IGCAR work may allow doctors to ‘see’ a fever

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Zaibudeen (left) and John Philip have developed a thermally tunable ferrofluid grating to measure body temperature.

Visual, non-invasive monitoring of body temperature of patients in hospitals without using a thermometer may become a reality thanks to the work carried out by a team of scientists led by Dr. John Philip, Head of the SMART section at the Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam near Chennai. The concept is based on ferrofluid emulsion contained in a thin film that changes colour with rise in temperature within a narrow range — 30-40 degree C. The results were published in the journal Optical Materials.

The emulsion has iron oxide nanoparticles-containing oil droplets dispersed in water. The stimuli-responsive materials change in their properties to stimulus such as stress, temperature, moisture, or magnetism. “Till now ferrofluid was used as a magnetic stimuli-responsive material and we have come up with several applications such as hermetic seal, optical filters and defect detection. We now found that in the presence of a temperature-sensitive polymer — poly(N-isopropylacrylamide or PNIPAM) — the ferrofluid emulsion can be used as a thermally tunable grating to produce different colours,” says Dr. Philip.

“Recently, we were looking at the interaction forces between droplets covered with thermoresponsive polymers. To our surprise, we found that the adsorbed polymer swells and collapse upon changing the temperature between 32 and 36 degree C. This change was clearly manifested as colour change. From this observation came the novel idea of using PNIPAM-stabilized emulsions as a multistimulii grating. This is a first-of-its-kind approach where the grating spacing can be tuned either by changing the temperature or by changing the magnetic field strength,” says Dr. Philip.

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When the temperature rises, the monomers come closer together, changing the colour from orange to yellow.

Up to about 34 degree C, the polymer is highly hydrated and swollen due to repulsive interaction between individual monomer segments. But when the temperature crosses 34 degree C, the polymer becomes dehydrated leading to a collapsed state (due to inter and intra attractive forces between monomers). The polymer can once again become hydrated and swollen when the temperature falls below 34 degree C. “By using certain additives, we can tune the collapse of the polymer to higher temperature to reflect fever conditions,” clarifies A.W. Zaibudeen, senior research fellow and the first author of the paper.

Using magnetic field, the scientists first achieved a particular ordering (spacing between the arrays of emulsion droplets) of emulsion and got a specific colour. When the polymer is added as a stabiliser and the temperature is increased the grating spacing of the polymer changes and gives rise to a different colour or spacing.

“The colour given off at normal temperature can be fixed by changing the emulsion property and magnetic field strength,” Dr. Philip says. If yellow is chosen to represent normal temperature, it will change to green when the temperature increases. Colour with higher wavelength is produced at lower temperature and colour of lower wavelength at higher temperature.

The researchers see numerous applications for their gratings — visual manifestation of environmental conditions (temperature and humidity) and selection of a particular colour from white light. In addition, there other potential specialised applications such as calorimetric sensors, photonic materials, optical devices and drug delivery systems. “I believe that once the proof of concept is demonstrated, the scientific community would come up with many more new ideas for practical applications,” Dr. Philip says.

Published in The Hindu on April 11, 2017

IIT Bombay uses mango leaves to make fluorescent graphene quantum dots

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The quantum dots that Mukesh Kumar Kumawat (left) and Rohit Srivastava have fabricated can be used for bioimaging and temperature measurement.

Using mango leaves to synthesise fluorescent graphene quantum dots (nanocrystals of semiconductor material), researchers from the Indian Institute of Technology (IIT) Bombay have been able to produce cheap probes for bioimaging and for intracellular temperature sensing.

Unlike the currently used dyes, quantum dots synthesised from mango leaves are biocompatible, have excellent photostability and show no cellular toxicity. The results were published in the journal ACS Sustainable Chemistry & Engineering.

To synthesise quantum dots, the researchers cut mango leaves into tiny pieces and froze them using liquid nitrogen. The frozen leaves were crushed into powder and dipped into alcohol. The extract was centrifuged and the supernatant evaporated in an evaporator and then heated in a microwave for five minutes to get a fine powder.

