Abstract: A method for dispensing charged particles includes applying a bias voltage to promote motion of charged molecules through a nanopore, detecting passage of at least one charged molecule through the nanopore, and manipulating an electrostatic potential barrier inside the nanopore, so as to prevent movement of additional charged molecules through the nanopore.

Abstract: Hybridization probes for hybridizing to the same target nucleic acid are disclosed, the hybridization probes comprising an electrically-active magnetic nanoparticle-labeled detector probe and a capture probe including a conjugating moiety for immobilization. Also disclosed is a biodetection method including the steps of: providing hybridization probes for hybridizing to the same target nucleic acid, the hybridization probes comprising an electrically-active magnetic nanoparticle-labeled detector probe and a capture probe; hybridizing the target nucleic acid with each of the electrically-active magnetic nanoparticle-labeled detector probe and a capture probe in a sample including the target nucleic acid; magnetically separating the hybridized target nucleic acid from the sample; capturing the hybridized target nucleic acid on a substrate through the capture probe; and measuring the oxidation-reduction signal of the electrically-active magnetic nanoparticle-labeled detector probe.

Abstract: Compositions and methods for nucleic acid sequencing include template constructs that comprise double stranded portions in a partially or completely contiguous constructs, to provide for redundant sequence determination through one or both of sequencing sense and antisense strands, and iteratively sequencing the entire construct multiple times. Additional sequence components are also optionally included within such template constructs. Methods are also provided for the use and preparation of these constructs as well as sequencing compositions for their application.

Abstract: In a molecular analysis system, there is provided a structure including a nanopore and first and second fluidic reservoirs. The two reservoirs are fluidically connected via the nanopore. A detector is connected to detect molecular species translocation of the nanopore, from one of the two fluidic reservoirs to the other of the two fluidic reservoirs. A controller is connected to generate a control signal to produce conditions at the nanopore to induce the molecular species to re-translocate the nanopore at least once after translocating the nanopore. This enables a method for molecular analysis in which a molecular species is translocated a plurality of times through a nanopore in a structure between two fluidic reservoirs separated by the structure.

Abstract: A nanodevice includes a reservoir filled with conductive fluid and a membrane separating the reservoir. A nanopore is formed through the membrane having electrode layers separated by insulating layers. A certain electrode layer has a first type of organic coating and a pair of electrode layers has a second type. The first type of organic coating forms a motion control transient bond to a molecule in the nanopore for motion control, and the second type forms first and second transient bonds to different bonding sites of a base of the molecule. When a voltage is applied to the pair of electrode layers a tunneling current is generated by the base in the nanopore, and the tunneling current travels via the first and second transient bonds formed to be measured as a current signature for distinguishing the base. The motion control transient bond is stronger than first and second transient bonds.

Abstract: The present invention is directed to a nucleic acid detection device and method that incorporates bio-nanosensor technology to detect duplex DNA. The device is particularly applicable in detecting the presence or absence of duplex DNA and its correlation to the diagnosis of infectious diseases. In one embodiment, the infectious disease is Lyme disease or a bacterial or viral infection. The device comprises a bio-nanosensor element comprising ssDNA primed nanotubes, either single walled or multi-walled. The method comprises contacting the bio-nanosensor element with a test solution potentially containing DNA of interest. DNA of interest that hybridizes to the ssDNA results in a measurable change in the electrical properties of the bio-nanosensor. Correlations between the results provided by the device and the presence of disease states can result in rapid diagnosis of diseases such as Lyme disease or foodborne infections such as salmonellosis.

Abstract: A sensor electrode for the detection of nucleotides in a biological sample is described. The sensitivity of the electrode is enhanced by the nanostructured sensor architecture that increases the available surface area of the electrode. The electrode detects nucleotides using standard electrochemical methods.

Abstract: The invention provides nucleic acid hybridization methods for detecting target nucleic acid sequences wherein complexes comprising nanoparticles non-covalently associated with single-stranded tartlet nucleic acid molecules are incubated with immobilized probe nucleic acid molecules. Because the nanoparticles function as competitors in the hybridization reaction between the target nucleic acid molecules and the probe nucleic acid molecules. The methods provide a high degree of discrimination between a perfectly matched target sequence and a sequence having at least a single-base-pair mismatch, even when the hybridization reaction is performed at room temperature. The invention also provides microarray methods and apparatus which incorporate the nanoparticle-assisted hybridization methods.

