TW468046B - Device and method for analyzing a biologic sample - Google Patents

Abstract

A device for separating fluid from a biologic sample when the sample has a fluid and non-fluid component. The devices is a point-of-care device through which data may be electronically collected and electronically transmitted for further evaluation. A method for separating fluid from a biologic sample is provided wherein the method comprises the step of bringing the fluid sample in fluid contact with the microspheres such that the fluid component moves by capillary action between the microspheres along capillary channels formed by the spaces between the spheres and leaving, for example, a cellular fraction behind. In the device of the present invention, the step of separating the fluid may be combined with other assay techniques for detecting and/or measuring one or more analytes which may be present in the fluid sample such as immunoassays and chromatographic assays. There may be further combined with groups of microspheres for use in the analyte detection step as well as the separation step whereby the microspheres act a labels for the analyte or as a source of label for the analyte.

Description

Printed by the Central Samples Bureau of the Ministry of Economic Affairs, Shellfish Consumer Cooperative, A7 ------------ B7 V. Description of the invention (1) Worry about 3L This invention relates to the use of appropriate small particles such as microspheres And analyte-specific labeling, a device that separates fluid components (such as plasma) from biological specimens (such as blood). The invention also relates to a device and method for quantitatively determining the amount of an analyte present in a biological stream. The present invention also relates to a method and a device for measuring radon, which measure one or more analytes in a biological fluid specimen using a measurement method and a device in a care place. The specimen may be a suspension prepared to test one or more microorganisms. The test results can be analyzed by a suitable analyzer, and the measurement results can be transmitted by a digital transmission system when necessary to allow further evaluation of the data. Background of the moon landing There are many examples of single-step determination of analytes in fluids. A commonly used measurement is a pregnancy test device, which involves contacting a urine specimen with a test patch, and the urine moves along the absorbent chromatography strip by capillary flow. The reagents in the film reacted to detect the presence of human chorionic gonadotropin (HCG) (usually indicated by colored lines). This is an example of a chromatographic assay. U.S. Patent No. 5,766,961 issued on June 16, 1998 and U.S. Patent No. 5,770,460 issued on June 23, 1998 both use "single step side flow non-absorbent measurement" as the name ^ " non-absorbent side flow " Refers to the dissolved or dispersed component of the liquid in the liquid stream (not permanently retained or removed by the furnace) being carried at approximately the same rate and flowing relatively unhindered across the stabilized membrane. This is different from the case where one or more ingredients are preferred to be absorbed or ingested in one or more ingredients (such as in a chromatographic structure) This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) (please Read the precautions on the back before filling in this page). Policy · 4 6 8 0 4 6 A7 ____B7 _-5. Description of the invention (2). In a single-step measurement, specimens (possibly containing the target analyte) are collected in the "sample storage area", and the specimens flow from this area to the " marked area " (&Quot; Determination marker ") An analyte-specific binding reagent coupled to the sample then flows to the " retention zone " where the analyte bound to the visible portion is retained. In July 1996 The invention described in US Patent No. 5,540,888 issued on the 30th and named "Liquid Transfer Measurement Device" is a device for biochemical diagnostic measurement. It includes two liquid flow channels made of porous material. After the liquid is simultaneously added to the end of the channel, the liquid is transferred to a common location by capillary flow. The channel is connected at a certain point, and then the two are arranged in a manner similar to a bridge circuit. By selecting the water resistance of the loop arm, fluid can be controlled to pass through the bridge. U.S. Patent No. 5,300,779, entitled "Capillary Flow Device", issued on April 5, 1994, describes a method and device for measuring an analyte in a specimen mixed with a reagent. The device defines a flow path. By agglutination The specific binding can change the flow rate, the light pattern of the flowing medium, or the absorption or scattering of light, thus allowing the measurement of the target analyte. Issued on May 5, 1992 and named "Multi-Analyte Device" as In the titled US Patent No. 5,110,724, the invention described is a measuring device for measuring a plurality of analytes in a drop-sized blood sample. The dispenser distributes a small volume of blood specimens to multiple delivery sites by capillary flow of blood specimens through the screening and distribution cells. Blood cells are separated from plasma. The test board in the device carries a plurality of absorbing pads, each of which contains a standard for detecting the size of this paper (Chinese National Standard (CNS) A4) (2 丨 〇 < 297 mm) -------- -. 装 — (Please read the notes on the back before filling out this page) Order printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives 468 046 Printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives Α7 Β7 V. Description of the invention (3 ) Select the reagent components for the analyte. The test board is mounted on the dispenser and faces the transfer position, where the exposed surface area of the potential strip is in contact with the associated specimen-transfer site to simultaneously transfer the specimen fluid from the site to the pad in the support. . In U.S. Patent No. 5,039,617 entitled "Capillary Flow Device and Method for Measuring " Activated Partial Prothrombin Kinase Time " (APTT)", the invention is described by applying a specimen to an energetic material. Measure the whole blood specimen in the capillary of the reagent that initiates the APTT analysis " Activated partial thromboplastin time " (APTT), where the clotting time is measured by the blood in the capillary stopping flow An example of evaluation. In US Pat. No. 4,753,776 entitled "A blood separation device comprising a filter and a capillary flow channel leaving the filter", a method for separating plasma from red blood cells is described. In this method, the driving force for moving plasma from the filter to the reaction zone of the device is the capillary power provided by the capillary. The filter is selected from glass microfiber filters with specific characteristics. A similar invention is described in U.S. Patent No. 5,135,719 issued on August 4, 1992 and named as a blood separation device including a filter and a capillary flow channel leaving the filter. The diameter of the glass fiber filter is Manufactured from 0.10 to 7.0 microns. In U.S. Patent No. 4,447,546, issued on May 8, 1984 and entitled "Fluorescent Immunoassay for Optical Fibers in Capillaries," a short capillary tube with a precise diameter is described, which contains optically arranged axially. Fibers and monolayer antibody-antigen complex components are fixed on it. The paper size applies Chinese National Standard (CNS) M specifications (21〇297 mm). (Please read the precautions on the back before filling this page) & quot 1 6 8 046 A7 B7 V. Description of the invention (4). The tube was immersed in the specimen. Issued on March ^ 1997 and the name of the invention is " Method and Device for Specific Binding Assay " US Pat. No. 5,61,07,77 discloses a well-known antibody-antigen binding assay. A specimen (a) containing an analyte (test substance) is mixed with an antibody (b) that binds to the test substance, and the antibody is Immobilized on a solid support, and another antibody (c) of the test substance is bound to a detectable label, thereby forming a complex between (b), the test substance and the substance, and the label is fixed and detected. Issued on July 24, 1990 and The invention is described in US Pat. No. 4,943,522, “Side Flow Non-Absorbent Membrane Assay”. The invention is described as a method and device for specific binding pairing assays (such as immunoassay). The test substrate is a porous membrane. , One of the members of the binding pair is fixed in the "instruction area", "applying a specimen and letting it flow sideways through the indication area and any analyte in the specimen will be used in combination with the specific immobilization mentioned above" Members are compounded and detected. A novel detection method is to use the retention of visible particles in the complex, for example, red blood cells of blood can be used to detect the visible particles of the complex. An example of a method for separating red blood cells from a whole blood specimen It is described in U.S. Patent No. 5,118,428 issued on June 2, 1992, and its invention name is "Method of Removing Red Blood Cells from a Whole Blood Sample". In the recorded invention, an acid-containing The solution removes red blood cells from the whole blood specimen. Then the agglutinated red blood cells are removed from the resulting suspension by filtration, centrifugation, or decantation, leaving blood that is substantially free of red blood cells Clear or plasma specimens. In the US patent entitled "Quantitative Analysis Device and Method", the paper size is suitable for Ning Guoguo Biaohua (〇 阳) 8 4 specifications (210 '(? ≪ 297)) -------- κ \ 策 丨 — (Please read the precautions on the back before filling out this page) h Order the printed materials for the consumer cooperation of the Central Bureau of Standards of the Ministry of Economic Affairs d 6 8 046 A7 B7 Central of the Ministry of Economic Affairs Printed by the Standards Bureau Consumer Cooperatives V. Invention Description (5) 5, 073,484, the analyte is measured along the liquid flow path, which includes a number of spaced reaction zones distributed along the flow path. The detection member is used to detect an analyte, a reactant, or a predetermined product in the reaction zone, and the number of detected zones indicates the amount of the analyte in the liquid. In US Patent No. 5,536,470, issued on July 16, 1986 and entitled "Test Carrier for Determining Analytes in Whole Blood", red blood cells cannot enter the detection side from the blood specimen application side, and Due to the analytical reaction, an optically detectable change has occurred. Β The current single step method of measuring and / or detecting an analyte has a serious drawback, that is, it only provides qualitative results and cannot provide quantitative results. That is, the presence or absence of the analyte can be measured, but the actual amount or concentration of the analyte in the specimen is still unknown. The measurement method of the present invention can provide quantitative results because the test is performed with a measurable volume. In the method of the prior art, 'Since the fluid must flow through the test strip, it is impossible to have consistent results for the exact volume of the test subject in repeated tests. 0 Use of chromatographic strips and glass fiber length Prior art methods of strips required larger initial volumes of biological specimens to fix proteins and labels on long strips. This is especially true when the biological fluid is blood and the plasma must first be separated from the blood sample. One advantage of the device and method of the present invention is that one or more analytes can be measured with a very small amount of fluid specimen. Another advantage of the measurement method and device of the present invention is that the test volume can be constant, so quantitative data can be obtained by repeated testing, and can be directly compared among multiple specimens or within one specimen. -8-. This paper size applies to China National Standard (CNS) A4 (210X297mm) I --------- i. ¥ .-- ./. {Please read the notes on the back before filling (This page) Order printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 4 68 046 A7 ____________B7___ V. Description of the invention (6) The # 胄 point of this month is its measuring device and method. During the measurement period of the fluid inspection, Plasma is separated from the whole blood. In other words, it is not necessary to separate the blood cell components before measuring the specimen 4. This is an important advantage because the image can be used in a patient care setting, such as the patient himself, or at the patient's bedside or in a physician's office. In a preferred embodiment of the present invention, the device and measurement method of the present invention provide a platform for a general care site, which is suitable for performing one or more diagnostic or prognostic measurements on one or more fluid specimens. Summary of the Invention According to one aspect of the present invention, a method for separating a fluid component from a biological specimen is provided. In one embodiment, the biological specimen is brought into contact with a group of microspheres, and the fluid components are separated from the specimen when the fluid portion flows through the microspheres by capillary action. In another embodiment, instead of microspheres, particles with non-uniform size and / or shape are used to separate the fluid portion from the biological specimen. According to one aspect of the present invention, there is provided a quantitative measurement method and device for measuring one or more analytes in a fluid specimen with a measurement method and device in a care place. The measurement method and device are designed for use by a patient or Use at the patient's bedside or physician's office. The test results are analyzed with a suitable analyzer, and the test results can be transmitted via a digital transmission system when needed 'to allow the data to be further evaluated by non-existing professionals. The role of microspheres or other particles is a dynamic filter to extract or separate the fluid part and separate it from the non-fluid part. "The channel may be • 9_ This paper size uses Chinese national standards | 〇« 7 八 4 Specifications (210X297mm) —- (Please read the notes on the back before filling in this page] Order 468046 Printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives A7 B7 V. Description of the invention (7) Temporary, since the beads The particles show motility during the separation step. So rapid, instantaneous capillary extraction is achieved by a dynamic capillary filter created by temporary capillary channels formed by microspheres or interstitial spaces between particles. In one aspect of the present invention, A measurement method and a portable measurement device for testing a small volume biological specimen (including blood) in an instant manner. In another aspect of the present invention, a method and a device for testing a biological fluid specimen are provided, in which a biological volume of a uniform volume is tested. One or more analytes in a medical examination and the data obtained from the test are used to collect and compile information such as a specific disease Finally, the collected data is used in a logical algorithmic neural network, which can provide diagnostic and / or prognostic information based on the individual test results of any given test subject. According to another aspect of the invention, In terms of blood analysis, by exposing whole blood to microspherical beads, and the beads allow the blood plasma to pass through the space formed between the microspheres by capillary action but not the blood cell components, the blood cell components and blood plasma can be Separation. The present invention is not limited to separating blood cells from blood plasma, but includes a wider range of applications in which microspherical beads can be used to separate fluid components from cellular components in biological fluids. Microspherical beads can Effectively used as a fluid filter. According to another aspect of the present invention, a device for separating plasma from blood in a specimen is provided. The device includes a plurality of microspheres arranged in abutting relationship and a plurality of capillaries are formed therebetween. Channel, so that when the polar sphere is placed in a fluid path with a blood sample National Standard (CNS) A4 specification (210X297 mm) (Please read the notes on the back before filling out this page) Order 4 6 8 0 4 6 Printed by the Central Standards Bureau of the Ministry of Economic Affairs, Consumer Cooperatives, printed A7 B7 V. Description of the invention (8) The blood cell component and the plasma component are separated by capillary flow of the plasma component, and are separated by a capillary channel formed by adjoining a space between microspheres. According to another aspect of the present invention, a device is provided, which is relatively The separation zone composed of large microspheres contains plural groups of smaller microspheres, each of which is impregnated with different marks and dispersed among the larger microspheres. The microspheres may have substantially the same diameter, or different Diameter. The size of the selected microspheres is determined according to the viscosity of the specimen or the size of the components that are expected to be excluded or separated. According to another aspect of the present invention, the microspheres are bundled into bundles with fluid permeable material, or the microspheres Adhesion is maintained by the surface tension of the fluid (such as plasma) passing through it. According to yet another aspect of the present invention, microspherical beads (or simply microspheres) are dried on the surface of the device. According to another aspect of the invention, the device includes a specimen holder and a microsphere placed adjacent to the liquid inlet on the specimen holder. According to another aspect of the invention, the device includes a plurality of smaller microspheres, the smaller microspheres being impregnated with at least one marker and dispersed among the plurality of larger microspheres such that the smaller microspheres occupy the larger microspheres In the interstitial space, the mark is released into the fluid when the fluid flows through the interstitial space between the larger microspheres. In the separation region composed of larger microspheres, there may be plural groups of smaller microspheres, each of which is impregnated with different marks and dispersed among the larger microspheres. Another alternative is that as the fluid flows along the capillary channel formed by the larger microsphere, the smaller microsphere can be moved and carried forward by the fluid. -11-This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm)

