How To Track Blood Flow In Tiny Vessels

Scientists have designed gold nanoparticles, no bigger than 100 nanometres, which can be coated and used to track blood flow in the smallest blood vessels in the body. By improving our understanding of blood flow in vivo the nanoprobes represent an opportunity to help in the early diagnosis of diseaseLight microscopy is a rapidly evolving field for understanding in vivo systems where high resolution is required. It is particularly crucial for cardiovascular research, where clinical studies are based on ultrasound technologies which inherently have lower resolution and provide limited information.

The ability to monitor blood flow in the sophisticated vascular tree (notably in the smallest elements of the microvasculaturecapillaries) can provide invaluable information to understand disease processes such as thrombosis and vascular inflammation. There are further applications for the improved delivery of therapeutics, such as targeting tumours.

Currently, blood flow in the microvasculature is poorly understood. Nanoscience is uniquely placed to help understand the processes happening in the micron-dimensioned vessels. Designing probes to monitor blood flow is challenging because of the environment; the high protein levels in plasma and the high red blood cell concentrations are detrimental to optical imaging. Conventional techniques rely on staining red blood cells, using organic dyes with short-lived usage due to photobleaching, as the tracking motif. The relatively large size of the red blood cells (7-8 micrometres), which are effectively the probes, limits the resolution in imaging and analysis of flow dynamics of the smallest vessels which are of a similar width. Therefore, to have more detailed resolution and information about the blood flow in the microvasculature, even smaller probes are required.

The key to these iridium-coated nanoparticles lies in both their small size, and in the characteristic luminescent properties. The iridium gives a luminescent signal in the visible spectrum, providing an optical window which can be detected in blood. It is also long-lived compared to organic fluorophores, while the tiny gold particles are shown to be ideal for tracking flow and detect clearly in tissues“, explains Professor Zoe Pikramenou, from the School of Chemistry at  the University of Birmingham.

The findings have been published in the journal Nanomedicine.


How To Draw Electricity from the Bloodstream

Men build dams and huge turbines to turn the energy of waterfalls and tides into electricity. To produce hydropower on a much smaller scale, Chinese scientists have now developed a lightweight power generator based on carbon nanotube fibers suitable to convert even the energy of flowing blood in blood vessels into electricity.

For thousands of years, people have used the energy of flowing or falling water for their purposes, first to power mechanical engines such as watermills, then to generate electricity by exploiting height differences in the landscape or sea tides. Using naturally flowing water as a sustainable power source has the advantage that there are (almost) no dependencies on weather or daylight. Even flexible, minute power generators that make use of the flow of biological fluids are conceivable. How such a system could work is explained by a research team from Fudan University in Shanghai, China. Huisheng Peng and his co-workers have developed a fiber with a thickness of less than a millimeter that generates electrical power when surrounded by flowing saline solution—in a thin tube or even in a blood vessel.

The construction principle of the fiber is quite simple. An ordered array of carbon nanotubes was continuously wrapped around a polymeric core. Carbon nanotubes are well known to be electroactive and mechanically stable; they can be spun and aligned in sheets. In the as-prepared electroactive threads, the carbon nanotube sheets coated the fiber core with a thickness of less than half a micron. For power generation, the thread or “fiber-shaped fluidic nanogenerator” (FFNG), as the authors call it, was connected to electrodes and immersed into flowing water or simply repeatedly dipped into a saline solution. “The electricity was derived from the relative movement between the FFNG and the solution,” the scientists explained. According to the theory, an electrical double layer is created around the fiber, and then the flowing solution distorts the symmetrical charge distribution, generating an electricity gradient along the long axis.

The power output efficiency of this system was high. Compared with other types of miniature energy-harvesting devices, the FFNG was reported to show a superior power conversion efficiency of more than 20%. Other advantages are elasticity, tunability, lightweight, and one-dimensionality, thus offering prospects of exciting technological applications. The FFNG can be made stretchable just by spinning the sheets around an elastic fiber substrate. If woven into fabrics, wearable electronics become thus a very interesting option for FFNG application. Another exciting application is the harvesting of electrical energy from the bloodstream for medical applications. First tests with frog nerves proved to be successful.

The findings are published in  the journal Angewandte Chemie.


A Single Drop Of Blood To Test Agressive Prostate Cancer

A new diagnostic developed by Alberta scientists will allow men to bypass painful biopsies to test for aggressive prostate cancer. The test incorporates a unique nanotechnology platform to make the diagnostic using only a single drop of blood, and is significantly more accurate than current screening methods.

