ONI’s microscope, the Nanoimager, has the footprint of a desktop computer, is about 30 times smaller and significantly less expensive than current super-resolution microscopes, and it will be manufactured in the UK.
ONI have raised £1.2m in a seed funding round from Oxford Sciences Innovation plc, Oxford Technology Management and Oxford-based investors Barnaby Martin and George Robinson.
This super-resolution microscope – developed by an interdisciplinary team led by Professor Achillefs Kapanidis and PhD student, Bo Jing, at Oxford’s Department of Physics – uses precise, rapid imaging of single fluorescent molecules and sophisticated software to generate striking images which differentiate objects spaced as close as 20 nanometers, a distance 200 times smaller than the length of an E. coli bacterium. This high performance offers much sharper images of live cells than conventional optical microscopy which is limited by diffraction.
Professor Kapanidis said: “The new microscope will take single-molecule imaging out of physics labs and centralised facilities, and into the hands of the chemist, the biologist, the biotechnologist. It is not only an excellent instrument for super-resolution imaging, but also a versatile, user-friendly toolbox that will help new users innovate with single molecules as their new currency.”
The new microscope can also help study how the tiny “biological machines” within cells assemble or break down biological structures such as proteins. These powerful capabilities can be exploited to screen chemical libraries for drug discovery, and to develop new generations of biosensors for detecting pathogens or disease markers. “It will unlock the users’ imagination and creativity,” Kapanidis said, “I wish I had this when I was a graduate student.”
Oxford Nanoimaging CEO Jeremy Warren said: “With Oxford Nanoimaging, we aim to democratise the use of super-resolution microscopy. Scientists who don’t have a lab equipped with specialist physics kit and a large budget can still access the information this very powerful technology provides. We anticipate that by our second year, 90 per cent of sales will be to groups outside of the UK creating a strong exporting business.”
Isis Innovation managing director Linda Naylor said: “In 2014, three prominent physicists won the Nobel Prize in Chemistry for starting super-resolution fluorescence microscopy and “bringing optical microscopy into the nano-dimension”. This Oxford spinout will make this advance accessible across the scientific world.”
In 2014, the Nobel Prize in physics was awarded for the discovery of the gallium-nitride-based blue-light LED and its use for new, efficient LED-based white lamps. The development efforts in this field, however, do not stop there. The active layers in this type of diode take up less than 1μm. This means that most of the material in planar LEDs now on the market, which are hundreds of micrometers thick, is not used. This provides a motivation to continue research on efficient LEDs with nanoscale dimensions.1
In the last few years, it has been shown that an efficient LED can be made as a 3D nanostructure, in which the active parts take up less than 1μm. This makes more efficient use of the materials involved and, at the same time, excludes structural defects that limit the LED performance from the active device volume. Nanometer-sized LED structures can take many different shapes, such as thin elongated wires, pyramids, cubes, or platelets. To grow each of these small objects, different sections—including contact layers and an active region where the light is produced—are used. Basic material properties, however, put constraints on what can be grown, which affects the choice of shape for the nano-LED. For visible-light LEDs, the III nitrides—gallium nitride (GaN), aluminum nitride, indium nitride, and their alloys—are very suitable since they offer bandgaps in the visible range of photon energies.
We have recently summarized the current status of the development of nanowire-based LEDs.1 These devices are mainly shaped like nanorods with hexagonal cross sections, where the different layers are grown in a concentric manner around a core section (see Figure 1). The active region that produces the light consists of indium gallium nitride (InGaN) quantum wells (QWs) on m-plane facets, where ‘m’ refers to a specific crystallography orientation. Such QWs do not suffer from any polarization fields since the m-plane is non-polar. All other layers in the structure—the core, underlayer, QW barrier layers, p-layer and p-contact layer—are grown from GaN. A disadvantage with this design is that emission wavelengths longer than green are difficult to produce because of limitations with incorporating indium in the m-plane. Furthermore, there is a large lattice misfit strain built into the active QW region for high concentrations of indium corresponding to long wavelengths. This eventually causes defects and a reduced radiative efficiency for the LED.