In n ^ i I. ^ ¾ ^^^ 1 I---^^^ 1 1 · ^ 1 «, words (please read the notes on the back before filling this page) System 468046 A7 ------- B7____ V. Description of the invention (9) According to another aspect of the present invention, a device including an indicator 'the indicator contains the identity information of the patient related to the measurement result' is provided, for example A barcode that can be read by a barcode reader. According to another aspect of the present invention, a method for separating a fluid from a biological specimen is provided. The specimen has a fluid component and a non-fluid component, and the method includes the following steps: (a) allowing the specimen to flow into a fluid pathway having a plurality of microspheres, the microspheres being configured in abutting relationship and forming a plurality of gaps therebetween. Space, the plurality of interstitial spaces are connected into a capillary channel, and (b) when the fluid component is separated by its capillary flow through the capillary channel, the fluid component is collected. According to another aspect of the present invention, there is provided a method for measuring using a device including a capillary chamber defined by first and second opposite surfaces spaced from a capillary and having a fluid inlet, and at least one kind of capillary chamber disposed on the capillary. Reagents in the chamber 'The method includes the following steps: 0) The fluid specimen is wheeled into a fluid path with a fluid inlet, so that the fluid specimen is drawn into the capillary chamber and reacts with the reagent by capillary action, and' (b ) Analyze the reagent to determine whether the reagent is bound to the analyte in the fluid sample. ^ According to another aspect of the present invention, the method further includes analyzing the reading reagent to determine the ratio of the reagent bound to the specimen β. According to another aspect of the present invention, the method further comprises performing a plurality of fluid samples of more than one species Multiple capillary chambers were measured. Applicable to Chinese National Standards (CNS > A4 specifications (210X297mm) in accordance with this 12- ^ paper & standard) ---- (Please read the note on the back, please fill in the entry #), staff of the Central Bureau of Standards, Ministry of Economic Affairs Consumption cooperatives India policy A7 B7 V. Description of the invention (10) In another aspect of the invention, the test results are recorded in a computer database or can be further applied to neural network logic calculations to produce one or more selected abnormal moods The determination also includes the step of applying a characteristic analysis receiver to the data to determine the statistical significance of the data. According to another aspect of the invention, the core or capillary is fed into a fluid-containing test. To remove the fluid sample from the capillary chamber. According to another aspect of the present invention, microspheres are used to separate cellular components from fluid components in biological fluids, such as separating plasma from whole blood, And the fluid composition can be tested in chromatography test strips. In addition, the microsphere beads of the present invention can be used as a filtration device in a standard nitrocellulose chromatography assay. It can also be used as a marking device. In all aspects of the invention described herein that use uniform microspheres with defined shapes and sizes, the microspheres can be used with non-uniformities of different sizes and / or shapes, which will be described further below. Particle replacement. For example, silica sand can be used to replace polyphenylene terephthalate microsphere beads. Β Other suitable particles are known to those skilled in the art who will benefit from the present invention. A more detailed description of the preferred embodiment is described in the following "Detailed Description of the Preferred Embodiment" and the accompanying drawings. Brief Description of Formula 1 In order to illustrate the present invention, the preferred form is shown in the drawings, but it is not intended to limit the present invention to The precise arrangement and structure shown "The present invention will be described in detail with reference to the drawings, in which the same numbers represent the same parts in several figures. N ^ i mt tn ^^^ 1 I (Please read the precautions on the back before filling in this Page] Order-13-

