength encodings for multiple microfiber patches, which in turn enabled synchronous multichannel sensing capabilities

By connecting microfiber grating patches in series, the researchers detected multiple physiological signals at different nodes of the human body simultaneously and distinguished them by different working wavelengths. Since the light-based physiological signals propagate at close to the speed of light in the microfiber grating group, the time synchronization is only limited by the FBG interrogator.

The researchers ultimately activated the monitoring technology by detecting the proximal ballistocardiograph signal and the distal pulse wave at each superficial artery in the human cardiovascular system and then calculating the pulse wave transmit time. By detecting mechanical signals at the proximal and distal ends of the cardiovascular system instead of electrophysiological activity signals, the monitoring technique can present the real dynamics of the systemic cardiovascular system, such as heartbeat, angiectasis, and pulse wave propagation.

In addition, the mechanism showed favorable repeatability and stability — under 10,000 stress circles.

In their development of the technique, the researchers presented three distinct hemodynamic monitoring modes. They said that the technology has the working capability of real-time and dynamic evaluation of local blood vessel health status in the whole cardiovascular system, demonstrating great potential in the diagnosis of cardiovascular diseases such as arrhythmia, angiosclerosis, hypertension, and thrombosis. Further, the advancement could serve to facilitate precise clinical diagnosis, the fast screening of lesions, and daily health management.

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More Efficient Microcombs on the Road to Commercialization

Researchers at Chalmers University have developed a method to make microcombs 10 times more efficient, opening pathways to discovery in space and health care, and paving the way for high-performance lasers in a range of technologies. The team has established a company to commercialize the new technology.

Laser frequency combs can measure frequency with extreme levels of precision, analogous to a ruler made of light. The principle is based on a laser sending photons that circulate within a small cavity — a so-called microresonator — where the light is divided into a wide range of frequencies. These frequencies are precisely positioned in relation to each other, like the markings on a ruler. Therefore, a new kind of light source can be created consisting of hundreds, or even thousands, of frequencies, like lasers beaming in unison.

Because virtually all optical measurements are connected to light frequencies, the microcomb has myriad applications, from calibrating instruments that measure signals at light-year distances in space in the search for exoplanets, to identifying and keeping track of health via exhaled air.

A fundamental problem with microcombs has been that their efficiency has been too weak to reach their transformative potential. The conversion efficiency between the laser and the microcomb was too weak, meaning that only a fraction of the power contained in the laser beam was usable.

According to Victor Torres-Company, professor of photonics at Chalmers, the new method breaks what was believed to be a fundamental limit for optical conversion efficiency. The method increases the laser power of the soliton microcomb by 10 times and raises its efficiency from about 1% to more than 50%.

Rather than using just one microresonator, the new method uses two. They form a unique ensemble with properties greater than the sum of its parts. One of the resonators enables the light coming from the laser to couple with the other resonator; similar to impedance matching in electronics.

According to the researchers, the high conversion efficiency and uniform spectrum make the devices ideal for applications in optical communications and dual-comb spectroscopy. With further engineering of the coupling region and dispersion, the researchers believe the results pave the way for the realization of octave-spanning microcombs and self-referencing using only integrated components.

Additionally, a shifted resonance can be achieved in multiple different systems, and it is not limited to the coupled-cavity design that the researchers have presented. As such, they said, the work provides important insights for realizing high-efficiency solitons using other schemes, like photonic crystal resonators or linearly coupled transverse modes, and, potentially, when using a feedthrough pump cavity.

The technology was recently patented and the researchers founded Iloomina AB, a company that will launch the technology onto a wider market.

According to Torres-Company, the new microcombs enable high-performance laser technology in numerous markets. “For example, frequency combs could be used in lidar modules for autonomous driving, or in GPS satellites and environmental sensing drones, or in data centers to enable bandwidth-intensive AI apps,” he said.

