Wednesday, July 1, 2009
Nanotech Leads to The Creation of Tiniest Light Bulbs
Scientists from the Max Planck Institute of Colloids and Interfaces have developed a new process to put together nanoparticles directly in the environment that is being studied. Additionally, this technique has led to the creation of tiny "light bulbs" that can be attached to specific proteins, opening a new modality for visualizing biochemical processes.
From a statement by the Max Planck Society:
"We used the fact that cells represent a closed reaction container as a model for the synthesis of nanoparticles," says Rumiana Dimova. Her group at the Max Planck Institute of Colloids and Interfaces studies membranes - the cell envelope. The scientist and her colleagues form bubbles that are around 50 micrometres in size from lecithin membranes, which are similar to biological membranes. Like cells, membrane bubbles - or vesicles as scientists refer to them - also provide a closed reaction container. The scientists load the membrane bubbles with one of two reactants for the nanoparticles.From this point, the researchers have developed two different sets of protocols. In one case, they produce bubbles loaded with one of the two reactants, sodium sulphide or cadmium chloride. The scientists then bring the bubbles with the different loads together and fuse two vesicles to form a bigger vesicle - this is done by subjecting the bubble cocktail to a short but very strong electrical pulse. The electric shock fuses the membranes of two adjacent bubbles.
In many cases, this results in the fusion of two bubbles containing different reactants. These then react to form cadmium sulphide, which is not water soluble and thus precipitates in the form of nanoparticles. "Because the reactants are only present to a limited extent in the fused bubbles, the particles only grow to a size of four nanometres," explains Rumiana Dimova. The scientists were able to track the entire process directly under the microscope because they had added different fluorescent molecules to the membranes of the differently loaded vesicles. The researchers were also able to see the nanoparticles forming as the particles shone like tiny lamps.
In the second process, the researchers only produce vesicles with one of the reactants. When the vesicles have formed, unlike in the first procedure, the researchers do not remove them from the production chamber. Instead, the bubbles remain attached to their substrate via small membrane channels, like balloons tied to strings, and stand in a solution that is the same as the one inside them. The researchers working with Rumiana Dimova then altered this situation: they substituted the solution with the first ingredient for the nanoparticles with a second component. This causes no change inside the vesicles at first. The second ingredient only creeps gradually between the substrate and membrane into the channel and to the vesicle. In the vesicle, where the other ingredient is already waiting, the nanoparticles grow again - this time to a size of 50 nanometres.
Press release: Making nanoparticles in artificial cells...
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Tuesday, June 23, 2009
Under Development: Micromagnetic-Microfluidic Blood Filter
The Ingber Lab at Harvard Medical School and Children's Hospital Boston has developed a magnetic blood filtering system to get rid of microbes from blood in situ. This system works by adding plastic-coated iron-oxide beads that are coated with antibodies for a specific pathogen. The beads will then strongly adhere to the pathogen in the blood and when passed through an electromagnet, the bead-pathogen complex can be separated from the rest of the blood. The end goal is to minimize the pathogen concentration to a level where drugs can be more effective at eliminating the remaining pathogen in the blood and reduce the mortality associated with sepsis.
In initial testing, the Ingber lab combined Candida albicans with blood and the antibody coated iron beads. The solution was then filtered through their system, a dialysis like device with electromagnets and up to 80 percent of the bead-pathogen complex were removed.
Image from Yung, C. W., et al, "Micromagnetic-microfluidic blood cleansing device" Lab Chip, 2009, 9, 1171-1177
This chart shows (a) the multi-fluorescence labeling of magnetic beads coated with antibodies for Candida albicans and (b) the effectiveness of the filtration of the bead-pathogen complex.
These types of microfluidic filter systems have the advantage of selective separation of the pathogen complexes from the flowing blood without the need for a filter membrane which can restrict flow and induce clotting while providing a large surface area to increase the efficiency of the entire prcoess. Dr. Don Ingber MD PhD, lab director, reports that animal testing is to commence this fall.
Popular Science : A Magnetic Machine Plucks Pathogens from Blood...
Lab Chip : Micromagnetic-microfluidic blood cleansing device...
Harvard Medical School and Children's Hospital : The Ingber Lab
Flashbacks: Sepsis Microfilter Being Developed ; Manipulating Cellular Signaling with Magnetic Fields
(hat tip: Gizmodo)
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Friday, June 5, 2009
Silver Based Nanofibrous Antibacterial Membranes Developed
Researchers from Tsinghua University in Beijing have developed nanofibrous antibacterial membranes that show a high degree of effectiveness against E.coli. Made out of silver and silver bromide nanoparticles brewed into titanium dioxide and apatite precursor, the technique can apparently be scaled to large production of all sorts of antibacterial applications.
Michael Berger from Nanowerk reports:
While the preparation of multicomponent materials is not new, their fabrication usually is based on the co-precipitation method where the resulting materials are generally obtained in powder form – which makes their practical application difficult because it requires further steps to prepare coatings or thin films. The novelty of the Chinese team's approach is the development of a facile and effective approach to produce membrane or film materials with comparable or even higher antibacterial activity."Using an electrospinning technique, we have prepared a new kind of free-standing antibacterial membranes, which contain silver, silver bromide, titanium dioxide, and hydroxyapatite as four active components," Gunagtao Li tells Nanowerk. "In this antibacterial membrane, each component serves a different function: apatite as the adsorption material for capturing bacteria, silver nanoparticles as the release-active antibacterial agent, silver bromide nanoparticles as the visible sensitive and release-active antibacterial agent, and titanium dioxide as the UV sensitive antibacterial material and substrate for other functional components."
