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US 6881550 B2 Abstract A method for determining the presence of an analyte in a fluid is described along with various components of an apparatus specifically designed to carry out the method. The method involves taking a reflectance reading from one surface of an inert porous matrix impregnated with a reagent that will interact with the analyte to produce a light-absorbing reaction product when the fluid being analyzed is applied to another surface and migrates through the matrix to the surface being read. Reflectance measurements are made at two separate wavelengths in order to eliminate interferences, and a timing circuit is triggered by an initial decrease in reflectance by the wetting of the surface whose reflectance is being measured by the fluid which passes through the inert matrix. Repeatability is insured by a normalization technique performed on the light source before each reading, and an alignment method operated on the reagent strip prior to emplacement on the apparatus. The method and apparatus are particularly suitable for the measurement of flucose levels in blood without requiring separation of red blood cells from serum or plasma.
Claims(7) 1. A method for determining glucose concentration, the method comprising:
applying an unmetered whole blood sample to a reagent test strip for use in an apparatus for determining the blood glucose concentration of a sample of whole blood, the apparatus including optical means for detecting intensity of light reflected from a reading surface portion of the reagent test strip, the reagent test strip comprising:
a sample receiving surface portion for receiving an unmeasured whole blood sample;
a reading surface portion, other than the sample receiving surface portion, from which reflectance is read by the apparatus; and
a notch for aligning the reading surface portion of the reagent test strip in register with the optical means in the apparatus;
allowing the unmetered whole blood sample to migrate to the reading surface portion; and
monitoring the reflectance of the reading surface portion using the optical means of the apparatus;
wherein the applying of the unmetered whole blood sample occurs while the reagent test strip is emplaced in the apparatus.
2. The method of
3. The method of
4. The method of
5. The method of
measuring, prior to the applying step, the reflectance of the reading surface portion.
6. The method of
7. The method of
determining, after the monitoring step, a further change in reflectance at the reading surface portion during the incubation period as a measure of the concentration of blood glucose in the unmetered whole blood sample.
Description This application is a Continuation of Ser. No. 09/784,993 filed Feb. 15, 2001, now U.S. Pat. No. 6,489,133 issued on Dec. 3, 2002. which is a Division of Ser. No. 09/323,442 filed May 28, 1999, now U.S. Pat. No. 6,268,162B1 issued Jul. 31, 2001, which is a Continuation of Ser. No. 08/965,745 filed Nov. 7, 1997, now U.S. Pat. No. 5,968,760 issued Oct. 19, 1999, which is a Continuation of Ser. No. 08/941,868 filed Sep. 30, 1997, now U.S. Pat. No. 5,843,692 issued Dec. 1, 1998, which is a Continuation of Ser. No. 08/691,154 filed Aug. 1, 1996, now abandoned, which is a Continuation of Ser. No. 08/408,064 filed Mar. 21, 1995, now U.S. Pat. No. 5,563,042 issued Oct. 8, 1996, which is a Continuation of Ser. No. 08/148,055 filed Nov. 5, 1993, now U.S. Pat. No. 5,426,032 issued Jun. 20, 1995, which is a Division of Ser. No. 08/006,859 filed Jan. 21, 1993, now abandoned, which is a Division of Ser. No. 07/819,431 filed Jan. 10, 1992, now abandoned, which is a Division of Ser. No. 07/187,602 filed Apr. 28, 1988, now U.S. Pat. No. 5,179,005 issued Jan. 12, 1993, which is a Continuation-in-part of Ser. No. 06/896,418 filed Aug. 13, 1986, now U.S. Pat. No. 4,935,346 issued Jun. 19, 1990. The present invention relates to a test device and method for the calorimetric determination of chemical and biochemical components (analytes) in aqueous fluids, particularly whole blood. In one preferred embodiment it concerns a test device and method for calorimetrically measuring the concentration of glucose in whole blood. The quantification of chemical and biochemical components in colored aqueous fluids, in particular colored biological fluids such as whole blood and urine and biological fluid derivatives such as blood serum and blood plasma, is of ever-increasing importance. Important applications exist in medical diagnosis and treatment and in the quantification of exposure to therapeutic drugs, intoxicants, hazardous chemicals and the like. In some instances, the amounts of materials being determined are either so miniscule�in the range of a microgram or less per deciliter�or so difficult to precisely determine that the apparatus employed is complicated and useful only to skilled laboratory personnel. In this case the results are generally not available for some hours or days after sampling. In other instances, there is often an emphasis on the ability of lay operators to perform the test routinely, quickly and reproducibly outside a laboratory setting with rapid or immediate information display. One common medical test is the measurement of blood glucose levels by diabetics. Current teaching counsels diabetic patients to measure their blood glucose level from two to seven times a day depending on the nature and severity of their individual cases. Based on the observed pattern in the measured glucose levels, the patient and physician together make adjustments in diet, exercise and insulin intake to better manage the disease. Clearly, this information should be available to the patient immediately. Currently a method widely used in the United States employs a test article of the type described in U.S. Pat. No. 3,298,789 issued Jan. 17, 1967 to Mast. In this method a sample of fresh, whole blood (typically 20-40 μl) is placed on an ethylcellulose-coated reagent pad containing an enzyme system having glucose oxidase and peroxidase activity. The enzyme system reacts with glucose and releases hydrogen peroxide. The pad also contains an indicator which reacts with the hydrogen peroxide in the presence of peroxidase to give a color proportional in intensity to the sample's glucose level. Another popular blood glucose test method employs similar chemistry but in place of the ethylcellulose-coated pad employs a water-resistant film through which the enzymes and indicator are dispersed. This type of system is disclosed in U.S. Pat. No. 3,630,957 issued Dec. 28, 1971 to Rey et al. In both cases the sample is allowed to remain in contact with the reagent pad for a specified time (typically one minute). Then in the first case the blood sample is washed off with a stream of water while in the second case it is wiped off the film. The reagent pad or film is then blotted dry and evaluated. The evaluation is made either by comparing color generated with a color chart or by placing the pad or film in a diffuse reflectance instrument to read a color intensity value. While the above methods have been used in glucose monitoring for years, they do have certain limitations. The sample size required is rather large for a finger stick test and is difficult to achieve for some people whose capillary blood does not express readily. In addition, these methods share a limitation with other simple lay-operator calorimetric determinations in that their result is based on an absolute color reading which is in turn related to the absolute extent of reaction between the sample and the test reagents. The fact that the sample must be washed or wiped off the reagent pad after the timed reaction interval requires that the user be ready at the end of the timed interval and wipe or apply a wash stream at the required time. The fact that the reaction is stopped by removing the sample leads to some uncertainty in the result, especially in the hands of the home user. Overwashing can give low results and underwashing can give high results. Another problem that often exists in simple lay-operator calorimetric determinations is the necessity for initiating a timing sequence when blood is applied to a reagent pad. A user will typically have conducted a finger stick to obtain a blood sample and will then be required to simultaneously apply the blood from the finger to a reagent pad while initiating a timing circuit with his or her other hand, thereby requiring the use of both hands simultaneously. This is particularly difficult since it is often necessary to insure that the timing circuit is started only when blood is applied to the reagent pad. All of the prior art methods require additional manipulations or additional circuitry to achieve this result. Accordingly, simplification of this aspect of reflectance reading instruments is desirable. The presence of red blood cells or other colored components often interferes with the measurements of these absolute values, thereby calling for exclusion of red blood cells in these two prior methods as they are most widely practiced. In the device of U.S. Pat. No. 3,298,789 an ethyl cellulose membrane prevents red blood cells from entering the reagent pad. Similarly, the water-resistant film of U.S. Pat. No. 3,630,957 prevents red blood cells from entering the pad. In both cases the rinse or wipe also acts to remove these potentially interfering red blood cells prior to measurement. Accordingly, there remains a need for a system of detecting analytes in colored liquids, such as blood, that does not require removal of excess liquid from a reflectance strip from which a reflectance reading is being obtained. Novel methods, compositions and apparatus are provided for diagnostic assays comprising a hydrophilic porous matrix containing a signal producing system and a reflectance measuring apparatus which is activated upon a change in reflectance of the matrix when fluid penetrates the matrix. The method comprises adding the sample, typically whole blood, to the matrix which filters out large particles, such as red blood cells, typically with the matrix present in the apparatus. The signal-producing system produces a product which further changes the reflectance of the matrix, which change can be related to the presence of an analyte in a sample. Exemplary of the diagnostic assay system is the determination of glucose in the whole blood, where the determination is made without interference from the blood and without a complicated protocol subject to use error. The present invention can be more readily understood by reference to the following detailed description when read in conjunction with the attached drawings, wherein: The Reagent Element The subject invention provides an improved rapid and simple methodology employing reliable and easy to operate apparatus for the determination of analytes such as glucose, particularly involving an enzyme substrate which results in the production of hydrogen peroxide as an enzyme product. The method involves applying to a porous matrix a small volume of whole blood, sufficient to saturate the matrix. It is to be noted that the present system is capable of determining glucose levels from optical readings of whole blood samples. Separation of plasma from blood in the sample is unnecessary, and the present invention avoids the requirement of this step. In addition, this system is capable of performing accurate readings as long as only a small volume saturates the matrix of the test strip. Above this threshold, the reading is volume independent. Bound to the matrix are one or more reagents of a signal producing system, which results in the production of a product resulting in an initial change in the amount of reflectance of the matrix. The matrix is typically present in a reflectance-measuring apparatus when blood is applied. The liquid sample penetrates the matrix, resulting in an initial change in reflectance at the measurement surface. A reading is then taken at one or more times after the initial change in reflectance to relate the further change in reflectance at the measurement surface or in the matrix as a result of formation of the reaction product to the amount of analyte in the sample. For measurements in blood, particularly glucose measurements, whole blood is typically used as the assay medium. The matrix contains an oxidase enzyme which produces hydrogen peroxide. Also contained in the matrix will be a second enzyme, particularly a peroxidase, and a dye system which produces a light-absorbing product in conjunction with the peroxidase. The light-absorbing product changes the reflectance signal of the matrix system. With whole blood, readings are taken at two different wavelengths, with the reading at one wavelength used to subtract out background interference caused by hematocrit, blood oxygenation, and other variables which may affect the result. Thus, the present invention is capable of analyzing samples of whole blood. A reagent element is employed which comprises the matrix and the members of the signal producing system contained within the matrix. The reagent element may include other components for particular applications. The