Biocompatible drug delivery for rheumatoid arthritis

by Hansraj Agrawal | May 13, 2023 | Science

A newly synthesised biocompatible therapeutic nano-micelle drug delivery system, combined with anti-inflammatory drugs, has shown improved potential to cure rheumatoid arthritis at the lab level. It can help ameliorate the pain associated with the condition as well as heal by restoring cartilage integrity to provide flexibility to the bone.

Inflammation plays an important role in the development of rheumatoid arthritis. As a result, treatment strategies have largely focused on providing symptomatic relief from pain, and a permanent cure is not available to date.

Methotrexate (MTX) is considered a gold standard therapy for the condition, but due to its severe side effects researchers are looking for alternative drugs or strategies.

Scientists from the Institute of Nano Science and Technology (INST), Mohali, explored the potential of the USFDA-approved anti-inflammatory drug 9-aminoacridine (9AA) and the natural compound caffeic acid, generally found in coffee or wine (reported to possess significant anti-arthritic potential), conjugated to nano-micelles — an amphiphilic molecule that forms a spherical structure when immersed in water — for the treatment of rheumatoid arthritis.

A research group led by scientist Dr Rehan Khan, along with senior research fellow Akshay Vyawahare, has developed a therapeutic nano-micelle loaded with anti-inflammatory drug 9AA.

When administered, it shows site-specific inhibition of inflammatory mediators due to the activation of the NR4A1 gene (nuclear receptor sub-family 4 group A member 1), which regulates inflammatory mechanism by inhibiting pro-inflammatory cytokines through fluorescent 9AA.

The nano-micelle itself has potential to provide therapeutic effect, but when combined with anti-inflammatory drug, it showed enhanced potential to cure rheumatoid arthritis experimentally by inhibiting joint damage and cartilage degradation, says a press release.

Near-infrared OLEDs

Researchers at IISER, Bhopal, have created a new family of organic molecules that emit light in the near-infrared (NIR) range, opening possibilities for OLEDs for various applications. Led by Prof Jeyaraman Sankar, the team’s research marks a significant breakthrough in the field, as developing NIR-emitting OLEDs has been a challenging endeavour worldwide.

The team’s new approach to obtaining stable electron-deficient molecules with NIR emission using nitration as a strategy is unique, says a press release.

Light-emitting diodes or LEDs are tiny light-emitting devices that are commonly used in applications such as television screens, gadget displays, and so on.

They are different from traditional filament bulbs, as bulbs emit light when heated, but LEDs emit light when electricity (in the form of electrons) passes through them. OLEDs are a form of LEDs where the light emitting materials are organic molecules — chemicals largely made of carbon and hydrogen.

Although visible light-emitting OLEDs have already found mass application in displays for gadgets, televisions, and lighting, producing NIR-emitting OLEDs is challenging due to their unique molecular energy structure. Light-emitting molecules generate light when electrons fall from a high-energy state (HOMO) to a low-energy state (LUMO) inside the molecule, and the colour of the emitted light depends on the energy difference between the two states. The energy difference in organic molecules corresponds to visible light, making visible light-emitting OLEDs easier to design.

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IIT-M scientists develop improved flow battery technology

by Hansraj Agrawal | May 13, 2023 | Science

Where space is not a constraint, flow batteries are deemed to be good energy storing devices. In conventional batteries, energy is stored in solid electrodes. In flow batteries, the storage of energy is in liquid redox electrolytes, which can be kept in tanks outside the cells — if you want to store more energy, you just make the tanks bigger. They can indeed be as big as you want, there is no limit. If you want more power, you only have to increase the number of cells or stack size.

Flow batteries have been around for some time, but industry is increasingly looking to them for applications such as storing electricity to handle the intermittency issue in solar and wind farms or maintaining grid stability.

In countries like Australia, where people live in far-flung areas, flow batteries are fast replacing conventional diesel gensets.

Researchers the world over are trying to improve the performance of flow batteries. In this, a team of scientists led by Prof Kothandaraman Ramanujam and Prof Sankararaman S, Department of Chemistry, Indian Institute of Technology, Madras, have developed a ‘non-aqueous all-organic redox flow battery’ (NORFB), which promises improved performance.