Li points out that, compared to the four component system in powder form reported previously, the fabricated materials show double the antibacterial inactivation of E.coli under the same evaluation conditions, indicating that the addition of the electrospun membrane could significantly improve antibacterial efficiency. Additionally, the used technique has the potential to be scaled up to the industrial scale.
More from Nanowerk...
Abstract in Nanotechnology: Multiaction antibacterial nanofibrous membranes fabricated by electrospinning: an excellent system for antibacterial applications
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Thursday, May 28, 2009
ViRob, a Cavities Crawler
At the upcoming ILSI-Biomed Israel 2009 conference (June 15-17 in Tel Aviv), researchers from the Medical Robotics Laboratory at the Israel Institute of Technology (Technion) will be showing off a microrobot called ViRob, that has only a 1millimeter diameter and can crawl through vessels and cavities, when controlled by an external magnetic field. The big idea behind the ViRob device is that it can be used to deliver pharmaceutical payloads to precise locations or pull a microcatheter through tortuous terrain.
Here's what organizers of ILSI-Biomed Israel 2009 conference tell Medgadget:
Researchers are currently examining the possibility of using ViRob as a treatment for lung cancer—the world’s deadliest cancer. ViRob could assist in targeted drug delivery to lung tumors as well as take samples from different areas within the body. In addition, a number of these micro robots could simultaneously treat a variety of metastases. Researchers also plan to install additional equipment on the robot, including cameras, miniature tongs and other miniature equipment.ViRob measures 1 millimeter in diameter and 14 mm in its entirety was developed in the lab of Prof. Shoham in the Medical Robotics Laboratory at the Israel Institute of Technology. The robot moves using an external electromagnetic ignition system, stimulated by an electromagnetic field with frequency and volume that do not agitate the body, enabling it to maneuver in different spaces and surfaces within diverse viscous fluids. The vibration created by the magnetic field propels the robot forward, as the tiny arms protruding from a central body grip the vessel wall. A basic prototype of the ViRob, which can move as fast as 9 mm per second, has been developed thusfar.
Link: ILSI-Biomed Israel 2009...
White paper from Technion...
A few videos below the fold demonstrating the ViRob:
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Wednesday, May 27, 2009
Speedy Test Identifies Living Bacteria
Identifying whether individual bacteria cells are alive or dead is important in a lot of industries from food safety to clinical diagnostics. Current methods typically involve culturing the bacteria to see if anything grows. Now a French collaboration has developed a nanotechnology technique that focuses on the physical properties of bacterial walls to differentiate between the dead from the alive.
From Nanowerk:
The researchers set up a fast and simple procedure – based on a conventional microcontact printing and a simple incubation technique to generate functionalized patterns so as to induce local bacteria deposition – that allowed them to produce reliable chemical patterns exhibiting different surface properties to induce selective adsorption of individual bacteria in liquid media at registered positions. "We have evidenced a selective adsorption of bacteria on these local chemical patterns, producing highly ordered arrays of single living bacteria with a success rate close to 100%," says Cerf. The team then used this controlled immobilization method to study the mechanical properties of dead or alive bacterial cell in aqueous environment. Using force spectroscopy before and after heating , they measured the Young moduli of the same cell. The cells with a damaged membrane (after heating) present a Young modulus twice as high (6.1 ± 1.5 MPa versus 3.0 ± 0.6 MPa) as that of healthy bacteria. At the same time it has been impossible to evidence a difference between the AFM images of the living and the dead cell.
More from Michael Berger at Nanowerk...
Abstract in Langmuir:Nanomechanical Properties of Dead or Alive Single-Patterned Bacteria
Image: Untreated bacteria deposition on a microstructured surface with APTES functionalized patterns (1100 µm x 1000 µm dark field image. Scale bar corresponds to 30 µm).
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Monday, May 18, 2009
Nanofountain Delivers Therapeutic Particles Into Cells
Researchers at Northwestern University used a novel tool called Nanofountain Probe to inject tiny diamonds into individual cells. The technology opens up the potential of studying new tumor treatment therapies and how they effect unique cells, and may as well lead to clinical devices that take advantage of the nanotechnology.
From Northwestern:
The group also used the same Nanofountain Probes to pattern dot arrays of drug-coated nanodiamonds directly on glass substrates. The production of these dot arrays, with dots that can be made smaller than 100 nanometers in diameter, provides the proof of concept by which to manufacture devices that will deliver these nanomaterials within the body.The work addresses two major challenges in the development and clinical application of nanomaterial-mediated drug-delivery schemes: dosage control and high spatial resolution.
In fundamental research and development, biologists are typically constrained to studying the effects of a drug on an entire cell population because it is difficult to deliver them to a single cell. To address this issue, the team used the Nanofountain Probe to target and inject single cells with a dose of nanodiamonds.
"This allows us to deliver a precise dose to one cell and observe its response relative to its neighbors," Ho [Dean Ho, assistant professor of mechanical and biomedical engineering] says. "This will allow us to investigate the ultimate efficacy of novel treatment strategies via a spectrum of internalization mechanisms."
