Tag Archives: Fantastic Voyage

Steering a synthetic nanorobot using light

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This news comes from the University of Hong Kong. A Nov. 8, 2016 news item on Nanowerk throws some light on the matter (Note: A link has been removed),

A team of researchers led by Dr Jinyao Tang of the Department of Chemistry, the University of Hong Kong, has developed the world’s first light-seeking synthetic Nano robot. With size comparable to a blood cell, those tiny robots have the potential to be injected into patients’ bodies, helping surgeons to remove tumors and enabling more precise engineering of targeted medications. The findings have been published in October [2016] earlier in leading scientific journal Nature Nanotechnology (“Programmable artificial phototactic microswimmer”).

An Oct. 24, 2016 University of Hong Kong press release (also on EurekAlert), which originated the news item, expands on the theme,

It has been a dream in science fiction for decades that tiny robots can fundamentally change our daily life. The famous science fiction  movie “Fantastic  Voyage” is a very good example, with a group of scientists driving their miniaturized nano-submarine inside human body to repair a damaged brain. In the film “Terminator  2,” billions of nanorobots were assembled into the amazing shapeshifting body: the T-1000. In the real world, it is quite challenging to make and design a sophisticated nanorobot with advanced functions.

The Nobel Prize in Chemistry 2016 was awarded to three scientists for “the design and synthesis of molecular machines.” They developed a set of mechanical components at molecular scale which may be  assembled into  more complicated nanomachines  to  manipulate single  molecule such as DNA or proteins in the future. The development of tiny nanoscale machines for biomedical applications has been a major trend of scientific research in recent years. Any breakthroughs will potentially open the door to new knowledge and treatments of diseases and development of new drugs.

One difficulty in nanorobot design is to make these nanostructures sense and respond to the environment. Given each nanorobot is only a few micrometer in size which is ~50 times smaller than the diameter of a human hair, it  is very difficult  to  squeeze  normal electronic sensors and circuits into  nanorobots with reasonable price. Currently, the only method to remotely control nanorobots is to  incorporate tiny magnetic inside the nanorobot and guide the motion via external magnetic field.

The  nanorobot developed by Dr Tang’s team use light as the propelling  force, and is the first research team globally to explore the light-guided nanorobots and demonstrated its feasibility and effectiveness. In their paper published in Nature  Nanotechnology, Dr Tang’s team  demonstrated  the  unprecedented ability of these light-controlled nanorobots as they are “dancing”  or even spell a word under light control. With a novel  nanotree structure, the nanorobots can respond to the light shining on it like  moths  being drawn to flames. Dr Tang described the motions as if “they can “see” the light and drive itself towards it”.

The team gained inspiration from natural green algae
for the nanorobot design. In nature, some green algae have evolved  with  the  ability  of  sensing  light  around  it.  Even just a single cell, these green  algae can sense the intensity of light and swim  towards the light source for photosynthesis. Dr  Jinyao  Tang’s team successfully developed the nanorobots after over three years’ efforts. With a novel nanotree structure, they are composed of two  common and low-price semiconductor materials: silicon  and titanium oxide. During  the  synthesis, silicon  and titanium oxide are shaped into nanowire and then further arranged into a tiny nanotree heterostructure.

Dr Tang said: “Although the current nanorobot cannot be used for disease treatment yet, we are working on the next generation nanorobotic system which is more efficient and biocompatible.”

“Light is a more effective option to communicate between microscopic world and macroscopic world. We can conceive that more complicated instructions can be sent to nanorobots which provide scientists with a new tool to further develop more functions into nanorobot and get us one step closer to daily life applications,” he added.

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

Programmable artificial phototactic microswimmer by Baohu Dai, Jizhuang Wang, Ze Xiong, Xiaojun Zhan, Wei Dai, Chien-Cheng Li, Shien-Ping Feng, & Jinyao Tang.  Nature Nanotechnology (2016)  doi:10.1038/nnano.2016.187 Published online 17 October 2016

So, this ‘bot’ seems to be a microbot or microrobot with some nanoscale features. In any event, the paper is behind a paywall.

Canada’s Nanorobotics Laboratory unveils its ‘medical interventional infrastructure’

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Located at the Polytechnique Montréal (Canada), the Nanorobotics Laboratory has built a one-of-a-kind ‘medical interventional infrastructure’, the result of a $4.6M investment from various levels of government and from private enterprise.

