New Navy Nanowire Excites Significantly Enhanced Surface Enhanced Raman Scattering (SERS) and Fluorescence (SEF) Signals-Shows Sensitivity to Parts per Billion

FIG. 1 U.S. Naval Research Laboratory Ga₂O₃ core/Ag shell nanowire composite drawing and SEM image.

In U.S. Patent 7,639,356 (Washington, DC) U.S. Naval Research Laboratory (NRL) scientists Sharka M. Prokes and Orest J Glembocki reveal a new surface enhanced Raman spectroscopy (SERS)-active substrate consisting of dielectric/Ag nanowire composites, which show very enhanced sensitivities, in the parts per billion range. The reason for such high sensitivities can be that the nanowire crossings lead to very large electric field enhancements in large regions around the nanowires, allowing a larger volume of molecules of interest to be detected.

Furthermore, the wires can also be dispersed in a liquid, allowing for stand-off sensing applications. The nanowires can also serve as taggants.

U.S. Patent 7,639,356, awarded to the U.S. Navy,  describes metal/wide band gap semiconductor nanowire composites which exhibit significantly enhanced surface enhanced Raman scattering (SERS) and fluorescence (SEF) signal and which can be used for very efficient chemical or biological sensors.

In one embodiment, the fabrication technique can be applicable to Ga₂O₃ semiconductor nanowires and other metal oxide nanowires, with controlled size diameters ranging from about 5 to about 100 nm. The composite can consist of the nanowire core structure, which can be coated with a silver metallic shell on the order of 3-10 nm.

An apparatus comprising a substrate and at least two nanowires on the substrate, the nanowires comprising a core and a metal shell, wherein the core is selected from the group consisting of a semiconductor and a dielectric, thereby forming a nanowire-composite to allow plasmon coupling for enhancements of the electric fields and enhancements of the surface enhanced Raman signal (SERS) and enhancements of the chemical or biological specificity and sensitivity.

A method of making a SERS-active substrate comprising providing a substrate and affixing a plurality of nanowires on the substrate thereby forming a nano-composite, creating plasmon coupling leading to enhanced electric fields in the vicinity of the nanowires and enhancements of the surface enhanced Raman signal (SERS) and enhancements of the chemical or biological specificity and sensitivity.

Raman scattering is often used in the chemical identification of materials. Light scattered from various vibrational modes in a material is red- and blue-shifted by the frequency of the vibrational modes.

The information that is obtained from Raman scattering is complementary to that of IR spectroscopy, but with the advantage of being performed with visible light. Because the Raman cross-sections of most materials are very small, the intensity of the Raman signal is often 8 orders of magnitude lower than the intensity of the exciting laser. Thus, rapid acquisition of Raman scattering requires the use of intense laser light, limiting the equipment to table top lasers. The situation is even more serious for small amounts of a species adsorbed on a surface of a material.

In the surface enhanced Raman scattering (SERS) effect rough metal surfaces (usually Ag) are used to increase the Raman signal of species adsorbed on the metal. Enhancements of up to 8 orders of magnitude have been observed. The SERS enhancement of molecules adsorbed on the roughened metal surface is caused by local electromagnetic fields that are created by the laser excitation of surface plasmons at the metal surface. Significant work has been done in SERS using various metals and geometry for the roughened features, including aggregate films, nano-particles, nano-shells and solid metal nanowire ordered arrays.

The two Navy scientists showed that local hot spots in the electric fields produced by localized plasmons excited in nanoparticles can produce large SERS effects. Furthermore, it has been suggested that using nanoparticles of appropriate size and geometry can lead to further enhancements by moving the plasmons absorption frequency close to that of the exciting laser. This adds resonant enhancement to the SERS process, further increasing the Raman signal.

FIG. 3 Comparison of SERS signal for Mesophotonics "Klarite" commercial substrate and NRL Ga₂O₃/Ag nanowire composites. 

FIG. 4 Schematic diagram showing how crossed nanowires can be used to construct a 3D array that may maximize crossing points, where the SERS enhancement may be greatest. 

