• 专利附录
  • 专利说明
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    • 专利摘要:
    The present invention relates to a system for drying chemical reagents on materials, in particular a system for producing articles for use in reagent test strips. By drying selected chemicals on the substrate that are pulled past a radiant energy source (preferably an IR source), rapid drying is achieved and a high quality product is obtained. Sufficient airflow may be provided to break up or disturb the bubble boundary layer on the drying solution to improve the drying rate. Any air stream provided should not disturb the surface of the solution. In addition, after being sufficiently dried in a shape stable state, an air impingement drying technique may be used in this system to finish drying the reagent material. The substrate on which the chemical is dried may include a reflective coating to facilitate use with high levels of radiant energy. It is suitable that metallic or metallized substrates are used to make the electrochemical test strips. Such test strips can be used in combination with various kits and can be conveniently read using known manual instruments.
    公开号:KR20030043770A
    申请号:KR1020020074662
    申请日:2002-11-28
    公开日:2003-06-02
    发明作者:딕케네스더블유.；오다케게리；제센아론
    申请人:라이프스캔, 인코포레이티드；
    IPC主号:
    专利说明:

    Solution drying system
    [12] The present invention relates to an approach for drying chemical compositions deposited on a substrate in solution form. The present invention is particularly suitable for drying solutions to prepare reagent test strips for use in analyte determination tests, in particular, electrochemical determination of blood analytes.
    [13] Analytical sample detection tests are well used in a variety of fields, including clinical laboratory testing, home testing, and the like, where the results of these tests play a leading role in the diagnosis and management of various conditions. More common assays include glucose, alcohol, formaldehyde, L-glutamic acid, glycerol, galactose, glycated proteins, creatinine, ketone bodies, ascorbic acid, lactic acid, leucine, malic acid, pyruvic acid, uric acid and steroids. Analytical sample detection is often performed in connection with physiological fluids such as tears, saliva, whole blood and blood-derived products. As the importance of analyte detection increases, a variety of analyte detection protocols and devices have been developed for both clinical and home use. Many detection protocols use reagent test strips to detect analyte in a sample.
    [14] As the demand for reagent test strips increases, the need for more efficient and flexible manufacturing methods increases. Still, only minor improvements have been made regarding the handling of reagent materials incorporated into test strips.
    [15] In preparing reagent test strips, substrates in which coatings of biological reagents, typically including heating instability or moisture sensitive biological components (after drying for preservation stability) in a low viscosity aqueous solution, are typically used to prepare one or more strips. Applies to Many existing systems designed to dry these biological reagents use high speed air impingement techniques to dry the coating applied in aqueous form to the substrate. Although effective to some extent, there are disadvantages associated with these current technologies, which are generally due to the high air impingement velocity and low heat that can be applied, which is essential for drying for an appropriate amount of time.
    [16] As such, significant attention has been given to the development of new technologies for drying liquid reagent compositions having low viscosity and surface tension applied to substrates. The present invention fulfills this need by providing a novel approach for drying a liquid coating or composition applied to a substrate. More specifically, the present invention avoids the problems typically associated with high speed air impingement drying, such as poor efficiency, low dehydration rate, solution disturbances due to airflow. Various features of the present invention provide improved manufacturing efficiency, reduced incidental manufacturing costs, and / or improved test strip quality. Those skilled in the art will clearly appreciate other possible advantages of the present invention.
    [17] The invention particularly relates to an apparatus and method for drying a solution having a viscosity of generally less than 100 centipoise (Cp), mostly about 1.5 Cp, applied to the surface of a substrate or material used to make a reagent test strip. Include. Finished products made using the described system also form part of the present invention. Typically, the product is in the form of a complete reagent test strip. Alternatively, a test strip precursor comprising a substrate material having at least a dry chemical solution thereon may be considered as a product of the present invention.
    [18] The present invention uses radiant energy to dry the solution applied to the substrate. Non-dispersive airflow can be provided to improve the drying rate. Substrates having a chemical coating dried thereon according to the invention can be used in various types of test strips. Suitably the substrate treated according to the invention comprises a metallic substrate. Such coatings dramatically increase the potential for energy applications. In addition, metallic or metal-coated substrates are suitably used for the electrochemical test strips.
    [1] 1 shows an overview of the invention from the front side;
    [2] 2 is a top view of the material coated with the solution to be dried in the IR dryer section of the present invention by the coater section.
    [3] 3A and 3B are bottom and side views, respectively, of a heating panel used in an IR dryer section.
    [4] 4 is a bottom view of the heating panel assembly used in the IR dryer section.
