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Advances in Molecular technologies enabling Molecular Robotics, the Ultimate Miniature Machines

The modern world is filled with macroscopic machines that perform work that we either find demanding or function in places or on length scales in which we cannot act. To date however, we have yet to develop a functional nanotechnology that operates on the scale of molecules or assemblies of molecules. Scientists from a range of disciplines are working to understand, design, and create the next generation of switches and motors to mechanize our world from the bottom up.

 

Molecular machines can be defined as devices that can produce useful work through the interaction of individual molecules at the molecular scale of length. A convenient unit of measurement at the molecular scale would be a nanometer. Hence, molecular machines also fall into the category of nanomachines. Molecular machines depend on inter- and intramolecular interactions for their function. These interactions include forces such as the ionic and Van der Waal’s forces and are a function of the geometry of the individual molecules.

 

Molecular machines can be subdivided into three broad categories—protein based, DNA-based, and chemical molecular motors. A majority of natural molecular machines are protein based, whereas the DNA-based molecular machines are mostly synthetic. Nature deploys proteins to perform various cellular tasks, from moving cargo to catalyzing reactions, whereas DNA has been retained as an information carrier. Hence, it is understandable that most of the natural machinery is built from proteins.

 

In biology, macromolecular machines frequently perform tasks essential for life such as DNA replication and ATP synthesis. The term is also common in nanotechnology where a number of highly complex molecular machines have been proposed that are aimed at the goal of constructing a molecular assembler.

 

A wide variety of artificial molecular machines (AMMs) have been synthesized by chemists which are rather simple and small compared to biological molecular machines. The first AMM, a molecular shuttle, was synthesized by Sir J. Fraser Stoddart.  A molecular shuttle is a rotaxane molecule where a ring is mechanically interlocked onto an axle with two bulky stoppers. The ring can move between two binding sites with various stimuli such as light, pH, solvents, and ions.

 

Molecular  machines have applications in various fields, including medicine, space exploration, electronics and military.

 

The advances in molecular machines may enable future molecular robots.  U.S. military may manufacture combat parts and supplies on the battlefield using robots made of molecules all working together as part of a molecular factory. The nanoscale factories could revolutionize military logistics by eliminating the need to transport or store parts and supplies for every possible contingency. The same technology may prove useful for tying together strands of molecules for superstrong, lightweight armor.

 

The potential benefits go far beyond the military, however. In addition to producing medicines and antidotes, molecular robots could help cure diseases caused by genetic disorders. The National Human Genome Research Institute lists nearly 50 such disorders, including autism, various cancers, cystic fibrosis and Parkinson’s disease. “We could one day perhaps replace those [genes] with artificial ones. It would be like molecular prosthetics,” Leigh says. “Using a molecular prosthetic may enable a disease to be cured.”

Advances in Molecular machines

Today a wide variety of AMMs exists. Molecular motors are molecules that are capable of rotary motion around a single or double bond. Molecular propeller is a molecule that can propel fluids when rotated, due to its special shape that is designed in analogy to macroscopic propellers. A molecular switch is a molecule that can be reversibly shifted between two or more stable states. A molecular shuttle is a molecule capable of shuttling molecules or ions from one location to another. Nanocars are single molecule vehicles that resemble macroscopic automobiles and are important for understanding how to control molecular diffusion on surfaces. Molecular tweezers are host molecules capable of holding items between their two arms. A molecular sensor is a molecule that interacts with an analyte to produce a detectable change. A molecular logic gate is a molecule that performs a logical operation on one or more logic inputs and produces a single logic output. A molecular assembler is a molecular machine able to guide chemical reactions by positioning reactive molecules with precision.

 

Physicists create self-directed molecular motors that walk on tracks

Molecular cargo transportation is an ongoing and vital undertaking in every cell of the human body. Nature transports intracellular cargos using bipedal molecular motors that walk along a mesh of molecular filaments called cytoskeletons. By mimicking Nature, the development of artificial track-walking molecular motors (nanowalkers), can potentially open up a wide range of nanoscale applications.
Prof WANG Zhisong and his research team from the Department of Physics, NUS have developed two sets of conceptually new mechanisms that enable artificial nanowalkers to move in a self-guided direction using their internal mechanics. The molecular motors developed by the research team are biomimetic bipeds made of engineered DNA molecules. These molecular motors can be powered either by chemical fuels (in which the motor catalyses a chemical reaction involving the fuel molecule and uses the released energy) or through light illumination. They produce translational motion if the track, which is formed via DNA assembly, is linear and rotational motion if the track forms a circle. Thus these “non-bridge-burning” molecular motors can function as a transporter or a rotor at the molecular level, depending on the track configuration. In contrast, a “bridge-burning” molecular motor on a circular track falls into forward or backward rotation randomly and is incapable of repetitive operation.