Abstract: Provided are methods for detecting, characterizing or separating DNA based on methylation. Heterogeneous DNA populations are separated based on DNA methylation by providing a membrane having a nanopore through which an electric field is applied. DNA of interest is introduced, and for a given threshold voltage across the nanopore, only DNA having a methylation parameter of interest may transit the pore, thereby facilitating detection, characterization, or separation of DNA based on methylation. The methods are optionally used to detect a disease state that is associated with DNA methylation including, but not limited to, cancer.

Abstract: A high-sensitivity field effect transistor using as a channel ultrafine fiber elements such as carbon nanotube, and a biosensor using it. The field effect transistor comprises a substrate, a source electrode and a drain electrode arranged on the substrate, a channel for electrically connecting the source electrode with the drain electrode, and a gate electrode causing polarization due to the movement of free electrons in the substrate. For example, the substrate has a support substrate consisting of semiconductor or metal, a first insulating film formed on a first surface of the support substrate, and a second insulating film formed on a second surface of the support substrate, the source electrode, the drain electrode, and the channel arranged on the first insulating film, the gate electrode disposed on the second insulating film.

Abstract: A method of using a sensor comprising a field effect transistor (FET) embedded in a nanopore includes placing the sensor in an electrolyte comprising at least one of biomolecules and deoxyribonucleic acid (DNA); placing an electrode in the electrolyte; applying a gate voltage in the sub-threshold regime to the electrode; applying a drain voltage to a drain of the FET; applying a source voltage to a source of the FET; detecting a change in a drain current in the sensor in response to the at least one of biomolecules and DNA passing through the nanopore.

Abstract: In some embodiments, an analyte detection system is provided that includes a nanochannel, an electrode arrangement, and a plurality of nanoFET devices disposed in the nanochannel. A plurality of nucleic acid base detection components can be used that include a plurality of nanopores, a plurality of nanochannels, a plurality of hybridization probes, combinations thereof, and the like. According to other embodiments of the present teachings, different coded molecules are hybridized to a target DNA molecule and used to detect the presence of various sequences along the target molecule. A kit including mixtures of coded molecules is also provided. In some embodiments, devices including nanochannels, nanopores, and the like, are used for manipulating movement of DNA molecules, for example, in preparation for a DNA sequencing detection. Nanopore structures and methods of making the same are also provided as are methods of nucleic acid sequencing using the nanopore structures.

Abstract: A nanoscale motion detector attaches a gold nanorod (30) to the rotating arm (26) of a molecular structure (10) to cause the nanoparticle to rotate. The molecular structure is an F1-ATPase enzyme. The gold nanorod is exposed to a light source. The long axis of the gold nanorod scatters red light when the nanorod is in a first position. The short axis of the gold nanorod scatters green light when the nanorod is in a second position. A polarizing filter filters the red and green light to detect the rotational motion by observing alternating red and green lights. A detection DNA stand (50) is coupled between the gold nanorod and the molecular structure. The detection DNA strand hybridizes with a target DNA strand (58) if the target DNA strand matches the detection DNA strand to form a structural link between the molecular structure and gold nanorod.

Abstract: In a molecular analysis system, there is provided a structure including a nanopore and first and second fluidic reservoirs. The two reservoirs are fluidically connected via the nanopore. A detector is connected to detect molecular species translocation of the nanopore, from one of the two fluidic reservoirs to the other of the two fluidic reservoirs. A controller is connected to generate a control signal to produce conditions at the nanopore to induce the molecular species to re-translocate the nanopore at least once after translocating the nanopore. This enables a method for molecular analysis in which a molecular species is translocated a plurality of times through a nanopore in a structure between two fluidic reservoirs separated by the structure.

Abstract: Techniques for controlling the position of a charged polymer inside a nanopore are provided. For example, one technique includes using electrostatic control to position a linear charged polymer inside a nanopore, and creating an electrostatic potential well inside the nanopore, wherein the electrostatic potential well controls a position of the linear charged polymer inside the nanopore.

Abstract: Described herein are novel devices for the study of transport characteristics of complex or simple fluids, interactions among molecules in suspension, interactions between molecules in suspension and wall-bound molecules, and biochemical sensing devices made of reservoirs for fluid containment linked by a nanotubes. Also disclosed are methods of delivering medicaments and monitoring fluidic interactions of molecules or analytes.

Abstract: A nanopore device is described wherein is provided a sample input (110), an input chamber (120), and first and second sample chambers (130, 140) connected to the input chambers (120) via first and second nanopores (135, 145).