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Lasers Help Mimic Biosystems as Team Prods Organisms’ Reproduction

Researchers at New York University (NYU) have devised a system of asynchronous, optically driven micro-rotors that could be used to study far-from-equilibrium phenomena such as turbulent weather and biosystems. The advancement could potentially be used to replicate natural phenomena in engineered systems.

In vortical flows, which are found in both meteorological and biological systems, particles move into orbital motion in the flow generated by their own rotation, resulting in a range of complex interactions. To better understand these dynamics, the researchers sought to replicate vortical flows at their most basic level. They created a system to move micro-particles using micro-rotors and a laser beam.

Direct observation of hydrodynamic coupling between artificial micro-rotors has been restricted by the details of the drive that is used, either through synchronization (using external magnetic fields) or confinement (using optical tweezers). The NYU system is enabled by a tweezing-free optical field.

The researchers designed a force-free torque field using a collimated beam of circularly polarized light and developed a synthetic route for birefringent, silica-coated colloids to show the spinning of hundreds of micro-particles using photonic angular momentum. They systematically quantified the micro-rotors’ optical and hydrodynamic properties. Unlike previous synthetic micro-rotor systems, the particles rotated asynchronously in the optical torque field while freely diffusing in the plane.

The researchers also found that the rotating particles affected each other’s orbital motion.

Analysis of the particles’ spinning rates revealed that pairs of rotating particles mutually advected one another, and that their translation and rotation were coupled hydrodynamically. The coupling was geometric, indicating that it could potentially have general application in active systems, from living organisms to robotic systems.

For example, the researchers found similarities in their system to the dynamics observed by other scientists in “dancing” algae, that is, in algae groupings that move in concert with each other.

“The spins of the synthetic particles reciprocate in the same fashion as that observed in algae — in contrast to previous work with artificial micro-rotors,” said Matan Yah Ben Zion, a doctoral student at the time of the work and now a researcher at Tel Aviv University. Synthetically, and on the micron scale, the researchers successfully reproduced an effect that is seen in living systems, he said.

The NYU system could be used to investigate isotropic rotating ensembles with broken time-reversal symmetry and parity in order to shed light on new material properties theoretically predicted in active matter. These include odd viscosity and quantum hall fluids. Free optical rotors using nonspherical particles could also be used to study the effect of morphology and steric interactions in tandem with hydrodynamic coupling.

Further, the NYU system of optical rotors, if combined with rotors driven by an external magnetic field, could enable the experimental study of ensembles of counter-rotating particles. In these mechanisms, optical rotors rotate independently from the magnetic rotors. Experimental investigation of an ensemble of counter-rotors could expand scientific understanding of far-from-equilibrium states of matter.

“Collectively, these findings suggest that the ‘dance of algae’ can be reproduced in a synthetic system, better establishing our understanding of living matter,” Ben Zion said. “Living organisms are made of materials that actively pump energy through their molecules, which produce a range of movements on a larger cellular scale.

“By engineering cellular-scale machines from the ground up, our work can offer new insights into the complexity of the natural world.”

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Breath-Activated Sensor for Diagnosing Diabetes

Currently, diagnosing diabetes and prediabetes means a visit to a doctor's office or lab work, both of which can be expensive and time-consuming. Research from Huanyu "Larry" Cheng at Penn State has yielded a sensor that can help diagnose diabetes and prediabetes on-site in a few minutes with just a breath sample.

Previous diagnostic methods have used glucose found in blood or sweat, but the current sensor however, this non-invasive test uses a sensor to detect acetone levels in breath. While acetone in breath is a normal byproduct from the burning of fat, an acetone level of 1.8 parts per million is a sign of diabetes.

“While we have sensors that can detect glucose in sweat, these require that we induce sweat through exercise, chemicals or a sauna, which are not always practical or convenient,” Cheng said. “This sensor only requires that you exhale into a bag, dip the sensor in, and wait a few minutes for results.”

While there have been other breath detection methods in the past, they have required lab analysis. Acetone can be detected and read on-site, making the new sensors cost-effective and convenient.

