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Etchant/Primer Composition, Etchant/Primer/Adhesive Monomer Composition, Kits & Methods using the Same for Improved Bonding to Dental Substrates

The present invention is directed to an etchant/primer composition, an etchant/primer/adhesive monomer composition, kits using the same and methods using the same for improved bonding to dental structures. The etchant/primer composition comprises a compound having the formula: RN(CH2 YCO2 M)2 wherein R=R1 or R2 ; R1 =an aromatic group; R2 =a conjugated unsaturated aliphatic group; Y=a single bond, CH2, CHCH3 or C.dbd.CH2 ; and each M is independently H, an alkali metal, an alkaline earth metal, aluminum, a transition or redox metal or an alkyl group having 1 to 18 carbon atoms, with the proviso that when both M groups are alkyl groups, said compound is capable of being easily hydrolyzed, displaced, or exchanged with other reagents present in the etchant/primer composition, a polar solvent system, and nitric acid. The etchant/primer/adhesive monomer composition comprises a compound having the formula (I) as noted above, a polar solvent system, an acid selected from the group consisting of nitric acid, hydrochloric acid, citric acid, lactic acid, glycolic acid, formic acid, pyruvic acid and combinations thereof, and adhesive monomer resin, and an initiator. The above-noted compositions are applied to dental structures requiring dental restoration for improved bonding of adhesive resins and polymers to dental structures.

Pre-Ceramic Polymers in Fabrication of Ceramic Composites

Composites in the form of a three-dimensional framework or skeleton of ceic particles are formed by a low cost, low temperature sintering process which decomposes a pre-ceramic inorganic or organic precursor. Upon heating, preferably in air, the precursor decomposes to form a ceramic phase in the form of necks between the individual ceramic particles. The properties of the resulting porous ceramic bodies can be modified, such as toughened by impregnation with monomers, oligomers or polymers which are polymerized or cured in situ. Such composites find use as cosmetic products or protheses for humans and animals, such as dental restoratives and bone implants. Methods of fabrication are disclosed which include the use of a pre-ceramic polymer as a binder for the ceramic particles which forms the necks of material between the individual ceramic particles upon firing.

Electrophoresis Gels

The present invention provides electrophoresis apparatus and electrophoresis methods employing gellan gum based gels employing divalent metal cation and diamine cross-linking agents. The gels are reversible under conditions that do not damage the biomolecules separated using the gels. The present invention also provides novel gellan gum-based gels which are cross-linked which employ a diamine cross-linking agent.

Immobilized Biological Membranes

A composition comprising an immobilized biological membrane is provided. The functional immobilized biological membrane consists of a support structure, a metal layered onto a surface of the support structure, an alkanethiol monolayer assembled onto the metal, and a biological membrane deposited on the alkanethiol monolayer. Also provided is a method of producing the immobilized biological membrane, wherein the method involves contacting an alkanethiol with a metal surface of a support structure in forming an alkanethiol monolayer assembled onto the metal, and depositing a biological membrane onto the alkanethiol monolayer such that the biological membrane becomes associated with the alkanethiol monolayer. Uses of the biological membrane include as a sensing indicator in a biosensor, as an adsorbent in a chromatography system, and as a coating for medical devices.

Optical Trap for Detection & Quantitation of Subzeptomolar Quantities of Analytes

Tightly focused beams of laser light are used as "optical tweezers" to trap and manipulate polarizable objects such as microspheres of glass or latex with diameters on the order of 4.5 µm. When analytes are allowed to adhere to the microspheres, small quantities of these analytes can be manipulated, thus allowing their detection and quantitation even when amounts and concentrations of the analytes are extremely small. Illustrative examples include measuring the strength needed to break antibody-antigen bonds and the detection of DNA sequences.

Process For UV-Photopatterning of Thiolate Monolayers Self-Assembled On Gold, Silver and Other Substrates

A process for creating a two dimensional spacial distribution pattern of ferent thiolate molecules on a substrate by illuminating a surface of a self-assembled monolayer of a first thiolate compound in the presence of oxygen with high frequency electromagnetic radiation distributed according to a desired pattern, and subsequently immersing the illuminated substrate in a solution of a second thiolate compound so that molecules of the first thiolate compound in illuminated areas of the monolayer are exchanged for molecules of said second thiolate compound; and a patterned biomolecular composite formed of a substrate which forms a self-assembled thiolate monolayer when immersed in a solution of a thiolate forming compound, a thiolate monolayer deposited on the substrate and composed of patterned areas of first and second thiolate compounds, respectively, the first thiolate compound having an affinity for specifically or nonspecifically adsorbing a biological molecule, and the second thiolate compound having essentially no affinity for the biological molecule, and at least one biological material adsorbed in a corresponding pattern on the patterned areas of the first thiolate compound in the thiolate monolayer.

Polyelectrolyte Derivatization of Microfluidic Devices

T Chip

A microchannel device is provided with a plastic substrate having a microchannel formed therein. Polyelectrolyte multilayers are disposed along selected surfaces of the microchannel. The polyelectrolyte layers comprise alternating net positively charged layers and net negatively charged layers. A microchannel lid has a surface facing the microchannel. In making the microchannel device, selected surfaces of the microchannel are alternatively exposed to solutions comprising positively charged polyelectrolytes and negatively charged polyelectrolytes to form the desired number of polyelectrolyte layers.

Device & Method for Microfluidic Flow Manipulation

Schematic of Mixing Flow

Disclosed is an apparatus and method for the mixing of two microfluidic channels wherein several wells are oriented diagonally across the width of a mixing channel. The device effectively mixes the confluent streams with electrokinetic flow, and to a lesser degree, with pressure driven flow. The device and method may be further adapted to split a pair of confluent streams into two or more streams of equal or non-equal concentrations of reactants. Further, under electrokinetic flow, the surfaces of said wells may be specially coated so that the differing electroosmotic mobility between the surfaces of the wells and the surfaces of the channel may increase the mixing efficiency. The device and method are applicable to the steady state mixing as well as the dynamic application of mixing a plug of reagent with a confluent stream.

Surface Charge Modification within Preformed Polymer Microchannels with Multiple Applications Including Modulating Electroosmotic Flow & Creating Microarrays

A method for modifying and controlling fluid flow in channels formed in substrates. The method involves exposing a portion of a fluid flow channel to light at a fluence which modifies the surface charge of the substrate at the exposure site. The method can be used to immobilize chemical compounds or biological species in the fluid flow channels at the modified surfaces. The method can be used to fabricate or modify microfluidic systems.

Liposome Immunoanalysis by Flow Injection Assay

A method of immunoanalysis combines immobilized immunochemistry with the technique of flow injection analysis, and employs microscopic spherical structures called liposomes, or lipid vesicles, as carriers of detectable reagents. Liposomes are modified on their surface with analytical reagents, and carry in their internal volume a very large number of fluorescent or electroactive molecules. Aspects of this embodiment of the invention include the chemistry for covalent immobilization of antibody fragments in a specified orientation, the use of liposomes in a flow injection analysis system, and the combination of automated sampling and analysis with reusable immunoreactants. Another aspect of the invention involves the non-covalent binding of liposomes to a receptor for use in a homogeneous assay. In another aspect of the invention the intensity of scattered light is quantitated as a measure of liposome aggregation in response to a concentration-dependent immunospecific reaction.