Before getting to the news release, here’s a video featuring Prof. Sylvain Martel who discusses his work by referencing the movie, Fantastic Voyage. There are subtitles for those whose French fails them,

From an Aug. 24, 2016 Polytechnique Montréal news release (also on EurekAlert),

Fifty years to the day after the film Fantastic Voyage was first shown in theatres, the Polytechnique Montréal Nanorobotics Laboratory is unveiling a unique medical interventional infrastructure devoted to the fight against cancer. The outcome of 15 years of research conducted by Professor Sylvain Martel and his team, it enables microscopic nanorobotic agents to be guided through the vascular systems of living bodies, delivering drugs to targeted areas.

An action-packed 100,000-kilometre journey in the human body

Fantastic Voyage recounted the adventure of a team of researchers shrunk to microscopic size who, aboard a miniature submarine, travelled into a patient’s body to conduct a medical operation in a surgically inoperable area. This science fiction classic has now been eclipsed by procedures and protocols developed by Professor Martel’s multidisciplinary team comprising engineers, scientists and experts from several medical specialties working together on these projects that herald the future of medicine.

“Our work represents a new vision of cancer treatments, with our goal being to develop the most effective transportation systems for the delivery of therapeutic agents right to tumour cells, to areas unreachable by conventional treatments,” says Professor Martel, holder of the Canada Research Chair in Medical Nanorobotics and Director of the Polytechnique Montréal Nanorobotics Laboratory.

Conveying nanorobotic agents into the bloodstream to reach the targeted area right up to the tiniest capillaries without getting lost in this network stretching about 100,000 kilometres—two-and-a-half times the Earth’s circumference—is a scenario that has been turned into reality. This is an adventure-filled journey for these microscopic vehicles that must confront the powerful onslaught of arterial blood flow, the mazes of the vascular network and the narrowness of the capillaries—just like the film’s heroes!

“Doctors” invisible to the naked eye

To conduct this fantastic voyage, Professor Martel’s team is developing various procedures, often playing a pioneering role. These include navigating carriers just a fraction of the thickness of a hair through the arteries using a clinical magnetic resonance imaging (MRI) platform, the first in the world to achieve this in a living organism, in 2006. This exploit was followed in 2011 by the guidance of drug-loaded micro-transporters into the liver of a rabbit.

Limits to the miniaturization of artificial nanorobots prevent them from penetrating the smallest blood vessels, however. For this, Professor Martel plans to have them play the role of Trojan horses, enclosing an “army” of special bacteria loaded with drugs that they will release at the edges of these small vessels.

Able to follow paths smaller than a red blood cell, these self-propelled bacteria move at high speed (200 microns per second, or 200 times their size per second). Once they are inside a tumour, they are able to naturally detect hypoxic (oxygen-starved) zones, which are the most active zones and the hardest to treat by conventional means, including radiotherapy, and then deliver the drug.

Professor Martel’s team has succeeded in using this procedure to administer therapeutic agents in colorectal tumours in mice, guiding them through a magnetic field. This has just been the subject of an article in the renowned journal Nature Nanotechnology, titled Magneto-gerotactic Bacteria Deliver Drug-containing Nanoliposomes to Tumour Hypoxic Regions. “This advanced procedure, which provides optimal targeting of a tumour while preserving surrounding healthy organs and tissue, unlike current chemotherapy or radiotherapy, heralds a new era in cancer treatment,” says Dr. Gerald Batist, Director of the McGill Centre for Translational Research in Cancer, based at the Jewish General Hospital, which is collaborating on the project.

Professor Martel’s projects also focus on the inaccessibility of certain parts of the body, such as the brain, to transporting agents. In 2015, his team also stood out by successfully opening a rat’s blood-brain barrier, temporarily and without damage, providing access to targeted areas of the brain. This feat was achieved through a slight rise in temperature caused by exposing nanoparticles to a radiofrequency field.

“At present, 98% of drug molecules cross the blood-brain barrier only with great difficulty,” notes Dr. Anne-Sophie Carret, a specialist in hematology-oncology at Montréal’s Centre hospitalier universitaire Sainte-Justine and one of the doctors collaborating on the project. “This means surgery is often the only way to treat some patients who have serious brain diseases. But certain tumours are inoperable because of their location. Radiation therapy, for its part, is not without medium- and long-term risk for the brain. This work therefore offers real hope to patients suffering from a brain tumour.”

