Abstract: A process for the preparation of polymers having nucleobases as side groups by means of multicomponent reactions, especially the Ugi reaction, is described. Because of the multicomponent nature of preparation, the properties of the polymers can be varied substantially better than has hitherto been possible and can be adapted to requirements for use as an antisense or antigen therapeutic agent or as a diagnostic agent.

Abstract: A tissue mimicking material for ultrasound phantoms has ultrasound speed and attenuation characteristics that are characteristic of human tissue and well suited for use in measuring and calibrating the potential biological effects of ultrasound equipment. The material is formed of an aqueous mixture of large organic water soluble molecules condensed from skim milk with a total solids content in the range of 10% to 30% by weight. The total fat content is less than 1% by weight, with the residual lipid particles of a size sufficiently small to remain in suspension without agglomerating and separating from the mixture over extended periods of time.

Abstract: A method for fluorophore bias removal in microarray experiments in which the fluorophores used in microarray experiment pairs are reversed. Further, a method for calculating the individual errors associated with each measurement made in nominally repeated microarray experiments. This error measurement is optionally coupled with rank based methods in order to determine a probability that a cellular constituent is up or down regulated in response to a perturbation. Finally, a method for determining the confidence in the weighted average of the expression level of a cellular constituent in nominally repeated microarray experiments.

Abstract: This invention describes methods and kits for determining instrument linearity of a flow cytometer and is particularly useful as a control particle for use in conjunction with absolute cell counting methods. The particle used in the practice of this invention comprises a small fluorescent bead.

Abstract: Target nucleated cells, and target cells containing remnant ribosomal material, which are present in a quiescent anticoagulated whole blood sample are optically detected, enumerated, and analyzed in a sample chamber that has a varying through plane thickness due to convergent opposing sample chamber walls. At least one of the convergent walls of the chamber is transparent so that the blood sample can be observed. The chamber's varying thickness produces a first lesser thickness region in the chamber wherein individual red cells and quiescent monolayers of red cells in the sample will reside after the sample is introduced into and fills the chamber. Larger formed constituents such as white blood cells and nucleated red blood cells present in the sample will reside in greater thickness regions of the chamber, and non-nucleated red cells which reside in such greater thickness regions will agglomerate to form rouleaux.

Abstract: Disclosed is a stabilized enzyme composition for use in clinical examination, comprising: (a) an enzyme component comprising at least two enzymes selected from the group consisting of alkaline phosphatase, creatine kinase and alanine aminotransferase; (b) a stabilizer component comprising effective stabilizing amounts of an albumin, and at least one saccharide selected from the group consisting of trehalose and sorbitol; and (c) an aqueous medium having dissolved therein the components (a) and (b). The enzyme composition of the present invention is stable for a prolonged period of time not only under non-freeze refrigeration conditions, but also under freezing conditions or under conditions for non-freeze refrigeration after thawing of the frozen composition, as compared to the conventional enzymatic compositions.

Abstract: The present invention is directed to a stable, non-hazardous solution for calibrating oxidation-reduction potential (ORP) measurement cells. The redox standard calibration solution of the present invention consists essentially of an aqueous solution containing the triiodide/iodide redox couple. In a preferred embodiment, the solution of the present invention consists essentially of an aqueous solution containing up to about 0.01 moles per liter of iodine (I2) and at least about 1 mole per liter of potassium iodide. In a most preferred embodiment, the solution of the present invention consists of an aqueous solution of 4 molar potassium iodide (KI) and 0.0067 molar iodine (I2).

Abstract: A multiple single use optical sensor includes a series of continuous sensor stripes deposited on a substrate web. At least one sample chamber is adapted to extend transversely across a discrete portion of the series of sensor stripes to facilitate analysis of a sample disposed therein. The sample chamber may be moved, or additional sample chambers provided to enable subsequent measurements of additional samples at unused discrete portions of the sensor stripes. The continuous nature of the sensor stripes provides consistency along the lengths thereof to enable calibration data obtained from one discrete portion of the sensor stripes to be utilized for testing an unknown sample an other discrete portion of the sensor stripes. This advantageously eliminates the need for any particular discrete portion of the sensor stripes to be contacted by more than one sample, for improved sensor performance.

