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Contraceptive hydrogel proves safe in rats

Researchers from India have developed a biodegradable gel for female contraception. Reporting their results in Materials Science & Engineering C, they found that the active ingredient styrene maleic anhydride (SMA) embedded in a biodegradable hydrogel kills sperm and prevents egg cell formation. Implanting the gel in female rats showed excellent bio-compatibility, paving the way for creation of a non-hormonal contraceptive implant. Such a gel would expand the hormonal and non-hormonal contraceptive options currently available for women, many of which cause side effects.

Potential for a non-hormonal female contraceptive

SMA is already in Phase III clinical trials as a male contraceptive implant in the vas deferens, the vessel transporting sperm in men. But in addition to killing sperm, SMA also disrupts the development of female egg cells. The astonishing combination of these two effects led the research team headed by Piyali Basak and Sujoy Guha to design a female version of the gel.

To achieve long-term dosing, their team wanted to incorporate SMA into a gel that would be inserted in the uterus, the female reproductive organ that nurtures the developing foetus till birth. A suitable gel has to be safe for the body, biodegradable and allow the incorporation of SMA without inactivating the drug.

To create such a gel, polycaprolactone (PCL) proved to be a good starting point. It is commonly used for medical applications as a biodegradable polymer; however, it is not flexible enough for this application. To achieve the required flexibility, the researchers mixed PCL with PEG (polyethylene glycol) and polymerized them as diacrylates (DA). The polymers were fabricated into a PCL-DA:PEG-DA hydrogel, a water-based gel made from an insoluble polymer. They then added five different concentrations of SMA and characterized the resulting gels.

Selecting the best concentration

First author Bhuvaneshwaran Subramanian and his team tested the physical properties and biodegradability of the gels, as well as the influence of exposure to ethanol, varying temperature and mechanical stress.

Research team — Sujoy Guha, Piyali Basak and Bhuvaneshwaran Subramanian. (Courtesy: B Subramanian)

Out of the five samples with different SMA concentrations, the team further evaluated the three most promising ones using sperm and rat uterine cells. As intended, the gel killed sperm but did not harm the uterine cells. The sample with the highest spermicidal activity was then chosen for implantation in a rat.

Because rats do not have a true uterus, the researchers implanted the hydrogel in the fallopian tubes, which serve as a model for the human uterus. The implanted gel had no effect on any of the tested tissues or organs and degraded after 150 days. Blood analysis revealed no signs of inflammation, toxicological symptoms or metabolic and hormonal changes.

These findings suggest that the SMA hydrogel should be safe for implantation in the female reproductive organs. The next step will be to investigate whether the combination of SMA and the PCL-DA:PEG-DA hydrogel also works as an effective contraceptive when implanted in rats.

Colour-changing probe maps stresses in soft materials

images of elongation test — The observed change in colour of elongated samples. (Courtesy: C Creton)

Directly measuring stresses in soft materials as they deform is no easy task, but a team of researchers in France and the US have now developed a colour-changing force-responsive probe that can do just that. The device, which is based on a force-sensitive molecule embedded in an elastic polymer (elastomer) network, can be used to build up a quantitative map of internal forces in a structure by optical means alone.

When a mechanical load is applied to an irregularly shaped object, the stresses and strains it produces will also be irregular. Measuring these internal forces is important for predicting where the object will break, but because soft materials often deform considerably before they fail, such measurements are particularly difficult to make.

At present, only a few techniques can directly measure stresses in soft materials. The most common method is to measure strains and then perform a mathematical simulation to calculate the corresponding stresses. Such calculations are, however, known to be unreliable for large strains and strong strain gradients.

Force-sensitive molecules

In recent years, researchers have been exploring ways of making stress sensors out of force-sensitive molecules incorporated into polymers. When these “mechanophore” molecules are activated by a force of a sufficient size, they undergo chemical reactions that cause their optical properties (such as fluorescence, luminescence and colour) to change.

One commonly used mechanophore is an organic compound known as a spiropyran. When a spiropyran-containing polymer network deforms, the forces on the bonds of this molecule cause it to transform into a chemical variant called merocyanine that absorbs visible light. By shining a light on the sample and monitoring its change in colour from transparent to blue, researchers can therefore directly measure the fraction of molecules that have undergone the chemical reaction. This, in turn, gives them a measure of the average stress applied on the material at the point at which the colour change is observed.

