text:
A biosensor includes a substrate with a layer of receptive material disposed thereon. The receptive material is specific for an analyte of interest. A pattern of active and inactive areas of the receptive material are defined in the receptive material layer by a masking process.
1. A method of making a biosensor, comprising the steps of:
forming a receptive material layer generally uniformly over a surface of a substrate member, the layer containing a receptive material specific for an analyte of interest;
defining at least one active area and at least one inactive area of the receptive material in a masking process wherein a blocking agent is used to render the receptive material inactive in the defined inactive area; and
wherein when the biosensor is exposed to a medium containing the analyte of interest, the analyte binds to the receptive material in the active areas and facilitates subsequent diffraction of transmitted light or reflected light in a diffraction pattern corresponding to the active areas.
2. The method as in
placing a mask over the substrate member, the mask having a configuration so as to shield at least one underlying area of the substrate while exposing at least one adjacent area;
exposing the mask and substrate to a stimulus for activating the blocking agent such that the blocking agent in the exposed areas affixes to the receptive material;
removing the mask from the substrate and disassociating the blocking agent from the receptive material in the areas that were underlying the mask;
wherein a resulting pattern of active and inactive areas of the receptive material are defined, the inactive areas corresponding to the areas exposed by the mask and the active areas corresponding to the areas shielded by the mask.
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The present invention relates generally to the field of detecting analytes in a medium, and more particularly to a process for preparing analyte-specific diffraction based diagnostic sensors to indicate the presence of the analyte in a medium.
There are many systems and devices available for detecting a wide variety of analytes in various media. Many of the prior systems and devices are, however, relatively expensive and require a trained technician to perform the test. A need has been recognized in the art for biosensor systems that are easy and inexpensive to manufacture, and capable of reliable and sensitive detection of analytes. Reference is made, for example, to U.S. Pat. Nos. 5,922,550; 6,060,256; and 6,221,579 B1.
Various advances have been made in the industry for producing biosensors. For example, U.S. Pat. No. 5,512,131 to Kumar, et al., describes a device that includes a polymer substrate having a metal coating. An analyte specific receptor layer is stamped onto the coated substrate. A diffraction pattern is generated when an analyte binds to the device. A visualization device, such as a spectrometer, is then used to determine the presence of the diffraction pattern. A drawback to this type of device is, however, the fact that the diffraction pattern is not discernible by the naked eye and, thus, a complex visualization device is needed to view the diffraction pattern. Also, the device is generally not able to detect smaller analytes that do not produce a noticeable diffraction pattern.
U.S. Pat. No. 5,482,830 to Bogart, et al., describes a device that includes a substrate which has an optically active surface exhibiting a first color in response to light impinging thereon. This first color is defined as a spectral distribution of the emanating light. The substrate also exhibits a second color which is different from the first color. The second color is exhibited in response to the same light when the analyte is present on the surface. The change from one color to another can be measured either by use of an instrument, or by the naked eye. A drawback with the device is, however, the relatively high cost of the device and problems associated with controlling the various layers that are placed on the wafer substrate.
Contact printing techniques have been explored for producing biosensors having a self-assembling monolayer. U.S. Pat. No. 5,922,550 describes a biosensor having a metalized film upon which is printed (contact printed) a specific predetermined pattern of an analyte-specific receptor. The receptor materials are bound to the self-assembling monolayer and are specific for a particular analyte or class of analytes. Attachment of a target analyte that is capable of scattering light to select areas of the metalized plastic film upon which the receptor is printed causes diffraction of transmitted and/or reflected light occurs via the physical dimensions and defined placement of the analyte. A diffraction image is produced which can be easily seen with the eye or, optionally, with a sensing device. U.S. Pat. No. 6,060,256 describes a similar device having a metalized film upon which is printed a specific predetermined pattern of analyte-specific receptor. The '256 patent is not limited to self-assembling monolayers, but teaches that any receptor which can be chemically coupled to a surface can be used. The invention of the '256 patent uses methods of contact printing of patterned monolayers utilizing derivatives of binders for microorganisms. One example of such a derivative is a thiol. The desired binding agents can be thiolated antibodies or antibody fragments, proteins, nucleic acids, sugars, carbohydrates, or any other functionality capable of binding an analyte. The derivatives are chemically bonded to metal surfaces such as metalized polymer films, for example via a thiol.
A potential issue of the contact printing techniques described above for producing diffraction-based biosensors is the possibility of contamination from the print (i.e., stamp) surface during the printing process. Also, there is the possibility of uneven application or inking of the substances due to pressure and contact variations inherent in the process, as well as surface energy variations.
The present invention relates to a biosensor system that is easy and inexpensive to manufacture, is capable of reliable and sensitive detection of analytes, and avoids possible drawbacks of conventional microcontact printing techniques.
Objects and advantages of the invention will be set forth in part in the following description, or may be obvious from the description, or may be learned through practice of the invention.
The present invention provides a relatively inexpensive yet sensitive biosensor device, a method for producing such biosensor devices, and a method for detecting analytes of interest present in a medium.
The biosensor includes a substrate member upon which a layer containing a receptive material has been applied generally uniformly over an entire surface of the substrate member. The substrate may be any one of a wide variety of suitable materials, including plastics, metal coated plastics and glass, functionalized plastics and glass, silicon wafers, foils, glass, etc. Desirably, the substrate is flexible, such as a polymeric film, in order to facilitate the manufacturing process. The receptive material layer may be applied by any number of known techniques, including dipping, spraying, rolling, and any other technique wherein the receptive material layer can be applied generally uniformly over the entire test surface of the substrate. The invention also includes contact printing methods of applying the coating, as long as such methods are conducted in a manner to prevent inconsistent inking and contamination from contact during the initial coating process.
The receptive material layer is defined into a pattern of active and inactive areas of receptive material in a masking process. The masking process is based generally on the principle that biosensor receptive materials are able to specifically recognize and bind to other molecules (ligands). An example is the antibody-antigen interaction. When affixed to a receptive material, the ligands act as a blocking agent to prevent the receptive material from thereafter binding with the analyte of interest in a test medium. The ligands can be more or less permanently affixed to the receptor sites using, for example, a cross-linking agent to "lock" the ligands to the receptive material. For example, the ligand may be modified with a photo-activatible cross-linking agent for this purpose. This principle can be exploited to form a layer of biomolecules or receptive material on a substrate surface that is patterned into active and inactive or "blocked" areas by use of a mask.
A generally uniform layer or coating of the blocking agent is applied over the receptive material layer. A mask having any desired pattern of shielded areas and exposed areas (blank, transparent, or translucent areas) is then placed over the substrate member. The mask and substrate combination are then exposed to a particular stimulus selected to activate the blocking agent under the exposed areas of the mask. The exposed areas thus define a pattern of inactive areas and the areas under the shielded areas of the mask define a pattern of active receptive material areas. After removal of the mask, the unactivated blocking agent is disassociated from the receptive material, for example in a subsequent rinsing or washing process.
It should be appreciated that the invention is not limited to any particular pattern defined by the mask. Virtually any number and combination of exposed shapes are possible. In one particular embodiment, the active area pattern is defined by about 10 micron diameter pixels at a spacing of about 5 microns apart over the test surface of the substrate.
Upon subsequent exposure of the biosensor to a medium containing an analyte of interest, the analyte binds to the receptive material in the active areas. The biosensor will then diffract transmitted light in a diffraction pattern corresponding to the active areas. The diffraction pattern may be visible to the naked eye or, optionally, viewed with a sensing device.
In the case where an analyte does not scatter visible light because the analyte is too small or does not have an appreciable refractive index difference compared to the surrounding medium, a diffraction-enhancing element, such as polymer microparticles, may be used. These microparticles are coated with a binder or receptive material that also specifically binds to the analyte. Upon subsequent coupling of the analyte to both the patterned biomolecules in the receptive material layer as well as the microparticles, a diffraction image is produced which can be easily seen with the eye or, optionally, with a sensing device.
By "diffraction" it is meant the phenomenon, observed when waves are obstructed by obstacles, of the disturbance spreading beyond the limits of the geometrical shadow of the object. The effect is marked when the size of the object is of the same order as the wavelength of the waves. In the present invention, the obstacles are analytes (with or without or attached microparticles) and the waves are light waves.
In another embodiment of the present invention, nutrients for a specific class of microorganisms can be incorporated into the receptive material layer. In this way, very low concentrations of microorganisms can be detected by first contacting the biosensor of the present invention with the nutrients incorporated therein and then incubating the biosensor under conditions appropriate for the growth of the bound microorganism. The microorganism is allowed to grow until there are enough organisms to form a diffraction pattern.