    [5] 5 is an enlarged view of the IR dryer section from the rear side.
    [6] 6 shows a product of the system of the invention at an intermediate stage of manufacture.
    [7] 7 is an exploded perspective view of a test strip made using the present invention.
    [8] * Description of the symbols for the main parts of the drawings *
    [9] 6: drying unit 8: substrate
    [10] 10: solution 12: die
    [11] 22: auxiliary drying unit
    [19] Each of the following figures schematically illustrates an aspect of the invention. Variations of the invention from what is shown in the figures can be envisioned.
    [20] In describing the present invention in more detail than provided in the foregoing "Detailed Description of the Invention", the drying system of the present invention and the method of use thereof are first described in more detail, and reagents that can be prepared using the system and method of the present invention. A review of the test strip precursor followed by a test strip made from the test strip precursor of the present invention and a method of using the test strip in the field of analyte detection.
    [21] However, before describing the present invention in detail, it should be understood that the present invention is not limited to the specific modifications described, but may naturally be modified. Various modifications may be made to the described invention, and equivalents may be substituted without departing from the true spirit and scope of the invention. In addition, various modifications may be made to adapt a particular situation, material and material composition, process, process step or steps, to the purposes, concepts, and scope of the invention. All such modifications are intended to be within the scope of the claims set forth herein. In addition, when a range of values is applied, all the values falling between the upper and lower limits of the range and any other declared value or a value included within the declared range are included in the present invention. The upper and lower limits of these smaller ranges may be independently included in the smaller ranges, which are also subject to the limits specifically included in the present invention and excluded from the declared ranges. In the case where the declared range includes one or both of these limits, the ranges excluding either or both of these included limits are included in the present invention. In addition, certain optional features of the variations of the invention declared herein may be declared and claimed independently or in combination with any one or more features declared herein.
    [22] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although certain methods and materials similar or equivalent to those described herein may be used in the practice or testing of the present invention, the preferred methods and materials are now described. All existing relevant materials (eg, publications, patents, patent applications, and hardware) mentioned herein are incorporated by reference in their entirety. The references are provided only those whose contents are disclosed prior to the filing date of this patent application. Nothing in this specification is intended as to allow the invention to not be construed as prior art to such materials.
    [23] As used in this specification and the appended claims, the singular forms "a", "and", "said" and "the" are used unless the content clearly dictates otherwise. This includes a large number of targets. On the contrary, the claims may be described with the exception of certain optional elements. This Declaration is intended to use such exclusive technical terms such as "only", "only", etc. in conjunction with the recitation of claim elements, or as a premise basis for using "exclusive" limitations.
    [24] Referring to FIG. 1, the elements of the present invention are shown in a manufacturing system 2. The system shown is a model TM-MC3 system manufactured by Hirano Texide Corporation Limited (Nara, Japan) adapted for use in the present invention. This may include the solution coating feature of the coating 4 as described in the US patent application entitled “Solution Striping System”, filed concurrently by the inventors of the present system.
    [25] 2 shows a top view of the characteristics of a coating system suitable for use in conjunction with a radiant energy drying system or drying section 6. In FIG. 2, a substrate or knitted material 8 is deposited and coated in the form of a strip or band in which solution 10 supplied to die 12 by one or more pumps is coated. A backing roller 16 is used to place the knit fabric as it advances past the die in the direction indicated by the thick arrow.
    [26] As shown in FIG. 1, the substrate 8 is provided in the form of a knitted fabric by a supply reel 18, after which the substrate with the reagent coating passes through various guide rollers and passes through the drying section 6. Accumulate on the winding reel 20. One or more auxiliary dryers 22 may be provided in series with the dryers 6. These may include features similar to those of the drying section 6, or may use air impingement drying techniques.
    [27] It is suitable for the various drying parts to be provided in the housing shown or behind the cover. Door (s) are included for access. When used in spin dryers, this structure provides a shield against unwanted exposure to reflected energy, acts like a wall of the oven, re-radiates absorbed energy, and speeds up the drying rate inside. This structure provides a closed environment in the case where a forced blowing method (especially a heating forced blowing) for drying is used in the auxiliary drying section.
    [28] The substrate or knit 8 preferably comprises a semi-rigid material capable of providing structural support to test strips that may be used. The substrate may comprise an inert material such as plastic (eg, PET, PETG, polyimide, polycarbonate, polystyrene or silicon), ceramic, glass, paper or plastic-paper laminate.