Mechanochemistry

“This field of study is called mechanochemistry – that is, chemistry triggered by mechanics,” explains Costantino Creton from the ESPCI in Paris, who led the new research effort. “It opens many possibilities for measuring internal forces using optical visualization techniques alone.”

Going from qualitative colour-change detection to quantitative mapping of heterogenous stress fields is not as easy as it sounds, however. For one, Creton and colleagues note that the spiropyran must be randomly and homogenously incorporated into the material being tested. The average force produced on the molecule must also be directly related to macroscopic stress applied, and the molecular sensor should activate before the material breaks.

A calibration curve

The researchers tested their technique on two elastomer materials with very different hardening properties. They began by incorporating spiropyran into these materials as a cross-linker and tracked the colour change of the molecule as they applied tension to the samples along a single axis. By varying the concentration of the spiropyran within the network of the elastomers, they produced a calibration curve of applied stress versus colour change. They then used this stress-colour curve to determine the stress distribution around pre-existing cracks within the samples. This stress distribution would be much more difficult to obtain using conventional techniques, as mentioned, since the materials host strong localized stress gradients.

Ink-free polymers colour under stress

Afterwards, the team, which also includes researchers from the University of Colorado at Boulder, compared the experimental stress fields with theoretical simulations of the same materials. The optical measurement exactly matched these calculations, thus validating the method, Creton says.

This internal probe technique, which is detailed in Science Advances, could be used to test statistical fracture modelling of soft, tough materials and more generally to quantify stresses in irregularly shaped objects from simple optical observations with a (red-green-blue) camera, he adds.

The researchers say they would now like to try out their approach on composite materials with a wider range of applications. “We would also like to test metamaterials, which have very heterogenous internal structures and complex mechanical behaviours,” Creton tells Physics World. These materials are artificially engineered compounds with properties such as a negative Poisson ratio that are rare or absent in natural materials.

Quantum dot solar cells get greener

Semiconducting nanocrystals called colloidal quantum dots (CQDs) are ideal for applications such as large-panel displays and photovoltaic cells thanks to their high efficiency and colour purity. Their main drawback is their toxicity, since they have traditionally been made from cadmium or other heavy metals, such as lead. Researchers at the Los Alamos National Laboratory in the US have now engineered cadmium-free QD solar cells that reach efficiencies on par with those of their environmentally-unfriendly counterparts. The key to the new devices’ high performance is their tolerance to defects, they say.

CQDs can be synthesized in solution, which means that films of these nanocrystals can be deposited quickly and easily on a range of flexible or rigid substrates – just like paint or ink. Such semiconducting nanocrystals are ideal for making highly-efficient inorganic solar cells that emit light via a process known as radiative recombination. Here, an electron in the valency energy band in the QD absorbs a photon and moves to the conduction band, leaving behind an electron vacancy, or hole. The excited electron and hole then recombine, releasing a photon.

The advantage of using CQDs as photovoltaic materials in solar cells is that they absorb light over a broad spectrum of solar radiation wavelengths. This is because the band gap of a CQD can be tuned over a large energy range by simply changing the size of the nanocrystals. Such a size-tuneable property has allowed the efficiencies of these QDs to rapidly approach those of traditional thin-film photovoltaics, such as PbS, CdTe and Pb-halide perovskite QDs.

Free from toxic elements

A team of researchers led by Victor Klimov have now developed high-efficiency QD solar cells that are free from any toxic elements. They made their new devices by reacting copper, indium and selenium and then adding zinc to the mix to produce zinc-doped QDs. They then incorporated these QDs into voids of a highly porous titanium dioxide (TiO₂) film, which plays the part of a charge-collecting electrode. The electrode was immersed in a Na₂S electrolyte.

When the QDs in the device absorb incoming photons from sunlight, tightly bound electrons in the valence band get excited into a high-mobility conduction band. These electrons subsequently migrate to the TiO₂ electrode, generating a current in the process.

The researchers say they were “pleasantly surprised” by the results of photovoltaic and spectroscopic measurements on the new devices. Because their QDs have a very complex composition – four elements are combined in the same nanosized particle – they are prone to (intragap) defects, Klimov explains. These defects act as traps in which electrons get stuck, which means that electrons and holes have time to recombine instead of being whisked apart to produce useful current.

“However, despite these imperfections, the ZCISe QDs showed near perfect performance in the new solar cells,” says Klimov. “Per each 100 absorbed photons, we detected 85 photogenerated electrons, implying that the photon-to-electron conversion efficiency was 85%.”

