Tag Archives: Nanotechnology

DNA nanotechnology could speed up pharmaceutical development while minimizing costs

A new tool speeds up development of vaccines and other pharmaceutical products by more than one million times while minimizing costs. The method works by using soap-like bubbles as nano-containers. With DNA nanotechnology, multiple ingredients can be mixed within the containers. Credit: Nikos Hatzakis, University of Copenhagen

A new tool speeds up development of vaccines and other pharmaceutical products by more than 1 million times while minimizing costs.

In search of pharmaceutical agents such as new vaccines, industry will routinely scan thousands of related candidate molecules. A novel technique allows this to take place on the nano scale, minimizing use of materials and energy. The work is published in the journal Nature Chemistry.

More than 40,000 molecules can be synthesized and analyzed within an area smaller than a pinhead. The method, developed through a highly interdisciplinary research effort in Denmark, promises to drastically reduce the amounts of material, energy, and economic cost for pharmaceutical companies.

The method works by using soap-like bubbles as nano-containers. With DNA nanotechnology, multiple ingredients can be mixed within the containers.

“The volumes are so small that the use of material can be compared to using one liter of water and one kilogram of material instead of the entire volumes of water in all oceans to test material corresponding to the entire mass of Mount Everest. This is an unprecedented save in effort, material, manpower, and energy,” says head of the team Nikos Hatzakis, Associate Professor at the Department of Chemistry, University of Copenhagen.

“Saving infinitely [on] amounts of time, energy and manpower would be fundamentally important for any synthesis development and evaluation of pharmaceuticals,” says Ph.D. Student Mette G. Malle, lead author of the article, and currently Postdoc researcher at Harvard University, U.S..

Results within just seven minutes

The work has been carried out in collaboration between the Hatzakis Group, University of Copenhagen, and Associate Professor Stefan Vogel, University of Southern Denmark. The project has been supported by a Villum Foundation Center of Excellence grant. The resulting solution is named “single particle combinatorial lipidic nanocontainer fusion based on DNA mediated fusion”—abbreviated SPARCLD.

The breakthrough involves integration of elements from normally quite distant disciplines: synthetic biochemistry, nanotechnology, DNA synthesis, combinational chemistry, and even Machine Learning, which is an AI (artificial intelligence) discipline.

The method works by using soap-like bubbles as nano-containers. With DNA nanotechnology, multiple ingredients can be mixed within the containers. Credit: Nikos Hatzakis, University of Copenhagen

“No single element in our solution is completely new, but they have never been combined so seamlessly,” explains Nikos Hatzakis.

The method provides results within just seven minutes.

“What we have is very close to a live read-out. This means that one can moderate the setup continuously based on the readings adding significant additional value. We expect this to be a key factor for industry wanting to implement the solution,” says Mette G. Malle.

‘Had to keep things hush-hush’

The individual researchers in the project have several industry collaborations, yet they do not know which companies may want to implement the new high-throughput method.

“We had to keep things hush-hush since we didn’t want to risk for others to publish something similar before us. Thus, we could not engage in conversations with industry or with other researchers that may use the method in various applications,” says Nikos Hatzakis.

Still, he can name some possible applications:

“A safe bet would be that both industry and academic groups involved in synthesis of long molecules such as polymers could be among the first to adopt the method. The same goes for ligands of relevance for pharmaceutical development. A particular beauty of the method [is] that it can be integrated further, allowing for direct addition of a relevant application.”

Here, examples could be RNA strings for the important biotech tool CRISPR, or an alternate for screening and detecting and synthesizing RNA for future pandemic vaccines.

“Our setup allows for integrating SPARCLD with post-combinatorial readout for combinations of protein-ligand reactions such as those relevant for use in CRISPR. Only, we have not been able to address this yet, since we wanted to publish our methodology first.”


New method may improve prostate cancer and high cholesterol treatments


More information:
Stefan Vogel, Single-particle combinatorial multiplexed liposome fusion mediated by DNA, Nature Chemistry (2022). DOI: 10.1038/s41557-022-00912-5. www.nature.com/articles/s41557-022-00912-5
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University of Copenhagen

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Revolutionary DNA Nanotechnology Speeds Up Development of Vaccines by More Than One Million Times

Revolutionary tool will meet future pandemics with accelerated response.

A new tool speeds up development of vaccines and other pharmaceutical products by more than one million times while minimizing costs.

In search of pharmaceutical agents such as new vaccines, industry will routinely scan thousands of related candidate molecules. A novel technique allows this to take place on the nano scale, minimizing use of materials and energy. The work is published in the prestigious journal Nature Chemistry.

More than 40,000 different molecules can be synthesized and analyzed within an area smaller than a pinhead. The method, developed through a highly interdisciplinary research effort in Denmark, promises to drastically reduce the amounts of material, energy, and economic cost for pharmaceutical companies.

