- Chemistry Find out what NIST is currently working on in Chemistry.
Jack Pevenstein
Technology Partnership Office
301-975-5519
nisttech@nist.gov
100 Bureau Drive, M/S 2200
Gaithersburg, MD, 20899
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.
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.
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.
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.
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.
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.
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.
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.
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.
A design and fabrication methodology, for silicon micromachined micro-hotplates which are manufactured using commercial CMOS foundries techniques with additional post-fabrication processing. The micro-hotplates are adaptable for a host of applications. The methodology for the fabrication of the micro-hotplates is based on commercial CMOS compatible micromachining techniques. The novel aspects of the micro-hotplates are in the design, choice and layout of the materials layers, and the applications for the devices. The micro-hotplates have advantages over other similar devices in the manufacture by a standard CMOS process which include low-cost and easy integration of VLSI circuits for drive, communication, and control. The micro-hotplates can be easily incorporated into arrays of micro-hotplates each with individualized circuits for control and sensing for independent operation.
A system is disclosed for performing x-ray photoelectron emission analysis which uses a collimated x-ray beam directed to an optically polished sample at a small grazing angle of incidence, a fixed sample/electron spectrometer geometry, and an x-ray detector for detecting x-rays reflected off of the sample. With the system, an enhancement of the x-ray field at layer interfaces in a multilayer sample can take place. The system permits depth profiling of an over layer on a substrate, such as a metal or metal oxide on a metal substrate. The enhancement permits absolute calibration of depth-dependence. The system reduces lineshape distortions due to inelastic electron scattering of exiting photoelectrons and eliminates energy distortions due to changes in the sample position relative to the focal point of the electron spectrometer.
Spectroscopic materials analysis wherein a sample under test is bombarded by electrons in a scanning electron microscope to produce an x-ray emission collected over a large solid angle by a polycapillary lens and focused onto the surface of a microcalorimeter detector. The x-ray lens is used to increase the effective collection area of the microcalorimeter detector used in an x-ray spectrometer. By increasing the collection angle, the time period for x-ray collection is reduced and the detector can be located farther from the x-ray source. The x-ray lens is effective over a broad energy range of x-rays, thus providing compatibility with spectroscopic analysis. The microcalorimeter can be calibrated to compensate for any variations in the transmission efficiency of the x-ray lens.
A simple, compact optical spectrometer employs solid-state nonlinear crystals for obtaining broadband multichannel infrared spectra with picosecond or femtosecond time resolution. Spectrally broad infrared pulses are produced by difference frequency mixing in a first LiIO3 crystal between the second harmonic of a picosecond Nd+3 :YAG laser and broadband output of a synchronously pumped dye laser, and a resultant broadband IR pulse is upconverted by a second LiIO3 crystal to yield a blue visible pulse which is dispersed by a 0.25 meter spectrograph onto a multichannel vidicon or reticon detector to obtain four wave-number resolution single-shot transient infrared spectra of a sample. The present invention enables rapid acquisition of ultrashort time infrared spectra over a broadly tunable spectral range (in the mid to near infrared) at minimal cost and by a simple but versatile optical system employing readily available components.
The dielectric slit die is an instrument that is designed to measure electrical, rheological, ultrasonics, optical and other properties of a flowing liquid. In one application, it is connected to the exit of an extruder, pump or mixing machine that passes liquefied material such as molten plastic, solvents, slurries, colloidal suspensions, and foodstuffs into the sensing region of the slit shaped die. Dielectric sensing is the primary element of the slit die, but in addition to the dielectric sensor, the die contains other sensing devices such as pressure, optical fiber, and ultrasonic sensors that simultaneously yield an array of materials property data. The slit die has a flexible design that permits interchangeability among sensors and sensor positions. The design also allows for the placement of additional sensors and instrumentation ports that expand the potential data package obtained.
The present invention relates to x-ray diffraction measurement by using moving x-ray source x-ray diffraction. The invention comprises a raster-scanned x-ray source, a specimen, a collimator, and a detector. The x-ray source is electronically scanned which allows a complete image of the x-ray diffraction characteristics of the specimen to be produced. The specimen is placed remote from the x-ray source and the detector. The collimator is located directly in front of the detector. The x-rays are diffracted by the specimen at certain angles, which cause them to travel through the collimator and to the detector. The detector may be placed in any radial location relative to the specimen in order to take the necessary measurements. The detector can detect the intensity and/or the wavelength of the diffracted x-rays. All information needed to solve the Bragg equation as well as the Laue equations is available. The x-ray source may be scanned electronically or mechanically. The present invention is used to perform texture analysis and phase identification.
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.
A method for the removal of carbonyl sulfide from liquefied petroleum is disclosed. Removal of carbonyl sulfide is accomplished by contacting a liquid petroleum gas stream containing a carbonyl sulfide as an impurity with a calixarene complexing agent as the principal agent for the removal of the carbonyl sulfide.
A composition formed from Group II fluorides in which the composition has little or no intrinsic birefringence at a selected wavelength. The composition is a mixed solid solution of CaF.sub.2 with a second crystal of SrF.sub.2 or BaF.sub.2. The resulting composition is in the form of Ca.sub.1-xSr.sub.xF.sub.2 or Ca.sub.1-xBa.sub.xF.sub.2, or a combination of SrF.sub.2 and BaF.sub.2, in the form of Ca.sub.1-x-ySr.sub.xBa.sub.yF.sub.2. The specific form of the composition that effectively nulls out the intrinsic birefringence at a selected wavelength within the UV range is determined in one preferred method from the magnitudes of the intrinsic birefringences of the components, CaF.sub.2, SrF.sub.2, and BaF.sub.2.
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.
A Gd.sub.5Ge.sub.2Si.sub.2 refrigerant compound is doped or alloyed with an effective amount of silicide-forming metal element such that the magnetic hysteresis losses in the doped Gd.sub.5Ge.sub.2Si.sub.2 compound are substantially reduced in comparison to the hysteresis losses of the undoped Gd.sub.5Ge.sub.2Si.sub.2 compound. The hysteresis losses can be nearly eliminated by doping the Gd.sub.5Ge.sub.2Si.sub.2 compound with iron, cobalt, manganese, copper, or gallium. The effective refrigeration capacities of the doped Gd.sub.5Ge.sub.2Si.sub.2 compound are significantly higher than for the undoped Gd.sub.5Ge.sub.2Si.sub.2 compound.
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.
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.
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.
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.
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.
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.
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.
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.
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.
The invention, a Particle Transfer Apparatus, facilitates the transfer of atmospheric particles for fibrous filter such as quartz fiber to a smooth substrate that is suitable for scanning electron micrscopy (SEM) and x-ray microanalyisis. The invention may also be suitable for transferring particles embedded in clothing textiles for this purpose.
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.
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.
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.
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.
Arrays of microfabricated hotplates have been used as substrate arrays for materials processing on a microscopic scale. Properties of individual elements (pixels) of the array, such as temperature and voltage bias, are controlled by addressing a given pixel with appropriate signals. Materials are deposited onto pixels with individually controlled deposition conditions (pixel temperature, bias). Pixels are also addressed to control properties during post-deposition processing steps such as heating in vacuum or various gases to alter stoichiometry of a single material, or to alloy multiple composition materials. The addressable heating characteristics may also be used for a maskless lithography on pixel elements. The result is an array of separately, but simultaneously, processed films. Properties of film elements may be measured using electrical contact pads. The array of processed films may be used for sensors, electronic devices, greatly accelerated materials development processes, and solid state physics, biology and chemistry studies.
Planar forms of chemically-sensitive materials have been combined, under temperature control, with the pixels of a specially-designed micro-hotplate array to produce a miniature device capable of analyzing chemical mixtures. The device uses integrated multiple elements having different adsorption properties and temperatures to collectively achieve chemical selectivity in sensing. The method of making and using selectively in sensing. The device of the present invention is manufactured by standard CMOS foundry techniques which allow the production of a range of devices that have improved sensing performance.
A method of comb-based spectroscopy with synchronous sampling for real-time averaging includes measuring the full complex response of a sample in a configuration analogous to a dispersive Fourier transform spectrometer, infrared time domain spectrometer, or a multiheterodyne laser spectrometer. An alternate configuration of a comb-based spectrometer for rapid, high resolution, high accuracy measurements of an arbitrary cw waveform.
Disclosed is a method for operating a sensor to differentiate between first and second analytes in a sample. The method comprises the steps of determining a input profile for the sensor which will enhance the difference in the output profiles of the sensor as between the first analyte and the second analyte; determining a first analyte output profile as observed when the input profile is applied to the sensor; determining a second analyte output profile as observed when the temperature profile is applied to the sensor; introducing the sensor to the sample while applying the temperature profile to the sensor, thereby obtaining a sample output profile; and evaluating the sample output profile as against the first and second analyte output profiles to thereby determine which of the analytes is present in the sample.
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.
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.
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.
A Gd.sub.5Ge.sub.2Si.sub.2 refrigerant compound is doped or alloyed with an effective amount of silicide-forming metal element such that the magnetic hysteresis losses in the doped Gd.sub.5Ge.sub.2Si.sub.2 compound are substantially reduced in comparison to the hysteresis losses of the undoped Gd.sub.5Ge.sub.2Si.sub.2 compound. The hysteresis losses can be nearly eliminated by doping the Gd.sub.5Ge.sub.2Si.sub.2 compound with iron, cobalt, manganese, copper, or gallium. The effective refrigeration capacities of the doped Gd.sub.5Ge.sub.2Si.sub.2 compound are significantly higher than for the undoped Gd.sub.5Ge.sub.2Si.sub.2 compound.
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.
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.
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.