The Extracellular Vesicle Fingerprint Predictive Score (EV-FPS) test uses machine learning to combine information from millions of cancer cell nanoparticles in the blood to recognize the unique fingerprint of aggressive cancer. The diagnostic, developed by members of the Alberta Prostate Cancer Research Initiative (APCaRI), was evaluated in a group of 377 Albertan men who were referred to their urologist with suspected prostate cancer. It was found that EV-FPS correctly identified men with aggressive prostate cancer 40 percent more accurately than the most common test—Prostate-Specific Antigen (PSA) blood test—in wide use today.

Higher sensitivity means that our test will miss fewer aggressive cancers,” said John Lewis, the Alberta Cancer Foundation‘s Frank and Carla Sojonky Chair of Prostate Cancer Research at the University of Alberta. “For this kind of test you want the sensitivity to be as high as possible because you don’t want to miss a single cancer that should be treated.”

According to the team, current tests such as the PSA and digital rectal exam (DRE) often lead to unneeded biopsies. Lewis says more than 50 per cent of men who undergo biopsy do not have prostate cancer, yet suffer the pain and side effects of the procedure such as infection or sepsis. Less than 20 per cent of men who receive a are diagnosed with the aggressive form of prostate cancer that could most benefit from treatment.

It’s estimated that successful implementation of the EV-FPS test could eventually eliminate up to 600-thousand unnecessary biopsies, 24-thousand hospitalizations and up to 50 per cent of unnecessary treatments for prostate each year in North America alone. Beyond cost savings to the health care system, the researchers say the diagnostic test will have a dramatic impact on the health care experience and quality of life for men and their families.

Compared to elevated total PSA alone, the EV-FPS test can more accurately predict the result of prostate biopsy in previously unscreened men,” said Adrian Fairey, urologist at the Northern Alberta Urology Centre and member of APCaRI. “This information can be used by clinicians to determine which men should be advised to undergo immediate prostate biopsy and which men should be advised to defer and continue screening.”


Nanoparticles From Air Pollution Travel Into Blood To Cause Heart Disease

Inhaled nanoparticles – like those released from vehicle exhausts – can work their way through the lungs and into the bloodstream, potentially raising the risk of heart attack and stroke, according to new research part-funded by the British Heart Foundation. The findings, published today in the journal ACS Nano, build on previous studies that have found tiny particles in air pollution are associated with an increased risk of cardiovascular disease, although the cause remains unproven. However, this research shows for the first time that inhaled nanoparticles can gain access to the blood in healthy individuals and people at risk of stroke. Most worryingly, these nanoparticles tend to build-up in diseased blood vessels where they could worsen coronary heart disease – the cause of a heart attack.

It is not currently possible to measure environmental nanoparticles in the blood. So, researchers from the University of Edinburgh, and the National Institute for Public Health and the Environment in the Netherlands, used a variety of specialist techniques to track the fate of harmless gold nanoparticles breathed in by volunteers. They were able to show that these nanoparticles can migrate from the lungs and into the bloodstream within 24 hours after exposure and were still detectable in the blood three months later. By looking at surgically removed plaques from people at high risk of stroke they were also able to find that the nanoparticles accumulated in the fatty plaques that grow inside blood vessels and cause heart attacks and strokesCardiovascular disease (CVD) – the main forms of which are coronary heart disease and stroke – accounts for 80% of all premature deaths from air pollution.


It is striking that particles in the air we breathe can get into our blood where they can be carried to different organs of the body. Only a very small proportion of inhaled particles will do this, however, if reactive particles like those in air pollution then reach susceptible areas of the body then even this small number of particles might have serious consequences,”  said Dr Mark Miller, Senior Research Fellow at the University of Edinburgh who led the study.


“Liquid Biopsy” Chip Detects Metastatic Cancer Cells in a Drop of Blood

A chip developed by mechanical engineers at Worcester Polytechnic Institute (WPI) can trap and identify metastatic cancer cells in a small amount of blood drawn from a cancer patient. The breakthrough technology uses a simple mechanical method that has been shown to be more effective in trapping cancer cells than the microfluidic approach employed in many existing devices.


The chip is tested in the lab. The electrodes detect electrical changes that occur when cancer cells are captured (click on the image to enjoy the video)

The WPI device uses antibodies attached to an array of carbon nanotubes at the bottom of a tiny well. Cancer cells settle to the bottom of the well, where they selectively bind to the antibodies based on their surface markers (unlike other devices, the chip can also trap tiny structures called exosomes produced by cancers cells). This “liquid biopsy,”  could become the basis of a simple lab test that could quickly detect early signs of metastasis and help physicians select treatments targeted at the specific cancer cells identified.