Refreshable Braille Reader

Refreshable Braille Reader: Patent 6,776,619

Apparatus and method for refreshable tactile display are disclosed, the apparatus being preferably embodied as a rotating-wheel refreshable Braille reader. The reader includes a housing having a reading aperture with a rotatable wheel assembly maintained therein so that a display surface of a rotating wheel passes the reading aperture. The wheel has endless rows of openings defined therethrough to the display surface, a pin held in each opening and freely movable therein. Actuators, at least equal in number to the rows of openings but substantially fewer in number than the openings, are held at a static location relative to the wheel for selectively moving pins in the rows so that Braille characters are arrayed at the display surface after passing the static location. Braille characters are thus streamed across the reading aperture of the housing.

Apparatus and Method Utilizing Bi-directional Relative Movement for Refreshable Tactile Display: Patent # 6,692,255

A refreshable Braille reader apparatus and method are disclosed, the apparatus preferably utilizing a rotating cylinder having endless rows of openings defined there through to a display surface with a pin held in each opening and freely movable therein. Static actuators at least equal in number to the rows of openings through the cylinder are maintained at a station adjacent to the surface of the cylinder, and are configured and positioned so that the pins are selectively contactable at either of their ends by different ones of the actuators during cylinder rotation in either forward or reverse direction thereby selectively placing first ends of the pins relative to the surface of the cylinder to allow streaming of Braille text across a display area in either forward or backward order depending upon selected direction of cylinder rotation.

Extended Refreshable Tactile Graphic Array for Scanned Tactile Display

Braille Imaging Device

Apparatus and methods for extended refreshable tactile graphic display are disclosed, the apparatus including an array of pins at a display surface, with pin setting actuators and display surface matrix preferably being separable units. The display matrix is provided by stacked functional layers, functions including temporary pin retention and pin locking.

Refreshable Scanning Tactile Graphic Display for Localized Sensory Stimulation

View of Tactile Display

Pressure-based refreshable scanning tactile graphic display apparatus and methods are disclosed for localized sensory stimulation. The apparatus include a display array having stimulus points embedded in a matrix, an energy source applied at the stimulus points through a modulator, a control unit, and a position sensing and feedback unit or units (such as a mouse-type device or data glove, for example). The energy source is preferably stored and pressurized fluid with application to selected stimulus points (pins, for example) preferably directed at a microvalve array under the control of a computer-based control unit.

 

Microfluidic Platform of Arrayed Switchable Spin-Valve Elements for High-Throughput Sorting & Manipulation of Magnetic Particles & Biomolecules

Arrays of spin-valve elements that can be selectively activated to trap, hold, manipulate and release magnetically tagged biological and chemical particles, including molecules and polymers. The spin-valve elements that can be selectively activated and deactivated by applying a momentary applied magnetic field thereto. The spin valve element array can be used for selectively sorting and transporting magnetic particles one particle at a time within the array. As the magnetically tagged particles are held by the spin-valve elements, application of an auxiliary magnetic field can be used to apply tension or torsion to the held particles or to move, e.g. rotate, the trapped particles. The arrays of spin-valve elements can be used in a variety of applications including drug screening, nucleic acid sequencing, structural control and analysis of RNA/DNA and proteins, medical diagnosis, and magnetic particle susceptibility and size homogenization for other medical applications.

Controlled Vesicle Self-Assembly In Continuous Two Phase Flow Microfluidic Channels

Methods for the formation of liposomes that encapsulate reagents in a continuous 2-phase flow microfluidic network with precision control of size, for example, from 100 nm to 300 nm, by manipulation of liquid flow rates are described. By creating a solvent-aqueous interfacial region in a microfluidic format that is homogenous and controllable on the length scale of a liposome, fine control of liposome size and polydispersity can be achieved.

Imaging Deblurring Method

PET Image Before/After

The present invention relates to a for a singular integral image deblurring comprising a direct procedure for classifying image smoothness and a class of fast, direct methods that recover fine-scale structure using Lipschitz (BESOV) space regularization, singular integrals, and the fast fourier transform.

Micron-Scale Differential Scanning Calorimeter on a Chip

A differential scanning microcalorimeter produced on a silicon chip enables microscopic scanning calorimetry measurements of small samples and thin films. The chip may be fabricated using standard CMOS processes. The microcalorimeter includes a reference zone and a sample zone. The reference and sample zones may be at opposite ends of a suspended platform or may reside on separate platforms. An integrated polysilicon heater provides heat to each zone. A thermopile consisting of a succession of thermocouple junctions generates a voltage representing the temperature difference between the reference and sample zones. Temperature differences between the zones provide information about the chemical reactions and phase transitions that occur in a sample placed in the sample zone.

Procedure for Digital Image Restoration (Continuation in Part)

The image restoration system and method of the present invention is applied to point spread functions p(x,y) which may be described in the Fourier domain as Ρ(.xi.,.eta.)=exp{-Σji=1 λi22)Βi }λi.gtoreq.0, 0<Βi<1, to improve noise performance and permit identification of fine detail. The novel method formulates the image restoration problem as a problem in the partial differential equations describing diffusion phenomena using a new type of a priori constraint. The restored image is obtained by minimizing a quadratic functional incorporating this new constraint. The solution of the minimization problem may be obtained directly by means of fast Fourier transform algorithms. The restoration method may be performed as a sequence of partial restorations as t↓0 wherein the partial restorations become sharper and noisier as t↓0, or as a single full restoration. The sequence of partial restorations may reveal features of the image before such features become obscured by noise and may permit adjustment of the parameters characterizing the blurring functions and constraints.

 

WORKFLOW MANAGEMENT EMPLOYING ROLE-BASED ACCESS CONTROL

A workflow sequence specified by a process definition is managed by a workflow management system which enacts each segment in the order specified by that process definition. Role-based access control (RBAC) is used to define membership of individuals in groups, i.e., to assign individuals to roles, and to then activate the roles with respect to the process at appropriate points in the sequence. Any individual belonging to the active role can perform the next step in the business process. Changes in the duties and responsibilities of individuals as they change job assignments are greatly simplified, as their role memberships are simply reassigned; the workflow process is unaffected.

Cavity Ringdown Spectroscopy System using Differential Heterodyne Detection

Identifies Trace Levels

A novel AC technique in cavity ringdown spectroscopy that permits IXIO-IO absorption sensitivity with microwatt level light power has been developed. Two cavity modes, one probing the empty cavity and the other probing intracavity absorption, are excited simultaneously, but their intensities are temporally out of phase, with one mode decaying and the other rising. Heterodyne detection between the two modes reveals the dynamic time constants associated with the empty cavity and the additional intracavity gas absorption. The method offers a quick comparison between the on-resonance and off-resonance information, a prerequisite to reaching the fundamental shot noise limit. This simple and yet important improvement of cavity ringdown spectroscopy should lead to enhanced performance in a wide range of applications.

 

Silylated Resins & the Synthesis Thereof

A silylated resin suitable for use as an adhesive binder for composites and in sealant and adhesive dental applications is represented by the general formula (I): STR1 in which: R1 is an aliphatic, cycloaliphatic, aryl, hydrocarbon, or fluorocarbon group; R2 is the same as R1 or a different aliphatic, cycloaliphatic, aryl, hydrocarbon, or fluorocarbon group; STR2 M2 is the same as M1 or a different functional or nonfunctional group selected from the group consisting of: STR3 n is 1-3; x is 1-20; and y is 1-20; which comprises the reaction product of the exchange reaction of a hydroxylated, aminated, or carboxylated acrylic resin represented by the general formula (II): STR4 in which: R4 is an aliphatic, cycloaliphatic, aryl, hydrocarbon, or fluorocarbon group with one or more protic functional groups selected from the group consisting of: OH, N--H, and CO2 H R5 is H or CH3; and R6 is H or CH3; with a trialkoxyorganosilane or triacyloxyorganosilane represented by the general formula (III): STR5 in which: R7, R8, and R9 each is: STR6 R10 is an aliphatic, or aryl group which can optionally be substituted with a group from the group of an acrylic group, a methacrylic group, an epoxy group, and a substituted amino, hydroxyl, or carboxylic acid group such as an ester or an amide.