Abstract: A DNA chip includes a substrate, at least one first electrode and at least one second electrode on the substrate, the first electrode and the second electrode being opposite to and separated from each other, multiple oligonucleotide probes, one end of the oligonucleotide probes being immobilized on the first electrode, and a charge-carrier transport layer on the second electrode, the charge-carrier layer contacting an other end of the oligonucleotide probes.

Abstract: A biomolecule analyzing system (10) that provides an expeditious, accurate and reliable method for analyzing a biomolecule (150). The system (10) includes two substrates (12,28) each having an inner edge (14,30), an outer edge (16,32) and an inner surfaces (20,36) from where extends a multiplicity of cilia (22). To the inner edges (14,30) is attached an input tube (82) that is also attached to a biomolecule sample reservoir (90). To the outer edges (16,32) is attached an output tube (106) that is also attached to a sample deposit chamber (120). The tubes (82,106) include a plurality of conductive plates (98) that are applied an electrical charge that causes the biomolecule (150) to traverse through the tubes (82,106). When the biomolecule (150) passes through the cilia (22) signals are produced that are applied to a pair of image capturing devices (40,50).

Abstract: A fine metal structure having its surface furnished with microprojections of high strength, high precision and large aspect ratio; and a process for producing the fine metal structure free of defects. There is provided a fine metal structure having its surface furnished with microprojections, characterized in that the microprojections have a minimum thickness or minimum diameter ranging from 10 nanometers to 10 micrometers and that the ratio between minimum thickness or minimum diameter (D) of microprojections and height of microprojections (H), H/D, is greater than 1.

Abstract: A gold nanoparticle composition is provided that includes a spherical gold nanoparticle and an organic ligand molecule. The organic ligand molecule bonds to the gold nanoparticle. Thus, the gold nanoparticle composition has at least one absorption peak wavelength (plasmon absorption wavelength) within the region of 600-1000 nm. Consequently, the gold nanoparticle composition self-heats when irradiated with electromagnetic waves having a wavelength of 600-1000 nm.

Abstract: Methods are described for performing a multiplexed analysis of a level of target analyte in a sample, employing an identifier and a labeling reagent. Either or both of the identifier and the labeling reagent comprises a SERS-active nanoparticle associated with a SERS-active reporter with a uniquely identifiable spectroscopic signature. Interrogation of the identifier and the labeling reagent is conducted by serial coincident detection. Such methods can provide enhanced multiplexed analysis of analytes in a sample, especially with regards to improving the type of identifying reagents that are employed.

Abstract: Crosslinked proteins, proteins and polymers, and polymers and methods of making the same are disclosed. In one illustrative embodiment, a method is provided comprising the steps of attaching a chelator to one or more polymers; creating a coordination complex between the first protein, the second protein, and a metal ion; and crosslinking the first and second proteins by exposing the coordination complex to an oxidant.

Abstract: A nanostructure comprising a core material of a nanometric size surrounded by an envelope of ordered fluid molecules is disclosed. The core material and the envelope of ordered fluid molecules are in a steady physical state. Also disclosed, a liquid composition comprising liquid and the nanostructure.

Abstract: Disclosed herein are methods of screening sequence selectivity of oligonucleotide-binding molecules using a gold nanoparticle based colorimetric assay.

Abstract: A biosensor for detecting the presence of a target analyte is disclosed. The biosensor is formed from microspheroidal particles which have had a binding partner for the target analyte immobilized on their surfaces. The binding partners may be nucleotides; peptides, proteins, enzymes, antibodies and so on. When the analyte binds to its partner, the whispering gallery mode (WGM) profiles of the microspheroidal particles change such that the profile peaks undergo a red-or blue-shift. The immobilised binding partners may include fluorophores and the like so that they emit fluorescence, phosphorescence, incandescence and the like. These fluorophores may take the form of a nanocrystal or quantum dot.

Abstract: The invention relates to a method for the molecular diagnosis of prostate cancer, comprising the in vitro analysis of the overexpression or underexpression of combinations of genes that can distinguish, with high statistical significance, tumorous prostate samples from non-tumorous prostate samples. The invention also relates to a kit for the molecular diagnosis of prostate cancer, which can perform the above-mentioned detection.