method requires applying a small volume of blood, which typically has not been subject to prior treatment (other than optional treatment with an anticoagulant), to the matrix. Timing of the measurement is activated or initialized by the apparatus' automatically detecting a change in reflectance of the matrix when fluid penetrates the matrix. The change in reflectance over a predetermined time period as a result of formation of reaction product is then related to the amount of analyte in a sample. The intensity of the light source used to analyze the sample is, of course, also carefully monitored and regulated, to insure the repeatability of the measurement. The first component of the present invention to be considered is a reagent element, conveniently in the shape of a pad, comprising an inert porous matrix and the component or components of a signal-producing system, which system is capable of reacting with an analyte to produce a light-absorbing reaction product, impregnated into the pores of the porous matrix. The signal-producing system does not significantly impede the flow of liquid through the matrix. In order to assist in reading reflectance, it is preferred that the matrix have at least one side which is substantially smooth and flat. Typically, the matrix will be formed into a thin sheet with at least one smooth, flat side. In use, the liquid sample being analyzed is applied to one side of the sheet whereby any assay compound present passes through the reagent element by means of capillary, wicking, gravity flow and/or diffusion actions. The components of the signal producing system present in the matrix will react to give a light absorbing reaction product. Incident light impinges upon the reagent element at a location other than the location to which the sample is applied. Light is thus reflected from the surface of the element as diffuse reflected light. This diffuse light is collected and measured, for example by the detector of a reflectance spectrophotometer. The amount of reflected light will be related to the amount of analyte in the sample, usually being an inverse function of the amount of analyte in the sample. The Matrix Each of the components necessary for producing the reagent element will be described in turn. The first component is the matrix itself. The matrix will be a hydrophilic porous matrix to which reagents may be covalently or noncovalently bound. The matrix will allow for the flow of an aqueous medium through the matrix. It will also allow for binding of protein compositions to the matrix without significantly adversely affecting the biological activity of the protein, e.g., enzymatic activity of an enzyme. To the extent that proteins are to be covalently bound, the matrix will have active sites for covalent bonding or may be activated by means known to the art. The composition of the matrix will be reflective and will be of sufficient thickness to permit the formation of a light-absorbing dye in the void volume or on the surface to substantially affect the reflectance from the matrix. The matrix may be of a uniform composition or a coating on a substrate providing the necessary structure and physical properties. The matrix will usually not deform on wetting, thus retaining its original conformation and size. The matrix will have a defined absorbance, so that the volume which is absorbed can be calibrated within reasonable limits, variations usually being maintained below about 50% preferably not greater than 10%. The matrix will have sufficient wet strength to allow for routine manufacture. The matrix will permit non-covalently bound reagents to be relatively uniformly distributed on the surface of the matrix. As exemplary of matrix surfaces are polyamides, particularly with samples involving whole blood. The polyamides are conveniently condensation polymers of monomers of from 4 to 8 carbon atoms, where the monomers are lactams or combinations of diamines and di-carboxylic acids. Other polymeric compositions having comparable properties may also find use. The polyamide compositions may be modified to introduce other functional groups which provide for charged structures, so that the surfaces of the matrix may be neutral, positive or negative, as well as neutral, basic or acidic. Preferred surfaces are positively charged. It has been determined that this positive charge enhances both stability and shelf-life. When used with whole blood, the porous matrix preferably has pores with an average diameter in the range of from about 0.1 to 2.0 μm, more preferably from about 0.6 to 1.0 μm. When the porous matrix contains pores having an average diameter of about 0.8 μm, the sample of blood will not cause a chromatographic effect. That is, the blood sample will not seek out the edges of the circular matrix. Rather, the blood remains seated within all the pores of the matrix and provides for a uniform readability of the entire matrix. In addition, this pore size maximizes the non-blotting effect of the blood. That is, the pore size is both adequately filled, but not overfilled, so that the hematocrit level of blood will not cause the sample to require blotting prior to reading of the sample. Also, it has been found that pores of this size are optimal when shelf-life and stability are taken into consideration. A preferred manner of preparing the porous material is to cast the hydrophilic polymer onto a core of non-woven fibers. The core fibers can be any fibrous material that produce the described integrity and strength, such as polyesters and polyamides. The reagent that will form the light-absorbing reaction product, which is discussed later in detail, is present within the pores of the matrix but does not block the matrix so that the liquid portion of the assay medium, e.g. blood, being analyzed can flow through the pores of the matrix, while particles, such as erythrocytes, are held at the surface. The matrix is substantially reflective so that it gives a diffuse reflectance without the use of a reflective backing. Preferably at least 25%, more preferably at least 50%, of the incident light applied to the matrix is reflected and emitted as diffuse reflectance. A matrix of less than about 0.5 mm thickness is usually employed, with from about 0.01 mm to about 0.3 mm being preferred. A thickness of from about 0.1 mm to about 0.2 mm is most preferred, particularly for a nylon matrix. Typically, the matrix will be attached to a holder in order to give it physical form and rigidity, although this may not be necessary. A liquid sample to be tested is applied to pad 11. Generally, with blood being exemplary of a sample being tested, the reagent pad will be on the order of about 10 mm2 to 100 mm2 in surface area, especially 10 mm2 to 50 mm2 in area (or having a diameter of about 2 mm to about 10 mm), which is normally a volume that 5-10 microliters of sample will more than saturate. Of course, once saturation is reached at above the threshold of about 5-10 microliters, no other requirement of blood amount is necessary. Diffuse reflectance measurements in the prior art have typically been taken using a reflective backing attached to or placed behind the matrix. No such backing is needed or will normally be present during the practice of the present invention, either as part of the reagent element or the reflectance apparatus. As can be seen from The hydrophilic layer (reagent element) may be attached to the support by any convenient means, e.g., a holder, clamp or adhesives; however, in the preferred method it is bonded to the backing. The bonding can be done with any non-reactive adhesive, by a thermal method in which the backing surface is melted enough to entrap some of the material used for the hydrophilic layer, or by microwave or ultrasonic bonding methods which likewise fuse the hydrophilic sample pads to the backing. It is important that the bonding be such as to not itself interfere substantially with the diffuse reflectance measurements or the reaction being measured, although this is unlikely to occur as no adhesive need be present at the location where the reading is taken. For example, an adhesive 13 can be applied to the backing strip 12 followed first by punching hole 14 into the combined strip and adhesive and then applying reagent pad 11 to the adhesive in the vicinity of hole 14 so that the peripheral portion of the reagent pad attaches to the backing strip. The Chemical Reagents Any signal producing system may be employed that is capable of reacting with the analyte in the sample to produce (either directly or indirectly) a compound that is characteristically absorptive at a wavelength other than a wavelength at which the assay medium substantially absorbs. Polyamide matrices are particularly useful for carrying out reactions in which a substrate-(analyte) reacts with an oxygen-utilizing oxidase enzyme in such a manner that a product is produced that further reacts with a dye intermediate to either directly or indirectly form a dye which absorbs in a predetermined wavelength range. For example, an ozidase enzyme can oxidize a substrate and produce hydrogen peroxide as a reaction product. The hydrogen peroxide can then react with a dye intermediate or precursor, in a catalysed or uncatalyzed reaction, to produce an oxidized form of the intermediate or precursor. This oxidized material may produce the colored product or react with a second precursor to form the final dye. Nonlimiting examples of analyses and typical reagents include the following materials shown in the following list: The analysis method of this invention relies on a change in absorbance, as measured by diffuse reflectance, which is dependent upon the amount of analyte present in a sample being tested. This change may be determined by measuring the change in the absorbance of the test sample between two or more points in time. The first step of the assay to be considered will be application of the sample to the matrix. In practice, an analysis could be carried out as follows: First a sample of aqueous fluid containing an analyte is obtained. Blood may be obtained by a finger stick, for example. An excess over threshold matrix saturation in the area where reflectance will be measured (i.e., about 5-10 microliters) of this fluid is applied to the reagent element or elements of the test device. Simultaneous starting of a timer is not required (as is commonly required in the prior art), as will become clear below, due to the initialization procedure practiced by the present invention. Excess fluid can be removed, such as by light blotting, but such removal is also not required. The test device is typically mounted in an instrument for reading light absorbance, e.g., color intensity by reflectance, prior to application of the sample. Absorbance is measured at certain points in time after application of the sample. Absorbance refers in this application not only to light within the visual wavelength range but also outside the visual wavelength range, such as infrared and ultraviolet radiation. From these measurements of absorbance a rate of color development can be calibrated in terms of analyte level. The Measuring Instrument A suitable instrument, such as a diffuse reflectance spectrophotometer with appropriate software, can be made to automatically read reflectance at certain points in time, calculate rate of reflectance change, and, using calibration factors, output the level of analyte in the aqueous fluid. Such a device is schematically shown in Light source 5 and/or detector 6 can be adapted to generate or respond to a particular wavelength light, if desired. The output of detector 6 is passed to amplifier 7, for example, a linear integrated circuit which converts the phototransistor current to a voltage. The output of amplifier 7 can be fed to track and hold circuit 8. This is a combination linear/digital integrated circuit which tracks or follows the analog voltage from amplifier 7 and, upon command from microprocessor 20, locks or holds the voltage at its level at that time. Analog-to-digital converter 19 takes the analog voltage from track and hold circuit 8 and converts it to, for example, a twelve-bit binary digital number upon command of microprocessor 20. Microprocessor 20 can be a digital integrated circuit. It serves the following control functions: 1) timing for the entire system; 2) reading of the output of analog/digital converter 19; 3) together with program and data memory 21, storing data corresponding to the reflectance measured at specified time intervals; 4) calculating analyte levels from the stored reflectances; and 5) outputting analyte concentration data to display 22. Memory 21 can be a digital integrated circuit which stores data and the microprocessor operating program. Reporting device 22 can take various hard copy and soft copy form. Usually it is a visual display, such as a liquid crystal (LCD) or LED display, but it can also be a tape printer, audible signal, or the like. The instrument also can include a start-stop switch and can provide an audible or visible time output to indicate times for applying samples, taking readings etc., if desired. Reflectance Switching In the present