Patent Description:
Testing of biological substances for testing the presence or amount of a substance in the body is important for knowing a health condition and determining a treatment method. Further, testing of a biological substance requires performing many kinds of tests in the present age where living environments are diversified, and thus there are needs of achieving higher speed and higher sensitivity of such testing. For example, in the treatment of allergic diseases, it is important to first understand the allergic diseases that the patient is suffering from. This is because there are various causes of allergies in recent years, and it is necessary to identify the cause in order to receive proper treatment such as one using a proper drug.

Various methods are known as such an allergy test method, and for example, as described in Patent Literature <NUM>, a method for quantifying the IgE antibody against a specific allergen in a blood sample collected from a subject by solid phase sandwich immunoassay is generally used. In this method, for example, a solid-phase carrier such as a glass filter on which a ligand-capturing antibody is adsorbed, and a protein adsorption site other than the ligand-capturing antibody adsorption site is sealed with a blocking agent such as casein is prepared, and on one hand, a ligand to which a specific allergen such as mite or pollen is bound is prepared, and this is mixed with a blood sample to form a complex between the specific allergen bound to a ligand and an IgE antibody against the specific allergen in the blood sample. Then, the mixed solution containing this complex is added to the above-described solid-phase carrier having a ligand-capturing antibody adsorbed thereon, to bind a part of one ligand in the complex to the ligand-capturing antibody, and then an anti-IgE antibody labeled with an enzyme or the like is added, and the part of the IgE antibody in the complex is bound to the labeled anti-IgE antibody. Next, excessive labeled anti-IgE antibody that has not bound to the complex is removed, and a coloration reaction depending on the type of label is performed to detect the labeled anti-IgE antibody bound to the IgE antibody. The obtained detection result is compared with a calibration curve prepared in advance using a standard IgE antibody to quantify the IgE antibody with respect to the specific allergen in the blood sample.

To perform the above described test, there is known a testing method by use of a biological reaction substrate in which one specific allergen is bound to a porous filter of the one biological reaction substrate, and an apparatus therefor. Moreover, as the biological reaction substrate, it is possible to use a reaction container for immunological measurement, which uses a glass fiber having an appropriate physical strength in the lower part of a porous filter (solid phase carrier), and combines, in the lower part thereof, an absorbing layer composed of cellulose for absorbing the solution which has passed through the solid phase carrier (see Patent Literature <NUM>).

Similarly, as described in Patent Literature <NUM>, a biochip analysis method capable of automating the reaction detection process between specimens and antigens and rapidly obtaining measurement results after the specimen is collected using a biochip in which antigens of various allergens are mounted as independent spots, that is, spaced spots, the specimen and the antigen are collected is disclosed.

Similarly, as described in Patent Literature <NUM>, a method of removing a cleaning solution and the like without using a suction nozzle while using a biochip on which antigens of various allergens are mounted as independent spots, that is, spaced spots, is disclosed.

Further, conventionally, various types of analyzers have been known as the analyzer for analyzing the reaction between a specimen such as blood and a reagent, and for example, an analyzer as shown in Patent Literature <NUM> is known. The analyzer described in Patent Literature <NUM> includes: one or more test cartridges each including at least a specimen cell storing a specimen, a reagent cell storing a reagent, and a reaction cell in which the specimen and the reagent are caused to react, and having a form in which each cell is arranged linearly; an apparatus housing having a space portion inside for a predetermined set stage and a test stage adjacent to the set stage; a cartridge holding device provided on the set stage and having a cartridge receiving portion for holding the one or more test cartridges; a cartridge conveying device provided in the test stage and for carrying-in the test cartridge held by the cartridge holding device linearly into the test stage, and carrying-out the test cartridge along a longitudinal direction along the arrangement direction of each cell of carried-in test cartridges in the test stage linearly, while carrying-out the test cartridge after test from the test stage to the set stage linearly, thereby returning it to a cartridge receiving portion of the cartridge holding device; a specimen reagent dispensing device provided corresponding to a dispensing position preset in a part of a conveying path of the test cartridge in the test stage, and for dispensing a specimen and a reagent of the concerned test cartridge to a reaction cell for the test cartridge in a state in which a target cell for dispensing of the test cartridge in the test stage, which has been carried-in by the cartridge conveying device is conveyed to the dispensing position of being conveyed and arranged at a dispensing position; a measuring device provided corresponding to a measurement position preset in a part of the conveyance path of the test cartridge in the test stage, and for measuring the reaction between a specimen and a reagent in a reaction cell, which are dispensed by the specimen reagent dispensing device, in a state in which the reaction cell of the test cartridge in the test stage, which has been conveyed by the cartridge conveying device, is conveyed to and disposed at the measurement position; a constant temperature bath which is heated by a heating source and keeps the liquid temperature in at least the reaction cell of the test cartridge in the test stage, which has been conveyed by the cartridge conveying device, at a preset constant environmental temperature; and a constant-temperature bath control device having a temperature detector capable of detecting internal environmental temperature of the test stage, and for controlling a set temperature of the heating source based on the internal environmental temperature detected by the temperature detector such that when the internal environmental temperature is lower than a predetermined threshold value, the set temperature of the heating source of the constant temperature bath is raised higher than when the internal environmental temperature is equal to or higher than the threshold value.