Abstract: Sensor platforms and methods of making them are described. A platform having a non-horizontally oriented sensor element comprising one or more nanostructures such as nanotubes is described. Under certain embodiments, a sensor element has or is made to have an affinity for an analyte. Under certain embodiments, such a sensor element comprises one or more pristine nanotubes. Under certain embodiments, the sensor element comprises derivatized or functionalized nanotubes. Under certain embodiments, a sensor is made by providing a support structure; providing one or more nanotubes on the structure to provide material for a sensor element; and providing circuitry to electrically sense the sensor element's electrical characterization. Under certain embodiments, the sensor element comprises pre-derivatized or pre-functionalized nanotubes. Under other embodiments, sensor material is derivatized or functionalized after provision on the structure or after patterning.

Abstract: The present invention comprises novel “one-step” methods for the production of gold sol and gold sol conjugates. The methods disclosed herein produce gold sol and colloidal gold conjugates with product with yields on the order of about 20 ODs. Since current methods in the art yield conjugates at concentrations on the order of about 2 ODs, the present invention represents an approximately 10-fold increase in production over conventional methods. The novel method provided herein also does not result in the production of undesired aggregate by-products that, in conventional methods, must be removed via centrifugation, filtration or other means. The new method is therefore less labor intensive and requires less time to complete than standard methods in the art for synthesizing pure colloidal gold conjugates.

Abstract: The present invention provides multiplexed methods for analyzing polynucleotides associated with sample tags. The multiplexed information is deconvoluted by single-molecule and more generally single-particle detection methods. In particular, a method for determining nucleic acid sequence information is provided.

Abstract: The present invention include fluorescent nanocrystals which have high fluorescence intensity, are water soluble, exhibit physical and chemical stability, and whose spectral properties are detectably modified as the size of functional groups bonded to the nanocrystal surface change when contacted with target molecules in a sample. The molecules in the sample add to or reduce the size of functional groups on the fluorescent nanocrystal proportional to the activity and amount of the target molecules. The present invention may be used to detect telomerase in a sample.

Abstract: The present invention relates to methods for detecting or quantifying an analyte in a test sample including providing at least one test mixture including a test sample, at least one marker complex, wherein each marker complex includes a particle, a marker, and one member of a coupling group, a first binding material selected to bind to a portion of the analyte, a second binding material selected to bind with a portion of the analyte other than the portion of the analyte for which the first binding material is selected, analyte analog, and/or marker conjugate. The at least one test mixture is passed through a membrane. The amount of marker on the membrane is detected and correlated to the presence or amount of analyte in the test sample.

Abstract: The present invention provides a device and methods of use thereof in concentrating a species of interest and/or controlling liquid flow in a device. The methods, inter-alia, make use of a device comprising microchannels, which are linked to nanochannels, whereby induction of an electric field in the nanochannel results in ion depletion in the linkage region between the microchannel and nanochannel, and a space charge layer is formed within the microchannel, which provides an energy barrier for said species of interest which enables its concentration in a region in the microchannel.

Abstract: There is disclosed a system for electrical charge detection comprising a nanoFET device. Also disclosed is a method of electrical charge detection for single molecule sequencing. The method includes attaching a macromolecule or assemblies thereof to a gate of a nanoFET device and flowing in a solution of charge tags, where a charge tag includes a nucleotide attached to a charge complex. The method also includes incorporating one charge tag into the macromolecule or assemblies thereof and cleaving the charge tags from the macromolecule or assemblies thereof. The method further includes detecting at least one of current and voltage from the nanoFET device.

Abstract: In a molecular analysis system, there is provided a structure including a nanopore and first and second fluidic reservoirs. The two reservoirs are fluidically connected via the nanopore. A detector is connected to detect molecular species translocation of the nanopore, from one of the two fluidic reservoirs to the other of the two fluidic reservoirs. A controller is connected to generate a control signal to produce conditions at the nanopore to induce the molecular species to re-translocate the nanopore at least once after translocating the nanopore. This enables a method for molecular analysis in which a molecular species is translocated a plurality of times through a nanopore in a structure between two fluidic reservoirs separated by the structure.

Abstract: Surface-enhanced Raman spectroscopic (SERS) systems and methods for detecting biomolecules of interest, such as a bacterium or virus are provided.

Abstract: A sensor system for detecting an effector or cofactor comprises (a) a nucleic acid enzyme; (b) a substrate for the nucleic acid enzyme, comprising a first polynucleotide; (c) a first set of particles comprising a second polynucleotide at least partially complementary to the substrate, where the polynucleotide is attached to the particles at its 3? terminus; and (d) a second set of particles comprising a third polynucleotide at least partially complementary to the substrate, where the polynucleotide is attached to the particles at its 5? terminus.

Abstract: Disclosed herein are methods of screening sequence selectivity of oligonucleotide-binding molecules using a gold nanoparticle based calorimetric assay.