Using mice fibroblast cells, a team led by Prof. Rohit Srivastava from the Department of Biosciences and Bioengineering at IIT Bombay evaluated the potential of quantum dots for bioimaging and temperature sensing applications. In mice cell in vitro studies, the graphene quantum dots were able to get into the cells easily without destroying the integrity, viability and multiplication of the cells. The quantum dots get into the cytoplasm of the cell.

The quantum dots, 2-8 nanometre in size, were found to emit red luminescence when excited by UV light. “Even when the excitation wavelength was 300-500 nanometre, the emission from the quantum dots was at 680 nanometre. The quantum dots exhibited excitation-independent emission,” says Mukeshchand Thakur from the Department of Biosciences and Bioengineering at IIT Bombay and one of the authors of the paper.

Since the quantum dots get into the cytoplasm of the cell, they can be used for cell cytoplasm labelling applications.The quantum dots have smaller and larger fluorescent units. When the excitation is at lower wavelength, the smaller units transfer energy to the larger units and there is red emission. And when the excitation is at higher wavelength, the red emission comes directly from the larger units, thus remaining excitation-independent.

“Since the quantum dots get into the cytoplasm of the cell, they can be used for cell cytoplasm labelling applications,” says Mukesh Kumar Kumawat from the Department of Biosciences and Bioengineering, IIT Bombay and the first author of the paper.

The quantum dots found inside the cells showed intense florescence at 25 degree C. As the temperature rises to 45 degree C, the intensity of fluorescence tends to decrease. As a result, the researchers found up to 95% reduction in fluorescence intensity when the temperature was increased by 20 degree C. “So quantum dots can be used for detecting temperature variation in the intracellular environment,” says Thakur.

“The graphene quantum dots can be used as a nanothermometre. Besides measuring intracellular temperature increase, they can be used for measuring temperature increase in cancer cells and when there is inflammation,” says Prof. Srivastava. “We are seeing interest by companies making imaging probes. There is also interest to use it as temperature probes.”

“Since the quantum dots emit red light, they can be used for making organic light-emitting diodes as well,” says Kumawat.

Published in The Hindu on April 8, 2017

IIT Madras researchers prove the superiority of arsenic water filter which got $18 million funding

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AVULA ANIK KUMAR AND OTHERS FROM IIT MADRAS SHOWED THAT THE AMOUNT OF ARSENIC LEACHED FROM A SATURATED FILTER WAS FAR LESS THAN THE BACKGROUND CONCENTRATION.

An exhaustive research carried out by a team of researchers led by Prof. T. Pradeep from the Department of Chemistry at the Indian Institute of Technology (IIT) Madras, spread over four years has put to rest the scepticism about the merits of the arsenic water filter developed by them. The water filter has been in operation for three and half years in about 900 sites in India serving close to 400,000 people.

Arsenic in drinking water is the largest natural mass poisoning in the history of humanity, affecting 13 crore people globally. The problem of arsenic in the environment, known for over 102 years, has not been solved satisfactorily, due to the non-availability of appropriate and affordable materials. Arsenic is a slow poison causing numerous health effects, including cancer and genetic anomalies.

The IIT technology makes use of confined metastable 2-line iron oxyhydroxides and its large adsorption capacity to remove arsenic in two different dissolved forms (arsenate and arsenite).  The filter was able to reduce the arsenic concentration in the water from 200 ppb to well below the WHO limit of 10 ppb. The results were published recently in the journal Advanced Materials.

“The arsenic removal capacity of the material filter was found to be 1.4 to 7.6 times better than all the other available materials,” says Prof. Pradeep. “The superior arsenic uptake capacity is due to its inherent structure. Nanostructured iron oxyhydroxide makes many sites available for arsenic uptake. The ions of arsenic adsorb on the nanoparticles at specific atomic positions. No nanoparticles are released into the purified water due to the biopolymer cages in which they are contained.”

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The team has now tested a three-stage water filter for domestic use. The output water contained arsenic and iron below the WHO limit.