The present invention provides a low-cost, disposable biosensor which can be mass produced. The biosensors of the present invention can be produced as a single test for detecting an analyte or it can be formatted as a multiple test device. The uses for the biosensors of the present invention include, but are not limited to, detection of chemical or biological contamination in garments, such as diapers, the detection of contamination by microorganisms in prepacked foods such as fruit juices or other beverages, and the use of the biosensors of the present invention in health diagnostic applications such as diagnostic kits for the detection of antigens, microorganisms, and blood constituents. It should be appreciated that the present invention is not limited to any particular use or application.
These and other features and advantages of the present invention will become apparent after a review of the following detailed description of the disclosed embodiments.
The invention will now be described in detail with reference to particular embodiments thereof. The embodiments are provided by way of explanation of the invention, and not meant as a limitation of the invention. For example, features described or illustrated as part of one embodiment may be used with another embodiment to yield still a further embodiment. It is intended that the present invention include these and other modifications and variations as come within the scope and spirit of the invention.
The present invention features improved biosensing devices, and methods for using such biosensing devices, for detecting and quantifying the presence or amount of an analyte of interest within a medium. The analytes that can be detected by the present invention include, but are not limited to, microorganisms such as bacteria, yeasts, fungi, proteins, small molecules, nucleic acids, and viruses. The biosensing devices according to the invention are relatively inexpensive and have advantages over conventional microcontact printed biosensors.
The present invention comprises, in broad terms, a process of defining an active pattern of analyte-specific receptor material on a substrate surface by photo-masking the substrate. A generally uniform coating or layer of the receptive material is applied to the substrate surface. A generally uniform coating or layer of a blocking agent is then applied over the receptive material layer. A mask is placed over the substrate, and the mask and substrate combination is then exposed to a stimulus, such as a light or energy source. In its basic form, the "mask" serves to shield or "protect" at least one area or section of the receptive material from the stimulus or energy source (e.g., as a lead gown shields a patient during an X-ray procedure) and to expose at least one adjacent area to the stimulus or energy source so as to cross-link the blocking agent in place in the exposed area. For example, the mask may be a generally transparent or translucent blank (e.g., strip of material) having any pattern of blocked regions printed or otherwise defined thereon. The exposed unblocked regions of the mask correspond to the inactive areas of the receptive material layer. Alternatively, the mask may simply be a single object placed upon the substrate. The area under the object would be shielded and thus define an active area of the receptive material and the area around the object would be exposed to the energy source and thus define an area of inactive receptive material. The object may alternately have any pattern of openings defined therethrough corresponding to the exposed areas.
In the exposed areas, the blocking agent is activated and bound to the receptive material to the extent that the receptive material is thereafter prevented from binding with the analyte of interest in a test medium. The unactivated blocking agent in the active receptive material areas is removed or disassociated from the receptive material by any suitable process, for example by washing or rinsing the substrate member with a solution sufficient to remove the blocking agent. Thus, upon removal of the mask and disassociation of the un-activated blocking agent, a pattern of active and inactive receptive material areas are defined. It should be understood that "pattern" includes as few as one active area and one inactive area.
Upon subsequent exposure of the biosensor to a medium containing the analyte of interest, such analyte will bind to the receptors in the active receptive material areas. The analyte facilitates diffraction of transmitted and/or reflected light in a visible diffraction pattern corresponding to the active areas. As discussed in greater detail below, an enhancer may be used for enhancing diffraction from extremely small analytes.
The term "blocking agent" is used herein to broadly encompass any material or substance that prevents or "blocks" the receptive material from interacting with the analyte of interest. Such an agent may serve this purpose by filling the biomolecule receptor sites of the receptive material. For example, in one embodiment, the blocking agent may be a ligand for which the receptive material has a particular affinity (i.e., the receptive material may be an antibody and the blocking agent may be a cognate antigen). By coating or applying a layer of the ligand to the receptive material, it is assured that the receptive material and ligand interact over essentially the entire layer of receptive material.
A masking process is then used to affix the ligands to the receptive material in certain areas (the inactive areas). A cross-linking agent may be used for affixing the ligands to the receptive material in the masking process. For example, the ligand may be modified with a cross-linking agent in which an end of the agent is photosensitive and another end is reactive with the receptive material. A suitable such cross-linking agent is N-hydroxy-succinimidyl-4-azidosalicylic acid (NHS-ASA). Other suitable cross-linking agents are commercially available or may be formed by any standard cross-linking chemistry or method for making bio-conjugates (e.g. disulfide bonding). In this case, the blocking agent (modified ligand) may be applied to the receptive material layer in a light-protected environment so that the cross-linking agent is not activated prior to the masking process. Upon being exposed to a light source through the exposed regions of the mask, the cross-linking agent affixes the ligand to the receptive material.
The mask is then removed from the substrate member, desirably in a light protected environment, and the unactivated blocking agent is disassociated from the receptive material in the active areas. This may be done in various ways, including rinsing the substrate with a solution that disrupts the normal interaction between the ligand and the receptive material. Pure water may serve this purpose. The water induces ionic strength shock and weakens the strength of the ionic bond between the ligand and receptive material. A solution having a relatively high salt content may also serve to weaken the bond. The bond may also be weakened by a solution having a particular pH, such as a glycine solution, or by temperature changes.
The analytes that are contemplated as being detected using the present invention include, but are not limited to, bacteria; yeasts; fungi; viruses; rheumatoid factor; antibodies, including, but not limited to IgG, IgM, IgA, IgD, and IgE antibodies; carcinoembryonic antigen; streptococcus Group A antigen; viral antigens; antigens associated with autoimmune disease, allergens, tumor antigens; streptococcus Group B antigen, HIV I or HIV II antigen; or host response (antibodies) to these and other viruses; antigens specific to RSV or host response (antibodies) to the virus; antigen; enzyme; hormone; polysaccharide; protein; lipid; carbohydrate; drug or nucleic acid; Salmonella species; Candida species, including, but not limited to Candida albicans and Candida tropicalis; Neisseria meningitides groups A, B, C, Y and W sub 135, Streptococcus pneumoniae, E. coli, Haemophilus influenza type A/B; an antigen derived from microorganisms; PSA (prostate specific antigen) and CRP (C-reactive protein) antigens; a hapten; a drug of abuse; a therapeutic drug; an environmental agent; and antigens specific to Hepatitis. In broad terms, the "analyte of interest" may be thought of as any agent whose presence or absence from a biological sample is indicative of a particular health state or condition.
It is also contemplated that nutrients for a specific class of microorganism can be incorporated into the receptive material layer. In this way, very low concentrations of microorganisms can be detected by exposing the biosensor of the present invention with the nutrients incorporated therein to the suspect medium and then incubating the biosensor under conditions appropriate for the growth of the bound microorganism. The microorganisms are allowed to grow until there are enough organisms to form a diffraction pattern. Of course, in some cases, the microorganism is present or can multiply enough to form a diffraction pattern without the presence of a nutrient in the active receptive material areas.
The receptive material is characterized by an ability to specifically bind the analyte or analytes of interest. The variety of materials that can be used as receptive material is limited only by the types of material which will combine selectively (with respect to any chosen sample) with a secondary partner. Subclasses of materials which fall in the overall class of receptive materials include toxins, antibodies, antibody fragments, antigens, hormone receptors, parasites, cells, haptens, metabolites, allergens, nucleic acids, nuclear materials, autoantibodies, blood proteins, cellular debris, enzymes, tissue proteins, enzyme substrates, coenzymes, neuron transmitters, viruses, viral particles, microorganisms, proteins, polysaccharides, chelators, drugs, aptamers, peptides, and any other member of a specific binding pair. This list only incorporates some of the many different materials that can be coated onto the substrate surface to produce a thin film assay system. Whatever the selected analyte of interest is, the receptive material is designed to bind specifically with the analyte of interest.
The matrix or medium containing the analyte of interest may be a liquid, a solid, or a gas, and can include a bodily fluid such as mucous, saliva, urine, fecal material, tissue, marrow, cerebral spinal fluid, serum, plasma, whole blood, sputum, buffered solutions, extracted solutions, semen, vaginal secretions, pericardial, gastric, peritoneal, pleural, or other washes and the like. The analyte of interest may be an antigen, an antibody, an enzyme, a DNA fragment, an intact gene, a RNA fragment, a small molecule, a metal, a toxin, an environmental agent, a nucleic acid, a cytoplasm component, pili or flagella component, protein, polysaccharide, drug, or any other material. For example, receptive material for bacteria may specifically bind a surface membrane component, protein or lipid, a polysaccharide, a nucleic acid, or an enzyme. The analyte which is specific to the bacteria may be a polysaccharide, an enzyme, a nucleic acid, a membrane component, or an antibody produced by the host in response to the bacteria. The presence or absence of the analyte may indicate an infectious disease (bacterial or viral), cancer or other metabolic disorder or condition. The presence or absence of the analyte may be an indication of food poisoning or other toxic exposure. The analyte may indicate drug abuse or may monitor levels of therapeutic agents.
