Tag Archives: University of Connecticut

Iron oxide nanoparticles for artificial skin with super powers

A January 28, 2019 news item on ScienceDaily describes the possibilities for a skin replacement material,

A new type of sensor could lead to artificial skin that someday helps burn victims ‘feel’ and safeguards the rest of us, University of Connecticut researchers suggest in a paper in Advanced Materials.

Our skin’s ability to perceive pressure, heat, cold, and vibration is a critical safety function that most people take for granted. But burn victims, those with prosthetic limbs, and others who have lost skin sensitivity for one reason or another, can’t take it for granted, and often injure themselves unintentionally.

Chemists Islam Mosa from UConn [University of Connecticut], and James Rusling from UConn and UConn Health, along with University of Toronto engineer Abdelsalam Ahmed, wanted to create a sensor that can mimic the sensing properties of skin. Such a sensor would need to be able to detect pressure, temperature, and vibration. But perhaps it could do other things too, the researchers thought.

“It would be very cool if it had abilities human skin does not; for example, the ability to detect magnetic fields, sound waves, and abnormal behaviors,” said Mosa.

A January 22, 2019 UConn news release (also on EurekAlert but dated January 28, 2019), which originated the news item, give more detail about the work,

Mosa and his colleagues created such a sensor with a silicone tube wrapped in a copper wire and filled with a special fluid made of tiny particles of iron oxide just one billionth of a meter long, called nanoparticles. The nanoparticles rub around the inside of the silicone tube and create an electric current. The copper wire surrounding the silicone tube picks up the current as a signal. When this tube is bumped by something experiencing pressure, the nanoparticles move and the electric signal changes. Sound waves also create waves in the nanoparticle fluid, and the electric signal changes in a different way than when the tube is bumped.

The researchers found that magnetic fields alter the signal too, in a way distinct from pressure or sound waves. Even a person moving around while carrying the sensor changes the electrical current, and the team found they could distinguish between the electrical signals caused by walking, running, jumping, and swimming.

Metal skin might sound like a superhero power, but this skin wouldn’t make the wearer Colossus from the X-men. Rather, Mosa and his colleagues hope it could help burn victims “feel” again, and perhaps act as an early warning for workers exposed to dangerously high magnetic fields. Because the rubber exterior is completely sealed and waterproof, it could also serve as a wearable monitor to alert parents if their child fell into deep water in a pool, for example.

“The inspiration was to make something durable that would last for a very long time, and could detect multiple hazards,” Mosa says. The team has yet to test the sensor for its response to heat and cold, but they suspect it will work for those as well. The next step is to make the sensor in a flat configuration, more like skin, and see if it still works.

Here’s a link to and a citation for the paper,

An Ultra‐Shapeable, Smart Sensing Platform Based on a Multimodal Ferrofluid‐Infused Surface by Abdelsalam Ahmed, Islam Hassan, Islam M. Mosa, Esraa Elsanadidy, Mohamed Sharafeldin, James F. Rusling, Shenqiang Ren. Advanced Materials DOI: https://doi.org/10.1002/adma.201807201 First published: 28 January 2019

This paper is behind a paywall.

A ‘vascular running of the bulls’; nanoparticles in your bloodstream

An Oct. 5, 2016 news item on phys.org announces research into how nanoparticles behave in the bloodstream (Note: A link has been removed),

Researchers at the University of Connecticut have uncovered new information about how particles behave in our bloodstream, an important advancement that could help pharmaceutical scientists develop more effective cancer drugs.

Making sure cancer medications reach the leaky blood vessels surrounding most tumor sites is one of the critical aspects of treatment and drug delivery. While surface chemistry, molecular interactions, and other factors come into play once drug-carrying particles arrive at a tumor, therapeutic medication doesn’t do very much good if it never reaches its intended target.

Anson Ma, an assistant professor of chemical and biomolecular engineering at UConn, used a microfluidic channel device to observe, track, and measure how individual particles behaved in a simulated blood vessel.