FIG. 5 Dilution of Ga₂O₃/Ag nanowire composites.

ASU Biophysicists Demonstrate Carbon Nanotubes' Potential For High-Speed Genetic Sequencing

 In the current issue of Science, Stuart Lindsay, director of Arizona State University’s Center for Single Molecule Biophysics at the Biodesign Institute, along with his colleagues, demonstrates the potential of a new DNA sequencing method in which a single-stranded ribbon of DNA is threaded through a carbon nanotube.

Credit: The Biodesign Institute at Arizona State University.

Faster sequencing of DNA holds enormous potential for biology and medicine, particularly for personalized diagnosis and customized treatment based on each individual's genomic makeup. At present however, sequencing technology remains cumbersome and cost prohibitive for most clinical applications, though this may be changing, thanks to a range of innovative new techniques.  

 In the current issue of Science, Stuart Lindsay, director of Arizona State University's Center for Single Molecule Biophysics at the Biodesign Institute, along with his colleagues, demonstrates the potential of one such method in which a single-stranded ribbon of DNA is threaded through a carbon nanotube, producing voltage spikes that provide information about the passage of DNA bases as they pass through the tube—a process known as translocation. 

 Carbon nanotubes are versatile, cylindrical structures used in nanotechnology, electronics, optics and other fields of materials science. They are composed of carbon allotropes—varied arrangements of carbon atoms, exhibiting unique properties of strength and electrical conductivity. 

Traditional methods for reading the genetic script, made up of four nucleotide bases, adenine, thymine, cytosine and guanine (labeled A,T,C,&G), typically rely on shredding the DNA molecule into hundreds of thousands of pieces, reading these abbreviated sections and finally, reconstructing the full genetic sequence with the aid of massive computing power. A decade ago, the first human genome—a sequence of over 3 billion chemical base pairs—was successfully decoded, in a biological tour de force. The undertaking required around 11 years of painstaking effort at a cost of $1 billion dollars. In addition to the laboriousness of existing techniques, accuracy is compromised, with errors accumulating in proportion to the number of fragments to be read.  

A new strategy involves the use of nanopores—orifices of molecular diameter that connect two fluid reservoirs. A constant voltage can be applied between two electrodes located at either end of the nanopore , inducing an ionic current to flow through the length of the nanopore's enclosed channel. At this scale, the passage of even a single molecule generates a detectable change in the flow of ionic current through the pore. This current is then electronically amplified and measured. Only fairly recently have state of the art micro-manufacturing techniques enabled researchers to construct nanopores at the scale of individual molecules, opening up many new possibilities for single-molecule manipulation and research. 

In the current study, single walled carbon nanotubes, 1-2 nm in diameter, were used for the conducting channels. When a current was induced through the nanotube, segments of single-stranded DNA (known as oligomeres) made up of either 60 or 120 nucleotides, were drawn into the opening of the nanotube and translocated from the anode side of the nanotube to the output cathode side, due to the negative charge carried by the DNA molecule. The velocity of DNA translocation is dependent on both the nucleotide structure and molecular weight of the DNA sample. 

The carbon nanotubes were grown on an oxidized silicon wafer. Results indicate that among the successfully formed nanotubes—those fully opened and without leakage along their length—a sharp spike in electrical activity is detected during the process of DNA translocation. Further, reversing the bias of the electrodes causes the current spikes to disappear; restoring the original bias caused the spikes to reappear.

Lindsay stresses that the transient current pulses, each containing roughly 10x7charges, represent an enormous amplification of the translocated charge. A technique known as quantitative polymerase chain reaction (qPCR) was used to verify that the particular carbon nanotubes displaying these anomalously sharp current spikes—around 20 percent of the total sample, were indeed those through which DNA translocation had occurred.

The team carried out molecular simulations to try to determine the mechanism for the anomalously large ionic currents detected in the nanotubes. Observation of current-voltage curves registered at varying ionic concentrations showed that ion movement through some of the tubes is very unusual, though understanding the precise mechanism by which DNA translocation gives rise to the observed current spikes will require further modeling. Nevertheless, the characteristic electrical signal of DNA translocation through tubes with high ionic conductance may provide a further refinement in ongoing efforts to apply nanopore technology for rapid DNA sequencing.

