USING NANO-SENSORS TO DIAGNOSE NEUROLOGICAL DISORDERS & FOR POWERFUL BRAIN-COMPUTER INTERFACES.
A team of scientists has developed a new kind of biosensor that can be injected straight into the bloodstream, and will then travel to your brain, where they will — according to the scientists behind the project — monitor your neural activity and even potentially thoughts.
The cell-sized nanosensors, aptly named NeuroSWARM3, can cross the blood-brain barrier to the brain, where they convert neural activity into electrical signals, allowing them to be read and interpreted by machinery, according to work by a team of University of California, Santa Cruz scientists that will be presented next week at a virtual Optical Society conference.
The tech could, the researchers say, help grant extra mobility to people with disabilities in addition to helping scientists understand human thoughtbetter than before. However, they haven’t yet been tested on humans or even animals.
“NeuroSWARM3 can convert the signals that accompany thoughts to remotely measurable signals for high precision brain-machine interfacing,” lead study author A. Ali Yanik said in a press release. “It will enable people suffering from physical disabilities to effectively interact with the external world and control wearable exoskeleton technology to overcome limitations of the body. It could also pick up early signatures of neural diseases.”
It’s also a notably different approach to the problem of brain-computer interfaces from most high profile attempts, including Elon Musk’s Neuralink, which are working on implant-based solutions instead of nanosensor swarms.
During tests, the team found that their nanosensor swarm is sensitive enough to pick up on the activity of individual brain cells. Single-neuron readings aren’t new, but the ability to detect them with free-floating sensors, and especially the ability to wirelessly broadcast them through a patient’s thick skull, is an impressive technological development. If further tests continue to pan out, those capabilities could make real-time neuroscientific research simpler and neurological medicine more sophisticated.
“We are just at the beginning stages of this novel technology, but I think we have a good foundation to build on,” Yanik added. “Our next goal is to start experiments in animals.”
Engineers turn bubbles into motors to propel minute vessels through landscapes of cells and particles suspended in fluid
Ever since nanotechnology became a real branch of engineering, its practitioners have been trying to design tiny structures that can work like submarines to navigate through the human body.
One stumbling block towards this goal has been what fuels and motor analogues could be used to propel and steer such nano-vessels around and inside blood vessels and organs without causing harm.
Researchers at Pennsylvania State University and the University of San Diego hit a wall with their research, because they were using toxic materials like hydrogen peroxide as fuel. A fortuitous discovery about the behaviour of bubbles has opened up a new avenue for their research, as they describe in Science Advances.
Working with material scientists at the Harbin Institute of technology in Shenzhen and surgeons at University of Michigan, Thomas Mallouk of the Department of Chemistry at Penn State was trying to move nano-vessels with acoustic levitation, a technique used to lift particles off microscope slides. Unexpectedly, he found that high-frequency sound waves made the vessels move at very fast speeds. Investigating this phenomenon further, Mallouk and his team designed microscale “rockets” that can use acoustics to zip around and steer in a liquid medium.
The rockets are not rocket-shaped. They resemble a round-bottomed cup 10µm in length and 5µm wide, 3D printed from a polymer and coated with a 10nm-thick layer of nickel and a 40nm-thick layer of gold.
The inside of the cup is then coated with trichlorosilane, which repels water. When submerged in fluid, an air bubble spontaneously forms inside the cup. When bombarded with ultrasound waves, the bubble vibrates, turning it into a motor and propelling it through the fluid. The vessel can be steered with precision by manipulating an external magnetic field. Each rocket has a characteristic resonant frequency, so individual vessels can be driven independently.
Steering of the vessels is so precise that Mallouk’s team made them move up microscopic staircase structures. The addition of fins to the cup structures allows them to be steered freely in three dimensions.
Moreover, the team describes using the vessels to push other particles or cells around, or tow them with precision through a crowded environment. The key to this is the small size of the vessels, Mallouk claims.
“This wasn’t available on a larger scale,” he said. “There’s a lot of control you can do at this length scale. At this particular length scale, we’re right at the crossover point between when the power is enough to affect other particles.”