 

Prof Wang said, “These new molecular motors can open up new nanoscale applications beyond those which can be achieved by state-of-the-art “bridge-burning” type motors. With optically or chemically-powered DNA motors, we can potentially realise biomaterials that can adapt their shape according to their environment (like an octopus). These biomaterials can be made from elastic fibres that embed molecular motors, exhibiting fine motion control that is similar to our muscles.”

 

LMU chemists have developed the first molecular motor that can be powered by light alone.

Chemists from LMU in Munich have developed a molecular motor that is powered by light. This means that molecules can carry out specific rotary movements by means of an external energy supply. They thus form an important basis for applications in nanotechnology. Molecules that change their structure under the influence of light are particularly suitable for nanoscale motors. Up to now, light-driven molecular motors have required additional reactions driven by heat. This is why they were previously dependent on the ambient temperature.

 

Henry Dube, LMU chemist, together with the student Aaron Gerwien, has now achieved the decisive breakthrough. They have developed a molecular motor that functions independently of temperature. It uses light as the driver and runs even faster at low temperatures. Until now, this was not possible. Molecular motors reacted to the ambient temperature. This also limited the field of application in nanotechnology.

 

In order to generate a complete 360-degree rotation with the rotary motion, a certain part of a molecule is to perform several rotary steps around another. The problem here is that the molecule must be prevented from turning back again. To do this, molecular motors require so-called ratchet steps. These are intermediate steps that change the molecule after a rotation in such a way that a back rotation is excluded. Normally, this is achieved by heat. Disadvantage: If the ambient temperature drops, the molecular motor runs all the slower – and it stops at cold temperatures.

 

Like earlier motor systems developed by Dube and his colleagues, the new motor is based on an organic substance called hemithioindigo. This molecule is made up of two different carbon skeletons, which are connected by a mobile double bond. “We have succeeded in modifying the molecule such that a complete rotation of one of the structural modules relative to the other requires only three reaction steps,” says Dube. Each rotational step is activated by visible light and there is no need for intermediate, thermally driven ratchet steps. Indeed, all three steps involved in the full rotation are promoted by a reduction in temperature, so that the rotation rate of the new molecules actually increases at lower temperatures.

 

“Each rotation step is made up of three different photoreactions, two of which we experimentally demonstrated directly for the first time only this year,” Dube explains. The researchers are confident that their motor’s novel driving mechanism and unique behavior will make it possible in the not too distant future for researchers to synthesize molecular machines which, thanks to their relative insensitivity to the precise environmental temperature, will enable unique applications not possible with hitherto known motors.

 

Molecular Robotics Builds the Ultimate Miniature Machines

Researchers at the University of Manchester in England have developed the first prototypes for robots made entirely of atoms, the building blocks of molecules. Molecules form the basis of everything on the planet and the planet itself, for that matter. The molecular robots—mobots?—are a millionth of a millimeter in size, meaning that a pile of a billion billion such robots would be the same volume and weight as a few grains of salt, according to a press release announcing the breakthrough. Each robot is made up of just 150 carbon, hydrogen, oxygen and nitrogen atoms and is capable of manipulating a single molecule. The robots can be programmed to move and build molecular cargo.

 

They operate by carrying out chemical reactions in special solutions, which can then be controlled and programmed by scientists to perform basic tasks. David Leigh, Royal Society research professor and Sir Samuel Hall chair of chemistry, University of Manchester, explains that robots in “the big world” may use fingerlike devices for gripping, but molecular robots use an atom, such as sulfur. “It’s sort of a sticky atom, if you like—an atom that can be made sticky or nonsticky. It can be sticky to pick something up, and then you can change the electronic properties of the atom to make it release, so you can grip and release,” Leigh says. “You can use electrostatics. You can make it charged to pick up something of the opposite charge, and then if you stop it being charged, it will drop it.”

 

One possibility for programming the itty-bitty bot is to switch it back and forth from acidic to nonacidic or basic. “If we give it a sequence changing the acidity of the environment the robot is in, we switch it between acidic and then basic and then acidic and then basic—acid and nonacid—it will do one thing. If you change that and leave your acid for longer, and then change the acidity again, it will do something different. That’s chemical programming,” he adds.

 

The result may be to switch the gripper on and off, or to twist the arm to point in one direction or another, or to pick up or put down cargo. “It’s those sorts of operations that are controlled by chemical stimuli. Or there are other sorts of stimuli we can use. We can use lights. We can use electrochemistry. It’s exactly the same principle. You program it in the same way you program a robotic arm in the big world. It’s just that it’s not using a code from a computer. It’s using a different way of interrogating the arm,” Leigh elaborates.

 

Building big-world objects with molecular robots is simply a matter of connecting the necessary molecules. After all, everything on the planet is made of molecules. “Molecules are made of atoms assembled together like Lego blocks. Just like you can make machines—cars and trains and pulleys and things like that—out of Legos, that’s what molecular machines look like,” Leigh offers.

 

But it’s really not that easy because big-world physics does not work in the molecular world. Building a molecule-size car, for example, is impossible. “Something like a gas engine simply can’t function at the molecular-length scale because heat is immediately dissipated, so you can’t build motors based on heat transfer. You can’t just shrink down the motorcar to the molecular world,” he notes.