invention, the reflectance circuit itself can be used to initiate timing by measuring a drop in reflectance that occurs when the aqueous portion of the suspension solution applied to the reagent pad (e.g., blood) migrates to the surface at which reflectance is being measured. Typically, the measuring device is turned on in a �ready� mode in which reflectance readings are automatically made at closely spaced intervals (typically about 0.2 seconds) from the typically off-white, substantially dry, unreacted reagent strip. The initial measurement is typically made prior to penetration of the matrix by fluid being analyzed but can be made after the fluid has been applied to a location on the reagent element other than where reflectance is being measured. The reflectance value is evaluated by the microprocessor, typically by storing successive values in memory and then comparing each value with the initial unreacted value. When the aqueous solution penetrates the reagent matrix, the drop in reflectance signals the start of the measuring time interval. Drops in reflectance of 5-50% can be used to initiate timing, typically a drop of about 10%. In this simple way there is exact synchronization of assay medium reaching the surface from which measurements are taken and initiation of the sequence of readings, with no requirement of activity by the user. Although the total systems described in this application are particularly directed to the use of polyamide matrices and particularly to the use of such matrices in determining the concentration of various sugars, such as glucose, and other materials of biological origin, there is no need to limit the reflectance switching aspect of the invention to such matrices. For example, the matrix used with reflectance switching may be formed from any water-insoluble hydrophilic material and any other type of reflectance assay. Particular Application to Glucose Assay A particular example with regard to detecting glucose in the presence of red blood cells will now be given in order that greater detail and particular advantage can be pointed out. Although this represents a preferred embodiment of the present invention, the invention is not limited to the detection of glucose in blood. The use of polyamide surfaces to form the reagent element provides a number of desirable characteristics in the present invention. These are that the reagent element is hydrophilic (i.e., takes up reagent and sample readily), does not deform on wetting (so as to provide a flat surface for reflectance reading), is compatible with enzymes (in order to impart good shelf stability), takes up a limited sample volume per unit volume of membrane (necessary in order to demonstrate an extended dynamic range of measurements), and shows sufficient wet strength to allow for routine manufacture. In a typical configuration, the method is carried out using an apparatus consisting of a plastic holder and the reagent element (the matrix having the signal producing system impregnated therein). The preferred matrix for use in preparing the reagent element is a nylon microfiltration membrane, particularly membranes made from nylon-66 cast on a core of non-woven polyester fibers. Numerous nylon microfiltration membranes of this class are produced commercially by the Pall Ultrafine Filtration Corporation, having average pore sizes from 0.1 to 3.0 mircrons. These materials have shown mechanical strength and flexibility, dimensional stability upon exposure to water, and rapid wetting. Many variations in specific chemical structure of the nylon are possible. These include unfunctionalized nylon-66 with charged end groups (sold under the trademark ULTRAPORE by Pall Ultrafine Filtration Corporation, �Pall�). Positive charges predominate below pH 6 while negative charges predominate above pH 6. In other membranes the nylon is functionalized before the membrane is formed to give membranes with different properties. Nylons functionalized with carboxy groups are negatively charged over a wide pH range (sold as CARBOXYDYNE by Pall). Nylons can also be functionalized with a high density of positively charged groups on its surface, typically quaternary amine groups, so that they display little variation in charge over a wide pH range (sold as POSIDYNE by Pall). Such materials are particularly well suited for the practice of the present invention. It has been found that keeping the pH of the solution below 4.8 will help stabilize the enzymes in solution. The most efficient level of stability has been found at pH 4.0. This results in shelf life at room temperature of 12-18 months. Consequently, a strip with positively charged ions is most desirable. It is also possible to use membranes having reactive functional groups designed for covalent immobilization of proteins (sold as BIODYNE IMMUNO AFFINITY membranes by Pall). Such materials can be used to covalently attach proteins, e.g. enzymes, used as reagents. Although all of these materials are usable, nylon having a high density of positively charged groups on its surface provide the best stability of reagents when formulated into a dry reagent pad. Unfunctionalized nylon gives the next best stability with the carboxylated nylons next best. Desirable results can be obtained with pore sizes ranging from about 0.2-2.0 μm, preferably about 0.5-1.2 μm, and most preferably about 0.8 μm, when used with whole blood. The form of the handle on which the reagent element is assembled is relatively unimportant as long as the handle allows access to one side of the reagent element by sample and to the other side of the reagent element by incident light whose reflectance is being measured. The handle also aids in inserting the reagent element into the absorbance measuring device so that it registers with the optical system. One example of a suitable handle is a mylar or other plastic strip to which a transfer adhesive such as 3M 465 or Y9460 transfer adhesive has been applied. A hole is punched into the plastic through the transfer adhesive. A reagent element, typically in the form of a thin pad, either containing reagents or to which reagents will later be added, is then applied to the handle by means of the transfer adhesive so that it is firmly attached to the handle in the area surrounding the hole that has been punched through the handle and the transfer adhesive. Such a device is illustrated in As further seen in Although a number of dyes could be used as indicators, the choice will depend upon the nature of the sample. It is necessary to select a dye having an absorbance at a wavelength different from the wavelength at which red blood cells absorb light, with whole blood as the assay medium, or other contaminants in the solution being analyzed with other assay media. The MBTH-DMAB dye couple (3-methyl-2-benzothiazolinone hydrazone hydrochloride and 3-dimethylaminobenzoic acid), although being previously described as suitable for color development for peroxidase labels in enzyme immunoassays, has never been used in a commercial glucose measuring reagent. This dye couple gives greater dynamic range and shows improved enzymatic stability as compared to traditional dyes used for glucose measurement, such as benzidine derivatives. This enzymatic stability also makes the MBTH-DMAB dye couple especially desirable in order to insure longer shelf life of the test strips. Furthermore, the MBTH-DMAB dye couple is not carcinogenic, a characteristic of most benzidine derivatives. Another dye couple that can be used in the measurement of glucose is the AAP-CTA (4-aminoantipyrene and chromotropic acid) couple. Although this couple does not provide as broad a dynamic range as MBTH-DMAB, it is stable and suitable for use in the practice of the present invention when measuring glucose. Again, the AAP-CTA dye couple provides an expanded dynamic range and greater enzymatic activity stability than the more widely used benzidine dyes. The use of the MBTH-DMAB couple allows for correction of hematocrit and degree of oxygenation of blood with a single correction factor. The more typically used benzidine dyes do not permit such a correction. The MBTH-DMAB dye forms a chromophore that absorbs at approximately 635 nm but not to any significant extent at 700 nm. Slight variations in measuring wavelengths (� about 10 nm) are permitted. At 700 nm both hematocrit and degree of oxygenation can be measured by measuring blood color. Furthermore, light emitting diodes (LED) are commercially available for both 635nm and 700 nm measurements, thereby simplifying mass-production of a device. By using the preferred membrane pore size described above and the subject reagent formulation, both hematocrit and oxygenation behavior can be corrected by measuring at the single 700 nm wavelength. Two additional conditions were found to provide particular stability and long shelf life for a glucose oxidase/peroxidase formulation on a polyamide matrix. Storage is enhanced at a pH in the range of 3.8 to 5.0 preferably about 3.8 to 4.3, most preferably about 4.0. Similarly, unexpectedly good storage and stability was found with mixture of a concentrated buffer system to the the reagents found in the matrix. The most effective buffer was found to be a 10% weight citrate buffer, with concentrations from about 5-15% being effective. These are weight/volume percentages of the solution in which the reagents are applied to the matrix. Other buffers can be used on the same molar basis. Greatest stability was achieved using a low pH, preferably about pH 4, an MBTH-DMAB dye system, and a high enzyme concentration of approximately 500-1000 M/ml of application solution. As previously indicated, such strips prepared using these parameters result in shelf life of about 12-18 months. In preparing the MBTH-DMAB reagent and the enzyme system that forms the remainder of the signal producing system, it is not necessary to maintain exact volumes and ratios although the suggested values below give good results. Reagents are readily absorbed by the matrix pad when the glucose oxidase is present in a solution at about 27-54% by volume, the peroxidase is present at a concentration of about 2.7-5.4 mg/ml, MBTH is present at a concentration of about 4-8 mg/ml, and DMAB is present at a concentration of about 8-16 mg/ml. The DMAB-MBTH weight ratio is preferably maintained in the range of 1:1 to 4:1, preferably about 1.5:1 to 2.5:1, most preferably about 2:1. The basic manufacturing techniques for the reagent element are, once established, straightforward. The membrane itself is strong and stable, particularly when a nylon membrane of the preferred embodiment is selected. Only two solutions are necessary for applying reagent, and these solutions are both readily formulated and stable. The first generally contains the dye components and the second generally contains the enzymes. When using the MBTH-DMAB dye couple, for example, the individual dyes are dissolved in an aqueous organic solvent, typically a 1:1 mixture of acetonitrile and water. The matrix is dipped into the solution, excess liquid is removed by blotting, and the matrix is then dried, typically at 50� C.-60� C. for 10-20 minutes. The matrix containing the dyes is then dipped into an aqueous solution containing the enzymes. A typical formulation would contain the peroxidase and glucose oxidase enzymes as well as any desired buffer, preservative, stabilizer, or the like. The matrix is then blotted to remove excess liquid and dried as before. A typical formulation for the glucose reagent is as follows: Dye Dip Combine:
Stir until all solids are dissolved and pour onto a glass plate or other flat surface. Dip a piece of Posidyne membrane (Pall Co.), blot off excess liquid, and dry at 56� C. for 15 minutes. Enzyme Dip Combine:
Stir until all solids are dissolved and pour onto a glass plate or other flat surface. Dip a piece of membrane previously impregnated with dyes, blot off excess liquid, and dry at 56� C. for 15 minutes. The electronic apparatus used to make the reflectance readings minimally contains a light source, a reflected light detector, an amplifier, an analog to digital converter, a microprocessor with memory and program, and a display device, as seen in FIG. 2. The light source typically consists of a light emitting diode (LED). Although it is possible to use a polychromatic light source and a light detector capable of measuring at two different wavelengths, a preferred apparatus would contain two LED sources or a single diode capable of emitting two distinct wavelengths of light. Commercially available LEDs producing the wavelengths of light described as being preferred in the present specification include a Hewlett Packard HLMP-1340 with an emission maximum at 635 nm and a Hewlett Packard QEMT-1045 is with a narrow-band emission maximum at 700 nm. Suitable commercially available light detectors include a Hammamatsu 5874-18X and a Litronix BPX-65. Although other methods of taking measurements are feasible, the following method has provided the desired results. Readings are taken by the photodetector at specified intervals after timing is initiated. The 635 nm LED is powered only during a brief measuring time span that begins approximately 20 seconds after the start time as indicated by the previously described reflectance switching system. If this reading indicates that a high level of glucose is present in the sample, a 30-second reading is taken and used in the final calculation in order to improve accuracy. Typically, high levels are considered to begin at about 250 mg/dl. The background is corrected with a 700 nm reading taken about 15 seconds after the start of the measurement period. The reading from the photodetector is integrated over the interval while the appropriate LED is activated, which is typically less than one second. The raw reflectance readings are then used for calculations performed by the microprocessor after the signal has been amplified and converted to a digital signal. Numerous microprocessors can be used to carry out the calculation. An AIM65 single-board microcomputer manufactured by Rockwell International has proven to be satisfactory. The present methods and apparatuses allow a very simple procedure with minimum operational steps on the part of the user. In use, the reagent strip 10 is placed in the detector so that the hole 14 in the strip 10 registers with the optics of the detecting system. The above-described notch 15/post 65 system, as seen in The measurement sequence is then initiated by pressing a button on the measuring apparatus that activates the microcomputer to take a measurement of reflected light from the unreacted reagent pad, called an Rdry reading. The cap 90 is then removed and a drop of blood is applied to the reagent strip 10, typically while the reagent strip 10 is registered with the optics and the reading device. It is preferred that the reagent strip be left in register with the optics in order to minimize handling. The cap 90 is then closed. The instrument is capable of sensing the application of blood or other sample by a decrease in the reflectance when the sample passes through the matrix and reflected light is measured on the opposite side. The decrease in reflectance initiates a timing sequence which is described in detail at other locations in this specification. The cap 90 should be replaced within 15 seconds of sample application, although this time may vary depending on the type of sample being measured. Results are typically displayed at approximately 30 seconds after blood application when a blood glucose sample is being measured, although a 20 second reaction is permissible for glucose samples having a concentration of glucose of less than 250 mg/dl. If other samples are being measured, suitable times for displaying the result may differ and can be readily determined from the characteristics of the reagent/sample selected. A particularly accurate evaluation of glucose level (or any other analyte being measured) can be made using the background current, i.e., the current from the photo detector with power on but with no light reflected from the reagent pad, in order to make a background correction. It has been demonstrated that over a 2-3 month period that this value does not change for a particular instrument prepared according to the preferred embodiments of this specification, and it is possible to program this background reading into the computer memory as a constant. With a slight modification of the procedure, however, this value can be measured (or normalized) with each analysis for more accurate results. Each LED is turned on prior to placement of the blood sample on the reagent strip 10 but with the reagent strip 10 in place. A reflectance value of the strip 10 is then measured, with the reagent strip 10 in place and the light protective cap 90 closed. If this measurement is different than the original measurement of the reflectance value, power to the LED is increased so that the reflectance will be the same. This insures that the measurement of blood glucose content is being made on the same repeatable scale for each blood glucose reading. The reason for instituting this method is twofold. First, the intensity of light emitting diodes will vary greatly from LED to LED, even when all the measuring LEDs are new. Second, the LED efficiency will vary with both temperature and the life of the LED. With this method, results are repeatable on the same scale. The raw data necessary for calculating a result in a glucose assay are a background current reported as background reflectance, Rb, as described above; a reading of the unreacted test strip, Rdry, which is about 95% opaque to light and is also described above; and an end point measurement. Using the preferred embodiments described herein, the end point is not particularly stable and must be precisely timed from the initial application of blood. However, the meter as described herein performs this timing automatically. For glucose concentrations below 250 mg/dl, a suitably stable end point is reached in 20 seconds, and a final reflectance, R20, is taken. For glucose concentrations up to 450 mg/dl, a 30-second reflectance reading, R30, is adequate. Although the system described herein displays good differentiation up to 800 mg/dl of glucose, the measurement is somewhat noisy and inaccurate above 450 mg/dl, although not so great as to cause a significant problem. Longer reaction times should provide more suitable readings for the higher levels of glucose concentration. The 700 nm reflectance reading for the dual wavelength measurement is typically taken at 15 seconds (R15). By this time blood will have completely saturated the reagent pad. Beyond 15 seconds the dye reaction continues to take place and is sensed, to a small part, by a 700 nm reading. Accordingly, since dye absorption by the 700 nm signal is a disadvantage, readings beyond 15 seconds are ignored in the calculations. The raw data described above are used to calculate parameters proportional to glucose concentration which can be more easily visualized than reflectance measurements. A logarithmic transformation of reflectance analogous to the relationship between absorbance and analyte concentration observed in transmission spectroscopy (Beer's Law) can be used if desired. A simplification of the Kubelka-Monk equations, derived specifically for reflectance spectroscopy, have proven particularly useful. In this derivation K/S is related to analyte concentration with K/S defined by Equation 1.
R*t is the reflectivity taken at a particular end point time, t, and is the absorbed fraction of the incident light beam described by Equation 2, where Rt is the end point reflectance, R20 or R30.
R*t varies from 0 for no reflected light (Rb) to 1 for total reflected light (Rdry). The use of reflectivity in the calculations greatly simplifies meter design as a highly stable source and a detection circuit become unnecessary since these components are monitored with each Rdry and Rb measurement. For a single wavelength reading K/S can be calculated at 20 seconds (K/S−20) or 30 seconds (K/S−30). The calibration curves relating these parameters to YSI (Yellow Springs Instruments) glucose measurements can be precisely described by the third order polynomial equation outlined in Equation 3.
The coefficients for these polynomials are listed in Table 1.
The single chemical species being measured in the preferred embodiments is the MBTH-DMAB inamine dye and the complex matrix being analyzed is whole blood distributed on a 0.8μ Posidynem membrane. A review entitled �Application of Near Infra Red Spectrophotometry to the Nondestructive Analysis of Foods: A Review of Experimental Results�, CRC Critical Reviews in Food Science and Nutrition, 18(3) 203-30 (1983), describes the use of instruments based on the measurement of an optical density difference ΔOD (λa−λb) where ODλa is the optical density of the wavelength corresponding to the absorption maximum of a component to be determined and ODλb is the optical density at a wavelength where the same component does not absorb significantly. The algorithm for dual wavelength measurement is by necessity more complex than for single wavelength measurement but is much more powerful. The first order correction applied by the 700 nm reading is a simple subtraction of background color due to blood. In order to make this correction, a relationship between absorbance at 635 nm and 700 nm due to blood color can be and was determined by measuring blood samples with 0 mg/dl glucose over a wide range of blood color. The color range was constructed by varying hematocrit, and fairly linear relationships were observed. From these lines the K/S−15 at 700 nm was normalized to give equivalence to the K/S−30 at 635 nm. This relationship is reported in Equation 4, where K/S−15n is the normalized K/S−15 at 700 nm.
Note that the equivalence of the normalized 700 nm signal and the 635 nm signal is only true at zero glucose. The expressions from which the calibration curves were derived are defined by Equations 5 and 6.
These curves are best fit by fourth-order polynomial equations similar to Equation 3 to which a fourth-order term in K/S is added. The computer-fit coefficients for these equations are listed in Table 2.
A second order correction to eliminate errors due to chromatography effects has also been developed. Low hematocrit samples have characteristically low 700 nm readings compared to higher hematocrit samples with the same 635 nm reading. When the ratio of (K/S−30)/(K/S−15) is plotted versus K/S−30 over a wide range of hematocrits and glucose concentrations, the resulting line on the graph indicates the border between samples which display chromatography effects (above the curve) and those that do not (below the curve). The K/S−30 for the samples above the curve are corrected by elevating the reading to correspond to a point on the curve with the same (K/S−30)/(K/S−15), as demonstrated by the correction made in FIG. 5. The correction factors reported above were tailored to fit a single instrument and a limited number of reagent preparations. The algorithm can be optimized for an individual instrument and reagent in the same manner that is described above. In summary, the system of the present invention minimizes operator actions and provides numerous advantages over prior art reflectance-reading methods. When compared to prior methods for determining glucose in blood, for example, there are several apparent advantages. First, the amount of sample required to saturate the thin reagent pad is small (typically 5-10 microliters), and is of course, volume independent once the threshold volume of blood is supplied to the reagent pad. Second, operator time required is only that necessary to apply the sample to the thin hydrophilic layer and close the cover (typically 4-7 seconds). Third, no simultaneous timing start is required. Fourth, whole blood can be used. The method does not require any separation or utilization of red-cell-free samples and likewise can be used with other deeply colored samples. Fifth, via the reflectance reading and normalization techniques applied in the present invention the system provides reliable, accurate, repeatable readings for the lifetime of the scanning system. Several unobvious advantages arise as a result of the practice of the present invention with whole blood. Normally, aqueous solutions (like blood) will penetrate a hydrophilic membrane to give a liquid layer on the opposite side of the membrane, a surface that is then not suited for a reflectance measurement. It has been discovered, however, that blood, apparently because of interactions of red blood cells and proteins in the blood with the matrix, will wet the polyamide matrix without having an excess liquid penetrate the porous matrix to interfere with the reflectance reading on the opposite side of the matrix. Furthermore, the thin membranes used in the present invention would be expected when wet to transmit light and return only a weak signal to the reflectance measuring device. Prior teachings have generally indicated that a reflective layer is necessary behind the matrix in order to reflect sufficient light. In other cases a white pad has been placed behind the reagent pad prior to color measurement. In the present case, neither a reflective layer nor a white pad is required. In fact, the invention is typically carried out with a light-absorbing surface behind the reagent element when incident light is impinged upon the matrix. This is accomplished using a light absorbing surface behind the reagent element, coupled with measuring reflectance at two different wavelengths. It allows acceptable reflectance measurements to be obtained without removal of excess liquid from the matrix, thereby eliminating a step typically required by previous teachings. The invention now being generally described, the same will be better understood by reference to the following specific examples which are presented for purposes of illustration only and are not to be considered limiting of the invention unless so specified. Reproducibility: One male blood sample (having a hematocrit level of 45) was used to collect the reproducibility data using the presently preferred embodiment of the system, called the MPX system. The results are set forth in Tables 3-5.