Apparatus & Method for Artificial Weathering

SPHERE

A method and apparatus for irradiating a specimen with a beam of radiation are provided. The method comprises the steps of providing an integrating sphere, a radiation source radiatively communicating with the sphere, and a specimen, the integrating sphere radiatively communicating with the specimen through an aperture in the sphere. The apparatus comprises a radiation source, an integrating sphere in radiative communication with the radiation source, and a specimen holder in radiative communication with the integrating sphere. The disclosed apparatus and method allow the irradiance of a beam of radiation impinging on the specimen to be maintained at a uniform level across the width of the beam to allow quantitative specimen evaluation.

FRICTION AND WEAR RESISTANT COATING FOR TITANIUM AND ITS ALLOYS

For titanium and titanium alloys in tribological applications under bound lubrication conditions, there are employed epoxy coatings adhered to the surface of the titanium or titanium alloy by a titanium oxide primer layer. The anti-wear properties of the epoxy coating can be improved by incorporation of an anti-wear filler such as diamond powder. These coatings improve the friction coefficient and anti-wear properties of the titanium and titanium alloys.

NON-DESTRUCTIVE METHOD FOR DETERMINING THE EXTENT OF CURE OF A POLYMERIZING MATERIAL AND THE SOLIDIFICATION OF A THERMOPLASTIC POLYMER BASED ON WAVELENGTH SHIFT OF FLUORESCENCE

The change in the peak fluorescence wavelength of a small amount of a fluorescent compound, i.e., a fluorophore, which has been dissolved in a polymerizing material or a thermoplastic polymer is used to determine the extent of cure or solidification, respectively. The measured wavelength-shift can either be compared with a previously determined correlation to obtain an absolute value for the extent of cure, or can be utilized to compare or maintain an acceptable extent of cure throughout a manufacturing or a clinical process. Similarly, in the processing of a thermoplastic polymer by injection molding, the measured wavelength shift can either be compared with a previously determined correlation to obtain an absolute value for the temperature of the polymer, or can be utilized to adjust the injection molding cycle so that the mold is opened at the optimum times. The fluorophores used in the method are preferably selected from a class of fluorophores comprising alpha, omega substituted linear alkenes having an electron accepting group attached at the alpha position and an electron donating group attached at the omega position.

High Nitrogen Stainless Steel

Disclosed is a high nitrogen stainless steel alloy and alloy powder comprising chromium (Cr), molybdenum (Mo), manganese (Mn), nickel (Ni), nitrogen (N) and iron (Fe). The composition of the stainless steel alloy and powder comprises between about 27 and about 30% by weight Cr, between about 1.5 and about 4.0% by weight Mo, Mn present and is present in an amount up to 15% by weight, at least about 8% by weight Ni, and about 0.8 to about 0.97% by weight N with the balance being iron. It has been discovered that forming an alloy of this chemistry using nitrogen gas atomization process, followed by a consolidation process, the alloy is less likely to form detrimental ferrite, stable nitride and sigma (.sigma.) phases, without the need for further processing, such as solution treating and quenching. This allows for the formation of stainless steel articles having a thicker cross-section with reduced processing cost.

Apparatus And Methods For Identifying and Comparing Lattice Structures and Determining Lattice Structure Symmetries

A converse transformation matrix generation approach is used either i) to relate a lattice structure of one crystalline material to the lattice structure(s) of one or more other crystalline materials for determining interlattice relationships which allow materials to be identified and classified relative to other materials; or ii) to relate a lattice structure of a material to itself for determining lattice symmetry. In particular, matrices which transform any primitive cell defining a lattice structure either into itself or into another cell defining a second lattice structure to within predetermined maximum tolerances of the cell parameters are generated.

Mixing Liquids & Entrainment Mixing of Vapor into Liquids

Schematic of Mixer

Disclosed is a fluid mixer that mixes liquids while simultaneously promoting rapid mixing entrainment of vapor in the liquid. The device includes a vertical rotor mounted centrally on a base assembly. The rotor comprises a tube which is hollow from an open top end to a bottom closed end, having an external screw thread in a right-side configuration relative from top to bottom and one or more holes located in the sidewall of the tube at the bottom of the hollow portion of the tube, preferably located centrally between two flanking surfaces of the screw thread. The base assembly comprises a stirbar and a supporting disk which contains a ceramic magnet. The base rests on the floor of a containment vessel. A magnetic stirring motor is centrally located sufficiently close to and beneath the containment vessel as to achieve magnetic flux coupling with the base magnet. Operation of the mixer develops a liquid vortex in the liquid phase material. As the speed increases, the external screw threads generate turbulence and draw vapor into the liquid from above the tube and urge the vapor into intimate contact with the turbulent, droplet-forming liquid. A circulation develops causing a vortex to develop. As the speed of circulation increases, the surface of the liquid is lowered until it matches the hole in the sidewall of the tube. The liquid enters the holes in the sidewall of the tube along with entrained vapor, and rises through the liquid in the hollow tube, and exits the open top end.

METHOD FOR CHEMICAL PRECIPITION OF METALLIC SILVER POWDER VIA A TWO SOLUTION TECHNIQUE

A method for the chemical precipitation of metallic silver powder employs a two solution technique in which a solution of a tin salt and a solution a silver salt are mixed in the presence of an inorganic or organic acid, alumina, an anionic surfactant, and a colloid to form a precipitation solution at a temperature and pH suitable to effect the chemical precipitation of silver. Almost 80% by weight of the precipitated powder agglomerate is less than 25 µm in diameter, and the individual powder particles which compose the agglomerate range in size from 0.2 to 2.0 µm. In addition to the favorable size distribution, silver particles precipitated in the presence of a gelatin colloid can be used with a minimal amount of sieving so that little work hardening is imparted to the particles. The powder can be annealed at a temperature of up to 750° C. for two hours in air with minimal sintering, and the acid-assisted hand consolidation of powder produced according to the present technique is capable of producing silver compacts which are nearly 80% dense. Advantageously, a hand consolidated silver compact which comprises the powder of the present invention equals or exceeds the transverse rupture strength, shear strength, creep, toughness, corrosion resistance, microleakage, and wear properties of conventional silver amalgam.

Humidity Chamber for Scanning Stylus Atomic Force Microscope (AFM) with Cantilever Tracking

The present invention provides a novel humidity chamber suitable for use with an atomic force microscope (AFM). The humidity chamber of the present invention employs an intricate geometrical design which can accommodate a scanned-stylus AFM with an optical lever. This geometrical design allows the invention to enclose one or more of the AFM scanner, tip assembly, optical lever detection system, sample and an optical microscope objective lens, without degrading the ability to operate the AFM or the related systems. The invention is comprised of two major pieces: a chamber within which the AFM scanning head assembly is placed, and an integrated sample platform and spring-loaded base-plate that allows samples to be loaded and unloaded without removal of the chamber from the AFM scanning head assembly. The sample platform, which extends up from the base-plate and is inserted into the chamber, can include a magnet that is securely attached to the base. Once the sample platform is positioned inside the chamber, a locking pin can be inserted between the chamber and the bottom portion of the sample platform to secure the sample platform and base-plate. The spring-loaded base allows the z-directional motors of the AFM to be used to position the sample just below the probe prior to scanning, while at the same time providing an essentially air-tight fit between the chamber and the AFM scanning head. An embodiment of the present invention is suitable for use with components that sense and control the relative humidity inside the chamber.