According to such an analyzer, since there is provided a constant temperature bath for keeping the liquid temperature in the reaction cell of the test cartridge at a preset constant environmental temperature after a specimen and a reagent are dispensed into the reaction cell of the test cartridge, it is possible to effectively prevent deterioration in the measurement accuracy associated with changes in the test cartridge and the environmental temperature.

However, as described in Patent Literature <NUM>, in a test method and an apparatus by use of a reaction container, although measurement can be performed in a relatively short period of time, such as <NUM> minutes for measuring one specimen, and about <NUM> minutes for measuring <NUM> specimens, it is necessary to prepare a specimen (such as blood) for each specific allergen so that a large amount of specimen is required. Therefore, in cases of infants, it may have been difficult to secure specimens necessary for measurement.

Moreover, the art described in Patent Literature <NUM> requires a suction nozzle for sucking each liquid supplied from each nozzle such as a cleaning nozzle, an antibody nozzle, and a reagent nozzle so that it takes time until completing suction of each liquid, and there is a risk that extraneous matter adhered to the suction nozzle adheres to the biochip, causing contamination.

Moreover, in the art described in Patent Literature <NUM>, while a labeled anti-IgE antibody is detected by performing a coloration reaction after causing an IgE antibody against a specific allergen, which specifically binds to antigens of various allergens immobilized on the second base portion, to bind to an anti-IgE antibody labeled with an enzyme or the like (labeled anti-IgE antibody), since the first base portion and the cover member are laminated on the upper part of the second base portion, it cannot be an effective method for detecting a reaction with a weak degree of coloration and detection at high sensitivity may not be possible.

As described above, in conventional allergy tests, higher test sensitivity and shorter testing time are desired, and since a large amount of blood or the like to be used as a specimen is required, reduction of the amount of specimen is also desired. Moreover, in an allergy test, it has been an issue to reduce the number of steps in a reaction operation to save the labor of the test staff, and, because the blood of the patient is handled as a specimen, it is required to reduce the risk of infection by a disease from which the patient is suffering.

Further, in the analyzer described in Patent Literature <NUM>, while after the specimen or the reagent is dispensed into the reaction cell, a predetermined amount of the specimen or the reagent is sucked and held, and after the test cartridge having the reaction cell is conveyed to the measurement position, the predetermined specimen and the reagent are ejected into the reaction cell to be measured to perform the test, such a method of sucking the specimen or the reagent has a problem that the apparatus becomes large sized, and the manufacturing cost of the apparatus also increases.

Patent Literature <NUM> discloses a device comprising a cassette having a hollow test chamber, a test strip disposed within the test chamber for receiving the test sample, and a temperature control member. The cassette has at least one aperture extending from an exterior of the cassette to the hollow test chamber. The test strip includes a reagent adapted to react with the at least one analyte to produce a reaction indicative of the presence of the analyte. The temperature control member is adapted to extend through the at least one aperture in the cassette and into the test chamber for controlling the temperature of the test chamber.

Further, although a method is known in which, to reduce the testing time, a specimen and a reagent are dispensed into a reaction cell, thereafter stirring the reaction cell, and then excessive specimen and reagent are drained, providing such stirring and drainage mechanisms causes problems such as increase in size of the analyzer and increase in manufacturing cost.