    [29] For use in electrochemical test strips, at least the surface of the substrate facing the reaction zone of the strip comprises a metal, wherein the relevant metals are palladium, gold, platinum, silver, indium, carbon, doped indium tin oxide, stainless Steels and various alloys of these metals. In many embodiments, precious metals such as gold, platinum or palladium are used.
    [30] In some cases, the substrate itself may be made of metal, in particular one of those described above. Generally, however, it is suitable that the substrate comprises a composite of metallic and / or conductive coatings (palladium, gold, platinum, silver, iridium, carbon, conductive carbon inks, doped tin oxide or stainless steel) and coated supports. Do. A further description of the substrate or support material that may be used in certain embodiments of the present invention is described in US Patent No. 6, entitled Logger Phillips et al., Entitled “Minimal Procedure System for Determination of Analytical Samples”. 4,935,346 and US Pat. No. 5,304,468, entitled "Reagent Test Strip and Blood Glucose Determination Device," issued April 19, 1994 to Logger Phillips et al.
    [31] When the metal-coated support is used as the substrate or knitted fabric 8, its thickness is typically in the range of about 0.002 to 0.014 in (51 to 356 μm), generally about 0.04 to 0.007 in (102 to 178 μm). The thickness of the metal layer is typically in the range of about 10 to 300 nm, generally about 20 to 40 nm. Gold or palladium coatings are suitable for this use. For ease of manufacture, it is suitable that the entire surface of the substrate 8 is coated with a metal.
    [32] Whatever type of substrate is used, the systems and methods of the present invention can be used to dry various different types of coating compositions applied to the surface of a substrate. In many embodiments, the coating 10 includes one or more reagent elements of the signal generation system. A "signal generation system" is one that provides a detectable signal in the presence of an analyte sample that can be used to determine the presence and / or concentration of an analyte sample in combination. The signal generation system may be a signal generation system that generates a color related to the presence or concentration of the analyte, or may be a signal generation system that generates a current that may be related to the presence or concentration of the analyte. Other types of systems can also be used.
    [33] Various different color signal generation systems are known. Relevant representative color signal generation systems include analyte oxidation signal generation systems. An "analyte sample oxidation signal generation system" is one that produces a detectable colorimetric signal that can induce analyte concentration in a sample, wherein the analyte is oxidized by a suitable enzyme, corresponding or proportional to the oxidized form. To produce hydrogen peroxide. Hydrogen peroxide is then used sequentially to generate detectable by-products from one or more indicator compounds, where the amount of detectable by-products generated by the signal generation system (ie, signal) is then correlated to the amount of analyte in the original sample. Will be. As such, the sample oxidation signal generation system that can be used in the subject test strip may be accurately characterized as a hydrogen peroxide based signal generation system.
    [34] As described above, the hydrogen peroxide based signal generation system includes an enzyme that oxidizes the analyte to produce a corresponding amount of hydrogen peroxide, wherein the amount is proportional to the amount of analyte present in the sample. Means that. The nature of this first enzyme depends on the nature of the sample to be tested, but is generally an oxidase. Thus, the first enzyme is glucose oxidase (if the sample is glucose), cholesterol oxidase (if the sample is cholesterol), alcohol oxidase (if the sample is alcohol), lactate oxidase (the sample is Lactate), and the like. Other oxidases for use with these and other related assays are known to the person skilled in the art and can be used. In these examples where the reagent test strip is designed to detect glucose concentration, the first enzyme is glucose oxidase. This glucose oxidase may be obtained from any convenient source (eg, naturally occurring in a source such as Asperus niger or penicillum) or may be produced recombinantly.
    [35] The second enzyme in the signal generation system is an enzyme that facilitates the conversion of one or more indicator compounds into detectable byproducts in the presence of hydrogen peroxide, wherein the amount of detectable byproducts that can be produced by this reaction is the amount of hydrogen peroxide present. Proportional to This second enzyme is generally a peroxidase, wherein suitable peroxidases include horseradish peroxidase (HRP), soybean peroxidase, recombinantly produced peroxidase and synthetic analogs with peroxidation activity, for example See Analika Chimica Ecta 233 (1990), 299-302, by Y. Ci, F. Wang.
    [36] The indicator compound or compounds are those that are formed or degraded by hydrogen peroxide in the presence of the peroxidase to produce an indicator dye that absorbs light within a predetermined wavelength range. The indicator dye is suitably absorbed strongly at a wavelength different from that strongly absorbed by the sample or test reagent. The oxidized form of the indicator can be colored or lightly colored or colorless final byproduct, which demonstrates the change in color. In other words, the test reagent may indicate the presence of an assay chamber (eg, glucose) in the sample by turning the colored area white or alternatively, colorizing the colorless area.