Humidity Chamber for Scanning Stylus Atomic Force Microscope (AFM) with Cantilever Tracking

The present invention provides a novel humidity chamber suitable for use with an atomic force microscope (AFM). The humidity chamber of the present invention employs an intricate geometrical design which can accommodate a scanned-stylus AFM with an optical lever. This geometrical design allows the invention to enclose one or more of the AFM scanner, tip assembly, optical lever detection system, sample and an optical microscope objective lens, without degrading the ability to operate the AFM or the related systems. The invention is comprised of two major pieces: a chamber within which the AFM scanning head assembly is placed, and an integrated sample platform and spring-loaded base-plate that allows samples to be loaded and unloaded without removal of the chamber from the AFM scanning head assembly. The sample platform, which extends up from the base-plate and is inserted into the chamber, can include a magnet that is securely attached to the base. Once the sample platform is positioned inside the chamber, a locking pin can be inserted between the chamber and the bottom portion of the sample platform to secure the sample platform and base-plate. The spring-loaded base allows the z-directional motors of the AFM to be used to position the sample just below the probe prior to scanning, while at the same time providing an essentially air-tight fit between the chamber and the AFM scanning head. An embodiment of the present invention is suitable for use with components that sense and control the relative humidity inside the chamber.

Designed Protein Pores as Components for Biosensors

Method of Stabilization of Functional Nanoscale Pores for Device Applications: Application # 20050191616

A membrane is disclosed made from a compound having a hydrophilic head group, an aliphatic tail group, and a polymerizable functional group. The membrane spans an aperte and may be polymerized. The membrane may be useful for DNA sequencing when the membrane includes an ion channel.

 

Single Molecule Mass Spectrometry in Solution Using a Solitary Nanopore: Docket # 08-003

The invention consists of a means to measure an electrical current passing through a stable nanopore under an applied voltage while partial occlusion of the pore occurs by molecules that reduce the electrical current because the pore's size is commensurate with the molecules'. The pores may be modified to interact selectively with chosen targets. Specific averaging methods are used that, in effect, act as signal averaging of the individual currents and allows these current levels to be assigned to molecules of different sizes. In addition, the time courses of the chemical interactions of the analytes with the pore can be found once the current levels are assigned. The set of current levels together with the time courses provide a novel two-dimensional method of analysis for charged and uncharged molecules in solution.

Zig-Zag Shape Biased Anisotropic Magneto-Resistive Sensor

ZigZag Sensor

A magnetoresistive sensing apparatus is disclosed, comprising a magnetic film having a zig-zag shaped structure, a central axis, and a magnetization associated with the magnetic film, wherein the zig-zag shaped structure biases the magnetization direction alternately at positive and negative angles thereof, thereby permitting the magnetoresistive sensing apparatus to be sensitive to a magnetic field parallel to the axis of the magnetoresistive sensing apparatus and insensitive to magnetic fields perpendicular to the axis.

Parallel X-Ray Nanotomography

A parallel nanotomography imaging system is provided having an x-ray source, which is preferably a laser-based x-ray source that generates x-rays that are collected using a collector optic and are received in a composite objective assembly. The composite objective assembly includes plural micro-objectives, each imaging the target. The x-ray image is received by an x-ray image formation and acquisition apparatus, and processed and/or displayed.

Improved Optical Image Processing Using Squeezed Light

Montage of actual quantum images

The phase-sensitive amplifier implementing our chi(3) 4-wave mixing source would be an enabling technology for image processing. A number of efforts in the newly labeled field of "quantum imaging" allow for better detection sensitivity or better image resolution if one is able to apply "squeezed" light with a broad range of spatial modes and frequencies. Such nonclassical light (a quantum mechanical treatment of the electromagnetic field is required) has proved difficult to produce in the past. Our present source is competitive with, but not quite as good as, the best available chi(2)-based systems in the degree of squeezing we have obtained. On the other hand, it is clearly superior to them in its ability to produce squeezed light in many spatial modes of the field. It will allow "noiseless image amplification" and "super-resolution" techniques to be employed in applications well beyond what has been demonstrated with chi(2) media. It should have uses in microscopy and image recovery from weak image data. In addition, a diode-based source should demonstrate squeezing at very low detection frequencies. This should allow the production of a very stable interferometer using our 4-wave mixing source. Such an interferometer would be an excellent detector for highly sensitive chemical detection by photothermal spectroscopy.

IRIS Digester-Evaporator Interface

A digester-evaporator interface for partially digesting a sample mixed in a solvent with an acid and for evaporating the solvent and the acid after partial digestion, said digester-evaporator including a digester portion and an evaporator portion. The digester includes at least one reaction coil having an input and an output, said at least one reaction coil adapted for receiving at its input a flow of a sample in a solvent and an acid suitable for partial digestion of the sample so as to partially mix and begin partial digestion in the reaction coil; a heating element arranged along a portion of the reaction coil; at least a portion of the reaction coil proximate to its output being preheated by the heating element to a degree sufficient to convert a partially digested sample into vapor; a collector spoon with carrier water for collecting sample vapor; and an evaporator portion including an evaporation chamber including a cover with a first opening having the substantially vertically-oriented tube extending from the cover, and the evaporation chamber includes an axial opening longitudinally arranged therein, and the evaporation chamber adapted to contain fluid at a bottom portion. The collector spoon is arranged in the top of the substantially vertically-oriented tube after a vapor sample has been collected from the digester portion, and a gas supply tube for supplying a preheated gas provided in a top of the substantially vertically-oriented tube and in the axial opening of the evaporation chamber so as to create a cyclonic gas flow into the chamber and carry the sample to a container area in a bottom portion of the chamber. The interface is especially useful in the separation and quantification of selenium containing proteins.

Microfluidic Passive Sorting & Storage of Liquid Plugs using Capillary Force

View of channels for sorting and storage

The invention consists in a microfluidic device that without any actuator (no valves) is capable of sorting liquid plugs chronologically and store them in pockets. To do so, it takes advantage of the fact that capillary forces are greater on small hydrophobic channels than in large hydrophobic microchannels.

Fabrication Method of Topographically Modulated Microstructures using Pattern Homogenization with UV Light

Schematic of process

A method for microfabrication of a microfluidic device having sub-millimeter three dimensional relief structures is disclosed. In this method, homogeneous surfaces, which do not exhibit apparent pixel geometry, emerge from the interaction of the overlapping of diffracted light under opaque pixels and the nonlinear polymerization properties of the photoresist material. The method requires a single photolithographic step and allows for the fabrication of microstructures over large areas (centimeters) with topographic modulation of features smaller than 100 micrometers. The method generates topography that is useful in a broad range of microfluidic applications.

SIMPLE MATRIX METHOD FOR STRAY-LIGHT CORRECTION IN IMAGING INSTRUMENTS

Adjusting Stray Light for Image Enhancement

This method uses stray light correction matrix derived from point spread functions (PSF) of an instrument. The correction of stray light errors is simply a matrix multiplication to the measured raw image. The correction is fast and can be used for correction of stray light errors in any types of measured images.