The team mimicked the average arsenic concentration seen in West Bengal — 200 ppb of arsenic — for carrying out several laboratory studies. Though studies were carried out at a pH of 7.8, the team found the adsorption capacity of the filter was not compromised in the pH range 4 to 10. “The pH of drinking water is in the range of 6.5 to 8.5.  But we tested the filter in a wide range of pH so it can be used for other purposes as well,” says Prof. Pradeep.

“A filter composed of 60 grams of the material can be used safely for removing arsenic (200 ppb) from 1150 litres of water and till such time the concentration of arsenic in the filtered water does not cross the WHO limit of 10 ppb,” he says. Once the filter has reached its saturation limit it has to be reactivated or recharged with new material.

Reactivation is done by soaking the material in sodium sulphate solution for an hour at room temperature. It is further incubated for about four hours after reducing the pH to 4. “Using this reactivation protocol we reused the same filter seven times,” he says.

Studies were carried out to test if the adsorbed arsenic leached from the filter. The team found that the amount of arsenic that got leached was 1 ppb in the case of arsenite and 2 ppb for arsenate. “Soil in the affected regions also contains arsenic, typically around 12 ppb of arsenic, which is the background concentration. The amount of arsenic leached from the saturated filter was far less than the background concentration,” Prof. Pradeep says. Leaching of arsenic from disposed filters was one of the biggest criticisms by a few researchers who had worked on arsenic filters. Arsenic, being an element, cannot be degraded further to simpler species.

Since the arsenic filter developed by the team has so far been in use at a community level, studies were carried out to test its performance as a domestic water filter. A domestic three-stage filter was developed to remove particulate matter, iron and arsenic. Input water containing 200 ppb of arsenic and 4 ppm of Fe(III) was passed through the filter for a total volume of 6,000 litres (translating to 15 litres of water per day for one year). “The output was below the WHO limit for both arsenic and iron throughout the experiment,” he says.

“For a family of five, arsenic-free drinking water can be produced at $2 per year,” he says.

In the course of the development of this technology, he and his former students incubated a company, InnoNano Research Pvt. Ltd. at IIT Madras. In July this year, the company received venture funding to the tune of $18 million.

“With this research, a home grown technology appears to be all set for global deployment. Knowledge is no more a limiting factor for solving the arsenic menace,” he said.

Related Stories:

With $18 million venture funding, IIT Madras Prof breaks the glass ceiling

IIT Madras: Affordable water purification using silver nanoparticles

Published in The Hindu on December 18, 2016

Chennai researchers turn leather waste into electrode-grade carbon

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Niketha Konikkara (left) and Dr. John Kennedy of VIT University in Chennai have produced excellent porous electrode material using leather solid waste as the starting material.

Researchers at the Vellore Institute of Technology (VIT) University, Chennai have successfully converted leather solid waste (wet blue leather splits) containing chromium (III) into porous carbon matrix for use as electrodes in supercapacitors using a simple, sequential, two-step process. This approach not only yielded “excellent porous electrode material for supercapacitors”, but also effectively addressed the management of chromium-containing leather solid waste, which is considered to be the major issue of leather manufacturing industry. The results were published in the Journal of Hazardous Materials.

Chromium (Cr) is widely used in leather tanning to as it imparts toughness to leather. Though Cr(III) present in leather waste is not toxic, it can undergo spontaneous oxidation into Cr(VI), which is toxic. The conventional disposal methods, such as land filling and incineration, cannot be considered as an ideal way of disposing the waste in an eco-friendly manner.

“The prime constituent of leather is collagen fibre. So we thought of converting the collagen fibre into carbon fibre without oxidising the Cr(III) to Cr(VI),” says Dr. L. John Kennedy from the Physics Division – Materials, School of Advanced Sciences, VIT University, Chennai and the corresponding author of the paper.

As a first step, the leather waste was precarbonised by heating it for four hours at 400 degree C. The precarbonised material was soaked in potassium hydroxide overnight and then heated at higher temperature in an inert atmosphere to produce porous carbon that contains inter-connected nanopores of all three sizes — micropores (less than 2 nm), mesopores (2-50 nm) and macropores (over 50 nm). Since the carbon contains all the three types of pores, it is called hierarchical porous carbons (HPCs).