Changing the acoustic stimulation adjusts the speed of the vessels. “If I want it to go slow, I can turn the power down, and if I want it to go really fast, I can turn the power up,” explains Jeff McNeill, a graduate student who works on nano-and microscale motor projects. “That’s a really useful tool.”
Mallouk is working with engineers and roboticists at Penn to equip the vessels with computer chips and sensors to give them autonomy and intelligence, which would allow them to be used for tasks including imaging and even surgery. “We’d like to have controllable robots that can do tasks inside the body: delivering medicine, diagnostic snooping,” he said.
How a new quantum sensor could improve cancer treatment
The development of medical imaging and monitoring methods has profoundly impacted the diagnosis and treatment of cancer. These non-invasive techniques allow health care practitioners to look for cancer in the body and determine if treatment is working.
But current techniques have limitations; namely, tumours need to be a specific size to be visible. Being able to detect cancer cells, even before there are enough to form a tumour, is a challenge that researchers around the world are looking to solve.
The solution may lie in nanotechnology
Researchers at the University of Waterloo’s Institute for Quantum Computing (IQC) have developed a quantum sensor that is promising to outperform existing technologies in monitoring the success of cancer treatments.
Artist’s rendering of the interaction of incident single photon pulses and a tapered semiconductor nanowire array photodetector.
“A sensor needs to be very efficient at detecting light,” explains principal investigator Michael Reimer, an IQC faculty member and professor in the Faculty of Engineering. “What’s unique about our sensor is that the light can be absorbed all the way, from UV to infrared. No commercially available device exists that can do that now.”
Current sensors reflect some of the light, and depending on the material, this reflection can add up to 30 percent of the light not being absorbed.
This next-generation quantum sensor designed in Reimer’s lab is very efficient and can detect light at the fundamental limit — a single photon — and refresh for the next one within nanoseconds. Researchers created an array of tapered nanowires that turn incoming photons into electric current that can be amplified and detected.
When applied to dose monitoring in cancer treatment, this enhanced ability to detect every photon means that a health practitioner could monitor the dose being given with incredible precision — ensuring enough is administered to kill the cancer cells, but not too much that it also kills healthy cells.
Moving quantum technology beyond the lab
Reimer published his findings in Nature Nanotechnology in March and is now working on a prototype to begin testing outside of his lab. Reimer’s goal is to commercialize the sensor in the next three to five years.
“I enjoy the fundamental research, but I’m also interested in bringing my research out of the lab and into the real world and making an impact to society,” says Reimer.
He is no stranger to bringing quantum technology to the marketplace. While completing his post doctorate at the Delft University of Technology in The Netherlands, Reimer was an integral part of the startup, Single Quantum, developing highly efficient single-photon detectors based on superconducting nanowires.
Reimer’s latest sensor has a wide range of applications beyond dose monitoring for cancer treatments. The technology also has the ability to significantly improve high-speed imaging from space and long-range, high-resolution 3D images.
“A broad range of industries and research fields will benefit from a quantum sensor with these capabilities,” said Reimer. “It impacts quantum communication to quantum lidar to biological applications. Anywhere you have photon-starved situations, you would want an efficient sensor.”
He is exploring all industries and opportunities to put this technology to use.
Breakthroughs come in unexpected places
After earning his undergraduate degree in physics at the University of Waterloo, Reimer moved to Germany to play professional hockey. While taking graduate courses at the Technical University of Munich, he met a professor of nanotechnology who sparked his interest in the field.
“I played hockey and science was my hobby,” says Reimer. “Science is still my hobby, and it’s amazing that it is now my job.” Reimer went on to complete his PhD at the University of Ottawa/National Research Council of Canada, and turned his attention to quantum light sources. Reimer is an internationally renowned expert in quantum light sources and sensors. The idea for the quantum sensor came from his initial research in quantum light sources.
“To get the light out from the quantum light source, we had to come up with a way that you don’t have reflections, so we made this tapered shape. We realized that if we can get the light out that way we could also do the reverse — that’s where the idea for the sensor came from.”
Reimer will be at the Waterloo Innovation Summit on October 1, to present his latest breakthrough and its potential impact on the health care sector. And while he works to bring the sensor to market, Reimer’s lab continues to push the boundaries of quantum photonics.