 

Leigh’s team announced last year the first-ever molecular robot, but the research has been going on for about 20 years and is still in its infancy. To make the robot work, the researchers studied nature’s molecular machines. “There are already working nanotechnology machines. That’s called biology,” Leigh says. “The way the cell works and the way that life works is that all the biological processes are actually run by molecular machines, but they’re all biological. They’re proteins, but they’re working just like machines do in the big world.”

 

Researchers indicate that the technology could one day offer a range of benefits in a variety of fields, including medical and military. The robots may be able to manufacture medicines or antidotes for chemical or biological warfare agents. “You could make antidotes for all sorts of nefarious or noxious agents. You wouldn’t need to carry with you all sorts of antidotes. Your molecular factory could just manufacture the antidote for the poison gas or whatever the substance was,” Leigh suggests.

 

On-demand manufacturing of parts and supplies is another possibility, a capability similar to today’s 3D printing. Military forces operating in remote places such as Afghanistan or the Arctic would not need to transport tons of supplies. “If you’re in the Arctic and you can’t get supplied with lots of different drugs, and you fall ill from pneumonia, you could use these to manufacture just the drug you want,” Leigh theorizes.

 

Strong, lightweight and flexible armor is another possibility. The University of Manchester team is receiving some funding from the Defense Advanced Research Projects Agency (DARPA) in the United States to explore the possibility of using the same technology to develop advanced materials. “The same technology we use for molecular machines we also use to weave molecular fabrics. We have a DARPA grant that’s to do with weaving molecular fabrics, which could be useful for making very strong, very lightweight materials,” Leigh reports.

 

Currently, no process exists for weaving molecular strands. Today’s armor relies instead on molecular strands lined up side by side “like pencils in a pencil case,” Leigh adds. “Those rigid rods are then twisted into fabrics. We’re trying to weave the individual strands themselves.”

 

Anne Fischer, a program manager in DARPA’s Defense Sciences Office, confirms the agency is providing funding for the research. “One of the areas professor Leigh’s group studies is molecular knots. These are precisely entangled molecules that form structures resembling knots: for example, the Celtic knot,” Fischer reveals in a written response to questions. “His work with DARPA is an extension of this concept, with a goal to chemically stitch molecular knots together in a two-dimensional woven structure.”

 

Those molecular knots may offer benefits beyond advanced armor. “Two-dimensional materials like graphene, boron nitride and molybdenum disulfide have attractive properties for a number of applications, including high-strength materials, electrical components or filtration membranes,” Fischer adds.

 

So far, however, the materials are not sophisticated enough to reach their full potential. “These materials are made of relatively simple building blocks—the atoms themselves. In contrast, the unit cell of the interwoven material in Leigh’s work is the molecular knot itself. These materials could enable tremendous variety in material architecture and potentially properties just by adjusting the knotted building blocks,” Fischer offers. “The Leigh group has pioneered work on molecular knots, and this exploratory effort is testing whether and how those knots can be connected in a two-dimensional array to ultimately realize tunable and desirable material properties.”

 

It is far too early to say with any certainty what the final results of the research might be, but Leigh hints that they could be revolutionary. “The ability to weave materials brought Stone Age man out of the cave because he was able to suddenly weave fabrics and keep himself warm. This could have similar effects. That’s what we think. Until we make them, we don’t know,” Leigh acknowledges.

 

 

We can see that will happen one day with molecular prosthetics, and we will be able to replace biological machines even with artificial molecular machines that are just as good,” Leigh explains.

 

They could potentially lead to programmable desktops—as in the top of a desk, not computers. Today’s desktop may be made of wood or any number of other materials, all of which are made of molecules, and its only function is to hold a computer, a mouse, a coffee cup and other objects. “If it was covered in a layer of molecular machines that could switch their properties, they might be able to switch the surface from being sticky to nonsticky, or they might be able to switch the surface from being hard to flexible, or they might even enable me to pass the coffee cup on the table toward me just by drawing a light with a laser pointer instead of my having to reach over and pick it up,” Leigh proposes. “It could just pass along the coffee cup from machine to machine, just like a moving stairway or moving walkway.”

 

Many of the technological advances in recent decades have been a result of machine miniaturization. Computers have become smaller but far more powerful. The chip inside a cellphone has more processing power than a room-size computer in the 1950s, Leigh notes. And it’s hard to get more miniature than molecules. “The same will be true of molecular robotics to build things. You will require far less energy than you need for the factories that we use today,” Leigh asserts. “Building machines out of molecules is the ultimate in miniaturization.”

 

 

 

References and resources also include:

https://phys.org/news/2018-01-physicists-self-directed-molecular-motors-tracks.html

https://www.en.uni-muenchen.de/news/newsarchiv/2018/dube_neuermotor.html

https://www.afcea.org/content/molecular-robotics-builds-ultimate-miniature-machines

About Rajesh Uppal

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