The method works by using soap-like bubbles as nano-containers. With

A new tool speeds up development of vaccines and other pharmaceutical products by more than one million times while minimizing costs. The method works by using soap-like bubbles as nano-containers. With DNA nanotechnology, multiple ingredients can be mixed within the containers. Credit: Nikos Hatzakis, University of Copenhagen

“The volumes are so small that the use of material can be compared to using one liter of water and one kilogram of material instead of the entire volumes of water in all oceans to test material corresponding to the entire mass of Mount Everest. This is an unprecedented save in effort, material, manpower, and energy,” illustrates head of the team Nikos Hatzakis, Associate Professor at the Department of Chemistry, University of Copenhagen.

“Saving infinitely amounts of time, energy and manpower would be fundamentally important for any synthesis development and evaluation of pharmaceuticals,” says PhD Student Mette G. Malle, lead author of the article, and currently Postdoc researcher at Harvard University, USA.

Results within just seven minutes

The work has been carried out in collaboration between the Hatzakis Group, University of Copenhagen, and Associate Professor Stefan Vogel, University of Southern Denmark. The project has been supported by a Villum Foundation Center of Excellence grant. The resulting solution is named “single particle combinatorial lipidic nanocontainer fusion based on DNA mediated fusion” – abbreviated SPARCLD.

The breakthrough involves integration of elements from normally quite distant disciplines: synthetic biochemistry, nanotechnology, DNA synthesis, combinational chemistry, and even Machine Learning which is an AI (artificial intelligence) discipline.

“No single element in our solution is completely new, but they have never been combined so seamlessly,” explains Nikos Hatzakis.

The method provides results within just seven minutes.

The method works by using soap-like bubbles as nano-containers. With DNA nanotechnology, multiple ingredients can be mixed within the containers. Credit: Nikos Hatzakis, University of Copenhagen

“What we have is very close to a live read-out. This means that one can moderate the setup continuously based on the readings adding significant additional value. We expect this to be a key factor for industry wanting to implement the solution,” says Mette G. Malle.

Had to keep things hush-hush

The individual researchers in the project have several industry collaborations, yet they do not know which companies may want to implement the new high-throughput method.

“We had to keep things hush-hush since we didn’t want to risk for others to publish something similar before us. Thus, we could not engage in conversations with industry or with other researchers that may use the method in various applications,” says Nikos Hatzakis.

Still, he can name some possible applications:

“A safe bet would be that both industry and academic groups involved in synthesis of long molecules such as polymers could be among the first to adopt the method. The same goes for ligands of relevance for pharmaceutical development. A particular beauty of the method that it can be integrated further, allowing for direct addition of a relevant application.”

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The Nanotechnology Revolution Is Here—We Just Haven’t Noticed Yet

Before there was a “metaverse,” before there were crypto millionaires, before nearly every kid in America wanted to be an influencer, the most-hyped thing in tech was “nanotechnology.” “Nano-,” for those who could use a refresher, means “one billionth,” and nanotechnology generally refers to materials manipulated at an atomic or molecular scale.

For decades, computer scientists and physicists speculated that, any minute now, nanotechnology was going to completely reshape our lives, unleashing a wave of humanity-saving inventions. Things haven’t unfolded as they predicted but, quietly, the nanotech revolution is under way.

You can thank the microchip. Engineers and scientists are using the same technology perfected over decades to make microchips to create a variety of other miniature marvels, from submicroscopic machines to new kinds of lenses. These nano-scale gizmos have become so integrated into the fabric of our lives, and the devices in our pockets, that we seem to have missed the fact that they are real-life examples of the nanotechnology revolution we were promised over the past half-century.

Among the routine items that have benefited from nanotechnology: air bags, cellphones, radar, inkjet printers, home projectors, and 5G and other fast wireless technology. Just around the bend, nanotechnology could enable ultra-tiny cameras, as well as a dizzying array of other kinds of sensors, able to detect everything from air pollution and black ice to hacking attempts and skin cancer.

Some of this technology is even at the heart of the current controversy over whether or not America’s 5G networks could make flying less safe.

It’s all still a far cry from the more outlandish past predictions about nanotech’s future. We don’t have molecule-size robots that patrol our bloodstream and repair damage, or microscopic factories capable of churning out endless copies of themselves until the entire planet has been reduced to what nanotech pioneer Eric Drexler in the 1980s worried would be nothing but a “gray goo.”

In the more distant future, this technology might yet enable the vision physicist Richard Feynman laid out in his famous 1959 lecture “There’s Plenty of Room at the Bottom,” in which he hypothesized about a way to build three-dimensional structures one atom at a time. Achieving even a fraction of what he proposed would open up tantalizing possibilities, from sensors that can detect viruses in the air before we inhale them to quantum computers in our pockets.