Metastasis is the process by which a cancer can spread from one organ to other parts of the body, typically by entering the bloodstream. Different types of tumors show a preference for specific organs and tissues; circulating breast cancer cells, for example, are likely to take root in bones, lungs, and the brain. The prognosis for metastatic cancer (also called stage IV cancer) is generally poor, so a technique that could detect these circulating tumor cells before they have a chance to form new colonies of tumors at distant sites could greatly increase a patient’s survival odds.

The focus on capturing circulating tumor cells is quite new,” said Balaji Panchapakesan, associate professor of mechanical engineering at WPI and director of the Small Systems Laboratory. “It is a very difficult challenge, not unlike looking for a needle in a haystack. There are billions of red blood cells, tens of thousands of white blood cells, and, perhaps, only a small number of tumor cells floating among them. We’ve shown how those cells can be captured with high precision.

The findings have been described in  the journal Nanotechnology,


How To Stop The Bleeding

Whether  occurs on the battlefield or the highway, saving lives often comes down to stopping the bleeding as quickly as possible. Many methods for controlling external bleeding exist, but at this point, only surgery can halt blood loss inside the body from injury to internal organs. Now, researchers have developed nanoparticles that congregate wherever injury occurs in the body to help it form blood clots, and they’ve validated these particles in test tubes and in vivo.

stopping the bleeding

Nanoparticles (green) help form clots in an injured liver. The researchers added color to the scanning electron microscopy image after it was taken

When you have uncontrolled internal bleeding, that’s when these particles could really make a difference,” says Erin B. Lavik, Sc.D. “Compared to injuries that aren’t treated with the nanoparticles, we can cut bleeding time in half and reduce total blood loss.

Trauma remains a top killer of children and younger adults, and doctors have few options for treating internal bleeding. To address this great need, Lavik’s team developed a nanoparticle that acts as a bridge, binding to activated platelets and helping them join together to form clots. To do this, the nanoparticle is decorated with a molecule that sticks to a glycoprotein found only on the activated platelets.

The researchers have presented their work at the 252nd National Meeting & Exposition of the American Chemical Society (ACS).


How To Remove Nanoparticles From Blood

Engineers at the University of California, San Diego developed a new technology that uses an oscillating electric field to easily and quickly isolate drug-delivery nanoparticles from blood. The technology could serve as a general tool to separate and recover nanoparticles from other complex fluids for medical, environmental, and industrial applications.

Nanoparticles, which are generally one thousand times smaller than the width of a human hair, are difficult to separate from plasma, the liquid component of blood, due to their small size and low density. Traditional methods to remove nanoparticles from plasma samples typically involve diluting the plasma, adding a high concentration sugar solution to the plasma and spinning it in a centrifuge, or attaching a targeting agent to the surface of the nanoparticles. These methods either alter the normal behavior of the nanoparticles or cannot be applied to some of the most common nanoparticle types.

nanoparticles in blood

Nanoparticle removal chip developed by researchers in Professor Michael Heller’s lab at the UC San Diego Jacobs School of Engineering. An oscillating electric field (purple arcs) separates drug-delivery nanoparticles (yellow spheres) from blood (red spheres) and pulls them towards rings surrounding the chip’s electrodes.

This is the first example of isolating a wide range of nanoparticles out of plasma with a minimum amount of manipulation,” said Stuart Ibsen, a postdoctoral fellow in the Department of NanoEngineering at UC San Diego and first author of the study published October in the journal Small.
We’ve designed a very versatile technique that can be used to recover nanoparticles in a lot of different processes.”


How To Fight Septic Shock, Save Millions

Last year, a Wyss Institute (Harvard) team of scientists described the development of a new device to treat sepsis that works by mimicking our spleen. It cleanses pathogens and toxins from blood circulating through a dialysis-like circuit. Now, the Wyss Institute team has developed an improved device that synergizes with conventional antibiotic therapies and that has been streamlined to better position it for near-term translation to the clinic. Sepsis is a common and frequently fatal medical complication that can occur when a person’s body attempts to fight off serious infection. Resulting widespread inflammation can cause organs to shut down, blood pressure to drop, and the heart to weaken. This can lead to septic shock, and more than 30 percent of septic patients in the United States eventually die. In most cases, the pathogen responsible for triggering the septic condition is never pinpointed, so clinicians blindly prescribe an antibiotic course in a blanket attempt to stave off infectious bacteria and halt the body’s dangerous inflammatory response.