From discovering the path to perfect photon entanglement to developing novel solid-state quantum devices, Reimer’s research is advancing technologies that could disrupt a multitude of industries and research fields.
What if drones and self-driving cars had the tingling “spidey senses” of Spider-Man?
They might actually detect and avoid objects better, says Andres Arrieta, an assistant professor of mechanical engineering at Purdue University, because they would process sensory information faster.
Better sensing capabilities would make it possible for drones to navigate in dangerous environments and for cars to prevent accidents caused by human error. Current state-of-the-art sensor technology doesn’t process data fast enough—but nature does.
And researchers wouldn’t have to create a radioactive spider to give autonomous machines superhero sensing abilities.
Instead, Purdue researchers have built sensors inspired by spiders, bats, birds and other animals, whose actual spidey senses are nerve endings linked to special neurons called mechanoreceptors.
The nerve endings—mechanosensors—only detect and process information essential to an animal’s survival. They come in the form of hair, cilia or feathers.
“There is already an explosion of data that intelligent systems can collect—and this rate is increasing faster than what conventional computing would be able to process,” said Arrieta, whose lab applies principles of nature to the design of structures, ranging from robots to aircraft wings.
“Nature doesn’t have to collect every piece of data; it filters out what it needs,” he said.
Many biological mechanosensors filter data—the information they receive from an environment—according to a threshold, such as changes in pressure or temperature.
A spider’s hairy mechanosensors, for example, are located on its legs. When a spider’s web vibrates at a frequency associated with prey or a mate, the mechanosensors detect it, generating a reflex in the spider that then reacts very quickly. The mechanosensors wouldn’t detect a lower frequency, such as that of dust on the web, because it’s unimportant to the spider’s survival.
The idea would be to integrate similar sensors straight into the shell of an autonomous machine, such as an airplane wing or the body of a car. The researchers demonstrated in a paper published in ACS Nano that engineered mechanosensors inspired by the hairs of spiders could be customized to detect predetermined forces. In real life, these forces would be associated with a certain object that an autonomous machine needs to avoid.
But the sensors they developed don’t just sense and filter at a very fast rate—they also compute, and without needing a power supply.
“There’s no distinction between hardware and software in nature; it’s all interconnected,” Arrieta said. “A sensor is meant to interpret data, as well as collect and filter it.”
In nature, once a particular level of force activates the mechanoreceptors associated with the hairy mechanosensor, these mechanoreceptors compute information by switching from one state to another.
Purdue researchers, in collaboration with Nanyang Technology University in Singapore and ETH Zürich, designed their sensors to do the same, and to use these on/off states to interpret signals. An intelligent machine would then react according to what these sensors compute.
These artificial mechanosensors are capable of sensing, filtering and computing very quickly because they are stiff, Arrieta said. The sensor material is designed to rapidly change shape when activated by an external force. Changing shape makes conductive particles within the material move closer to each other, which then allows electricity to flow through the sensor and carry a signal. This signal informs how the autonomous system should respond.
“With the help of machine learning algorithms, we could train these sensors to function autonomously with minimum energy consumption,” Arrieta said. “There are also no barriers to manufacturing these sensors to be in a variety of sizes.”
An interdisciplinary initiative is helping KAUST be at the forefront of a digital revolution, where sensors can find a use just about anywhere.
The ability to track minuscule but important changes across a range of systems—from the body to the borough and beyond—seems limitless with the emerging array of novel devices that are tiny, self-powering and wirelessly connected. KAUST’s Sensor Initiative comprises a broad range of experts, from marine scientists to electrical engineers, who are innovating solutions to some of the most challenging obstacles in sensor technology. Together, they are powering up to transform the exciting intersection between small interconnected devices and the world around us.
Capacity to monitor our surroundings also reveals new potential in environmental and community protection. For example, a sensor that can detect a flood or a fire can save lives; a sensor that can track animals could help to better manage an ecosystem; and a sensor that can read plant condition could promote sustainable farming.