Versatile, Simple Microfluidics for Field Portable Applications

Fluidic Temperature Gradient Focusing: Docket # 01-029


The present invention concerns a method and device for concentrating and separating ionic species in solution within fluid conduits which include channels, microchannels and capillary tubes. The concentration is achieved by balancing the electrophoretic velocity of an analyte against the bulk flow of solution in the presence of a temperature gradient. Unlike previous methods, such as salt bridges or electrodes, which severely limit the type of analyte that can be concentrated, this invention can be adapted for use with any charged analyte, including fluorescent dyes, amino acids, proteins, DNA, cells and particles. Additionally, the use of a temperature gradient prevents the need for an electric field gradient which tends to be difficult to construct and require a control of voltage on an additional electrode. Finally, this invention can be used to achieve higher degrees of sample concentration, which can provide up to or, in some instances, exceed a 10,000-fold concentration of a dilute analyte.

 

Mixing Reactions by Temperature Gradient Focusing: Docket # 01-029CIP1


A method is provided for observing mixing interactions and reactions of two materials in a fluid. The method in one form provides for concentrating by balancing electrophoretic velocities of a material against the bulk flow of fluid in the presence of a temperature gradient. Using an appropriate fluid, the temperature gradient can generate a corresponding gradient in the electrophoretic velocity of the material so that the electrophoretic and bulk velocities sum to zero at a unique position and the material will be focused at that position. A second material can then be introduced into the fluid and allowed to move through and interact with the focused band of the first material. Products of the interaction can then be detected as they are focused at a different position along the gradient. The method can be adapted to study the temperature dependence of the molecular interaction.

 

Chiral Temperature Gradient Focusing: Docket # 01-029CIP2


The present invention combines the high resolution of chiral capillary electrophoresis with the high concentration enhancement and low detection limits of temperature gradient focusing. The temperature gradient focusing allows for higher degrees of sample concentration, such as more than a 10,000 fold concentration of a dilute material, when compared with any prior single sample preconcentration method. Additionally, the electrophoretic velocity gradient is formed in response to the temperature gradient without the need for externally manipulated voltages or complicated and difficult to fabricate semi-permeable structures. Finally, the present invention is able to separate stereoisomers of a material which have different affinities for the additive. Essentially, with the addition of a chiral additive, the present focusing method allows for simultaneous separation and concentration of materials that cannot be separated using temperature gradient focusing based purely upon their electrophoretic mobilities. One benefit of being able to separate chiral stereoisomers is that many drugs and drug candidates are chiral and in most cases, one stereoisomer is more desired for drug use than the other. In some instances, one stereoisomer is a beneficial drug, whereas the other results in adverse side effects.

 

 

Adaptable Anomaly Detector

Embodiments of the present invention provide an inexpensive and fast pulse characterization platform capable of real time operation, suitable for acquisition of single-photon data. Embodiments of the present invention include both a digital multi-channel data acquisition instrument and an analog pulse acquisition instrument suitable for a wide range of applications in physics laboratories. An FPGA performs multi-channel acquisition in real time, time stamps single events and determines if the events fit a predetermined signature, which causes the events to be categorized as a coincidence. The indications of coincidences are then communicated to a host computer for further processing as desired.

Length Separation of Carbon Nanotubes by Centrifugation in a Dense Liquid

Sorting nanotubes

The invention is the exploitation of a difference in scaling with length of the hydrodynaiic drag on a nanotube, and the buoyancy force of the same nanotube to sort the nanotubes by their length. The buoyancy is generated by using a commercial density medium, a surfactant, such as sodium deoxycholate, that forms a miceller shell around the nanotube. The surfactat shell acts both to keep the nanotube individually dispersed, and as a buoyant volume with an effective density different from the surrounding medium.

DIMENSIONAL REFERENCE FOR TOMOGRAPHY

NIST Phantom

The invention is a system for obtaining a dimensional reference within a CT image. The system consists of a set of 3 spheres (for 2D; aID version would use 2 spheres; a 3D version would require 4 spheres) with a precise spacing. The material of the spheres is chosen to have x-ray absorption properties somewhat near bone. (In terms of Hounsfield units, about +500 HU to +1200 HU is useful; on this scale, bone is +1000 HU, water is 0 HU, and air is -1000 HU. Said otherwise, the attenuation length of the material should be about 2/3 to 40% of water.) The spheres need to be precisely round on the scale of a CT pixel which is typically 0.33 mm. We have found reasonably priced commercial spheres with tolerances of 0.0254 mm.

Gradient Elution Electrophoresis

GEMBE Device

Gradient elution moving boundary electrophoresis (GEMBE) is a recently described technique for electrophoretic separations in short (1-3 cm) capillaries or microchannels. With GEMBE, the electrophoretic migration of analytes is opposed by a bulk counterflow of separation buffer through the separation channel. The counterflow velocity is varied over the course of a separation so that analytes with different electrophoretic mobilities enter the separation channel at different times and are detected as moving boundary, stepwise increases in the detector response. The infinite analysis is technology is an implementation of the GEMBE technique in which a very short (0.03-3.5 mm) capillary or microchannel is used as both the separation channel and a conductivity detection cell. Because the channel is so short, only a single moving boundary “step” is present in the channel at any given time, and the measured current through the channel can therefore be used to give a signal comparable to what is normally generated by more complicated detector arrangements.

HLPR Chair: Home Lift Position & Rehabilitation Apparatus

On HLPR Chair 2, the "seat slide with passive extend" design includes a pair of thin, passive, linear slides beneath the seat and a set of springs that allow both the seat and footrest to slide with respect to the rotate seat retract U-plate. This allows a standard size seat to be attached to HLPR Chair 2. The original seat rotate design on HLPR Chair 1 allowed only a seat as long as the seat lift actuator. Hence, a short seat was required to allow only the seat to completely rotate up out of the way of the patients' bottom to access seats, beds and toilets. The HLPR Chair 2 seat slide design wil now allow larger and/or less agile patients to use the HLPR Chair.

HARVESTING OF PROCESSED CARBON NANOTUBES

A method of harvesting carbon nanotubes (CNTs) is provided. According to this method, CNT bundles, comprising CNTs associated with metallic catalysts and having amorphous carbon coatings are agitated in an aqueous liquid containing a dispersant with free-flowing grit particles to disassociate the CNTs from the metallic catalysts, remove the amorphous carbon of the amorphous carbon coatings and shorten the CNTs via shearing.

Flexible Memory Devices

Flexible Memory Devices

We report the fabrication and characterization of a two-terminal rewriteable nonvolatile flexible memory device that consists of a titanium dioxide layer, formed by using a room-temperature processed sol gel, with aluminum contacts on an inexpensive commercially-available flexible polymer sheet (an overhead transparency). This device shows a nonvolatile memory behavior with on/off ratios up to 1000:1, which can be cycled between write, read, and erase states by applying voltages with magnitudes of less than 10 V. The devices have the potential to meet the needs of flexible, rewritable memory while providing the advantages of simplified room temperature fabrication and relatively low drive voltage operation.

Non-Linear Raman Image Contrast Enhancement

microspectrometer design

The invention disclosed herein is a novel and simple method of suppressing non-resonant background (NRB) in broadband coherent anti-Stokes Raman scattering (CARS) microscopy to improve sensitivity and signal-to-noise ratio.

RECIRCULATING TEMPERATURE WAVE FOCUSING CHROMATOGRAPHY

The invention is a device and method for performing chromatography in an equilibrium gradient focusing mode rather than a transient, migration-based mode. The present invention utilizes temperature gradient focusing (TGF) for a wide array of chromatography applications.  The invention is based upon a discovery that by recirculating a moving temperature wave through a system preferably comprising two or more chromatography columns, analytes accumulate at select locations on the temperature wave.  Thus, analyte peaks become narrower and more intense as the temperature wave is circulated about the system.  The resulting focusing of analyte peaks enables higher resolution and lower detection limits for the system.