8 046 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (11) Figure 1 is an exploded perspective view of an embodiment of the device of the present invention. Fig. 2 is a longitudinal sectional view of the preferred embodiment illustrated in Fig. 1 along line 1A_1A. Fig. 2A is an end view of the device illustrated in Fig. 2 taken from perspective lines 2A-2A. Fig. 3 is a side view of the embodiment described in Example 1, which illustrates the relationship between the cover sheet and the beads when curling starts. Fig. 4 is also a side view of the embodiment described in Example 1, which illustrates curling after formation. Fig. 5 is another side view of the embodiment described in Example 1, which illustrates the relative positions of the coverslips and the beads on the microscope slide. FIG. 6 is a top view of the embodiment described in Example 1. FIG. Fig. 7 is a side view of the embodiment described in Example 2, illustrating a mark modification. Fig. 7A is a side view of another embodiment described in Example 2, which illustrates the replacement of a marker gasket with microsphere beads. Fig. 8 illustrates an example of the R 0 C curve illustrating the prediction test result of the neural network risk analysis test. Fig. 9 is a magnified 400 times photomicrograph obtained using a low magnification microscope, showing the appearance of unseparated yogurt made on a shelf of a biopsy sheet. Fig. 10 is a low magnification microscope used. The obtained microscope picture at a magnification of 400 times' shows the fluid portion of the yogurt as shown in FIG. 9 after the microsphere beads with a 15-micron straight grip were separated. -14- This paper size applies to Chinese national standards (CNS > A4 * L (210X297 mm) (Please read the precautions on the back before filling out this page). Order A7 468046 B7 ----:-V. Invention Explanation (12) FIG. 11 is a microphotograph of 400 times magnification obtained by using a low magnification microscope, which shows the fluid portion of the yogurt as shown in FIG. 9 after the microsphere beads with a diameter of 10 micrometers are separated. A 400x magnification photomicrograph obtained using a low magnification microscope, showing the appearance of unisolated E. coli and bread suspension applied to a shelf of a biopsy sheet. Figure 13 is a magnification obtained using a low magnification microscope. A 400x photomicrograph showing the fluid portion of the E. coli / bread suspension seen in Figure 12 after separation of microsphere beads with a diameter of 15 microns. Figure 14 is a 400x magnified microscope obtained using a low magnification microscope Photo 'It shows the appearance of unseparated cow dung applied to the shelf of the biopsy sheet.' FIG. 15 is a 400 × magnified photomicrograph obtained using a low magnification microscope, which shows the cow dung seen in FIG. 14. Using 15 micron diameter microsphere beads after separation. Figure 16 is a 400x magnification photomicrograph obtained using a low magnification microscope, which shows the microspherical beads with 10 micron diameter of cattle feces seen in Fig. 14 The separated fluid part. Fig. 17 is a photomicrograph obtained using a low magnification microscope, showing silica sand applied to the shelf of the biopsy sheet and showing a millimeter scale to illustrate the size of the silica sand particles. Fig. 18 is a magnified photo taken at a magnification of 0 using a low magnification microscope, which shows the fluid portion of the E. coli / bread suspension seen in Fig. 12 after being separated with silica sand particles. -15- This paper is suitable for Ningguo country Standard (CNS) Α4 Specification (21 ^ 297 mm) _ f Please read the notes on the back before filling out this page) Policy _ Ordered by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs, printed 468046 Cooperative Neem A7 B7 V. Description of the invention (13) Figure 19 is a magnified 4,000 times photomicrograph obtained using a low magnification microscope, which shows the oxidized silica sand particles of cow dung seen in Figure 14 Ilk portion after separation. Detailed Description of the Preferred Embodiments The present invention relates to a method for separating fluid components from biological specimens using microspherical beads or particles. The present invention also relates to a method for analyzing the presence of an analyte in a biological fluid * Device and method. The invention also relates to an accurate quantification of the amount of one or more analytes present in a biological fluid sample. On the other hand, the present invention can also provide qualitative rather than quantitative results. The present invention also relates to an interpretable test result and an assay that can be used to further identify a patient or animal suffering from or possibly suffering from certain conditions in the future. The present invention also relates to a prognostic measurement technique, in which the test results defined by the present invention can be used to predict the possibility of a certain disease or state of the patient or animal in the future. Although the preferred embodiments described herein describe testing of human biological specimens, it should be understood that the assay and method can be used to evaluate biological specimens of other animals as well. "More specifically, the present invention clearly Veterinary Services are Applicable "Furthermore, the term" fluid specimen "as used in this specification is intended to be broadly interpreted to include suspensions and other specimens whose fluid portion can be separated by fluid flow and / or capillary action. In a biological fluid sample with a fluid component and a non-fluid component, the fluid component containing the analyte of interest of the present invention can be used to measure any of the following (alone or a combination thereof): a) Analyzed in the sample Existence of things, -16- This paper size is applicable to Chinese Standard (CNS) A4 specification (210X297mm --------- /, stupid— < please read the note on the back before filling This page) Order. A7 4 6 8 0 4 6 B7 V. Description of the invention (14) b) The absence of the analyte in the specimen, c) The concentration of the analyte in the specimen, ^^ 1- ^^^ 1 —ϋ IΓ · * · ^^ υ— n [Hr 1 JJ. (Please read the precautions on the back before filling out this page) d) The amount of analyte in the specimen. Suitable analytes that can be measured by the assays and devices of the present invention include soluble analytes (including but not limited to): enzymes, proteins, bacteria, viruses, antigens, antibodies, immunoglobulins, drugs and hormones. Other suitable analytes are known to those skilled in the art. The assay and device of the present invention can be used to detect and measure drugs of abuse in human biological specimens such as performance-enhancing drugs or other market drugs. Some biological specimens can be tested without first separating the cells into cells; however, for example, in the case of blood, cell components can interfere with the assay. In the case of biological specimens, if cellular components need to be removed prior to the measurement for better results, the fluid component must be separated from any cellular components. In the case of blood, for example, blood aggregates need to be separated from whole blood so that the cellular components of the blood do not interfere with the test for the analytes present in the plasma. Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs It is surprisingly found in the present invention that the fluid component and the non-fluid component of a biological specimen can be separated by applying the specimen to the microspherical bead group. When a specimen is applied, the fluid component will flow between the microsphere beads, thereby separating it from the cellular component in a simple and effective manner. When the fluid component moves through the space formed between the clustered beads by capillary action, the beads are used as a component to separate the fluid component from the non-fluid component. Therefore, in the case of blood, the blood group is separated from the blood cells in the blood sample. In the present invention, it is surprisingly recognized that microspheres have the ability to quickly and efficiently separate plasma from whole blood. -17- This paper size applies to Chinese national standards (CNS > A4 specifications (2I0X297 mm).) Printed by the cooperative ^ 6 Β Ο 4 6 Α7 ------- 5! _ V. Ability of invention description (15). For the purpose of this patent application, the space between beads is called & quot "Interstitial space" 4 " hole ". Xianxin fluid flows from one interstitial space to the next by capillary action. In this application, 'the fluid flows through the interstitial space of the beads as along the inter-bead space. The channel flows. This channel is called "capillary f channel, because the fluid apparently flows between the beads by the" capillary "action. When the microspheres are clustered together, a gap is formed between the microsphere beads. The size of the space formed between the microspheres is a function of the radius of the surface of the microspheres. For the purpose of the present invention, the radius of the surface is the same as the diameter of the microspheres. To understand the size of the microspheres and the space between the microspheres Ruler of the hole formed It is known that the ratio of the diameter of the microspheres to the diameter of the pores is about 1: 0.4. In the case of separating plasma from whole blood, a pore size of 4 microns is considered to be the most appropriate. Therefore, for this particular embodiment, The bead size should be 10 microns. This allows the fluid solution to flow, but still prevents the cells from passing through the pores. When the fluid is present, the small spaces formed between the beads provide some sort of capillary phenomenon. 11 It has also been surprisingly found to have an uneven size And shaped particles can also operate in accordance with the principles of the invention taught herein. Specific examples of non-uniform particles are described in Example 7 below. It should be understood that the principles taught in the following description of microsphere beads can also be applied to other The use of similar separation particles such as oxidized hair and other equivalents. In the present invention, the use of 'microspheres is to separate blood packs from whole blood -18- This paper applies Chinese National Standard (CNS) A4 Specifications (210X297mm) ί Please read the notes on the back before filling this page) Stupid. Ding. Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 468 046 A7 --------— B7 V. Invention Description (16 ) Stool, an effective component, because the red blood cells and white blood cells in the blood will stay on one side of the beads, and the plasma portion of the blood sample will pass through the gap space or hole formed between the beads by capillary-like action Beads. The capillary action observed in the present invention is considered to be related to the surface tension exerted by the microspheres on the fluid, so that the fluid is pulled forward. When the fluid is pulled forward between the microspheres, it provides the microspheres Additional advantages of any reagent movement in the zone. For example, microspheres can be impregnated with a secondary antibody or another detection molecule. Microsphere beads are effective fluid filters, so they can be used in any location with simple fluid filtration , Separation or separation. Since Xianxin microspheres can be filtered by capillary action to separate or separate fluid components from non-fluid components, microsphere filters can be referred to as capillary filters and the term is used herein for this purpose. The capillary filter is a kind of dynamic filter, because it can be seen under the microscope that the beads move during the separation of the fluid components—some of the beads move, others remain stationary, but overall movement of the beads is observed under a microscope. It is expected that as the beads move, some capillary channels will close and others will open. In this sense, capillary channels may be temporary. It is also expected that the interstitial spaces between the beads or particles show the same temporaryness as the beads or particles move during the separation of the fluid. An analyte-specific antibody can be bound to the microsphere, for example, by adsorption or coupling. When the plasma-containing fluid passes through the capillary channel formed by the microsphere, the analyte will move the second antibody contained in the microsphere, and then react with the first antibody contained in the biochip. However, -19- this paper size applies to the national standard (0 milk) 8 4 specifications (210 father 297 public epidemic) " {Please read the note on the back before filling this page) 袈 ·

'1T Printed by the Central Laboratories of the Ministry of Economic Affairs, Shellfish Consumer Cooperative 468046 A7 B7 V. Description of the invention (17) Microspheres can only be used to separate cell components from fluid components, and microspheres do not have to be labeled with antibodies. Prior art techniques used chromatographic paper or other fibrous materials to draw fluid components of a biological specimen away from cellular components to test the fluid portion without interference from cells or other substances present in the specimen. The microspheres of the present invention are superior to those of the prior art because they enhance fluid flow without being limited by the fibers present in the chromatography paper. Another advantage provided by microspheres is that they provide an excellent surface for proteins such as antibodies or other appropriate labels to bind. The size of the microspherical beads used to separate the fluid components can be changed according to the viscosity of the specimen. Larger beads should be used for more viscous specimens to allow faster fluid flow between the beads. Furthermore, when beads are used as labels and bound to analytes, beads of different colors can be used to help the beads be seen. The bound beads also increase the density of any bound analyte for subsequent detection with a spectrophotometer. The regularity of the beads also implies that refractive differences can be used to detect and measure bound analytes. The biological specimen can be applied to the top of the beads or to the sides of the beads. In a preferred embodiment, latex microspherical beads are used, such as those sold under the trade name Bang'sTM. The beads are supplied in the form of a liquid suspension. The beads can be kept wet or dried during use. The present invention can also use other types of beads, including glass beads, as long as the beads can separate the fluid components. -Microspheres that can quickly separate fluid components from biological specimens can be included in the assay to detect and quantify the analytes present in the specimen. τ -20- This paper size applies Chinese National Standard (CNS) Α4 size (210X297 mm) (please read the precautions on the back before filling this page) Order printed by the Central Consumers Bureau of the Ministry of Economy 4 6 BQ 4 6 V. Description of the invention (18) According to one aspect of the present invention, a method for separating a fluid specimen from a biological specimen by using micro-spherical beads is included in a single-step assay to analyze the fluid specimen provided. Possible species—one or more analytes. The test is performed in a chamber with a defined volume. In a preferred embodiment, the cell contains microspherical beads for separating a fluid sample and a detection member for detecting and / or measuring an analyte in the sample. The detection means can be selected from any of several known methods for detecting an analyte in a sample. "Example T" Analyte can be identified by a detection protein such as an antibody or antigen specific to the analyte 1 When the analyte binds to the detection protein, the density changes and can be measured. Another method is to combine the detection protein with another detectable label. For example, the detection protein is attached to the beads, so that when the detection molecule is combined with the analyte, the density will increase and it will be measured or set. Other suitable markings include metals such as gold, glory markings, chemical markings or color markings. According to one aspect of the invention, the invention relates to a thin-plate or cassette-type diagnostic or prognostic test device for use in a care setting for measuring a biological specimen such as blood. The present invention teaches a small and portable measuring device called " biochip sheet " (biochip) to perform the simple measurement taught by the present invention. In the device of the present invention there are two pairs of bearing surfaces to define a specific volume 'in which the amount can be determined-drops of blood, urine, saliva or other biological fluids. In the-preferred embodiment, the surface of the foot in question is a cover sheet and-a microscope slide, but this invention 21 _ This paper size applies to Chinese national standards (CNS > A4 * L lattice (21 ^ 297) ) ----- (Please read the precautions on the back before filling out this page) Stupid. Ordered by the Central Standards Bureau of the Ministry of Economic Affairs, Consumer Cooperatives, Printed 468046, Invention Description (a, not intended to be limited to these special embodiments. This Invention—Important party Z specimens enter the space of a defined volume by capillary action. Therefore, this piece is called a capillary chamber in this article. In the case of a microscope cover: " In the example of the film, the capillary chamber is the cover. The volume of the space between the bottom of the slide and the top of the slide. According to a preferred embodiment of the present invention, the amount of fluid that exists between the cover slide and the slide is determined by the volume of the space between the slides. So it can be designed The “small test system” allows precise and extremely small volumes, some of which can be as small as a few microliters. In order to measure the concentration of the analyte in the sample and compare the test results with each other, the fluid test is performed each time the test is performed. Physical fitness Has a consistent test volume. In this way, the measured value of the analyte can be directly evaluated and 4 different volumes can be adjusted. The concentration or amount of the analyte can be directly evaluated without difficulty and consistent between experiments. The defined volume is provided in the biopsy cell of the present invention. According to one aspect of the present invention, the volume of fluid used for measuring the analyte is standardized. According to another aspect of the present invention, since the present invention uses only one drop of blood ( For example, from acupuncture of fingers) without using a larger volume of blood (only blood from a test tube can be obtained with a needle) is the most practical way to perform these tests, so the present invention provides a method for plasma in a very small blood volume Method for separating from blood cells. In a preferred embodiment, the thin-sheet test device for biopsy includes a small volume-determinable chamber. The chamber is defined by the first and second relative bearing tables: the position where the surface is placed is Can make them separated by a distance, and -22- This paper size is common in China Solid Standard (CNS) A4 size (210X297), (please read the note on the back first) (Fill in this page again) ... Stupid ------ Order 0. 468 046 A7 B7 DuPont Packing Cooperate with Shellers and Consumers of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the Invention (20) This distance is narrow enough to allow fluids to flow through the capillary tube The action flows from two surfaces to three. The chamber has a certain volume when a certain space is formed. The chamber has one or more fluid inlet points that allow fluid specimens to enter. 'In the case of f, the chamber was also It is called a capillary chamber because the capillary system of the flow system enters. For the purpose of the present invention, the configuration of the two bearing surfaces joined together is called " biochip ", but it can also be called The present invention provides a portable, portable test system that can be standardized. In a particularly preferred embodiment, the bottom surface is, for example, a microscope slide and the top surface is a microscope cover. Microscope slides and coverslips are easily available and are therefore useful loading surfaces. In another embodiment, two microscope slides can be installed one on top of the other, or any two plates, as long as there is a certain space between the plates and a measurable volume to allow the fluid sample to flow into the person by capillary action. Both are OK. Once in the capillary chamber, the fluid specimen is held at the ends or edges of the two surfaces by surface tension. The device has a small size, which allows it to be manually inserted into the analyzer so that the analyzer can be used to measure the reaction products between the analyte and the molecules for detection. To illustrate certain preferred embodiments, the bearing surface will be referred to as a "plate", but the invention is not limited to flat plates. Likewise, all types of surfaces capable of binding to proteins, antigens and other detection molecules are considered to be within the scope of the present invention. More specific and the composition of the bearing surface includes glass, plastic and Jinsi without limitation-belongs to 0 23 This paper size is applicable to China National Standard (CNS) VIII 4 (210x297 public envy) (Please read the precautions on the back first (Fill in this page again) Policy. Order the employee cooperation of the China Prospective Bureau of the Ministry of Economic Affairs Du Yin 褽 1. 6 8 〇4β Α7 I____ B7 V. Description of the invention (21) In a preferred embodiment of the present invention, a drop of biological The specimen is placed on the surface of the microscope slide, and before entering the capillary chamber, the cellular component of the specimen is removed by moving the body component through a group of microsphere beads. For example, in the case of blood, Plasma is separated from the cellular components of the blood by moving through the capillary channel formed between the beads, and then the fluid enters the test cell, where the analyte reacts with the reagent in the cell and the reaction product is used to measure the test. Analytes present in the body. Once the fluid enters the defined space, it is exposed to one or more reagents on the inner surface of the bearing surface. So the reagents are exposed to the capillary chamber Neutralization can be used to react with one or more analytes that may be present in a fluid sample that will eventually fill the capillary chamber. The reagent is labeled and the amount of analyte present in the fluid sample is based on the analyte and Measurement of reaction products of reagents in small A. Then compare the test results with the standard calibration curve to determine the amount of analyte present in the specimen. In a preferred embodiment of the present invention, the reagent is one or more analytes Specific antibodies' The antibodies are preferably adhered to the bearing surface by protein printing. In another embodiment, the antigen is present on the inside of the bearing surface and the amount of antigen-specific antibodies in the specimen is measured. When proteins or other detection molecules When bound to a load-bearing surface, it will extend into a defined space where it will react with the analyte in the specimen. The molecules for detection that exist on the inner surface of the load-bearing surface may be known to those skilled in the art Either of these methods is bonded to the surface. The molecules for detection are coated by one of several techniques known in the art-24-This paper is for China Home Standard (CNS) Α4 Specification (210Χ2 who mm) (Please read the back of the Notes then fill out this S ·) stupid