Here’s who invested, how much they invested, and what the Nanorobotics Laboratory got for its money,

This new investment in the Nanorobotics Laboratory represents $4.6 million in infrastructure, with contributions of $1.85 million each from the Canada Foundation for Innovation (CFI), and the Government of Québec. Companies including Siemens Canada and Mécanik have also made strategic contributions to the project. This laboratory now combines platforms to help develop medical protocols for transferring the procedures developed by Professor Martel to a
clinical setting.

The laboratory contains the following equipment:

  • a clinical MRI platform to navigate microscopic carriers directly into specific areas in the vascular system and for 3D visualization of these carriers in the body;
  • a specially-developed platform that generates the required magnetic field sequences to guide special bacteria loaded with therapeutic agents into tumours;
  • a robotic station (consisting of a robotized bed) for moving a patient from one platform to another;
  • a hyperthermia platform for temporary opening of the blood-brain barrier;
  • a mobile X-ray system;
  • a facility to increase the production of these cancer-fighting bacteria.

Sylvain Martel’s most recent work with nanorobotic agents (as cited in the news release) was featured here in an Aug. 16, 2016 post.

A 244-atom submarine powered by light

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James Tour lab researchers at Rice University announce in a Nov. 16, 2015 news item on Nanowerk,

Though they’re not quite ready for boarding a lá “Fantastic Voyage,” nanoscale submarines created at Rice University are proving themselves seaworthy.

Each of the single-molecule, 244-atom submersibles built in the Rice lab of chemist James Tour has a motor powered by ultraviolet light. With each full revolution, the motor’s tail-like propeller moves the sub forward 18 nanometers.
And with the motors running at more than a million RPM, that translates into speed. Though the sub’s top speed amounts to less than 1 inch per second, Tour said that’s a breakneck pace on the molecular scale.

“These are the fastest-moving molecules ever seen in solution,” he said.

Expressed in a different way, the researchers reported this month in the American Chemical Society journal Nano Letters that their light-driven nanosubmersibles show an “enhancement in diffusion” of 26 percent. That means the subs diffuse, or spread out, much faster than they already do due to Brownian motion, the random way particles spread in a solution.

While they can’t be steered yet, the study proves molecular motors are powerful enough to drive the sub-10-nanometer subs through solutions of moving molecules of about the same size.

“This is akin to a person walking across a basketball court with 1,000 people throwing basketballs at him,” Tour said.

A Nov. 16, 2015 Rice University news release (also on EurekAlert), which originated the news item, provides context and details about the research,

Tour’s group has extensive experience with molecular machines. A decade ago, his lab introduced the world to nanocars, single-molecule cars with four wheels, axles and independent suspensions that could be “driven” across a surface.

Tour said many scientists have created microscopic machines with motors over the years, but most have either used or generated toxic chemicals. He said a motor that was conceived in the last decade by a group in the Netherlands proved suitable for Rice’s submersibles, which were produced in a 20-step chemical synthesis.

“These motors are well-known and used for different things,” said lead author and Rice graduate student Victor García-López. “But we were the first ones to propose they can be used to propel nanocars and now submersibles.”

The motors, which operate more like a bacteria’s flagellum than a propeller, complete each revolution in four steps. When excited by light, the double bond that holds the rotor to the body becomes a single bond, allowing it to rotate a quarter step. As the motor seeks to return to a lower energy state, it jumps adjacent atoms for another quarter turn. The process repeats as long as the light is on.

For comparison tests, the lab also made submersibles with no motors, slow motors and motors that paddle back and forth. All versions of the submersibles have pontoons that fluoresce red when excited by a laser, according to the researchers. (Yellow, sadly, was not an option.)

“One of the challenges was arming the motors with the appropriate fluorophores for tracking without altering the fast rotation,” García-López said.

Once built, the team turned to Gufeng Wang at North Carolina State University to measure how well the nanosubs moved.

“We had used scanning tunneling microscopy and fluorescence microscopy to watch our cars drive, but that wouldn’t work for the submersibles,” Tour said. “They would drift out of focus pretty quickly.”

The North Carolina team sandwiched a drop of diluted acetonitrile liquid containing a few nanosubs between two slides and used a custom confocal fluorescence microscope to hit it from opposite sides with both ultraviolet light (for the motor) and a red laser (for the pontoons).

