Posts belonging to Category Biomedical engineering

Gene Researchers Have Created Green Mice

These are no Frankenstein mice. Their green feet come courtesy of a fluorescent green jelly fish gene added to their own genome. This allows a team of British scientists to test out gene editing using CRISPR-Cas9 technology.


“We take what were or would have been green embryos and we make them into non-green embryos, so it’s a really great way of demonstrating the method“, said Dr. Anthony Perry, reproductive biologist at the University of Bath.

The technique uses the ribonucleic acid molecule CRISPR together with the Cas9 protein enzyme. CRISPR guides the Cas9 protein to a defective part of a genome where it acts like molecular scissors to cut out a specific part of the DNA. This could revolutionise how we treat diseases with a genetic component, like sickle cell anaemia. The technique is being pioneered in the U.S.
We now have a technology that allows correction of a sequence that would lead to normally functioning cells. And I think you know the opportunities with this are really exciting and really profound. There are many diseases that are have known genetic causes that we now have in principle a way to cure,“explains Jennifer Doudna, Professor of cell biology at the University of Berkeley.
Last year two teams of U.S. based scientists used CRISPR-Cas9 technology in mice to correct the genetic mutation that causes sickle cell disease. Although researchers aren’t yet close to using CRISPR-Cas9 to edit human embryos for implantation into the womb – some are already warning against it.

Dr David King, Director of  Human Genetics Alert, comments: “It will immediately create this new form of what we call consumer eugenics, that’s to say eugenics driven by the free market and consumer preferences in which people choose the cosmetic characteristics and the abilities of their children and try to basically enhance their children to perform better than other people’s children.” Other potential applications of the technology could be to make food crops and livestock animal species disease-resistant. The British team say CRISPR-Cas9 presents a golden opportunity to prevent genetic disease.


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 Fix Duchenne Muscular Dystrophy

Scientists at the University of California, Berkeley, have engineered a new way to deliver CRISPR-Cas9 gene-editing technology inside cells and have demonstrated in mice that the technology can repair the mutation that causes Duchenne muscular dystrophy, a severe muscle-wasting disease. A new study shows that a single injection of CRISPR-Gold, as the new delivery system is called, into mice with Duchenne muscular dystrophy led to an 18-times-higher correction rate and a two-fold increase in a strength and agility test compared to control groups.

Since 2012, when study co-author Jennifer Doudna, a professor of molecular and cell biology and of chemistry at UC Berkeley, and colleague Emmanuelle Charpentier, of the Max Planck Institute for Infection Biology, repurposed the Cas9 protein to create a cheap, precise and easy-to-use gene editor, researchers have hoped that therapies based on CRISPR-Cas9 would one day revolutionize the treatment of genetic diseases. Yet developing treatments for genetic diseases remains a big challenge in medicine. This is because most genetic diseases can be cured only if the disease-causing gene mutation is corrected back to the normal sequence, and this is impossible to do with conventional therapeutics.

CRISPR/Cas9, however, can correct gene mutations by cutting the mutated DNA and triggering homology-directed DNA repair. However, strategies for safely delivering the necessary components (Cas9, guide RNA that directs Cas9 to a specific gene, and donor DNA) into cells need to be developed before the potential of CRISPR-Cas9-based therapeutics can be realized. A common technique to deliver CRISPR-Cas9 into cells employs viruses, but that technique has a number of complications. CRISPR-Gold does not need viruses.

In the new study, research lead by the laboratories of Berkeley bioengineering professors Niren Murthy and Irina Conboy demonstrated that their novel approach, called CRISPR-Gold because gold nanoparticles are a key component, can deliver Cas9 – the protein that binds and cuts DNA – along with guide RNA and donor DNA into the cells of a living organism to fix a gene mutation.

CRISPR-Gold is the first example of a delivery vehicle that can deliver all of the CRISPR components needed to correct gene mutations, without the use of viruses,” Murthy said.

The study was published in the journal Nature Biomedical Engineering.


One-Two Knockout Punch To Eradicate Super Bugs

Light-activated nanoparticles, also known as quantum dots, can provide a crucial boost in effectiveness for antibiotic treatments used to combat drug-resistant superbugs such as E. coli and Salmonella, new CU Boulder research shows. Multi-drug resistant pathogens, which evolve their defenses faster than new antibiotic treatments can be developed to treat them, cost the United States an estimated $20 billion in direct healthcare costs and an additional $35 billion in lost productivity in 2013. Rather than attacking the infecting bacteria conventionally, the dots release superoxide, a chemical species that interferes with the bacteria’s metabolic and cellular processes, triggering a fight response that makes it more susceptible to the original antibiotic.