The blood was divided into aliquots and spiked with glucose across a range of 25-800 mg/dl. Twenty determinations were made at each glucose test level from strips taken at random from a 500 strip sample (Lot FJ4-49B). The results of this study lead to the following conclusions:
Recovery: For comparison of the present preferred method called MPX against a typical prior art method using a Yellow Springs Instrument Model 23A glucose analyzer manufactured by Yellow Springs Instrument Co., Yellow Springs, Ohio (YSI), blood from 36 donors was tested. The donors were divided equally between males and females and ranged in hematocrit from 35 to 55%. The blood samples were used within 30 hours of collection, with lithium heparin as the anti-coagulant. Each blood sample was divided into aliquots and spiked with glucose to give 152 samples in the range of 0-700 mg/dl glucose. Each sample was tested in duplicate for a total of 304 data points. Response curves were constructed for the appropriate equation (see Tables 1 and 2). These MPX glucose values were then plotted vs. the YSI values to give scattergrams, as seen in Comparison of MPX Systems: For both the 20-second and 30-second measurement times there is visually more scatter in the single-wavelength scattergrams than the dual-wavelength scattergrams. The 20-second reading becomes very scattered above 250 mg/dl but the 30-second measurement does not have wide scatter until the glucose level is greater than 500 mg/dl. These scattergrams were quantitated by determining the. deviations from YSI at various glucose ranges. The following results were obtained.
In conclusion, the two MPX systems gave optimum quantitation in the 0-450 mg/dl range.
Stability: Most of the bench-scale work carried out in optimizing stability was completed using hand-dipped 0.8μ Posidyne� membrane disks. The specific dye/enzyme formulation was set forth previously.
A study of the 56� C. stressing of this membrane over a 19-day period showed no major difference for strips stressed with or without adhesive. In both cases the 19-day decline in glucose value was less than 15% at low test levels (80-100 mg/dl) and also at 300 mg/dl. Another 56� C. study using hand-dipped 0.8p Posidyne� membrane with twice the normal concentration of enzyme and dye was completed. Two separate preparations of the same formulation were made up and the stability measured over a 14-day period. The average results of the two studies were compared. Changes were within �10% over the 14-day period at both the high and low glucose test level. Sample Size: The sample size requirements for the MPX System are demonstrated in Table 9.
The volumes reported in the table were transferred to the reagent pad 10 shown in At the lower glucose concentration the single wavelength result has some dependence on sample size, which is completely eliminated using the dual wavelength measurement. Although this dependence with the single wavelength might be considered acceptable, it is clearly undesirable. Reproducibility: Experimental measurements described above were always run in replicate, usually 2, 3 or 4 determinations per data point. These sets have always shown close agreement even for samples with extreme hematocrits or extreme oxygen levels. covariances were well below 5%. It appears, therefore, that reproducibility is very good to excellent. The subject invention provides for many commercially or have been described in the literature. The protocols are simple and require little technical skill and are relatively free of operator error. The assays can be carried out rapidly. They use inexpensive and relatively harmless reagents, important considerations for materials employed in the home. The user obtains results which can be understood and used in conjunction with maintenance therapy. In addition, the reagents have long shelf lives, so that the results obtained will be reliable for long periods of time. The equipment is simple and reliable and substantially automatic. All patents and other publications specifically identified in this specification are indicative of the level of skill of those of ordinary skill in the art to which this invention pertains and are herein individually incorporated by reference to the same extent as would occur if each reference were specifically and individually incorporated by reference. The invention now being fully described, it will be apparent to one of ordinary skill in the art that many modifications and changes can be made thereto without departing from the spirit or scope of the invention as defined in the following claims. Patent Citations
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Sensory Storytime | |
Event Type: Children's Storytime Date: 10/30/2012 Start Time: 4:00 PM End Time: 4:30 PM Description: Sensory Storytime for children with special needs and a caregiver. This program is designed for kids who may have a hard time sitting still or focusing in big groups.
Library: Oak Park Public Library Main BranchLocation: First Floor - Storytime Room Contact: Children's Dept. Contact Number: 708-452-3420 |

subset: commoncrawl


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New York Giants Apparel, Jerseys & Gear
Show your Big Blue pride all year round and shop our huge inventory of the latest gear and merchandise here at the New York Giants store at Fanatics.com! Whether you're looking for Giants decor items and collectibles to decorate your home and office or apparel to cheer them on during each and every game, you will be able to find everything right here. Browse our collections of New York Giants jerseys, tees, hats, sweatshirts and more in men's, women's and kids' sizes so you can find some for all fans to show they G-Men some support. Shop for all your favorite NY Giants apparel and gear today and be sure to check back for the newest arrivals that will be added all season long!
Shop: Giants Jerseys | Giants Hats | Giants T-Shirts | Giants Sweatshirts | Giants Accessories
New York Giants Shop
Ereck Flowers New York Giants Nike 2015 NFL Draft 9th Overall Pick Game Jersey - Royal
Price: $99.95
Sale: $99.95
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Celebrate your New York Giants fandom with this 2015 NFL Draft Game jersey! This jersey features screen print graphics and is tailored for movement. Make sure you're part of the 2015 NFL Draft action ...
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New York Giants Store: Shop Giants Merchandise
Look no further than Fanatics.com for everything you need to root your New York Giants on to another Super Bowl run! First, start with your fan apparel. Shop for everything you need from Nike Giants jerseys to zip up hoodies to show your Giants pride all season long. Our apparel comes from some of the best brands out there, like Nike, New Era, '47 Brand and more! Also, with sizes and styles in men's, women's and kids', you will be able to find the perfect fan attire for any Giants fan you're shopping for!
Secondly, be sure to show your Giants pride to everyone around you with any of the merchandise and collectibles we carry! From tailgating and home and office gear to autographed Giants memorabilia, you can find everything you're looking for to show your Giants support and remember the team's finest moments in franchise history. Browse our huge collections of Giants apparel, gear and merchandise today and be sure to come back as new collections are always being added!


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Product Features:
- Sensible styling that complements any home
- For use as soap or lotion dispenser
- Large capacity 13 ounce bottle included
- Refillable from above the deck
- Includes refill funnel
- Lifetime hardware and finish warranty
- Extra secure mounting assembly
- All necessary mounting hardware included
Additional Delta Links
This Delta item can also be referenced by the following color/finish specific model #:
- Delta RP1001AR
Arctic Stainless - Delta RP1001BS
Biscuit - Delta RP1001BL
Black - Delta RP1001BN
Brilliance Brushed Nickel - Delta RP1001NN
Brilliance Pearl Nickel - Delta RP1001PB
Brilliance Polished Brass - Delta RP1001PN
Brilliance Polished Nickel - Delta RP1001SS
Brilliance Stainless - Delta RP1001CZ
Champagne Bronze - Delta RP1001
Chrome - Delta RP1001-CB*
Chrome / Polished Brass - Delta RP1001MW
Matte White - Delta RP1001RB
Venetian Bronze - Delta RP1001WH
*Discontinued model or finish
More Than Just a Store - Your Reasons to Shop
Discover the best online deals for the RP1001 and everything else for your home from the leading online home improvement store.
We're committed to providing you with the best assortment of Delta products with over 400 warehouses across the country.
Our knowledgeable product specialists work to bring you the best prices on every product and provide unmatched customer service. Your satisfaction is our highest priority!
Manufacturer Resources
Installation Resource Center
Whether you are installing the product yourself or hiring a professional, our installation Resource Center has everything you need to get your project done. Visit the Installation Resource Center to get started.


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Running a Sonar Analysis with the Sonar Runner (Recommended Way)
Create a 'sonar-project.propeties' file and place it in the same folder as the Solution file (".sln").
Here is the simplest 'sonar-project.properties' file that you can write to be able to run a Sonar analysis on your project:sonar-project.propertiesRun the following command from your Solution folder:
Running a Sonar Analysis with Maven
As it used to be the case for the .NET Plugins, Maven can be used to launch Sonar analyses on your C# code base.
If you are familiar with maven, you can also use the maven-dotnet-plugin in order to compile and package dotnet projects. If you already use CI tools such as Jenkins or Hudson on java maven projects, you can use the maven-dotnet-plugin to handle dotnet projects the same way
The POM file
Simplest "pom.xml" file for Maven |
Above, a very simple pom.xml file that can be used instead of the sonar-project.properties of the Sonar Runner. If you want to use maven compile and run the tests of your visual studio solution, you also need to declare the maven-dotnet-plugin. Please take a look at the examples provided on the maven-dotnet-plugin site.
The settings file
You need to configure somewhere the location of the external tools used by Sonar such as FxCop, Gendarme or StyleCop. The C# plugins options pages describes the properties needed in the settings.xml. Below an xml fragment describing a maven profile you could add in your settings.xml file :
You can also use property keys used by the maven dotnet plugin. Feel free to take a look at the examples on the maven dotnet plugins.
Activating External Tools
Your .NET solution must be compiled if you want to use the following plugins:
- FxCop
- Gendarme
- Gallio
- NDeps
If you do not want to use some of the external tools for your analysis, you can deactivate them by adding the following properties to your configuration file:
Advanced Settings
Every plugin defines its own properties that are documented on the below pages:
Paths and File Patterns
Each time you need to define the location of a file or a set of files, use '/' instead of '\' (even if that looks weird on a Windows box)
If you need to specify a path, this path may be absolute or relative. Relative paths may start from the location of the sln file or the csproj files, depending of the property specified. Relative paths may use "../" to climb in the folder hierarchy.
When several files need to be specified, for example for properties such as "sonar.dotnet.assemblies", "Ant style" wildcard patterns can be used. "*" means any file or any directory. "**" means any directory and subdirectory :
Above pattern will select any dll files prefixed by "Foo" anywhere in a project.