    [37] Indicator compounds useful in the present invention include 1 and 2 component colorimetric substrates. One component systems include aromatic amines, aromatic alcohols, azines and benzidines such as tetramethyl benzidine-HCl. Suitable two-component systems are those in which one component is MBTH, MBTH derivatives (see, eg, those described in US Patent Application No. 08 / 302,575, referred to herein), or 4-aminoantipyrine, and the remaining components are aromatic amines, aromatic alcohols. , Complex amines, complex alcohols or those that are aromatic or fatty aldehydes. Exemplary two component systems include 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) in combination with 3-dimethylaminobenzoic acid (DMAB); MBTH in combination with 3,5-dichloro-2-highoxybenzene-sulphonic acid (DCHBS); And 3-methyl-2-benzokiazolinone hydrazone N-sulfonyl benzenesulfonate monosodium (MBTHSB) in combination with 8-anilino-1 naphthalene sulfonic acid ammonium (ANS). In certain embodiments, die bonded MBTHSB-ANS is suitable.
    [38] Signal generation systems that generate fluorescence detectable by-products (or, for example, detectable non-fluorescent materials of a fluorescent background) can also be used in the present invention, which are novel for forgerradish peroxidases from Kiyoshi Zaits, Yosuke Okura. Fluorescent substrates: described in rapid and sensory assays for hydrogen peroxide and peroxidase (Analytical Biochemistry (1980) 109, 109-113).
    [39] Signal generation systems that generate current (eg, as used in electrochemical test strips) are particularly relevant to the present invention. Such reagent systems include redox reagent systems, which provide species measured by the electrodes and are therefore used to derive analyte sample concentrations in physiological samples. Redox reagent systems are typically present in a reaction zone that includes at least the enzyme (s) and the mediator. In many embodiments, the enzyme member (s) of the redox reagent system is an enzyme or plurality of enzymes that cooperate to oxidize the assay sample of interest. In other words, the enzyme component of the redox reagent system consists of a set of two or more enzymes that cooperate to oxidize a single analyte or related analyte. Relevant enzymes include oxidases, dehydrogenases, lipases, kinases, dephorases, quinoproteins and the like.
    [40] The specific enzyme present in the reaction zone depends on the specific sample designed to be detected by the electrochemical test strip, where representative enzymes are glucose oxidase, glucose dehydrogenase, cholesterol esterase, cholesterol oxidase, fiboprotein lipase, glycerol Kinases, glycerol-3-phosphate oxidase, lactate oxidase, lactate dehydrogenase, pyruvate oxidase, alcohol oxidase, bilirubin oxidase, uricase and the like. In many preferred embodiments where the assay of interest is glucose, the enzyme component of the redox reagent system is an enzyme that oxidizes glucose, such as glucose oxidase or glucose dehydrogenase.
    [41] The second component of the redox reagent system is the mediator component, which consists of one or more mediators. A variety of different mediators are known in the art and include ferriadin, phenazine ethosulfate, phenazine methosulfate, 2,6-dimethyl-1,4-benzoquinone, 2,5-dichloro-1,4-benzo Quinones, ferrocene derivatives, osmium bipyridyl compounds, ruthenium compounds, and the like. In these examples where the glucose and glucose oxidase or glucose dehydrogenase of the relevant analyte is an enzyme component, it is a particular related mediator, ferricyanide and the like.
    [42] Other reagents that may be present in the reaction zone include buffers, citraconates, citrate, maleic, maleic, phosphate, "good" buffers, and the like. Still other auxiliaries that may be present include divalent cations such as calcium chloride and magnesium chloride; Surfactant types such as Triton, Macol, Tetronic, Silwet, Zonyl and Pluronic; Stabilizers such as albumin, sucrose, trehalotm, mannitol and lactose.
    [43] For producing an electrochemical test strip, it is suitable that a redox system comprising at least an enzyme and a mediator as described above is used for the coating 10. In solution, the system suitably comprises a mixture of about 6% protein, about 30% salt and about 64% water. It is most suitable for the fluid to have a viscosity of approximately 1.5 Cp. Still, it should be understood that various kinds of solutions can be dried with the system of the present invention. Most suitably the solution comprises a reagent solution. Indeed, the advantages of the present system are most evident in connection with the drying of solutions in which chemical activity must be maintained and in solutions with lower viscosities, in particular those with viscosities below 100 Cp.