We’ve developed a one-two knockout punch,” said Prashant Nagpal, an assistant professor in CU Boulder’s Department of Chemical and Biological Engineering (CHBE) and the co-lead author of the study. “The bacteria’s natural fight reaction [to the dots] actually leaves it more vulnerable.”

We are thinking more like the bug,” explains Anushree Chatterjee, an assistant professor in CHBE and the co-lead author of the study. “This is a novel strategy that plays against the infection’s normal strength and catalyzes the antibiotic instead.” The dots reduced the effective antibiotic resistance of the clinical isolate infections by a factor of 1,000 without producing adverse side effects.

The findings have been published today in the journal Science Advances.


Graphene, Not Glass, Is The Key To Better Optics

A lens just a billionth of a metre thick could transform phone cameras. Researchers at Swinburne University in Melbourne, Australia, have created ultra-thin lenses that cap an optical fibre, and can produce images with the quality and sharpness of much larger glass lenses.

Compared with current lenses, our graphene lens only needs one film to achieve the same resolution,” says Professor Baohua Jia, a research leader at Swinburne’s Centre for Micro-Photonics. “In the future, mobile phones could be much thinner, without having to sacrifice the quality of their cameras. Our lens also allows infrared light to pass through, which glass lenses don’t.”

Producing graphene can be costly and challenging, so Baohua and her colleagues used a laser to pattern layers of graphene oxide (graphene combined with oxygen). By then removing the oxygen, they produced low-cost, patterned films of graphene, a thousand times thinner than a human hair. “By patterning the graphene oxide film in this way, its optical and electrical properties can be altered, which allowed us to place them in different devices,” she says.

Warm objects give off infrared light, so mobile phones with graphene lenses could be used to scan for hotspots in the human body and help in the early identification of diseases like breast cancer. By attaching the lens to a fibre optic tip, endoscopes — instruments that are currently several millimetres wide—could be made a million times smaller. The team is also investigating graphene’s amazing properties for their potential use as supercapacitors, capable of storing very large amounts of energy, which could replace conventional batteries.

Baohua’s work on graphene lenses was published in Nature Communications.


Nanogels For Heart Attack Patients

Heart disease and heart-related illnesses are a leading cause of death around the world, but treatment options are limited. Now, one group reports in ACS Nano that encapsulating stem cells in a nanogel could help repair damage to the heart.

Myocardial infarction, also known as a heart attack, causes damage to the muscular walls of the heart. Scientists have tried different methods to repair this damage. For example, one method involves directly implanting stem cells in the heart wall, but the cells often don’t take hold, and sometimes they trigger an immune reaction. Another treatment option being explored is injectable hydrogels, substances that are composed of water and a polymer. Naturally occurring polymers such as keratin and collagen have been used but they are expensive, and their composition can vary between batches. So Ke Cheng, Hu Zhang, Jinying Zhang and colleagues wanted to see whether placing stem cells in inexpensive hydrogels with designed tiny pores that are made in the laboratory would work.

The team encapsulated stem cells in nanogels, which are initially liquid but then turn into a soft gel when at body temperature. The nanogel didn’t adversely affect stem cell growth or function, and the encased stem cells didn’t trigger a rejection response. When these enveloped cells were injected into mouse and pig hearts, the researchers observed increased cell retention and regeneration compared to directly injecting just the stem cells. In addition, the heart walls were strengthened. Finally, the group successfully tested the encapsulated stem cells in mouse and pig models of myocardial infarction.


Nano Robots Build Molecules

Scientists at The University of Manchester have created the world’s first ‘molecular robot’ that is capable of performing basic tasks including building other molecules.

The tiny robots, which are a millionth of a millimetre in size, can be programmed to move and build molecular cargo, using a tiny robotic arm.

Each individual robot is capable of manipulating a single molecule and is made up of just 150 carbon, hydrogen, oxygen and nitrogen atoms. To put that size into context, a billion billion of these robots piled on top of each other would still only be the same size as a single grain of salt. The robots operate by carrying out chemical reactions in special solutions which can then be controlled and programmed by scientists to perform the basic tasks.

In the future such robots could be used for medical purposes, advanced manufacturing processes and even building molecular factories and assembly lines.