You can combine an absolute path prefix with wildcards :
This will select any dll files in any subfolder of the "lib" folder of the drive "T:".
If you need to reference assembly files outside your solution folder, you can use absolute paths or "../". For example :
Above pattern can be used to specify all the dll files of a lib folder located at the same level as the root folder of your visual studio solution.
As of version 1.4, $(SolutionDir) is not the only special expression that can be used in file patterns. Below the exhaustive list of supported expressions:
Expression | Description |
$(SolutionDir) | Root directory of the solution, this is the directory where the sln file used by sonar is located |
$(ProjectName) | Name of the currently analysed project of the solution. |
$(AssemblyName) | Name of the assembly generated by the currently analysed solution. Works only for non asp projects. |
$(AssemblyVersion) | Version of the assembly generated by the currently analysed solution. |
$(OutputType) | Type of the generated assembly. Can be "dll" or "exe" |
$(RootNamespace) | Root namespace of the currently analysed project. |
So if the solution you need to analyze use a "post compilation" msbuild/nant task that copies the generated assemblies somewhere into a "BUILD" directory, you can set the property "sonar.dotnet.assemblies" with this pattern:
Tools such as Gendarme and FxCop will be executed once for each project of the solution. For each project, the expressions "AssemblyName" and "OutputType" will be evaluated in order to locate the project assembly.


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Showing 1-17 of 17 items found in Food & Drink
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Southern Illinois Wine Trail
Illinois' newest wine trail connects six wineries dotted throughout the southeast corner of the state. Visitors can enjoy both breathtaking vistas and friendly rural communities, all while sampling excellent red and white wines.
Chocolate Factory
The Chocolate Factory prides itself in offering quality gourmet chocolates in a wide variety of mouth watering flavor, formulated with only the finest ingredients. Our irresistible silky smooth blended chocolates make delicious rich candies for any occasion!
Riverview Mansion Hotel
The Riverview Mansion Hotel of Golconda is a full service Bed & Breakfast. In addition to the finest Victorian style accommodations available in Southern Illinois, there is also a lounge serving the best selection of local wines, as well as a restaurant. The hotel is open year round with advance reservations encouraged. All major credit cards accepted. The enchanted hotel setting with its expansive grounds and facilities is the perfect venue in which to enjoy the huge variety of hand-crafted, award winning wines from not only Illinois, but also the best from Indiana, Missouri and Kentucky micro-vineyards. Harvest season will be a unique time at the mansion with Oktoberfest festivals. This will be the opportunity to share the seasons best wines complimented with tantalizing artisan meats and cheeses. Festival weekends will provide just the incentive to bring in the best in local and regional musical talent. Indoor and outdoor entertainment! Our wine shop exhibits a wide array of gifts and specialty items.
Shawnee Winery
Come relax with us a while and enjoy the lovely Southern Illinois down-home atmosphere. Make yourself comfortable in our tasting room or have a seat outside on our country porch. Open 7 days a week for locally made wine.
Hogg Hollow Winery
View works by local artists and enjoy free wine tasting at this Golconda winery.
Cache River Basin Vineyard and Winery
The winery is known for its white wine made from grapes grown in Southern Illinois. The winery and vineyard are located in a scenic setting just south of the Heron Pond turn-off.
Wineaux's Restaurant
Located at Cache River Basin Vineyard and Winery, Wineaux's offers American cuisine, including certified Angus Beef steaks and burgers, ribs and seafood. Specializing in food cooked with wine!
The Shawnee Grill
Casual dining offering salads, sandwiches, steaks, chicken, seafood & pasta for lunch & dinner. We seat 100 people.
Connie's at the Gambit
Located at the Gambit Golf Club, this casual restaurant features dishes such as the grilled rib eye with red wine glaze and sautéed flounder with swiss chard. For a group, reserve the large banquet room.
Fat Edd's Roadhouse
Located two blocks from Harrah's Fat Edd's Roadhouse offers a variety of foods and drinks. Many appetizers such as peel-n-eat shrimp and great food choices from salads to Roadhouse platters. They also offer a full bar. Open daily 11:00 am to 10:00 pm.
Bill's BBQ
Visit this Metropolis icon for barbecue done the old fashion way! In business since 1965 and located just 2 blocks from Ft. Massac State Park, you will enjoy some of the best breakfast sandwiches and BBQ in town! Open 4:00 am - 4:00 pm Tuesday - Saturday.
Cubby Bear's Pizza
Chicago Style Pizza at its best. Even though you are 6 hours away from Chicago you will feel like you are on the streets of the Windy City every time you bite into one of the handmade pizzas at Cubby Bears. A pizza buffet makes it easy to sample all that Cubby's has to offer. Sandwiches and pasta also available. 11:00 a.m.-9:00 p.m. Daily
Down-home cookin' at Rube's is served up three meals a day. The cooks in the kitchen specialize in cooking "the way your mamma made it'" so you'll find something to your liking on the menu. Daily specials are sure to please even the pickiest eater. 6:00 a.m. - 7:00 p.m. Monday – Friday 6:00 a.m. - 1:00 p.m. Saturday 6:00 a.m. - 3:00 p.m. Sunday
China House Buffet
Bringing the atmosphere of China to Metropolis, The China House Buffet has opened in a newly remodeled facility. This deluxe buffet has everything you could possibly want and more. From Chinese favorites, pizza, American classics, seafood, salad and desserts you will find something you will enjoy. Located across U.S. 45 from Ft. Massac State Park. 11:00 a.m.-9:30 p.m. daily.
El'Tequila Mexican Restaurant
Located directly across from Ft. Massac State Park you will feel like you have stepped across the border into old Mexico. Select from the finest traditional Mexican cuisine or have a drink from the bar. 11:00 a.m.-10:00 p.m. daily
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Showing 97-174 of 174 items found in Shopping
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Colonial Flowers & Gifts, Inc.
Unique store using antiques to enhance displays. Flowers and gifts.
Sandwich Antique Mart
Held at the Sandwich Fairgrounds, this market offers treasures from the 19th and 20th centuries. More than 500 exhibitors sell authentic antiques and collectibles on select Sundays from spring through fall.
Laughing Cat Antiques Shop
The Laughing Cat Antiques Shop is the purrfect place to find that vintage treasure, your own personal key to the past! We have 17 dealers here to make sure you have plenty to choose from. you will find vintage Indian jewelry as well as rhinestone and sterling. Come in, walk down memory lane, and see our eclectic mix of antiques, rare antique post office items, depression glass, antique dolls, advertising signs, and Victorian children's items. We also have a primitives room for you, featuring the most fantastic American primitives...a must see!
Decades is a unique shopping experience with many unique items from retro to vintage. Handmade items from jewelry, aprons, clothes, cards, etc.
The Confectionery
Besides creams and clusters and toffee and caramels, The Confectionary also make hard to find pieces including divinity, chocolate dipped ginger, sponge candy (seasonally) and sugar free chocolate clusters (made with real chocolate). Their batches are small and much of the work is done the old fashioned way: by hand.
Angel Kisses of St. Charles
Religious articles, baptism gifts, books, exquisite angel and religious figurines.
CITY:St. Charles
Cradles & All
Unique children's furniture store specializing in bedding and accessories from baby through teen. Gift items, custom orders and baby shower registry available.
Geneva Running Outfitters
Experience a unique approach to fulfill all of your running & walking needs with personalized shoe fittings, apparel and accessories.
Becky Beck's Jewelry Store
Becky Beck's Jewelry Store has been serving the DeKalb, Il area since 1992. Owner-operated, Becky and her expert staff are committed to providing their clients a comfortable, enjoyable jewelry buying experience, guided by a professional, knowledgeable Associate.
Catholic Gift Store
The Catholic Gift Store offers you a unique selection of quality Catholic gifts and books.
Sweet Earth
At Sweet Earth our gifts say more!. We engrave on almost everything. We have the tools and experience to help you create a unique gift. We repair both fine and costume jewelry-AND all the work is done in the store by qualified professionals. We change watch batteries and remove links. We have the largest selection of beads & jewelry making products in the area. Every year in March we host our BEAD-A-THON. For that personalized touch, we provide engraving services and plenty of engravable gifts for every occasion. We can even put your message on your own treasures, engraving on a wide variety of materials including metals, glass and crystal. We carry beautiful gift ideas from linens and home decor to toys and puppets, greeting cards and wrappings.
Lavish Thrift
Take some time and buy a unique gift for your special family and friends. We carry vintage and new jewelry, artwork, a basket of books for the avid reader, statues of dogs, stuffed bunny rabbits, selection of Gypsy Rose scarves, mittens, hats, pins as well as gently used clothing and purses. Come with an open mind...and you won't need that open wallet.
We specialize in rare, exceptional antiques, estate items, vintage and marcasite jewelry. We also feature furniture, fine art, oil paintings, porcelain, clocks, sterling, glassware and more.
CITY:St. Charles
North Central Cyclery, Inc.
We proudly carry a variety of bicycles includig Trek, Gary Fisher, Surly Salsa, Ridley, Haro, and Mirraco. We believe these companies give us the best opportunity to serve almost any rider walking in our door. We also carry a wide variety of products from other companies including Bontrager, Saris, Crank Brothers and more. We have access to many products not present in our store and we gladly make special orders for customers, so if you are interestd in something specific, please let us know! We also support, plan, coordinate or participate in almost every cycling event in DeKalb County. These events are the cornerstone of our business. We also host many in-store seminars on bike maintenance, bike fit, training, commuting, and bike safety.
The Tawny Tortoise
Retail sales of specialty foods, gifts, dolls; Dollmenders doll repair; Cutlery Corner knife/scissor sharpening; Homewares cutting boards/ wine & pot racks; Sherry's Floral Creations. Open Monday - Saturday 9:30am - 7:00pm. Sunday 11:am - 3:00 pm.
Cracker Jax
Cracker Jax began in 1984 as a vintage clothing store and has since transformed into the magical place it is today! All senses are delighted as you shop 15 cases of new and vintage jewelry, eclectic clothing, soy candles, oils, incense, gemstones of every kind, unique gifts, stunning greeting cards, books, antique and shabby chic furniture, art and one-of-a-kind treasures. We are lovers of all things beautiful!