The research team’s goal: to learn more about the physics influencing a particle’s behavior as it travels in our blood and to determine which particle size might be the most effective for delivering drugs to their targets. The team’s experimental findings mark the first time such quantitative data has been gathered. …

“Even before particles reach a target site, you have to worry about what is going to happen with them after they get injected into the bloodstream,” Ma says. “Are they going to clump together? How are they going to move around? Are they going to get swept away and flushed out of our bodies?”

Using a high-powered fluorescence microscope in UConn’s Complex Fluids Lab, Ma was able to observe particles being carried along in the simulated blood vessel in what could be described as a vascular Running of the Bulls [emphasis mine]. Red blood cells race through the middle of the channel as the particles – highlighted under the fluorescent light – get carried along in the rush, bumping and bouncing off the blood cells until they are pushed to open spaces – called the cell-free layer – along the vessel’s walls.

Nanocarrier particles injected into the bloodstream bounce off red and white blood cells and platelets, and are pushed toward the blood vessel walls. This physical interaction, measured and quantified for the first time by engineering professor Anson Ma’s lab, provides important information for drug developers. (Image courtesy of Anson Ma)

Nanocarrier particles injected into the bloodstream bounce off red and white blood cells and platelets, and are pushed toward the blood vessel walls. This physical interaction, measured and quantified for the first time by engineering professor Anson Ma’s lab, provides important information for drug developers. (Image courtesy of Anson Ma)

An Oct. 4, 2016 University of Connecticut news release, which originated the news item, provides more detail about the research,

What Ma found was that larger particles – the optimum size appeared to be about 2 microns – were most likely to get pushed to the cell-free layer, where their chances of carrying medication into a tumor site are greatest. The research team also determined that 2 microns was the largest size that should be used if particles are going to have any chance of going through the leaky blood vessel walls into the tumor site.

“When it comes to using particles for the delivery of cancer drugs, size matters,” Ma says. “When you have a bigger particle, the chance of it bumping into blood cells is much higher, there are a lot more collisions, and they tend to get pushed to the blood vessel walls.”

The results were somewhat surprising. In preparing their hypothesis, the research team estimated that smaller particles were probably the most effective since they would move the most in collisions with blood cells, much like what happens when a small ball bounces off a larger one. But just the opposite proved true. The smaller particles appeared to skirt through the mass of moving blood cells and were less likely to experience the “trampoline” effect and get bounced to the cell-free layer, says Ma.

Ma proposed the study after talking to a UConn pharmaceutical scientist about drug development at a campus event five years ago.

“We had a great conversation about how drugs are made and then I asked, ‘But how can you be sure where the particles go?’” Ma recalls, laughing. “I’m an engineer. That’s how we think. I was curious. This was an engineering question. So I said, ‘Let’s write a proposal!’”

The proposal was funded by the National Science Foundation’s Early-concept Grants for Exploratory Research or EAGER program, which supports exploratory work in its early stages on untested, but potentially transformative, research ideas or approaches.

Knowing how particles behave in our circulatory system should help improve targeted drug delivery, Ma says, which in turn will further reduce the toxic side effects caused by potent cancer drugs missing their target and impacting the body’s healthy tissue.

The findings were particularly meaningful for Ma, who lost two of his grandparents to cancer and who has long wanted to contribute to cancer research in a meaningful way as an engineer.

Measuring how particles of different sizes move in the bloodstream may also be beneficial in bioimaging, where scientists and doctors want to keep particles circulating in the bloodstream long enough for imaging to occur. In that case, smaller particles would be better, says Ma.

Moving forward, Ma would like to explore other aspects of particle flow in our circulatory system, such as how particles behave when they pass through a constricted area, such as from a blood vessel to a capillary. Capillaries are only about 7 microns in diameter. The average human hair is 100 microns.  Ma says he would like to know how that constricted space might impact particle flow or the ability of particles to accumulate near the vessel walls.