NANOFABRICATION PROCESS AND NANODEVICE [3D Nanofabrication Process & Nanoparticle Sorting Device]

A nanofabrication Process for use with a photoresist that is disposed on a substrate includes the steps of exposing the photoresist to a grayscale radiation pattern, developing the photoresist to remove the irradiated portions and form a patterned topography having a plurality of nanoscale critical dimensions, and selectively etching the photoresist and the substrate to transfer a corresponding topography having a plurality of nanoscale critical dimensions into the substrate. 

 

Chemical Modification of Substrates by Photo-Ablation in Different Local Atmospheres & Chemical Environments

A method for simultaneously forming microstructures in substrates and altering their chemical character. The method involves exposing a surface portion of a substrate to light source, which is strong enough and of the appropriate wavelength to cause ablation of the substrate. The ablation of the substrate is controlled to form microstructures therein, such as channels. The ablation is conducted under a chemical atmosphere, which causes a change in the chemical functionality of the microstructures. The chemical atmosphere can be a gas, liquid or solid that is provided on the substrate surface. The method can be used to fabricate or modify microfluidic systems.

Nanometrology for Particles, Lines, Arrays and Overlays

An optical method with the potential to discriminate between changes in the physical parameters of a target as represented in the properties of light scattered off of the target. For example, whether a change in the scattered light is due to a change in the height or width of a line.

The Microfluidic Palette: Generation of Multiple Chemical Gradients within a Microfluidic Chamber

The NIST microfluidic palette

The invention consists in a microfluidic device that generates multiple chemical gradients simultaneously within a microfluidic chamber. The chemical gradients are generated without convection, only by diffusion, and they can be maintained over long periods of time, or be modified dynamically.

Description of the microfluidic device:

The device consists of a main microfluidic chamber where there is no convection (no flow movement) and where mixing is done by diffusion. The chamber is accessed by "convection-diffusion units". A convection-diffusion unit consists of a microchannel that has matched flow at its inlet and outlet; thus, even if the microchannel has an opening to the microfluidic chamber, all the liquid that is introduced through the inlet has to come out through the outlet (conservation of mass) making it impossible to get into the chamber except by diffusion. If the inlet and outlet of each convection-diffusion unit were not exactly matched, difference in pressure among microchannels would generate convection through the chamber ruining the diffusion-only premise inside the microfluidic chamber.

The convection-diffusion units decouple convection in the microchannels from diffusion in the chamber. Therefore, if a solution of a drug is introduced through inlet 1 and retrieved through outlet 1, the concentration of this drug at the opening 1 to the chamber will be the same as at the channel. If only buffer flows through channels 2 and 3, the concentration of the drug at the openings 2 and 3 necessarily will be zero. Thus, in the microfluidic chamber, opening 1 works as a diffusive source of the drug, while opening 2 and 3 work as sinks, and all the space in between (after some transient time) will have a static gradient in concentration of the drug.

FREQUENCY COMB CAVITY ENHANCED SPECTROSCOPY

Comb Spectroscopy

We invent and demonstrate a qualitatively new form of cavity ringdown
spectroscopy utilizing a broad bandwidth optical frequency comb coherently
coupled to a high finesse optical cavity inside which molecular samples are located.
125,000 optical comb components, each coupled into a specific longitudinal cavity
mode, undergo ring down decays when the cavity input is shut off This provides
sensitive intracavity absOlption information simultaneously available across 100
nm in the visible and near IR spectral region. By placing various atomic and
molecular species (Ar, C2H2, O2, H20, NH3) inside the cavity, we demonstrate realtime,
quantitative measurements of the trace presence, transition strengths and
linewidths, and population redistributions due to collisions and temperature
changes. This novel capability to sensitively and quantitatively monitor multispecies
molecular spectra over a large optical bandwidth in real-time provides a
new spectroscopic paradigm for studying molecular vibrational dynamics, chemical
reactions, and trace analysis.

Covalently Immobilized Fluorinated Carboxylic Acid Stationary Phase for Liquid Chromatography

A stationary phase for a liquid chromatography and process for making is provided. The stationary phase material may have a modified base substrate and a fluorinated carboxylic acid covalently bonded thereto through an amide or ester bond. The stationary phase may have a substantially consistent shape selectivity characteristic with an .alpha..sub.TBN/BaP of less than 1 within a temperature range of at least 10-70.degree. C. Advantageously, a fluorinated stationary phase has a shape selectivity characteristic exhibited with an .alpha..sub.TBN/BaP of less than 1 with a mobile phase having up to at least 30% water. A process for making the stationary involves mixing a substrate material or fluorinated carboxylic acid with a reactive alkylsilane linker and at least one organic solvent to form a first solution. The other of the substrate material or fluorinated carboxylic acid is then added to the first solution, or to a product separated from the first solution, to form a second solution. The second solution is reacted to form the stationary phase.

Novel, Anti-bacterial Monomers, Oligomers and Polymers for Dental and Biomedical Applications

Polymers with quaternary ammonium functional groups in their molecular structures constitute an important class of biocidal materials. Because of the widespread incidence of dental caries there is a need for effective anti-bacterial polymeric dental and biomedical materials, e.g., restorations, adhesives, sealants, endodontic materials, denture and maxillofacial materials, and bone cements. For example, a major cause for the clinical failure of composite restorations is bacterial infiltration at the filling-tooth interface, which leads to secondary or recurrent caries and requires the replacement of the filling and removal of the carious tooth structure. One approach to prevent the occurrence of recurrent caries is to use polymeric materials with anti-microbial properties. In this research it is demonstrated that the classical, facile Menschutkin reaction can be adapted
to the synthesis of multi-functional, thermosetting monomers and resins that have one or more quaternary ammonium groups in their chemical structures.

MICROPATTERNING OF BIOLOGICAL MOLECULES USING LASER ABLATION

The advent of micro-lithography techniques into the study of cell biology have greatly increased our understanding of how cellular functioning is in part regulated by the interaction of cells with the extracellular matrix (ECM). Currently many techniques have used micro-contact patterning (MCP) to apply ECM proteins in distinct localized patterns. These techniques require the fabrication of silicone-based stamps to either “ink” proteins directly or indirectly onto a gold coated surface, limiting the user to a specified stamp shape and size.

 

To bypass the necessity of a physical stamp we have devised a technique to generate submicron sized spots using a tunable multi-photon laser coupled to a confocal microscope to photo ablate hydrophilic poly vinyl alcohol (PVA) hydro gels and self assembled monolayers. Through controlled photo ablation, PVA layers are locally removed allowing deposition of ECM proteins into distinct patterns. By using a software-controlled region of interest (ROI) function, we are able to precisely control patterns, generating up to several hundred within 30 seconds. The use of ROI's produces a "virtual mask" that can be created in any shape or pattern and is easily modified. Unlike MCP techniques, micro photo ablation (MPA) allows live cell imaging of multiple

fluorophores and is possible even with total internal reflection fluorescence (TIRF) microscopy. In addition, MPA allows kinetic quantification of ECM-cell interactions. This technique uses a self-assembled monolayer (SAMs) model for application together with localized photo ablation allows the versatility to create protein spots of any size or shape easily on the same cover slip. Furthermore, this process can be repeated multiple times to directly conjugate different proteins to the same local region allowing the investigation of how single cells probe their surroundings to discern different ECM proteins.

AN ATOMIC MAGNETOMETER AND METHOD OF SENSING MAGNETIC FIELDS

Schematic

A magnetometer and method of use is presently disclosed.  The magnetometer has at least one sensor void of extraneous metallic components, electrical contacts and electrically conducting pathways.  The sensor contains an active material vapor, such as an alkali vapor, that alters at least one measurable parameter of light passing there through, when in a magnetic field.  The sensor may have an absorptive material configured to absorb laser light and thereby activate or heat the active material vapor.   

Compact Atomic Magnetometer and Gyroscope Based on a Diverging Laser Beam

An atomic magnetometer that simultaneously achieves high sensitivity, simple fabrication and small size. This design is based on a diverging (or converging) beam of light (in a single spatial optical mode) that passes through an alkali atom vapor cell and that contains a distribution of beam propagation vectors. The existence of more than one propagation direction permits longitudinal optical pumping of the atomic system and simultaneous detection of the transverse atomic polarization. The design could be implemented with a micromachined alkali vapor cell and light from a single semiconductor laser. A small modification to the cell contents and excitation geometry allows for use as a gyroscope.

Integrated Microchip Incorporating Atomic Magnetometers and Microfluidic Channels for Detection of NMR and MRI

microchip with atomic magnetometer and microfluidic channel

A microfluidic chip incorporating an alkali vapor cell and microfluidic channel is described, which can be used to detect the nuclear magnetism of a polarized sample of nuclei in a fluid.  Small magnetic fields in the vicinity of the vapor cell can be measured by optically polarizing and probing the spin precession in said small magnetic field.  This can then be used to detect the magnetic field due to the sample of nuclei in the adjacent microfluidic channel. The nuclear magnetism in the microfluidic channel can be modulated by applying an appropriate series of radio or audio frequency pulses upstream from the microfluidic chip to yield a sensitive means of detecting nuclear magnetic resonance and magnetic resonance imaging.

Anti-HER2 IgY antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast cancer cells

Single-walled nanotubes--cylinders of carbon about a nanometer in diameter--have been highly touted for potential applications such as ultrastrong fibers, electrical wires in molecular devices, or hydrogen storage components for fuel cells. Thanks to a new development by researchers at the National Institute of Standards and Technology (NIST) and five partners, you can add one more application to the list: detection and destruction of an aggressive form of breast cancer.

Glycoprotein – Colloidal Particle Conjugates

A method of characterizing glycans attached to glycoproteins is provided herein.  The method comprises a first step of immobilizing the glycoproteins on colloidal particles forming glycoprotein/colloidal particles.  The glycans on the glycooproteins may then be identified by either binding the glycoprotein/colloidal particles with one or more binding agents and assessing the aggregation of the glycoprotein/colloidal particles or by cleaving glycans from the glycoprotein/colloidal particles with a cleaving agent and analyzing the glycans.

 

Microfluidic Apparatus to Control Liposome Formation

An apparatus to create a homogenous liposome population without post-processing using laminar flow/diffusive mixing, and for reducing waste discharge of the therapeutic or compound to be encapsulated and delivered by the liposomes.

FLUID DELIVERY SYSTEM

A fluid delivery system is described which provides stable flow rates over a range of different flow rates and while multiple fluids are being concurrently delivered.  The delivery system includes one or more reservoirs each containing a respective fluid to be transferred.  The reservoir(s) are positioned within a secondary fluid selected such that the reservoir(s) and their contents, i.e. the fluids to be transferred, float within the secondary fluid.  One end of a flow conduit is submerged in each fluid to be transferred.  A pressure differential is then induced in the flow conduit whereby fluid flow therin occurs.

HIGHLY SENSITIVE OXYGEN SENSOR FOR CELL CULTURE

An oxygen sensor comprising an oxygen sensing compound and configured to substantially mitigate leaching of the oxygen sensing compound from the oxygen sensor to an outer surface thereof is provided.  The oxygen sensor may comprise one or more layers.  A first portion of the oxygen sensor is configured to be permeable to gas and comprises an oxygen sensing material.  A second portion is disposed with or on the first portion and is configured to be permeable to gas and substantially impermeable to the oxygen sensing material.

Versatile, Simple Microfluidics for Field Portable Applications (Continuation-in-part #1 U.S. patent)

Mixing Reactions by Temperature Gradient Focusing: Docket # 01-029CIP1


A method is provided for observing mixing interactions and reactions of two materials in a fluid. The method in one form provides for concentrating by balancing electrophoretic velocities of a material against the bulk flow of fluid in the presence of a temperature gradient. Using an appropriate fluid, the temperature gradient can generate a corresponding gradient in the electrophoretic velocity of the material so that the electrophoretic and bulk velocities sum to zero at a unique position and the material will be focused at that position. A second material can then be introduced into the fluid and allowed to move through and interact with the focused band of the first material. Products of the interaction can then be detected as they are focused at a different position along the gradient. The method can be adapted to study the temperature dependence of the molecular interaction.

Fluidic Temperature Gradient Focusing: Docket # 01-029


The present invention concerns a method and device for concentrating and separating ionic species in solution within fluid conduits which include channels, microchannels and capillary tubes. The concentration is achieved by balancing the electrophoretic velocity of an analyte against the bulk flow of solution in the presence of a temperature gradient. Unlike previous methods, such as salt bridges or electrodes, which severely limit the type of analyte that can be concentrated, this invention can be adapted for use with any charged analyte, including fluorescent dyes, amino acids, proteins, DNA, cells and particles. Additionally, the use of a temperature gradient prevents the need for an electric field gradient which tends to be difficult to construct and require a control of voltage on an additional electrode. Finally, this invention can be used to achieve higher degrees of sample concentration, which can provide up to or, in some instances, exceed a 10,000-fold concentration of a dilute analyte.

 

Chiral Temperature Gradient Focusing: Docket # 01-029CIP2


The present invention combines the high resolution of chiral capillary electrophoresis with the high concentration enhancement and low detection limits of temperature gradient focusing. The temperature gradient focusing allows for higher degrees of sample concentration, such as more than a 10,000 fold concentration of a dilute material, when compared with any prior single sample preconcentration method. Additionally, the electrophoretic velocity gradient is formed in response to the temperature gradient without the need for externally manipulated voltages or complicated and difficult to fabricate semi-permeable structures. Finally, the present invention is able to separate stereoisomers of a material which have different affinities for the additive. Essentially, with the addition of a chiral additive, the present focusing method allows for simultaneous separation and concentration of materials that cannot be separated using temperature gradient focusing based purely upon their electrophoretic mobilities. One benefit of being able to separate chiral stereoisomers is that many drugs and drug candidates are chiral and in most cases, one stereoisomer is more desired for drug use than the other. In some instances, one stereoisomer is a beneficial drug, whereas the other results in adverse side effects.

 

 

 

Versatile, Simple Microfluidics for Field Portable Applications (Continuation-in-part #2 U.S. patent)

Chiral Temperature Gradient Focusing: Docket # 01-029CIP2


The present invention combines the high resolution of chiral capillary electrophoresis with the high concentration enhancement and low detection limits of temperature gradient focusing. The temperature gradient focusing allows for higher degrees of sample concentration, such as more than a 10,000 fold concentration of a dilute material, when compared with any prior single sample preconcentration method. Additionally, the electrophoretic velocity gradient is formed in response to the temperature gradient without the need for externally manipulated voltages or complicated and difficult to fabricate semi-permeable structures. Finally, the present invention is able to separate stereoisomers of a material which have different affinities for the additive. Essentially, with the addition of a chiral additive, the present focusing method allows for simultaneous separation and concentration of materials that cannot be separated using temperature gradient focusing based purely upon their electrophoretic mobilities. One benefit of being able to separate chiral stereoisomers is that many drugs and drug candidates are chiral and in most cases, one stereoisomer is more desired for drug use than the other. In some instances, one stereoisomer is a beneficial drug, whereas the other results in adverse side effects.