JR Antiques and Collectibles
Specializing in antiques, collectibles, furniture, primitives and much more.
BBK Sports
Sporting goods retailer and team sales. Equipment and apparel for baseball, softball, soccer, football, basketball, and volleyball.
CITY:St. Charles
Carter's Cottage Interiors
Carter's Cottage Interiors is pleased to offer a pleasant in store shopping experience filled with antiques, shabby chic/french country furiniture and decor, hoosier cabinets, crocks, DeKalb seed sacks, DeKalb farm/seed signs and many primitives.
The Little Traveler - Geneva
This historic mansion features 36 rooms filled with treasures from around the world and a history over 80 years in the making.
New Game in Town
New Game in Town is a great little shop specializing in Magic the Gathering and other CCGs, Darts and Dart Supplies, Comic Books, Miniatures, Dungeons and Dragons and other RPGs. Come in and play!
Mae's Fine Design
Mae's Fine Designs deals with the same jewelry trade companies as the big mall jewelry stores deal with, but without the high up-scale pricing. Come in to find the perfect piece of jewelry for your loved one. Mae's has everything from engagement rings to necklaces. We also offer simple repairs such as broken chain to full customize channel set diamond ring.
The Natural Gardens
Nursery specializing in Native & Ornamental Perennials & grasses since 1953.
CITY:St. Charles
Courage combined with inventiveness is the definition of Moxie. Moxie offers the most random, quirky, beautiful, interesting, useful and unpredictable goods around. Including: clothing-vintage and new, baby gifts, stuff for kids of all ages, gourmet foods and kitchen gadgets, art, home accents, books and music, and jewelry.
Bike Rack
The area's best selection of bikes, recumbents, accessories and clothing. Rentals: bikes, tandems, trailer cycles, recumbent bikes and trikes. Home of Creative Mobility featuring bikes for special needs. Just west of Randall.
CITY:St. Charles
Inboden's Meat Market and Full Service Catering
Inboden's Meats Ltd. is your premier specialty meat butcher, baker, fresh greens and gourmet retail store. In addition, they carry a wonderful selection of unique beer and wine to compliment your meal. People from all areas of Illinois come to Inboden's to enjoy our fresh cuts of meat, breads and pastries baked daily, fresh hand picked produce, and friendly atmosphere. Inboden's has been serving the public since 1962. A family-owned business, Inboden's has the appeal of a small town classic meat and grocery market. Inboden's sells only the finest USDA Top Choice & USDA Prime Meats. All of our meats are naturally aged to provide tenderness and rich flavor. We use no chemical tenderizers of flavoring.
Graham Crackers Comics
Graham Crackers has comics new and old for a variety of ages. Toys, posters, magazines and buttons can also be found here. Stop in their store today and become an owner of one of their great finds.
Anderson's Coins & Collectibles
Kids of all ages will find something to love in the unique and ever-changing selection of toys, which includes Star Wars and Star Trek items, Lionel, Marx and other brands of trains, Coco Cola memorabilia model kits, Barbies, vintage super heroes, Hot Wheels, vintage die-cast, posters and more.
CITY:St. Charles
Made Just For You Gifts
Made Just for You Gifts celebrates creativity and originality. Our mostly local crafters have printed, sewn, sawed, arranged, or glued their hand crafted gift and home decor items. Come in and explore our shop. Our friendly staff will be waiting with ice tea or warm cider to help you find something made just for you.
An Artisan Bread Bakery featuring a delicious variety of fresh-baked breads, buns and more. Breadsmith is open Tuesday through Sunday. Stop in and see what makes us the special choice of bread lovers!
CITY:St. Charles
First Street Plaza
Visit the many shops located in the new development along the river. There is a large parking garage adjacent for shoppers' convenience and 2 Visitor Information Centers.
CITY:St. Charles
Dick Pond Athletics
Dick Pond Athletics is America's running shoe store specializing in footwear, clothing and accessories for runners, walkers and triathletes. Open daily. Across from Salerno's on the Fox Restaurant on Second Street (Rt. 31)
CITY:St. Charles
Artemisia Home & Interior Decorating
A unique blend of antiques and elements. Unusual artisan works and uncommon finds including one-of-a-kind jewelry and accessories.
Village Flower Shop
Your local florist specializing in creating customized floral designs for any occasion. Open M-F 9am-5:30pm and Saturdays 9:00a-4:00pm
La Vita
Fine cigars, gourmet coffee, boutique wine. Featuring the #1 coffee imported from Italy. Largest cigar selection in the Midwest.
CITY:St. Charles
Theives Market
In Pheasant Run Resort. Open 7 days a week. A distinctive shop offering fresh-ground or whole bean coffee, teas, gourmet jams and food items, and a unique array of gifts.
CITY:St. Charles
JP Jewelers Inc.
A fine jewelry store. Family owned and operated since 1993. Full service for jewelry and watch repair. Offering custom design.
CITY:St. Charles
Nathan Winston Services
Nathan Winston Services was started in 1976 as a rubber stamp shop. Growth continued with the addition of engraving as we opened a full time retail store in 1985. Today we offer stamps, plaques, acrylics, clocks, and engraved and sublimated awards. We maintain our level of professionalism well above the standard. We are proud to be one of DeKalb's Business of the Year recipients, and Marking Device Magazine's Small Business of the year.
Circa Vintage Gallery
Enjoy a whimsical journey through time. Explore unique vintage finds; Paintings, sculpture, photography, jewelry, home decor and furniture.
CITY:St. Charles
Bourbon Street Gallery
The Bourbon Street Gallery -- in the Bourbon Street area in Pheasant Run Resort & Spa. The gallery showcases the works of new, emerging and established Chicago artists.
CITY:St. Charles
Ducky's Formal Wear
Ducky's specializes in Tuxedo rentals. They can match all dress colors and have over 100 different choices to choose from. Surely they can meet your needs. Ducky's offers great desingers such as Joseph Abboud, Fubu, Chaps, Ralph lauren, Perry Ellis and more! Ducky's has not forgotten about the ladies. They also carry a wide selection of prom dresses. Come in and visit where there courteous knowledable staff is waiting to serve you!
Express Yourself
Specializing in Mommy's and their babies, Express Yourself carries a variety of nursing materials including covers, tops, pumps, diaper bags, wraps, slings, diaper accessories, cloth diapers, and much, much, more! Express Yourself also offers classes on cloth diapering, and is home to Bitty Birdie Blessins Clothing Line. If you are expecting this is a great place to start preparing for your little one!
Duck Soup Coop
Duck Soup Coop sells a wide variety of products including items such as bulk seeds, grains, teas, coffees, legumes, and many organic items. You may also find housewares, gifts, pet foods, vitamins, and cruelty free body care products.
King's Mill Refinishing
Beautiful hand-rubbed finishes, brass & metal polishing & repair, hand painting & stenciling, gold leafing, hand carving, woven cane, Rush splint & wicker, upholstery & slip covers, and hand-tied Oriental rugs.
CITY:St. Charles
Blue Moon Bikes Cycle & Fitness
Blue Moon Bikes is a full service bicycle shop specializing in: new and classic bicycles, antique bikes, parts, bike restoration and repair, as well as trading and buying old bikes. Blue Moon Bikes is run by a group of bicycle specialists.
Wool & Company
Wool and Company is a full service knitting and crochet store with an extensive gift selection. We spread our love of knitting in a fun, creative and informative way.
CITY:St. Charles
Trellis Farm & Garden
Your local Purina Feed Dealership offering the best in equine, small animal and wild bird needs. The new face of feed, seed and urban gardening.
CITY:St. Charles
The Picket Fence
The Picket Fence offers a variety of gifts including candles, home accessories, and cards.
Town House Books
Independent book store in 1853 Greek revival townhouse, housing thousands of titles for all ages.
CITY:St. Charles
Heinz Brothers Greenhouse Garden Center
Open daily, year-round. A greenhouse, garden center and gift shop offering annuals, perennials, bulbs, ground covers, potting needs, garden art, tools and everything else imaginable for the gardener.
CITY:St. Charles
Paw Lickin' Good Treats
Paw Lickin' Good Treats is a bakery dedicated to your dog or cat. The meet the demand for high quality, holistic food in the area. They are constantly on the lookout to bring in new and healthy new lines. On top of food and treats, Paw Lickin' Good Treats also carry bake your own cake, collars, harnesses, grooming materials, apparel, toys, nutritional supplements, and more. Even the pickiest eater will find something tasty here!
Blumen Gardens
Our retail gardens and shop have become a gardener's lush retreat of two city blocks tucked away in the historic industrial district and neighborhood of beautiful Sycamore. Ponds, statuary, plants and other garden necessities. Seasonal operation.
Custom Furniture
Two stories of quality, solid wood furniture since 1938. Huge selection of finished, unfinished home, office furniture by Amish and other American manufactures.
CITY:St. Charles
Have To Have
Have to Have carries women's clothing sizes 0-14, Miss Me Jeans, shoes, jewelry, purses and gifts. Open Tuesday-Friday 10:00am-5:00pm, Saturdays 10:00am-5:00pm and Sundays Noon-4:00pm. Closed Mondays.
The Wine Exchange
Featuring wines from across the Globe. Local & Hotel Delivery Available. Saturday tastings 1pm-5pm.
CITY:St. Charles
Panache Etcetera Inc
Boutique -- home accessories, antiques, furniture, jewelry, apparel, bath and body.
CITY:St. Charles
Consignment Gallery
We consign and sell new and used upscale quality brand name furniture, accessories and art. Because of our growth, we are now offering residential and commercial staging and offer an estate sale service.
CITY:St. Charles
Tranquility Skin & Body Care Center
Salon specializing in customized skin care, manicures, pedicures and waxing.
CITY:St. Charles
Glitter has over 100,000 different items in stock and new items added weekly. Choose from a wide selection of jewelry, cosmetics and clothing in sizes from youth girl to 3X. Hours: Mon. - Sat. 10am - 8pm and Sun. 11am - 5pm
21 - 20
Girl's Night Out
Girls Night Out is a monthly shopping event in Downtown DeKalb! Every third Thursday of the month from 5 - 8 pm downtown will host a themed Girls Night Out shopping event! July's theme is Sizzling Sidewalk Sales. Come downtown to see all the sidewalk sales, specials, and entertainment! Free Admission (815)751-4734 / firstname.lastname@example.com / https://www.facebook.com/downtowndekalb
Wandering Dragon Game Shoppe
Located in the heart of historic, downtown Plainfield, with its comfortable, "Old World" feel, Game Library, spacious Event Area and eight game rooms available to rent for private parties, The Wandering Dragon is not just an amazing board game store, but a home away from home for family and friends to gather and get lost in some fun.