The pores of different sizes are formed by pore drilling and pore widening due to the combined effect of potassium hydroxide and temperature. In addition to pore formation, graphitic stable carbon structure is also formed. The chromium present in the leather induces graphitisation in the carbon material; the graphitic content present in the material improves its electrical conductivity property. “We are not only taking care of chromium disposal, the metal actually improves the property of the carbon,” he says.

Hierarchical porous carbon is considered as a promising material for making electrodes that can be used in supercapacitor devices.

The three types of interconnected pores in the hierarchical porous carbon have very different roles in making the carbon as a good electrode material. While the micropores enhances the electrical double layer formation, the mesopores provides ion-transport pathways with low resistance, and the macropores serve as ion-buffering reservoirs to reduce the diffusion distance.

At 900 degree C, the specific capacitance value was 1960 Farad per gram using one molar of potassium chloride electrolyte; the specific capacitance value was less at lower temperatures. “The mesopore volume increases with increasing temperature and this leads to higher specific capacitance,” Dr. Kennedy says.

As the hierarchical porous carbon is highly porous and has higher surface area adequate ions diffuse into the inner pores of the electrode material. Since more ions are adsorbed on these electrodes unlike in normal electrodes, the charge storage capacity becomes higher.

“We have explored and proved the potential of converting hazardous leather waste to an excellent electrode material for energy storage device concept,” he says.

Published in The Hindu on November 27, 2016

IIT Madras researchers with a Midas touch, on a nanoscale

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(From left) Prof. T. Pradeep, K.R. Krishnadas, Atanu Ghosh, Ganapati Natarajan (standing) and Ananya Baksi (not in the photo) transformed nanoparticles of silver to gold.

In a breakthrough, a team of researchers from the Indian Institute of Technology (IIT) Madras has successfully transformed nanoscale pieces of silver to gold and gold to silver by replacing their atoms one at a time. The shape and structure of these materials before and after transformation are identical, although they are completely different chemically. The result were published today (November 10) in the journal Nature Communications.

“This is like transforming a silver Nataraja sitting on your table to a gold equivalent, by atom-by-atom changes. Although this is possible only in the nanoscale, that too with limited systems today, there is a hope that such changes can occur in the macroscopic world in future” says Prof. T. Pradeep, from the Department of Chemistry, IIT Madras and the corresponding author of the paper.

When nanoparticles of gold and silver, which have different mass but identical atomic arrangements, are mixed in solution at room temperature an atom by atom replacement takes place. Within a few minutes the silver nanoparticle becomes a gold nanoparticle and the gold nanoparticle becomes a silver nanoparticle. Generally, nanoscale materials are more reactive as they have higher energy compared with bulk matter.

A structure of gold just becomes another identical structure of silver or vice versa. No principle of science is violated.“If changing objects atom by atom is easily possible, tomorrow we can produce novel alloys that might have very different, unknown properties,” says Prof. Pradeep.

“This is not the medieval magic of converting everything to gold. Here, gold does not become silver. Instead, a structure of gold just becomes another identical structure of silver or vice versa. Number of atoms of gold and silver are the same. No principle of science is violated,” he says. “We are only creating conditions such that one structure transforms to another.”

During such transformations, alloys of different compositions of gold (Au) and silver (Ag) are formed. For instance, when silver nanoparticle composed of 25 atoms react with a gold nanoparticle composed of 25 atoms, one atom from the silver nanoparticle is replaced with one atom of gold particle, to form an AuAg24 alloy. The silver atom removed from the silver nanoparticle in turn takes the place of the gold atom in the gold nanoparticle to form an AgAu24 alloy.

As the reaction proceeds, the number of atoms of one metal in an alloy keeps increasing while the other metal keeps decreasing. In other words, the gold-rich alloy gradually gets richer in silver, and by successive single atom changes it becomes a pure silver nanoparticle. Similarly, the silver-rich alloy gradually becomes richer in gold and becomes a pure gold nanoparticle.