    [44] With regard to the hardware used in the system of the present invention, FIGS. 3A and 3B show a preferred heating element used for transferring radiant energy into the drying section 6. The device shown is a panel or heater board 24 produced by Radiant Energy Systems (Wayne, NY). For each board 24, eight resistance heaters 26 are provided in conjunction with the ceramic heat well 28 and associated electrical connections 30. The heater is set to emit medium wavelength infrared energy. Instead of using one or more heater panels 24, multiple discrete heaters may be provided in series. Suitable industrial type infrared drying units are also produced by Radiant Energy Systems under model number SFA-24. Alternatively, one or more quartz tube heaters may be used to provide radiant (especially IR) energy for drying the knitted phase solution according to the present invention. Sun Mite ™ heater Model No. FFH-912B by Posttoria (Comstock, Mich.) Has demonstrated a good effect on this.
    [45] 4 shows the best arrangement for the heater element. Three heater boards 24 are shown in a line. The screen 32 is provided in front of the heater element. When using good medium-wavelength infrared energy, the screen functions to smooth radiation and randomization and energy application.
    [46] 5 shows the apparatus of FIG. 4 in place in the drying section 6. Although six heater boards 24 are shown, it is suitable that the energy is applied only by the elements on the knitted fabric 8 moving as shown by the straight arrows. The heater element 216 is preferably located at a height between about 1 to 5 inches (25.4 and 127 mm) above the substrate on which the coating is deposited. This spacing is more suitably between about 2 to 4 inches (50.8 to 101.6 mm). The amount of energy applied along the knit or substrate is suitably between about 3.5 and 8 watts per square inch.
    [47] When the knit includes a surface that reflects most of the impact, it is particularly suitable to apply this high amount of energy along the knit. With coatings with low emissivity (about 0.1), such as platinum or palladium, high energy levels do not destroy the substrate. In some cases, the same effect can be achieved using a substrate that passes energy or is transparent.
    [48] In either case, the solution 10 typically absorbs energy. That is, it has a high emissivity (about 0.9). Thus, the applied IR energy has the effect necessary for drying but not otherwise.
    [49] Even under the high intensity drying conditions according to the present invention, it is possible to dry the reagent coating without significant effect on reagent activity. By way of example, where protein-based reagents are included in the coating, the drying conditions used are set so that the protein reagents are not modified beyond their utility. In particular, the solution applied to the surface of the substrate comprises an enzyme and the activity of the enzyme coating composition following drying according to the present invention does not show a significant loss of activity as determined by the DCIP / PMS method. The low absorption of water in the coating and the effect of evaporative cooling of the solution phase on water volatilization protect the protein from denaturation.
    [50] The latter effect has the same utility as drying with only heating air, but there are no other advantages that can be applied to drying with radiant energy. Attempting rapid drying with air impingement techniques to achieve the performance available in this system can easily destroy reagent coating activity or melt knit fabrics.
    [51] In the present invention, one or more temperature sensors 34 may be provided in the dryer 6. Thermocouples and / or IR sensors may be used. They can be used to monitor the temperature of the fabric, the atmosphere in the dryer or the air temperature. Even in reflective coatings on knitted fabrics having high reflectivity or low emissivity, the plastics (coated polyester knits) with the coating applied thereon can be affected by temperatures of about 300 ° F. (150 ° C.) or more. Feedback from the temperature sensors can be used to set or adjust the dryer temperature to avoid damaging the reagent material or knitted fabric coated thereon.
    [52] In the present invention, knitting processing rates as high as 100 ft per minute (ie, the rate at which the solution can be dried on a substrate) can be achieved. More typically, processing speeds between 5 and 25 to 50 feet per minute are realized. The highest manufacturing speed can be obtained in conjunction with the setting in which the heater element is used in conjunction with one or more fans 36 which provide an unobstructed air stream to destroy the bubble barrier of the solution dried in the spin dryer 6. have.
    [53] As mentioned above, one or more optional auxiliary drying units 22 may be used in the present invention. Typically each includes an air impingement dryer using heated forced blowing. The auxiliary dryer 22 is useful for improving the knitting processing speed by completing the drying after the shape of the beads of the solution applied on the substrate is substantially fixed by the radiation energy drying.
    [54] In general, impingement drying provides a problem factor, especially when drying low viscosity solutions. Simple air impingement drying introduces both cross-web and down-web reagent strips inconsistent with the process of the present invention.
    [55] At the most basic level, it is easy to understand how high velocity air impingement on a solution can cause waves to cause non-uniformly dried products along the length of the stripe of the solution. However, the effect on the cross section of a drying reagent prepared using only air impingement drying is unclear. Solution coatings dried only by air impingement techniques exhibit an exaggerated U-shaped cross section. This profile arises due to the osmotic migration of reagents over time towards the faster drying edges.