< 1T A7 B7 468046 5. Description of the invention (22), printed or bonded to one board or another board. Many immunoassay techniques are known to those skilled in the art, such as documented in " Principle and Implementation of Immunology " (1997), C.P. Price and D.J, Newman eds. (Stockton

Press) 'and this document is incorporated as a reference and part of this patent application. The distance between the two plates is limited only by the ability of the two plates to effectively draw fluid (such as the plasma between the two plates by capillary action) and the ability to maintain a defined volume of fluid. The size of the board is also governed by practicality such as the volume expected to be tested. A plate with a larger surface area should get a larger volume. According to the present invention, a fluid specimen such as a drop of blood is placed on one edge of the two plates and is drawn into the space between the two plates. The fluid specimen can be pulled in against the second plate by any means known to those skilled in the art. In the simplest form, the specimen is brought into direct contact with the edge, for example by touching the plate with a patient's finger, so that a portion of the fluid specimen is pulled into the space and completely fills the volume defined by the space. The important point in this measurement is that the specimen is always completely filled with a defined volume so that appropriate quantitative analysis can be performed. In the standardized model, the volume is the same for each biopsy sheet. In another preferred embodiment, the plates are joined together so that the fluid sample is easily removed from, for example, the end opposite the fluid inlet. In another example, the space between the two plates can be divided into several lanes and the volume of each lane is also known. This method allows multiple tests on a single specimen. When it is desired to measure the plasma protein in blood specimens, the plasma 25 · wood paper size shall be in accordance with the Chinese National Standard (CNS) A4 specification (2I0X297). {Please read the precautions on the back before filling in this page)

Du Pianzhuang, Shellfish Consumer Co-operation, Central Bureau of Standards, Ministry of Economic Affairs 4 68 04 6 A7 B7 V. Description of Invention (23):-~ 1 Separate from blood cells. In the present invention, it is desirable that the test result be obtained from the beginning to the end in a short period of time! To the extent of calling the bell. The present invention ^ ^ ^-(Please read the precautions on the back before filling out this page)-The advantage is that since the microsphere beads are used to separate the plasma from the blood specimen, it can be avoided by using glass fiber or chromatographic length The delay that occurs when slicing, so that the fluid specimen can enter the test chamber in a shorter time compared to previous techniques. Furthermore, it is not necessary to use cumbersome equipment such as a centrifuge for cell separation. All these advantages allow the test to be performed in a care setting. O The invention is superior to previous techniques. The biopsy sheet device of the invention allows several measurements on a specimen. This speeds up the process of obtaining test results and minimizes the number of specimens required for testing. The analyte-specific antibody itself can be labeled with any of several labels known to those skilled in these assays. Examples of preferred markers include fluorescent markers, color markers, another microsphere, gold particles, or any high imaging molecule. Other markers are applicable as long as the presence of the marker can be detected. Similarly, microsphere beads having a diameter smaller than the diameter of the test beads can be used so that the smaller beads move through the larger beads as the fluid specimen (e.g., plasma) moves. So the smaller beads can be labeled. The central standard of the Ministry of Economic Affairs is printed by the employee consumer cooperative. When a fluid sample containing the analyte enters the defined space between the two plates, further antibody-antigen reactions may occur. In the present invention, the upper plate ', such as a cover sheet, has an analyte-specific reagent bound to its surface, which surface is in contact with a fluid. In a preferred embodiment of the present invention, the analyte-specific reagent is printed on the inner surface of the support surface with a protein printer. Suitable protein printing devices are well known on the market. -26- Ben Kukang scale applies Chinese National Standard (CNS) A4 specification (210X297 mm) '4 68 046 Employees' Cooperatives of the Central Economic and Technical Bureau of the Ministry of Economic Affairs, Cooperative A7 B7 V. Description of Invention (24) — ~ These devices Including inkjet, spray, piezoelectric and spray protein printers. A piezoelectric printer is preferred. Analyte_specific reagent is used as a detection molecule, which is usually a protein. These dividers adhere to glass, metal, and plastic surfaces. Preferred surfaces include polystyrene or polypropylene. The use of this printing device is advantageous in the present invention because it allows several different analyte-specific detection molecules to be printed on a plate or cover sheet, so that different "flow channels" are defined and a single flow can be used The physical examination evaluates different analytes simultaneously. Additional background and correction channels can be provided in the same test cell. After the analyte reacts with the analyte-specific detection molecule, a detectable reaction product is produced. The bearing surface of the biopsy sheet is relatively colorless or transparent, so that colored, fluorescent or other reaction products can be read with a suitable spectrophotometer or other suitable detector coupled to the reader. When the analyte reacts separately with the analyte-specific detection, the density of the reaction channel changes. In a preferred embodiment of the invention, the change in density is measured to determine the amount of analyte present in the specimen. In order to reduce background interference, a cover is provided in the preferred embodiment of the present invention to increase the sensitivity of the measurement. Referring to FIG. 1, the cover 32, except for the openings 36, 38, and 40 corresponding to the flow channels 26, 28, and 30 on the plate , Yu are made of opaque material. The cover is designed just above the upper plate so that only the flow channel itself can be read. When judging the change in the density of the readout channel, the use of a cover has the advantages of reducing the amount of background interference and setting a basic value. In a preferred embodiment of the present invention, the biopsy sheet is designed to be read by a portable spectrophotometer. The spectrophotometer can read, for example, -27- This paper standard is applicable to China National Standards (CNS > M specifications (21〇 > < 297 male thin) (Please read the precautions on the back before filling in this page) ----- × .Λ ------ 1T -------. }-· Printed by the Central Laboratories Bureau of the Ministry of Economic Affairs, Shellfish Consumer Cooperative, 468 046 Α7 Β7 V. Description of the Invention (25) The color change after the analyte reacts with the labeled antibody. The spectrophotometer 'depends on the test reagent used It can also read out changes in density, film thickness, mass absorption or diffraction. Once the required data has been calculated by the analyzer (such as a spectrophotometer), the results can be transmitted via telephone lines, mobile phones or other computer network systems Borrow by digital transmission. In addition, if the radio frequency sensor is housed in a bioassay sheet detection system, changes caused during the antibody / analyte reaction can be detected or measured by radio frequency changes. Schematics are now discussed , Illustrated in exploded perspective in Figure 1 A preferred embodiment of the biopsy sheet for this application is described. It is provided with two bearing plates 10 and 12. The two plates define a fixed volume therebetween, indicated by the reference number 14. The lower plate 12 is higher than the upper plate 10. A long shelf is provided as an application area 16 on which the biological specimens 18 can be applied. The shelf is not necessary for the present invention, but provides a place where the specimens can be separated by microsphere beads. Beads The pellet can be placed at the entrance of the capillary chamber 14 within the range of the plate, and the specimen can be applied to the edge of the biopsy sheet, where the specimen enters the chamber by capillary action. Those who are fixed to the application area 16 also have microsphere beads. The collection point 20 of the granules may also include a marking area 22. The microspherical beads may be grouped or bundled in a fluid-permeable material. For the purpose of illustration, the microspherical beads 20 and the markings are shown in Figs. The zone 22 is represented by separate defined areas, but the microsphere beads themselves can also carry marks, and in this embodiment, the two zones can be merged into one zone, where the microsphere beads play two roles: separating fluids and providing marks To expose the fluid In this mark "• 28 This paper size applies Chinese National Standard (CNS) A4 specification (210 × 297 mm) {Please read the notes on the back before filling this page) Order _ 468 046 A7 B7_____ V. Description of the invention (26) (Please read the note_item on the back before filling this page] There can be more than one size of microsphere beads. In one embodiment, 'smaller microspheres are placed in the interstitial space formed by larger beads. Smaller beads can carry a second label that can bind to the analyte as it passes through the bead. The label is either bound to the analyte in the fluid 'or a label attached to the small bead On the analyte in the fluid, the beads then follow the fluid into the capillary chamber. At the same time, any cellular components in the fluid sample cannot pass through the microsphere bead filter. The patient's identity data can be fixed on the plate 10 or 12 as long as it does not interfere with the test detection area on the bioassay sheet, or it will not interfere with the bioassay after the analyte reacts with the substance bound to the surface of the carrier plate. The interpretation of the sheet is sufficient. The plates 10 and 12 are preferably colorless and / or transparent. Three detection areas 26, 28, and 30 are printed on the inner surface of the carrier plate 10: the calibration area 26, the detection area 28, and the basic value area 30. The three detection areas are drawn only to illustrate how the biopsy sheet is structured; however, there may be several runners and the number of runners for calibration and / or background varies depending on which is tested. Printed by the Shell Standard Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economics The test need not be limited to three channels. Several runners can be defined. In a preferred embodiment of the present invention, the three runners are printed on a plate to allow evaluation of background readings and correction of biopsy sheets. It should be understood that the background and correction detection area need not all be on the same biopsy sheet. However, it is advisable to perform the background and calibration interpretation on the specimen carrier plate for the same measurement as the test analyte 'to reduce the deviation of the test results. A background cover 32 may be provided if necessary. The cover is designed to cover the outer surface of the carrier plate 10 without blocking the coated or printed detection area or flow path. -29- Zhang scale applies to the Zhongguanjia standard (CNS} A4 specification (2 丨 GX297) (Centi) ': --- Printed by the Shellfish Consumer Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs 32. 4 6 8 0 4 6 A7 B7 V. Invention Description (27). So the openings 36, 38, and 40 exist on the cover, for example Reduce the background interference when the test result is judged. The background cover is made of opaque material. It has openings 36, 38, and 40 corresponding to the detection areas 26, 28, and 30 on the inner surface of the upper plate. The opening 40 in the cover does not have to have The corresponding test area 30 is illustrated, and the opening 40 is only required to be exposed to the non-existent part of the reagent on the plate 10. Although FIG. 1 illustrates both the antibody / labeling area 22 and the microsphere area 20, these two areas depend on the type of test May or may not be present. When the fluid sample 18 is applied to the application zone 16, it passes through the antibody / labeling zone 22 (if present) and microspheres before reaching the first meeting of the two plates 10 and 12. Edge 34 Bead zone 20 (if present). Although this arrangement of the invention can be done, However, it is best that the microsphere bead region 20 and / or the marking region abut against the edge 34 of the carrier plate 10. An example of this configuration is shown in Figs. 5 and 6. This configuration allows the fluid specimen to travel the shortest distance And this in turn minimizes the amount of fluid specimen required for the test, which will be further explained in Example 1. The fluid specimen is drawn below the edge 34 into a cell 14 defining a known volume. The body should have a volume sufficient to pass through the application area 16, through the microspheres and the marking area, and completely fill the chamber 14. The biopsy sheet of the present invention can be made small in size so that a drop of blood is sufficient for testing the test body. According to The principles taught here can be made in many sizes. Although the size of I cm x 3 cm is a device with conventional sizes, the optimal size of the sheet is mainly determined by the nature of the test to be performed. As illustrated in Figure 1, the shelf The portion 16 extends on the bottom plate. The biological specimen is applied on the shelf portion. In some other embodiments, the part to be tested (please note the ii notice on the back before filling in this page).