In the present, creating real-life nanomachines means capitalizing on the hundreds of billions of dollars invested in perfecting the manufacture of microchips since their introduction, also in 1959. Chip companies’ march to make faster, more power-efficient chips has led to the development of fantastically complicated and expensive equipment. By using the same types of machines, techniques and “fabs”—as microchip factories are known—builders of nanomachines can use the steady progress of Moore’s Law to make their devices ever smaller.

ASML, one of the world’s leading manufacturers of the equipment that makes microchips, researches and builds its equipment with its primary customers in mind—the Intels, Samsungs and TSMCs of the world, says CEO

Peter Wennink.

But it has also always had a division that works with clients who want to make things other than conventional microchips, and designs its technology so that it can be customized to their needs, he adds.

These include microelectromechanical systems—MEMS for short—which represent a classic example of tiny machines made with chip fabrication equipment. MEMS have gotten radically smaller over the decades.

Take your smartphone. To transmit and receive the different radio frequencies required for it to talk to cell towers or connect to your Wi-Fi or wireless earbuds, it must filter out all the stray interference that, more than ever, affects those bands of spectrum.

So it uses tiny radio filters without which none of our wireless devices could function. Where microchips and radio antennae are static, entirely solid-state devices, the radio filters they depend on actually move, says

George Holmes,

CEO of Resonant, a company that makes the filters. They vibrate at the same frequency as the signal to be received or transmitted, or sometimes at the frequency to be filtered out, like a cluster of tiny tuning forks.

A technician assembles a system to test Resonant’s ultra-small radio filter for 5G wireless communication systems.



Photo:

Resonant

That means that when your phone is sitting on your desk, streaming music to your earbuds, there are dozens of little elements inside, most shaped like tiny combs, vibrating billions of times a second. They work precisely because they are tiny. Only something so small—existing on a scale at which the bonds between atoms are much stronger relative to an object’s size—could vibrate at these frequencies and not shake itself to bits.

Similarly, for the ground-sensing radar in planes to work properly, it has to filter out interference from, among other things, America’s rapidly proliferating 5G cellphone networks. The problem, says Mr. Holmes, is that radars in older planes were designed and built before anyone knew 5G networks would be a thing. Fixing this problem could be expensive, as it could mean replacing or updating some of those old radars. The fear of airlines and the FAA is, in essence, that for the lack of sufficient microscopic combs vibrating at a few hundreds of millions or billions of times a second in order to tune out a nearby cellphone tower, a plane could be lost.

Our phones also contain many other MEMS. The system that lets them (and smartwatches and other health trackers) know their orientation, as well as the magnitude and direction of their acceleration, is no bigger than a grain of rice today. When it was first invented and installed in the Apollo spacecraft, it was bigger than a basketball. Similar and equally tiny sensors tell air bags when to deploy. The system of rapidly-twitching, red blood cell-size mirrors that make home projectors possible are also MEMS; ditto the nozzles on inkjet printers.

Another example of modern nanomachines manipulates light rather than electricity. A new kind of lens, known as a “metalens,” has been shown in the laboratory to be able to bend and shape light in ways that used to require a whole stack of conventional lenses, says Juejun Hu, an associate professor of materials science at MIT. The advantage of metalenses is that they are thin and nearly flat—at least to the naked eye.

Under an electron microscope, the surface of a metalens looks like a plush carpet. At this scale, the metalens is clearly covered with minuscule pillars—each one-thousandth the width of a human hair—sticking up from its surface. This texture allows a metalens to bend light in a way that’s analogous to the way that conventional lenses do. (The way these little silicon “fibers” work is novel enough that they forced physicists to rethink their understanding of how light and matter interact.)

A handful of startups are translating metalens technology to commercial applications. Among them is Metalenz, which just announced a deal with semiconductor manufacturer

STMicroelectronics

to make 3-D sensors for smartphones. This application of metalenses could allow a greater variety of phone manufacturers to achieve the kind of 3-D sensing that enables

Apple’s

Face ID technology.

Unlocking your phone with your face is just the beginning, says Metalenz CEO Robert Devlin. Metalenses also have abilities that can be difficult to reproduce with conventional lenses. For example, because they facilitate the detection of polarized light, they can “see” things conventional lenses can’t. That could include detecting levels of light pollution, allowing the cameras on automobile safety and self-driving systems to detect black ice, and giving our phone cameras the ability to detect skin cancer, says Mr. Devlin.

Shrinking nanomachines further, and getting to the theoretical limit of tininess—the point at which humans are manipulating individual atoms—will require technologies radically different than the ones we currently use to manufacture even the most advanced microchips, says Dr. Andrei Fedorov, a professor at the Georgia Institute of Technology. His team, among others, has published research in which they use electron beams to etch patterns in sheets of graphene and other two-dimensional materials—or to build up structures made of carbon atoms atop them.