    [56] As is evident by the improved consistency of the reagent test strip consisting of the reagent coating dried according to the invention, a more uniform cross section is obtained utilizing the radiant energy. The rapid drying possibilities provided by the present invention alleviate edge accumulation by reducing the time available for migration by osmotic generation.
    [57] In addition, down web consistency is improved because the solution is not disturbed when prone to migration. Since the radiating part 6 applies sufficient energy to effectively fix the shape of the coating, even if the auxiliary air impingement dryer 22 is used in the system 2, no ripples or disturbances are apparent in the dried reagents. Do not.
    [58] Rapid shape accuracy with radiant energy helps to produce consistent products in different directions. Substrates that are hydrophilic or include hydrophilic coatings (which may often be good for electrochemical test strips, US Patent Application No. 09 / 497,269, entitled "Electrochemical Test Strips for Use in Analyzing Samples") When using a low viscosity or low surface tension solution in combination with a US patent application entitled "Solution Striping System", the solution tends to "wet" the substrate rapidly. The solution tends to flow transversely and coats a wider area than desired without retaining stripes or beads based on the application. The immediate drying effect achieved by the present qkfuad by applying the radiant energy is sufficient to stop it, fixing the boundaries of the reagents. Thus, expensive reagents are not lost by migration. This approach provides a sufficient improvement in dried stripe width accuracy and placement precision.
    [59] In addition, thicker coating areas of the reagents can be achieved without requiring multiple solution coatings. If it is not desirable to change the surface tension of the reagent or the surface energy of the substrate to be coated, there are several alternatives for controlling the stripe width and thickness. The ability to quickly fix the shape of a thick coating achieves goodness of its application.
    [60] In an electrochemical test strip, the dried reagent coating functions as an active area in the electrochemical cell. Sufficient concentration of reagent components is needed to achieve a satisfactory result. This was confirmed by the inventors that low concentrations of reagents result in poor test results. Thus, the ability to apply a relatively thicker reagent coating on the substrate for inclusion of the test strip offers the possibility for improved test strip accuracy.
    [61] Various types of products can be made using the features of the present invention. 6 shows a test strip precursor 54 in a card for making an electrochemical test strip. It comprises a substrate or knitted fabric 8 as shown in FIG. 4 and is cut in two between reagent stripes to form two 2-inches (5.4 cm) wide cards, and the notch 56 as shown. It is further modified to have. The precursor may further include an opposing knit 58 and a spacer 60 therebetween. Cut, punched, and stamped to form the test strip end 62 are shown, respectively.
    [62] A continuous process, such as a continuous web process (such as rolls of various materials joined together to produce a precursor) or a discontinuous process (eg, the strip portion is first cut and then joined together) to process the precursor member. It can be used to Other modes of multi-component strip fabrication can also be used.
    [63] The spacer suitably comprises a double-adhesive adhesive product. It may be made of any convenient material, and representative materials include PET, PETG, polyimide, polycarbonate, and the like. Knit 8 is suitably plastic with sputter deposited palladium and functions as a "working" electrode, and knit 58 is suitably gold coated plastic and functions as a "reference" electrode. Each knit portion may have a thickness in the range of about 0.005 to 0.010 in (127 μm to 245 μm).
    [64] The test strip precursor may be continuous tape-like or base card (eg, parallelogram or shorter length, similar shape) prior to the manufacturing stage shown in FIG. 6. As such, the test strip precursor may vary significantly depending on whether it is tape-shaped or shorter (ie card-like). In addition, the width of the test strip precursor may vary depending on the characteristics of the particular test strip being manufactured for this TEk. In general, the width of the test strip precursor (or coated substrate only) may range from about 0.5 to 4.5 inches (13 to 114 mm). Of course, this can be wider to accommodate additional stripes of solution.
    [65] As implied above, the width and depth of the solution coating applied to the substrate or knit 8 may vary depending on the properties of the product to be manufactured. For test strip fabrication, the striping width can typically be in the range of about 0.05 to 0.5 inches (1.3 to 13 mm) and the thickness range can be about 5 to 50 microns. In particular, for use in electrochemical test strips, when the stripe or band of aqueous reagent material is wet, it is most suitable to be excreted about 0.065 to 0.200 in (1.7 to 5.1 mm) wide and about 15 to 25 microns deep.
    [66] As shown in FIG. 6, after being cut into the card, precursor 54 is fragmented to produce individual test strips 62. Similar to the precursor, the test strip can be cut manually or by automated means (eg, laser fragmentation means, rotary die cutting means, etc.). Precursors can be cut in stages or in a single operation as shown and described. The pattern used for cutting may be set by a program, guide, map, image or other directional means indicating or indicating how the test strip precursor should be cut into the reagent test strip. The pattern may or may not be visible on the test strip blank prior to cutting / fragmentation. If the pattern is visible, the image may be apparent from the marking of complete contours, partial contours, indicators or strips. For additional details on how the test strip is made, see US Patent Application No. 09 / 737,179, entitled "Reagent Test Strip Manufacturing Method."
    [67] 7 illustrates an exploded view of a single representative electrochemical test strip 62. The test strip of the subject comprises a reference electrode 64 and a working electrode 66, which are separated by a spacer member 60, which is an enema region of the spacer adjacent to the reagent patch 72 formed from the dried solution stripe. It is cut to define a reaction zone or area 68 in communication with the side port 70 defined by the spacing of.
    [68] For the use of such electrochemical test strips, an aqueous liquid sample (eg blood) is placed in the reaction zone. The amount of physiological sample introduced into the reaction zone of the test strip may vary, but is generally in the range of about 0.1 to 10 microliters, generally in the range of about 0.3 to 0.6 microliters. The sample may be introduced into the reaction zone using any convenient protocol, where the sample is injected into the reaction zone, absorbed into the reaction zone, or otherwise introduced through the port.
    [69] The analyte component is reacted with a redox reagent coating to form an oxidizable (or reducible) substance in an amount corresponding to the concentration of the analyte component (ie, analyte). The amount of oxidizable (or reducible) material present is then estimated by electrochemical measurements.
    [70] The measurements made may vary depending on the particular characteristics of the test and the device in which the electrochemical test strip is used (eg, depending on whether the test is analytical, amperometric or potential analysis). The measurement using the test strip 62 is suitably achieved by a oximeter probe inserted between the electrode members in contact with their respective inner surface. In general, measurements are taken over a period of time after sample introduction into the reaction zone. Methods of performing electrochemical measurements are further described in US Pat. Nos. 4,224,125, 4,545,382 and 5,266,179 and WO 97/18465 and WO 99/49307.
    [71] Following detection of the electrochemical signal generated in the reaction zone, the amount of analyte present in the sample is typically determined by correlating the electrochemical signal generated from a series of control or standard values obtained previously. In many embodiments, the electrochemical signal measurement step and the sample concentration derivation step are automatically performed by a device designed to operate with the test strip to produce a value of the sample concentration of the sample applied to the test strip. A representative reading device for automatically performing these steps so that the user only needs to apply a sample to the reaction zone and then read the final assay sample concentration results from the device, a co-pending US patent application filed June 15, 1999 Further described in No. 09 / 333,793.
    [72] The reaction zone in which the activity takes place is suitable to have a volume of at least about 0.1 μl, typically at least 0.3 μl, generally at least about 0.6 μl, which volume may be as large as 10 μl or more. The size of the region is determined by the nature of the spacer 60. Although the spacer layer is shown to form a rectangular reaction region in which the above-mentioned activity occurs, other structures are possible (eg, square, triangular, circular, irregular reaction regions, etc.). The thickness of the spacer layer may generally be in the range of about 0.001 to 0.020 inches (25 to 500 μm), and generally in the range of about 0.003 to 0.005 inches (76 to 127 μm). The manner in which the spacer layer is cut also determines the properties of the port 70. The cross-sectional areas of the inlet and outlet ports can be varied as long as they are large and long enough to provide effective introduction and discharge of fluid into the reaction zone.
    [73] As described, the actuation and reference electrodes are generally constructed in an elongate strip shape. Generally, the length of the electrode is in the range of about 0.75 to 2 inches (1.9 to 5.1 cm), and generally about 0.79 to 1.1 inches (2.0 to 2.8 cm). The electrode width ranges from about 0.15 to 0.30 in (0.38 to 0.76 cm), generally about 0.20 to 0.27 in (0.51 to 0.67 cm). In certain embodiments, the length of one of the electrodes is shorter than the rest, where in certain embodiments it is shorter than about 0.135 inches (3.5 mm). The electrode and spacer widths are preferably matched by overlapping elements. In the most preferred embodiment, electrode 64 is 1.265 in (35 cm) long, electrode 66 is 1.5 in (3.8 cm) long, each 0.25 in (6.4 mm) wide at its maximum, 0.103 at its minimum in (2.6 mm) wide, the port 70 is 0.065 in (1.65 mm) wide, and the reaction zone has an area of about 0.0064 in 2 (0.041 cm 2 ). The electrodes generally have a thickness in the range of about 10 to 100 nm, preferably between about 18 to 22 nm. The spacers employed in the strip are placed back 0.3 inches (7.6 mm) leaving openings between the electrodes that are 0.165 in (4.2 mm) deep from the end electrode 66.
    [74] The test strip according to the invention may be provided in a package in combination with a means or / or surveyor or reader for obtaining a physiological sample as described above. In the case where the physiological sample tested by the strip is blood, the subject kit may include tools such as needles for pricking fingers, nim means, and the like. In addition, the test strip kit may comprise a control solution or standard (eg, a glucose control solution containing a standardized concentration of glucose). Finally, the kit may comprise an instrument for using the test strip according to the invention to determine analyte sample concentration of a physiological sample. These instruments may be present on one or more container (s), packaging, label inserts associated with the subject test strip.
    [75] While the invention has been described with reference to a single embodiment, which optionally includes various features, the invention is not limited to the described settings. The invention is not limited to the stated use or the exemplary description provided herein. The concept of the invention is limited only by the context or legal scope of the following claims.
    权利要求:
    Claims (10)
    [1" claim-type="Currently amended] Coating the substrate with reagents in solution,
    Exposing the solution to radiation energy provided by one or more radiant energy heaters.
    [2" claim-type="Currently amended] The method of claim 1, wherein during exposure to radiant energy, only a sufficient level of airflow is introduced into the solution to break the bubble barrier of the solution.
    [3" claim-type="Currently amended] The method of claim 1 or 2, wherein the substrate is provided in a roll and fed past the energy source.
    [4" claim-type="Currently amended] A reagent coated substrate prepared by the method of any one of claims 1 to 3 to produce a dried reagent having a substantially uniform thickness.
    [5" claim-type="Currently amended] The reagent coated substrate of claim 4, wherein the substrate comprises an inert back support material and a metallic coating.
    [6" claim-type="Currently amended] The reagent coating substrate of claim 4 or 5, wherein the reagent coating substrate is present in the test strip precursor.
    [7" claim-type="Currently amended] 6. A reagent coated substrate according to claim 4 or 5, wherein the reagent coated substrate is present in the reagent test strip.
    [8" claim-type="Currently amended] A reagent test strip comprising the substrate of any one of claims 4 to 7 in combination with a manual survey meter,
    Wherein the reagent test strip and the meter are used to determine the concentration of analyte sample in a physiological sample applied to interfere with each other.
    [9" claim-type="Currently amended] A reagent test strip comprising the substrate of any one of claims 4 to 7 combined in a package with a set of directions for use of one or more test strips;
    Means for obtaining a physiological sample,
    A kit used to determine the concentration of analyte in a physiological sample comprising an analyte standard.
    [10" claim-type="Currently amended] Applying a fluid sample to a reagent test strip comprising the reagent coating substrate of any one of claims 4-7;
    Detecting a signal from the reagent test strip;
    Correlating the detected signal with the concentration of analyte in the sample to determine the concentration of the analyte in the fluid sample.
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    同族专利:
    公开号 | 公开日
    AT492810T|2011-01-15|
    JP4650870B2|2011-03-16|
    HK1053698A1|2011-08-12|
    JP2003247975A|2003-09-05|
    TW200303976A|2003-09-16|
    PL357431A1|2003-06-02|
    RU2292245C2|2007-01-27|
    EP1324038A2|2003-07-02|
    SG121749A1|2006-05-26|
    ES2357420T3|2011-04-26|
    CA2413255A1|2003-05-28|
    NO20025547L|2003-05-30|
    NO20025547D0|2002-11-19|
    US20040137141A1|2004-07-15|
    IL152915A|2006-08-20|
    CN1326691C|2007-07-18|
    CN1423128A|2003-06-11|
    IL152915D0|2003-06-24|
    DE60238662D1|2011-02-03|
    TWI308958B|2009-04-21|
    MXPA02011627A|2004-09-03|
    EP1324038B1|2010-12-22|
    EP1324038A3|2005-04-20|
    US6749887B1|2004-06-15|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    法律状态:
    2001-11-28|Priority to US09/996,631
    2001-11-28|Priority to US09/996,631
    2002-11-28|Application filed by 라이프스캔, 인코포레이티드
    2003-06-02|Publication of KR20030043770A
    优先权:
    申请号 | 申请日 | 专利标题
    US09/996,631|US6749887B1|2001-11-28|2001-11-28|Solution drying system|
    US09/996,631|2001-11-28|
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