A patch consisting of three layers of polymers can be loaded with nanoparticles and attached to living cells to give them nanotech backpacks that could be useful for carrying chemotherapy and imaging agents to tumors, or to align cells in certain patterns for tissue engineering. From “Scientists create tiny backpacks for cells” written by Anne Trafton, MIT News Office (found via PhysOrg.com/a>):

MIT engineers have outfitted cells with tiny “backpacks” that could allow them to deliver chemotherapy agents, diagnose tumors or become building blocks for tissue engineering.

Michael Rubner, director of MIT’s Center for Materials Science and Engineering and senior author of a paper on the work that appeared online in Nano Letters [abstract], said he believes this is the first time anyone has attached such a synthetic patch to a cell.

The polymer backpacks allow researchers to use cells to ferry tiny cargoes and manipulate their movements using magnetic fields. Since each patch covers only a small portion of the cell surface, it does not interfere with the cell’s normal functions or prevent it from interacting with the external environment.

“The goal is to perturb the cell as little as possible,” said Robert Cohen, the St. Laurent Professor of Chemical Engineering at MIT and an author of the paper.

The researchers worked with B and T cells, two types of immune cells that can home to various tissues in the body, including tumors, infection sites, and lymphoid tissues — a trait that could be exploited to achieve targeted drug or vaccine delivery.

“The idea is that we use cells as vectors to carry materials to tumors, infection sites or other tissue sites,” said Darrell Irvine, an author of the paper and associate professor of materials science and engineering and biological engineering.

Cellular backpacks carrying chemotherapy agents could target tumor cells, while cells equipped with patches carrying imaging agents could help identify tumors by binding to protein markers expressed by cancer cells.

Another possible application is in tissue engineering. Patches could be designed that allow researchers to align cells in a certain pattern, eliminating the need for a tissue scaffold.

—Jim

Re-engineering a simple nanotech device to make it more functional, Chinese scientists have developed an improved DNA tweezers that is able to capture, hold, and release a target molecule in a controlled manner. To do so, they took advantage of an alternative type of DNA base pair that allows a third strand of DNA to bind to a DNA double helix to form triple strand DNA under certain conditions. From a Nanowerk Spotlight, written by Michael Berger “The gripping potential of DNA nanotechnology“:

The exciting potential applications for DNA tweezers include their use in constructing various molecular devices dedicated to repairing a functional unit in a cell, harnessing the delivery of drug molecules to pathogenic cells, or assembling nanoscale devices.

There have been several earlier versions of similar DNA devices that can be operated to have open and close actions but it still has been a challenge to make them behave like real tweezers that can be handled to grasp and transfer an object. A team of Chinese scientists has now demonstrated a very simple design to fabricate a close-to-reality ‘grasp’ and ‘release’ function for a pair of DNA tweezers.

“The most challenging part to make this tweezer function available has to do with the structural simplicity of DNA tweezers that only have two mechanical arms — which is not a good setup for stably capturing something” Dr. Zhaoxiang Deng tells Nanowerk. “We have successfully circumvented this challenge thanks to the helical wrapping action of the DNA target around the tweezers’ arms during the formation of Hoogsteen bonds …, which greatly increases the probability for the target to be held between the tweezers’ arms.”

Based on this, Deng, a professor in the Department of Chemistry at the University of Science & Technology of China in Hefei, Anhui Province, together with his group, has successfully built a pair of DNA tweezers that can capture, hold, and release an object with easy control. They have reported their findings in the October 14, 2008 online edition of Journal of American Chemical Society (”Catch and Release: DNA Tweezers that Can Capture, Hold, and Release an Object under Control“).

Berger’s nicely illustrated article explains clearly how this improved tweezers functions. We are particularly happy to see that Prof Deng is thinking about how to eventually use his improved DNA nanodevice as one part of complex molecular machine systems.

“Also, if you imagine a nanofactory, you would need a mechanical hand to deal with many different tasks such as taking one part from an upstream worker, processing it and then handing it over to a downstream worker. In this process, a device like the one we have invented might find some uses even though it might be too early to think about these questions.”

The team is currently considering the integration of different DNA mechanical devices including the tweezers toward multiplexed and cooperative functions. Deng mentions that the simple demonstration devices that currently exist can only perform a simple task at a time; something which is not suitable for the construction of highly advanced nanofabrication systems and other nano devices. He notes that the ability to be integrated into larger assemblies is an inherent merit of DNA structures, which makes it possible to combine different functional units in a single platform and also allows them to be individually addressable after being coded using DNA sequences.