Defect-mediated photoconversion

According to the Los Alamos team, who report their work in Nature Energy, the defects in their material actually help the photoconversion process along, rather than impeding it. In particular, the material’s high photovoltaic efficiency stems from a peculiar mechanism involving two types of intragap defects, they explain. The first, identified as shallow surface-located electron traps, enhance electron transfer between the QDs and TiO₂ electrode. The second, identified as Cu¹⁺ hole-trapping defects, help transfer holes between the QDs and the electrolyte.

The traditional assumption that surface defects are always detrimental thus does not seem to hold true for ZCISe QDs, they say. Indeed, the structures may even be protecting electrons and holes from unwanted recombination. This implies that surface traps are electronically coupled to the TiO₂ electrode and, importantly, that the energy of these traps is high enough for electrons to transfer efficiently into the TiO₂ conduction band.

The high photoconversion efficiencies, combined with the remarkable defect tolerance and toxic-element-free composition of these QDs makes them promising materials for a commercially viable solar-cell technology, they conclude.

Electron accelerator recycles energy

Physicists usually have no shortage of plans to build very expensive particle accelerators – but some researchers are working to make accelerator technology cheaper, and one way is to recycle much of the energy initially used to accelerate particles. A collaboration in the US has now shown it can successfully operate such an “energy recovery linac” by combining superconducting cavities with precisely designed permanent magnets.

The synchrotron has long been a popular way of accelerating electrons and other charged particles. Energy is transferred to bunches of charged particles by sending them through a series of radiofrequency cavities while magnets keep them on a circular path for thousands of orbits. These machines are widely used both as high-energy colliders and as sources of very bright X-rays for a wide range of science.

While this cyclic acceleration produces very high average powers, the bunches of particles will gradually spread out and lose intensity as well as polarization. As a result, linear accelerators (linacs) are used to create the brightest particle beams. These fire particles in a single shot along a straight section of cavities, yielding bunches with very high energies and exceptional intensities. But these machines also have a downside – they consume a huge amount of energy per shot, which limits their firing rate.

Best of both worlds

Energy recovery linacs (ERLs) are designed to combine the best of both worlds. These devices send electrons through a linac and then guide them around a circuit back to the accelerator entrance – with just a few having had their energy tapped along the way. This process takes place N times, with the particles gaining energy on each turn. Then the logic is reversed, thanks to a shift in the electrons’ path length of half a cavity wavelength. The particles travel another N times around the circuit, but rather than absorbing additional energy from the cavities they instead give it back. Once their turns are complete and they have shed all the energy they originally acquired, they are dumped.

With most of this energy transferred to other electrons subsequently injected into the circuit, which themselves go through the same 2N cycles, an ERL can accelerate a given number of particles using a small fraction of the energy consumed by the equivalent linac. In principle, this allows such a device either to generate much higher luminosities from a given electricity budget, or to consume less power for a given luminosity. While the latter option would reduce operating costs, both should lower construction costs – given that linac cavities are more expensive to build than the magnets used to steer electrons.

The idea is not new, having been put forward originally by Maury Tigner at Cornell University in the US in 1965. However, the scheme had to overcome a number of hurdles in the intervening decades. One has been developing the superconducting cavities that make linacs more energy-efficient. Another challenge has been merging beams at the linac entrance and separating them at its exit, as well as dealing with the higher-order modes inside cavities that can cause particle bunches to break up. Difficulties notwithstanding, the scheme has been put into practice at several locations including Novosibirsk State University in Russia, which operated a copper-cavity ERL with multiple turns (N=4) for the first time.

Multiple passes

The latest work, carried out by Georg Hoffstaetter of Cornell University and colleagues, makes progress by instead demonstrating multiple passes using a superconducting linac. The Cornell Brookhaven Energy-Recovery-Linac Test Accelerator (CBETA) has been built and tested at Cornell but relies on magnets developed by Dejan Trbojevic and team at Brookhaven National Laboratory. These are quite different to the electromagnets used in synchrotrons, whose fields ramp up to prevent electrons from flying out of the machine as they pick up speed — but cannot accommodate electrons with different energies. Instead, the CBETA magnets generate a field shaped so that it can simultaneously guide eight sets of electrons, with four different energies, around the circuit back to the linac. Being permanent, rather than electromagnetic, these “fixed-field alternating-gradient” magnets provide an additional energy-saving feature over traditional linacs.