It This paper size applies to the Chinese national standard (CNS specification (210X297 mm) 468 046 A7 B7. Printed by the Bayer Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of the invention (28), such as microscope slides, can be quite large, but The measurement performed on the slide itself is extremely small. The measurement can be miniaturized to a volume suitable for sample fluids as small as about 1 microliter. Figure 2 is a cross-sectional view taken along line 2-2, and its explanatory diagram The same components in Figure 丨 Figure 2A is an end view of Figure 2 along the line 2A-2A, which illustrates that the end of the device can be opened to allow fluid to be removed from the cell. Cases where fluid is desired to be removed from the cell For example, when you want to test all specimens, β can apply the appropriate core material to the open end to pull the fluid out and allow additional fluid to enter the chamber. This can be a continuous or discontinuous process. Figures 1, 2 and 2A illustrate that the sticking points 58 hold the plates 10 and 12 together in one direction. The sticking points 58 are also provided in Figure 6 (another embodiment of the invention). Figures 7 and FIG. 7A illustrates another example in a single step radon assay. Separation by microspheres. In this example, the microspheres are used in conjunction with chromatography paper. The biological specimen 18 is placed on a surface such as a microscope slide 52, which can be placed directly on the microsphere beads 50 (As exemplified by the illustration) on or next to it. The fluid component of the specimen then flows through the beads 50 and is separated from the non-fluid components present in the specimen 18. The beads adjoin or are close to the glass fiber filter septum 60 ' The glass fiber cymbal cymbal 60 ° β-linked marker cymbal 62 »The marker gasket 62 is usually a glass fiber gasket impregnated with a marker, and the marker can be used to mark the analyte in a fluid sample. Fluid flow Through the filter 60 and the marking pad 62. When the fluid flows through the marking septum, any analytes present in the fluid will be marked. The fluid then flows into the nitrocellulose chromatography strip -31-This paper applies to China National Standards (CNS > 8 4 ^ grids (2 丨 οχ2 ”mm) --------- Clothing — (Please read the notes on the back before filling this page) Order the Central Standards Bureau of the Ministry of Economic Affairs Printed by the Consumer Cooperative 468046 A7 B7 V. Description of the Invention (29) Tablet 64 The test results are interpreted, usually based on the color change or appearance of the nitrocellulose strips. In addition, since the microspheres 50 are used as filters, the glass fiber filter 62 can be completely removed (not shown). Finally, as illustrated in FIG. 7A, the glass fiber marker gasket 62 may be replaced with microspherical beads 66. In this example, 'beads 66 are used as a source of markings instead of filters' and glass fiber filters 60, 60 As a separator between two sets of beads 50 and 66. For applications where fluid composition is not needed, 'microsphere 66 can be used to directly label the analytes present in the fluid' without the need for a microsphere filter 50 or broken glass fiber spacer 60 ,. Figures 7 and 7A illustrate how to modify the current measurement method using the microsphere bead technology of the present invention as taught herein. The measurement device and technique of the present invention are very useful for a small number of fluid samples. Although this article specifically describes proteins, any other indicator (marker) can be applied as long as it can design a marker system that can detect and measure the indicator. For example, the invention can be used to measure and / or detect the presence of microorganisms such as bacteria, viruses, fungi or other infectious organisms. The biopsy sheet device of the present invention can be calibrated according to the type of measurement and the type of analyte, so that a standard value table can be established. The measurement system of the present invention can detect the amount of a specific hormone, even the amount of a drug in a patient's system, and the standardized data can be used to diagnose and / or prognosticate a specific individual. Once the standard value table is established, regular data collection and data bases are established based on the patient's medical history, current health status, and test results. -32--This paper size is applicable to China National Standard (CNS) A4 (210X297). ≪ Please read the precautions on the back before filling in this page). 4 6 8 0 4 6 Central Bureau of Standards, Ministry of Economic Affairs Beigong Consumer Cooperative Co., Ltd. Yinli A7 B7 V. Description of the invention (30) When needed, the data can be transmitted digitally via computer networks through modems, international networks, cables, telephone lines, satellites or other similar technologies. These databases can be used to develop neural network calculations to evaluate current patient test results and diagnoses, and to predict certain health consequences for specific individuals. An example of the neural network calculation is described in Example 3 below and the sample receiver operator curve (Roc) is illustrated and illustrated in FIG. 8. The development of applied neural network algorithms will be able to assess medical conditions. In order to have predictable consequences that can be relied upon, a large amount of patient data must first be accumulated. The neural network can determine the concentration of the analyte for diagnosis or prognosis by the standardized measurement of the present invention through logical calculations. The data and algorithms are encoded in an electronic chip that is placed in a reader (such as a spectrophotometer) so that the report printed from the reader provides the test results while providing a specific diagnosis or prognosis . In neural network calculations, the results of diagnostic or prognostic tests will reach the optimum as the number of data increases. The more data the patient has, the more accurate the predictions and / or diagnoses obtained. Based on the analysis of the measured data and comparison with the database contained in the electronic memory chip set in the provided analyzer, the accurate percentage can be calculated and provided to the physician or technician. Current technology allows a standard curve to be displayed on the reader itself when the test results are printed. According to another aspect of the present invention, in addition to the use of a spectrophotometer, a thin sheet for biopsy contains a radio frequency sensor β in the carrier plate 10. When a reaction occurs in one or more detection areas, a measurable change in radio frequency occurs , And by appropriate means for detecting changes in radio frequency -33- This paper size applies to Chinese National Standard (CNS) Α4 specification (210X 297 meals) (Please read the note on the back before filling this page) Order from the economy In the ministry, printed by the Consumer Standards Cooperative of the Central Bureau of Standards 4 6 BQ 4 6 A7 ---------- B7 V. Description of the invention (31) Detecting the change of radio frequency, and measuring the presence or absence of the response, even Degree of reaction. In the present invention, more than one test can be performed simultaneously on the same biopsy sheet, so the certainty of diagnosis or prognosis can be improved. As the number of bids increases, the certainty of the measurement increases. One of the many uses of the biopsy sheet / cassette of the present invention is to use a drop of patient's blood to measure blood proteins to indicate peripheral vascular disease. When the fluid portion and the non-fluid portion of the specimen are separated during the separation / filtration step ', the microspheres are observed under an optical microscope. It was observed that some microspheres were in motion 'while others remained stationary. Separation is dynamic and the role of beads or particles in separation is a dynamic capillary action. The separation or extraction of the fluid part is instantaneous. The invention can also be applied to particles other than the microspherical beads described herein. More specifically, the separation technology of the present invention also works with non-uniform particles (including silica particles, such as sand particles), as shown in Figure 7 below. "Even if these particles are not necessarily spherical, the size is not uniform. Operational. As illustrated by the examples herein, the use of non-uniform and / or non-spherical particles or beads can achieve proper separation / filtration. Heterogeneity makes the separation efficiency lower because it is slower, but at least it can still achieve effective separation for qualitative determination. For example, in Example 7 where grit was used, since fewer organisms were separated from the specimen during the same period as the separation with microspherical beads (as described in Examples 4, 5 and 6), the separation appears to Not very efficient. However, -34- This paper size applies to China National Standard (CNS) A4 (210X297 cm) --------- ^ f I (Please read the precautions on the back before filling this page) Order-A7 B7 The Consumer Cooperative Cooperative of the Central Procurement Bureau of the Ministry of Economy 4 68 046 V. Description of Invention (32) The organism will eventually be successfully separated and can be further tested or determined. The advantages of using silica or other similar particles over microspherical beads are that they are cheaper and easier to obtain in lower and developing countries. The assay and device of the present invention are used to identify the presence of harmful and pathogenic bacteria (such as E. coli strain 0157: H7, Salmonella, Listeria, Chlamydia virus and other bacteria) and microorganisms such as viruses in certain biological specimens. Especially useful. For example, the assay of the present invention can be used to test certain pathogenic bacteria in food specimens. It can also be used in human or animal medicine to diagnose infectious diseases. Dynamic separation by the method taught by the present invention is illustrated and illustrated in Figures 9-18 and Examples 4-7. From this example, it has been proved that the microspherical beads of the present invention can be popularized as ordinary particles and the present invention is not limited to spherical beads, but includes particles of uneven size and shape, as described in Example 7, Use grit as a filter on the biopsy sheet. Silica sand particles are expected to be much cheaper than commercially available microsphere beads, making the technology more versatile. Although the use of oxidized silica sand is not very efficient, that is, there are fewer bacteria isolated in the same time zone, but it is sufficient for many purposes. Another advantage of using oxidized dream-type particles is that silica is known in the art. Selective binding of proteins and nucleic acids. Silica-based separation particles can be used to design certain protein and / or nucleic acid localization mechanisms. In all Examples 4 to 7, the 'separation is almost instantaneous and the size limitation is determined by the type of bacteria, microorganisms, or other analytes that are expected to separate. Β It is expected that those skilled in the art will know how 35- The M's scale is applicable to the Chinese National Standard (CNS) M specifications (2 丨 0 > < 297 public attack) {Please read the note on the back before filling this page}