All matter is made up of atoms and these are the basic building blocks that form molecules. Our robot is literally a molecular robot constructed of atoms just like you can build a very simple robot out of Lego bricks, explains Professor David Leigh, who led the research at University’s School of Chemistry. “The robot then responds to a series of simple commands that are programmed with chemical inputs by a scientistIt is similar to the way robots are used on a car assembly line. Those robots pick up a panel and position it so that it can be riveted in the correct way to build the bodywork of a car. So, just like the robot in the factory, our molecular version can be programmed to position and rivet components in different ways to build different products, just on a much smaller scale at a molecular level.”

The research has been published in Nature.


New Treatment To Kill Cancer

Raise your hand if you haven’t been touched by cancer,” says Mylisa Parette to a roomful of strangers. Parette, the research manager for Keystone Nano (KN), has occasional opportunities to present her company’s technologies to business groups and wants to emphasize the scope of the problem that still confronts society. “It’s easier to see the effects of cancer when nobody raises their hand,” she says. Despite 40 years of the War on Cancer, one in two men and one in three women will be diagnosed with the disease at some point in their lifetime. Parette and her Keystone Nano colleagues are working on a new approach to cancer treatment. The company was formed from the collaboration of two Penn State faculty members who realized that the nanoparticle research that the one was undertaking could be used to solve the drug delivery problems that the other was facing.

Mark Kester, a pharmacologist at Penn State College of Medicine in Hershey, was working with a new drug that showed real promise as a cancer therapy but that could be dangerous if injected directly into the bloodstream. Jim Adair, a materials scientist in University Park, was creating nontoxic nanoparticles that could enclose drugs that might normally be toxic or hydrophobic and were small enough to be taken up by cells.

The two combined their efforts and, licensing the resulting technology from Penn State, they joined with entrepreneur Jeff Davidson, founder of the Biotechnology Institute and the Pennsylvania Biotechnology Association, to form Keystone Nano. The new company’s first hire was Parette, whose job is to translate the lab-scale technology into something that can be ramped up to an industrial scale, and to prepare that technology for FDA approval leading to clinical trials.

Davidson, Parette, and KN’s research team work out of the Zetachron building, a long, one-story science incubator a mile from Penn State’s University Park campus. Operated by the Centre County Industrial Development Corporation, the building was originally the home of the successful Penn State spin-out company that gave it its name. A second Keystone Nano lab was recently opened in the Hershey Center for Applied Research, a biotech incubator adjacent to Penn State College of Medicine.

Our excitement is that we think our technology has shown efficacy in a whole range of animal models,” Davidson, Keystone CEO, remarks during a recent meeting in the shared conference room at Zetachron. “We understand the method of action, the active ingredient. We think it has every chance of being useful in treating disease. Our question is, how do we push this forward from where we are today to determining, one way or another, that it really does work?

Keystone Nano is pioneering two approaches to cancer therapy, both of which rely on advances in nanotechnology to infiltrate tumors and deliver a therapeutic agent. The approach nearest to clinical trials is a ceramide nanoliposome, or what Davidson calls a “nano fat ball around an active ingredient.” Kester, in whose lab the approach was developed, thinks of it as a basketball with a thick bilayer coating that contains 30 percent active ceramide and a hollow interior that can hold another cancer drug.


Skin Patches Melt Fat

Researchers have devised a medicated skin patch that can turn energy-storing white fat into energy-burning brown fat locally while raising the body’s overall metabolism. The patch could be used to burn off pockets of unwanted fat such as “love handles” and treat metabolic disorders, such as obesity and diabetes, according to researchers at Columbia University Medical Center (CUMC) and the University of North Carolina. Humans have two types of fat. White fat stores excess energy in large triglyceride droplets. Brown fat has smaller droplets and a high number of mitochondria that burn fat to produce heat. Newborns have a relative abundance of brown fat, which protects against exposure to cold temperatures. But by adulthood, most brown fat is lost.

For years, researchers have been searching for therapies that can transform an adult’s white fat into brown fat—a process named browning—which can happen naturally when the body is exposed to cold temperatures—as a treatment for obesity and diabetes.


There are several clinically available drugs that promote browning, but all must be given as pills or injections,” said study co-leader Li Qiang, PhD, assistant professor of pathology & cell biology at Columbia. “This exposes the whole body to the drugs, which can lead to side effects such as stomach upset, weight gain, and bone fractures. Our skin patch appears to alleviate these complications by delivering most drugs directly to fat tissue.