Critical to successful rapid sequencing through nanopores is the precise control of DNA translocation. The hope is that genetic reading can be significantly accelerated, while still allowing enough time for DNA bases to be identified by electrical current traces. Carbon nanotubes provide an attractive alternative, making the control of nanopore characteristics easier and more reliable.

If the process can be perfected, Lindsay emphasizes, DNA sequencing could be carried out thousands of times faster than through existing methods, at a fraction of the cost. Realizing the one-patient-one-genome goal of personalized medicine would provide essential diagnostic information and help pioneer individualized treatments for a wide range of diseases. 

To see Biodesign Institute at Arizona State University scientist Dr. Stuart Lindsay explain the potential of a sequencing method in which a single-stranded ribbon of DNA is threaded through a carbon nanotube in a video follow this link: http://www.eurekalert.org/multimedia/pub/19288.php?from=151548

Massively Parallel Dip Pen Nano-Lithography Using Two-Dimensional Pen Arrays Enables Patterned Phospholipid Membranes for Biochemical Sensors, Drug Screening and Delivery

U. S. Patent Application 20090325816 details Northwestern University’s instrument for massively parallel dip pen nano-lithography using two-dimensional pen arrays.  The device has a patterning rate between 100,000 to 4 million dots per minute. Patterns can be created with lines and dots as small as 20 nanometers. Substrates can be coated and patterned with, for example, 25 million structures, to 1 billion structures to form devices for use in biosensors, drug discovery, drug delivery and other biochemical applications.

Inventors Northwester University Dr. Chad A. Mirkin  (Director of the International Institute for Nanotechnology), with Peng Sun, Yuhuang Wang and Steven Lenhert developed instruments for massive parallel printing of structures and nanostructures, including lipids, at high speed with high resolution and high quality using two dimensional arrays comprising cantilevers and tip-based transfer of material to a surface.

Micro- and nanoscopic heterogeneities, such as lipid rafts and focal adhesions, are vital to the biological function of lipid bilayer membranes. Lithographically patterned phospholipid membranes can be used as cell-surface models and have been used in several applications, including biochemical sensors, drug screening and delivery, the analysis of cell-cell interactions, and to address fundamental biological questions in membrane trafficking.  

Northwestern's  method allows both high-resolution patterning and parallel deposition of different phospholipid materials over large areas. Massively parallel lithography with two-dimensional pen arrays is suitable for the rapid fabrication and integration of large-scale phospholipid nanostructure libraries on a variety of substrates.

The array is designed so only tips touch the surface. This can be accomplished by long tips and bent cantilevers and alignment. The instrument includes: a two-dimensional array of a plurality of cantilevers, wherein the array comprises a plurality of base rows, each base row comprising a plurality of cantilevers, wherein each of the cantilevers comprise tips at the cantilever end away from the base, wherein the number of cantilevers is greater than 250, and wherein the tips have an apex height relative to the cantilever of at least four microns, and a support for the array. Combinatorial arrays and bioarrays can be prepared. The arrays can be manufactured by micromachining methods.

FIG. 1. Dip Pen Nanolithography (DPN)  patterning with 55,000 AFM cantilevers in parallel: (a) Optical micrograph of part of the 2D array of cantilevers used for patterning. Inset shows an SEM image of the tips. (b) Large area SEM image (left) of part of an 88,000,000 gold dot array (40.times.40 within each block) on an oxidized silicon substrate. A representative AFM topographical image (right) of part of a block. (c) Representative optical micrograph (inset shows AFM image) of .about.55,000 features drawn in the form of the face of the 2005 US five cent coins. The coin bears a picture of Thomas Jefferson, who helped develop the polygraph, a macroscopic letter duplicator that relies on an array of pens. 