Conventional flow batteries feature aqueous (water-based) electrolytes like hydrochloric acid, sulphuric acid, and alkali metal hydroxides, which bring forth two problems. One, the water interferes by undergoing electrolysis and, therefore, reducing the operating voltage limit and energy density (amount of energy packed per unit volume or gram); and two, they corrode battery components.

Thus, as an alternative, researchers have been looking for electrolytes that are non-aqueous and organic.

The IIT-M researchers have developed a new type of electrolyte using ‘pyrylium salts’, which are a class of organic chemicals.

Technically, with suitable structural modifications these chemicals allow high-voltage operation, namely they can store more energy. Ramanujam told Quantum that the team achieved current densities of 40 mA/sq cm, which is pretty high (as the redox materials were charged and acting as conducting medium). The team used ‘2-, 4-, 6-triphenylpyrylium tetrafluoroborate’ as the anolyte, and ‘N-decylphenothiazine’ as the catholyte. Ramanujam said these chemicals can be produced easily and are cheap.

The electrolyte is designed to carry more current density as well as voltage. The battery has been demonstrated with an average coulombic efficiency of 97 per cent.

While the anolyte material offers high solubility and reversibility, it is not as stable as desired. However, re-engineering the molecule can impart the desired stability.

A scientific paper by Ramanujam, Sankararaman and their student Priya Vallayil in the Journal of Energy Storage concludes that pyrylium salts are a “new family of anolyte material that can be used as a potential anolyte for non-aqueous flow battery applications”.

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Furry supermodel

by Hansraj Agrawal | Apr 29, 2023 | Science

In 1925, diphtheria — a disease that can be fatal in children — broke out in Nome, Alaska. Serum containing antibodies had to be rushed to the remote town. The task fell upon a sled driver and his team of dogs. The sled drove for about 1,100 km in five-and-a-half days, under punishing conditions of blizzard and white-out, delivered the medicine, and saved many lives.

One of the heroic sled dogs was Balto, whose legendary energy is reminiscent of the canine Buck in Jack London’s The Call of the Wild, recently made into a Harrison Ford movie. Balto, incidentally, has been immortalised in a sculpture that stands in Central Park, New York.

Recently, a bunch of scientists led by Katherine Moon, a geneticist at the University of California, Santa Cruz, decided to study Balto’s DNA from the dog’s taxidermy remains. Apart from determining that Balto was more genetically diverse than most dogs of today, they also figured out how he looked. Balto, according to them, stood 21.7 inches tall and had a double layered coat of fur that was mostly black with a little white. Their findings agree well with the few photographs available of Balto. It is a marvel of science that a relic of a dead cell can tell so much.

Elaine Ostrander, a dog geneticist who was not part of Moon’s study, told Science magazine that Balto’s genes could be a blueprint for promoting healthier dogs today.

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Why this Tata Steel experiment made the world take notice

by Hansraj Agrawal | Apr 29, 2023 | Science

It was a tiny experiment, but it made the world sit up and take notice.

Because, if taken to fruition, it has the potential to replace up to 20 per cent of the coke used in steel making with hydrogen — a very big deal in reducing carbon dioxide emissions.

On April 23, Tata Steel announced that it successfully injected a small quantity of hydrogen into one of its blast furnaces (6 kg per tonne of hot metal, for four days). Globally, only two such attempts have been reported before. The first was a 2015 Japanese project called Course50, which involved indirect injection of hydrogen in the form of coke oven gas. The other was a 2021 experiment at the German company Thyssenkrupp, where 0.5 kg of hydrogen per tonne of hot metal was injected for a few hours. Neither compares with what Tata Steel did in scale or duration.

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“It was a resounding success,” Dr Debashish Bhattacharjee, Vice-President (Technology and R&D), Tata Steel, told Quantum. The experiment generated “enormous amounts of data”, he said, adding that it graduated “from pen-and-paper to real life”.

Given the grave concerns over climate change, replacing carbon dioxide-emitting coke with hydrogen has become the holy grail of the steel industry, which, according to the International Energy Agency, emitted some 2.8 billion tonnes, or about 7 per cent of the global emissions of the greenhouse gas from energy use in 2020.