Hoffstaetter and colleagues carried out the first test of CBETA in June last year, showing that the machine could recuperate 99.8% of its input energy after accelerating and decelerating electrons in single passes. Then just before Christmas, the researchers demonstrated the full complement of eight passes. As they report in a paper accepted for publication in Physical Review Letters, they took electrons 6 MeV kinetic energy and stepped their energy up to 42, 78, 114 and 150 MeV, before stepping the energy down so that it ended up back at 6 MeV.

The researchers say that the CBETA technology could be used in a variety of applications including medical isotope production, cancer therapy or in the manufacture of microchips. It has also been designed to show how to “cool” ions that will be collided in the $2bn Electron-Ion Collider approved for construction at the Brookhaven lab in January. Designed to probe the composition of protons and neutrons with unprecedented precision, the collider relies on minimizing particles’ energy to maximize collision rates.

Having shown that CBETA can work in principle, Hoffstaetter and colleagues are now working to boost its performance. To protect equipment and personnel, they restricted the machine’s current on the December run to just a few nanoamps. But they now want to raise that towards a target of 40 mA. “A push to high current will be the next stage of this accelerator,” they write.

Two new frequency combs could boost telecoms and molecular fingerprinting

Frequency combs are one of the most important developments in metrology in the 21st century, but conventional combs are bulky and highly sensitive to external perturbations. Now two independent groups present key developments in solid state frequency combs that could lead to robust, convenient combs for use outside the laboratory. The first is an integrated, telecommunications-wavelength comb that stabilizes itself every time it is turned on. The second uses a completely new mechanism to generate frequency comb emission in the mid-infrared – a region crucial for molecular spectroscopy.

Frequency combs are pulsed lasers often described as rulers of light because they produce extremely short pulses that comprise light at regularly spaced frequencies. By fixing one of these frequencies very precisely – for example using an atomic clock – one can measure the frequency of a light signal by studying how far along the comb it falls from this reference frequency. Frequency combs have proved immensely useful in the laboratory for building better atomic clocks, improving time and frequency standards and also doing ultracold atomic and molecular spectroscopy.

The use of traditional frequency combs, however, is constrained by their need for high-power, ultrastable lasers, amplifiers and other components such as isolators to prevent feedback from destabilizing the laser. In the past decade or so, researchers have sought more user-friendly devices for applications such as fibre-optic multiplexing, time-keeping and molecular detection.

Simple components

In 2018, researchers at Columbia University in New York City led by Michal Lipson and Alexander Gaeta unveiled a solid-state, telecoms-compatible frequency comb that eliminated many specialist components. It used a low-power, electrically-pumped semiconductor laser. When a solid-state microresonator was injected with light at 1579 nm wavelength, Kerr non-linearity caused sidebands to appear at precisely spaced frequencies. The proportion of the energy in these modes gradually increased, forming a frequency comb.

Although this was a huge breakthrough, there were difficulties. A complex process was required to achieve and maintain the comb operation, and even then it did not reliably produce phase- and intensity-stable pulses called solitons. “If it’s not producing solitons, it’s not a quiet comb”, explains John Bowers of the University of California, Santa Barbara, “If you want to make an atomic clock, or a lidar, or a wavelength division multiplexing transmission system, you don’t want modulation instability. It’s not useful for most applications.”

Now, Santa Barbara researchers led by Bowers, together with scientists at Caltech and EPFL in Switzerland, unveil an integrated, solid-state laser that solves these problems. Whereas traditional frequency combs need to prevent feedback between a microresonator and the laser, this latest design utilized feedback.

Much lower noise

A cheap semiconductor laser called a distributed feedback (DFB) laser was integrated into a chip that was placed a small, precisely-controlled distance from a microresonator mounted on another chip. A physically complex non-linear interaction between the laser cavity and the microresonator created a very simple result: every time the laser was switched on, the microresonator automatically tuned itself to produce solitons. Remarkably, the resulting frequency comb had orders of magnitude lower noise than the original laser: “DFB lasers are crappy,” says Bowers, “People pay $60,000 for a laser to get linewidths that aren’t as good as this.” Moreover, the soliton state tolerated environmental disturbances such as temperature fluctuations.

The researchers hope their device could make frequency combs much more widespread: “We believe we can very soon integrate this all onto a single chip,” says Bowers. “It could be a millimetre long, it could be mass produced, it could be quite cheap, and it wouldn’t take a PhD to run. That’s what’s exciting about this.”

Turnkey system

Gaeta is impressed: “You can argue that microresonator combs have been the most active field in non-linear photonics in the past decade,” he says. “My work with Michal Lipson was the first real integrated system and these guys have made an another important step in further integrating it and making the system ‘turnkey’. It’s an important advance in taking this technology into the field.”

Meanwhile at Harvard University, Federico Capasso and colleagues focussed on creating frequency combs that operate in the mid-infrared region at 2.5-10 µm wavelength – a part of the electromagnetic spectrum in which molecules have unique spectral fingerprints. While quantum cascade lasers (QCLs) are readily available in this region, turning them into frequency combs has proven very difficult.

Surprising result

Capasso’s team investigated the possibility of producing a mid-infrared frequency comb from a quantum cascade ring laser, which behaves as its own microresonator when electrically injected. Traditional QCL frequency combs rely on bar-shaped cavities to create standing waves – something that does not happen in a symmetric ring cavity. So, the researchers added a defect to the ring to break this symmetry and allow standing waves to form. “Purely as controls, we put a few perfect rings on the chip,” explains Harvard’s Marco Piccardo. “To our surprise, these were also forming frequency combs…This is where we started scratching our heads.”

After much theoretical analysis of the laser physics, the researchers realized that the explanation lay in an instability in a non-linear differential equation called the complex Ginzburg-Landau equation, which describes spatially extended systems of coupled non-linear oscillators: “It’s not observed in bars,” says Piccardo, “The fact that a ring laser can go into this frequency comb regime is a new type of turbulent instability for quantum cascade lasers – although it’s been observed before in very different physical systems like superconductors and Bose-Einstein condensates.” The process happens in two stages: first, the single laser mode breaks up into a turbulent, unstable waveform. Eventually energy becomes concentrated in the harmonics of the original laser frequency, forming a frequency comb – albeit one with only around nine teeth.

“There is much, much more to do,” says Piccardo. “Plenty of interesting physics was so far shown to be restricted to the world of Kerr combs. I think all this can now be shown to be possible in QCLs and on this we just made a first step. I don’t think the two systems are competitors because they are going to impact on different spectral ranges, but I think we can learn from each other.”

Both Capasso’s and Bowers’ teams have described their results in Nature.

“Both these papers have in common the problem of trying to make devices that can be hooked up to a battery to produce a broadband comb source,” says Scott Diddams, who is at the National Institute of Standards and Technology in Boulder, Colorado and was not involved with either group. “The Bowers paper is much more about the nitty gritty of solving a hard problem that is going to make frequency combs prolific. The Capasso paper is an interesting, non-linear optical and general non-linear science result, but it will require additional engineering to increase the bandwidth to make it more useful for frequency comb spectroscopy.”

Exotic locales for alien life, meet a 16-year-old satellite scientist

Breakthrough Listen is an organization that searches for evidence of technological life by surveying one million nearby stars in the Milky Way as well as 100 nearby galaxies. The search has been going for five years and uses a wide range of radio and optical bands.

Needless to say, no definitive evidence of life has been found. In a bid to expand the scope of the search, Breakthrough Listen has come up with a catalogue of “Exotica”, which includes 700 distinct objects that will targeted in the search. The idea is to go beyond the usual targets of stars that could have Earth-like planets and look at “one of everything” in the observable universe.

The targets range from comets to galaxies as well as some of the most rare and violent celestial phenomena. Examples include Tabby’s Star, which has a bizarre dimming behaviour; and the interstellar object ’Oumuamua, which passed near Earth in 2017.

Cubestat scientist

Julie Sage runs experiments in space on cubesats and hosts a science news channel on YouTube – not bad for a 16-year-old. In this Via Satellite podcast, Sage talks about the challenges of being a young scientist, space exploration and communicating science to young people.

In the video below, Sage talks about Physics World‘s favourite crustacean: the mighty mantis shrimp.

In-line spectral monitoring gets ready to shine

Ocean Insight, a US manufacturer of specialist spectral systems, software and optical solutions, has high hopes for its Liquid Transmission Measurement System (LTMS), a spectroscopy-based unit for real-time, in-line optical monitoring of liquid concentration levels in a range of industrial plating, colouring and coating applications.

The modular system comprises a rugged optical sensing platform – spectrometer, control unit and machine-learning software – within a compact benchtop configuration that’s suitable for day-to-day deployment into harsh industrial environments. As such, the LTMS is able to generate high-precision colour and concentration measurements from the factory floor on a 24/7 basis, with flow-cell set-up and automatic fluid handling or built-in cuvette holder.

Right now, the LTMS is being sold directly into industry end-users and, once tailored to the customer’s requirements, comes ready to use “out of the box” in the manufacturing facility. “Alternatively, if the end-user has a preferred OEM integrator, the LTMS can be incorporated as part of their existing ‘smart factory system’, with or without fluid-handling capability,” explains Scott Scargle, director of strategic markets at Ocean Insight.

Getting the priorities right

Despite a myriad of potential LTMS applications, Ocean Insight’s near-term focus for the product is in the consumer electronics and food processing industries. Colour consistency of external parts – for Bluetooth speakers, MP3 players and the like – is a major pain-point in the consumer electronics supply chain, with batch-to-batch consistency of anodized aluminium being notoriously difficult to control.

Anodization is an electrolytic process to create a protective, anti-corrosion layer on the aluminium surface – a coating that can subsequently be dyed and decorated in a range of colours. Trouble is, anodization chemistry remains something of a black art, with colour materials and finishing (CMF) designers and contract manufacturers forced to work with wide colour tolerances and complex production processes.

Scott_Scargle-lores — Scott Scargle: “Our scientists and engineers create value in all sorts of ways.” (Courtesy: Ocean Insight)

If that’s the problem, the LTMS looks a lot like the answer. With its ability to measure solution concentrations in the anodization tank out on the factory floor, those CMF tolerances can actually get a lot tighter – which translates into enhanced repeatability, less scrap and streamlined product development cycles. “In short,” notes Scargle, “the LTMS gives the CMF designers a wider colour palette to choose from, while the contract manufacturers can make their parts with better consistency.”

In the food-processing industry, meanwhile, the LTMS is being lined up to support specialist coating applications on a range of foodstuffs. A case in point is the wax coatings that packing-houses apply to citrus fruits – typically to prolong the shelf-life and enhance the visual appeal of the fruit, also to act as a carrier for antifungal agents. “It’s a balancing act,” says Scargle. “The LTMS can be used to make sure concentration levels are within a certain tolerance to meet health and safety requirements, while high enough to maintain a level of effectiveness.”

Another use-case is the application of pesticides to food crops. Before a pesticide mix is applied in the field, for example, the LTMS is able to verify that the concentration falls within a window of acceptance to meet statutory safety guidelines. “Equally important,” adds Scargle, “the LTMS can be used to check the rinse water after the pesticide storage tank is cleaned, ensuring there are no unwanted residuals left behind that may end up being sprayed on crops later.”

Benefits and efficiencies

When it comes to customer upside, one of the big advantages of the LTMS is in-line deployment – a feature that makes it possible to more readily address quality issues as they occur. Consider an aluminium anodization coating tank, the electrolytes of which need to be analysed versus pass/fail criteria on a regular basis. Traditionally that testing has relied on expensive analytical equipment – for example, high-performance liquid chromatography (HPLC) – in a central laboratory (or more often an offsite testing facility for smaller contract manufacturers).

All of which is time-consuming, manually intensive and can mean significant process downtime while the results are pending. “The LTMS essentially eliminates that whole walk-to-lab workflow,” says Lu Luo, sales director at Ocean Insight and head of the company’s development facility in Rochester, New York. “It’s about the benefits of real-time, in-line diagnostics – the workflow and resource efficiencies plus greater process uptime – versus manually intensive and centralized lab testing.” What’s more, the LTMS workflow is such that scientific staff are no longer tied up on routine quality-control tasks. “It’s a portable unit and can be operated from a user-friendly interface by a technician,” Luo adds.

Lu_Luo-lores — Lu Luo: “The LTMS essentially eliminates that whole walk-to-lab workflow.” (Courtesy: Ocean Insight)

Another notable feature of the LTMS is the innovative use of machine-learning technology. Each customer gets a tailored system that’s “trained” for their specific optical sensing applications versus a number of chemical solutions. “The machine-learning models provide a direct answer on solution concentrations for pass–fail manufacturing decisions – either on the technician’s display or sent digitally to a central manufacturing execution system,” says Luo.

It’s a neat innovation that comes with in-built scalability. “Customers can step-and-repeat for different liquids and coating solutions, training new machine-learning models as they go and growing their database of models,” Luo adds.

Ultimately, the LTMS represents a further signal of intent from Ocean Insight as it seeks to reinforce its credentials as the “Applied Spectral Knowledge Company” across the photonics value chain – optical components, systems, software and industrial solutions. “We are a global optical solutions company – helping research customers to unlock new scientific insights and industry customers to deliver new commercial opportunities,” notes Scargle.

“Our scientists and engineers create value in all sorts of ways,” he concludes, “whether that’s feasibility testing through our lab services group; machine-learning advances from our Ocean Intelligence group; or custom product development in our solutions engineering team.”

Active rotation plays a role in the jamming–unjamming transition in living cells

New research offers insight into the role of rotation in the self-assembly of living cells. The work is described in Soft Matter and was done by Linda Ravazzano at the University of Milan under the supervision of Stefano Zapperi and in collaboration with Caterina La Porta’s research group.

Computer simulations and experiments with algae provided the team with information about the jamming and unjamming of cells at high densities. This research could lead to a better understanding of the differences between healthy and cancerous cells in human tissue.

The self-assembly of cells into tissues sits firmly at the interface of physics and biology. Cells are complex biological systems that sense changes in their environment and communicate with other cells, but they can also exhibit self-organization that is driven purely by thermodynamics.

Out of equilibrium

The motion of a cell (its motility) requires a constant input of energy and therefore motile cells exist out of equilibrium. Such systems of motile elements belong to the category of active matter. Startling dynamic behaviours have been observed in active systems, including motility induced phase separation and accumulation at solid boundaries. Most active matter research focuses on self-propulsion, but collective dynamics are also observed in systems of self-rotating particles.

C. reinhardtii is a single celled alga with a light sensitive eyespot, which scans its environment by rotating as it swims. Ravazzano and colleagues investigated the extent to which the collective behaviour of the algae can be reproduced by computer simulations of rotating disks. They then showed in simulation that rotation can induce jamming–unjamming transitions at high volume fractions.

Self- assembly of active particles is generally observed at high densities where interactions between the particles become significant. However, algae tend to aggregate in response to stress and so may behave collectively in dilute suspensions. The addition of sodium chloride to the medium induces the algae to form rotating clusters. This was also observed in simulations of disks subject to active torque, but only in the presence of adhesion between the disks. This indicates the significance of the stress induced aggregation and the active torque in the motion of the algae.

Active torque and jamming

The jamming transition occurs when, without crystallizing, a system of particles becomes so closely packed that it behaves as a solid. This phenomenon, which has been observed in living cells, generally occurs when the density of the system is increased.

C. reinhardtii cells do not exhibit jamming at high density, because when they become crowded, their motility increases. Ravazzano and colleagues suggest that the active rotation of the algae increases in response to crowding, which opposes jamming.

This hypothesis was tested in simulation by preparing the disks with zero propulsion at the passive jamming volume fraction and increasing the rotation. A transition from a jammed to an unjammed state at a threshold torque was observed. Though more research on the response of the algae is needed, it is evidently possible for active torque to trigger unjamming.

The addition of self-propulsion to the model complicates the self-assembly behaviour. As the torque is increased, the system first jams and then unjams. The explanation offered by the Milan team is that a crossover between propulsion and rotation determines the behaviour of the algae.

At low torques, the self-propelled particles avoid jamming because they move coherently, but the rotation randomizes their motion and they undergo jamming as it is increased. At higher torques, the rotation dominates over self- propulsion and the unjamming transition is observed as before.

The outlook

In their paper describing the study, the researchers highlight the similarities between the jamming transition of the disks and the change from a solid to liquid like state observed in healthy versus cancerous cells. They also remark on the “possible role for rotations in collective cell migration,” and give the observed formation of vortices in confined epithelial cells as an example.

Men and women go separate ways: why inquiry-based labs exacerbate gender imbalance

Laboratory sessions that are designed to emphasize and teach experimentation skills lead to gender imbalances among students, with men and women taking on different roles. That is according to a study by researchers in the US, which found no significant differences in role division in more traditional labs that attempt to reinforce lecture content (Phys. Rev. Phys. Educ. Res. 16 010129).

In their study, the researchers observed students enrolled in a mechanics class as part of a calculus-based physics course. Students attended the same lectures, but two different lab courses: one set up to reinforce knowledge introduced elsewhere on the course, and the other designed to teach experimentation skills. In the traditional lab sessions students were given instructions of experimental procedures and worksheets to complete. However, the experimentation lab students were expected to make decisions about the design and analysis of their experiments. The study included 143 students: 109 men, 32 women and two students who did not disclose their gender.