“We have all of this complex geometry in our bodies,” says Ma. “Most people just assume there is no impact when a particle moves from a bigger channel to a smaller channel because they haven’t quantified it. Our plan is to do some experiments to look at this more carefully, building on the work that we just published.”

Here’s a link to and a citation for the paper,

Direct Tracking of Particles and Quantification of Margination in Blood Flow by Erik J. Carbon, Brice H. Bognet, Grant M. Bouchillon, Andrea L. Kadilak, Leslie M. Shor, Michael D. Ward, Anson W.K. Ma. Biophysical Journal Volume 111, Issue 7, p1487–1495, 4 October 2016  DOI: http://dx.doi.org/10.1016/j.bpj.2016.08.026

This paper is behind a paywall.

Malaria vaccine with self-assembling nanoparticles

This research was published in April 2013 so I’m not sure what has occasioned a Sept. 2014 push for publicity. Still, it’s interesting work which may lead to a more effective vaccine for malaria than some of the other solutions being tested.  From a Sept. 4, 2014 news item on Nanowerk,

A self-assembling nanoparticle designed by a University of Connecticut (UConn) professor is the key component of a potent new malaria vaccine that is showing promise in early tests.

For years, scientists trying to develop a malaria vaccine have been stymied by the malaria parasite’s ability to transform itself and “hide” in the liver and red blood cells of an infected person to avoid detection by the immune system.

But a novel protein nanoparticle developed by Peter Burkhard, a professor in the Department of Molecular & Cell Biology, in collaboration with David Lanar, an infectious disease specialist with the Walter Reed Army Institute of Research, has shown to be effective at getting the immune system to attack the most lethal species of malaria parasite, Plasmodium falciparum, after it enters the body and before it has a chance to hide and aggressively spread.

Sept. 3, 2014 University of Connecticut news release by Colin Poitras, which originated the news item, describes the particle and the research in greater detail,

The key to the vaccine’s success lies in the nanoparticle’s perfect icosahedral symmetry (think of the pattern on a soccer ball) and ability to carry on its surface up to 60 copies of the parasite’s protein. The proteins are arranged in a dense, carefully constructed cluster that the immune system perceives as a threat, prompting it to release large amounts of antibodies that can attack and kill the parasite.

In tests with mice, the vaccine was 90-100 percent effective in eradicating the Plasmodium falciparum parasite and maintaining long-term immunity over 15 months. That success rate is considerably higher than the reported success rate for RTS,S, the world’s most advanced malaria vaccine candidate currently undergoing phase 3 clinical trials, which is the last stage of testing before licensing.

“Both vaccines are similar, it’s just that the density of the RTS,S protein displays is much lower than ours,” says Burkhard. “The homogeneity of our vaccine is much higher, which produces a stronger immune system response. That is why we are confident that ours will be an improvement.

“Every single protein chain that forms our particle displays one of the pathogen’s protein molecules that are recognized by the immune system,” adds Burkhard, an expert in structural biology affiliated with UConn’s Institute of Materials Science. “With RTS,S, only about 14 percent of the vaccine’s protein is from the malaria parasite. We are able to achieve our high density because of the design of the nanoparticle, which we control.”

Here’s an image illustrating the nanoparticle,

This self-assembling protein nanoparticle relies on rigid protein structures called ‘coiled coils’ (blue and green in the image) to create a stable framework upon which scientists can attach malaria parasite antigens. Early tests show that injecting the nanoparticles into the body as a vaccine initiates a strong immune system response that destroys a malarial parasite when it enters the body and before it has time to spread. (Image courtesy of Peter Burkhard)

This self-assembling protein nanoparticle relies on rigid protein structures called ‘coiled coils’ (blue and green in the image) to create a stable framework upon which scientists can attach malaria parasite antigens. Early tests show that injecting the nanoparticles into the body as a vaccine initiates a strong immune system response that destroys a malarial parasite when it enters the body and before it has time to spread. (Image courtesy of Peter Burkhard)