—Jim

Robert A. Freitas Jr. brings to our attention a major step on the road to advanced nanotech, published a couple weeks ago in Science (abstract). He writes:

This paper reports purely mechanical-based covalent bond-making and bond-breaking (true mechanosynthesis) involving atom by atom substitution of silicon (Si) atoms for tin (Sn) atoms in an Sn monolayer surface on a Si(111) surface; also demonstrates atomically precise exchange of lead (Pb) and indium (In) on Si(111) surface. This is the first report of a complex pattern being drawn on a 2D surface, literally atom by atom, purely via mechanical forces.

Working on a single atomic layer of tin atoms grown on a single-crystal silicon surface, the Japanese-European collaboration maneuvered an atomic force microscope (AFM) tip precisely (plus or minus 0.01 nm) over a single silicon atom defect in the tin surface, and were able to reversibly exchange a tin atom on the apex of the tip and the silicon atom on the surface. These experiments were done at room temperature and, unlike earlier demonstrations in which a scanning tunneling microscope (STM) tip was used to interchange atoms weakly bond to a metallic surface through use of an electrical bias, this demonstration used mechanical force to interchange strongly bound atoms.

To characterize what was happening between the atoms involved, the researchers did a first principles quantum mechanics simulation of the tip-surface interactions. The simulations show that the key step happens when the outermost atom of the tip and the target atom on the surface have an equal number of bonds with the surrounding atoms so that they lose the property of being part of the tip or the surface.

The method used here of vertical interchange of atoms between tip and surface was found to be about ten times faster than previous lateral manipulations of atoms with the AFM. Using vertical manipulation as an atomic pen, the authors wrote the chemical symbol for silicon (Si) with 12 silicon atoms on the tin surface. In supplementary material, the authors report doing similar manipulations with lead and indium atoms on a silicon surface. They propose that:

This manipulation technique may pave the way toward selective semiconductor doping, practical implementation of quantum computing, or atomic-based spintronics. The possibility of combining sophisticated vertical and lateral atom manipulations with the capability of AFM for single-atom chemical identification may bring closer the advent of future atomic-level applications, even at room temperature.

—Jim

By nearly eliminating the light lost to solar cells by reflection, a multilayer nanotech coating promises to increase solar cell efficiency. From ScienceDaily “Solar Power Game-changer: ‘Near Perfect’ Absorption Of Sunlight, From All Angles“:

Researchers at Rensselaer Polytechnic Institute have discovered and demonstrated a new method for overcoming two major hurdles facing solar energy. By developing a new antireflective coating that boosts the amount of sunlight captured by solar panels and allows those panels to absorb the entire solar spectrum from nearly any angle, the research team has moved academia and industry closer to realizing high-efficiency, cost-effective solar power.

“To get maximum efficiency when converting solar power into electricity, you want a solar panel that can absorb nearly every single photon of light, regardless of the sun’s position in the sky,” said Shawn-Yu Lin, professor of physics at Rensselaer and a member of the university’s Future Chips Constellation, who led the research project. “Our new antireflective coating makes this possible.”

An untreated silicon solar cell only absorbs 67.4 percent of sunlight shone upon it — meaning that nearly one-third of that sunlight is reflected away and thus unharvestable. From an economic and efficiency perspective, this unharvested light is wasted potential and a major barrier hampering the proliferation and widespread adoption of solar power.

After a silicon surface was treated with Lin’s new nanoengineered reflective coating, however, the material absorbed 96.21 percent of sunlight shone upon it — meaning that only 3.79 percent of the sunlight was reflected and unharvested. This huge gain in absorption was consistent across the entire spectrum of sunlight, from UV to visible light and infrared, and moves solar power a significant step forward toward economic viability.

Lin’s new coating also successfully tackles the tricky challenge of angles.

The research was published in Optics Letters (abstract)
—Jim

A better understanding of how biomineralization converts ordinary minerals to biological mineral structures with extraordinary hardness and fracture resistance may lead to superhard materials for nanotech applications. In the case of sea urchin spicules, the process involves a fractal-like or random walk process by which 40-100 nm particles of amorphous calcium carbonate are converted into a single crystal of calcite with a very unusual geometry. From the University of Wisconsin-Madison, via AAAS EurekAlert “Sea urchin yields a key secret of biomineralization“:

The teeth and bones of mammals, the protective shells of mollusks, and the needle-sharp spines of sea urchins and other marine creatures are made-from-scratch wonders of nature.

Used to crush food, for structural support and for defense, the materials of which shells, teeth and bones are composed are the strongest and most durable in the animal world, and scientists and engineers have long sought to mimic them.

Now, harnessing the process of biomineralization may be closer to reality as an international team of scientists has detailed a key and previously hidden mechanism to transform amorphous calcium carbonate into calcite, the stuff of seashells. The new insight promises to inform the development of new, superhard materials, microelectronics and micromechanical devices.

In a report today (Oct. 27) in the Proceedings of the National Academy of Sciences (PNAS), a group led by University of Wisconsin-Madison physicist Pupa Gilbert describes how the lowly sea urchin transforms calcium carbonate — the same material that forms “lime” deposits in pipes and boilers — into the crystals that make up the flint-hard shells and spines of marine animals. The mechanism, the authors write, could “well represent a common strategy in biomineralization….”

“If we can harness these mechanisms, it will be fantastically important for technology,” argues Gilbert, a UW-Madison professor of physics. “This is nature’s bottom-up nanofabrication. Maybe one day we will be able to use it to build microelectronic or micromechanical devices.”

Gilbert, who worked with colleagues from Israel’s Weizmann Institute of Science, the University of California at Berkeley and the Lawrence Berkeley National Laboratory, used a novel microscope that employs the soft-X-rays produced by synchrotron radiation to observe how the sea urchin builds its spicules, the sharp crystalline “bones” that constitute the animal’s endoskeleton at the larval stage.

Similar to teeth and bones, the sea urchin spicule is a biomineral, a composite of organic material and mineral components that the animal synthesizes from scratch, using the most readily available elements in sea water: calcium, oxygen and carbon. The fully formed spicule is composed of a single crystal with an unusual morphology. It has no facets and within 48 hours of fertilization assumes a shape that looks very much like the Mercedes-Benz logo.

These crystal shapes, as those of tooth enamel, eggshells or snails, are very different from the familiar faceted crystals grown through non-biological processes in nature. “To achieve such unusual — and presumably more functional — morphologies, the organisms deposit a disordered amorphous mineral phase first, and then let it slowly transform into a crystal, in which the atoms are neatly aligned into a lattice with a specific and regular orientation, while maintaining the unusual morphology,” Gilbert notes.

—Jim

You might think that by now the definitions of terms like “nanotechnology” and “nanosystems” would be firmly established. In fact the process of arriving at an international consensus is more difficult than you might expect. Representing Foresight in the effort to define these and other terms is David R. Forrest, Ph.D., President of the Institute for Molecular Manufacturing and a Senior Fellow at the Foresight Nanotech Institute, who serves as Foresight’s representative on the Technical Advisory Group to the American National Standards Institute (ANSI) on the ISO Technical Committee on Nanotechnology (TC/229). From Dr. Forrest’s report on “Foresight’s Standards Work for Molecular Nanosystems“:

The process is glacial: ISO has been at this for three years now and there is still no ratified definition of “Nanotechnology” let alone the myriad of other related terms. Foresight’s continued presence and participation in the ISO process helps to maintain a focus on nanosystems, maintains our stature in the international Nanotechnology community as a leader in education and policy issues, and underscores our commitment to consensus standards as a cornerstone of responsible development of molecular nanotechnology.

—Jim

One of the advantages of nanotech treatments for cancer is that nanoparticles can be large enough to introduce more than one type of therapeutic molecule into the same cancer cell. Another advantage is that nanoparticles can protect and deliver into cells molecules that would never make it into the cancer cell unassisted. Now scientists at Pennsylvania State University have demonstrated that nanoparticles can introduce two very promising, but easily degraded, therapeutic molecules into a laboratory model of human skin, and that together they are much more effective than either is alone is slowing the development of deadly melanoma skin cancer. From the National Cancer Institute’s Alliance for Nanotechnology in Cancer “Nanoparticles Target Multiple Cancer Genes, Shrink Tumors More Effectively“:

Nanoparticles filled with small interfering RNA (siRNA) molecules targeting two genes that trigger melanoma have shown that they can inhibit the development of melanoma, the most dangerous type of skin cancer. The nanoparticles, administered in conjuction with ultrasound irradiation, exerted their effects only on malignant tissue, leaving healthy tissue alone.

“It is a very selective and targeted approach,” said Gavin Robertson, Ph.D., who led the team of researchers from the Penn State College of Medicine. “And unlike most other cancer drugs that inadvertently affect a bunch of proteins, we are able to knock out single genes.”

The Penn State researchers speculated that siRNA could turn off the two cancer-causing genes and potentially treat the deadly disease more effectively. “siRNA checks the expression of the two genes, which then lowers the abnormal levels of the cancer causing proteins in cells,” explained Dr. Robertson. This research appears in the journal Cancer Research [abstract].

In recent years, researchers have zeroed in on two key genes—B-Raf and Akt3—that play key roles in the development of melanoma. Mutations in the B-Raf gene, the most frequently mutated gene in melanoma, lead to the production of a mutant form of the B-Raf protein, which then helps mole cells survive and grow. B-Raf mutations alone, however, do not trigger melanoma development. That event requires a second protein, called Akt3, that regulates the activity of the mutated B-Raf, which aids the development of melanoma. The siRNA agents used in this study specifically target Akt3 and the mutant B-Raf and therefore do not affect normal cells.

However, although knocking out specific genes may seem like a straightforward task, delivering the siRNA drug to cancerous cells is another story, because not only do protective layers in the skin keep drugs out but also chemicals in the skin quickly degrade the siRNA. To clear these two hurdles, Dr. Robertson and his team engineered lipid-based nanoparticles that can incorporate siRNA into their hollow interiors. The researchers then used a portable ultrasound device to temporarily create microscopic holes in the surface of the skin, allowing the drug-filled particles to leak into tumor cells beneath.

When the researchers exposed lab-generated skin containing early cancerous lesions to the treatment 10 days after the skin was created, the siRNA reduced the ability of cells containing the mutant B-Raf to multiply by nearly 60 to 70 percent and more than halved the size of lesions after 3 weeks. “This is essentially human skin with human melanoma cells, which provides an accurate picture of how the drug is acting,” said Dr. Robertson.

—Jim

Organisms that live in extreme environments may provide building blocks for nanotech applications that need to withstand extreme environments. A virus that infects a microorganism that lives in volcanic springs looks particularly promising. From Norwich BioScience Institutes, via AAAS EurekAlert “Extreme nature helps scientists design nano materials“:

Scientists are using designs in nature from extreme environments to overcome the challenges of producing materials on the nanometre scale. A team from the UK’s John Innes Centre, the Scripps Research Institute in California and the Institut Pasteur in Paris have identified a stable, modifiable virus that could be used as a nanobuilding block.

Viral nanoparticles (VNPs) are ideally sized, can be produced in large quantities, and are very stable and robust. They can self-assemble with very high precision, but are also amenable to modification by chemical means or genetic engineering.

Some applications of VNPs require them to withstand extremely harsh conditions. Uses in electrical systems may expose them to high temperatures, and biomedical uses can involve exposure to highly acidic conditions. VNPs able to remain functional in these conditions are therefore desirable. The team identified viruses from the hot acidic sulphurous springs in Iceland. One of these, SIRV2, was assessed for its suitability for use as a viral nanobuilding block.

SIRV2 is a virus that infects Sulfolobus islandicus, a single-celled microorganism that grows optimally at 80°C and at pH 3, and it was also able to withstand other harsh environments created in the laboratory. This shows that the rigid, rod-shaped SIRV2 virus capsule must be very stable, an important characteristic for use as a nanobuilding block. To be potentially useful as a VNP, the viral capsule also needs to be open to modification or decoration with functional chemical groups.

The researchers found that, depending on the chemistry used, modifications could be targeted specifically to the ends of the virus particle, to its body, or both. This spatially controlled modification is unique to this VNP, and opens up new possibilities when the nanobuilding blocks are built up into arrays or layers. Since the virus body and ends can be selectively labelled it is expected that arrays with different physical properties can be fabricated, for example by aligning particles body-to-body versus self-assembly end-to-end. This option is not possible with other rod-shaped VNPs.

“Future applications may be found in liquid crystal assembly, nanoscale templating, nanoelectronic and biomedical applications.” said Dr Dave Evans of the John Innes Centre.

“Further studies towards the development of these VNPs for materials are currently underway”, said Dr Nicole F. Steinmetz of the Scripps Research Institute. “We are looking into the use of the particles to generate complex structures such as rings or tetrapods”.

The research was published in the journal Advanced Functional Materials [abstract].
—Jim

On 5 June 2008, Robert Freitas and Ralph Merkle of the Institute for Molecular Manufacturing (IMM) submitted to IEEE Spectrum the following response to the article “Rupturing the Nanotech Rapture” by Richard A.L. Jones (IEEE Spectrum, June 2008 issue). Their brief letter is reproduced below because Spectrum has chosen to publish only one of the responses it received on this topic.

Several items that Richard Jones mentions are well-known research challenges, not showstoppers. All have been previously identified as such along with many other technical challenges not mentioned by Jones that we’ve been aware of for years. Unfortunately, the article also evidences numerous confusions: (1) The adhesivity of proteins to nanoparticle surfaces can (and has) been engineered; (2) nanorobot gears will reside within sealed housings, safe from exposure to potentially jamming environmental bioparticles; (3) microscale diamond particles are well-documented as biocompatible and chemically inert; (4) unlike biological molecular motors, thermal noise is not essential to the operation of diamondoid molecular motors; (5) most nanodiamond crystals don’t graphitize if properly passivated; (6) theory has long supported the idea that contacting incommensurate surfaces should easily slide and superlubricity has been demonstrated experimentally, potentially allowing dramatic reductions in friction inside properly designed rigid nanomachinery; (7) it is hardly surprising that nanorobots, like most manufactured objects, must be fabricated in a controlled environment that differs from the application environment; (8) there are no obvious physical similarities between a microscale nanorobot navigating inside a human body (a viscous environment where adhesive forces control) and a macroscale rubber clock bouncing inside a clothes dryer (a ballistic environment where inertia and gravitational forces control); and (9) there have been zero years, not 15 years, of “intense research” on diamondoid nanomachinery (as opposed to “nanotechnology”). Such intense research, while clearly valuable, awaits adequate funding — as is now just beginning.

Robert A. Freitas Jr.
Ralph C. Merkle
Institute for Molecular Manufacturing (www.imm.org)

—Jim

To develop nanotech therapies for cancer, it would be useful to be able to follow the distribution of nanoparticles in the patient to see if they are in fact accumulating in the targeted tumor(s). A noninvasive Raman microscope has allowed scientists to track carbon nanotubes injected into living mice. From the National Cancer Institute’s Alliance for Nanotechnology in Cancer “Seeing Nanotubes Targeting Tumors In Vivo“:

Carbon nanotubes have significant potential for delivering both imaging and therapeutic agents to tumors, but there is still a need to better quantify how well these rolled-up sheets of graphite can target tumors. Now, thanks to the development of a microscope capable of measuring Raman spectroscopic signals from living mice, researchers have a noninvasive tool to study where carbon nanotubes travel once they are injected into the blood stream.

Reporting its work in the journal Nano Letters [abstract], a team of investigators led by Sanjiv Gambhir, M.D., Ph.D., principal investigator of the Center for Cancer Nanotechnology Excellence Focused on Therapy Response (CCNE-TR), based at Stanford University, and Hongjie Dai, Ph.D., also a member of the CCNE-TR, described its use of an optimized Raman microscope to track two different sets of carbon nanotubes as they transited through the body of living mice. One of the nanotubes was covered with the tumor-targeting peptide known as RGD; the other set was used without any added functionality.

…Using this Raman microscope, the investigators were able to track differences in nanotube trafficking between the targeted and untargeted nanotubes. Although both sets of nanotubes showed an initial spike in tumor accumulation, the concentration of untargeted nanotubes in tumors began dropping as early as 20 minutes after injection. In contrast, the tumor concentration of the targeted nanotubes remained elevated for at least 72 hours after injection. In animals treated with the targeted nanotubes, tumors were readily visible as early as 2 hours postinjection and for at least 72 hours.

Not mentioned in either the NCI article or in the abstract is the question of how deep inside the body tissues can be imaged by the Raman microscope. If the microscope can penetrate a couple centimeters, for example, essentially all of a mouse but only the outermost tissue of a human could be imaged.
—Jim