To take advantage of the market opportunities for sensors in both medical and environmental fields, KAUST holds an annual meeting of biologists, engineers and chemists to discuss technology development. Since 2015, these meetings have produced ambitious collaborations that aim to improve the science that underpins next-gen sensors as well as to take them to the market.
Get ready to plug and play
Khaled Salama, professor of electrical engineering and director of the Sensor Initiative, explains that what sets KAUST apart are the University’s human resources and outstanding lab facilities that underpin its innovative sensor technologies. With the onslaught of data coming from the hundreds of billions of sensors in our cities, cars, homes and offices, we need machine learning to help us understand the data, the supercomputing power to manage it and the expertise to make sure the machines do it all effectively.
“KAUST has strength in materials research, which is where our expertise can be used for developing sensors with transducer components that can be quickly swapped out and replaced with ones customized for different biological or environmental applications,” says Salama.
“Some can stick to your skin and monitor your vital signs through changes in your sweat while others can be placed in petroleum installations to monitor hazardous gases,” says Salama. “We’re not bound to one specific application, and each new development gives us a chance to answer some fundamental scientific questions along the way.”
Say goodbye to batteries, as you know them
KAUST is deploying tiny sensors across the University’s campus to model future smart cities that can continuously monitor air quality or help self-driving cars navigate. Implementing this vision means making devices that are as self-sufficient as possible.
“If you have sensors containing regular batteries, they might last a thousand cycles,” says Husam Alshareef, professor of materials science. “We have to get them to last millions of times longer.”
Alshareef and several international collaborators are building a technology known as microsupercapacitors—next-generation batteries—to resolve challenges around energy storage. Through a special vacuum deposition process, the team has transformed ruthenium oxide into a thin-film electrode that can hold massive amounts of charge and quickly release it on demand.
Get plant smart with winged sensors
Professor Muhammad Hussain is a strong believer in the importance of availability in the sensor market. He insists that his sensors not only provide solutions to everyday problems but also that they be affordable to all. That said, he does not forgo creativity for affordability. Hussain’s plant sensors are flexible, inexpensive and range in size from 1-20 mm in diameter. When placed on a plant leaf, they can detect temperature, humidity and growth, data that can be used to help farmers farm smart—minimizing nutrient and water waste. But what makes them especially remarkable is their beautiful butterfly shape. When asked why he chose the butterfly shape Hussain told us, “Butterflies are aesthetically beautiful and natural in a plant environment. Their large wings allow us to integrate many different sensors, which is especially useful for the artificial intelligence chip we are currently integrating into the system. Ultimately, we aim to create a fully interactive system such that the butterfly can deliver nutrients or gather more data.”
One of the advanced sensors being developed at KAUST is the smart bandage from the group of Atif Shamim in the electrical engineering program. This gadget uses carbon-based transducers to directly contact chronic wounds and to predict signs of infection based on blood pH levels.
Shamim notes that wireless communication is crucial if sensors and other components of the Internet of things are to be integrated with everyday items. His team has pioneered the use of low-energy Bluetooth radio networks to help connect smart devices with each other and also with network servers.
“Even though the Internet of things is about inanimate objects, they have to make decisions for you,” says Shamim. “They need to sense and they need to communicate.”
Shamim is partnering with other KAUST researchers, including Jürgen Kosel, who specializes in using the property of magnetism in his sensor work to track animal behavior in the Red Sea. The team created stickers—each containing a self-powered, Bluetooth-connected position sensor—that are small enough to be attached to crabs, turtles and giant clams in the Red Sea.
Kosel and his group aimed to tackle the primary challenge associated with remote tracking of marine life—the tendency for water to scatter the radiofrequency waves used by most sensors for geolocation. Working with the KAUST Nanofabrication Core Lab to fabricate thin-film structures, the team created flexible sensors that reveal their global position using magnetic signals that easily access subsurface environments.
“Magnetic fields can penetrate many materials without affecting them, and that includes humans and other animals,” says Kosel. “We’ve shown that you can even derive how much energy a marine animal consumes using magnetic sensors that monitor water flow.”