One of the most commonly encountered assay protocols for which this technology can be utilized is an immunoassay. However, the general considerations apply to nucleic acid probes, enzyme/substrate, and other ligand/receptor assay formats. For immunoassays, an antibody may serve as the receptive material or it may be the analyte of interest. The receptive material, for example an antibody or an antigen, must form a stable, relatively dense, reactive layer on the substrate surface of the test device. If an antigen is to be detected and an antibody is the receptive material, the antibody must be specific to the antigen of interest; and the antibody (receptive material) must bind the antigen (analyte) with sufficient avidity that the antigen is retained at the test surface. In some cases, the analyte may not simply bind the receptive material, but may cause a detectable modification of the receptive material to occur. This interaction could cause an increase in mass at the test surface or a decrease in the amount of receptive material on the test surface. An example of the latter is the interaction of a degradative enzyme or material with a specific, immobilized substrate. In this case, one would see a diffraction pattern before interaction with the analyte of interest, but the diffraction pattern would disappear if the analyte were present. The specific mechanism through which binding, hybridization, or interaction of the analyte with the receptive material occurs is not important to this invention, but may impact the reaction conditions used in the final assay protocol.
In addition to producing a simple diffraction image, patterns of analytes can be such as to allow for the development of a holographic sensing image and/or a change in visible color. Thus, the appearance of a hologram or a change in an existing hologram will indicate a positive response. The pattern made by the diffraction of the transmitted light can be any shape including, but not limited to, the transformation of a pattern from one pattern to another upon binding of the analyte to the receptive material. In particularly preferred embodiments, the diffraction pattern becomes discernible in less than one hour after contact of the analyte with the biosensing device of the present invention.
The diffraction grating which produces the diffraction of light upon interaction with the analyte should have a minimum periodicity of about Į the wavelength and a refractive index different from that of the surrounding medium. Very small analytes, such as viruses or molecules, can be detected indirectly by using a larger, "diffraction enhancing element," such as a microparticle, that is specific for the small analyte. One embodiment in which the small analyte can be detected comprises coating the enhancing particle, such as a latex bead or polystyrene bead, with a receptive material, such as an antibody, that specifically binds to the analyte of interest Particles that can be used in the present invention include, but are not limited to, glass, cellulose, synthetic polymers or plastics, latex, polystyrene, polycarbonate, proteins, bacterial or fungal cells, silica, cellulose acetate, carbon, and the like. The particles are desirably spherical in shape, but the structural and spatial configuration of the particles is not critical to the present invention. For instance, the particles could be slivers, ellipsoids, cubes, random shape and the like. A desirable particle size ranges from a diameter of approximately 0.1 micron to 50 microns, desirably between approximately 0.1 micron and to 2.0 microns. The composition of the particle is not critical to the present invention.
Desirably, the receptive material layer on the substrate will specifically bind to an epitope on the analyte that is different from the epitope used in the binding to the enhancing particle. Thus, for detecting a small analyte, such as viral particles, in a medium, the medium is first exposed to the latex particles having the virus-specific receptive material thereon. The small analytes of interest in the medium will bind to the latex particles. Then, the latex particles are optionally washed and exposed to the biosensor film with the pattern of active receptive material areas containing the virus-specific antibodies. The antibodies then bind to the viral particles on the latex bead thereby immobilizing the latex beads in the same pattern as the active areas on the film. Because the bound latex beads will cause diffraction of the visible light, a diffraction pattern is formed, indicating the presence of the viral particle in the liquid. Other combinations using diffraction enhancing particles are described, for example, in U.S. Pat. No. 6,221,579 incorporated herein for all purposes.
Any one of a wide variety of materials may serve as the substrate to which the receptive material is applied. Such materials are well known to those skilled in the art. For example, the substrate may be formed of any one of a number of suitable plastics, metal coated plastics and glass, functionalized plastics and glass, silicon wafers, foils, glass, etc. Rather than requiring a rigid substrate for the photopatterning process described herein, it has been found that thermoplastic films are quite suitable. Such films include, but are not limited to, polymers such as: polyethylene-terephthalate (MYLAR«), acrylonitrile-butadiene-styrene, acrylonitrile-methyl acrylate copolymer, cellophane, cellulosic polymers such as ethyl cellulose, cellulose acetate, cellulose acetate butyrate, cellulose propionate, cellulose triacetate, cellulose triacetate, polyethylene, polyethylene—vinyl acetate copolymers, ionomers (ethylene polymers) polyethylene-nylon copolymers, polypropylene, methyl pentene polymers, polyvinyl fluoride, and aromatic polysulfones. Preferably, the plastic film has an optical transparency of greater than 80%. Other suitable thermoplastics and suppliers may be found, for example, in reference works such as the Modern Plastics Encyclopedia (McGraw-Hill Publishing Co., N.Y. 1923–1996).
In one embodiment of the invention, the thermoplastic film may have a metal coating. The film with metal coating thereon may have an optical transparency of between approximately 5 percent and 95 percent. A more desired optical transparency for the thermoplastic film used in the present invention is between approximately 20 percent and 80 percent. In a desired embodiment of the present invention, the thermoplastic film has at least an approximately 80 percent optical transparency, and the thickness of the metal coating is such as to maintain an optical transparency greater than about 20 percent, so that diffraction patterns can be produced by either reflected or transmitted light. This corresponds to a metal coating thickness of about 20 nanometers. However, in other embodiments of the invention, the metal thickness may be between approximately 1 nanometer and 1000 nanometers.
The preferred metal for deposition on the film is gold. However, silver, titanium, aluminum, chromium, copper, iron, zirconium, platinum, titanium, and nickel, as well as oxides of these metals, may be used. Chromium oxide can be used to make metalized layers.
The receptive material and blocking agent may be applied to the substrate by any conventional method. The materials are applied so that it generally uniformly covers an entire (for example, upper) surface of the substrate. Non-contact methods for applying the receptive material may be desired so as to eliminate the possibility of contamination by contact during application. Suitable application methods include, but are not limited to, dipping, spraying, rolling, spin coating, and any other technique wherein the receptive material layer and blocking agent can be applied generally uniformly over the entire test surface of the substrate. Simple physisorption can occur on many materials, such as polystryene, glass, nylon, polycarbonate, metals, or other materials well known to those skilled in the art. One particular embodiment of immobilizing the analyte-specific receptive material layer involves molecular attachment, such as that possible between thiol or disulfide-containing compounds and gold. Typically, a gold coating of about 5 to about 2000 nanometers thick is supported on a silicon wafer, glass, or polymer film (such as a MYLAR« film). The analyte-specific receptor attaches to the gold surface upon exposure of a solution of the receptive material.
Although not preferred, the invention also includes contact printing methods of applying the receptive material and blocking agent.
The technique selected should minimize the amount of receptive material required for coating a large number of test surfaces and maintain the stability/functionality of the receptive material during application. The technique should also apply or adhere the receptive material to the substrate in a uniform and reproducible fashion.
It is also contemplated that the receptive material layer may be formed on the substrate as a self-assembling monolayer of alkanethiolates, carboxylic acids, hydroxamic acids, and phosphonic acids on metalized thermoplastic films. The self-assembling monolayers have receptive material bound thereto. Reference is made to U.S. Pat. No. 5,922,550 for a more detailed description of such self-assembling monolayers and methods for producing the monolayers. The '550 patent is incorporated herein in its entirety for all purposes.
The mask may be formed of any suitable material that protects or blocks portions of the underlying substrate from the irradiating stimulus or energy source. A material that has proven useful for defining patterns of active and inactive receptive material regions on a gold-plated MYLAR« film coated with an antibody solution is a transparent or translucent polymer film (such as MYLAR«) having a pattern of shielded regions printed thereon. This type of mask is useful for light sources with a wavelength down greater than or equal to about 330 nanometers. For light sources having a wavelength below about 330 nanometers, a quartz or fused silica mask having chrome or other metal plated shielded regions defined thereon may be used. The mask may define any pattern of active and inactive regions of the receptive material. The active regions creating the visible diffraction pattern may be of virtually any size, shape, and pattern. It may be desired to select a size and pattern so as to maximize the visible diffraction contrast between the active and inactive regions. As one example, it has been found suitable if the active regions are defined as generally circular with a diameter of about 10 microns and spaced from each other by about 5 microns.
The biosensors according to the invention have a wide range of uses in any number of fields. The uses for the biosensors of the present invention include, but are not limited to, detection of chemical or biological contamination in garments, such as diapers, generally the detection of contamination by microorganisms in prepacked foods such as meats, fruit juices or other beverages, and the use of the biosensors of the present invention in health diagnostic applications such as diagnostic kits for the detection of proteins, hormones, antigens, nucleic acids, DNA, microorganisms, and blood constituents. The present invention can also be used on contact lenses, eyeglasses, window panes, pharmaceutical vials, solvent containers, water bottles, band-aids, wipes, and the like to detect contamination. In one embodiment, the present invention is contemplated in a dipstick form in which the patterned substrate is mounted at the end of the dipstick. In use the dipstick is dipped into the liquid in which the suspected analyte may be present and allowed to remain for several minutes. The dipstick is then removed and then, either a light is projected through the substrate or the substrate is observed with a light reflected from the substrate. If a diffraction pattern is observed, then the analyte is present in the liquid.