Beyond the broad research focused on developing these drug-delivery schemes, manufacturing devices to execute the delivery will require the ability to precisely place doses of drug-coated nanomaterials. Ho and colleagues previously developed a polymer patch that could be used to deliver chemotherapy drugs locally to sites where cancerous tumors have been removed. This patch is embedded with a layer of drug-coated nanodiamonds, which moderate the release of the drug. The patch is capable of controlled and sustained low levels of release over a period of months, reducing the need for chemotherapy following the removal of a tumor.
"An attractive enhancement will be to use the Nanofountain Probe to replace the continuous drug-nanodiamond films currently used in these devices with patterned arrays composed of multiple drugs," Ho says. "This allows high-fidelity spatial tuning of dosing in intelligent devices for comprehensive treatment."
"One of the most significant aspects of this work is the Nanofountain Probe's ability to deliver nanomaterials coated with a broad range of drugs and other biological agents," Espinosa [Horacio Espinosa, professor of mechanical engineering] says. "The injection technique is currently being explored for delivery of a wide variety of bio-agents, including DNA, viruses and other therapeutically relevant materials."
Press release: New Tool For Next-generation Cancer Treatments Using Nanodiamonds
Abstract in journal Small: Nanofountain-Probe-Based High-Resolution Patterning and Single-Cell Injection of Functionalized Nanodiamonds
Image: NFP (nano fountain probe) chips on a wafer, Cantilevers and Apertured tip of an NFP
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Micro-device to Control Bacteria Movement
We have previously reported on implantable micro-devices that can be directed to specific locations in the body. Now comes word that researchers at the NanoRobotics Laboratory at École Polytechnique de Montréal have developed a solar-powered micro-device less than the size of one tenth of a millimeter in square area to perform basic sensing of the surrounding environment and indirectly control the movement of bacteria in a petri dish.
Dr. Sylvain Martel, the Director of the NanoRobotics Laboratory, presented his lab's results International Conference on Robotics and Automation in Kobe Japan.
This sensor measures the surrounding pH level of the solution it is in. As the pH rises, an electromagnetic pulse is emitted by the micro-device. A computer detects this emission and directs magnetically-sensitive bacteria towards the device. Upon arrival, the bacteria then push the micro-device closer to higher pH concentration regions. Because of the size limitation of the device a photovoltaic, or solar cell, is employed to power the sensor and the electromagnetic pulsing.
"It's like having a propulsion engine on demand," Dr. Sylvain Martel remarked.
This video, from MIT Technology Review, shows ~3,000 bacteria maneuvering a V-shaped robot around via computer control system.
This is a continuation of the lab's previous work in developing micro-devices phage-based biosensors that are propelled by magnetic fields under computer guidance. The types of sensors and controlled movement of bacteria have great potential in medical applications of the future including pathogen detection and focused treatment.
MIT Technology Review: Tiny Machine Commands a Swarm of Bacteria
École Polytechnique de Montréal: Nanorobotics Laboratory
Flashback : Tiny Implantable Devices to Help Treat Chronic Pain
(hat tip: Engadget)
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Friday, May 15, 2009
Nanotechnology Leading to Neural-Network-on-a-Chip Devices
Building the next generation of neural interfaces will require improving how axons are guided to create a "highway of nerve fibers" that can serve as an efficient passage of information. Nanowerk is reporting on research at Lund University in Sweden that uses free-standing nanowire patterns to potentially create neural networks on a chip.
From Nanowerk:
In new work that was recently published in Langmuir (Rectifying and Sorting of Regenerating Axons by Free-Standing Nanowire Patterns: A Highway for Nerve Fibers), the Swedish team shows that it is possible to impose a growth direction at a specific location on a substrate, something which is very important for neural chip construction for example.Prinz [Christelle Prinz, a postdoc researcher in the Division of Solid State Physics at Lund University] explains that they have used a rectifier pattern made of arrays of short rows of electron beam lithography (EBL)-defined nanowires to sort axons coming from different places on a substrate. The short rows of nanowires are oriented at an angle of 30° compared to the growth direction. The arrays define highways for axonal growth, preventing the axons to turn around and change their growth direction.
"We not only show that patterns of nanowires can be used to rectify axonal outgrowth but we also demonstrate that axons from two different populations can be fully separated, thus creating the possibility to address two populations of axons on a chip surface," says Prinz. "These results, together with our earlier findings, provide a basis for the advanced control of neuronal growth on a chip, where a large range of functionalities can be implemented, including chemical sensors and electrodes to investigate neuronal function at high temporal and spatial resolution."
Read on at Nanowerk...
Abstract in Langmuir: Rectifying and Sorting of Regenerating Axons by Free-Standing Nanowire Patterns: A Highway for Nerve Fibers
Image: Confocal microscopy of bidirectionally rectified axonal outgrowth. (a) Nerve fibers from the green fluorescent protein (GFP)-expressing neurons from a ganglion mounted to the right. (b) The same image now showing the result of anti β-tubulin-labeled nerve fibers. The new (red) fibers originate from the wild-type ganglion mounted to the left. Because all fibers stain red, the GFP fibers now appear yellow. Scale bars 25 µm. Credit: American Chemical Society
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Thursday, May 7, 2009
Gold Nanoparticles Recruited to Destroy Difficult to Reach Tumors
MIT researchers have developed a group of gold nanoparticles that may soon be used by oncologists to find, locate, and kill tumors. By resonating when near-infrared light is introduced, the nanoparticles can heat up enough to cook surrounding tumor cells out of existence.