The news release goes on to explain why malaria is considered a major, global health problem and how the researchers approached the problem with developing a malaria vaccine for humans,

The search for a malaria vaccine is one of the most important research projects in global public health. The disease is commonly transported through the bites of nighttime mosquitoes. Those infected suffer from severe fevers, chills, and a flu-like illness. In severe cases, malaria causes seizures, severe anemia, respiratory distress, and kidney failure. Each year, more than 200 million cases of malaria are reported worldwide. The World Health Organization estimated that 627,000 people died from malaria in 2012, many of them children living in sub-Saharan Africa.

It took the researchers more than 10 years to finalize the precise assembly of the nanoparticle as the critical carrier of the vaccine and find the right parts of the malaria protein to trigger an effective immune response. The research was further complicated by the fact that the malaria parasite that impacts mice used in lab tests is structurally different from the one infecting humans.

The scientists used a creative approach to get around the problem.

“Testing the vaccine’s efficacy was difficult because the parasite that causes malaria in humans only grows in humans,” Lanar says. “But we developed a little trick. We took a mouse malaria parasite and put in its DNA a piece of DNA from the human malaria parasite that we wanted our vaccine to attack. That allowed us to conduct inexpensive mouse studies to test the vaccine before going to expensive human trials.”

The pair’s research has been supported by a $2 million grant from the National Institutes of Health and $2 million from the U.S. Military Infectious Disease Research Program. A request for an additional $7 million in funding from the U.S. Army to conduct the next phase of vaccine development, including manufacturing and human trials, is pending.

“We are on schedule to manufacture the vaccine for human use early next year,” says Lanar. “It will take about six months to finish quality control and toxicology studies on the final product and get permission from the FDA to do human trials.”

Lanar says the team hopes to begin early testing in humans in 2016 and, if the results are promising, field trials in malaria endemic areas will follow in 2017. The required field trial testing could last five years or more before the vaccine is available for licensure and public use, Lanar says.

Martin Edlund, CEO of Malaria No More, a New York-based nonprofit focused on fighting deaths from malaria, says, “This research presents a promising new approach to developing a malaria vaccine. Innovative work such as what’s being done at the University of Connecticut puts us closer than we’ve ever been to ending one of the world’s oldest, costliest, and deadliest diseases.”

A Switzerland-based company, Alpha-O-Peptides, founded by Burkhard, holds the patent on the self-assembling nanoparticle used in the malaria vaccine. Burkhard is also exploring other potential uses for the nanoparticle, including a vaccine that will fight animal flu and one that will help people with nicotine addiction. Professor Mazhar Khan from UConn’s Department of Pathobiology is collaborating with Burkhard on the animal flu vaccine.

Here’s a link to and a citation for the paper,

Mechanisms of protective immune responses induced by the Plasmodium falciparum circumsporozoite protein-based, self-assembling protein nanoparticle vaccine by Margaret E McCoy, Hannah E Golden, Tais APF Doll, Yongkun Yang, Stephen A Kaba, Peter Burkhard, and David E Lanar. Malaria Journal 2013, 12:136 doi:10.1186/1475-2875-12-136

This is an open access article.

Nanotechnology-enabled detection of landmines with the naked eye

Researchers at the University of Connecticut have developed a device that makes the location of buried landmines and other hidden explosive devices visible to the naked eye. Colin Poitras in his May 4, 0212 posting on the University of Connecticut website provides some background information about landmines and their detection,

Each year, as many as 25,000 people are maimed or killed by landmines around the world, including large numbers of civilians.

While landmines are inexpensive to produce – about $3-$30 each, depending on the model – finding and clearing them can cost as much as $1,000 per mine. It is a slow and deliberative process. Specially trained dogs are the gold standard, but they can be distracted by larger mine fields and eventually tire. Metal detectors are good, but they are often too sensitive, causing lengthy and expensive delays for the removal of an object that may turn out to be merely a buried tin can.

A UConn chemical engineering doctoral student hopes to help. Ying Wang, working in conjunction with her advisor, associate professor Yu Lei, has developed a prototype portable sensing system that can be used to detect hidden explosives like landmines accurately, efficiently, and at little cost.

The Aug. 2, 2012 news item on Nanowerk provides some information about the device ,

A chemical sensing system developed by engineers at the University of Connecticut is believed to be the first of its kind capable of detecting vapors from buried landmines and other explosive devices with the naked eye rather than advanced scientific instrumentation.

The research was first reported in the May 11, 2012 online edition of Advanced Functional Materials.

The key to the system is a fluorescent nanofiberous film that can detect ultra-trace levels of explosive vapors and buried explosives when applied to an area where explosives are suspected. A chemical reaction marking the location of the explosive device occurs when the film is exposed to handheld ultraviolet light.

Detection of buried explosives. (Image courtesy of Ying Wang) Downloaded from the University of Connecticut website: http://today.uconn.edu/blog/2012/05/improving-the-detection-of-landmines/

The Aug. 2, 2012 news item on e! Science News provides additional detail about this detection system,

The system can detect nitroaromatics such as those found in TNT and 2,4-DNT (the military’s primary explosive and the principle components in landmines) as well as the elements used in harder to detect plastic explosives such as HMX, RDX, Tetryl, and PETN. The ultra-sensitive system can detect elements at levels as low as 10 parts per billion (TNT), 74 parts per trillion (Tetryl), 5 ppt (RDX), 7 ppt (PETN) and 0.1 ppt (HMX) released from one billionth of a gram of explosive residue.

If there is no explosive vapor present, the recyclable film retains a bright fluorescent cyan blue color when exposed to ultraviolet light. If explosive molecules are present, the fluorescence is quenched and a dark circle identifying the threat forms on the film within minutes.

“Our initial results have been very promising,” says UConn Dr. Ying Wang, who developed the system as a chemical engineering doctoral student working under the supervision of UConn Associate Engineering Professor Yu Lei. “We are now in the process of arranging a large-scale field test in Sweden.”

Rather than using sophisticated chemical modifications or costly synthetic polymers in preparing the sensing material, UConn scientists prepared their ultra-thin film by simply electrospinning pyrene with polystyrene in the presence of an organic salt (tetrabutylammonium hexafluorophosphate or TBAH). This resulted in a highly porous nanofiberous membrane that absorbs explosive vapors at ultra-trace levels quickly and reliably. The film also has excellent sensitivity against common interferences such as ammonium nitrate and inorganic nitrates. Initial vapor detection took place within seconds with more than 90 percent fluorescent quenching efficiency within six minutes.

Poitras’ posting notes the researchers have teamed with a landmine removal company (Note: I have removed some links),

One of the world’s top private landmine clearing companies, located in South Sudan, is currently working with Lei and Wang in arranging a large-scale field test. The results of the field test could be of interest to the United Nations, which has worked to make war zones plagued by old landmines safer through its United Nations Mine Action Service. It is estimated that there are about 110 million active landmines lurking underground in 64 countries across the globe. The mines not only threaten people’s lives, they can paralyze communities by limiting the use of land for farming and roads for trade.

“When I started working with landmines, I was thrilled,” says Wang, who received her bachelor’s degree in chemical engineering from Xiamen University in China in 2004 and her master’s degree in biochemical engineering from Xiamen University in 2007. “I knew this would be a really good application of our work. It can save lives.”

Wang and Lei are currently working with UConn’s Center for Science and Technology Commercialization (CSTC) in obtaining a U.S. patent for their explosive detection systems.

I last wrote about landmine detection systems in an Aug. 22, 2011 posting which centered on an ‘ultra’ portable system.

There are a number of ‘landmine’ programmes, I found these two: United Nations Mine Action Service, aka, E-MINE: Electronic Mine Information Network and the United Nations Association of the United States of America Adopt-A-Minefield Program.