6 6 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Α7 Β7 V. Description of the invention (33) The type of bacteria that is present selects the size of the particles. If the bacteria is unknown, those skilled in the art will select the particle size based on the predicted size and generally choose the bead size according to the above ratio of 0.4: 1. The preferred embodiment of the present invention is explained in more detail in the following examples. These examples are not intended to limit the scope of the accompanying patent applications. Example 1: Confirmation of plasma flow and separation from human blood As illustrated in FIGS. 3 to 6, about 15 microliters of 10 micron latex microsphere beads (Bang'sTM) 50 were dropped on a glass slide 52 And let it dry. A cover glass 54 is placed on the glass slide and its edges are pushed toward and along the dried beads. The cover slip separates the dried beads from the slide and causes the dried beads to roll ' thereby forming a curl 56. The coverslip was then placed on a glass slide and the edges of the coverslip were touched with H curl M (as shown in Figures 5 and 6). The coverslip is placed squarely on the glass slide with its edge aligned parallel to one of the curled edges of the dried beads, and the edge is opened to allow fluid to flow through the beads and into the cover glass and slide Capillary chamber formed. The cover slip was glued with nail polish on its four corners 58 to fix it on the microscope slide. The point at which the cover slip was fixed was the point at which fluid was allowed to flow freely under the coverslip without intentional capillary action. A drop of 20 microliters of human whole blood 18 was placed on the remaining 5 to 10 microliters of microsphere beads. In other words, the specimen of human whole blood is placed on the remaining beads that do not form a curled portion, and the plasma components are allowed to move freely through the curled portion of the microsphere beads by capillary action and into the cover glass and the slide. The defined space (ie the capillary chamber) ^ observe the effect under a binocular optical microscope. When adding blood samples to the beads, plasma-36- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling this page) Order 468 04 6 Printed by the Central Standards Bureau of the Ministry of Economic Affairs, Shellfish Consumer Cooperative, A7 B7 V. Description of Invention (34) Immediately began to separate from whole blood. When the curl is soaked with plasma, the capillary action between the cover glass and the slide pulls the pure cell-free plasma under the cover glass into the compartment defined between the cover glass and the slide. The cell defines a known space 'whose volume can be calculated and predetermined. This proves that microsphere beads can easily and effectively separate plasma from whole blood, and enter the capillary compartment through the capillary channel formed between the microsphere beads. Example 2: The combination of microsphere separation and strip analysis in the measurement of analytes in human blood samples. This example (shown in Figure 7) demonstrates that the use of microspheres can remove plasma from Isolated from blood samples of human whole blood. Plasma was separated with latex microsphere beads (Bang'sTM) 50 and then pulled into standard nitrocellulose chromatography strips. Fiberglass gaskets (usually used to retain red blood cells in prior art) were replaced with approximately 20 microliters of 10 micron latex beads. A drop of human blood (about 60 microliters) was placed on surface 52, in contact with the latex microspheres. The glass fiber septum 60 is used as an effective spacer between the bead 50 and the marking gasket 64, but it is also used as a second filter. The glass fiber filter 60 can be completely eliminated and the microsphere beads 50 and the marking gasket 64 can be directly used. Adjacent (not shown). It was observed that the blood soaked the bead pile and the clear plasma flowed to the nitrocellulose chromatography strips in about 2 minutes. This can be observed with the naked eye or under a microscope. This example demonstrates that the microsphere method for separating plasma from blood can also be used with standard nitrocellulose chromatography strips. As far as the test using this chromatography strip is concerned, this clearly shows that there is-yes- 37- This paper size applies to China National Standards (CNS) M specifications (210X297 mm) (Please read the precautions on the back before filling out this page)-* 1T. 468 046 A7 Employees ’cooperation with China Standards Bureau, Ministry of Economic Affairs Printing of B7 V. Invention Description (35). Figure 7A depicts another preferred embodiment in which the fiberglass mat 62 ' microsphere beads 66 are used in the calibration area of the test. A fiberglass mat 60 was used as a barrier between the two sets of beads 50 and 66. Wong. Example 3: Neural crest index break neural network is a mathematical function N (W, a), the input of the analyte vector a = (al 'a2 ......, an) and the output number in Between 0 and 1. Use digital logic calculation model {p = (bl, b2 '.... bn' T)} during digital logic training (where bl '...' bn is the protein vector for digital logic calculation 'and T is the target output Value) adjusts the weighting parameter w. In the example of the coagulation test, T is 1 for coagulation and 0 for uncoagulated. Adjust parameter W to minimize the error E = Σ (N (W, a) -T) 2,

P also maintains good performance on new test data. Once the network is logically calculated 'select the network cut-off point C to classify the test data. TST (C, b, T) is the test result of test vector a, the predetermined cut-off point c and the target output T. {If N (a)> C, 1 TST (C, b, T) = {{Otherwise 0 Now analyze the sensitivity and specificity of the test. If T = 1 and TST (C, b, T) = 1, then it is a true positive. If T == 0 and TST (C, b, T) = 1 ', then it is a false positive. If T = 0 and TST (C, b, T) = 0, it is true negative. If T = 1 and TST (C, b, T) = 0, it is false negative. -38-(Please read the precautions on the back before filling this page). Standards General Chinese National Standards (CNS > (210X297)) 4 β 8 〇 4 S Α7 Β7 V. Description of the invention (36) Sensitivity = TP / (TP + FN) Specificity = TN / (TN + FP) Pair Draw sensitivity vs. specificity at various cut-off points to get the ROC (receiver operator characteristic) curve. The neural network starts with a set of logical calculation models {p = (II, 12 ···· .II, TAR). , Where Ij is the input value and TAR is the target value (TAR = 0 or TAR = 1). I want to logically calculate the neural network to get an output value close to the standard stem value. The neural network has 3 layers: The first input layer, the second hidden layer, and the third output layer: _ _ C _ / (Please read the precautions on the back before filling out this page) • ^ τ Printed input hidden output nerve by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Yuan borrowing a set of weights {w (i, j, k)} connection. For example, w (1,2,4) connects the second neuron in the first layer and the fourth neuron in the second layer. For each model, we give a The number refers to the activation of each neuron, which measures the probability of activation. The activation is defined as follows: -39- This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 6 8 0 4 6 A7 B7 V. Description of the invention (37) The error is calculated as follows: ERMS = SQRT {Sum {(ta (2, l)) A2}} where the sum is for all models. Adjust the weights so that ERMS is minimized while maintaining good performance on new data Quantitative analysis flow chart --------- π-- (Please read the notes on the back before filling this page) Printed by Shellfish Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs

-40- The size of the paper is applicable to China National Standard (CNS) A4 (210X297 mm)

4 68 046 a? _______B7 V. Description of the invention (38) _ II Compare the output value (OUT) and cut-off point (CUT) of the neural network {* OUT > CUT, then the test result is positive = {__ {Others are negative (Please read the note on the back before filling in this card) Printing Example 4: The Central Laboratories of the Ministry of Economic Affairs, Consumer Cooperatives, Printing Example 4: Although the lactic acid bacterium is from the milk, it is about 10 microliters of yogurt containing lactic acid bacteria Placed on the measurement device of the present invention (referred to herein as a "bioassay sheet". When there are no beads for separation on the biopsy sheet, as shown in FIG. 9, a solid is observed in the field of view Particles. Before the separation, only a few bacteria were seen in the field of view (Figure 9). In contrast, as shown in Figure 10, the separation of microsphere beads with a diameter of 15 microns showed that bacteria and samples were well separated. Figure 9 The solid particles seen in the method did not appear. After separation, only bacteria were found in the separated fluid part. The separation occurred almost instantaneously. Microsphere beads provide a fast and convenient method of separating bacteria and acids. The remaining solid particles in the cheese are separated, thereby allowing the The isolated bacteria are further tested. This allows to determine the type of bacteria present in the specimen. For example, the type of bacteria or other microorganisms can be determined by special antigen tests to determine the type of bacteria or microorganisms present. When used for isolation When the 10 micron micro-spherical beads are carried out, the paper size shown in Figure 丨 1 is applicable to the Chinese national standard (CNS > M specification (2 丨 0 > < 297 Gongchu)): Policy ----- 1T- ---- L}}-468 046 Printing of A7 B7 by the Masonry Consumer Cooperative of the Central Bureau of Procurement, Ministry of Economic Affairs V. Invention Description (39) Similar results. Figure Π shows that the number of bacteria in each field of view is smaller However, it still shows that bacteria and yogurt are effectively separated. FExample 5 · Isolation of Euglena bacillus from Fuzi of Bakery County In this example, E. coli was successfully separated from the bread suspension by the method and device of the present invention. First, prepare a mixture of bread and NaCI. Weigh 200 亳 g of bread ° Bread suspension prepared by repeatedly mixing 500 microliters of 150 mM NaC] with bread. Add E. coli (DH5a strain) in 100 microliter portions to Bread suspension. The suspension Mix again to make an E. coli / bread suspension. Place 100 μl of the E. coli / bread suspension on the "bioassay sheet" and microsphere beads to remove bacteria-containing fluid components from the specimen almost instantaneously. Isolated, but no solid particles were separated from the specimen. Figure 12 shows a typical field of view of an unisolated E. coli / bread suspension. Figure 13 shows the fluid portion of a 15 micron diameter microsphere bead isolated Bacteria were isolated. Good separation was observed. FExample 6: Isolation of fine anise from bovine stalks In this example, bacteria from cow dung were isolated using the technique of the present invention. 500 mg of cow dung and 500 microliters of 150 NaCI were combined and mixed to form a suspension. Five microliters of the suspension was used for separation and placed on the biopsy sheet. Micrographs before (Figure 14) and after (Figures 15 and 16) are shown. In this example the separation was achieved with 5 micron microsphere beads. The specimen is placed on the biopsy sheet and the microsphere beads separate the fluid component containing bacteria from the specimen almost instantaneously. The isolated bacteria are now stained for further identification. "15 micron diameter beads (Figure 15) -42- This paper size applies to China's national standard (CNS > A4 size (210X297 mm) ------ --- 衣 — {Please read the precautions on the back before filling in this page) Order 468046 Shellfish Consumer Cooperation of the Central Standards Bureau of the Ministry of Economic Affairs, printed on the fifth, description of the invention (40) and use 10 micron diameter beads (picture 16) All achieved good separation. Example 7: Catching the air with gasified Miaosha_ In this example, other types of particles are tested in addition to the commercially available standard polystyrene beads. In order to test the applicability of silica-based particles, microsphere beads were replaced with grit (silica sand). Three tests were performed: cow dung, coliform / bread suspension, and blood. Silica sand is mixed with water to form a slurry and applied to a biopsy sheet. The size of the grit on the biopsy sheet can be seen from the 1 mm ruler (Figure 丨 7). Although good separation was observed as shown in cow dung) and Figure 19 (E. coli / bread suspension), the separation was not as good as the same experiment described in Examples 5 and 6 above, where polystyrene beads were used for filtration step. Similarly, the efficiency of separation with this particle is poor because it has non-uniform particle size and shape. However, sand particles / silica sand are clearly still a suitable substitute for polystyrene microbeads because it Clear separation. Whole blood was applied to the biopsy sheet and allowed to pass through silica grit. In this example, because of the larger particle size (compared to 10 micron microsphere beads), red blood cells flow through the particles for filtration. Obtain a uniform blood smear. Those skilled in the art will recognize or be able to confirm many equivalents to the embodiments of the present invention specifically described above using routine experiments. Such equivalents are included in the scope of the following patent application parks. -43-

(Please read the notes on the back before completing this I ·)

0 I! 1-^ n II.

Claims (1)