In another embodiment of the present invention, a multiple analyte test is constructed on the same support. A strip may be provided with several patterned substrate sections. Each section has a different receptive material that is different for different analytes. It can be seen that the present invention can be formatted in any array with a variety of patterned substrates thereby allowing the user of the biosensor device of the present invention to detect the presence of multiple analytes in a medium using a single test.
In yet another embodiment of the present invention, the biosensor can be attached to an adhesively backed sticker or decal which can then be placed on a hard surface or container wall. The biosensor can be placed on the inside surface of a container such as a food package or a glass vial. The biosensor can then be visualized to determine whether there is microbial contamination.
It should be understood that resort may be had to various other embodiments, modifications, and equivalents to the embodiments of the invention described herein which, after reading the description of the invention herein, may suggest themselves to those skilled in the art without departing from the scope and spirit of the present invention.
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A method and apparatus of transmitting time critical messages over a network is provided. Data which has minimal bandwidth requirements, such as data packets utilized in applications such as twitch games, is received or generated in a network device. The data is classified as minimal bandwidth data and prioritized relative to other data for transmission before the other data. The data is then transmitted by the device to a second device on the network before the other data is transmitted.
1. A method of transmitting data over a network path comprising a plurality of nodes, said method comprising:
classifying said data which have minimal bandwidth requirements in a first classification as first data in a first node on said network path;
assigning a higher priority to said first data relative to other data without minimal bandwidth requirements for transmission;
transmitting said first data before transmitting said other data; and
maintaining said higher priority for said first data by said plurality of nodes of said network path.
2. A method of transmitting data over a network path according to claim 1, wherein the step of maintaining said higher priority further comprises:
receiving said first data at a second node on said network path;
determining said first classification for said first data;
further assigning a higher priority to said first data relative to further said other data for transmission; and
transmitting said first data from said second node before transmitting further said other data.
3. A method of transmitting data over a network path according to claim 1 further comprising the step of reserving resources within said plurality of nodes on said network path.
4. A method of transmitting data over a network path according to claim 3 wherein said step of reserving resources within said plurality of nodes includes the step of implementing a resource reservation protocol between each of said plurality of nodes.
5. A method of transmitting data over a network path according to claim 2 wherein said first node is a source host, and said second node is a network router, and said first node generates data having minimum bandwidth requirements from a twitch game application executed on said first node.
6. A method of transmitting a data packet over a network, said network comprising a plurality of network devices connected by a connection medium, said method comprising:
reserving network resources within said network devices using a first network protocol;
reserving a subset of said network resources within said network devices using a second network protocol; and
transmitting said data packet from one of said network devices to a second of said network devices using said second network protocol, said second network protocol placing and maintaining said data packet at a first priority level in a data queue utilized by said first network protocol.
7. A method as in claim 6, wherein said step of reserving network resources within said network devices comprises the step of sending a first message from one of said plurality of network devices to at least one of the remainder of said plurality of network devices.
8. A method as in claim 7, wherein said first network protocol is a resource reservation protocol, and wherein said first message is a resource reservation request.
9. A method as in claim 7, wherein said step of reserving a subset of said network resources within said network devices comprises the step of sending a second message from one of said plurality of network devices to at least one of the remainder of said plurality of network devices, said second message containing fields which define characteristics associated with said data packet.
10. A method as in claim 7, wherein said second network protocol is an extension of said first network protocol, and said step of reserving a subset of said network resources includes the step of defining one or more data parameter fields within a predetermined field associated with said first message.
11. A method as in claim 10, wherein the step of reserving a subset of network resources further includes the steps of:
defining the number of bits contained within said data packet;
defining the number of data packets to be transmitted within a unit of time; and
defining one or more special handling requirements for the transmission of said data packets.
12. A method as in claim 11, wherein said step of defining special handling requirements includes at least one of the following steps:
bundling a predetermined number of data packets to be transmitted concurrently over said network;
compressing said data packet prior to transmission over said network; or
reducing the reserved subset of network resources in correspondence with said number of bits contained within said data packet and said number of data packets to be transmitted.
13. A method of executing a command over a network, said network comprising a first computer, a second computer, and a plurality of network devices coupled between said first computer and second computer, said method comprising:
classifying said command as having minimal bandwidth requirements;
reserving network resources within said network devices using a network protocol; and
transmitting said command from said first computer to at least one of said plurality of network devices using said network protocol, said network protocol placing and maintaining said command at a predetermined priority level in a data queue utilized by said at least one of said plurality of network devices.
14. A method as in claim 13 wherein said network protocol includes means for defining a first protocol message, said first protocol message including one or more header fields and a message parameter field.
15. A method as in claim 14 wherein said message parameter field includes a message parameter subfields for specifying characteristics associated with one or more data packets encapsulated within said command.
16. A method as in claim 15 wherein said characteristics include the size of said one or more data packets, the transmission rate of said one or more data packets, and predefined functions defining the transmission of said data packets, said predefined functions including bundling a plurality of said data packets for concurrent transmission, and compressing said one or more data packets prior to transmission.
17. A device for transmitting and receiving messages on a network, the device comprising:
a processor; and
a memory coupled to the processor, the memory having stored therein instructions which, when executed by the processor, cause said device to:
generate data having minimal bandwidth requirements;
classify said data as having minimal bandwidth requirements;
assign a higher priority to said data relative to other data without minimal bandwidth requirements for transmission; and
transmit said data before transmitting said other data.
18. A device as in claim 17, wherein said instructions further cause said device to reserve resources within said plurality of nodes on said network.
19. A device for transmitting and receiving messages on a network, the device comprising:
a processor; and
a memory coupled to the processor, the memory having stored therein instructions which, when executed by the processor, cause said device to:
receive data over said network from a second device on said network;
classify said data as having minimal bandwidth requirements if said second device has classified said data as having minimal bandwidth requirements;
assign a higher priority to said data relative to other data without minimal bandwidth requirements for transmission; and
transmit said data from said device before transmitting said other data.
20. A memory containing a sequence of instructions, said sequence of instructions being executable on a processor, and wherein execution of said sequence of instructions by said processor causes said processor to perform the steps of:
generating data, said data having minimal bandwidth requirements;
classifying said data as having minimal bandwidth requirements;
assigning a higher priority to said data relative to other data without minimal bandwidth requirements for transmission; and
transmitting said data before transmitting said other data.
21. A memory containing a sequence of instructions, said sequence of instructions being executable on a processor, and wherein execution of said sequence of instructions by said processor causes said processor to perform the steps of:
receiving data, said data having minimal bandwidth requirements;
determining a classification for said data;
assigning a higher priority to said data relative to other data without minimal bandwidth requirements for transmission; and
transmitting said data from before transmitting said other data.
The present invention relates generally to the field of computer networking, and more particularly to the reservation of network resources for low bandwidth messages requiring minimum transmission latency.
Certain computer applications, such as dynamic simulations and "twitch" games require time-critical user input and computer response. Twitch games are a class of computer games exemplified by fighting or combat games in which a user controls a character and inputs movement and firing or hitting commands at a high rate. Twitch games are characterized by a high degree of user interaction, and since user input is on the order of seconds or fractions of a second, this input requires immediate registration and response from the computer in order to maintain the playability and realism of the game. Twitch games thus require the user to respond quickly to computer signals, and the computer to quickly respond to user input. Any delay by the computer to the user input would thus result in the improper flow or execution of the game or simulation.
Twitch games are also characterized by the transmission of messages of a small size and of only a few different types. Users of twitch games input commands through a device such as a joystick or keypad. These devices typically allow only a limited number of commands, such as lateral and vertical movement and various punching, kicking and firing commands as required by the games. Because the commands invoke relatively non-complex responses from the computer, the commands can be encoded within messages of a small size. For example, in a typical twitch game the command to fire a gun can be encoded and sent in a command word requiring only 8-bits.
Many computer games and simulation programs were originally written for and executed on single computer consoles such as arcade machines. These machines typically allow for player against computer, or multi-player play through multiple input devices on the console. With the growth of personal computer use and network access, however, many computer games are increasingly being played between players on personal computers over a network or modem link.