To assess the roles students took, the researchers observed the lab sessions at five-minute intervals, noting what each student was handling. The choice was a desktop computer, lab equipment, a personal laptop, a notebook or “other” – a broad category designed to ensure all student time was accounted for. In the inquiry-led labs men systematically handled the equipment more, while video analysis showed that women spent about twice as much time as men on laptops.

The study also revealed that students rarely discussed the roles they would assume, and there were no instances of students being explicitly allocated roles by other group members or lab instructors. The researchers suggest that the differences they saw are driven by subtle verbal and non-verbal interactions at the individual level that accumulate to create class-level patterns.

Lead author Natasha Holmes from Cornell University says that it is unclear if there are negative implications from this finding, but it needs to be explored. It could, she explains, reinforce gender stereotypes, which is concerning in a field like physics that has significant diversity issues. “If looking around the room you see that all the male students are handling the equipment what sort of message is that sending?” Holmes told Physics World. “There is a risk that there are implications down the line for students’ feelings of whether they belong.”

Holmes and her colleagues have previously highlighted the benefits of inquiry-led labs, showing that they boost student engagement. Indeed, she says there is “overwhelming evidence that traditional labs are unproductive”. The team says that this latest work does not distract from this, but shows that active steps need to be taken when redesigning lab courses to ensure gendered roles are not reinforced. In particular, inquiry-led labs, with the work structure removed, attention needs to be paid to the group dynamics.

Cellular nanosponges could neutralize SARS-CoV-2

The research community around the world has never been more engaged in developing treatments for a new disease than it has for COVID-19. The Liangfang Zhang research group at the University of California San Diego, working in collaboration with the Anthony Griffiths research group from Boston University School of Medicine, is no exception.

Reporting their findings in Nanoletters, the research teams have jointly demonstrated a unique approach that might stop SARS-CoV-2, the COVID-19 virus, from infecting human cells.

Cellular decoys

The researchers have developed two types of cellular nanosponge that bind to SARS-CoV-2 before it can enter human cells. These nanosponges consist of polymeric nanoparticles covered with membranes from one of the two human cell types that are known to be invaded by the virus, namely lung epithelial cells and macrophages. This means that the surfaces of the nanoparticles feature the exact same receptors and proteins that the virus would normally bind to. In a sense, the nanosponges act as cellular decoys by mimicking human cells and therefore offering alternative binding sites to SARS-CoV-2.

Nanosponges schematic — Schematic of the working principle of the nanosponges. Polymeric nanoparticles are cloaked with human cell membranes so that SARS-CoV-2 is surrounded by the nanosponges before it can enter any host cell. (Courtesy: *ACS Nanoletters* 10.1021/acs.nanolett.0c02278)

The key idea is to deploy many of these nanosponges, so that they can surround the virus, effectively soaking it up before it can enter any host cell. And if the virus cannot enter a cell, it cannot replicate and is neutralized, therefore preventing the spread of the infection to the rest of the body.

The researchers first tested the preliminary safety of the fabricated nanosponges in mouse models. They found that a 3-day exposure to both types of nanosponge did not damage the animals’ lung tissue. In addition, blood markers as well as platelets, red and white blood cell counts were not negatively affected, therefore ruling out any short-term toxic effects.

Next, the team tested the efficacy of the nanosponges in vitro, by exposing monkey cell cultures to the virus in the presence of the nanosponges. Both types of nanosponge reduced the infectivity of SARS-CoV-2 in a dose-dependent manner, with the best result leading to a reduction of up to 90% compared with non-treated cultures.

A treatment for COVID-19?

These nanosponges might represent a unique solution to the race for a treatment of COVID-19. They are relatively easy to fabricate, and come with the added benefit of being insensitive to viral mutations and potentially applicable to other types of coronavirus.

“Because the cellular nanosponges are not targeting a specific virus, as other drugs normally do, these sponges are potentially agnostic to viral mutations and viral species. As long as the virus still attacks human lung epithelial cells or human macrophages, these nanosponges can bind to the virus and neutralize it,” says senior author Liangfang Zhang.

Zhang adds that the team is now focused on testing the efficacy of these nanosponges in appropriate animal models of COVID-19. If the data are positive, they will advance the nanosponges towards human clinical trials.

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