World’s first fibre optic ultrasonic imaging probe for future nanoscale disease diagnostics

Scientists at the University of Nottingham have developed an ultrasonic imaging system, which can be deployed on the tip of a hair-thin optical fibre, and will be insertable into the human body to visualise cell abnormalities in 3D.

The new technology produces microscopic and nanoscopic resolution images that will one day help clinicians to examine cells inhabiting hard-to-reach parts of the body, such as the gastrointestinal tract, and offer more effective diagnoses for diseases ranging from gastric cancer to bacterial meningitis.

The high level of performance the technology delivers is currently only possible in state-of-the-art research labs with large, scientific instruments — whereas this compact system has the potential to bring it into clinical settings to improve patient care.

The Engineering and Physical Sciences Research Council (EPSRC) -funded innovation also reduces the need for conventional fluorescent labels — chemicals used to examine cell biology under a microscope — which can be harmful to human cells in large doses.

The findings are being reported in a new paper, entitled ‘Phonon imaging in 3D with a fibre probe’ published in the journal, Light: Science & Applications ("Phonon imaging in 3D with a fibre probe”)

Paper author, Salvatore La Cavera, an EPSRC Doctoral Prize Fellow from the University of Nottingham Optics and Photonics Research Group, said of the ultrasonic imaging system: “We believe its ability to measure the stiffness of a specimen, its bio-compatibility, and its endoscopic-potential, all while accessing the nanoscale, are what set it apart. These features set the technology up for future measurements inside the body; towards the ultimate goal of minimally invasive point-of-care diagnostics.”

Currently, at the prototype stage, the non-invasive imaging tool, described by the researchers as a “phonon probe”, is capable of being inserted into a standard optical endoscope, which is a thin tube with a powerful light and camera at the end that is navigated into the body to find,  analyse,  and operate on cancerous lesions, among many other diseases. Combining optical and phonon technologies could be advantageous; speeding up the clinical workflow process and reducing the number of invasive test procedures for patients.

3D mapping capabilities

Just as a physician might conduct a physical examination to feel for abnormal ‘stiffness’ in tissue under the skin that could indicate tumours, the phonon probe will take this ‘3D mapping’ concept to a cellular level.

By scanning the ultrasonic probe in space, it can reproduce a three-dimensional map of stiffness and spatial features of microscopic structures at, and below, the surface of a specimen (e.g. tissue); it does this with the power to image small objects like a large-scale microscope, and the contrast to differentiate objects like an ultrasonic probe.

“Techniques capable of measuring if a tumour cell is stiff have been realised with laboratory microscopes, but these powerful tools are cumbersome, immobile, and unadaptable to patient-facing clinical settings. Nanoscale ultrasonic technology in an endoscopic capacity is poised to make that leap,” adds Salvatore La Cavera.

The optical fibre imaging sensor has a diameter of 125 micrometres approximately the size a human hair. Читать запись полность. »

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Researchers found potential new nanoparticles to treat brain cancer