Accordingly, the present invention has been made to solve such problems and has its object to provide a biochemical reaction substrate which can achieve higher test sensitivity and shorter testing time in an allergy test, which can also reduce a required amount of blood or the like to be used as a specimen and decrease the number of test steps, thereby facilitating performance of the test, and which is to be used in an allergy test in which an infection risk of the test staff is reduced.

Further, the present invention has been made to solve such problems and has its object to provide an analyzer which enables downsizing of the analyzer and suppression of production cost thereof even when mechanisms of stirring and drainage of the reaction cell are added to reduce the testing time.

The present invention provides a biochemical reaction substrate according to claim <NUM> and an analyzer according to claim <NUM>.

According to the present invention, since the reaction plate has a reaction area in which a specific binding substance (for example, an antigen (allergen)) that specifically reacts with the substance to be tested in the specimen is immobilized and a flow passage that connects the absorber and the reaction area, and the cover has an injection hole for injecting a specimen or the like into the reaction plate, the number of testing steps can be reduced (for example, since the cleaning solution is drained, the number of steps to absorb the cleaning solution from the reaction area is omitted) and the test can be easily performed. Moreover, since an allergy test can be performed without the test staff directly contacting the blood or the like to be used as the specimen, it is possible to reduce the risk of infection of test staff.

Moreover, since reaction between many types of allergens and antigens can be detected in the reaction area, it is possible to reduce a required amount of blood or the like to be used as a specimen.

Furthermore, according to the present invention, since the installation area, the dispensing area, the stirring area, the drainage area, and the detection area are arranged on the same straight line, it is possible to achieve downsizing of the analyzer even when the testing time is reduced by performing stirring and drainage of the chip device into which the specimen and the reagent are dispensed.

Hereinafter, a biochemical reaction substrate and an analyzer according to the present invention will be described with reference to the drawings. It should be noted that the following embodiments do not limit the invention according to each claim, and all the combinations of the features described in the embodiments are not necessarily essential to the solution of the invention.

<FIG> is a perspective view of a biochemical reaction substrate according to an embodiment of the present invention; <FIG> is an exploded view of a biochemical reaction substrate according to an embodiment of the present invention; <FIG> is a perspective view of a reaction plate to be used for a biochemical reaction substrate according to an embodiment of the present invention; <FIG> is a top view of a storage container to be used for a biochemical reaction substrate according to an embodiment of the present invention; <FIG> is a bottom view of a cover to be used for a biochemical reaction substrate according to an embodiment of the present invention; <FIG> is a top view to illustrate an arrangement state of antigen (allergen) in a reaction area of the reaction plate; <FIG> is a bottom view to illustrate a variant of the cover to be used for the biochemical reaction substrate according to an embodiment of the present invention; <FIG> is a top view to illustrate a variant of the reaction plate to be used for the biochemical reaction substrate according to an embodiment of the present invention; <FIG> is an A-A cross-sectional view in <FIG>; <FIG> is a B-B cross-sectional view in <FIG>; <FIG> is a top view to illustrate another arrangement state of antigen (allergen) in a reaction area of the reaction plate; <FIG> is a perspective view of an analyzer according to an embodiment of the present invention; <FIG> is a diagram to illustrate an internal structure of the analyzer according to an embodiment of the present invention; <FIG> is a perspective view to illustrate an internal structure of the analyzer according to an embodiment of the present invention; <FIG> is a perspective view to illustrate an installation area of the analyzer according to an embodiment of the present invention; <FIG> is a perspective view to illustrate a barcode reading area of the analyzer according to an embodiment of the present invention; <FIG> is a perspective view to illustrate a dispensing area of the analyzer according to an embodiment of the present invention; <FIG> is a perspective view to illustrate a stirring area of the analyzer according to an embodiment of the present invention; <FIG> is a perspective view to illustrate a drainage area of the analyzer according to an embodiment of the present invention; <FIG> is a perspective view to illustrate a tilting mechanism of the analyzer according to an embodiment of the present invention; <FIG> is a perspective view to illustrate a tilting mechanism of the analyzer according to an embodiment of the present invention, showing a state in which a tilting cam is in abutment with a stopper; <FIG> is a perspective view to illustrate a tilting mechanism of the analyzer according to an embodiment of the present invention, showing a state in which a substrate holding portion is tilted; <FIG> is a perspective view to illustrate a detection area of the analyzer according to an embodiment of the present invention; <FIG> is a diagram to illustrate detection results of the analyzer according to an embodiment of the present invention, illustrating the arrangement of antigens in the reaction area; <FIG> is a diagram to illustrate detection results of the analyzer according to an embodiment of the present invention, showing a state of being exposed for <NUM> seconds; <FIG> is a diagram to illustrate detection results of the analyzer according to an embodiment of the present invention, showing a state of being exposed for <NUM> seconds; and <FIG> is a diagram to illustrate detection results of the analyzer according to an embodiment of the present invention, showing a state of being exposed for <NUM> seconds.