 

The instruments can be used to control multi-bilayer stacking (FIG. 1); phospholipid patterns including fluorophore doping (FIG. 2); parallel writing of multiple inks including for testing membrane fluidity; and generation of fluorescent micrographs. DPN printing makes can use an atomic force microscope tip to directly deposit molecular inks onto a surface, reproducibly allowing line widths below 20 nm in the case of alkanethiols on gold.

FIG. 2. A schematic diagram of the fabrication process for 2D cantilever arrays.

The ability for DPN to operate under ambient conditions makes it particularly well suited to the fabrication of biomolecular arrays. This unique capability has been demonstrated by the fabrication of DNA and protein arrays with sub-100-nm lateral resolution. The fabrication of small spot sizes locally concentrates the analyte, which enables the detection of very low bulk analyte concentrations.

 Importantly, DPN has an advantage over other types of lithography in that many different chemical functionalities can be integrated onto a single surface without the risk of feature cross-contamination, as in the previously used indirect methods. Since the line widths and spot sizes in DPN are independent of the contact force of the microscope tip on the substrate, the technique can be readily carried out in parallel with arrays of cantilevers over centimeter length scales. 

FIG. 3. Optical micrograph of part of a 2D 55,000 pen array. Insets are SEM images of the pen array from side view (top), and top view (bottom), respectively.

FIG. 9. SEM image of single dip pen pyramidal tip, where the measured tip apex height is 8.8 microns and the base is 11.0 microns.

FIG. 10. Illustrating measurement of angle of cantilever bending and distance of cantilever bending.

 

Professor Mirkin is a chemist and a world renowned nanoscience expert, who is known for his development of nanoparticle-based biodetection schemes, the invention of Dip-Pen Nanolithography, and contributions to supramolecular chemistry, nanoelectronics, and nanooptics. He is the author of over 400 manuscripts and over 360 patents and applications, and the founder of three companies, Nanosphere, NanoInk, and Aurasense which are commercializing nanotechnology applications in the life science and semiconductor industries.  NanoInk is commercializing Dip Pin Nanolithography. 

Micron Technology Patent Details Nanocrystal Write Once Read Only Memory For Archival Storage- High Work Function Nanoparticles Enable High Density DRAM

Micron Technology, Inc. (Boise, ID) inventor Leonard Forbes discloses details of nanocrystal write once read only memory for archival storage in U.S. Patent 7,639,528.  

Forbes developed structures and methods for write once read only memory employing charge trapping. The write once read only memory cell includes a metal oxide semiconductor field effect transistor (MOSFET) in a substrate. The MOSFET has a first source/drain region, a second source/drain region, and a channel region between the first and the second source/drain regions. A gate insulator is formed opposing the channel region.  

The novel programmed MOSFETs conduct significantly less current than conventional MOSFETs, particularly at low drain voltages. Electrons will remain trapped in the number of high work function nanoparticles, or nanocrystals, within the gate oxide gate unless negative gate voltages are applied. The electrons will not be removed from the number of high work function nanoparticles, or nanocrystals, within a gate oxide when positive or zero gate voltages are applied. Erasure can be accomplished by applying negative gate voltages and/or increasing the temperature with negative gate bias applied to cause the trapped electrons to be re-emitted back into the silicon channel of the MOSFET. 

The gate insulator includes a number of high work function nanoparticles. A gate is formed on the gate insulator. A plug is coupled to the first source/drain region and couples the first source/drain region to an array plate. A transmission line is coupled to the second source/drain region. The MOSFET is a programmed MOSFET having a charge trapped in the number of high work function nanoparticles in the gate insulator adjacent to the first source/drain region.

Applications containing the novel memory cell include electronic systems for use in memory modules, device drivers, power modules, communication modems, processor modules, and application-specific modules, and may include multilayer, multichip modules. Such circuitry can further be a subcomponent of a variety of electronic systems, such as a clock, a television, a cell phone, a personal computer, an automobile, an industrial control system, an aircraft, and others.