Abstract: Tissue-mimicking material suitable for phantoms for use with at least ultrasound and MRI have sections of material in contact with each other which mimic ultrasound and magnetic resonance imaging properties of human tissues, and preferably also computed tomography properties, so that the phantom can be used for the testing of imaging by various types of medical imagers. A suitable tissue-mimicking material for use in phantoms of this type includes an aqueous mixture of large organic water soluble molecules, a copper salt, a chelating agent for binding the copper ions in the salt, and a gel-forming material. Small glass beads may be intermixed therewith to provide a selected ultrasound attenuation coefficient without substantially affecting the MRI properties of the material. Larger glass beads may be used in a section to control primarily the ultrasound backscatter coefficient without significant effect on the ultrasound attenuation coefficient.

Abstract: A three-phase suspension suitable for use as an erythrocyte sedimentation rate (ESR) control having the following three components: (1) a synthetic plasma base, (2) an aggregating agent such as a high molecular weight polymer or combination of high molecular weight polymers, and (3) chemically fixed mammalian red blood cells. The control is designed to allow the user to monitor the accuracy and precision of analytical methods for determining the sedimentation rate of human erythrocytes in whole blood specimens. Chemical fixing of the red blood cells provides the ESR control with the capability of providing useful results in the presence of citrate and/or saline.

Abstract: Reagent composition and quantities used to prepare a simple, solid stable and reproducible protein assay and reproducible solventless protein assay standard. The method of preparing the protein assay and protein assay standards is also described. A solidifying agent such as a solid acid is added to the dye reagent solution prior to removal of solvent so as to produce a solid dye assay reagent.

Abstract: A system, composition and method for the stabilization of biological specimens, which employs a chemical fixative.

Abstract: Sensors for determining the presence and concentration of bio-molecules in a biological sample are provided in the form of polymer brushes, which comprise a substrate having a surface that is modified with a water-dispersible or water-soluble polymer segment having functional groups that bind probes. The method of synthesis of such sensors preferably includes use of controlled free radical polymerization techniques, and in particular the use of an iniferter initiator, which allows for controlled architecture polymers to modify the surface of the substrate. In this manner functional groups in the polymer chain are removed from the surface, which allows for solution chemistry to be more realistically reproduced with the benefits of a solid bound probe.

Abstract: A method of testing the purity or stability to degradation of a sample of lamotrigine or a pharmaceutical dosage form comprising lamotrigine comprises assaying the said sample for the presence of a compound selected from 3-amino-6-(2,3-dichlorophenyl)-1,2,4-triazine-5-(4H)-one (compound A) and N-[5-amino-6-(2,3-dichlorophenyl)-1,2,4-triazine-3-yl]-2,3-dichlorobenzamide (compound B). A process for producing compound B, which is novel, is also disclosed.

Abstract: A three-phase suspension suitable for use as an erythrocyte sedimentation rate control having the following three components: (1) a synthetic plasma base, (2) a high molecular weight polymer, and (3) mammalian red blood cells. The control is designed to allow the user to monitor the accuracy and precision of analytical methods for determining the sedimentation rate of human erythrocytes in whole blood specimens.

Abstract: The present invention relates to the use of sterol esters for the long-term stabilization of biological fluids, in particular even those which are obtained by lyophilization and subsequent reconstitution.

Abstract: Tissue-mimicking material suitable for phantoms for use with at least ultrasound and MRI have sections of material in contact with each other which mimic ultrasound and magnetic resonance imaging properties of human tissues, and preferably also computed tomography properties, so that the phantom can be used for the testing of imaging by various types of medical imagers. A suitable tissue-mimicking material for use in phantoms of this type includes an aqueous mixture of large organic water soluble molecules, a copper salt, a chelating agent for binding the copper ions in the salt, and a gel-forming material. Small glass beads may be intermixed therewith to provide a selected ultrasound attenuation coefficient without substantially affecting the MRI properties of the material. Larger glass beads may be used in a section to control primarily the ultrasound backscatter coefficient without significant effect on the ultrasound attenuation coefficient.