Researchers reported a comprehensive investigation of a promising type of nanoparticle that could potentially be used for intractable brain cancers in combined therapy. The study, which was led by Dr Moeava Tehei and researchers from the University of Wollongong in combination with clinical partners, characterised and evaluated the properties of nanoparticles made from lanthanum manganite, that were doped with silver atoms. The investigators found that the nanoparticles had a potential clinical application for their synergistic effects to be used in combination with radiation treatment, hyperthermia (using heat to kill cancer cells) and their intrinsic toxicity to cancer cells. The research was published in Materials Science & Engineering C («First extensive study of silver-doped lanthanum manganite nanoparticles for inducing selective chemotherapy and radio-toxicity enhancement»). Nanoparticles are small enough to cross the blood-brain barrier that prohibits other therapies. In addition to a wide variety of other methods of analysis, studies of the magnetic properties were undertaken at ANSTO. The magnetic properties were important because they could be used to get the nanoparticles to the target cancer site and in magnetic hyperthermia treatment. Dr Kirrily Rule, a co-author on the paper, supervised investigations of magnetic and chemical changes to nanoparticles of silver-doped lanthanum manganite at two temperatures on the high-resolution powder diffractometer Echidna at ANSTO’s Australian Centre for Neutron Scattering. Although an expert in the magnetic behaviour of low-dimensional materials with quantum properties, Rule said she was excited by the opportunity to change focus and assist in medical physics-related research. The magnetic behaviour of the nanoparticles at two temperatures was important to the study because the magnetic properties of the silver-doped nanoparticles change at different transition temperatures. The magnetism measurements on Echidna were performed at 10 degrees Kelvin and 300 Kelvin. At about 300 degrees Kelvin, close to body temperature, the magnetic ordering stops. “There is a critical temperature region for hyperthermia treatment,” said Rule. The magnetisation results indicated that the nanomaterial was more likely to order ferromagnetically and that the ordering temperature when the magnetic moments aligned, was higher for a higher percentage of silver. “So, it appears that the silver was responsible for the higher transition temperatures of these nanoparticles,” said Rule. The most promising sample for hyperthermia and cancer toxicity was lanthanum manganite that was doped with a 10 per cent concentration of silver, as it retained a level of ferromagnetism at 300 degrees Kelvin. However, Dr Tehei said that the 5 per cent doping may turn out to be the most interesting when combined with radiation because of its selectivity and cancer toxicity. This suggested to the investigators that the temperature range for hyperthermia treatments could be manipulated by modifying the doping percentage. Importantly, the biological effects of the nanoparticles and doped nanoparticles were toxic to cancer cells but not the normal cells. The research helped elucidate how the doped nanoparticles were killing cancer cells by producing high levels of reactive oxidative stress. Source: ANSTO,  Nanowerk News,  Apr. 16, 2021

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Building mRNA vaccines for COVID19

Building mRNA vaccines for COVID-19
Coronaviruses invade cells through surface molecules called spike proteins (named for the fact that they physically jut out from the rest of the virus), which take on different shapes in different coronaviruses. The SARS-CoV-2 specific spike protein is therefore a crucial antigen – i.e. a substance that induces the immune system to produce antibodies against it – that can be exploited for vaccine design.
And this is how an mRNA vaccine against COVID-19 works: Once the virus genome is sequenced – that means it is available as a digital copy – researchers can design an mRNA sequence that encodes the blueprint for the virus spike protein. Once tested for efficacy and safety in clinical trials, the mRNA molecule can then be synthesized on an industrial scale in robotic factories.
This mRNA molecule is wrapped with a lipid nanoparticle envelope, which protects it from degradation, and then directly delivered into cells. There, ribosomes get to work and read the mRNA as just any other blueprint – only this time they synthesize the spike protein. The finished spike proteins are then attached to the surface of cells where they are recognized by the immune system, eventually triggering the desired immune response against the virus.In other words: Once you get your vaccine jab, the genetic instructions contained in the mRNA molecules are injected into the upper arm and the ribosomes in the muscle cells translate them to make a critical fragment of the viral protein directly inside your body. This 'preview' of what the real virus looks like gives the immune system time to design powerful antibodies that can neutralize the real virus if it ever gets in contact with it.The protein production inside the muscle cells initiated by the injected mRNA injection reaches peak levels for 24 to 48 hours and can last for a few more days. Thereafter, the mRNA molecules get disassembled by the body.

The revolutionary impact of mRNA technology

mRNA COVID-19 vaccines have demonstrated in a very convincing way that biotechnologies have entered the industrial age. What we are seeing here is nothing less than the rise of bio platforms that give us the ability to engineer bits of biology, such as mRNA, to create programmable medicines and vaccines.

More generally, if it is indeed possible that mRNA can be used to make the full set of proteins in life, then it becomes possible to treat an incredible broad range of human diseases. This is at the core of the industrialized platforms that Moderna, BioNTech and others are building.

Essentially, an mRNA technology platform functions very much like an operating system on a computer. It is designed so that it can plug and play interchangeably with different programs. In this case, the 'program' or 'app' is the unique mRNA sequence that codes for a specific protein.

mRNA as the technological basis for therapeutics and vaccines is characterized by a great flexibility with respect to production and application. In essence, mRNA is an information-carrying molecule that can be industrialized – as opposed to traditional therapeutic molecules that have to be elaborately designed and synthesized from scratch for each application (i.e. medicine).