This chemistry occurs between a 25-atom piece of gold protected by molecular groups called ligands and a corresponding silver piece composed of 25 atoms of silver and the same number of ligands. These two nanoparticles, also called clusters, are made separately in solution.

Various alloys can be made and their composition can be controlled by controlling the ratio of the two clusters used. “The properties of alloys with different composition could be very new. We do not know what such capabilities give us,” he says. “The most fascinating aspect of this science is that it demonstrates the molecular nature of nanoscale matter.”

Related stories and links:

IIT Madras researchers’ cheaper solution to make brackish water potable

With $18 million venture funding, IIT Madras Prof breaks the glass ceiling

IIT Madras: A novel way to produce safer drinking water

IIT Madras: Affordable water purification using silver nanoparticles

IIT Madras: Graphene nanoribbons produced by a novel method

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Published in The Hindu on November 10, 2016

IISER Kolkata makes targeted delivery of cancer drug possible

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Dr. Sayan Bhattacharyya (left) and Sutanu Kapri have covalently bound cancer drug to nanospheres to deliver it inside only cancerous cells.

Targeted delivery of anticancer drugs exclusively to cancer cells and controlled release of the drugs in a sustained manner inside cancer cells has been achieved by a group of researchers from the Indian Institute of Science Education and Research (IISER) Kolkata. Porous carbon nanospheres about 150 nm in diameter and packed with drugs inside the pores has been designed in such a way that they cannot get inside normal cells and kill them. The results were published in the journal Carbon.

A team led by Dr. Sayan Bhattacharyya from the Department of Chemical Sciences, IISER Kolkata, used the commonly available lemon grass to synthesise the porous carbon nanospheres, which act as drug carriers. “It’s a very simple and cheap process to produce carbon nanospheres from lemon grass. Also, it is possible to scale up the production,” Dr. Bhattacharyya says.

The anticancer drug doxorubicin is covalently bound both inside the 3.6-3.8 nm diameter pores and also on the surface of the nanospheres. “Since the inside of the cancer cell is acidic (pH 5.5-6), the hydrazone covalent bond gets broken slowly to release the drug. As normal cells have a neutral pH the covalent bonds are less likely to be broken and therefore the drug cannot be released,” says Sutanu Kapri from the Department of Chemical Sciences, IISER, Kolkata, and the first author of the paper. “Also, in the presence of acidic environment, a proton gets added to the amine group of the drug and helps in the release of the drug from the pores.”

The checks and balances in targeted delivery ensures that negligible amount of cancer drug is available inside normal cells.To make the targeted delivery nearly fail-proof, the researchers attached folic acid to the nanospheres. The folic acid attaches to the folate receptors found on the surface of cancer cells and the nanospheres gain entry into cancer cells. Normal cells contain very few folate receptors and so nanospheres are nearly prevented from getting inside. Due to poor folate expression in normal cells, even after 15 hours, the amount of drug available inside normal cells was negligible compared with cancerous cells.

“The efficiency of nanospheres to get inside healthy cells will be less compared with cancerous cells. The larger the size of particles, the slimmer the chances of getting inside cells,” says Dr. Sankar Maiti from the Department of Biological Science, IISER, Kolkata, and one of the authors of the paper, while explaining how the relatively large (150 nm) nanospheres selectively target only the cancerous cells.

All these checks and balances ensure that drug release is minimal inside the healthy cells. In contrast, conventional chemotherapy is not designed to target only the cancerous cells. As a result, cancer treatment tends to kill more of healthy cells than cancerous cells.

Controlled release

Besides targeted delivery, the researchers had designed the nanospheres for controlled release of the anticancer drug. “Usually, there is a sudden burst of drug inside cancerous cells. But we can control the release of the drug inside cancerous cells over a 24-48-hour period, useful for clinical applications. This is mainly because the drug is chemically trapped inside the pores of the nanocarriers,” says Dr. Bhattacharyya.

Since the nanospheres contain numerous pores, the surface area increases, and a greater quantity of drug can be loaded inside the nanocarriers. Unlike when drugs are physically adsorbed on the surface of a nanocarrier, there is slim possibility of premature release of the drug into blood when the drug is bound to a nanocarrier.