Debashish Bhattacharjee, Vice-President (Technology and R&D), Tata Steel

On paper it is easy. Carbon in coke pulls oxygen away from iron ore to leave behind pure iron; hydrogen does just the same, but with no greenhouse gas emissions. The problem, however, is that the world has invested billions of dollars in building huge blast furnaces to make steel.

Blast furnaces don’t care how little iron there is in the ore, so you can use low-grade ores (which are predominant in India). But putting hydrogen into blast furnaces is fraught with difficulties. Hydrogen needs external energy (endothermic) and the reactions inside the blast furnace are very different, leading to issues of structural stability. (It is easier to use hydrogen with the electric arc furnace, but these require high-grade ores.)

“As long as you have blast furnaces, you would need coke,” says Bhattacharjee.

While you can’t replace coke with hydrogen in a blast furnace, you can replace a part of it, and keep increasing that part till you cannot do it any more — that is, until the structural stability becomes an unavoidable issue.

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Tata Steel (indeed the global steel industry) knows that the way forward is to replace as much coke as possible with hydrogen (preferably, green hydrogen) and deal with the attendant carbon dioxide emissions through other means, such as fixing the gas in some useful compound or burying it underground.

A global first

Tata Steel’s experiment is a significant step in that direction because, for the first time, this quantity of hydrogen (though not green) has been injected into a live blast furnace for four days. The experiment has “added to our knowledge”, says Bhattacharjee. “We know what to look for, which sensors to use, what will work, and what will not work.”

He stresses that the safety issues are equally important. Hydrogen, which can catch fire, must be handled with care. Tata Steel has learned to check for leaks using helium. During the experiment, there was no safety-related incident.

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Tata Steel is currently doing a lot of data crunching — hence it does not wish to give out more details, but once the technology is mastered, it is possible to replace a fifth of the coke used today with hydrogen.

It is learnt that the global steel industry has been asking the company for more information about the experiment.

Meanwhile, Tata Steel is also experimenting with other furnace charges, such as biochar, coal-bed methane and coke oven gas (like the Japanese).

At the other end, Tata Steel is trying to neutralise the unavoidable carbon dioxide emission by injecting it into cooling towers, where the gas becomes carbonates of calcium or magnesium, which can be slagged off and sold.

Also read: Robust domestic demand boosts Tata Steel, JSW Steel output

HIsarna project

‘HIsarna’ is the name that Tata Steel has chosen for the radically different route of steel making it has invented, at its Netherlands plant. It uses coke, but the gas that comes out of the furnace has a high concentration (80 per cent) of carbon dioxide, making it amenable to capture and neutralisation.

At present, Tata Steel has a small pilot plant in The Netherlands, but Bhattacharjee says that the company will put up a “demonstration plant” in India that is five-times the size of the one in The Netherlands.

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New quantum material for superfast data transmission

by Hansraj Agrawal | Apr 29, 2023 | Science

A recent chance discovery of a quantum material can have far-reaching implications in quantum computing and superfast data transmission.

Brewing a mixture of manganese and tin in quartz tubes, followed by gradual cooling, led to a mixture of compounds that may possibly be able to host small and energy-efficient information cells. These information cells have the potential to develop high-density, low-power, and multi-functional devices for memory and logic applications.

Researcher Achintya Low of the SN Bose National Centre for Basic Sciences, Kolkata, brewed a mixture of manganese and tin powder in 7:3 proportion, sealed it in an evacuated quartz tube at 1,000 degrees C for 24 hours, and cooled the mixture very slowly.

When sufficiently cooled, the quartz tubes were transferred to a centrifuge to separate the crystals from the residue. The crystals were tiny but visible to the naked eye. The chemical composition of these crystals was supposed to be three manganese atoms to one tin atom per unit cell.

‘Energy dispersive X-ray spectroscopy’ showed that some crystals had a ‘defect’ — instead of three manganese atoms, they had 2.8 or 2.65 manganese atoms to one tin atom per unit cell.

The researchers suggested that the crystals with 2.8 manganese atoms per unit cell were highly likely to host magnetic skyrmions — the small and energy-efficient information cells that have the potential to develop high-density, low-power, and multi-functional devices for memory and logic applications.

Memory devices built with skyrmions are likely to replace hard disc devices because of their reliable mechanical stability, faster addressing time, and higher storage density. Thus the crystals with 2.8 manganese atoms per unit cell will find application in quantum computing and superfast data transmission, says a press release.