Abstract: A method of making a molecularly imprinted porous structure makes use of a surfactant analog of the molecule to be imprinted that has the imprint molecule portion serving as the surfactant headgroup. The surfactant analog is allowed to self-assemble in a mixture to create at least one supramolecular structure having exposed imprint groups. The imprinted porous structure is formed by adding reactive monomers to the mixture and allowing the monomers to polymerize, with the supramolecular structure serving as a template. The resulting solid structure has a shape that is complementary to the shape of the supramolecular structure and has cavities that are the mirror image of the imprint group. Similarly, molecularly imprinted particles may be made by using the surfactant to create a water-in-oil microemulsion wherein the imprint groups are exposed to the water phase.

Abstract: A method is provided for calibrating a noninvasive glucose monitor for prospective noninvasive glucose determination. Spectroscopic transflectance readings are measured on the patient's skin using a noninvasive glucose monitor. The patient's blood glucose level is measured with an invasive glucose monitor. The noninvasive and invasive measurements are correlated to form an individual algorithm for each patient. Preferably, the position of the patient's skin with respect to the probe of the noninvasive monitor is spatially adjusted while collecting the transflectance measurements such that multiple readings are taken on the patient's skin. The measurements are preferably taken over a period of time and over a plurality of glucose levels in the patient.

Abstract: This invention provides for a rapid and convenient method of simultaneous collection of both genomic and diagnostic information from a single sample on a bibulous pad by differential extraction of the diagnostic information from the genomic information. It is a surprising discovery of this invention that a PCR assay on the contents of the bibulous pad provides results comparable in reliability, specificity, and sensitivity to the best available serum (blood) based assays. The assays of this invention can be used to confirm each other, either by detecting the genomic information leading to the diagnostic information, or by detecting in the genomic information, a predisposition to a disease and confirming the presence of the disease through diagnostic testing.

Abstract: A matrix for tissue culture comprising two kinds of sponges having at least one different physical property and/or at least one different chemical property; a method for culturing tissue using said matrix for tissue culture comprising inoculating and culturing first cell on a first sponge, laminating a second sponge thereon, and inoculating and culturing second cell on said second sponge; a method for fixing a cultured tissue comprising placing a cultured tissue in gelatin solution solated by elevating temperature, lowering temperature to gelatinize gelatin to fix the cultured tissue by said gelatinated gelatin; and an artificial skin fixed comprising dermis layer fixed by gelatin and epidermis layer laminated on the dermis layer.

Abstract: Rapid characterization and screening of polymer samples to determine average molecular weight, molecular weight distribution and other properties is disclosed. Rapid flow characterization systems and methods, including liquid chromatography and flow-injection analysis systems and methods are preferably employed. High throughput, automated sampling systems and methods, high-temperature characterization systems and methods, and rapid, indirect calibration compositions and methods are also disclosed. The described methods, systems, and devices have primary applications in combinatorial polymer research and in industrial process control.

Abstract: The invention describes quality control devices for assays that measure analytes in cells and tissue samples, and methods of use thereof. In particular, the quality control device comprises a matrix affixed with synthetic controls in different concentrations, or different synthetic controls. The quality control device can be adhered to a microscope slide and processed simultaneously with a tissue sample.

Abstract: Method and reagent for the determination of iron in a biological sample in which the bound iron is released, the released iron is reduced to Fe2+, a color reagent solution is added and the color complex that is formed is measured photometrically, characterized in that a water-soluble EDTA-complexing compound in particular an indium and/or scandium salt is added to the sample.

Abstract: A rapid fluorescence staining method for facilitating flow cytometry analysis of reticulocytes is described. The method comprises contacting cells with a cocktail containing a detergent, sphering agent, and a cell impermeable dye, such as TO-PRO-3, for about one minute. Advantageously, the inventors have found that the cocktail permits the dye to penetrate the cell membrane rapidly.

Abstract: Apparatus and methods for supplying a portion of a fluid stream and, alternately, a fluid of known composition and concentration to an analyzer are provided. The fluid stream is directed through a series of connected chambers formed in an integral housing. A sampling needle has an inlet in one of the chambers and an outlet in fluid communication with the analyzer. When desired, a tube or vial containing a known fluid may be inserted into a chamber containing the sampling needle, so that the known fluid will be supplied to the analyzer. A second needle provides ventilation to the vial to prevent the formation of a vacuum as the known fluid is drained from the vial.

Abstract: Disclosed is CPG, a combination of a chlorhexidine salt (such as chlorhexidine digluconate, chlorhexidine diacetate, or chlorhexidine dichloride) and n-propyl gallate that can be used at ambient temperatures as a urine preservative.

Abstract: The invention pertains to a calibration layer comprising an optically transparent polymer containing an amount of photobleachable luminscent material present in such a way that the final polymer film contains less than 10 wt. % of luminophore and has an optical attenuation of less than 0.3 absorption units in the wavelength region of interest. The invention further is concerned with a method of calibration of an optical image device, preferably an optical or Raman microscope, by using the decrease in luminescence as the result of photobleaching between two consecutive images for calibration.

Abstract: The present invention relates to stabilized compositions of troponin capable of serving as standard and/or control in immunoassays intended for assaying cardiac and/or skeletal troponin(s) in the blood serum or blood plasma of humans or animals. These stabilized compositions comprise, in aqueous solution, troponin I, troponin T and troponin C in the form of an I-T-C ternary complex.

Abstract: New human papilloma virus (HPV) vaccine formulations exhibit enhanced long-term stability. Formulation components can include: virus-like particles (VLPs) absorbed onto aluminum, a salt, non-ionic surfactant, and a buffer. Additional formulations also contain a polymeric polyanionic stabilizer and a salt either in the presence or absence buffering agents and nonionic detergent.

Abstract: Human Papillomavirus vaccine formulations which contain virus-like particles (VLPs) can be made more stable and have an enhanced shelf-life, by treating the VLPs to a disassembly and reassembly process. Also provided are formulation buffers to long term stable storage of VLPs.

Abstract: A method for preparing a solventless protein standard is disclosed in which a solventless dye indicator and a predetermined amount of solventless protein are placed in an appropriate receptacle such as the well of a multiwell plate. This results in a solventless protein standard in which the solventless protein and the solventless dye are contained within the same receptacle. When an appropriate solvent is added to the receptacle, the protein and dye react together to produce a color change which is detectable, and which can be used as a standard for a protein assay using that dye. Also claimed is the solventless protein assay standard produced by the process.

Abstract: An improved apparatus and method for evaluating platelet functionality of a blood sample. The apparatus includes a plurality of test cells. Each of the cells includes a platelet function restoration agent, an anticoagulant agent, and a clotting reagent. At least one of the cells also includes a platelet activating agent. The clotting time is determined for each of the aliquot portions, and the relative clotting times of the aliquot portions in the cells are determinative of the platelet functionality of the sample. The method includes the steps of combining a platelet function restoration agent, an anticoagulant agent, a platelet activating agent, and the sample of blood to be tested to form a test mixture. The platelets of the sample are activated by adding a clotting reagent to the test mixture at the start of the activated clotting time test, and the activated clotting time test is terminated upon detecting a predetermined change in a property of the test mixture.

Abstract: A method and apparatus for differentiating and enumerating the five major sub-populations of leukocytes in a blood sample (i.e., lymphocytes, monocytes, eosinophils, neutrophils and basophils) uses multiangle light scatter and DC (Coulter) volume measurements. Light scattering characteristics of the leukocytes are determined within five different angular ranges, all being lower than 40 degrees. The invention is particularly useful in differentiating and enumerating the basophil sub-population which has heretofore required more complex apparatus and/or chemical processing.

Abstract: A blood analyzing instrument includes a single transducer for simultaneously measuring the DC volume, RF conductivity, light scattering and fluorescence characteristics of blood cells passing through a cell-interrogation zone. Preferably, the transducer includes an electro-optical flow cell which defines a cell-interrogation zone having a square transverse cross-section measuring approximately 50×50 microns, and having a length, measured in the direction of cell flow, of approximately 65 microns.

Abstract: The present invention is an additive preparation for use in bodily fluid collection devices. The additive preparation has an additive, an organic acid and a metal carbonate compound. The preparation effervesces when in contact with a body fluid sample, thereby efficiently dispersing in a body fluid sample. The formulation is desirably tabulated to provide an effective, easily stored, and handled preparation. However, a binding or bulking agent may be added to the additive preparation formulation to provide binding and lubricating properties to the formulation. A binding agent enables granulating of the formulation without the forming of a pellet.

Abstract: Aqueous blood-sample diluting reagent and method of its use for compelling a morphological change in a blood sample to yield an MCV value assayed at elapsed time after the sample is drawn to be consistent within a diagnostically acceptable range with the original, immediate post-drawing MCV value. Selection of a small amount of a predetermined surfactant added within a limited range of concentration, and of a salt for adjusting osmotic pressure of the sample is thereby determined. The blood sample is treated with an anti-coagulant agent immediately post-drawing, and for assay in a particle analyzer at post-drawing elapsed time is diluted with the reagent solution. The reagent has an osmotic pressure (&pgr;) of approximately 150-400 mOsm/kg and a pH of 6.0-8.5. The surfactant is present in a 0.0005% to 0.5% concentration and has a hydrophile-lipophile balance (HLB) of 10-20.

Abstract: Hematology control compositions and systems used to measure a plurality of parameters in a blood sample are provided. The hematology control compositions are particularly useful as a control for multi-parameter, automated instrument systems. The control compositions comprise a reticulocyte component, a white blood cell component, a red blood cell component, a nucleated red blood cell component, a platelet component and a reticulated platelet component. Methods of making and using the control compositions are also provided.

Abstract: A method for testing a cell suspension comprises the steps of: (1) diluting a portion of the cell suspension such that the liquid of the diluted suspension has the same osmolality as the extra cellular liquid of the cell suspension (plasma), and (2) subjecting the cells in the diluted suspension formed in step (1) to a cell size measurement while suspended in said diluted suspension. The method involves the testing of cells at their in vivo osmolality, thereby minimizing the possibility of swelling over time and mimicking the cells in vivo condition in respect of its osmotic environment.

Abstract: The present invention is directed to tracer-containing chemical compositions and to the use of at least one perfluorocarbon tracer in such compositions to provide a means of identifying and quantitatively analyzing such compositions.

Abstract: In accordance with the present invention, a method of conducting an assay of a sample containing an analyte of interest includes the step of forming a mixture so as to bring a metal-ligand complex into interactive proximity with the sample containing the analyte of interest. The mixture is irradiated with electromagnetic light energy so as to cause emission of light indicative of the analyte of interest. The emitted light is measured, and the measurement of the emitted light is utilized to measure the analyte of interest. The metal-ligand complex can be [Re(bcp)(CO)3(4-COOHPy)]+, [Os(phen)2(aphen)]2+, [Os(tpy)(triphos)]2+, [Os(tppz)2]2+, and [Os(ttpy)2]2+, or the like. Also, the present invention is directed to a metal-ligand complex of the formula [Re(bcp)(CO)3(4-COOHPy)]+.

Abstract: This invention relates to lytic reagents and methods of using the lytic reagents for automatically determining leukocyte subpopulations in blood. More specifically, the new lytic reagents selectively lyse red blood cells and certain leukocyte subpopulations, which enables the differentiation of at least one subpopulation of leukocytes. The lytic reagents contain an ethoxylated long chain amine, a quaternary ammonium salt and an acid. When used in combination with a second lytic reagent system, one is able to obtain at least a five part differential of leukocytes by impedance and light scatter measurements, by impedance and radio frequency measurements, or by radio frequency and light scatter measurements.

Abstract: This invention relates to lytic reagents and methods of using the lytic reagents for automatically determining leukocyte subpopulations in blood. More specifically, the new lytic reagents selectively lyse red blood cells and certain leukocyte subpopulations, which enables the differentiation of at least one subpopulation of leukocytes. The lytic reagents contain a polyoxyethylene based surfactant, a quatemary ammonium salt and an acid. When used in combination with a second lytic reagent system, one is able to obtain at least a five part differential of leukocytes by impedance and light scatter measurements, by impedance and radio frequency measurements, or by radio frequency and light scatter measurements.

Abstract: Hematology control compositions and systems used to measure a plurality of parameters in a blood sample are provided. The hematology control compositions are particularly useful as a control for multi-parameter, automated instrument systems. The control compositions comprise a reticulocyte component, a white blood cell component, a red blood cell component, a nucleated red blood cell component, a platelet component and a reticulated platelet component. Methods of making and using the control compositions are also provided.

Abstract: Control materials containing specified concentrations of the osteoporosis markers deoxypyridinoline, pyridinoline, C-telopeptide and N-telopeptide in a matrix that is substantially the same as that of human urine are prepared by selecting amounts of human urine that contain sufficient quantities of the markers to achieve the target levels upon concentration, lyophilizing the selected urine, optionally after clarification by filtering, freezing and thawing, and pH adjustments, then reconstituting the lyophilized material, and combining and/or diluting the lyophilized material, either before or after reconstitution, to adjust the marker contents to the target levels. Surprisingly, the markers survive this process sufficiently intact to serve as reliable control materials of known composition and concentration.

Abstract: A diagnostic test strip for determining the presence of a specified analyte in a fluid sample is described. The test strip has a test membrane sandwiched between two layers of a plastic sheath. The upper layer of the sheath has a sample well into which a liquid sample is placed. The test membrane has a sample receiving zone typically containing a buffer and a fatty acid sarcosinate. Adjacent to the sample receiving zone is a reagent zone containing reagent chemicals including gold colloid particles coated with antibodies to the specified analyte. In fluid connection with the reagent zone is a test zone containing immobilized molecules of the specified analyte. Preferably, in fluid connection with the test zone is a control zone containing an indicator that changes color when wetted by the sample and a liquid sink zone to absorb excess liquid in the sample.

Abstract: The invention relates to a process for the production of plasmas with added annexins for use as a control or standard in all functional clotting tests which are used for the detection of a lupus anticoagulant.

Abstract: Blood samples are stabilized for methemoglobin determination with a buffer composition containing (a) carbon monoxide-containing water; (b) sodium tetraborate or potassium tetraborate; and (c) KCN or NaCN. The buffer composition preferably may also have an erythrocytolysis agent. The buffer fixes the valence state of heme iron at a concentration representative of the blood at the time of collection, and maintains that fixed state for an extended period of time preventing further methemoglobin formation. The buffer also prevents reduction of existing target analyte, i.e., methemoglobin (ferric hemoglobin, Fe3+ hemoglobin) to normal reduced hemoglobin (ferrous hemoglobin, Fe2+ hemoglobin).

Abstract: Systems and methods for deriving standardized formulations and extracts of herbal remedies, plant extracts, and the like, based upon the rate of absorption and plasma concentration levels attained thereby, when such compositions are administered orally. According to a preferred embodiment, the system comprises a harvested section of small intestine from a mammal and interposed between a first solution having a known quantity of the pharmaceutical composition suspended or dissolved therewithin and a second solution comprising liquid plasma or a buffer solution. The section of intestinal tissue is oriented such that the mucosal layer is oriented toward the first solution whereas the muscularis is oriented toward the second solution. The second solution is periodically analyzed, both qualitatively and quantitatively, to determine the presence and concentration of one or more markers, and in particular any sub-component or metabolites thereof, that has diffused across the intestinal tissue.

Abstract: The present invention relates to stable compositions useful as primary standards and calibrators and controls comprising a cardiac troponin I (cTnI) such as native, recombinant, addition and deletion forms thereof, whether or not complexed with other troponin subunits such as TnC and/or TnT, in an inactivated human serum. The compositions are obtained by incubating troponin complexes with human serum. The compositions are characterized by an immunodetectability ratio of epitopes on the N-terminal segment to epitopes on the C-terminal segment substantially equivalent to that of pooled, fresh serum from acute myocardial infarction patients.