Sense the future of sensors
For the Emeritus Senior Vice President for Research, Jean Frechet, the possibilities are great: “With our expertise and resources, we have built bridges across disciplines by bringing together researchers from KAUST and other institutions. They inspire each other to solve challenges as diverse as the survival of marine life, communications for the 21st century, and the exploitation of big data. The KAUST Sensor Initiative will stimulate the next generation and contribute to diversifying the country’s economy as we design and engineer sensors that collect the data we need to address global challenges.”
What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.
Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices to report on what they perceive.
Electronically active 2-D materials have been the subject of much research since the introduction of graphene in 2004. Even though they are often touted for their strength, they’re difficult to move to where they’re needed without destroying them.
The Ajayan and Lou groups, along with the lab of Rice engineer Jacob Robinson, have a new way to keep the materials and their associated circuitry, including electrodes, intact as they’re moved to curved or other smooth surfaces.
The results of their work appear in the American Chemical Society journal ACS Nano.
The Rice team tested the concept by making a 10-nanometer-thick indium selenide photodetector with gold electrodes and placing it onto an optical fiber. Because it was so close, the near-field sensor effectively coupled with an evanescent field—the oscillating electromagnetic wave that rides the surface of the fiber—and accurately detected the flow of information inside.
The benefit is that these sensors can now be imbedded into such fibers where they can monitor performance without adding weight or hindering the signal flow.
“This paper proposes several interesting possibilities for applying 2-D devices in real applications,” Lou said. “For example, optical fibers at the bottom of the ocean are thousands of miles long, and if there’s a problem, it’s hard to know where it occurred. If you have these sensors at different locations, you can sense the damage to the fiber.”
Lou said labs have gotten good at transferring the growing roster of 2-D materials from one surface to another, but the addition of electrodes and other components complicates the process. “Think about a transistor,” he said. “It has source, drain and gate electrodes and a dielectric (insulator) on top, and all of these have to be transferred intact. That’s a very big challenge, because all of those materials are different.”
Raw 2-D materials are often moved with a layer of polymethyl methacrylate (PMMA), more commonly known as Plexiglas, on top, and the Rice researchers make use of that technique. But they needed a robust bottom layer that would not only keep the circuit intact during the move but could also be removed before attaching the device to its target. (The PMMA is also removed when the circuit reaches its destination.)
The ideal solution was poly-dimethyl-glutarimide (PMGI), which can be used as a device fabrication platform and easily etched away before transfer to the target. “We’ve spent quite some time to develop this sacrificial layer,” Lou said. PMGI appears to work for any 2-D material, as the researchers experimented successfully with molybdenum diselenide and other materials as well.
The Rice labs have only developed passive sensors so far, but the researchers believe their technique will make active sensors or devices possible for telecommunication, biosensing, plasmonics and other applications.
NIST researchers carried out simulations of a graphene membrane featuring oxygen-lined pores and immersed in a liquid solution of potassium ions (charged atoms), which under certain conditions can be trapped in the pores. Slight stretching of the graphene greatly increases the flow of ions through the pores. Credit: NIST
Researchers at the National Institute of Standards and Technology (NIST) have conducted simulations suggesting that graphene, in addition to its many other useful features, can be modified with special pores to act as a tunable filter or strainer for ions (charged atoms) in a liquid.
The concept, which may also work with other membrane materials, could have applications such as nanoscale mechanical sensors, drug delivery, water purification and sieves or pumps for ion mixtures similar to biological ion channels, which are critical to the function of living cells. The researchis describedin the November 26 issue ofNature Materials.
“Imagine something like a fine-mesh kitchen strainer with sugar flowing through it,” project leader Alex Smolyanitsky said. “You stretch that strainer in such a way that every hole in the mesh becomes 1-2 percent larger. You’d expect that the flow through that mesh will be increased by roughly the same amount. Well, here it actually increases 1,000 percent. I think that’s pretty cool, with tons of applications.”
If it can be achieved experimentally, this graphene sieve would be the first artificial ion channel offering an exponential increase in ion flow when stretched, offering possibilities for fast ion separations or pumps or precise salinity control. Collaborators plan laboratory studies of these systems, Smolyanitsky said.
Graphene is a layer of carbon atoms arranged in hexagons, similar in shape to chicken wire, that conducts electricity. The NIST molecular dynamics simulations focused on a graphene sheet 5.5 by 6.4 nanometers (nm) in size and featuring small holes lined with oxygen atoms. These pores are crown ethers—electrically neutral circular molecules known to trap metal ions. A previous NIST simulation study showed this type of graphene membrane might be used fornanofluidic computing.
In the simulations, the graphene was suspended in water containing potassium chloride, a salt that splits into potassium and chlorine ions. The crown ether pores can trap potassium ions, which have a positive charge. The trapping and release rates can be controlled electrically. An electric field of various strengths was applied to drive the ion current flowing through the membrane.
Researchers then simulated tugging on the membrane with various degrees of force to stretch and dilate the pores, greatly increasing the flow of potassium ions through the membrane. Stretching in all directions had the biggest effect, but even tugging in just one direction had a partial effect.
Researchers found that the unexpectedly large increase in ion flow was due to a subtle interplay of a number of factors, including the thinness of graphene; interactions between ions and the surrounding liquid; and the ion-pore interactions, which weaken when pores are slightly stretched. There is a very sensitive balance between ions and their surroundings, Smolyanitsky said.
Paper: A. Fang, K. Kroenlein, D. Riccardi and A. Smolyanitsky. Highly mechanosensitive ion channels from graphene-embedded crown ethers.Nature Materials. Published online November 26, 2018. DOI:10.1038/s41563-018-0220-4
London audience told by Israeli-Christian professor about a new device which can ‘smell’ 17 diseases on a person’s breath
Professor Hossam Haick, an Israeli Christian, delivered Technion UK’s Ron Arad lecture at the Royal College of Physicians last week.
The electronic ‘nose’ he developed can smell 17 diseases on a person’s breath, including Alzheimer’s, Parkinson’s, tuberculous, diabetes and lung cancer.
The non-intrusive medical device, which works by identifying as disease’s bio-markers, has attracted the attention of billionaires such as Bill and Melinda Gates, whose foundation focuses on the diagnostics of diseases.
“Every disease has a unique signature – a ‘breath print,’” Haick said. “The challenge is to bring the best science we have proven into reality by developing a smaller device that captures all the components of a disease appearing in the breath.”
Haick works at the Department of Chemical Engineering and the Russell Berrie Nanotechnology Institute at the Technion in Israel and is an expert in the field of nanotechnology and non-invasive disease diagnosis. (Left) Professor Hossam Haick at the Technion Ron Arad Dinner Credit: John Rifkin
The University said the latest advances in his research mean that it has the potential to identify diseases though sensors in mobile phones and wearable technology, and with more analysis and data it may even be able to predict cancer in the future.
“We cannot develop this technology in Israel without developing the best science,” he said. “Integrating the software, machine learning and academic intelligence will make a critical change in the early detection and prevention of cancerous diseases.”
San Diego based Grolltex was granted a patent by the USPTO for a new multi-modal ‘super’ sensor design made of single layer graphene.
The patent, titled “Graphene-based multi-modal sensor” describes a one atom thick architecture and utilizes several of Grolltex’ 2D materials technologies to produce what the company internally calls ‘The smallest, most sensitive sensor in the world’.
The company is working on initial applications for these sensors that are targeting the bio-sensing and defense fields as leading-edge users of this technology.
“Our single atom thick sensor design, in the strain sensor configuration, is so sensitive that it captures a robust and repeatable signal on the contractility strength of individual ‘cardio myocytes’ or heart cells as they beat”, said Jeff Draa, company co-founder and CEO.
“This can be a holy grail for fields such as cardiotoxicity testing as it has the capacity to be a significant time and money saver in the new drug testing and approval process”.
Additionally, the single layer graphene sensor covered by this patent has a very high threshold for thermal coefficient of resistance, meaning it experiences little to no signal drift when exposed to extreme levels of heat. This makes it an ideal sensor for measuring micro strain in high speed aeronautical vehicles.