To apply the treatment, the drugs are first encased in nanoparticles, each roughly 250 nanometers (nm) in diameter—too small to be seen by the naked eye. (In comparison, a human hair is about 100,000 nm wide.) The nanoparticles are then loaded into a centimeter-square skin patch containing dozens of microscopic needles. When applied to skin, the needles painlessly pierce the skin and gradually release the drug from nanoparticles into underlying tissue.

The findings, from experiments in mice, were published online today in ACS Nano.


Magnetic Cellular ‘Legos’ For Tissue Engineering

By incorporating magnetic nanoparticles in cells and developing a system using miniaturized magnets, researchers from 3 associated universities* in Paris (France) , have succeeded in creating cellular magneticLegos.” They were able to aggregate cells using only magnets and without an external supporting matrix, with the cells then forming a tissue that can be deformed at will. This approach, which is detailed in Nature Communications, could prove to be a powerful tool for biophysical studies, as well as the regenerative medicine of tomorrow.

Nanotechnology has quickly swept across the medical field by proposing sometimes unprecedented solutions at the furthest limits of current treatments, thereby becoming central to diagnosis and therapy, notably for the regeneration of tissue. A current challenge for regenerative medicine is to create a cohesive and organized cellular assembly without using an external supporting matrix. This is a particularly substantial challenge when it involves synthesizing thick and/or large-sized tissue, or when these tissues must be stimulated like their in vivo counterparts (such as cardiac tissue or cartilage) in order to improve their functionality.

The researchers met this challenge by using magnetism to act on the cells at a distance, in order to assemble, organize, and stimulate them. Cells, which are the building blocks of tissue, are thus magnetized in advance through the incorporation of magnetic nanoparticles, thus becoming true cellular magnetic “Legos” that can be moved and stacked using external magnets. In this new system acting as a magnetic tissue stretcher, the magnetized cells are trapped on a first micromagnet, before a second, mobile magnet traps the aggregate formed by the cells. The movement of the two magnets can stretch or compress the resulting tissue at will.

Researchers first used embryonic stem cells to test their system. They began by showing that the incorporation of nanoparticles had no impact on either the functioning of the stem cell or its capacity for differentiation. These functional magnetic stem cells were then tested in the stretcher, in which they remarkably differentiated toward cardiac cell precursors when stimulation imposed “magnetic beating” imitating the contraction of the heart. These results demonstrate the role that purely mechanical factors can play in cell differentiation.

This “all-in-one” approach, which makes it possible to build and manipulate tissue within the same system, could thus prove to be a powerful tool both for biophysical studies and tissue engineering.

* Laboratoire Matière et Systèmes Complexes (CNRS/Université Paris Diderot), in collaboration with the Laboratoire Adaptation Biologique et Vieillissement (CNRS/UPMC) and the Centre de Recherche Cardiovasculaire de Paris (Inserm/Université Paris Descartes)


Rapid, Cheap Liver Cancer Test

University of Utah researchers say they are designing a diagnostic method that will be able to accurately identify signs of liver cancer within minutes, saving critical time for patients of the stealthy disease. The new type of test could forever change how people screen for the disease, said Marc Porter, a U. chemical engineering and chemistry professor who is leading the research along with Dr. Courtney Scaife, a surgeon who both practices and teaches surgery for the university. Porter said the long-term vision is for the tool itself to become as automatic and portable as a pregnancy test, though additional technology — called a spectrometer — is currently needed to precisely measure the results of the test.

A small domino-sized cartridge holds a membrane for a new field test for liver cancer developed by researchers from the University of Utah. The test doesn’t involve sending a specimen to a blood lab and cuts the wait time for results from two weeks to two minutes. It can be administered wherever the patient is, which will be valuable for developing nations with little access to hospitals.

It’s really compact, it’s simple and low cost,” he said of the test kit.

Liver cancer is difficult to survive because typically it is highly developed by the time symptoms show up, Porter said. It is the second deadliest form of cancer worldwide, resulting in about 788,000 deaths in 2015, according to the World Health Organization. “All too often, the cancer is diagnosed past when you can actually have surgical intervention,” Porter said.

Currently, a blood test taken to determine the presence of liver cancer is usually sent to a lab offsite, where it takes days or even up to two weeks to test and return, said Vincent Horiuchi, spokesman for the U.’s College of Engineering. Those days are precious time that is lost in the fight against the disease, he said.


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.