Fluidic Temperature Gradient Focusing: Docket # 01-029


The present invention concerns a method and device for concentrating and separating ionic species in solution within fluid conduits which include channels, microchannels and capillary tubes. The concentration is achieved by balancing the electrophoretic velocity of an analyte against the bulk flow of solution in the presence of a temperature gradient. Unlike previous methods, such as salt bridges or electrodes, which severely limit the type of analyte that can be concentrated, this invention can be adapted for use with any charged analyte, including fluorescent dyes, amino acids, proteins, DNA, cells and particles. Additionally, the use of a temperature gradient prevents the need for an electric field gradient which tends to be difficult to construct and require a control of voltage on an additional electrode. Finally, this invention can be used to achieve higher degrees of sample concentration, which can provide up to or, in some instances, exceed a 10,000-fold concentration of a dilute analyte.

 

Mixing Reactions by Temperature Gradient Focusing: Docket # 01-029CIP1


A method is provided for observing mixing interactions and reactions of two materials in a fluid. The method in one form provides for concentrating by balancing electrophoretic velocities of a material against the bulk flow of fluid in the presence of a temperature gradient. Using an appropriate fluid, the temperature gradient can generate a corresponding gradient in the electrophoretic velocity of the material so that the electrophoretic and bulk velocities sum to zero at a unique position and the material will be focused at that position. A second material can then be introduced into the fluid and allowed to move through and interact with the focused band of the first material. Products of the interaction can then be detected as they are focused at a different position along the gradient. The method can be adapted to study the temperature dependence of the molecular interaction.

Device & Method for Microfluidic Flow Manipulation (Continuation Patent)

Disclosed is an apparatus and method for the mixing of two microfluidic channels wherein several wells are oriented diagonally across the width of a mixing channel. The device effectively mixes the confluent streams with electrokinetic flow, and to a lesser degree, with pressure driven flow. The device and method may be further adapted to split a pair of confluent streams into two or more streams of equal or non-equal concentrations of reactants. Further, under electrokinetic flow, the surfaces of said wells may be specially coated so that the differing electroosmotic mobility between the surfaces of the wells and the surfaces of the channel may increase the mixing efficiency. The device and method are applicable to the steady state mixing as well as the dynamic application of mixing a plug of reagent with a confluent stream.

Gradient Elution Electrophoresis (Continuation-in-part Patent Application)

Gradient elution moving boundary electrophoresis (GEMBE) is a recently described technique for electrophoretic separations in short (1-3 cm) capillaries or microchannels. With GEMBE, the electrophoretic migration of analytes is opposed by a bulk counterflow of separation buffer through the separation channel. The counterflow velocity is varied over the course of a separation so that analytes with different electrophoretic mobilities enter the separation channel at different times and are detected as moving boundary, stepwise increases in the detector response. The infinite analysis is technology is an implementation of the GEMBE technique in which a very short (0.03-3.5 mm) capillary or microchannel is used as both the separation channel and a conductivity detection cell. Because the channel is so short, only a single moving boundary “step” is present in the channel at any given time, and the measured current through the channel can therefore be used to give a signal comparable to what is normally generated by more complicated detector arrangements.

Microfluidic Platform of Arrayed Switchable Spin-Valve Elements for High-Throughput Sorting & Manipulation of Magnetic Particles & Biomolecules (Divisional Patent Application)

Arrays of spin-valve elements that can be selectively activated to trap, hold, manipulate and release magnetically tagged biological and chemical particles, including molecules and polymers. The spin-valve elements that can be selectively activated and deactivated by applying a momentary applied magnetic field thereto. The spin valve element array can be used for selectively sorting and transporting magnetic particles one particle at a time within the array. As the magnetically tagged particles are held by the spin-valve elements, application of an auxiliary magnetic field can be used to apply tension or torsion to the held particles or to move, e.g. rotate, the trapped particles. The arrays of spin-valve elements can be used in a variety of applications including drug screening, nucleic acid sequencing, structural control and analysis of RNA/DNA and proteins, medical diagnosis, and magnetic particle susceptibility and size homogenization for other medical applications.

Refreshable Braille Reader: Apparatus & Method Utilizing Bi-Directional Relative Movement (Continuation-in-part Patent)

Apparatus and Method Utilizing Bi-directional Relative Movement for Refreshable Tactile Display: Patent # 6,692,255

A refreshable Braille reader apparatus and method are disclosed, the apparatus preferably utilizing a rotating cylinder having endless rows of openings defined there through to a display surface with a pin held in each opening and freely movable therein. Static actuators at least equal in number to the rows of openings through the cylinder are maintained at a station adjacent to the surface of the cylinder, and are configured and positioned so that the pins are selectively contactable at either of their ends by different ones of the actuators during cylinder rotation in either forward or reverse direction thereby selectively placing first ends of the pins relative to the surface of the cylinder to allow streaming of Braille text across a display area in either forward or backward order depending upon selected direction of cylinder rotation.

Micellar Gradient Focusing

A method and device are provided for affinity gradient focusing for directing at least one analyte in a solution containing a pseudostationary phase and located in a channel such as a capillary or a microchannel. The method includes establishing a steady-state spatial gradient in a retention factor of the pseudostationary phase for the at least one analyte. The analyte is caused to be moved within the channel whereby the concentration of the at least one analyte changes at one or more positions along the gradient. The pseudostationary phase is charged and the analyte is either neutral or charged or alternatively, the pseudostationary phase is neutral and the analyte is charged. The device may include a fluid channel, a pseudostationary phase having a retention factor gradient, an electrical current source and a pump system for establishing the bulk flow in the solution in the channel.

CHIRPED-PULSE FOURIER TRANSFORM SPECTROSCOPY AT MILLIMETER AND THZ FREQUENCIES

A broadband trace gas sensor based on chirp-pulse terahertz spectroscopy. The advent of developed solid-state phase-coherent sources and sensitive heterodyne detectors for the terahertz frequency range has made it possible to generate and detect precise arbitrary waveforms at THz frequencies with ultra-low phase noise. In order to maximize sensitivity, the sample gas is first polarized using  sub-microsec chirped THz pulses generated in an amplifier/multiplier chain (AMC) also referred to as an active multiplier chain. The absorpiton signals and the free inductive decays (FIDs) are then detected on a sub-microsec time scale using a sub-harmonic heterodyne reciever. This approach allows for a rapid broadband multi-component sensing with low parts in 10 degree (ppb) sensitivies and spectral frequency accuracy of <20 kHz in real-time. Such a system can be configured into a portable, easy to use, and relatively inexpensive sensing platofrm. This technique will be applicable to any THz frequency range (including the millimeter range below 200 GHz) where phase coherent souces are available. Currently, AMC sources and sub-harmonic heterodyne detectors (mixers) are commerically available up to about 2 THz.

APPARATUS AND METHOD FOR PROUDUCING AND USING MULTIPLE ELECTRON BEAMS WITH QUANTIZED ORBITAL ANGULAR MOMENTUM IN AN ELECTRON MICROSCOPE

The following is a description of an apparatus and method for producing and applying electron beams imprinted with phase vortices in an electron microscope. These beams have helical electron wavefronts, and each electron carries and quantized amount of orbital angular momentum and an associated magnetic dipole. Helicity-dependent absorption and scattering of electrons in a specimen, referred to here as electron helical dichroism, can be used to provide new types of information about the sample, but this requires a rapid way to switch the helicty of the probing beam. The invention described here produces multiple beams with different helicities that can be rapidly switched between.