From MIT news office:
Gold nanoparticles can absorb different frequencies of light, depending on their shape. Rod-shaped particles, such as those used by von Maltzahn and Bhatia [Geoffrey von Maltzahn and Sangeeta Bhatia, graduate student and MIT professor respectively], absorb light at near-infrared frequency; this light heats the rods but passes harmlessly through human tissue.In a study reported in the team's Cancer Research paper, tumors in mice that received an intravenous injection of nanorods plus near-infrared laser treatment disappeared within 15 days. Those mice survived for three months with no evidence of reoccurrence, until the end of the study, while mice that received no treatment or only the nanorods or laser, did not.
Once the nanorods are injected, they disperse uniformly throughout the bloodstream. Bhatia's team developed a polymer coating for the particles that allows them to survive in the bloodstream longer than any other gold nanoparticles (the half-life is greater than 17 hours).
In designing the particles, the researchers took advantage of the fact that blood vessels located near tumors have tiny pores just large enough for the nanorods to enter. Nanorods accumulate in the tumors, and within three days, the liver and spleen clear any that don't reach the tumor.
During a single exposure to a near-infrared laser, the nanorods heat up to 70 degree Celsius, hot enough to kill tumor cells. Additionally, heating them to a lower temperature weakens tumor cells enough to enhance the effectiveness of existing chemotherapy treatments, raising the possibility of using the nanorods as a supplement to those treatments.
The nanorods could also be used to kill tumor cells left behind after surgery. The nanorods can be more than 1,000 times more precise than a surgeon's scalpel, says von Maltzahn, so they could potentially remove residual cells the surgeon can't get.
The nanorods' homing abilities also make them a promising tool for diagnosing tumors. After the particles are injected, they can be imaged using a technique known as Raman scattering. Any tissue that lights up, other than the liver or spleen, could harbor an invasive tumor.
In the Advanced Materials paper, the researchers showed they could enhance the nanorods' imaging abilities by adding molecules that absorb near-infrared light to their surface. Because of this surface-enhanced Raman scattering, very low concentrations of nanorods - to only a few parts per trillion in water [gf1]- can be detected.
Another advantage of the nanorods is that by coating them with different types of light-scattering molecules, they can be designed to simultaneously gather multiple types of information - not only whether there is a tumor, but whether it is at risk of invading other tissues, whether it's a primary or secondary tumor, or where it originated.
Press release: Targeting tumors using tiny gold particles ...
Abstract in Cancer Research: Computationally Guided Photothermal Tumor Therapy Using Long-Circulating Gold Nanorod Antennas
Abstract in Advanced Materials: SERS-Coded Gold Nanorods as a Multifunctional Platform for Densely Multiplexed Near-Infrared Imaging and Photothermal Heating
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Monday, May 4, 2009
NSF: Safer Nano Cancer Detector
Investigators at the University of California, San Diego developed the first biodegradable fluorescent nanoparticle, based on mesoporous silica, that has a host of interesting and important clinical properties.
The National Science Foundation elaborates:
Chemistry professor Michael Sailor and a team including National Science Foundation supported researchers at the University of California, San Diego, report developing the first nanoscale "quantum dot" particle that glows brightly enough to allow physicians to examine internal organs and lasts long enough to release cancer drugs before breaking down into harmless by-products.The research is another step towards mainstreaming the use of nanotechnology in medicine. Many researchers say using nanomaterials for medical reasons is the health field's next major frontier. The payoff, they say, could be lower drug toxicity, lower treatment costs, more efficient drug use, and better patient diagnosis.
"There are a lot of nanomaterials that have an ability to do fluorescence imaging," says Sailor, referring to a useful property that potentially could help doctors further see organs, diagnose patients and perform surgeries. "But they're generally toxic and not appropriate for putting into people."
The problem results from toxic organic or inorganic chemicals used to make the materials glow. For example, fluorescent semiconductor nanoparticles known as quantum dots can release potentially harmful heavy metals when they break down. A paramount issue in determining the efficacy of nanomaterials is the body's ability to harmlessly get rid of residual leftovers after the nanomaterial helps diagnose or treat a disease.
So Sailor's team designed a new, non-toxic quantum dot nanoparticle made from silicon wafers, the same high-purity wafers that go into the manufacture of computer chips. Reseachers took the thin wafers and ran electric current through them drilling billions of pores. They then used ultrasound waves to break the wafer into bits as small as 100 nanometers.
The resulting spongy silicon particles contained nano-scale features capable of displaying quantum confinement effects, or the so-called "quantum dots." The ones in the UCSD experiment glowed a reddish color when exposed to red, blue, or ultraviolet light.
When nanoparticles were tested in mice, researchers saw tumors glow for several hours, then dim as the particles degraded. The number of nanoparticles dropped noticeably in a week, and they were undetectable after four weeks. They performed a battery of toxicity assays and saw no evidence of toxicity. However, the researchers stopped short of concluding these new nanoparticles were completely harmless."Very high doses of any substance can be harmful," says Sailor. "The important conclusion from this work is that the materials are nontoxic at the concentrations we need to use to see tumors."
The fact that their quantum dots are made from silicon is key. "A major contributing factor is the fact that these materials degrade into silicic acid, a form of silicon that is commonly present in the human body and that is needed for proper bone and tissue growth," Sailor says.
Examples where such materials should be useful include the early diagnosis and treatment of cancer. Nanoparticles that glow can reveal tumors too small to detect by other means. During surgery, they can allow the doctor to better find and remove all traces of a cancerous growth. In addition, they can enable targeted delivery of drugs and make it possible to use smaller, safer doses.
Images: Top: Bright red-orange photoluminescence observed from porous silicon nanoparticles with human HeLa cells, magnified 1000x and viewed in the reflection from a silicon wafer. Prepared from high-purity silicon wafers, these nanoparticles provide a non-toxic and biodegradable alternative to conventional quantum dots for in-vitro and in-vivo fluorescence imaging. The cell nuclei are stained blue. Bottom: Images of a mouse hindquarter containing a tumor. The first image is a regular photograph, and the other three, taken in a time series after injecting the mouse with dextran-coated silicon nanoparticles, show intensity color maps of the red emission channel. The red color shows the brightest fluorescence of the silicon nanoparticles, which initially localize in the tumor and then slowly disappear. Time after injection is indicated in the upper left of each image. The tumor is an MDA-MB-435 xenograft. Note that a strong signal is observed in the tumor 2 hours after injection, indicating significant passive accumulation by the EPR effect.
Mesoporous silica flashbacks: Nanostructured Porous Silicon Activates "Dead" Enzymes; Membrane, 50 Atoms Thick, Sorts Biomolecules; 'Smart Petri Dish' for Drug Interactions and Cancer Screening; Mesoporous Silica Nanoparticles Improve Delivery of Hydrophobic Anticancer Drugs
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Friday, April 17, 2009
Scientists Augment Scorpion Venom with Nanoparticles; Promise Super Brain Cancer Killer
University of Washington researchers are reporting that they created chlorotoxin-bound nanoparticles that have an augmented anti brain cancer properties. These novel compounds, composed of an iron oxide nanoparticle core linked to an amine-functionalized poly(ethylene glycol) silane and chlorotoxin, a scorpion venom, seem to have substantially enhanced cellular uptake, hence their anticancer properties.
Chlorotoxin binds to a surface protein overexpressed by many types of tumors, including brain cancer. Previous research by Zhang's group combined chlorotoxin with nanometer-scale particles of iron oxide, which fluoresce at that size, for both magnetic resonance and optical imaging.Chlorotoxin also disrupts the spread of invasive tumors -- specifically, it slows cell invasion, the ability of the cancerous cell to penetrate the protective matrix surrounding the cell and travel to a different area of the body to start a new cancer. The MMP-2 on the cell's surface, which is the binding site for chlorotoxin, is hyperactive in highly invasive tumors such as brain cancer. Researchers believe MMP-2 helps the cancerous cell break through the protective matrix to invade new regions of the body. But when chlorotoxin binds to MMP-2, both get drawn into the cancerous cell.
Other researchers are currently conducting human trials using chlorotoxin to slow cancer's spread.
Zhang's group investigated chlorotoxin action when it is attached to nanoparticles and found the resultant complex doubles the therapy's effect compared to chlorotoxin alone. Adding nanoparticles often improves a therapy, partly because the combination lasts longer in the body and so has a better chance of reaching the tumor. Combining also boosts the effect because therapeutic molecules clump around each nanoparticle. In the newly published study an average of 10 chlorotoxin molecules were attached to each nanoparticle. Each clump thus offers many therapeutic molecules that can simultaneously latch on to many MMP-2 proteins.
Experiments were performed using mouse brain-cancer cells that were grown in the lab. The imaging results confirm that adding nanoparticles means more of the MMP-2 ends up safely tucked away inside the cell, thus preventing MMP-2 from helping the cancer spread.
Further images showed that the cells containing nanoparticles plus chlorotoxin were unable to elongate, whereas cells containing only nanoparticles or only chlorotoxin could stretch out. This suggests that the nanoparticle-plus-chlorotoxin disabled the machinery on the cell's surface that allows cells to change shape, yet another step required for a tumor cell to slip through the body.
"We hypothesized the mechanism and we have all the data to prove our hypothesis," Zhang said. Further experiments will involve testing on mice.
So far most cancer research has combined nanoparticles either with chemotherapy that kills cancer cells, or therapy seeking to disrupt the genetic activity of a cancerous cell. This is the first time that nanoparticles have been combined with a therapy that physically stops cancer's spread.
Slowing the spread of cancer would be especially useful for treating highly invasive tumors such as brain cancer. MMP-2 also shows signs of being overactive in cancers of the breast, colon, skin, lung, prostate and ovaries, and researchers believe that the technique could slow the spread of these other tumors.
Press release: Scorpion venom with nanoparticles slows spread of brain cancer...
Abstract: Inhibition of Tumor-Cell Invasion with Chlorotoxin-Bound Superparamagnetic Nanoparticles
Image: In a, chlorotoxin molecules, colored blue and green, attach themselves to a central nanoparticle. In b, each nanoprobe offers many chlorotoxin molecules that can simultaneously latch on to many MMP-2s, depicted here in yellow, which are thought to help tumor cells travel through the body. In c, over time nanoprobes draw more and more of the MMP-2 surface proteins into the cell, slowing the tumor's spread.
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Thursday, April 16, 2009
New Developments for DNA Nanomachines
The promise of DNA nanomachines that can change shape due to specific triggers, and in such a way create complicated systems, is not a new notion. In the latest edition of Nature Nanotechnology, Indian scientists are reporting the development of an interesting DNA pH sensor, a DNA nanomachine that "maps spatial and temporal pH changes inside living cells."
Nanowerk explains:
"We named our DNA nanomachine the I-switch" Yamuna Krishnan tells Nanowerk. "The device is externally triggered by protons and functions as a pH sensor based on fluorescence resonance energy transfer (FRET) inside living cells. We demonstrate the ability of this DNA nanomachine to function inside living cells by using it to map spatio-temporal pH changes associated with endosome maturation. Our studies show that it is able to function as efficiently inside the endosome of a living cell as it does in a test tube."Krishnan is a scientist at the National Centre for Biological Sciences in Bangalore, India, where she heads the Chemical Biology Group. The DNA assembly developed by her team is a robust pH-triggered nanoswitch with reasonably fast response times, sustained efficiency over several cycles, and a working cycle that does not generate toxic byproducts (the byproducts of a complete cycle for the I-switch are salt and water).
The I-switch has a pH sensitivity between pH 5.5 and 6.8 – which is ideal for monitoring changes in intracellular pH – and offers complementary information to that obtained through the use of small-molecule fluorescent pH probes. Krishnan points out that, unlike such pH probes, the I-switch is a FRET-based sensor that is equally bright at both physiological and acidic values of pH.
More from Nanowerk...
Abstract: A DNA nanomachine that maps spatial and temporal pH changes inside living cells
Image: Drosophila cells with the I-switch inside their endosomes. (Image: Dr. Krishnan, National Centre for Biological Sciences)
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Tuesday, April 14, 2009
Graphene Thought to Create Biological Microsensor
Graphene, a recently invented material that can have a thickness of as little as one atom, is beginning to see potential use in biosciences. Because of the material's physical structure, when traversing the surface of graphene, its electrons can travel at almost the speed of light at room temperature. Thus any contaminants on the surface can slow down electron speed, a characteristic that can be used to sense the presence of particular DNA strands or other biomolecules. Vikas Berry, a research scientist at Kansas State University, has been studying graphene's properties.
One of Berry's developments is a graphene-based DNA sensor. When electrons flow on the graphene, they change speed if they encounter DNA. The researchers notice this change by measuring the electrical conductivity. The work was published in Nano-Letters."Most DNA sensors are optical, but this one is electrical," Berry said. "We are currently collaborating with researchers from Harvard Medical School to sense cancer cells in blood."
Another area he is exploring is loading graphene with antibodies and flowing bacteria across the surface.
"Most researchers focus on pristine graphene, but we're making it dirty," he said.
Berry and Nihar Mohanty, a graduate student in chemical engineering, used a type of bacteria commonly found in rice and interfaced it with graphene. They found that the graphene with tethered antibodies will wrap itself around an individual bacterium, which remains alive for 12 hours.
Berry said that possible applications include a high-efficiency bacteria-operated battery, where by using geobater, a type of bacteria known to produce electrons, can be wrapped with graphene to produce electricity. The research was presented at the annual American Physical Society conference in Pittsburgh and the American Institute for Chemical Engineers conference in Philadelphia.
"Materials science is an incredible field with several exploitable quantum effects occurring at molecular scale, and biology is a remarkable field with a variety of specific biochemical mechanisms," Berry said. "But for the most part the two fields are isolated. If you join these two fields, the possibilities are going to be immense. For example, one can think of a bacterium as a machine with molecular scale components and one can exploit the functioning of those components in a material device."
For his doctoral research, Berry used bacteria to make a humidity sensor.
"That was only possible through combining materials science with biological science," he said.
Another area of his current research is compressing and stretching molecular-junctions between nanoparticles. Berry said that his group has developed a molecular-spring device where they can compress and stretch molecules, which then act like springs, allowing researchers to study how they relax back. He said that this technology could be used to create molecular-timers in which the spring action from a decompressed molecule on a chip could trigger a circuit, for instance.
Berry said for stretching the molecules, Kabeer Jasuja, a doctoral student in chemical engineering, came up with the idea to place the device on a centrifuge to stretch the molecules with centrifugal force.
Abstract in Nano Letters: Graphene-Based Single-Bacterium Resolution Biodevice and DNA Transistor: Interfacing Graphene Derivatives with Nanoscale and Microscale Biocomponents...
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Monday, April 13, 2009
Scientists Create a programmable DNA origami seed
A team of Caltech scientists managed to create specialized DNA "seeds" that can activate a mixture of DNA to combine into a preprogrammed pattern. This ability to create self assembling DNA structures, known as algorithmic crystals, that can be coded for in advance, may lead to all sorts of scientific and clinical uses.
In the work, the researchers designed several different versions of a DNA origami rectangle, 95 by 75 nanometers, which served as the seeds for the growth of different types of ribbon-like crystals of DNA. The seeds were combined in a test tube with other bits of DNA, called "tiles," heated, and then cooled slowly."As it cools, the first origami seed and the individual tiles form, as their component DNA molecules begin sticking to each other and folding into shape--but the tiles and origami don't stick to each other yet," Winfree explains.
"Then, at a lower temperature, the tiles start to stick to each other and to the origami. The critical concept here is that the DNA tiles will only form crystals if the process gets started by a seed, upon which they can grow," he says.
In this way, the DNA ribbons self-assemble themselves, but only into forms such as ribbons with particular widths and ribbons with stripe patterns prescribed by the original seed.
The work, Winfree says, "exhibits a degree of control over information-directed molecular self-assembly that is unprecedented in accuracy and complexity, which makes me feel that we are finally beginning to understand how to program information into molecules and have that information direct algorithmic processes."
Press release: Caltech Scientists Control Complex Nucleation Processes using DNA Origami Seeds ...
Abstract in PNAS: An information-bearing seed for nucleating algorithmic self-assembly
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Tuesday, March 31, 2009
DNA Acts as Smart Glue for Nanostructures
Brookhaven physicists have developed a way to use DNA to guide nanoparticles to stick together in a very specific way. Conveniently, the DNA strands themselves act as the binding glue to keep the particles together.
From the statement issued by Brookhaven NL press office:
The Brookhaven team has previously used DNA, the molecule that carries life’s genetic code, to link up nanoparticles in various arrangements, including 3-D nano-crystals. The idea is that nanoparticles coated with complementary strands of DNA — segments of genetic code sequence that bind only with one another like highly specific Velcro — help the nanoparticles find and stick to one another in highly specific ways. By varying the use of complementary DNA and strands that don’t match, scientists can exert precision control over the attractive and repulsive forces between the nanoparticles to achieve the desired construction. Note that the short DNA linker strands used in these studies were constructed artificially in the laboratory and don’t “code” for any proteins, as genes do.The latest advance has been to use the DNA linkers to attach some of the DNA-coated nanoparticles to a solid surface to further constrain and control how the nanoparticles can link up. This yields even greater precision, and therefore a more predictable, reproducible high-throughput construction technique for building clusters from nanoparticles.
“When a particle is attached to a support surface, it cannot react with other molecules or particles in the same way as a free-floating particle,” explained Brookhaven physicist Oleg Gang, who led the research at the Lab’s Center for Functional Nanomaterials. This is because the support surface blocks about half of the particle’s reactive surface. Attaching a DNA linker or other particle that specifically interacts with the bound particle then allows for the rational assembly of desired particle clusters.
“By controlling the number of DNA linkers and their length, we can regulate interparticle distances and a cluster’s architecture,” said Gang. “Together with the high specificity of DNA interactions, this surface-anchored technique permits precise assembly of nano-objects into more complex structures.”Instead of assembling millions and millions of nanoparticles into 3-D nanocrystals, as was done in the previous work, this technique allows the assembly of much smaller structures from individual particles. In the Nature Materials paper, the scientists describe the details for producing symmetrical, two-particle linkages, known as dimers, as well as small, asymmetrical clusters of particles — both with high yields and low levels of other, unwanted assemblies.
Here's video of Oleg Gang expounding on the research:
Article in Nature Materials: Stepwise surface encoding for high-throughput assembly of nanoclusters
Image 1: (a) (1) DNA linker strands (squiggly lines) are used to attach DNA-coated nanoparticles to a surface. (2) Linker strands are attached to the top side of the nanoparticle. (b) (3a) A nanoparticle of a second type with complementary DNA encoding recognizes the exposed linker strands and attaches to the surface-anchored nanoparticle. (4a and 5a) The assembled structure is released from the surface support, resulting in a two-particle, dimer cluster. (c) (3b) Alternatively, the immobilized particles produced in step (a) are released from the surface, leaving the opposite-side linker strands free to bind with multiple particles (4b) to form asymmetric "Janus" clusters.
Image 2: This transmission electron micrograph shows nanoparticle dimers (two-particle clusters) assembled and released through the DNA-encoded solid-support approach.
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Tuesday, March 17, 2009
New Nanoparticles Provide Options for Tumor Hunting
Researchers at Purdue University have developed new composite gold and ferromagnetic metal nanoparticles capable of attaching themselves to tumors. The new combination allows for the particles to be imaged in the body through either fluorescent microscopy or MRI.
Scientists have developed probes that use gold nanorods or magnetic particles, but Irudayaraj's [Joseph Irudayaraj, Purdue University associate professor of agricultural and biological engineering] nanoprobes use both, making them easier to track with different imaging devices as they move toward cancer cells.The magnetic particles can be traced through the use of an MRI machine, while the gold nanorods are luminescent and can be traced through microscopy, a more sensitive and precise process. Irudayaraj said an MRI is less precise than optical luminescence in tracking the probes, but has the advantage of being able to track them deeper in tissue, expanding the probes' possible applications.
The probes, which are about 1,000 times smaller than the diameter of a human hair, contain the antibody Herceptin, used in treatment of metastatic breast cancer. The probes would be injected into the body through a saline buffering fluid, and the Herceptin would find and attach to protein markers on the surface of cancer cells.
"When the cancer cell expresses a protein marker that is complementary to Herceptin, then it binds to that marker," Irudayaraj said. "We are advancing the technology to add other drugs that can be delivered by the probes."
Irudayaraj said better tracking of the nanoprobes could allow doctors to pinpoint the location of known tumors and better treat the cancer.
The novel probes were tested in cultured cancer cells. Irudayaraj said the next step would be to run a series of tests in mice models to determine the dose and stability of the probes.
Press release: Nanoscopic probes can track down and attack cancer cells
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Friday, March 13, 2009
Metallic Nanoclusters Change Color While Sensing Environment
A collaboration of Finnish-German scientists have demonstrated that clusters of silver particles can be used as surface sensors for molecular analysis. Because clusters of only a few atoms are being used, the technology could potentially lead to tiny injectable sensors tuned to look for specific biochemical markers.
Nanowerk explains:
Ras [Robin Ras, senior researcher in the Molecular Materials group at Helsinki University of Technology] and his collaborators have systematically investigated the optical properties of silver (Ag) nanoclusters in solution – prepared in different water/methanol mixtures –and their response to the environment. What they found is that the spectral properties or color of the cluster solutions can be tuned to a great extent by selecting appropriate solvents. This property is called solvatochromism. The spectral shifts are not related to a change in nanocluster size."The clusters we examined were only few atoms in size such as Ag2 and Ag3" says Ras. "We found that the solvatochromism of the nanoclusters is analogous with that of metal nanoparticles but has a completely different origin. The solvatochromic effect for metal nanoparticles is well-known, and their photophysical properties are determined by surface plasmons. On the other hand, the photophysical properties of metal nanoclusters differ in character and are controlled by quantum confinement that results in discrete energy levels, therefore it was not evident that metal nanoclusters would also have solvatochromic properties."
Read on at Nanowerk...
Abstract in Angewandte Chemie International Edition...
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Monday, March 9, 2009
Carbon Nanotubes Used to Stitch Materials Together
Engineers at Massachusetts Institute of Technology devised a method to use carbon nanotubes as a stitching material for composites. Because nanotubes could be made into some of the strongest known fibers, the technology should allow the development of new generation of medical prostheses and novel medical materials.
Wardle wondered whether it would make sense to reinforce the plies in advanced composites with nanotubes aligned perpendicular to the carbon-fiber plies. Using computer models of how such a material would fracture, "we convinced ourselves that reinforcing with nanotubes should work far better than all other approaches," Wardle said. His team went on to develop processing techniques for creating the nanotubes and for incorporating them into existing aerospace composites, work that was published last year in two separate journals.How does nanostitching work? The polymer glue between two carbon-fiber layers is heated, becoming more liquid-like. Billions of nanotubes positioned perpendicular to each carbon-fiber layer are then sucked up into the glue on both sides of each layer. Because the nanotubes are 1000 times smaller than the carbon fibers, they don't detrimentally affect the much larger carbon fibers, but instead fill the spaces around them, stitching the layers together.
"So we're putting the strongest fibers known to humankind [the nanotubes] in the place where the composite is weakest, and where they're needed most," Wardle said. He noted that these dramatic improvements can be achieved with nanotubes comprising less than one percent of the mass of the overall composite. In addition, he said, the nanotubes should add only a few percent to the cost of the composite, "while providing substantial improvements in bulk multifunctional properties."
Press release: 'Nanostitching' could lead to much stronger airplane skins, more
Images: Top: Brian Wardle, the Charles Stark Draper Assistant Professor in the Department of Aeronautics and Astronautics, shows an advanced composite material held together by "nanostitching," a technique developed at MIT that could make airplane skins and other products stronger. Side: Schematic showing carbon nanotubes bridging the gap between plies of an advanced composite.
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Thursday, March 5, 2009
Scientists Grow Micro Tubes for Tiny Chemical Devices
Researchers from the University of Glasgow have developed a way to grow microfluidic systems from materials that can function as sensors and catalysts in chemical reactions. The technology, that uses electric fields to guide the formation of the tubular structures, should help in developing smaller and more complicated labs-on-a-chip devices for all sorts of medical applications.
From MIT Technology Review:
The inorganic crystals that the researchers use belong to a class of chemicals known as polyoxometalates. These negatively charged clusters of metal and oxygen atoms are excellent catalysts for many different reactions in the chemical industry. They are also good at sensing and adsorbing gases, and are used to remove toxic compounds like nitrogen oxides and sulphur dioxide from flue-gas streams. By using different metal atoms, researchers can create polyoxometalates with various chemical properties. "Polyoxometalates have large structural diversity and versatility, as well as a lot of options to modify physical and chemical behavior," says Paul Kogerler, a professor of chemistry at RWTH Aachen University, in Germany.To create their microtubes, the Glasgow researchers use crystals containing tungsten. When they put these negatively charged metal-oxide crystals in water and add positively charged fluorescent molecules, the crystals start to sprout tubes in just a few seconds.
Cronin explains that the positive and negative molecules join up to form a membrane on the crystal's surface. The pressure inside this membrane builds up until it ruptures and the metal-oxide material inside pours out in a jet. As it streams out, it automatically starts to form a hollow tube through which more and more material can flow out. The tube grows until all that's left of the crystal is the hollow membrane shell.
More from MIT Technology Review...
Full article in Nature Chemistry...
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