But sepsis can be caused by a wide-ranging variety of pathogens that are not susceptible to antibiotics, including viruses, fungi and parasites. What’s more, even when antibiotics are effective at killing invading bacteria, the dead pathogens fragment and release toxins into the patient’s bloodstream.
The inflammatory cascade that leads to sepsis is triggered by pathogens, and specifically by the toxins they release,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who leads the Wyss team developing the device and is the Judah Folkman Professor of Vascular Biology at Boston Children’s Hospital and Harvard Medical School and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Science. “Thus, the most effective strategy is to treat with the best antibiotics you can muster, while also removing the toxins and remaining pathogens from the patient’s blood as quickly as possible.”

The Wyss team’s blood-cleansing approach can be administered quickly, even without identifying the infectious agent. This is because it uses the Wyss Institute‘s proprietary pathogen-capturing agent, FcMBL, that binds all types of live and dead infectious microbes, including bacteria, fungi, viruses, as well as toxins they release. FcMBL is a genetically engineered blood protein inspired by a naturally-occurring human molecule called Mannose Binding Lectin (MBL), which is found in the innate immune system and binds to toxic invaders, marking them for capture by immune cells in the spleen.

The findings are described in the October volume 67 of Biomaterials.


20 Pence Reusable Sensor To Detect Diabetes

A low-cost, reusable sensor which uses nanotechnology to screen for and monitor diabetes and other conditions, has been developed by an interdisciplinary team of researchers from the University of Cambridge, for use both in clinics and home settings. According to the International Diabetes Federation, there are an estimated 175 million undiagnosed diabetic patients worldwide, 80% of whom live in low- and middle– income countries. Development of non-invasive and accurate diagnostics that are easily manufactured, robust and reusable will allow for simple monitoring of high-risk individuals in any environment, particularly in the developing world.

These sensors can be used to screen for diabetes in resource-poor countries, where disposable test strips and other equipment are simply not affordable,” said Ali Yetisen, a PhD candidate in the Department of Chemical Engineering & Biotechnology, who led the research. The sensors can be produced at a fraction of the cost of commercially-available test strips. A single sensor would cost 20 pence to produce, and can be reused up to 400 times
The sensors use nanotechnology to monitor levels of glucose, lactate and fructose in individuals with diabetes or urinary tract infections, and change colour when levels reach a certain concentration. They can be used to test compounds in samples such as urine, blood, saliva or tear fluid. Recently, the team has also partnered with a non-governmental organisation to deploy the technology for field use in Ghana early next year.


Pour, Shake and Stir !

A diagnostic “cocktail” containing a single drop of blood, a dribble of water, and a dose of DNA powder with gold particles could mean rapid diagnosis and treatment of the world’s leading diseases in the near future. The cocktail diagnostic is a homegrown brew being developed by University of Toronto’s Institute of Biomaterials and Biomedical Engineering (IBBME) PhD student Kyryl Zagorovsky and Professor Warren Chan that could change the way infectious diseases, from HPV and HIV to malaria, are diagnosed. And it involves the same technology used in over-the-counter pregnancy tests.
There’s been a lot of emphasis in developing simple diagnostics,” says IBBME Professor and Canada Research Chair in Nanobiotechnology, Warren Chan. “The question is, how do you make it simple enough, portable enough?” Zagorovsky’s rapid diagnostic biosensor will allow technicians to test for multiple diseases at one time with one small sample, and with high accuracy and sensitivity. The biosensor relies upon gold particles in much the same vein as your average pregnancy test. With a pregnancy test, gold particles turn the test window red because the particles are linked with an antigen that detects a certain hormone in the urine of a pregnant woman. “Gold is the best medium,” explains Chan, “because it’s easy to see. It emits a very intense colour.”

How To Capture Circulating Cancer Cells?

A glass plate with a nanoscale roughness could be a simple way for scientists to capture and study the circulating tumor cells that carry cancer around the body through the bloodstream. Engineering and medical researchers at the University of Michigan have devised such a set-up, which they say takes advantage of cancer cells‘ stronger drive to settle and bind compared with normal blood cells.

This false-color microscopic image shows cancer cells selectively adhering to patterned nanorough letters (UM) on a glass surface

Circulating tumor cells are believed to contribute to cancer metastasis, the grim process of the disease spreading from its original site to distant tissues. Blood tests that count these cells can help doctors predict how long a patient with widespread cancer will live. “Our system can capture the majority of circulating tumor cells regardless of their surface proteins or their physical sizes, and this could include cancer progenitor or initiating cells,” said Jianping Fu, assistant professor of mechanical engineering and biomedical engineering and a senior author of a paper on the technique published online in ACS Nano.