Utilization of a modification of well established DRAM technology and arrays will serve to afford an inexpensive memory device. The high density of DRAM array structures will afford the storage of a large volume of digital data or images at a very low cost per bit. There are many applications where the data need only be written once for archival storage. The thicker gate insulators, lower operating voltages and larger work functions of the nanocrystals acting as floating gates will insure long retention and archival storage.

The MOSFETs can be programmed by operation in the reverse direction and utilizing avalanche hot electron injection to trap electrons in a number of high work function nanoparticles, or nanocrystals, within a gate oxide of the MOSFET. When the programmed MOSFET is subsequently operated in the forward direction the electrons, trapped in the number of high work function nanoparticles, or nanocrystals, within the gate oxide, are near the source and cause the channel to have two different threshold voltage regions.

The key high work function nanoparticles include nanocrystals selected from the group of p-type nanocrystals of silicon germanium for gates, p-type nanocrystals gates of other semiconductors as silicon carbide, silicon oxycarbide, gallium nitride (GaN), and aluminum gallium nitride (AlGaN). The nanocrystals are isolated from one another and not in conductive contact. In still other embodiments, the number of high work function nanoparticles include heavily doped p-type polysilicon floating and isolated nanocrystals with a vacuum work function of 5.3 eV. 

Danish Nano Research in Nerve Cell Communication Help the Fight Against Nerve Pain Following Amputation and Diabetes

New Danish nano research gives important insights in nerve cell communication that will help the fight against nerve pain following amputation and diabetes. Researchers from the Nano-Science Center and the Department of Neuroscience and Pharmacology at the University of Copenhagen have with nanotechnology techniques studied the way proteins recognize the small membrane vesicles that transmit signalling molecules from one nerve cell to another. The research has been published in the respected journal EMBO Journal.

Communication between nerve cells is vital for our bodies to function. Part of this communication happens through vesicles containing signalling molecules called neurotransmitters. The vesicle fuses with the nerve cell membrane; the neurotransmitters are released and quickly recorded by the next nerve cell. It is crucial that new vesicles constantly are produced for the nerve cell communication continuously to take place. If parts of this communication do not work, it leads to nerve pain like phantom pain following amputation.

New discoveries on a nanoscale

In patients with nerve pain, part of the pathological picture is a defect in a protein domain called BAR. Danish scientists studied how BAR binds to small membrane vesicles of different size. We expect that the new knowledge can be used to combat nerve pain in the future, explains Associate Professor Dimitrios Stamou, Bio-Nanotechnology Laboratory, Nano-Science Center and the Department of Neuroscience and Pharmacology. Dimitrios Stamou has led the work.

The researchers have used nanotechnology techniques, which give them the unique opportunity to study the binding of proteins to individual vesicles. Earlier studies have been performed in solutions where you measure a large number of vesicles and proteins at a time. This gives an average value of binding and ”masks out” a large number of important information that can be retrieved by measurements on single vesicles, says Dimitrios Stamou. 

Confocal microscopy images. Right: Brain-lipid vesicles. Smaller “dots” indicate smaller vesicles. Left: BAR domain protein. The intensity of the dot indicates the amount of BAR bound to the vesicle. The smaller the vesicle, the more curved membrane, and the more binding of BAR.

Error in communication

More and more studies – this study included, show that the curvature of the membrane is absolutely central to the binding of proteins to cell membranes – the greater the curvature, the greater the binding. This also applies to nerve cells in the brain. It therefore provides an important insight for the overall understanding of how nerve cells communicate with each other and for treating diseases where the communication has failed.

"To our great surprise we find that BAR binds to the membrane vesicles via small cracks in the vesicle membrane. We had expected that BAR bound to the small round membrane vesicles both because of its banana shaped structure, which fits with the shape of the vesicle, and by means of an attraction between “the banana’s” positive surface and vesicle’s negative surface. But instead, it is the hydrophobic part of BAR that is involved in binding," explains Associate Professor Dimitrios Stamou, Bio-Nanotechnology Laboratory, Nano-Science Center and the Department of Neuroscience and Pharmacology.