Figure 1. Top left: Electroluminescence from the first blue nanowire LED fabricated by Glo AB in April 2007. Bottom left: Blue, green, yellow, and red examples from current state-of-the-art nanowire LEDs, grown by Glo-USA Inc. in 2013. Center: Side-view of a scanning electron microscope (SEM) image, showing nanowire LEDs monolithically grown on a wafer of gallium nitride on silicon. The edge of the top contact layer is visible, and both the contacted and non-contacted LEDs can be seen. Right: SEM image illustrating the air-bridge process. Images provided courtesy of QuNano AB and Glo AB.1 p-GaN: p-Type gallium nitride. p-AlGaN: p-Type aluminum gallium nitride.
In our latest work,2 we aim to solve these problems. The main concept driving our research is the need to create a ternary InGaN alloy in the form of a fully relaxed and dislocation-free c-oriented micro-substrate, where ‘c’ refers to another crystallography orientation. Our basic idea is to use the c-plane for the growth of the main LED structure, which improves the indium incorporation, with the use of a pre-fabricated indium-containing c-facet. This provides an opportunity to extend the possible emission wavelengths towards the red (see Figure 2). To handle the polarization fields existing in the c-plane structures, all layers in the structure should be made of InGaN, thereby reducing the strain. Importantly, this also also relaxes the otherwise stringent limitation on the QW width (because of the piezoelectric field in the QWs), which is typical for planar c-plane structures.
Figure 2. Top left: Schematic side-view cross section of a red-emitting LED. Bottom left: Top-view SEM image of a vertically grown pn-junction. The scale bar indicates 250nm. Right: Electrically driven red-emitting LED for the structure shown to the left. n/p-InGaN: n-Type/p-Type indium gallium nitride. QW: Quantum well. SQW: Single QW.
In our work, we demonstrate how a unique sequence of growth and processing steps—initiated by a nanowire structure—enables the formation of c-oriented platelets of fully relaxed, still dislocation-free, InGaN micro-substrates. On top of these substrates, it is now possible to grow dislocation-free, more indium-rich InGaN QWs that are designed to emit throughout the green to red spectral range. We have not yet established the typical efficiency of these LEDs, but we estimate it to be a few percent at present. This is considerably better than for typical planar red LEDs, even though these efficiencies were reached without any real optimization efforts.
In summary, we have shown that InGaN-based nano-LED structures show promise for solving the problems associated with long-wavelength nitride LEDs. There is a demand for LEDs covering all visible wavelengths using the GaN-InGaN material system. The first applications of our device, which does not require very high output power from the LEDs, may be for display technology. In fact, we can fabricate InGaN nano-LEDs that emit at blue and green wavelengths in one processing step on the same wafer. This provides additional opportunities and flexibility for display design. In the future we aim to create a flat substrate on to which we can form an active QW with an even higher indium-concentration, corresponding to emission of longer wavelengths (e.g. green, yellow, and red).
The past 70 years have seen the way we live and work transformed by two tiny inventions. The electronic transistor and the microchip are what make all modern electronics possible, and since their development in the 1940s they’ve been getting smaller. Today, one chip can contain as many as 5 billion transistors. If cars had followed the same development pathway, we would now be able to drive them at 300,000mph and they would cost just £3 each.
But to keep this progress going we need to be able to create circuits on the extremely small, nanometre scale. A nanometre (nm) is one billionth of a metre and so this kind of engineering involves manipulating individual atoms. We can do this, for example, by firing a beam of electrons at a material, or by vaporising it and depositing the resulting gaseous atoms layer by layer onto a base.
The real challenge is using such techniques reliably to manufacture working nanoscale devices. The physical properties of matter, such as its melting point, electrical conductivity and chemical reactivity, become very different at the nanoscale, so shrinking a device can affect its performance. If we can master this technology, however, then we have the opportunity to improve not just electronics but all sorts of areas of modern life.
1. Doctors inside your body
Wearable fitness technology means we can monitor our health by strapping gadgets to ourselves. There are even prototype electronic tattoos that can sense our vital signs. But by scaling down this technology, we could go further by implanting or injecting tiny sensors inside our bodies. This would capture much more detailed information with less hassle to the patient, enabling doctors to personalise their treatment.
The possibilities are endless, ranging from monitoring inflammation and post-surgery recovery to more exotic applications whereby electronic devices actually interfere with our body’s signals for controlling organ function. Although these technologies might sound like a thing of the far future, multi-billion healthcare firms such as GlaxoSmithKline are already working on ways to develop so-called “electroceuticals”.
2. Sensors, sensors, everywhere
These sensors rely on newly-invented nanomaterials and manufacturing techniques to make them smaller, more complex and more energy efficient. For example, sensors with very fine features can now be printed in large quantities on flexible rolls of plastic at low cost. This opens up the possibility of placing sensors at lots of points over critical infrastructure to constantly check that everything is running correctly. Bridges, aircraft and even nuclear power plants could benefit.
3. Self-healing structures
If cracks do appear then nanotechnology could play a further role. Changing the structure of materials at the nanoscale can give them some amazing properties – by giving them a texture that repels water, for example. In the future, nanotechnology coatings or additives will even have the potential to allow materials to “heal” when damaged or worn. For example, dispersing nanoparticles throughout a material means that they can migrate to fill in any cracks that appear. This could produce self-healing materials for everything from aircraft cockpits to microelectronics, preventing small fractures from turning into large, more problematic cracks.
4. Making big data possible
All these sensors will produce more information than we’ve ever had to deal with before – so we’ll need the technology to process it and spot the patterns that will alert us to problems. The same will be true if we want to use the “big data” from traffic sensors to help manage congestion and prevent accidents, or prevent crime by using statistics to more effectively allocate police resources.
Here, nanotechnology is helping to create ultra-dense memory that will allow us to store this wealth of data. But it’s also providing the inspiration for ultra-efficient algorithms for processing, encrypting and communicating data without compromising its reliability. Nature has several examples of big-data processes efficiently being performed in real-time by tiny structures, such as the parts of the eye and ear that turn external signals into information for the brain.
Computer architectures inspired by the brain could also use energy more efficiently and so would struggle less with excess heat – one of the key problems with shrinking electronic devices further.
The common trick in both applications is to use nanotexturing or nanomaterials (for example nanowires or carbon nanotubes) that turn a flat surface into a three-dimensional one with a much greater surface area. This means that there is more space for the reactions that enable energy storage or generation to take place, so the devices operate more efficiently
In the future, nanotechnology could also enable objects to harvest energy from their environment. New nano-materials and concepts are currently being developed that show potential for producing energy from movement, light, variations in temperature, glucose and other sources with high conversion efficiency.
The Sicrys family of conductive inks are based on technology that produce narrower conductive patterns with minimum waste results when used during digital inkjet printing. The inks were developed to be used for the mass production of printed electronics and that industry’s extremely demanding requirements. PV Nano Cell, the developer of advanced single-crystal nanometric conductive digital inks, and their dispersion technology is capable of producing some highly efficient electronics. Products made with the inks offer improved conductivity, superior electrical properties and produce less waste than traditionally manufactured electronics. The company has just introduced their new copper Sicrys conductive ink, which is actually the first copper-based nanometric solution available on the market.
PV Nano Cell will be showing off their entire portfolio of Sicrys conductive inks to LOPEC 2016, the international printed electronics event being held in Munich, Germany on April 6th and 7th. Their new inks are a huge leap forward in the race to perfect the process of 3D printing electronics, and products made with them will have applications in computing, wearable devices and is likely to play a large role in the continued development of the Internet of Things. The Sicrys inks are expected to finally make the mass production of printed electronics possible, something that has never been viable previously.
“LOPEC 2016 will be particularly exciting, as 3D printed electronics are on the verge of becoming reality. 3D printed electronics with embedded electronics within the structural material will revolutionize the use of electronics and data usage. Printed electronics will soon become integrated into daily life, from customized electronics to medical devices,” explained PV Nano Cell CEO Fernando de la Vega.
The cost effective and sustainable Series inks will allow huge leaps forward in the manufacturing of things like mobile phone antennas and fully-functional printed circuit boards. The materials will lead to thinner and smaller smartphones and other Internet of Things connected devices. PV Nano Cell’s Sicrys conductive ink materials are made using single crystal nanoparticles, that are ideal for 3D printing on flexible materials like plastic, fabric or even paper. Their newly developed copper nanometric conductive ink offers the same high-grade performance of Sicrys silver ink but also offers exceptional cost-efficiency, making 3D printed electronics cheaper and more accessible to everyone.
Founded back in 2009, PV Nano Cell manufactures their Sicrys family of conductive inks for companies all over the world. In addition to the success that they are starting to find with the Sicrys materials, they also manufacture a full range of 3D printed electronics applications, 3D printed circuit boards, RFID, sensors and smartphone touchscreens. One of the largest parts of the company is their extensive R&D division which constantly seeks to push the current boundaries of technology further.
PV Nano Cell was recently awarded the IDTechEx 2015 for Best Development in Materials for 3D Printing. They will be featuring their industrial inkjet printing applications this year at LOPEC 2016. If you’re going to be in Munich then you can check out their technology on exhibit at Hall B0, Booth 109 at LOPEC (April 6th and 7th). And you can find out more about PV Nano Cell and their conductive ink materials by going to their website. Do you think these new inks will have an impact on electronics? DIscuss in the PV Nano Cell New 3D Printing Inks forum over at 3DPB.com.
A new tool is emerging in the fight against antibiotic-resistant bacterial disease. Beyond the global efforts to limit overuse and abuse of antibiotic drugs, nanomedicine is finding additional ways to attack these superbugs.
Nanoparticles, a million times smaller than a millimeter, are proving to be stable, easy to deliver and readily incorporated into cells.
In recent work, a group of researchers at the University of Colorado, of which I am a member, has used nanoscale quantum dots – minuscule semiconductor particles with specific light-absorption properties – to kill drug-resistant superbugs without harming the surrounding healthy tissue.
Once introduced into the body, the quantum dots do nothing until they are activated by having a light shined on them. Any visible light source (a lamp, room light or even sunlight) can be used for this. So far our research has focused on topical infections on the skin; deeper inside the body, brighter lights or more nanoparticles may be needed.
When activated by light, the quantum dots start generating electrons that attach to dissolved oxygen in the cells, creating radical ions. Those ions interrupt biochemical reactions which cells rely on for communication and basic life functions. In this way, we can target and kill very specific bacterial cells that cause illnesses.
The superbug threat
Antibiotics are used not just to treat active bacterial infections; they are also routinely given to patients undergoing surgery, and people with compromised immune systems from diseases like HIV and cancer.
Bacteria that are resistant to more than one antibiotic drug – or “superbugs,” as they are commonly called – infect more than 2 million Americans a year, and kill 23,000 of them. Globally, they kill more than 700,000 people each year.
Projections by a United Kingdom government research panel suggest that if unchecked, superbugs could kill more than 10 million people each year by 2050. That would far outpace all other major causes of death – including diabetes, cancer, diarrhea and road accidents. The economic cost is estimated at US$100 trillion by 2050.
Focusing on a target
There are other nano-scale medicines for fighting infectious bacteria. When exposed to light, they heat up, killing all cells around them – not just the disease-causing ones. They therefore require special tools such as proteins or antibodies that selectively stick to desired cell types, to deliver them to very specific locations. That in turn requires the ability to accurately identify target cells.
Our method is an improvement because it allows more specific targeting of cells to be treated. Quantum dots with different sizes and electrical properties can help create different disruptive ions. That can allow doctors to choose disruptors to kill invading bacteria without harming nearby healthy tissue.
The activated quantum dots upset the balance of chemical processes, called “reduction-oxidation” or “redox” for short, in disease-causing bacteria in order to kill them.
Using this method and only a normal light bulb, we were able to eliminate a broad range of antibiotic-resistant bacteria. The bacteria were provided to us in the form of actual clinical samples from the University of Colorado School of Medicine. They included some of the most dangerous drug-resistant infections: methicillin-resistant Staphylococcus aureus; extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Salmonella typhimurium; multi-drug-resistant Escherichia coli; and carbapenem-resistant Escherichia coli.
We were also able to make nanoparticles with different reactions to light, including having no response or even improving cellular reproduction. Increasing the growth of superbugs is not desirable, but this discovery may allow us encourage the growth of useful bacteria, such as in bioreactors, which can help manufacture of biofuels and antibiotic drugs.
Taking the next steps
So far our work has been in test tubes in controlled labs; our next step is to study this technique in animals. If successful, this technology could boost the fight against multi-drug-resistant bacteria in the short term and well out into the future.
It might, for example, spur the creation of a new class of light-activated drugs, lead to development of special fabrics with LED lights for phototherapy, and even form the basis of self-disinfecting surfaces and medical equipment.
And while the bacteria will continue to evolve to seek survival, our ability to control the specific reaction of the quantum dots once activated could let us move more quickly in this fight where defeat is not an option.
Nanotechnology has helped scientists cure mice which have breast cancer in its terminal stage. The study could be a turning point in treating the disease with clinical trials on human patients expected to be conducted as early as next year.
“I would never want to over-promise to the thousands of patients looking for a cure but the data is astounding,” Mauro Ferrari, president of the Houston Methodist Research Institute in Texas and a co-senior author of the paper said in the press release published by the Houston Methodist leading medicine website. The study, conducted by a team of researchers from Houston Methodist Research Institute, was published in the journal Nature Biotechnology.
The new treatment for breast cancer, which used the so-called “nanoparticle generator” proved to be effective in mice and, therefore, has colossal potential to be transformed in order to treat the disease in humans, scientists said. The generator successfully interferes with the tumor cell’s ability to develop drug resistance.
“This may sound like science fiction, like we’ve penetrated and destroyed the Death Star, but what we discovered is transformational. We invented a method that actually makes the nanoparticles inside the cancer and releases the drug particles at the site of the cellular nucleus. With this injectable nanoparticle generator, we were able to do what standard chemotherapy drugs, vaccines, radiation, and other nanoparticles have all failed to do,” said Ferrari.
During their research Ferrari and his colleagues used a chemotherapy drug called doxorubicin but hid it inside microscopic silicon discs. This way the cancer cells lost their ability to resist the treatment. When the disc was inside a tumor cell, it broke down and the anti-cancer doxorubicin was released.
The study showed that half of the mice that had been injected with the new drug had no traces of cancer for eight months. This is tantamount to 24 years in humans, the scientists explained.
“If this research bears out in humans and we see even a fraction of the survival time, we are still talking about dramatically extending life for many years.
“That’s essentially a providing a cure in a patient population that is now being told there is none,” Ferrari said.
Although the new method was only tested for curing breast cancer, Ferrari expressed a strong hope that it could be also used in fighting other cancer types.
According to the scientist, the discovery could completely turn the current cancer treatment head over hills.
“We are talking about changing the landscape of metastatic disease, so it’s no longer a death sentence,” he said.
“Lung and liver metastases are the two main reasons why we lose cancer patients. The results we have proven with this paper is that we can provide a functional cure; we can essentially cure long-term, [giving] disease-free survival for about 50 per cent of the animals that we provided this therapy to.”
The scientists plan to obtain approval from the Federal Drug Administration and begin clinical trials in humans in 2017.
No more tough breaks. As “smart” electronics get smaller and softer, scientists are developing new medical devices that could be applied to — or in some cases, implanted in — our bodies. And these soft and stretchy devices shouldn’t make your skin crawl, because they’re designed to blend right in, experts say.
We want to solve the mismatch between rigid wafer-based electronics and the soft, dynamic human body, said Nanshu Lu, an assistant professor of aerospace engineering and engineering mechanics at the University of Texas at Austin.
Lu, who previously studied with John Rogers, a soft-materials and electronics expert at the University of Illinois Urbana-Champaign, focuses her research on stretchable bioelectronics. Lu and her colleagues have invented a cheaper and faster method for manufacturing electronic skin patches called epidermal electronics, reducing what was a multiday process to 20 minutes. [Bionic Humans: Top 10 Technologies]
Lu spoke with Live Science about emerging bioelectronics that are smart and flexible enough to essentially meld with the human body. From the latest advancements in smart tattoos to injectable brain monitoring to stretchable electronics for drug delivery, here are five fascinating technologies that could soon be on (or inside) your body.
Smart temporary tattoos
“When you integrate electronics on your skin, it feels like part of you,” Lu said. “You don’t feel it, but it is still working.” That’s the idea behind “smart” temporary tattoos that John Rogers and his colleagues are developing. Their tattoos, also known as biostamps, contain flexible circuitry that can be powered wirelessly and are stretchy enough to move with skin.
These wireless smart tattoos could address clinically important — but currently unmet — needs, Rogers told Live Science. Although there are numerous potential applications, his team is focused now on how biostamps could be used to monitor patients in neonatal intensive care units and sleep labs. MC10, the Massachusetts-based company Rogers helped start, is conducting clinical trials and expects to launch its first regulated products later this year.
Skin-mounted biochemical sensors
Another new body-meld technology in development is a wearable biochemical sensor that can analyze sweat through skin-mounted devices and send information wirelessly to a smartphone. These futuristic sensors are being designed by Joseph Wang, a professor of nanoengineering at the University of California, San Diego, and director of the Center for Wearable Sensors.
“We look at sweat, saliva and tears to provide information about performance, fitness and medical status,” Wang told Live Science.
Earlier this year, members of Wang’s lab presented a proof-of-concept, flexible, temporary tattoo for diabetics that could continuously monitor glucose levels without using needle pricks. He also led a team that created a mouth-guard sensor that can check levels of health markers that usually require drawing blood, like uric acid, an early indicator for diabetes and gout. Wang said the Center for Wearable Sensors is pushing to commercialize these emerging sensor technologies with the help of local and international companies.
Nanomaterial drug delivery
Dae-Hyeong Kim, an associate professor of chemical and biological engineering at Seoul National University in South Korea, and his colleagues are pursuing nanotechnologies to enable next-generation biomedical systems. Kim’s research could one day yield nanomaterial-enabled electronics for drug delivery and tissue engineering, according to Lu. “He has made stretchable memory, where you can store data on the tattoo, ” she said. [10 Technologies That Will Transform Your Life]
In 2014, Kim’s research group made a stretchable, wearable electronic patch that contains data storage, diagnostic tools and medicine. “The multifunctional patch can monitor movement disorders of Parkinson’s disease,” Kim told Live Science. Collected data gets recorded in the gold nanoparticle device’s memory.
When the patch detects tremor patterns, heat and temperature sensors inside it release controlled amounts of drugs that are delivered through carefully designed nanoparticles, he explained.
Injectable brain monitors
Although implantable technology exists for monitoring patients with epilepsy or brain damage, Lu pointed out that these devices are still sharp and rigid, making long-term monitoring a challenge. She compared soft brain tissue to a bowl of tofu constantly in motion. “We want something that can measure the brain, that can stimulate the brain, that can interact with the brain — without any mechanical strain or loading,” she said.
Enter Charles Lieber, a Harvard University chemistry professor whose research group focuses on nanoscale science and technology. His group’s devices are so small that they can be injected into brain tissue through a needle. After injection, nanoscale electronic mesh opens up that can monitor brain activity, stimulate tissue and even interact with neurons. “That,” said Lu, “is very cutting edge.”
Long-term implantable devices
Stéphanie Lacour and Grégoire Courtine, scientists at the École Polytechnique Fédérale de Lausanne’s School of Engineering, announced in early 2015 that they had developed a new implant for treating spinal cord injuries. The small e-Dura device is implanted directly on the spinal cord underneath its protective membrane, called the dura mater. From there, it can deliver electrical and chemical stimulation during rehabilitation.
The device’s elasticity and biocompatibility reduce the possibility of inflammation or tissue damage, meaning it could stay implanted for a long time. Paralyzed rats implanted with the device were able to walk after several weeks of training, the researchers reported in the journal Science.
Lu called e-Dura one of the best-functioning, long-term implantable flexible stimulators. “It shows the possibilities of using implantable, flexible devices for rehabilitation and treatment,” she said.
Meanwhile, technologies that replicate human touch are growing increasingly sophisticated. Stanford University chemical engineering professor Zhenan Bao has spent years developing artificial skin that can sense pressure and temperature and heal itself. Her team’s latest version contains a sensor array that can distinguish between pressure differences like a firm or limp handshake.
Lu said she and her colleagues in this highly multidisciplinary field hope to make all wafer-based electronics more epidermallike. “All those electronic components that used to be rigid and brittle now have a chance to become soft and stretchable,” she said.