For starters, mRNA molecules are far simpler than proteins. mRNA is manufactured by chemical rather than biological synthesis, so it is much quicker than conventional vaccines to be redesigned, scaled up and mass-produced.

An excellent primer on the development of mRNA-vaccine technologies explains why: «Any protein can be encoded and expressed by mRNA, in principle enabling the development of prophylactic and therapeutic vaccines fighting diseases as diverse as infections and cancer as well as protein replacement therapies.»

And this is very the disruptive effect of the mRNA platform happens: If a therapy requires a certain protein to be encoded, only the sequence of the messenger RNA molecule needs to be changed, leaving its physicochemical characteristics largely unaffected. In the above computer analogy, that is like writing a new piece of software that runs on the same operating system.

The disruptive force of emerging bio platforms

This means that diverse products can be manufactured using the same established production

process – the same equipment, the same operators – without any adjustment and thereby saving massive amounts of time and money compared with other vaccine or therapeutics platforms. Читать запись полность. »

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Role of nanotechnology in the race to find a Covid-19 vaccine

Today I would like to acquaint readers of my blog with a summary of the data published on the site Nanowerk about the role of nanotechnology in the race for the Covid-19 vaccine.

Nicole Steinmetz, professor of nanoengineering at UC San Diego and corresponding author on the study, spoke with Nanowerk about the findings in this paper. Steinmetz believes “it is an exciting time for nanotechnology and nanoparticle delivery of nucleic acid-based vaccines and subunit vaccines are poised to make an impact.”

The COVID-19 pandemic has left the world reeling following its inception in Wuhan, China. While global efforts are being directed towards a vaccine, thus far none have passed the trial stage. Until humanity achieves herd immunity to this virus, either through exposure and infection or through inoculation, there can be little hope of our returning to our pre-COVID-19 life.

Fortunately, there are over two hundred academic laboratories and companies around the world searching for a vaccine, and the pace at which they are progressing is unprecedented. One nanotechnology formulation achieved clinical trials a month prior to other conventional approaches. However, due to the stiff regulatory requirements on vaccines to ensure safety, there remain various hurdles that companies must surmount in order to establish a viable vaccine.

Nanotechnological approaches have received a boost despite their lack of clinical trials. As an example, mRNA vaccines have been developing for thirty years but were not previously approved. Due to the adaptability of such technology, prior vaccine candidates can be repurposed using previously developed nanostructures.

Nanoparticles and viruses operate on the same scale, and thus there are various nanotechnological aides which are being used in the development of potential vaccines. Nanoparticles are capable of entering the cell through biological channels, and can deliver antigens there. Antigens are typically delivered via either lipid nanoparticles (LNPs), which encapsulate the antigens, or via other benign viruses including Ads.

Due to the scale of nanoparticles, they are capable of traveling in vivo differently than other molecules. The lymphatic system, which is critical in orchestrating immune responses, has typically proved challenging to access. However, with the advent of nanoparticles, previously inaccessible pathways have become accessible, with certain trial vaccines attempting to use these to transport antigens.

Besides delivering antigens themselves, nanoparticles can also be enlisted to provide adjuvants to cells. Adjuvants effectively catalyze the immune response, allowing the cell to more easily recognize and respond to antigens. Encapsulating both the antigen and adjuvant in the same envelope provides for better-targeted delivery and response from the cell.

The presence of adjuvants may also reduce the amount of antigen required to engender a response, and thus render a dose-sparing effect. This dose-sparing may drive the cost of immunization down, and render wide-spread inoculations more feasible. Without co-delivery of adjuvants and antigens, antigens are more likely to break down in the body. Читать запись полность. »

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Nanostructured surface inactivates SARS-CoV-2 coronavirus within six hours

While the number of bacterial and viral infections has been steadily rising, the emergence of the novel Covid-19 pandemic has caused a surging demand for antimicrobial treatments that can keep surfaces clean, particularly in health care settings. However, all of these surfaces and coatings have been developed to combat bacteria but not to kill off viruses.