Beyond using acetone as the biomarker, Cheng said another novelty of the sensor came down to design and materials — primarily laser-induced graphene. To create this material, a CO2 laser is used to burn the carbon-containing materials, such as the polyimide film in this work, to create patterned porous graphene with large defects desirable for sensing.

The porous nature of the graphene helps to let the gas pass through, which means there is a higher likelihood of the acetone molecules being captured. By itself, laser graphene didn’t identify acetone as precisely as needed, which the team remedied by combining the graphene with zinc oxide.

“A junction formed between these two materials that allowed for greater selective detection of acetone as opposed to other molecules,” Cheng said.

Cheng said another challenge was that the sensor surface could also absorb water molecules, and because breath is humid, the water molecules could compete with the target acetone molecule. To address this, the researchers introduced a selective membrane, or moisture barrier layer, that could block water but allow the acetone to permeate the layer.

Currently, the method requires that a person breathe directly into a bag to avoid interference from factors such as airflow in the ambient environment. The next step is to improve the sensor so that it can be used directly under the nose or attached to the inside of a mask, since the gas can be detected in the condensation of the exhaled breath. He said he also plans to investigate how an acetone-detecting breath sensor could be used to optimize health initiatives for individuals.

“If we could better understand how acetone levels in the breath change with diet and exercise, in the same way we see fluctuations in glucose levels depending on when and what a person eats, it would be a very exciting opportunity to use this for health applications beyond diagnosing diabetes,” Cheng said.

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Light-Activated Biomimetic Gel Offers Potential for Corneal Repair

Tens of millions of people around the world suffer from corneal diseases, with only a small fraction eligible for corneal transplantation. In a recent study, researchers at the University of Ottawa showed that biomimetic materials activated with low-energy blue light can reshape and thicken damaged corneal tissue to promote healing and recovery. The research results could provide a safe way to treat corneal thinning, as well as a practical alternative to corneal transplantation.

Further, the dosage of pulsed blue light needed to activate the biomaterial is minimal, which mitigates the possibility of cytotoxic effects from the light.

The biomaterial is injected within the corneal tissue after a tiny pocket is surgically created. The injectable biomaterial, which is in the form of a viscous liquid, is made from short peptides and glycosaminoglycans that assemble into a hydrogel when irradiated with low-energy blue light. The hydrogel hardens and forms a tissue-like 3D structure with properties similar to those found in pig corneas. The use of low-energy pulsed light irradiation allows the researchers to safely use photocuring to photo-crosslink the biomimetic materials designed for injection into thinning corneas.

Data showed that the materials used to obtain experimental test results could remain in an animal model for several weeks. As a result, professor Emilio Alarcon and the other researchers anticipate that the material will remain stable and be nontoxic in human corneas.

In their study, the researchers observed that the way the light was delivered affected the formation of the hydrogel. Pulsed irradiation allowed for better recovery of the oxygen levels within the hydrogel, compared to a continuous dosage of light. Pulsing the light for 2.5 s on, 2.5 s off produced optimal results.

To keep the light dosage under standard safety values, the researchers selected a low in vivo radiance dosage of 8.5 mW cm−2 for 10 min of pulsed light, which is equivalent to only 5 min of light exposure. This radiance level is below the category of low risk when direct blue light is exposed to the eye for up to 166 min. The researchers performed in vivo experiments for light toxicity on animal models to verify the safety of their light irradiation regime.

In vivo experiments using a rat model indicated that the light-activated hydrogel could thicken corneas without side effects. The researchers also successfully tested the technology in an ex vivo pig cornea model.

According to Alarcon, the researchers developed the technology to be clinically translatable; all components must be designed to be manufacturable following strict standards for sterility. In clinical conditions, reducing the amount of light delivered to the eye will translate into a faster and safer procedure. It will shorten the period during which eye movement must be minimized to ensure stability of the injected biomaterial volume and shape until it turns into a soft hydrogel. Good control of the corneal front surface curvature is of primary importance for adequate refraction of the light within the eye.