The microscope’s laser defined a column of light in the solution within which tracking occurred, García-López said. “That way, the NC State team could guarantee it was analyzing only one molecule at a time,” he said.

Rice’s researchers hope future nanosubs will be able to carry cargoes for medical and other purposes. “There’s a path forward,” García-López said. “This is the first step, and we’ve proven the concept. Now we need to explore opportunities and potential applications.”

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

Unimolecular Submersible Nanomachines. Synthesis, Actuation, and Monitoring by Víctor García-López, Pinn-Tsong Chiang, Fang Chen, Gedeng Ruan, Angel A. Martí, Anatoly B. Kolomeisky, Gufeng Wang, and James M. Tour. Nano Lett., Article ASAP DOI: 10.1021/acs.nanolett.5b03764 Publication Date (Web): November 5, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

There is an illustration of the 244-atom submersible,

Rice University scientists have created light-driven, single-molecule submersibles that contain just 244 atoms. Illustration by Loïc Samuel

Rice University scientists have created light-driven, single-molecule submersibles that contain just 244 atoms. Illustration by Loïc Samuel

Remote-controlled microcarriers and nanorobotics in Québec

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They are called therapeutic magnetic microcarriers (TMMC) and they are drug delivery agents which have recently been successfully sent through a living rabbit’s bloodstream to a targeted area for successful administration of a drug. We’re in Fantastic Voyage (for those who don’t know the 1966 movie, it was more notable for then bombshell Raquel Welch’s presence than the science used to shrink a submarine filled with scientists to a microscopic size then injected into a dying diplomat’s bloodstream in an attempt to save his life) territory.

This latest breatkthrough comes from Sylvain Martel’s Nanorobotics Laboratory at Polytechnique Montréal (Québec, Canada). From the March 16, 2011 news item on Nanowerk,

Known for being the world’s first researcher to have guided a magnetic sphere through a living artery, Professor Martel is announcing a spectacular new breakthrough in the field of nanomedicine. Using a magnetic resonance imaging (MRI) system, his team successfully guided microcarriers loaded with a dose of anti-cancer drug through the bloodstream of a living rabbit, right up to a targeted area in the liver, where the drug was successfully administered. This is a medical first that will help improve chemoembolization, a current treatment for liver cancer.

The therapeutic magnetic microcarriers (TMMCs) were developed by Pierre Pouponneau, a PhD candidate under the joint direction of Professors Jean-Christophe Leroux and Martel. These tiny drug-delivery agents, made from biodegradable polymer and measuring 50 micrometers in diameter — just under the breadth of a hair — encapsulate a dose of a therapeutic agent (in this case, doxorubicin) as well as magnetic nanoparticles. Essentially tiny magnets, the nanoparticles are what allow the upgraded MRI system to guide the microcarriers through the blood vessels to the targeted organ. During the experiments, the TMMCs injected into the bloodstream were guided through the hepatic artery to the targeted part of the liver where the drug was progressively released.

Martel’s work was last highlighted here in my April 6, 2010 posting. At that time he was working with bacteria which he and his team had guided into assembling into pyramid shapes. The team had also guided these bacteria through the bloodstream of a rat.  There’s more about this earlier work with bacteria in a July 28, 2010 article by Monique Roy-Sole on the Innovation Canada website. As you may have guessed from the ‘pyramids’,  Martel’s inspiration for that work came from Egypt,

Martel was inspired by the story of the pyramid of Djoser, built by an estimated 5,000 slaves around 2600 BC, and considered to be the earliest large-scale stone structure known to humankind. He decided to employ 5,000 bacteria in a drop of water as mini workers to construct a similar step pyramid in less than 15 minutes.

As for Martel’s first breakthrough (from Sole’s article),

In 2007, he and researchers from École Polytechnique and the Centre Hospitalier de l’Université de Montréal successfully injected a tiny magnetic device, measuring 1.5 millimetres in diameter, into the carotid artery of a pig, controlling and tracking its travels in the bloodstream with a clinical magnetic resonance imaging (MRI) scanner. Since then, Martel and his team have been working at reducing the size of the device so it can circulate in smaller blood vessels. This would allow doctors to diagnose and treat areas of the body that current instruments, such as catheters, cannot reach.

I hope this proves to be successful. As anyone who’s had a family member or friend undergo cancer treatments knows, the procedures and medicines are crude in that they destroy healthy as well as diseased tissue. Hopefully, this kind of work will make the cures less drastic.