Urban Grace
Urban Grace, located in downtown DeKalb, Illinois, sells CeCe Caldwell's Paints, provides monthly workshops catered to individual techniques using CeCe Caldwell's products, and will also custom paint furniture.
Bend General Store
They are exclusively owned & managed by lifelong St. Charles residents. They have endeavored to embrace St. Charles past, and bring uniquely old world small town experience to our fellow residents.
CITY:St. Charles
Specializing in all dog care. Dog training; doggie day care; overnight dog boarding; pet sitting; dog grooming; pooch parties.
CITY:St. Charles
6 - 7
Kane County Flea Market
The best in the Midwest or anywhere. Up to 1,000 dealers display and sell antiques, collectibles and "fancy junque." A country breakfast is served on Sundays.
CITY:St. Charles
Hy-Vee operates more than 230 retail stores in eight Midwestern states, including Illinois, Iowa, Kansas, Minnesota, Missouri, Nebraska, South Dakota and Wisconsin.
Whiskey Acres
Meet farmcrafted spirits. Grown from the finest grain, handcrafted and distilled on our fifth generation family farm. From us to you. From Seed to Spirit. Production Underway! • Tasting room & cocktail patio opens Summer 2015 Bourbon, Corn Whiskeys, Rye Whiskey & Vodka
Sep 24
DeKalb Farmer's Market
The DeKalb Farmers Market features locally-grown produce, wine, baked goods, flowers and artisan crafts. Every Thursday (June 4th - Sept 24th) 10am - 2pm Van Buer Plaza on the corner of North Second & Locust St. in DeKalb. For more information call 815-756-6306 or visit http://www.dekalb.org
Sweet Revival Antiques
Located in Kings, Illinois this coffee/antique shop, located in a historic church, is open every week Wednesday through Saturday and hours are Wednesday, Thursday, and Saturday 8-2 and Friday 8-6. We have packaged gourmet coffees, sweets, and antiques all in a beautiful, historic building.
Harvest Lane Vintage
Scheduled sales once or twice a month featuring a fresh selection of vintage, industrial, farmhouse items for yourself and your home.
CITY:St. Charles


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Jefferson School of Pharmacy
The Jefferson Difference
Welcome to the Jefferson School of Pharmacy, an integral part of one of the nation's premier academic healthcare centers. Click here to find out about the success of our graduates.
Founded in 2008, we have built an innovative Doctor of Pharmacy program that effectively prepares our graduates for interesting and challenging pharmacy practice roles across the health care continuum. Underpinning our curriculum is an accomplished and diverse team of healthcare leaders, teachers, researchers and preceptors (practitioners) who make up our faculty. Collectively, this group brings a broad range of experiences and perspectives to our students and they are recognized for their leadership in national and international pharmacy and healthcare membership organizations as well as their research in pharmaceutics, pharmacology, health outcomes, the clinical sciences and related fields.
Our classroom, laboratory, and pharmacy-practice experiences and extracurricular activities at the Jefferson School of Pharmacy are designed to enable our student pharmacists to become competent and confident practitioners who apply their knowledge and skills to care for individual patients as well as improve the overall health of our community.
Why Choose Jefferson School of Pharmacy in Philadelphia?
As part of Thomas Jefferson University, the largest freestanding academic medical center in Philadelphia, the Jefferson School of Pharmacy is a partner in one of the country's most successful and highly recognized interprofessional healthcare learning environments, with a dynamic center of education recognized for progressive care, practice, education and research.
Collaboration is a Jefferson hallmark, and students and faculty have many opportunities to partner with peers across our entire organization and in clinical settings throughout the region. The Jefferson School of Pharmacy benefits from an integral partnership with the Thomas Jefferson University Hospitals Department of Pharmacy Services which is nationally renowned for excellence in practice and training.
The Jefferson School of Pharmacy is part of a legacy of collaborative teaching, research and service uniquely positioned to impact the health and well-being of our community, our country and the world.
In the News
Jefferson School of Pharmacy Student Recognized for Medication Safety Intervention
JSP Faculty Member Elected Officer of Regional Pharmacist Organization
JSP Faculty Researcher Featured in Special Issue of Experimental Physiology
Sunday Shoyele, PhD Receives Funding to Develop Novel Drug Delivery Technology
September 2014 JSP Awards & Distinctions


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Without Faith
Do you seek God diligently? Do you make use of prayer, Bible study, worship, and the sacraments, baptism and the Lord's Supper? Do you awake in the morning resolved to seek God, no matter what comes your way? Take some ...Read More
Taken Up by God
Two thousand years ago, God spoke to His people face to face in the person of Christ Jesus. One day, Jesus will return, and we will live in the direct presence of God forevermore. We show our longing for this ...Read More
Acceptable Sacrifice
Do you trust that God will provide for you? Do you believe that God will really give you all that you need? Take some time to look at the things you can offer to God — for example, time, money, ...Read More
The Universe Created
Western believers have a tendency to become practical deists. We confess that God created the world, but our cultural worship at the altar of naturalism leads many of us to go about our daily lives as if God no longer ...Read More
Things Hoped For
The arrival of the new heavens and the new earth is one example of a promise that has yet to be fulfilled. But the resurrection and ascension of Christ guarantees that the whole created order will be transformed. Ask the ...Read More
Being Faithful
We often do not feel like righteous people, nonetheless we are declared righteous on account of our faith in Christ. As such, we must live a life that reflects this reality. If you have broken a promise recently, go apologize, ...Read More
Living by Faith
Dr. Sproul says that "living by faith means that sometimes we hold on to a barren cliff with our fingernails with all our strength as we trust in an invisible God." This is what Abraham did when he was commanded ...Read More
Dying in Faith
The resurrection of Christ guarantees that He has made an effectual sacrifice for sin and that we too will one day be resurrected. It guarantees the justice of God and gives us hope in the midst of this evil world. ...Read More
Redeemed by Faith
We cannot live our lives before the face of God until we are clear that it is the perfect obedience of Christ alone that saves us. If we think that we earn our own righteousness, we have not been justified, ...Read More
The Faithful God
It is easy for Christians to talk about the trustworthiness of our God. Sometimes, however, we discuss God's faithfulness openly without really believing that He will fulfill His promises to us. Look at your life to find areas where you ...Read More
Daily readings to encourage your heart and mind in the pursuit of God and his glory.Topics
- All
- Angels and Demons
- Atonement
- Basic Reformed Theology
- Irresistible Grace
- Limited Atonement
- Perseverance of the Saints
- Total Depravity
- Unconditional Election
- The Church
- Church Discipline
- Church Leadership
- Creeds and Confessions
- God
- Holiness
- Sovereignty
- Heaven and Hell
- Heresies
- The Holy Spirit
- Jesus Christ
- Cross
- Incarnation
- Resurrection
- Justification
- Last Things
- Man and Sin
- Sacraments
- Salvation
- Faith
- Regeneration
- Scripture
- Systematic Theology
- Theological Views
- Roman Catholicism
- Music
- Apologetics
- False Teaching
- Atheism
- Christianity and Culture
- Creation
- Ethics
- Philosophy
- Science
- Bible Figures
- Bible Interpretation
- Bibles
- Books of the Bible
- Gospels
- Covenants
- General Reference Works
- Introduction to the Bible
- Jesus' Ministry
- Life of Jesus
- New Testament
- Old Testament
- Parables
- Prophecy
- Sermon on the Mount
- Ten Commandments
- The Lord's Prayer
- Controversies in the Church
- Arts
- Bible Translation
- Covenant Theology
- Creationism
- Inclusivism
- Law and Gospel
- Lordship Salvation
- Politics
- Sabbath
- Spiritual Gifts
- Stewardship of Creation
- Theonomy
- Women in Ministry
- Marriage and Family
- Divorce
- Parenting
- Practical Theology
- Discipleship
- Evangelism and Missions
- Grief and Death
- Pastoral Ministry
- Preaching
- Worship
- Spiritual Growth
- Anxiety and Worry
- Apostasy
- Assurance
- Conscience
- Depression
- Doubt
- Fellowship
- Godliness
- Guilt
- Humility
- Joy
- Knowing God's Will
- Legalism
- Love
- Money and Stewardship
- Oaths and Vows
- Prayer
- Pride
- Repentance and Forgiveness
- Sanctification and Growth
- Service
- Spiritual Fruit
- Suffering
- Thankfulness
- Vocation
- Ancient Church
- Biography
- Enlightenment and Modernism
- Reformation
- Twentieth Century


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To find a doctor, call 800-667-5356 or click below:
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En Español (Spanish Version)
Definition | Causes | Risk Factors | Symptoms | Diagnosis | Treatment | Prevention
Rickets is disease resulting from a vitamin D , calcium, or phosphate shortage in children. It causes bones to soften and weaken.
Copyright © Nucleus Medical Media, Inc.
Rickets results when there is a vitamin D, calcium, or phosphorous shortage in a child's body. This may occur when:
Vitamin D controls how calcium is absorbed in the body. It also controls levels of calcium and phosphate in bone. Vitamin D is absorbed in the intestines from food. Vitamin D is also produced by the skin during exposure to sunlight.
Most often, rickets is caused by a shortage of vitamin D. This can result from:
Less often, rickets can be caused by other disorders that affect vitamin D absorption or calcium metabolism such as:
Factors that may increase your child's chances of getting rickets include:
Symptoms may include:
The doctor will ask about your child's symptoms and medical history. A physical exam will be done.
Your child's bodily fluid and bone may be tested. This can be done with:
Pictures may be taken of structures inside your child's body. This can be done with an x-ray .
Treatment attempts to:
Treatment of the underlying cause may include:
Treatment to relieve or correct symptoms may include:
To help prevent rickets, your child should: