Tag Archives: Nanomachines

You need a quantum mechanic for an atom-sized machine

This news comes from the National University of Singapore’s Centre for Quantum Technologies according to a May 4, 2020 news item on Nanowerk (Note: A link has been removed),

Here’s a new chapter in the story of the miniaturisation of machines: researchers in a laboratory in Singapore have shown that a single atom can function as either an engine or a fridge. Such a device could be engineered into future computers and fuel cells to control energy flows.

“Think about how your computer or laptop has a lot of things inside it that heat up. Today you cool that with a fan that blows air. In nanomachines or quantum computers, small devices that do cooling could be something useful,” says Dario Poletti from the Singapore University of Technology and Design (SUTD).

This work gives new insight into the mechanics of such devices. The work is a collaboration involving researchers at the Centre for Quantum Technologies (CQT) and Department of Physics at the National University of Singapore (NUS), SUTD and at the University of Augsburg in Germany. The results were published in the peer-reviewed journal npj Quantum Information (“Single-atom energy-conversion device with a quantum load”).

The researchers have included an exceptionally pretty illustration with the press release,

Caption: Experiments with a single-atom device help researchers understand what quantum effects come into play when machinery shrinks to the atomic scale. Credit: Aki Honda / Centre for Quantum Technologies, National University of Singapore

A May 4, 2020 National University of Singapore press release (also on EurekAlert), which originated the news item, delves further into the work,

Engines and refrigerators are both machines described by thermodynamics, a branch of science that tells us how energy moves within a system and how we can extract useful work. A classical engine turns energy into useful work. A refrigerator does work to transfer heat, reducing the local temperature. They are, in some sense, opposites.

People have made small heat engines before using a single atom, a single molecule and defects in diamond. A key difference about this device is that it shows quantumness in its action. “We want to understand how we can build thermodynamic devices with just a few atoms. The physics is not well understood so our work is important to know what is possible,” says Manas Mukherjee, a Principal Investigator at CQT, NUS, who led the experimental work.

The researchers studied the thermodynamics of a single barium atom. They devised a scheme in which lasers move one of the atom’s electrons between two energy levels as part of a cycle, causing some energy to be pushed into the atom’s vibrations. Like a car engine consumes petrol to both move pistons and charge up its battery, the atom uses energy from lasers as fuel to increase its vibrating motion. The atom’s vibrations act like a battery, storing energy that can be extracted later. Rearrange the cycle and the atom acts like a fridge, removing energy from the vibrations.

In either mode of operation, quantum effects show up in correlations between the atom’s electronic states and vibrations. “At this scale, the energy transfer between the engine and the load is a bit fuzzy. It is no longer possible to simply do work on the load, you are bound to transfer some heat,” says Poletti. He worked out the theory with collaborators Jiangbin Gong at NUS Physics and Peter Hänggi in Augsburg. The fuzziness makes the process less efficient, but the experimentalists could still make it work.

Mukherjee and colleagues Noah Van Horne, Dahyun Yum and Tarun Dutta used a barium atom from which an electron (a negative charge) is removed. This makes the atom positively charged, so it can be more easily held still inside a metal chamber by electrical fields. All other air is removed from around it. The atom is then zapped with lasers to move it through a four-stage cycle.

The researchers measured the atom’s vibration after applying 2 to 15 cycles. They repeated a given number of cycles up to 150 times, measuring on average how much vibrational energy was present at the end. They could see the vibrational energy increasing when the atom was zapped with an engine cycle, and decreasing when the zaps followed the fridge cycle.

Understanding the atom-sized machine involved both complicated calculations and observations. The team needed to track two thermodynamic quantities known as ergotropy, which is the energy that can be converted to useful work, and entropy, which is related to disorder in the system. Both ergotropy and entropy increase as the atom-machine runs. There’s still a simple way of looking at it, says first author and PhD student Van Horne, “Loosely speaking, we’ve designed a little machine that creates entropy as it is filled up with free energy, much like kids when they are given too much sugar.”

Here’s a link to and a citation for the paper,

Single-atom energy-conversion device with a quantum load by Noah Van Horne, Dahyun Yum, Tarun Dutta, Peter Hänggi, Jiangbin Gong, Dario Poletti & Manas Mukherjee. npj Quantum Information volume 6, Article number: 37 (2020) Published: 01 May 2020

This paper is open access.

McGill University team gets better understanding of nonribosomal peptide synthetases (NRPSs) also described as nanomachines

This research from McGill University (Montréal, Canada) focuses on enzymes and their possible utility as nanomachines for producing drugs. (For the uninitiated, nano means billionth, which, in turn, means these enzymes are measured at the nanoscale.)

An April 30, 2020 McGill University news release (also on EurekAlert) describes the work,

Many of the drugs and medicines that we rely on today are natural products taken from microbes like bacteria and fungi. Within these microbes, the drugs are made by tiny natural machines – mega-enzymes known as nonribosomal peptide synthetases (NRPSs). A research team led by McGill University has gained a better understanding of the structures of NRPSs and the processes by which they work. This improved understanding of NRPSs could potentially allow bacteria and fungi to be leveraged for the production of desired new compounds and lead to the creation of new potent antibiotics, immunosuppressants and other modern drugs.

“NRPSs are really fantastic enzymes that take small molecules like amino acids or other similar sized building blocks and assemble them into natural, biologically active, potent compounds, many of which are drugs,” said Martin Schmeing, Associate Professor in the Department of Biochemistry at McGill University, and corresponding author on the article that was recently published in Nature Chemical Biology. “An NRPS works like a factory assembly line that consists of a series of robotic workstations. Each station has multi-step workflows and moving parts that allow it to add one building block substrate to the growing drug, elongating and modifying it, and then passing it off to the next little workstation, all on the same huge enzyme.”

Ultra-intensive light beam allows scientists to see proteins

n their paper featured on the cover of the May 2020 issue of Nature Chemical Biology, the team reports visualizing an NRPS mechanical system by using the CMCF beamline at the Canadian Light Source (CLS). The CLS is a Canadian national lab [these types of labs are sometimes called synchrotrons] that produces the ultra-intense beams of X-rays required to image proteins, as even mega-enzymes are too small to see with any light microscope.

“Scientists have long been excited about the potential of bioengineering NRPSs by identifying the order of building blocks and reorganizing the workstations in the enzyme to create new drugs, but the effort has rarely been successful,” said Schmeing. “This is the first time anyone has seen how these enzymes transform keto acids into a building block that can be put into a peptide drug. This helps us understand how the NRPSs can use so very many building blocks to make the many different compounds and therapeutics.”

Here’s a link to and a citation for the paper,

Structural basis of keto acid utilization in nonribosomal depsipeptide synthesis by Diego A. Alonzo, Clarisse Chiche-Lapierre, Michael J. Tarry, Jimin Wang & T. Martin Schmeing. Nature Chemical Biology volume 16, pages493–496(2020) Published: 17 February 2020

This paper is behind a paywall.

Training drugs

This summarizes some of what’s happening in nanomedicine and provides a plug (boost) for the  University of Cambridge’s nanotechnology programmes (from a June 26, 2017 news item on Nanowerk),

Nanotechnology is creating new opportunities for fighting disease – from delivering drugs in smart packaging to nanobots powered by the world’s tiniest engines.

Chemotherapy benefits a great many patients but the side effects can be brutal.
When a patient is injected with an anti-cancer drug, the idea is that the molecules will seek out and destroy rogue tumour cells. However, relatively large amounts need to be administered to reach the target in high enough concentrations to be effective. As a result of this high drug concentration, healthy cells may be killed as well as cancer cells, leaving many patients weak, nauseated and vulnerable to infection.

One way that researchers are attempting to improve the safety and efficacy of drugs is to use a relatively new area of research known as nanothrapeutics to target drug delivery just to the cells that need it.

Professor Sir Mark Welland is Head of the Electrical Engineering Division at Cambridge. In recent years, his research has focused on nanotherapeutics, working in collaboration with clinicians and industry to develop better, safer drugs. He and his colleagues don’t design new drugs; instead, they design and build smart packaging for existing drugs.

The University of Cambridge has produced a video interview (referencing a 1966 movie ‘Fantastic Voyage‘ in its title)  with Sir Mark Welland,

A June 23, 2017 University of Cambridge press release, which originated the news item, delves further into the topic of nanotherapeutics (nanomedicine) and nanomachines,

Nanotherapeutics come in many different configurations, but the easiest way to think about them is as small, benign particles filled with a drug. They can be injected in the same way as a normal drug, and are carried through the bloodstream to the target organ, tissue or cell. At this point, a change in the local environment, such as pH, or the use of light or ultrasound, causes the nanoparticles to release their cargo.

Nano-sized tools are increasingly being looked at for diagnosis, drug delivery and therapy. “There are a huge number of possibilities right now, and probably more to come, which is why there’s been so much interest,” says Welland. Using clever chemistry and engineering at the nanoscale, drugs can be ‘taught’ to behave like a Trojan horse, or to hold their fire until just the right moment, or to recognise the target they’re looking for.

“We always try to use techniques that can be scaled up – we avoid using expensive chemistries or expensive equipment, and we’ve been reasonably successful in that,” he adds. “By keeping costs down and using scalable techniques, we’ve got a far better chance of making a successful treatment for patients.”

In 2014, he and collaborators demonstrated that gold nanoparticles could be used to ‘smuggle’ chemotherapy drugs into cancer cells in glioblastoma multiforme, the most common and aggressive type of brain cancer in adults, which is notoriously difficult to treat. The team engineered nanostructures containing gold and cisplatin, a conventional chemotherapy drug. A coating on the particles made them attracted to tumour cells from glioblastoma patients, so that the nanostructures bound and were absorbed into the cancer cells.

Once inside, these nanostructures were exposed to radiotherapy. This caused the gold to release electrons that damaged the cancer cell’s DNA and its overall structure, enhancing the impact of the chemotherapy drug. The process was so effective that 20 days later, the cell culture showed no evidence of any revival, suggesting that the tumour cells had been destroyed.

While the technique is still several years away from use in humans, tests have begun in mice. Welland’s group is working with MedImmune, the biologics R&D arm of pharmaceutical company AstraZeneca, to study the stability of drugs and to design ways to deliver them more effectively using nanotechnology.

“One of the great advantages of working with MedImmune is they understand precisely what the requirements are for a drug to be approved. We would shut down lines of research where we thought it was never going to get to the point of approval by the regulators,” says Welland. “It’s important to be pragmatic about it so that only the approaches with the best chance of working in patients are taken forward.”

The researchers are also targeting diseases like tuberculosis (TB). With funding from the Rosetrees Trust, Welland and postdoctoral researcher Dr Íris da luz Batalha are working with Professor Andres Floto in the Department of Medicine to improve the efficacy of TB drugs.

Their solution has been to design and develop nontoxic, biodegradable polymers that can be ‘fused’ with TB drug molecules. As polymer molecules have a long, chain-like shape, drugs can be attached along the length of the polymer backbone, meaning that very large amounts of the drug can be loaded onto each polymer molecule. The polymers are stable in the bloodstream and release the drugs they carry when they reach the target cell. Inside the cell, the pH drops, which causes the polymer to release the drug.

In fact, the polymers worked so well for TB drugs that another of Welland’s postdoctoral researchers, Dr Myriam Ouberaï, has formed a start-up company, Spirea, which is raising funding to develop the polymers for use with oncology drugs. Ouberaï is hoping to establish a collaboration with a pharma company in the next two years.

“Designing these particles, loading them with drugs and making them clever so that they release their cargo in a controlled and precise way: it’s quite a technical challenge,” adds Welland. “The main reason I’m interested in the challenge is I want to see something working in the clinic – I want to see something working in patients.”

Could nanotechnology move beyond therapeutics to a time when nanomachines keep us healthy by patrolling, monitoring and repairing the body?

Nanomachines have long been a dream of scientists and public alike. But working out how to make them move has meant they’ve remained in the realm of science fiction.

But last year, Professor Jeremy Baumberg and colleagues in Cambridge and the University of Bath developed the world’s tiniest engine – just a few billionths of a metre [nanometre] in size. It’s biocompatible, cost-effective to manufacture, fast to respond and energy efficient.

The forces exerted by these ‘ANTs’ (for ‘actuating nano-transducers’) are nearly a hundred times larger than those for any known device, motor or muscle. To make them, tiny charged particles of gold, bound together with a temperature-responsive polymer gel, are heated with a laser. As the polymer coatings expel water from the gel and collapse, a large amount of elastic energy is stored in a fraction of a second. On cooling, the particles spring apart and release energy.

The researchers hope to use this ability of ANTs to produce very large forces relative to their weight to develop three-dimensional machines that swim, have pumps that take on fluid to sense the environment and are small enough to move around our bloodstream.

Working with Cambridge Enterprise, the University’s commercialisation arm, the team in Cambridge’s Nanophotonics Centre hopes to commercialise the technology for microfluidics bio-applications. The work is funded by the Engineering and Physical Sciences Research Council and the European Research Council.

“There’s a revolution happening in personalised healthcare, and for that we need sensors not just on the outside but on the inside,” explains Baumberg, who leads an interdisciplinary Strategic Research Network and Doctoral Training Centre focused on nanoscience and nanotechnology.

“Nanoscience is driving this. We are now building technology that allows us to even imagine these futures.”

I have featured Welland and his work here before and noted his penchant for wanting to insert nanodevices into humans as per this excerpt from an April 30, 2010 posting,
Getting back to the Cambridge University video, do go and watch it on the Nanowerk site. It is fun and very informative and approximately 17 mins. I noticed that they reused part of their Nokia morph animation (last mentioned on this blog here) and offered some thoughts from Professor Mark Welland, the team leader on that project. Interestingly, Welland was talking about yet another possibility. (Sometimes I think nano goes too far!) He was suggesting that we could have chips/devices in our brains that would allow us to think about phoning someone and an immediate connection would be made to that person. Bluntly—no. Just think what would happen if the marketers got access and I don’t even want to think what a person who suffers psychotic breaks (i.e., hearing voices) would do with even more input. Welland starts to talk at the 11 minute mark (I think). For an alternative take on the video and more details, visit Dexter Johnson’s blog, Nanoclast, for this posting. Hint, he likes the idea of a phone in the brain much better than I do.

I’m not sure what could have occasioned this latest press release and related video featuring Welland and nanotherapeutics other than guessing that it was a slow news period.