Quite surprisingly, so far the effect of nanostructured surfaces on viruses has never been investigated.

In new work reported in ACS Biomaterials Science & Engineering («Antiviral Nanostructured Surfaces Reduce the Viability of SARS-CoV-2»), researchers from the Centre for Biomedical Technologies at Queensland University of Technology have successfully produced durable antiviral surfaces that inactivate SARS-CoV-2 within 6 hours.

In contrast, on various non-nanostructured surfaces or smooth surfaces, the SARS-COV-2 virus remained viable for up to 48 hours.

«Our results provide evidence that surfaces that are structured with specific nanoscale surface features are effective in preventing SARS-CoV-2 and the subsequent environmental spread,» Jafar Hasan, the paper's first author, tells Nanowerk. «Such nanostructured surfaces can be used in hospital environments such as trolleys, bed-rails, door-knobs, etc. These surfaces can be extended to other industrial sectors and public infrastructure such as transportation, where fomites or contaminated surfaces are carriers for viral infections.»

This research has grown out of earlier work (ACS Biomaterials Science & Engineering, «Antiviral and Antibacterial Nanostructured Surfaces with Excellent Mechanical Properties for Hospital Applications») where the team, led by Prof. Prasad K.D.V. Yarlagadda, showed that nanoscale topography can kill and inactivate a wide range of bacteria and viruses. Читать запись полность. »

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Combatting COVID-19 at the nano level

Today I bring to your attention a very recent report on the application of nanotechnology for the manufacture of masks against COVID-19. I want to share new interesting data with my readers, so I am giving a message completely without any changes. The message has a title “Combatting COVID-19 at the nano level”. It was published in the Nanowerk News.

Copper, a metal commonly used throughout history for its antibacterial properties, is being utilized by researchers at IUPUI’s Integrated Nanosystems Development Institute to solve a problem very relevant today: making reusable face masks safer and more comfortable for daily use.

“We wondered how we could use our existing technology to turn something used in ancient times, like copper, into protection against COVID-19,” said Mangilal Agarwal, director of the Integrated Nanosystems Development Institute and professor of mechanical and energy engineering. “Any virus sitting on the surface that comes in contact with copper will be killed because of the antiviral properties.”

Agarwal and Hamid Dalir, associate professor, are applying a patented technology developed at IUPUI to manufacture reusable face masks using copper, a metal often used in the production of high-touch objects like doorknobs and handles. Their goal is to improve filter performance by trapping and disabling airborne virus particles.

“These masks have copper oxide applied at the nano level and would offer ultimate protection against virus risks like COVID-19,” Agarwal said. “Some cloth masks allow the small airborne particles to pass through, but with our technology, it would be close to 100% proof that you have the capability incorporated in the mask to deactivate the virus and improve filter performance.”

The technology – initially developed at IUPUI to make composite materials cheaper, lighter and stronger using nanomaterials – could be used to coat household masks with a layer of fabric protection inlaid with copper nanoparticles that disable virus particles as they reach the surface. The general public would be able to wear a reusable mask that offers the same superior level of protection as masks worn by healthcare providers, such as N95 masks.

“To make any fabric into a mask or filter, we have to provide the nanostructure, and we can put that nanostructure on a roll-to-roll printing machine with the fibers at nanoscale,” Agarwal said. “We are using electrospinning, using the electric field to spray the nanofibers onto the fabric.”

Agarwal and Dalir disclosed their technology to the Indiana University Innovation and Commercialization Office, and are looking to commercialize it through their startup. They plan to work with local companies manufacturing COVID-19 supplies under the Defense Protection Act.

Beyond face masks, the technology can be applied to other methods for fighting COVID-19, such as HEPA filters found in HVAC systems. Without good filters, Agarwal said, airborne virus particles could circulate between indoor areas. By applying the copper material to the filters, there could be virus free air circulation in buildings and hospitals.

“Our technology is good for masks and filters because we are not changing the manufacturing process,” Dalir said. “We just get the rolls of the mask and filter, manufacture and enhance it with copper-coated fabric and then use it as it would be used conventionally.”