These sensors are so small and thin, they can be layered into the skins of airplanes, helicopters or other high stress vehicles to real-time measure and detect micro stress at architectures and levels not currently possible with today’s sensing technologies. These sensors could also be discreetly placed within critical structures such as bridges or buildings.
MIT researchers have designed nanosensorsthat can profile tumors and may yield insight into how they will respond to certain therapies. The system is based on levels of enzymes called proteases, which cancer cells use to remodel their surroundings.
Once adapted for humans, this type of sensor could be used to determine how aggressive a tumor is and help doctors choose the best treatment, says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science and a member of MIT’s Koch Institute for Integrative Cancer Research.
“This approach is exciting because people are developing therapies that are protease-activated,” Bhatia says. “Ideally you’d like to be able to stratify patients based on their protease activity and identify which ones would be good candidates for these therapies.”
Once injected into the tumor site, the nanosensors are activated by a magnetic fieldthat is harmless to healthy tissue. After interacting with and being modified by the target tumor proteins, the sensors are secreted in the urine, where they can be easily detected in less than an hour.
Bhatia and Polina Anikeeva, the Class of 1942 Associate Professor of Materials Science and Engineering, are the senior authors of the paper, which appears in the journal Nano Letters. The paper’s lead authors are Koch Institute postdoc Simone Schurle and graduate student Jaideep Dudani.
Heat and release
Tumors, especially aggressive ones, often have elevated protease levels. These enzymes help tumors spread by cleaving proteins that compose the extracellular matrix, which normally surrounds cells and holds them in place.
In 2014, Bhatia and colleagues reported using nanoparticles that interact with a type of protease known as matrix metalloproteinases (MMPs) to diagnose cancer. In that study, the researchers delivered nanoparticles carrying peptides, or short protein fragments, designed to be cleaved by the MMPs. If MMPs were present, hundreds of cleaved peptides would be excreted in the urine, where they could be detected with a simple paper test similar to a pregnancy test.
In the new study, the researchers wanted to adapt the sensors so that they could report on the traits of tumors in a known location. To do that, they needed to ensure that the sensors were only producing a signal from the target organ, unaffected by background signals that might be produced in the bloodstream. They first designed sensors that could be activated with light once they reached their target. That required the use of ultraviolet light, however, which doesn’t penetrate very far into tissue.
“We started thinking about what kinds of energy we might use that could penetrate further into the body,” says Bhatia, who is also a member of MIT’s Institute for Medical Engineering and Science.
To achieve that, Bhatia teamed up with Anikeeva, who specializes in using magnetic fields to remotely activate materials. The researchers decided to encapsulate Bhatia’s protease-sensing nanoparticles along with magnetic particles that heat up when exposed to an alternating magnetic field. The field is produced by a small magnetic coil that changes polarity some half million times per second.
The heat-sensitive material that encapsulates the particles disintegrates as the magnetic particles heat up, allowing the protease sensors to be released. However, the particles do not produce enough heat to damage nearby tissue.
“It has been challenging to examine tumor-specific protease activities from patients’ biofluids because these proteases are also present in blood and other organs,” says Ji Ho (Joe) Park, an associate professor of bio and brain engineering at the Korea Advanced Institute of Science and Technology.
“The strength of this work is the magnetothermally responsive protease nanosensors with spatiotemporal controllability,” says Park, who was not involved in the research. “With these nanosensors, the MIT researchers could assay protease activities involved more in tumor progression by reducing off-target activation significantly.”
In a study of mice, the researchers showed that they could use these particles to correctly profile different types of colon tumors based on how much protease they produce.
Cancer treatments based on proteases, now in clinical trials, consist of antibodies that target a tumor protein but have “veils” that prevent them from being activated before reaching the tumor. The veils are cleaved by proteases, so this therapy would be most effective for patients with high protease levels.
The MIT team is also exploring using this type of sensor to image cancerous lesions that spread to the liver from other organs. Surgically removing such lesions works best if there are fewer than four, so measuring them could help doctors choose the best treatment.
Bhatia says this type of sensor could be adapted to other tumors as well, because the magnetic field can penetrate deep into the body. This approach could also be expanded to make diagnoses based on detecting other kinds of enzymes, including those that cut sugar chains or lipids.