i 68 046 A8 B8 C8 D8 2. 4. Printed by the Consumers' Cooperative of the Central Samples Bureau of the Ministry of Economic Affairs «-5. The scope of patent application-a device for separating fluid from biological specimens, which has fluid components and non-fluids The device includes a plurality of microspheres, which are configured in a β-connected relationship and form a gap space therebetween, so that the gap spaces are connected into a plurality of capillary channels, whereby the microspheres are arranged in a fluid path with a biological specimen During neutralization, the non-fluid component of the specimen is separated from the fluid component by capillary flow of the fluid component through the capillary channel. The device according to item 1 of the scope of patent application, wherein a plurality of smaller microspheres are dispersed among a plurality of larger microspheres, and the plurality of larger microspheres are arranged in a generally B-connected relationship and a gap is formed therebetween. Space, so that the interstitial space is connected into a plurality of capillary channels, and the sizes of the plurality of smaller microspheres are small enough to allow them to occupy the interstitial space formed by the larger microspheres and migrate through the capillary channel, when the fluid component flows through the capillary channel The smaller microspheres can be carried forward by the fluid component. According to the device of claim 2 of the patent application, the light microspheres are marked with at least one mark. The device according to item 3 of the patent application park, wherein the label is selected from the group consisting of a radioactive label, a fluorescent label, a metal, a protein, a peptide, an antigen, and an antibody. According to the cleavage of item 3 of the patent application park, wherein the biological fluid contains the analyte and the antibody labeled as specific to the analyte 6, the device of the item 2 of the patent application park, wherein the plurality of Minor-44 · Private paper magic t applies to China Garden Standard (CNS) A4 specifications (21〇 Father 297 Public 3 " (Please read the precautions on the back before filling this page) Stupid · Order 6 4 ο 8 6 ABCD 6. The patent application Fanyuan microspheres still include a plurality of groups of microspheres, each group of which is impregnated with different marks and each group is dispersed among the larger microspheres in a separation area composed of larger microspheres. 7 ' The device according to item 1 of the patent application park, wherein the microspheres have different diameters. The device according to item 1 of the patent application parks, wherein the microspheres have substantially the same diameter. 9. According to the device 1 of patent application parks, The device according to item 1, wherein the size of the microsphere is selected according to the viscosity of the specimen. 10. The device according to item 丨 of the patent application park, wherein the microspheres are bundled into a bundle with a fluid-permeable material. Ιι_ According to the application The device according to item 1 of the utility model, in which the microspheres are kept in adjacency by the surface tension of the fluid or by drying the microspheres. 12. According to the device of the patent application park item 丨, it contains a fluid_transporting member, which can The specimen is delivered to a fluid path with microspheres. 13. The device according to any one of claims 1 to 12, wherein the biological specimen is blood and the fluid component is plasma. 14. A measuring device 'which contains A combination of the following components: Central Standards Bureau of the Ministry of Economic Affairs w: printed by industrial and consumer cooperatives (please read the precautions on the back before filling out this page) at least one small room defined by the first and second opposite sides, where the two opposite sides are between The distance enables the fluid to be drawn into the cell by capillary action, the cell has at least one fluid inlet through which fluid can be drawn into the cell, and at least one reagent disposed in the cell; thereby being Fluid samples delivered into fluid channels with fluid inlets -45- Printed bags of the Shellfish Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 4 68 046 ι D8 VI. Scope of patent application The capillary action is pulled into the capillary chamber, so that the fluid of a predetermined volume is substantially filled with the capillary chamber. 15. The measuring device according to item 14 of the scope of patent application * which includes a fluid-transporting member that can transport the specimen to a fluid passage with a fluid inlet. 16. The measuring device according to item 14 of the patent application park, which is used for analyzing a biological specimen, the specimen has a fluid component and a non-fluid component, wherein the dynamic capillary filter is arranged in a fluid having a fluid inlet to the cell. In the passage, the dynamic capillary filter includes a plurality of microspheres, which are arranged in an abutting relationship and form a gap space therebetween, so that the gap spaces are connected into a plurality of capillary channels, whereby the microspheres are arranged in a biological test body. In the fluid path, the capillary component of the fluid passes through the interstitial space between the adjacent microspheres to separate the non-fluid component from the fluid component, and the fluid component is pulled into the fluid inlet to cause the fluid to fill the capillary chamber. 17. The measuring device according to item 16 of the scope of patent application, which comprises a specimen holder adjacent to the fluid inlet, wherein the microspheres are arranged on the specimen holder. 18. The measuring device according to item 16 of the scope of patent application, wherein the plurality of smaller microspheres are marked with at least one mark and dispersed among the plurality of larger microspheres, so that the smaller microspheres occupy the gap between the larger microspheres Space, and release the mark into the fluid as it flows through the interstitial space between the larger microspheres. 19. The measuring device according to item 18 of the scope of patent application, which comprises a plurality of smaller microspheres, each of which is impregnated with a different label and the larger microspheres are dispersed in a separation region composed of larger microspheres between. -46- This paper size is based on the national standard (CNS) _A4 size (210X297mm) (Please read the precautions on the back before filling out this page) Order ABCD 46BQAS VI. Patent application scope 20. According to the patent application Fanyuan No. 14 continued to configure the left point "Γ", in which the reagent was placed in a strip attached to the inner surface of the capillary chamber. (Please read the note ^^ on the back before filling out this page) 21 · ΪΠ! The measuring device of Item 20 of the Patent Fan Garden, in which the reagent. Package: 浐 Two are printed or coated inside the capillary chamber On the surface 22. The measuring device according to item 14 of the patent application park, wherein a plurality of reagents are arranged in a capillary chamber for performing a plurality of types of measurement on a fluid sample. 23. The measuring device according to claim 22, wherein the reagent includes a protein, an antibody, a nucleic acid, a lipid, a steroid, a heterocyclic compound, a drug, or any combination thereof. 24. The measuring device according to item 14 of the patent application, which includes a plurality of capillary chambers to perform multiple determinations of one or more fluid specimens. 25. According to the measuring device of item 2 of the patent application, An analyzer that detects the ratio of reagents bound to an analyte in a fluid sample. 26. The measuring device according to item 25 of the patent application park, which further includes a calibration bar for setting a base value for calibration of the analyzer. Printed by the Consumer Cooperatives of the Central Bureau of the Ministry of Economic Affairs of the People's Republic of China 27. The measuring device according to item 14 or 25 of the patent application park, which also includes an indicator, which contains the patient's identity information related to the measurement result. 28. The measuring device according to item 27 of the patent application park, wherein the indication includes a bar code and the analyzer includes a bar code reader. Device 29. The measuring device according to item 25 of the scope of patent application, in which the analysis -47- This paper size is applicable to the national standard (CNS) A4 specification (210X297 mm). 4 6 8 04-6 Bs D8 6. The scope of patent application includes a spectrophotometer. 30. The measuring device according to item 25 of the patent application park, wherein the analyzer is capable of transmitting data digitally via a digital transmission system. 31. The measuring device according to item 14 or 25 of the scope of patent application, which includes a cover covering the biopsy sheet, the cover being transparent above the reagent and above the portion of the biopsy sheet surrounding the reagent It is opaque. 32. —A method for separating a fluid from a biological specimen, the specimen having a fluid component and a non-fluid component, and the method comprising the following steps: (a) flowing a specimen into a fluid path having a plurality of microspheres, such The microspheres are configured in a contiguous relationship and form a plurality of interstitial spaces therebetween, the plurality of interstitial spaces are connected into a capillary channel, and (b) the fluid component is collected when the fluid component is separated by its capillary flow through the capillary channel . 33. The method according to item 32 of the application, wherein the biological specimen is blood and the fluid component is plasma. 34. The method according to item 32 or 33 of the scope of patent application, which further includes a step of dispersing a plurality of smaller microspheres impregnated with at least one marker between a plurality of larger microspheres, so that the smaller microspheres are smaller. Occupies interstitial spaces between larger microspheres, and releases markers into the plasma as plasma flows through the interstitial spaces between larger microspheres. 35. A method according to item 32 or 33 of the scope of the patent application, in which smaller microspheres of a plurality of groups impregnated with different marks are dispersed among larger microspheres in a separation region composed of larger microspheres. -48- This paper size is applicable to Chinese National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before filling this page)-Order A8 B8 C8 D8 4 6 8 04 6 VI. Apply for a patent Fan Yuan 36. The method according to item 32 or 33 of the patented Fan Yuan, wherein the microspheres have different diameters. 37. The method according to item 32 or 33 of the patent application park, wherein the microspheres have the same diameter. 38. The method according to item 32 or 33 of the patent application park, wherein the microspheres are bundled with a fluid-permeable material. 39. The method according to item w or 33 of the patent application park, wherein the microspheres are kept in adjacency relationship by the surface tension of the plasma or by drying the microspheres. 40. A method according to claim 32 or 33, wherein a fluid-transporting member is provided to transport a biological specimen to a fluid path with microspheres. 41. A method for measuring using a device, the device comprising a capillary chamber defined by first and second opposite faces spaced from a capillary and having a fluid inlet, and at least one reagent disposed in the capillary chamber, the method comprising the following Steps: (a) transport the fluid sample into the fluid path with the fluid inlet, so that the fluid sample is drawn into the capillary chamber by capillary action and reacts with the reagent, and '(b) analyze the reagent to determine whether the reagent Binding to a fluid sample analyte. 42. The method according to item 41 of the patent application, which further comprises the step of determining the ratio of the reagent bound to the specimen. 43. The method according to item 42 of the scope of application for patents, which also includes a capillary tube-49- this paper size, uses the Chinese National Standard (CNS) Bagu 1 grid (210X297 mm) -------- -------- (Please read the notes on the back before filling out this page) Order printed by the Central Labor Bureau of the Ministry of Economic Affairs, the Zhenggong Consumer Cooperative 4 6 8 04 6 ABCD Cooperative seal «. VI. Steps for determining the volume of a fluid specimen that substantially fills a capillary chamber with a known volume as small as the scope of the patent application. 44. The method according to item 41 of the scope of patent application, which is used to analyze a biological specimen 'the specimen has a fluid component and a non-matrix component, wherein the dynamic capillary filter is configured in a fluid path having a fluid inlet to the cell In the dynamic capillary filter, a plurality of microspheres are arranged in a herring relationship and form a gap space therebetween, so that the gap space is connected into a plurality of capillary channels; and the method includes capillary flow through the fluid component through the capillary Capillary channel to separate the fluid component from the non-fluid component of the biological sample. 45_ The method according to item 44 of the patent application park, wherein the biological specimen is blood and the fluid component is plasma. 46. The method according to item 41 of the scope of patent application, wherein the reagent is arranged in a strip attached to the inner surface of the capillary chamber. 47. The method according to item 46 of the patent application, wherein the reagent contains a selected anti-drug printed on the inner surface of the capillary chamber 48. The method according to item 46 of the patent application range, wherein a plurality of reagents are formulated Tan is in a capillary chamber for performing multiple measurements on fluid samples. 49. The method according to item 47 of the application, wherein the reagent includes protein and antibodies. 50. The method according to item 48 of the patent application is reported, wherein the reagents include proteins, carcasses, nucleic acids, lipids, steroids, heterocyclic compounds, drugs of abuse or any combination thereof. 51. The method according to item 41 of the scope of patent application, which includes a plurality of hairs (please read the precautions on the back before filling out this page)-. 私--_ -50- A8 B8 C8 D8 468046 VI. The scope of the patent application is small ▲ to perform multiple determinations on one or more fluid specimens. 52. According to the method of item 41 of the scope of patent application, it also includes the use of a printed on a biopsy sheet. Calibrate the strip calibration analyzer to set the base value. 53. According to the method of finding item 41 of the patent scope, it further comprises the step of correlating the measurement result with the patient's identity information contained in the indicator fixed to the biopsy diaphragm. 54. The method according to item 53 of the patent application, wherein the indicator includes a bar code. 55 'The method according to item 41 of the patent application park further includes the step of recording the measurement results in a computer database. 56. According to the method of Patent Application No. 55, it also includes the step of compiling data from a plurality of measurements in a database. 57. According to: The method according to item 55 of the patent, which also includes applying a logic algorithm to the data to obtain one or more norms of the selected anomaly. 58. According to the method of the Chinese Patent Application No. 56, the method further includes the step of analyzing the receiver's operational characteristics to determine the statistical significance of the data. 59. According to the method of Patent Application No. 57 in the patent application, it also includes a step of analyzing the operational characteristics of a logarithmic receiver to determine the statistical significance of the data. 60. The method according to item 41 of the scope of patent application, which further includes an analysis reagent to determine whether the reagent is bound to the analyte in the fluid sample ^ -51-i The paper is applicable to China National Sample Standard (CNS) Α4 ^ Ύ ^ · ^ 297 Public Magic V-- (please read the notes on the back ^^ before filling in this page), 1T Seal of the Zhengong Consumer Cooperative, Shiyang Bureau of the Ministry of Economic Affairs 4 68 046 Ag B8 C8 D8 VI. Application Prior to the patent scope step, the step of removing a fluid specimen from a capillary chamber after a desired time interval. 61. The method according to item 60 of the scope of patent application, wherein the core or capillary carries a liquid that communicates with the liquid sample to remove the liquid sample from the capillary chamber. 62. —A method for analyzing an analyte in a fluid component of a biological sample, the sample having a fluid component and a non-fluid component, the method includes the following steps: (a) let the sample enter a fluid path with a dynamic capillary filter The capillary filter includes a plurality of microspheres configured to be in abutting relationship and forming a plurality of interstitial spaces therebetween, and the interstitial spaces are connected to form a capillary channel, thereby separating fluid components from non-fluid components; (b) detecting a fluid The analyte in the composition to determine the presence of the analyte; and (c) contact the fluid component with the nitrocellulose chromatography strip to separate it on the nitrocellulose chromatography strip. Printed by the Central Government Bureau of the Ministry of Economic Affairs of the Shellfish Consumer Cooperative (please read the notes on the back before filling out this page) 63. According to the method in the 62nd patent application scope, in step (b), the analyte is borrowed The fluid component is detected by allowing the fluid component to enter the fluid path with the nitrocellulose strip, wherein the nitrocellulose strip is impregnated with a marker specific to the analyte, and the marker will interact with the fluid of the specimen. The analyte present in the composition is bound. 64. The method according to item 62 of the scope of patent application, wherein in step (b), the analyte is detected by allowing a fluid component to enter a fluid path having a second group of microspheres, and the second group of microspheres is Analytical analytes-52- This paper size uses Chinese National Standard (CNS) A4g (2I0X297mm) Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 4 6B 046 si D8 The marker will bind to the analyte present in the fluid component of the specimen. 65. A device for separating fluid from a biological specimen, the specimen having a fluid component and a non-fluid component, the device contains a plurality of particles, which are configured to be in abutting relationship and form a gap space therebetween, so that the gap space A plurality of capillary channels are connected to thereby separate non-fluid components from fluid components by capillary flow of the fluid components through the capillary channels when the particles are arranged in a fluid path with a biological specimen. 66. The device according to item 65 of the patent application, wherein the plurality of particles are inconsistent in shape. 67. The device according to item 65 of the patent application, wherein the plurality of particles have inconsistent sizes. 68. The device according to item 65 of the patent application, wherein the plurality of particles have inconsistent shapes and sizes. 69. The device according to item 65 of the application, wherein the particles are silica particles. 70. The measuring device according to item 14 of the scope of patent application, which is used for analyzing a biological specimen, wherein the specimen has a fluid component and a non-fluid component, wherein the dynamic capillary filter is arranged in a fluid having a fluid inlet to the chamber. In the passage, the dynamic capillary filter includes a plurality of particles, which are arranged in an abutting relationship and form a gap space therebetween, so that the gap space is connected into a plurality of capillary channels, whereby the particles are arranged in a fluid path with a biological specimen. At the time, the capillary of the fluid component flows through the interstitial space between adjacent particles, so that the specimen is wrong. 53-This paper size applies to the Chinese National Standard (CNS) Α4 grid (210 × 297 mm) (Please read the back Note: Please fill in this page again.) Order A8, B8, C8, D8, 468046 points, patent application scope, fluid components are separated from fluid components, and fluid components are pulled into the fluid inlet, causing the fluid to fill the capillary chamber. {Please read the precautions on the back before filling out this page) 71 ♦ The measurement device according to item 70 of the scope of patent application, which includes a specimen holder adjacent to the fluid inlet, in which particles are arranged on the specimen holder. 72. The measuring device according to item 71 of the patent application park, wherein the particles are silica particles. 73_ — A method for separating a fluid from a biological specimen, the specimen having a fluid component and a non-fluid component, and the method includes the following steps: (a) let the sample flow into a fluid path with a plurality of particles, and the particles are It is arranged in a contiguous relationship and a plurality of interstitial spaces are formed therebetween, the plurality of interstitial spaces are connected into a capillary channel, and (b) the fluid component is collected when the fluid component is separated by its capillary flow through the capillary channel. 74. The method according to item 73 of the patent application, wherein the particles are inconsistent in size and / or shape * 75. The method according to item 73 or 74 of the patent application, wherein the particles are silica particles. Printed by the Consumer Goods Cooperative of the Central Government Bureau of the Ministry of Economic Affairs 76. According to the method of patent application No. 73, it is used to analyze biological specimens. The specimens have fluid components and non-fluid components. The dynamic capillary filter is Arranged in a fluid path having a fluid inlet to the chamber, the dynamic capillary filter includes a plurality of particles arranged in a herring relationship and forms a gap space therebetween such that the gap space is connected into a plurality of capillary channels; and This method includes the steps of separating biological components from the fluid components and non-fluid components of the specimen by applying capillary flow through the capillary channel through the capillary channel. ^ 77, The method according to item 76 of the patent application, wherein the particles are oxidized particles. 78. —A method for analyzing an analyte in a fluid component of a biological specimen, the specimen having a fluid component and a non-fluid component, the method includes the following steps: 丨 (a) let the specimen enter a dynamic capillary filter In the fluid path, the capillary filter includes a plurality of particles, which are configured in a connected relationship and form a plurality of interstitial spaces therebetween, the interstitial spaces are connected into a capillary channel, thereby separating fluid components from non-fluid components; (b) Detecting the analyte in the fluid component to determine the presence of the analyte; and (c) contacting the fluid component with the nitrocellulose chromatography strip to separate the nitrocellulose chromatography strip. 79. The method according to item 78 of the application, wherein the particles are silica particles. (Please read the note on the back before filling in this page) Order-Printed by the Central Standards Bureau of the Ministry of Economic Affairs, Printed by the Consumers Cooperatives -55- 'Paper Free to Use in China and China (CNS) Α4 Specification (2 〖0 × 297 公公%)