Contact

Associate Professor Dimitrios Stamou, Bio-Nanotechnology Laboratory, Nano-Science Center and the Department of Neuroscience and Pharmacology, University of Copenhagen e-mail: stamou@nano.ku.dk or  +45 41 16 04 68

Communication Officer Gitte Frandsen, Nano-Science Center, University of Copenhagen, e-mail: gf@nano.ku.dk or +45 28 75 04 58

Link to EMBO J paper

Amphipathic motifs in BAR domains are essential for membrane curvature sensing
http://www.nature.com/emboj/journal/v28/n21/full/emboj2009261a.html

Cultured Blood Cells with John Hopkins “Nanosense” May Help Design New Therapies & Diagnostic Tests for Cardiac Diseases

Johns Hopkins researchers developed this chip to culture heart cells that more closely resemble natural cardiac tissue. 

Photo: Will Kirk/homewoodphoto.jhu.edu

Johns Hopkins biomedical engineers, working with colleagues in Korea, have produced a laboratory chip with nanoscopic grooves and ridges capable of growing cardiac tissue that more closely resembles natural heart muscle. Surprisingly, heart cells cultured in this way used a “nanosense” to collect instructions for growth and function solely from the physical patterns on the nanotextured chip and did not require any special chemical cues to steer the tissue development in distinct ways. The scientists say this tool could be used to design new therapies or diagnostic tests for cardiac disease.

Leslie Tung, left, and Andre Levchenko, right, both of the Department of Biomedical Engineering, with Deok-Ho Kim, a doctoral student in Levchenko’s lab, who holds a nanopatterned chip able to cue heart cells to behave like natural heart tissue.

Photo: Will Kirk/homewoodphoto.jhu.edu

The device and experiments using it are described in this week’s online Early Edition issue of Proceedings of the National Academy of Sciences. The work, a collaboration with Seoul National University, represents an important advance for researchers who grow cells in the lab to learn more about cardiac disorders and possible remedies.

“Heart muscle cells grown on the smooth surface of a Petri dish would possess some, but never all, of the same physiological characteristics of an actual heart in a living organism,” said Andre Levchenko, an associate professor of biomedical engineering in Johns Hopkins’ Whiting School of Engineering. “That’s because heart muscle cells—cardiomyocytes—take cues from the highly structured extracellular matrix, or ECM, which is a scaffold made of fibers that supports all tissue growth in mammals. These cues from the ECM influence tissue structure and function, but when you grow cells on a smooth surface in the lab, the physical signals can be missing. To address this, we developed a chip whose surface and softness mimic the ECM. The result was lab-grown heart tissue that more closely resembles the real thing.”

Levchenko said that when he and his colleagues examined the natural heart tissue taken from a living animal, they “immediately noticed that the cell layer closest to the extracellular matrix grew in a highly elongated and linear fashion. The cells orient with the direction of the fibers in the matrix, which suggests that ECM fibers give structural or functional instructions to the myocardium, a general term for the heart muscle.” These instructions, Levchenko said, are delivered on the nanoscale—activity at the scale of one-billionth of a meter and a thousand times smaller than the width of a human hair.

Levchenko and his Korean colleagues, working with Deok-Ho Kim, a biomedical engineering doctoral student in Levchenko’s lab and the lead author of the PNAS article, developed a two-dimensional hydrogel surface simulating the rigidity, size and shape of the fibers found throughout a natural ECM network.

This biofriendly surface made of nontoxic polyethylene glycol displays an array of long ridges resembling the folded pattern of corrugated cardboard. The ridged hydrogel sits upon a glass slide about the size of a U.S. dollar coin. The team made a variety of chips with ridge widths spanning from 150 to 800 nanometers, groove widths ranging from 50 to 800 nanometers and ridge heights varying from 200 to 500 nanometers. This allowed researchers to control the surface texture over more than five orders of magnitude of length.

“We were pleased to find that within just two days the cells became longer and grew along the ridges on the surface of the slide,” Kim said. Furthermore, the researchers found improved coupling between adjacent cells, an arrangement that more closely resembled the architecture found in natural layers of heart muscle tissue. Cells grown on smooth, unpatterned hydrogels, however, remained smaller and less organized, with poorer cell-to-cell coupling between layers. “It was very exciting to observe engineered heart cells behave on a tiny chip in two dimensions like they would in the native heart in three dimensions,” Kim said.

Collaborating with Leslie Tung, a professor of biomedical engineering in the Johns Hopkins School of Medicine, the researchers found that after a few more days of growth, cells on the nanopatterned surface began to conduct electric waves and contract strongly in a specific direction, as intact heart muscle would. “Perhaps most surprisingly, these tissue functions and the structure of the engineered heart tissue could be controlled by simply altering the nanoscale properties of the scaffold. That shows us that heart cells have an acute ‘nanosense,’” Levchenko said.

“This nanoscale sensitivity was due to the ability of cells to deform in sticking to the crevices in the nanotextured surface and probably not because of the presence of any molecular cue,” Levchenko said. “These results show that the ECM serves as a powerful cue for cell growth, as well as a supporting structure, and that it can control heart cell function on the nanoscale separately in different parts of this vital organ. By mimicking this ECM property, we could start designing better-engineered heart tissue.”

Looking ahead, Levchenko said that he anticipates that engineering surfaces with similar nanoscale features in three dimensions, instead of just two, could provide an even more potent way to control the structure and function of cultured cardiac tissue.

In addition to Kim, Levchenko and Tung, authors on this paper are postdoctoral fellow Elizabeth A. Lipke and doctoral students Raymond Cheong and Susan Edmonds Thompson, all from the Johns Hopkins School of Medicine Department of Biomedical Engineering; Michael Delannoy, assistant director of the Johns Hopkins School of Medicine Microscope Facility Center; and Pilnam Kim and Kahp-Yang Suh, both of Seoul National University.

Tung and Levchenko are affiliated faculty members of the Johns Hopkins Institute for NanoBioTechnology. Thompson is a member of INBT’s Integrative Graduate Education and Research Traineeship in nanobiotechnology. Funding for this research was provided by the National Institutes of Health and the American Heart Association.

Related Web sites

Andre Levchenko’s Lab

Leslie Tung’s Lab

Johns Hopkins Institute for NanoBioTechnology

Story by Mary Spiro

Iranian Chemists Functionalize Carbon Nanotubes to Detect Cysteamine in Biological Compounds

Iranian chemists made a modified glassy carbon electrode with a functionalized carbon nanotube which is able to electrochemically measure the cysteamine present in biological specimens.

Nanotechnology has opened new horizons for the use of nanoparticles and carbon nanotubes in analytical chemistry and detection of some biological and chemical compounds. One of the interesting applications of nanoparticles and carbon nanotubes is to facilitate electron transfer reactions.

"Since some of amino acids are sulfuric compounds, their electrochemical oxidation on the surface of common electrodes are very slow. As a consequence, we can't detect them on the current electrodes surfaces and measure," Fereshteh Chekin, one of researchers told the news service of Iran Nanotechnology Initiative Council (INIC).

To overcome this limitation, different mediums were utilized and modified chemical electrodes were made. In this regard, the researchers fabricated modified glassy carbon electrode by means of functionalized carbon nanotube to electrochemically measure cysteamine.

The stabilization of electron transfer mediums like carbon nanotubes and naphthoquinone compounds on electrode beds was characterized by SEM images. This naphthoquinone functionalized modified electrode was used as an electrochemical sensor in voltammetric measurement of cysteamine.

"The present study is a fundamental research which could be used in the measurement of cysteamine present in biological specimens at clinical laboratories and research centers", Chekin added.

The present study is published at Journal of Electroanalytical Chemistry, volume 633, pages 187 to 192, 2009.

Exploding Silicon Nanobombs Kill Cancer with No Toxicity to Normal Cells Nor Side Effects say Korean Researchers

Korean researchers at the Inha-Industry Partnership Institute have developed a new weapon for the war on cancer: silicon nanobombs. The smart nanobombs kill cancer cells but leave normal cells unharmed.  

FIG. 10 from Inha-Industry Partnership Institute’s U.S Patent Application 20090326520  is a capture image of a cancer killing silicon nanobomb explosion occurring upon the irradiation of NIR light onto porous silicon nanobombs with sulfur entrapped within its pores. Silicon nanobombs have been successfully used to kill breast cancer cells.

Inha-Industry Partnership Institute (Incheon, KR) researchers Chongmu Lee, Hohyeong Kim and Chanseok Hong developed a method for treating cancer using a porous silicon nanobomb. The porous silicon nanobomb can be exploded by NIR light irradiation at a low intensity to selectively destroy cancer cells. Also, porous silicon itself shows good biocompatibility and biodegradability. According to U.S. Patent Application 20090326520,  the silicon nanobomb can be used as an efficient method for treating cancer without the accumulation of toxic side effects.

The porous silicon nanobomb of the present invention can be heated by NIR light with an irradiation intensity of from 100 to 400 mW/cm², which is only about one hundredth of that required for heating nanoshells, that is, 35 W/ cm². For carbon nanotubes, the irradiation intensity of NIR light amounts to 1 to 4 W/cm² Therefore, the nanobombs are useful in the treatment of cancer without damaging normal cells, in contrast to nanoshells and carbon nanotubes.

Thermotherapy is a minimally invasive cancer treatment technique that can replace invasive surgical treatment. Entailing a relatively simple operation in addition to minimal invasiveness, thermotherapy makes possible a short recovery time. Also, thermotherapy is a type of physical therapy with fewer limitations than chemotherapy and is typically used in combination with both of the invasive therapies. In addition, it allows repeated treatments without the accumulation of toxic side effects. Thermotherapy (or thermal ablation therapy) includes laser-induced thermotherapy, microwave and radiofrequency (RF) ablation, magnetic thermal ablation, and focused ultrasound.

Most of them, however, have shortcomings in that the treatment takes a long period of time and that its lesion boundaries are not well defined. Alternatively proposed was magnetic thermotherapy based on using alternating current to heat oxide nanoparticles in tumor cells. Although disadvantageous in that it requires a large quantity of iron for sufficient thermal effects, this magnetic thermotherapy has an advantage over the other thermotherapies in that it can selectively heat only the cells filled with oxides of iron.

Inha-Industry Partnership Institute’s method for treating cancer uses biocompatible and biodegradable porous silicon nanobombs which can generate heat sufficient to selectively kill cancer cells upon exposure to NIR light at a low intensity, with accompaniment of neither toxicity to normal cells nor side effects.

FIG. 1 is a schematic diagram of an electrochemical anodization cell for use in the preparation of nano-porous silicon

FIG. 2 is an scanning electron microscope (SEM) image showing nano-porous silicon in a plan view.

FIG. 3 is an SEM showing nano-porous silicon in a cross-sectional view

FIG. 9 is a captured  image of an explosion occurring upon the irradiation of NIR light onto the porous silicon bombs with NaClO₄.1H₂O entrapped within the pores thereof.  As seen in FIGS. 9 and 10, the bombs of sulfur (FIG. 10) were exploded on a larger scale than were the bombs of NaClO₄.1H₂O (FIG. 9).

FIG. 11 is optical microphotographs of breast cancer cells before NIR irradiation. FIG. 11 is microphotographs of PSi/S/NaCl-treated breast cancer cells before exposure to NIR light, and

FIG. 12 is that of after exposure to NIR light for 20 min. A drama is seen between the cells of FIGS. 12 and 11.

Upon NIR exposure in the presence of the PSi suspension, the cells seemed to be blown up and burnt black. Explosion was observed to occur inside the cell clusters as inferred from the morphology of dead cells. Also, the bubbles showed that the cells were blown up in the explosion. Bubbles found around dead cells were evidence of the vigorous boiling of the NaCl solution within porous silicon particles, implying that the explosion of porous silicon particles resulted from the temperature elevation of the NaCl solution localized within the silicon particles to exceed the boiling point.