Portable uric acid detector

A new flexible bio-electronic uric acid detecting device has been fabricated for various applications such as wearable sensors and point-of-care diagnostics.

Uric acid is one of the most important antioxidants that maintain blood pressure stability and reduce oxidative stress in living beings.

The usual range of uric acid in blood is 0.14-0.4 millimole per cubic decimetre, and for urine 1.5-4.5 millimole per cubic decimetre.

However, fluctuating uric acid levels due to lack of balance between its production and excretion cause diseases like hyperuricemia, which in turn may lead to gout disease, type 2 diabetes, increased risk of cardiovascular diseases, Lesch–Nyhan syndrome, hypertension, and renal disorders.

Researchers at the Institute of Advanced Study in Science and Technology (IASST) fabricated a device made of reduced phosphorene quantum dots — a new class of zero-dimensional functional nanostructures with unique physicochemical and surface properties. The quantum dots show distinctive electrical performance in biomedical applications and can be used in fabricating high-performance electrical biosensors.

The fabricated device shows reversibility in interaction with uric acid, which enables repeat use of the device for sensing experiments. It outperforms all currently available devices in effectiveness and cost because it doesn’t need any enzymes.

The response of the fabricated device was investigated with samples like human blood serum and artificial urine. The device is simple, portable, cost-effective, and easy to fabricate for detecting uric acid, says a press release.

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A chip off the AI block

by Hansraj Agrawal | Apr 29, 2023 | Science

Memory and processing being two separate pieces of hardware was never a big deal — until now. With the advent of artificial intelligence and its branches, machine learning and deep neural network, more time and energy is needed for information to jump back and forth between ‘processing’ and ‘memory’, and is therefore avoidable.

Scientists are investigating ways of unifying processing and memory, leading to a new branch of electronics called ‘in-memory computing’. A ‘deep neural network’ could have millions of nodes organised into layers to perform a certain computation from input data. Any unification of logic and memory would be a big help.

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Bhaswar Chakrabarti, an assistant professor in the department of electrical engineering, Indian Institute of Technology, Madras, is among the scientists investigating how to unify processing and memory. “I have always been intrigued by ‘memory’,” Chakrabarti told Quantum, “both in humans and machines.” So, he embarked on designing a memory chip that can offer an “alternative computational paradigm” with higher performance and energy efficiency.

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Among the various in-memory computing hardware, the one that Chakrabarti found particularly interesting was the ‘content-addressable memory’ (CAM). Basically, when you search a memory device to retrieve information, you don’t search by the ‘address’ and instead go straight into the ‘content’. CAM, therefore, “is a promising candidate for wide application in data-intensive, high-performance search operations”, he says.

Chakrabarti began designing a CAM that would be useful in applications such as network routing, CPU caching and deep learning. His idea was to use a special type of transistor that is the in-thing in the electronics industry today, the ‘ferroelectric field effect transistors’ or FeFET. (Transistors are a part of an electronic circuit, where they amplify and regulate the flow of electricity in the circuit.) The FeFETs are made using a compound called indium gallium zinc oxide, and they “are being vigorously investigated for deployment in in-memory computing”. Chakrabarti sourced FeFETs from the Fraunhofer Institute of Germany, which collaborated in the research effort.

Chakrabarti has designed a new CAM cell using FeFET transistors which, he says, “significantly improves density and energy efficiency compared with conventional ‘complementary metal-oxide-semiconductor’-based cells. To illustrate, the design uses eight times fewer transistors than the conventional ones.

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Chakrabarti and his fellow scientists have published a paper on their research in Applied Electronic Materials. “Simulation shows that the proposed CAM has sufficient decision range to perform the search operations. We have also demonstrated the impact of retention degradation on the feasibility of the multi-bit operation in IGZO-based CAM cells. Our proposed CAM is highly promising for energy-efficient in-memory computing platforms, compared with other solutions, because of its simple one FeFET−one transistor architecture and multi-bit operation,” the paper says.

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Chakrabarti says there is still work needed before a chip based on this design can be deployed in industry. Memory arrays would need to be developed and peripherals would need to be tweaked to sync with this new type of chip. Nevertheless, the new CAM is a breakthrough in the area of electronics in the era of artificial intelligence.

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