Graphene and its kin are already the subject of intense research as an alternative to silicon in the microchips of the future. But Dr. Fedorov says that future could include building three-dimensional structures atop two-dimensional sheets of graphene. Being able to do so with atomic precision could allow, among other things, creating the kind of structures required for the next generation of ultrapowerful quantum computers which governments and tech companies alike are trying to build.

Most of Dr. Fedorov’s research is supported by the Semiconductor Research Corp., a nonprofit sponsored by nearly every major advanced chip manufacturing and design company on earth, set up in the early 1980s to pursue fundamental research that could someday be used in electronics manufacturing. So it’s not implausible that the semiconductor industry, in its exploration of technologies that could take us beyond the limits of today’s microchips, could someday employ techniques pioneered by his team or the many others working on similar technologies.

The end goal is the ability to use an electron beam to rapidly remove, add or modify the atoms on a surface. The result is a system that resembles 3-D printing—at the atomic scale.

When Dr. Fedorov gives talks about his research, he tells audiences about what Richard Feynman proposed in 1959. “I say, ‘This is the vision,’ and then I say, ‘Sixty years later, we realized Feynman’s vision. It’s now in our hands.’”

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Researchers Found a Way to Send Tiny Robots Into Mouse Brains

Generations of laboratory mice like these recently became host to microscopic robot swarms.
Photo: Getty Images (Getty Images)

In a mind-bending development, a team of researchers in China have managed to treat brain tumors in mice by delivering drugs to the tissues using microscopic robots. The robots jumped from the mice’s bloodstreams into their brains by being coated in E. coli, which tricked the rodents’ immune systems into attacking them, absorbing the robots and the cancer-fighting drugs in the process.

The team’s research was published today in the journal Science Robotics. It comes on the heels of previous research by members of the same team, which saw liquid-coated nanorobots remotely propelled through the jelly-like fluid of the eye. Besides being an obvious recipe for an episode of “The Magic School Bus,” the research had obvious applications for ophthalmological research and medical treatments.

“It’s not just the blood-brain barrier,” said lead author Zhiguang Wu, a chemist at the Harbin Institute for Technology in China, in an email. “Most barriers in dense tissues are difficult obstacles to overcome in moving microrobots around a body.”

The crafts are magnetic, and the researchers use a rotating magnetic field to pull them around remotely. On microscales—we’re talking incremental movements about 1% the width of a hair—the researchers were able to make the hybrid bio-bots wend paths like in the video game Snake. They’re dubbed “neutrobots” because they infiltrate the brain in the casing of neutrophils, a type of white blood cell.

“The biggest challenge of the work was how to achieve a swarm intelligence of neutrobots,” Wu said. “Like robot swarms in the macroscale world, the micro/nanorobot swarms enable sophisticated manipulation to accomplish complex tasks.”

It ultimately took Wu’s team eight years to actualize the microscopic robot swarms capable of bridging the gap between the rodent bloodstream in the animal’s tail, where the bots were injected, and its brain, where gliomas—tumors that emerge from the brain’s glial cells—resided. Part of the issue is that the mice’s white blood cells didn’t dig the flavor of the magnetic robots. To overcome that issue, Wu’s team coated the bots in bits of E. coli membrane, which the white blood cells easily recognize as a unwelcome invader. That made the robots much more palatable, and the white blood cells enveloped them. From inside those cells, the robots were then able to roll the cells toward the brain; a Trojan horse for the 21st century (in this case, one that benefits the residents of Troy). The neutrobots made it into the brains and were able to deliver the drug directly to the targeted tumors.

Wu said the applications of the robots are manifold, and more breakthroughs could be on the horizon. “The neutrobots are not exclusively designed for the treatment of glioma,” he said, explaining that they’re “a platform for active delivery for the therapy of various brain diseases such as cerebral thrombosis, apoplexy, and epilepsy.”

A neutrobot nestled up against a glioma tumor in a mouse brain.
Image: Zhang et al., Sci Robot. 6, eaaz9519 (2021)

Whether it’s surgery or drug delivery, robots are slowly but surely making their way into our most personal of domains. Of course, they’re still just in mouse brains for now, but future applications in humans seem increasingly likely.

“The use of neutrophils in microrobot design is a fascinating strategy for overcoming biological barriers,” wrote robotic engineers Junsun Hwang and Hongsoo Choi, who weren’t affiliated with the new work, in an accompanying article. “However, bench-to-bedside translation with respect to targeted drug delivery by neutrobots or microrobots is still some way off.”

Currently, experts lack the ability to see what the robots are doing clearly in real time, which would be vital for any medical use of the droids down the line. But in the rat race of robotics research, it’s clear that humans are pushing their inanimate swarms in the direction of progress.

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