Abstract: A method for separation of mixtures in fluidic systems through electrokinetic transport by use of nanochannels when the fluidic systems approach the size of an electrical double layer, thereby allowing separation based on charge. The disclosed apparatus comprises a T-chip with a nanochannel section. The method and apparatus are useful for separation of many molecular species, including peptides, proteins, and DNA.

Abstract: A modified isolated polypeptide comprising an amino acid sequence encoding a photocatalytic unit of a photosynthetic organism being capable of covalent attachment to a solid surface and having a photocatalytic activity when attached thereto is disclosed.

Abstract: A method by which silicon nanostructures may be selectively coated with molecules or biomolecules using an electrochemical process. This chemical process may be employed as a method for coating many different nanostructures within a circuit, each with a different molecular or biomolecular material. The density of devices within a circuit of devices that can be coated with different molecules is limited only by the ability to electronically address each device separately. This invention has applications toward the fabrication of molecular electronic circuitry and toward the fabrication of nanoelectronic molecular sensor arrays.

Abstract: There is provided a first reservoir containing a liquid solution including a molecule to be characterized and a second reservoir for containing a liquid solution including a molecule that has been characterized. A solid state support structure is provided including an aperture having a molecular entrance providing a fluidic connection to the first reservoir and a molecular exit providing a fluidic connection to the second reservoir. First and second electron transport probes are each disposed on the support structure with a surface abutting a perimeter of the aperture. At least one of the probes comprises a fullerene structure, e.g., a carbon nanotube. A voltage source is connected between the probes to apply a voltage bias across the aperture. An electrical current monitor is connected between the probes for monitoring changes in electron transport between the probes corresponding to translocation of a molecule through the aperture.

Abstract: The invention is drawn to novel gold nanoparticles that are used in a dual optical method for sensitive and selective detection of antigens. The gold nanoparticle aggregates are synthesized from gold hydrochloride and sulfur salts in an aqueous solution. The aggregates can be selectively sized using a spectral notch filter that results in an improved product with versatile uses. The gold nanoparticles can also be used in improved optical communications devices.

Abstract: Control beads are disclosed that allow for improved quantitation of analytes in multiplexed bead assays. The control beads have a range of concentrations of calibration moieties that provide for the preparation of a titration curve. The titration curve can be used to quantify the concentration of the analytes. The titration curve can be used to correlate the signal obtained from a bead with the concentration (or absolute number of molecules) of the analyte bound to the bead.

Abstract: The present patent application describes a cantilever for atomic force microscopy (AFM), which includes a cantilever body having a fixed end and a free end, the free end having a surface region being chemically modified by a dendron in which a plurality of termini of the branched region of the dendron are bound to the surface, and a terminus of the linear region of the dendron is functionalized.

Abstract: The present invention is directed to methods and apparatus for analyzing a sample for the presence of one or more analytes. The sample is contacted with a channel comprising (i) a plurality of features wherein each of the features comprises a binding partner for one of the respective analytes and (ii) a plurality of silicon CMOS sensors, each of the sensors being optically coupled to a corresponding feature. The contacting is carried out under conditions for binding of an analyte to a respective binding partner. The analytes are treated to introduce a luciferase prior to or after the contacting. The luciferase has a brightness that is at least 100 times greater than firefly luciferase. Light emitted at each of the features is detected by means of the silicon CMOS sensors. The amount of light emitted at each of the features is related to the presence and/or amount of an analyte in the sample.

Abstract: The present invention results from the examination of tissue from hepatic carcinomas to identify genes differentially expressed between cancerous liver tissue and diseased but non-cancerous liver tissue. The invention includes diagnostic, screening, drug design and therapeutic methods using these genes, as well as solid supports comprising oligonucleotide arrays that are complementary to or hybridize to the differentially expressed genes.

Abstract: Systems and methods for nanopore flow cells are provided.

Abstract: Elongated molecules are stretched across a substrate by controlled fluid flow.

Abstract: The present invention provides a nanostructured device comprising a substrate including nanotroughs therein; and a lipid bilayer suspended on or supported in the substrate. A separation method is also provided comprising the steps of supporting or suspending a lipid bilayer on a substrate; wherein the substrate comprises nanostructures and wherein the lipid bilayer comprises at least one membrane associated biomolecule; and applying a driving force to the lipid bilayer to separate the membrane associated biomolecule from the lipid bilayer and to drive the membrane associated biomolecule into the nanostructures.