Although testing in large animal models will be necessary prior to clinical human trials, the researchers have begun the patent application process for the technology.

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Single-Cell Analysis Optofluidics Tool Delivers on Demand

An on-demand optical system for exporting target droplets from a static droplet array (SDA) provides a simple way to export specific cells or analytes for analysis without compromising efficiency or accuracy. Researchers at the Qingdao Institute of Bioenergy and Bioprocess Technology of the Chinese Academy of Sciences developed the system, called optical on-demand droplet release (OODR). The developers and their collaborators believe that OODR could promote SDAs as a valuable tool for use with high-capacity screening assays with applications in diverse fields. They said that the technique in its current stage of development has the potential to be used in single-molecule/cell analysis, drug screening, and phenotype-based cell sorting.

The OODR system incorporates a 1064-nm laser-responsive indium tin oxide (ITO) layer into a microchamber, array-based, droplet microfluidic chip. When the laser is focused onto the ITO layer of the chip, local heating causes microbubbles to form. The microbubbles push the droplets out of the chamber on a selective basis.

The researchers fabricated the chip using a low-cost, readily available ITO glass as a photoresponsive layer. The ITO layer was bonded to a PDMS layer with an array of microchambers to provide the capability to selectively release target droplets and enable the SDA to work rapidly.

According to the researchers, the size of the microbubble proved to be critical to the successful release of the droplet based on the chip design used by the team. They identified the optimal size for the microbubble as 40 μm, and they tuned the laser to the range necessary to generate the amount of heat needed to form a correctly sized microbubble without degrading the integrity of the cell. Under the appropriate conditions, OODR can release a droplet within three seconds.

OODR precisely heats the ITO layer, via laser, to create microbubbles that allow for the selective pushing of a target droplet out of the chamber on the microfluidics chip. This is based on the microdroplet single-cell sorting system, such as EasySort Compact, for example. The team used the EasySort Compact system to achieve automatic single-cell sorting, said professor Bo Ma.

Once the released droplet is pushed out of the chamber, it is carried by the flow to the outlet. The droplet can be easily exported in the one-droplet-one-tube (ODOT) manner by a pipette tip, via the inherent capillary force, which allows the movement of liquid without applying external force. The droplet is exported into a well or tube in a high-throughput manner for further analysis.

The released droplet is identified by using white or fluorescent imaging. These images can be used to sort the morphology of the target bacteria, which can be a challenge without a static image for reference.

The researchers used OODR to selectively release droplets containing fluorescein sodium from an SDA consisting of 6400 microchambers. OODR achieved a success rate of about 100% (nine out of 6400 droplets were successfully released). It also exhibited low residual, with only about 5% of the droplet volume remaining in the chamber.

The team demonstrated on-demand release of single-cell and multicell droplets for both E. coli and yeast, based on white or fluorescence imaging. The successful use of OODR with E. coli and yeast cells suggests that the system is applicable to other types of cells. According to Ma, the technique not only targets single cells, but enables the sorting of microdroplets that contain one cell, multiple cells, and/or reagents only.

Beyond avoiding causing any effect to the cell’s ability to be cultivated, or accuracy, the researchers said, the successful cultivation of the cell-containing droplets in an ODOT manner indicates that the isolation method has minimal impact on cell viability. This, they said, is essential when further live-cell analyses are needed. It also demonstrates the potential to seamlessly couple OODR with downstream ODOT-based assays, such as human or microbial single-cell sequencing. OODR also reduces the sample size and amount of reagent needed for analysis, making SDA more efficient and cost-effective. And the current system is user-friendly, the researchers said.

Professor Jian Xu said that the team is currently using artificial intelligence and machine learning to automate the system via EasySort. This will reduce human involvement in the system’s operation, making it easier for nonprofessionals to use, which could further expand the use of OODR and SDA.

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