Compared with freely available anticancer drug, the researchers found that the quantity of drug carried by nanospheres was 10 times more inside cancerous cells. Though nanocarriers cannot enter the nucleus, higher doses of the drug ended up inside the nucleus after 15 hours.

“So nanocarriers can effectively deliver drug in a controlled manner at targeted sites only if they have a porous structure, the drug remains inside pores and is covalently bound to nanospheres and is released only when the pH is acidic,” says Dr. Bhattacharyya.

Published in The Hindu on October 22, 2016

BHU researchers use laser to remove blood clots

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Prof. Debabrata Dash (sitting) and Nitesh Singh were able to easily disintegrate blood clots by combining photothermal ablation with streptokinase (a drug-dissolving drug) at 30-50 times less than the therapeutic dosage.

It is now possible to remove blood clots in a less risky way, thanks to research carried out by scientists at the Institute of Medical Sciences, Banaras Hindu University, Varanasi.

A team led by Prof. Debabrata Dash from the Department of Biochemistry  has for the first time used photothermal therapy using near-infrared (NIR) laser and NIR-absorbing gold nanorods to disintegrate freshly formed clots and clots formed a few hours ago. The disintegration of clots was accelerated when the therapy was combined with clot-dissolving drugs given at 30-50 times less than the therapeutic dosage. The results were published in the journal Nano Research.

There is an inherent risk of severe bleeding, haemorrhagic stroke and embolism when clot-dissolving drugs such as streptokinase are used at therapeutic dosages.  So the drug is generally administered only under medical supervision.

“Though we have studied freshly formed clot and clots that are a few hours old, the combination therapy should be effective even for aged clots,” says Prof. Dash, who is the corresponding author of the paper. “Since the near-infrared laser can penetrate up to a few centimetres depth, it can be used for treating blood clots present in superficial veins.”

How it works

When a clot forms, fibrin monomers are held together by weak noncovalent bonds. After some time, the clotting factor XIII forms covalent bonds that cross-links the monomers and stabilises the clot.

“We reasoned that heat supplied locally to the clot should loosen the noncovalent interaction between fibrin strands, thus facilitating reduction in the clot mass,” says Prof. Dash.

Heat (50-55 degree C) supplied locally to the clot for 45 minutes using near-infrared laser and gold nanorods led to nearly 18 per cent reduction in the clot mass. Since anti-fibrin antibodies are ligated on the surface of gold nanorods, the nanoparticles would get attached to the fibrin-rich blood clots when injected into the blood. So the heating would largely be localised to the area where the clot is present.

Photothermal ablation used in combination with low-dose of streptokinase led to nearly 21 per cent lysis in fresh clots.“We focussed on non-covalent interaction. When we exposed the fibrin to near-infrared laser, heat generated locally led to disruption of the non-covalent bonds resulting in loosening of the strands and a reduction in the size of the clot. This allows clot-busting drugs like streptokinase to easily get inside the clot and break it down,” says Nitesh Singh from the Department of Biochemistry, Institute of Medical Sciences at BHU and the first author of the paper.

In the case of in vitro studies, photothermal ablation used in combination with low-dose of streptokinase led to nearly 20 per cent lysis in clots that were more than three hours old; the disintegration was 21 per cent in the case of fresh clots.  Since pressure from flowing blood is seen in arteries and veins the extent of clot disintegration should be higher when thermal ablation and chemotherapy is combined with fluid pressure seen in blood vessels. Indeed, nearly 41 per cent disintegration under arterial blood flow pressure and 19.5 per cent under venous pressure condition were seen in in vitro studies.

The team replicated the study in mice. Freshly induced clots in the femoral vein of mice were irradiated with laser and treated with sub-therapeutic dose of streptokinase. From being completely occluded, normal blood flow in the vein was restored after the combination treatment. “Vein tissues examined under microscope showed ‘significant reduction’ in the extent of blockage after laser irradiation. Clot clearance improved further when combination treatment was used,” says Singh.

“Our work on mice was to test if the combination therapy was effective against clots. We will be studying the amount of clot reduction in future studies,” Singh says.