Their company, Multiscale Integrated Technology Solutions, was recently selected as one of five Hoosier startup winners of the Elevate Nexus Statewide Pitch Competition, a program designed to support Indiana startups.

“Elevate Nexus is being funded by a grant from the U.S. Economic Development Administration and the 21st Century Research and Technology Fund to help startups that have shown potential for commercialization to get connected with entrepreneurs to build on existing operational strategies," Dalir said. "What we're trying to do is raise the existing entrepreneurship support vehicles as well as attract investment in our startup at an earlier level so that we can have the opportunity to further grow and cultivate new investors as we de-risk our venture.”

The commercialization of their technology has the potential to greatly impact lives here in Indiana and around the world – providing a safe solution against the spread of COVID-19.

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Carbon nanotubes pave the way for human breath analysis of lung disease

 

Point-of-care health monitoring is still a challenging technology under development. Various sensors can be integrated into wearable devices for the monitoring of different health parameters like temperature and pulse rate. However to provide deep health analyses and a prediction for the existence of disease still requires the use of complicated diagnostic tools like MRI, computer tomography, etc, or body liquids analysis from blood, saliva, etc.

Breath is one of the main sources of human health parameters that can be used for predicting the state of different internal organs. Exhaled breath composition is very complex and the existence of disease marker molecules can be as low as 1 ppm (one part per million). That means that using breath for health monitoring purposes requires highly sensitive tools with a recognition ability down to single molecules.

Among a number of methods for breath analysis, the most promising one is based on the concept of an electronic nose. Here, the task for certain disease pattern recognition is moves from hardware to software using advanced methods of data analysis. This concept provides both miniaturizations of sensor designs and fast response times. Yet the development of sensor platforms that provide high sensitivity to the informative molecules with high humidity background in the exhaled breath is still challenging.

A team of researchers from Università Cattolica del Sacro Cuore (Italy), Skolkovo Institute of Science and Technology (Russia) and National Research University of Electronic Technology (Russia), has developed a method for fast, on-site and still accurate breath analysis that does not need special preparation of breath samples. The method is based on an electronic nose platform that uses a set of single-walled carbon nanotube (SWCNTs) sensors deposited on flexible substrates and modified by different semiconducting organic molecules. Carbon nanotubes are widely used for electronic nose development because of their high sensitivity to environmental gases, high stability, and intrinsic variations in electronic properties that make them perfect for use in electronic nose platforms. The researchers suggested improving the recognition properties of the SWCNT sensors by additional functionalization that increases the sensors' specificity to different gases, making sub-ppm analysis possible.

The researchers demonstrated the performance of this method by analyzing Various gases and vapors (ammonia, ethanol, acetone, 2-propanol, sodium hypochlorite, benzene, hydrogen sulfide, and nitrogen dioxide). The sensitivity was demonstrated down to 0.25 ppm for each nanotube sensor area of about 1 cm2 with high level of discrimination between gases. The best detection limit was demonstrated for ammonia for nanotubes covered by PANI molecules and hydrogen sulfide for CNT covered by TCTA molecules of 0.014 and 0.064 ppm, respectively.

Moreover, the team demonstrated that these sensors can be used for chronic obstructive pulmonary disease (COPD) recognition based on breath analyses of 21 individuals. Advanced data analysis methods based on principle component analyses provided a clear distinction between subjects with and without COPD.

The research team, led by Prof. L. Sangaletti, has demonstrated the high performance of their proposed sensing platform in-breath recognition with relatively fast response times without the need for complicated breath treatment. In the case of COPD, they observed that the analysis can be improved by properly targeting the molecules specific to the decease.

The main benefit of such an electronic nose platform is the possibility of future miniaturization and integration on a chip compatible with conventional microelectronics technologies, paving the way for on-site analysis using smartphones.

This project was funded in part by the ANAPNOI project (Catholic University of the Sacred Heart) and the Russian Science Foundation.

Nanowerk May 13, 2020

A Nanowerk exclusive provided by National Research University of Electronic Technology

 

 

 

 

 

 

 

 

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