Although use of general purpose computer networks for the execution of real-time and time critical applications has increased, these networks are typically ill-suited for such applications because of transmission protocols that introduce an unacceptable degree of network latency. Latency is the minimum time required to transmit a packet through the network devices and lines constituting the network. A primary determinant of the latency of a network is the amount of transmission bandwidth available in each network device. As the complexity of a network and the amount of traffic over a network increases, this bandwidth is consumed and latency correspondingly increases. For many applications, increased latency results in slower transmission which does not jeopardize program execution. However for applications such as twitch games, increased latency could render a game or simulation unplayable.
One approach to playing twitch games over a computer network has been to utilize special low latency networks specifically designed for real-time and time critical applications. This approach has the disadvantage of being expensive and impractical for casual users. A second approach has been to dedicate a general purpose transmission medium to the time-critical application. This method may provide sufficient bandwidth for the application, but typically requires that no other application transmit messages over the network at the same time. This approach thus denies the use of the network to general purpose traffic while a game or simulation is being played.
It is thus desirable to provide a method of executing time-critical computer applications, such as twitch games, over general purpose networks without the network latency associated with such networks. One of the primary general purpose networks gaining widespread use is the Internet. Messages are transmitted over the Internet using the Transmission Control Protocol/Internet Protocol (TCP/IP). The TCP/IP protocol is based on the principle of "best effort" transmission between entities on the network. Messages on the Internet are non-prioritized and implement collision mechanisms in order to reach their destination. Because of the non-deterministic nature of TCP/IP message transmission, the Internet is not well suited to applications requiring time-critical response.
A recent extension to TCP/IP protocol has introduced the concept of reservation of network resources within individual network devices on the Internet as an attempt to facilitate the execution of real-time applications across the Internet. Such resources include memory and buffer space within computers and routers on the network. The reservation of such resources provides adequate network bandwidth for deterministic transmission of application messages which require time-critical response. However, present reservation protocols do not provide priority queuing for small data packets which require extremely low latency transmission but do not require substantial network bandwidth. Therefore, what is further needed is a mechanism for extending resource reservation protocols to accommodate the prioritization of low bandwidth, minimum latency messages of small packet sizes.
The present invention discloses a method and apparatus for transmitting small, time critical messages through a network channel with reduced latency. A host computer generates data which has minimal bandwidth requirements. The host classifies the data as minimal bandwidth data and prioritizes the data relative to other data for transmission before the other data. The host then transmits the data to a second device on the network before transmitting the other data.
In one embodiment of the present invention, the minimal bandwidth data is received by the second device which determines the classification of the data. If the data requires minimal bandwidth transmission, the second device prioritizes the data relative to other data and transmits the data to the next network device before transmitting the other data.
In a further embodiment of the present invention, resources within the host and routers which transmit the minimal bandwidth data are reserved by a resource reservation protocol. This protocol includes an extension which classifies the data as requiring minimal bandwidth and prioritizes the data in the data transmission queues of the hosts and routers.
Other features of the present invention will be apparent from the accompanying drawings and from the detailed description which follows.
The present invention is illustrated by way of example and not limitation in the figures of the accompanying drawings, in which like references indicate similar elements and in which:
FIG. 1 illustrates a network including hosts sending and receiving bandwidth reservation messages.
FIG. 2 is a block diagram of a computer system which may be used to implement an embodiment of the present invention.
FIG. 3 illustrates a software module used to request a twitch enabled RSVP channel.
FIG. 4 is a flow chart illustrating the transmission of a twitch packet through a twitch enabled RSVP channel.
FIG. 5 illustrates a twitch enabled router for use in a multi-cast network configuration.
FIG. 6 illustrates a network containing twitch enabled routers according to one embodiment of the present invention.
FIG. 7 is a flow chart illustrating the transmission of a twitch packet through a twitch enabled network.
A method and apparatus for routing messages of a small packet size through a low bandwidth, minimum latency network path is described. In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the present invention. It will be evident, however, to one skilled in the art that the present invention may be practiced without these specific details. In other instances, well-known structures and devices are shown in block diagram form to facilitate explanation.
According to the present invention, host computer systems and routers in a network are used to transmit messages using a guaranteed Quality of Service protocol. Quality of Service provides firm bounds on end-to-end message queuing delays. This service makes it possible to provide a service that guarantees both transmission delay and network bandwidth. As will be described below in detail, the present invention includes an extension to a network resource reservation protocol for the transmission of small packet size messages through a reserved resource network.
According to one embodiment, the resource reservation and message transmission and other aspects of the present invention are implemented by a central processing unit (CPU) in a host computer or a network router executing sequences of instructions stored in a memory. The memory may be a random access memory (RAM), read-only memory (ROM), a persistent store, such as a mass storage device, or any combination of these devices. Execution of the sequences of instructions causes the CPU to perform steps according to the present invention.
The instructions may be loaded into the memory of the host computer or router from a persistent store and/or from one or more other host computer systems over a network connection. For example, a source host computer may transmit a sequence of instructions to a target host computer in response to a message transmitted to the source host over a network by the target host. As the target host receives the instructions over the network connection, the target host stores the instructions in memory. The target host may store the instructions for later execution or execute the instructions as they arrive over the network connection. In some cases, the downloaded instructions may be directly supported by the CPU. Consequently, execution of the instructions may be performed directly by the CPU. In other cases, the instructions may not be directly executable by the CPU. Under these circumstances, the instructions may be executed by causing the CPU to execute an interpreter that interprets the instructions, or by causing the CPU to execute instructions which convert the received instructions to instructions which can be directly executed by the CPU.
In other embodiments, hardwired circuitry may be used in place of, or in combination with, software instructions to implement the present invention. Thus, the present invention is not limited to any specific combination of hardware circuitry and software, nor to any particular source for the instructions executed by the target.
FIG. 1 illustrates a network system 100 in which Resource Reservation Protocol (RSVP) is implemented. The RSVP protocol is defined in detail in the Internet draft-standard, "Resource Reservation Protocol (RSVP)--Version 1 Functional Specification," May 6, 1996. Although the present invention is henceforth described in terms of RSVP, it should be recognized that the present invention is not limited to use with RSVP or any other particular resource reservation protocol. Further, the present invention is not necessarily limited to the context of performing resource reservations.
In FIG. 1, it is assumed that a sending host 101, and a receiving host 102 each implement RSVP. The sending host 101 is coupled to the network 108 by a router 104. Similarly, receiving host 102 is coupled to the network 108 by router 106. The network 108 may be the Internet, a Wide Area Network (WAN), a local area network (LAN), or any combination thereof. The sending host 101 transmits PATH messages across network 108 to the receiving host 102. The PATH messages contain information required by the receiving host 102 to allow the receiving host 102 to make bandwidth reservation requests. These bandwidth reservation requests are sent by the receiving host 102 to the sending host 101 in the form of reserve (RESV) messages, which propagate, in one implementation, along the same path to the sending host 101 as taken by the PATH messages.
FIG. 2 illustrates a block diagram of a host computer in the network of FIG. 1. The architecture depicted in FIG. 2 is also applicable to a network router used in conjunction with the present invention. The computer system 200 includes a processor 202 coupled through a bus 201 to a random access memory (RAM) 204, a read only memory (ROM) 206, and a mass storage device 207 such as a disk or tape drive for storing data and instructions. An alphanumeric input device 221, such as a keyboard, is coupled to bus 201 for communicating information and command selections to processor 202. Another type of user input device is cursor control unit 222, such as a mouse or joystick, for communicating direction commands which control cursor movement on display 220, which is also coupled to processor 202 through bus 201. If computer system 200 is implemented in a host computer, the network interface 223 provides a network connection. This connection is typically to a network router, but can also be directly to another host computer. If computer system 200 is implemented in a router, the network interface 223 provides a network interface to a host computer or another router. Note that the architecture of FIG. 2 is provided only for purposes of illustration, and that a host computer or a router used in conjunction with the present invention is not limited to this specific architecture.
The present invention includes a reservation protocol for the reservation of network resources within routers for twitch packets transmitted over the network. Twitch packets are generated and utilized by time critical applications such as computer action games or real-time simulations. Because twitch packets are used in time-critical applications, they require a specialized quality of service when transmitted over a network. The current Internet architecture embodied in the Internet Protocol (IP) network protocol offers simple point-to-point best-effort service. This best-effort service is typically inadequate for the transmission of twitch packets because of network latencies and the indeterminacy of network transmissions. For a network to provide the appropriate quality of service, or bound on delay, it must allow for the data traffic streams (flows), to reserve network resources. Such resources could include a share of the bandwidth or a number of buffers within the routers.
Twitch packets are characterized by small packet size, typically on the order of 100 bits or less. Moreover, twitch packets are typically generated and sent for a limited number of commands within an application. For example, in an action game, twitch packets are used to encode commands for character movement and hitting action, all other game commands are non-twitch commands which do not require transmission via a guaranteed quality of service. Thus, twitch packets lend themselves to a reservation protocol which reserves a channel for the transmission of small packets of a limited number of types. For a network to deliver a quantitatively specified quality of service to a particular flow, it is usually necessary to set aside certain resources, such as a share of bandwidth or a number of buffers for that flow, within routers along the flow path.
The special handling required by twitch packets to ensure that they are transmitted with as little latency as possible requires that the hosts and routers on the transmission route set up a specialized quality of service. Implementation of this specialized quality of service requires communication between each of the hosts and routers comprising the network over which the twitch packets will be transmitted. Such communication among the network elements could be implemented through the transmission of special messages between each of the network elements, or a separate wire connection between each of the elements for notification of special handling requirements. Other embodiments include implementation of a proprietary message protocol for encoding and transmitting twitch packets between network elements, or extending existing protocols to include special handling mechanisms for twitch packets.
FIG. 3 illustrates a host computer and network router which implement a reservation protocol for twitch packets according to one embodiment of the present invention. Host 302 is coupled to router 304 through network line 330. Twitch game application 306 running on host 302 generates twitch packets. Twitch game application 306 communicates to the network through twitch reservation process 308 and classifier 310. Classifier 310 marks packets specified by twitch game application 306 as twitch packets. Classifier 310 is coupled to packet scheduler 312 which places twitch packets classified by classifier 310 at the beginning of the transmission queue within host 302. Host 302 transmits a reservation request to twitch reservation process 318 in router 304 over reservation request line 334. Twitch reservation process 318 within router 304 sends a reservation request to routing process 316 which is coupled to classifier 320 within router 304. Twitch reservation process 318 also sends a reservation request to packet scheduler 322 within router 304.
Data is sent from packet scheduler 312 from host 302 over data line 332 to classifier 320 in router 304. Data packets which have been marked as twitch packets are then sent to the front of the transmission queue by a queue management process within packet scheduler 322 in router 304. Twitch packet data is then sent from router 304 over output data line 336 from packet scheduler 322 in router 304 to the next downstream hop in the network.
The twitch enabled host and router thus operate as follows: twitch game application 306 generates twitch packets, and twitch reservation process 308 within host 302 sends a twitch packets to classifier 310. Twitch packets within the host are classified as twitch packets and scheduled to the front of the queue in packet scheduler 312. These packets are then sent to the next downstream hop, in this case router 304. Classifier 320 in router 304 decodes data packets according to twitch packet characteristics. The packet scheduler 322 in router 304 gives twitch packets priority to the front of the queue in router 304. Thus, twitch packets are classified within classifiers 310 and 320 and scheduled at the front of the respective queues by packet schedulers 312 and 322. In this manner, packets transmitted along twitch enabled routers and hosts are classified and given priority at the front of transmission queues and thereby transmitted with lower delay than normal network traffic.
Twitch reservation processes 308 and 318 in host 302 and router 304 respectively, reserve network bandwidth within hosts and router elements in a network. The twitch reservation process specifies the maximum size of each twitch packet to be transmitted from the host or router and specifies the maximum number of twitch packets to be sent in a unit of time. These specifications are transmitted from one twitch reservation process to the next twitch reservation process, along reservation request line 334. Twitch reservation processes in a downstream router respond by reserving network resources within the router such as buffers or share of bandwidth in response to the reservation request, and reserves resources to the extent available for packets of the specified size and the specified number. Twitch packets possessing the appropriate classification ID type are transmitted from and between twitch enabled routers without requiring IP protocol headers. Packet scheduler 322 within router 304 includes a queue manager unit 324. Queue manager unit 324 controls the queuing and transmission of data from router 304. Queue manager 324 prioritizes data traffic received from upstream hops, prioritizes control traffic, and prioritizes twitch traffic. Upon receiving packets classified as twitch packets by twitch reservation process 318 and classifier 320, the packet scheduler 322 and queue manager 324 place twitch packets in a higher priority queue than data packets and control traffic.
Standard queuing algorithms familiar to those skilled in the art could be utilized to implement priority queuing within packet scheduler 322. Such queuing algorithms should increase the priority of twitch packets as compared to regular data and control traffic and they should also prevent queue overflow and starvation of upstream hops. Standard queuing algorithms could also be utilized to implement flow control within packet scheduler 322 or queue manager 324. One such algorithm is a "leaky bucket" algorithm which enables a device to act as a stable buffer by providing a constant rate outflow for variable rate inflow.
In one embodiment, packet scheduler 322 and queue manager 324 implement an algorithm which reduce buffer requirements for small packet size twitch packets and reserve buffers only in the number specified by twitch reservation process 308 in the downstream hop. This dynamic buffering arrangement helps offset the cost of the router in providing network resources to the higher priority queuing given to twitch packets.
The packet and queue management elements within the host and router devices may also include mechanisms which facilitate special handling of the twitch packets between network hops. Such special handling could include functions such as bundling multiple twitch packets in a single packet to be sent as one packet to the next upstream hop, or compressing twitch packets for even greater transfer efficiency. One extension to the twitch protocol includes an option to bundle twitch packets for simultaneous transmission. Within a host or router, twitch packets which are to be bundled are tagged by the classifier, grouped by the packet scheduler, and prioritized and transmitted as a bundle by the queue manager.
Similarly, a second extension to the twitch protocol includes an option to compress twitch packets for compressed transmission. Twitch packets which are to be compressed are tagged by the classifier, compressed by a compression element within the host or router, and prioritized and transmitted by the packet scheduler and queue manager. A host or router which receives compressed twitch packets may also contain a decompression element for decompressing the compressed twitch packets. Standard compression algorithms familiar to those skilled in the art could be utilized to implement the compression and decompression functions.
FIG. 4 is a flow chart which illustrates the transmission of a twitch packet over a network consisting of a twitch enabled host and a twitch enabled router as shown in FIG. 3. In step 402, the router 304 receives a data packet from host 302 for transmission to a downstream hop. In step 404, the classifier 320 within router 304 checks whether the data packet is a twitch packet, if the data packet is not a twitch packet, the data packet is placed in the regular data transmission queue by packet scheduler 322. That packet is then sent out on data line 336 in the regular queue order in step 406. If the packet is a twitch packet, packet scheduler 322 places the twitch packet at the beginning of the queue in a twitch queue step 408. Any special handling requirements such as bundling or compression are also determined in step 404, and resolved in step 408. In step 410 the queue manager 324 checks whether the twitch rate exceeds the leaky bucket algorithm rate which buffers the transmission rate of data from the queue. If the twitch rate does exceed the leaky bucket rate, the twitch packet is placed in the regular transmission queue. If not, the twitch packet is transmitted using the twitch channel reserved by twitch reservation process 318. The twitch packet is then sent over data link 336 from router 304 to the next downstream hop.
In one embodiment of the present invention, the twitch reservation protocol is implemented as an extension to the Resource Reservation Protocol (RSVP). RSVP reserves network resources within links comprising hosts and routers along a network and thereby guarantees a minimum quality of service for transmission of data along the network. Within the RSVP protocol, the minimum size and the maximum size of a datagram is specified within a traffic specification. Current versions of RSVP do not reserve greater resources for packet sizes of a specified small size, nor do they control the queue order of packets depending on their packet size. The present invention extends the RSVP protocol by providing a mechanism whereby packets of a specified small size are queued in a priority higher than regular datagram and control traffic.
There are two fundamental RSVP message types RESV and PATH. Each receiver host sends RSVP reservation request (RESV) messages upstream toward the senders. These messages must follow exactly the reverse of the paths the data packets will use, upstream to all the sender hosts included in the sender selection. They create and maintain reservation state in each node along the paths. RESV messages must finally be delivered to the sender hosts themselves so that the hosts can set up appropriate traffic control parameters for the first hop. Each RSVP sender host transmits RSVP PATH messages downstream along the routes provided by the routing protocols following the paths of the data. These PATH messages store pass state in each node (router) along the way. This PATH state includes at least the unicast IP address of the previous hop node which is used to route RESV messages hop by hop in the reverse direction.
FIG. 5 illustrates a router which implements RSVP protocol with the twitch protocol extension. Router 502 is a multi-cast router which includes two inputs labeled a and b and two outputs labeled c and d. Upstream hops, which could be either upstream routers or a sending host, are numbered 504 and 506. Downstream hops, which could either be downstream routers or a receiving host, are numbered 508 and 510. Downstream hops, whether they are routers or the receiving host, send reservation requests RESV packets upstream to output nodes c and d. Router 502 propagates these reservation requests to the upstream nodes 504 and 506. Upstream nodes 504 and 506 transmit data to ports a and b in router 502. Router 502 transmits these data packets to downstream nodes 508 and 510 through output nodes c and d. Thus, reservation requests are transmitted upstream through router 502 from nodes 508 and 510 to nodes 504 and 506. Data nodes are transmitted in the opposite direction from nodes 504 and 506 through router 502 to downstream nodes 508 and 510.
FIG. 6 illustrates a network comprising sending host 601 and receiving host 602 coupled to three routers 604, 606 and 608. FIG. 6 illustrates a network in which each router is connected to a single upstream hop and a single downstream hop. However, FIG. 6 also applies to a multi-cast network in which each router may be connected to multiple upstream or downstream hops. In the multi-cast network, the routers implement the architecture illustrated in FIG. 5 for router 502. Note that the network illustrated in FIG. 6 is identical to the network illustrated in FIG. 1 except that network element 108 of FIG. 1 comprises a single router, which is router 606 in FIG. 6.
The sending host 601 transmits PATH messages across the network to the receiving host 602. The PATH messages contain information required by the receiving host 602 to allow the receiving host 602 to make bandwidth reservation requests to nodes along the network. These bandwidth reservation requests are sent by the receiving hosts 602 to the sending host 601 in the form of reserve (RESV) messages which propagate along the same path to the sending host 601 as taken by the PATH messages. Note that RSVP is designed for soft state--that is, RESV messages must be sent by the receiving message at regular intervals in order to maintain (i.e., "refresh") the reservation. In an alternative embodiment, the twitch extension for the RSVP protocol may be implemented for hard state--that is the network maintains a reservation status for twitch channels until a teardown message is sent to re-establish a non-reserved state.
The RSVP PATH message consists of a TSPEC object which carries the traffic specification generated by each data source within an RSVP session. This is transported unchanged through the network and is delivered to both intermediate network routers and the receiving application. The RSVP FLOWSPEC object carries reservation request information generated by receiving hosts. The information in the FLOWSPEC flows upstream toward data sources. It may be used or updated at intermediate network elements before arriving at the sending application. Thus, sending hosts specify the traffic they expect to generate in TSPEC objects and send them within PATH messages across the network to the receiving host. In turn, the receiving host sends network reservation requests within the FLOWSPEC to each node between the receiving host and the sending host. The nodes between the receiving host and sending hosts respond to the FLOWSPEC object sent by the receiving host by reserving the specified bandwidth requested.
The RSVP sender TSPEC object carries information about a data source's generated traffic. In one embodiment, the present invention adds fields to the existing sender TSPEC that is specified in the Version 1 of the Functional Specification of RSVP. Table 1 illustrates the existing sender TSPEC object as extended for twitch reservations. Field 1 comprises the fields within the existing TSPEC and may contain fields for token bucket rate, token bucket size, peak data rate, minimum policed unit, and maximum packet size. In the present invention, fields are added to specify the twitch packet size and the twitch packet rate with a binary field which specifies whether the traffic has twitch characteristics or is a twitch packet. This field would be decoded by classifier 310 and classifier 320 as a twitch packet within twitch reservation processes 308 and 318. The twitch RSVP TSPEC also includes a field which specifies the maximum number of messages to be sent within a session. Thus, the twitch RSVP TSPEC requests a reservation for N messages, each message to have a size of n bytes of data. A typical twitch packet may be an 8 byte word which encodes a command to move a character or to fire a weapon. The twitch RSVP TSPEC requests a reservation for N number of such packets in t units of time of each packet to be of size n.
TABLE 1______________________________________TSPEC Object With Twitch Extension______________________________________1 Standard RSVP TSPEC Header2 Standard RSVP TSPEC Fields3 Twitch Header4 Maximum Twitch Data Rate5 Maximum Twitch Packet Size______________________________________
The RSVP FLOWSPEC object carries information necessary to make reservation requests from the receivers to the network and to each link router along the network. This includes an indication of which quality of service control service is being requested and the parameters needed for that service. The quality of service control service requested is indicated by the service number in the FLOWSPEC's per service header. In one embodiment of the present invention, receivers send a twitch FLOWSPEC object. The twitch FLOWSPEC object contains fields which extend the standard RSVP FLOWSPEC object for reservation of the twitch channel within nodes along a network.
The standard RSVP FLOWSPEC object is illustrated in Table 2 and may include fields for token bucket rate, token bucket size, peak data rate, minimum policed unit and maximum packet size. The twitch extension to the RSVP FLOWSPEC adds fields for number of twitch packets sent within a unit of time that is the twitch data rate the maximum number of twitch packets and the maximum twitch packet size. The twitch reservation process 308 and 318 within twitch enabled routers and hosts as illustrated in FIG. 3 reserve twitch channels in response to the twitch RSVP FLOWSPEC as was requested by the twitch RSVP TSPEC. Note that within the RSVP specification, several different qualities of service may be requested by the RSVP FLOWSPEC. The present invention is intended to work with any of these specified qualities of service, such as guaranteed service, and controlled load services.
TABLE 2______________________________________FLOWSPEC Object With Twitch Extension______________________________________1 Standard RSVP FLOWSPEC Header2 Standard RSVP FLOWSPEC Fields3 Twitch Header4 Maximum Requested Twitch Rate5 Maximum Requested Twitch Packet Size______________________________________
FIG. 7 is a flow chart illustrating the process of reserving a twitch channel within nodes of a network and propagating a twitch message generated by a twitch application on a sending host to a receiving host along the network illustrated in FIG. 6. In step 700, the sending host 601 sends a TSPEC within a PATH message specifying that twitch message traffic will be transmitted to the receiving host 602. The TSPEC within the PATH message is propagated from the sending host 601 along the network through the network routers to the receiving host 602. In response to the PATH message the receiving host 602 transmits a FLOWSPEC requesting reservation of twitch channels within routers along the network, step 702. The reservation request matches the requested resources within the TSPEC from the sending host. The RSVP protocols do not affect the routing algorithms which are implemented within the hosts and the routers.
In step 703, router 608 receives the FLOWSPEC from the receiving host 602 and reserves twitch bandwidth in accordance with the request within the FLOWSPEC, and propagates the request to the next hop. The reserved resources could be a proportion of the bandwidth within the router or the number of memory buffers within the router. The FLOWSPEC is propagated from router 608 to router 606. In step 704, router 606 reserves twitch bandwidth in accordance with the FLOWSPEC request and propagates the request to the next hop. In step 706, router 604 receives the FLOWSPEC request from router 606 and reserves twitch bandwidth in accordance with the FLOWSPEC request. Router 604 then propagates the request to the next hop.
In step 708 the sender host receives a twitch command from the user. In the context of a twitch game, this could be input from a joystick or similar input device to invoke an action command on the sending host. In step 710, router 604 receives the twitch message from sending host 601, places that message at a priority level in its transmission queue and transmits the message to the next hop. At step 712, router 606 receives the twitch message from router 604, places the message at a priority level in its transmission queue and transmits the message to the next hop. At step 714, router 608 receives the twitch message from router 606 places that message at a priority level in the transmission queue, and transmits the message to the next hop, step 714. At step 716 the receiving host 602 receives the twitch message from router 608 decodes the parameter encoded within the twitch message and executes the instruction corresponding to the parameter. Because the twitch message has been sent from the sending host 601 to the receiving host 602 at a priority level within each of the routers along the path, the twitch message has propagated with a minimum of delay and a minimum of latency, thus enhancing the playability of the action game and the realism of the simulation.
Thus, a method and apparatus have been described for the transmission of low bandwidth messages across a network with reduced latency. Although the present invention has been described with reference to specific exemplary embodiments, it will be evident that various modifications and changes may be made to these embodiments without departing from the broader spirit and scope of the invention as set forth in the claims. Accordingly, the specification and drawing are to be regarded in an illustrative rather than a restrictive sense.
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Will he be the next 3 point shooter we need? Amethreeo or Ametrio, I hope be becomes that outside threat that we need.
Member since 07 December 2011 | Blog
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21-3 Bucks
"When they belong to a generation which is going to bankrupt my generation on the way to their graves."
I think the boomers did pretty well for the spoiled brats that are now supposed to be leaders and help build our country.
DJ, you are making some people irritated for a football site that is to be void of politics namely me.
The article wasn't too bad for somebody with PMS. I hope you feel better in a couple of days DJ. 11W like my college asked me for money and I gave to both. Now I feel cheated. Shitty Teachers, really. Have you ever taught? Don't make assumptions that you know nothing about.
Thanks from me too. I got too jumpy and made some assumptions. I trust Urban. I trust Urban. I trust Urban. I trust Urban.
Don't get these two Jim's mixed up. I love Urban and I like all the comments posted. :)
With the posting on YouTube by EE, do you think he will still be a Buckeye? This scares the crap out of me.
I agree that we should hold ourselves to higher standards with dignity and character. I don't like for our team or university to get tagged with uncomplimentary claims. In the real world, things like this go on quite a bit. My friend's job was a headhunter. That was a dog eat dog job. Urban is not breaking rules, but I hate the talk that is probably going on behind our backs. I might just be too sensitive, but I like Urban's results.
I understand that Kellen Winslow was his instructor.
I voted yes. Don't forget Thad's record and his recruiting. Indiana and meatchicken may challenge, but the Bucks have the talent.
Agree, but he just doesn't seem to be getting the respect he deserves.
Thanks for your comment. I just made a bonehead statement about the D1 offer and thinking about BCS schools.
Who is their coach, Bollman?
He will love playing in the Shoe.
Wonder if her name is Woody Hudy?
I agree with you about Burger. I can't believe he didn't get a scholly for a D1 school. OSU is very lucky to get him to walk on. He must be very well coached or just have great instincts. He flies to the ball and lays the wood. He reminds me of AJ Hawk. (maybe a stretch but I really like him)
He really plays fast and with good instincts. Needs work on technique but we have the coaches to take care of this.
Was this the same school where Sanzenbacher played?
@ M Man It's blasphemy I tell ya!
Woulda, Coulda, Shoulda - OSU kicked a lot of asses and won the B1G many times in the process.
I second that.
This seemed like a movie where WB's body went into DT and Sully. The numbers were all wrong. WB took more shots than any player in Buckeye history. I don't know how proud he is of that record. He had all the talent to be excetional but not the mindset. Good luck in the future WB.


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PETS LOST & FOUND: LOST CHIHUAHUA on Friday, July 24th, around noon. Her name is BELLA. She's a small white and tan Chihuahua with pink nose and belly, curled tail, and her ears are really big. She is 4-1/2 years old. No chip and not spayed. She ran away from 27th Street...More info Email a friend
PETS LOST & FOUND: Found this chihuahua on 157 Ave and Miller. She's safe and I will keep her if I don't find her owners. I would like to find her owners if possible. She does not have a chip and she has not been neutered. Need documented proof, vet information, photographs...More info Email a friend
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CATS: Beautiful young bluepoint and blue-creampoint females, CFA. Parents on premises. Healthy and playful. Vet health certificate, all shots and deworming included at reasonable price of $345. Experienced hobby breeder #U02-005513, West of Aventura near I-...More info Email a friend
PETS LOST & FOUND: Please help me find him! He is very sick with mange and is currently under treatment. This condition is highly contagious and can cause him a lot of discomfort, if not medicated. If you've seen him, please contact me as soon as possible. Last seen on...More info Email a friend
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text: No recent wiki edits to this page. OverviewFuel is one of the many characters in Mother 3. He is the son of Lighter and Coaleen. In the events of Mother 3, Fuel is rescued by Flint when he gets trapped in a burning building. Fuel then joins Flint's party for a short amount of time, throwing rocks and healing Flint from time to time. It is notable that when Fuel is used in later chapters (through the use of the debug room), he doesn't use his older sprite. In addition, one costume for Ness in Super Smash Bros. Brawl looks similar to Fuel's clothing.


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Getting In
Schools & Colleges
- School of Agriculture & Environmental Sciences
- College of Arts & Sciences
- School of Business & Economics
- School of Education
Katherine Wilkerson
Administrative AssociateOffice: 101 Marteena HallPhone: 336-285-2105 336-285-2108Fax: 336-334-7423email: email@example.com
Mrs. Katherine Wilkerson is the Administrative Associate for the Physics Department. She has been with the university since 2004 and with the Physics Department since June 2009. She is your "go-to" person for help with registration and questions.
She is the current Secretary for the NC A&T Staff Senate and has been an active member of the Staff Senate since 2009.
In her spare time, she enjoys working outside, horseback riding, reading, and vacationing on the Outer Banks.


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Job Seekers, Sign In
Academic Advisor OR Senior Academic Advisor « Position Deleted on 2/12/2013 »
|University of Nevada Las Vegas
|Las Vegas, NV
|Application Due:
|Open Until Filled
|Full Time
This position is no longer an active posting on HigherEdJobsThe University of Nevada, Las Vegas invites applications for Academic Advisor OR Senior Academic Advisor.
PROFILE of the UNIVERSITY
UNLV is a comprehensive research university of approximately 27,000 students and 2,800 faculty and staff dedicated to teaching, research, and service. The university has internationally recognized programs in hotel administration and creative writing; professional degrees in law, architecture, and dental medicine; and leading programs in fine arts, sciences and education. UNLV is located on a 332-acre main campus and two satellite campuses in dynamic Southern Nevada. For more information, visit us on-line at: http://www.unlv.edu.
ROLE of the POSITION
Candidate for this position will report to the Director of Advising in the UNLV College of Sciences. Candidate will be responsible for disseminating information for 12 degree programs and related issues to 2500 students with majors in biology, chemistry, geoscience, mathematics and physics/astronomy. Position requires working with students on complicated issues regarding their degree progress and/or life issues, as well as participating in college and university outreach activities. Refers students to university resources as required. Requires excellent English interpersonal communication and computer skills. Ability to easily learn additional computer or other technology skills as required. Conscientious attention to detail is a must. Candidates for the Advisor 2 position must have experience acting as a team leader with other advisors and work closely with a Director.
An Academic Advisor position requires a Bachelor's Degree from a regionally accredited college or university and one year advising or related experience. A Senior Academic Advisor requires a Master's Degree from a regionally accredited college or university and at least one (1) year of related professional work experience OR a Bachelor's degree from a regionally accredited college or university and three (3) years of related professional work experience. Experience in the sciences desirable, but not required..
Salary competitive with those at similarly situated institutions. Position is contingent upon funding.
Submit a letter of interest, a detailed resume listing qualifications and experience, and the names, addresses, and telephone numbers of at least three professional references who may be contacted. Applicants should fully describe their qualifications and experience, with specific reference to each of the minimum and preferred qualifications because this is the information on which the initial review of materials will be based. Applications will begin to be reviewed on January 8 2013, with reviews continuing until the position is closed.
This position will remain open until filled. Materials should be addressed to Miriam Frankel, Search Committee Chair, and are to be submitted via on-line application at https://hrsearch.unlv.edu. For assistance with UNLV's on-line applicant portal, contact UNLV Employment Services at (702) 895-2894 or email@example.com.
UNLV is an Affirmative Action / Equal Opportunity educator and employer committed to excellence through diversity.
© Copyright 2015 Internet Employment Linkage, Inc.


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Global Student Friendship
Our email: firstname.lastname@example.com!
Please come and meet us at ODU's Fall 2014 Involvement Fair at ODU Kaufmann Mall on Thursday, 28 Aug 2014 from 10:00 AM - 2:00 PM.
Our team (some members were not in the picture) during a team meeting in March 2014!
The Founder and Leader of Global Student Friendship was awarded the 2013 MONARCH LEGACY AWARD by Old Dominion University for a member or members of the Old Dominion University community whose actions made a significant impact on the campus community, especially for founding Global Student Friendship which has reached more than 4,000 international students and has expanded into a Hampton Roads Chapter that serves internationals in the entire region. Thanks for the great partnership with all serving friends, supporters, and prayers from all people.
The Founder and Leader of Global Student Friendship was awarded the International Student/Scholar Ministry TIMOTHY AWARD by a non-profit organization called Association of Christians Ministering among Internationals whose members are from the US, Europe, Asia, Africa, Australia and around the world. Thanks for the great partnership with all serving friends, supporters, and prayers from all people.
GSF Volunteer Team is part of the success story of Old Dominion University receiving the 2013 US President Higher Education Community Service Honor Roll.
Link: http://www.odu.edu/news/2013/3/community_service_ho
More than 200 New and Returning Internationals from 23 nations and American friends attended the 2013 Welcome Bus Tour and Luncheon/Reception for ODU New Internationals. We want to thank organization that made our Welcome events successful: the US NAVY, ODU, student volunteers from ODU's Indian Student Association, ODU's Chinese Student and Scholar Association, ODU's Persian Student Association, Ret. US. Navy Capt. John Gorman, Bill Thompson, bus drivers, and volunteers from local churches. We also want to thank the First Presbyterian Church for hosting this wonderful events and local churches for filling out the Welcome bags for our International students.


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The Council for Adult and Experiential Learning invites you to join us in Baltimore, Maryland this November for the CAEL International Conference. This year's theme: "Where to Grow from Here: Scaling What Works for Adult Students", tackles issues of scalability within educational systems. How do we grow our educational systems to effectively reach greater numbers of adult learners? The conference will be held November 18-20, 2015 at the Baltimore Hilton.
The annual conference brings together over 500 participants to learn, network, and work together to make lifelong learning accessible to adults around the world. Attendees include college faculty and administrators, HR professionals, workforce developers and representatives from labor and government.
Click here to register for the conference.
See information about the location and hotel for our 2015 Conference.
View the schedule at a glance and pre and post-conference workshops! Check back for information on keynote speakers and sessions!
Become a conference exhibitor or sponsor, and you will reach college faculty and administrators, employers, and policymakers who care about adult learners.
View photos, videos, and PowerPoint presentations from last year's conference.