As shown in <FIG> and <FIG>, a biochemical reaction substrate <NUM> according to the present embodiment can store a reaction plate <NUM> therein, and has a cover <NUM> and a storage container <NUM>. A substantially circular injection hole <NUM> is formed in the cover <NUM>, and the injection hole <NUM> is configured to be disposed at a position corresponding to a reaction area <NUM> of the reaction plate <NUM> in a state where the reaction plate <NUM> is stored. Moreover, a concave heated portion <NUM> is formed on the bottom of the storage container <NUM>, and is configured such that a heater of a testing device to be described later can abut against and heat the reaction area <NUM>.

As shown in <FIG>, an absorber storing portion <NUM> which stores a reaction plate storing portion <NUM> for storing the reaction plate <NUM>, and an absorber storing portion <NUM> for storing an absorber <NUM> made of a porous material such as sponge capable of absorbing a sufficient amount of liquid is formed in the storage container <NUM>. Note that in a state where the reaction plate <NUM> and the absorber <NUM> are stored in the storage container <NUM>, the distal end of the flow passage <NUM> formed in the reaction plate <NUM> is disposed so as to abut against the absorber <NUM>.

As shown in <FIG>, the reaction plate <NUM> includes: a planar base portion <NUM> that can be fitted into the reaction plate storing portion <NUM> formed in the storage container <NUM> without any difficulty; a flow-out prevention wall <NUM> standing upright from the base portion <NUM>; and a flow passage <NUM>. The flow-out prevention wall <NUM> is a substantially annular wall, and the inside of the flow-out prevention wall <NUM> is defined as a reaction area <NUM>.

Moreover, at a position facing the absorber <NUM> from the reaction area <NUM>, a flow passage <NUM> is formed so as to extend from the outer peripheral edge of the flow-out prevention wall <NUM> and such that the distance between a pair of side walls is gradually decreased. The flow passage <NUM> is formed to drain the specimen or the like dispensed to the reaction area <NUM> and cause the absorber <NUM> to absorb it, and the flow passage <NUM> has a slope <NUM> formed in such a way to climb up from the reaction area <NUM> such that the specimen or the like can be discharged from the reaction area <NUM> toward the absorber <NUM> without waste by tilting the biochemical reaction substrate <NUM>. The slope <NUM> is preferably formed to be inclined from the base portion <NUM> by about <NUM>° to <NUM>°, a more preferable angle of inclination is <NUM>° to <NUM>°, a further preferable angle is <NUM>° to <NUM>°, and a suitable angle is <NUM>°. The larger the angle of inclination of the flow passage, the more the leakage can be prevented, but a situation in which discharging is difficult becomes likely to occur. Therefore, by adopting a preferable angle, it is possible to achieve the object of the present invention. The proximal end of the flow passage <NUM> on the reaction area <NUM> side is configured to be as wide as possible to smoothly guide the specimen or the like on the reaction area <NUM> to the distal end on the absorber <NUM> side, and the distal end side of the flow passage <NUM> is formed such that the slope <NUM> abuts against the absorber <NUM> at an acute angle.

As described above, in the reaction plate <NUM> used in the biochemical reaction substrate <NUM> according to the present embodiment, since the flow-out prevention wall <NUM> is formed so as to surround the reaction area <NUM>, and the slope <NUM> is provided in the flow passage <NUM>, it becomes possible, in the allergy test, to prevent the specimen or the like from flowing out from the reaction area <NUM> even when the biochemical reaction substrate <NUM> is stirred, and to easily discharge the specimen or the like from the flow passage <NUM> when the specimen or the like is drained after stirring. In addition, non-specific adsorption can be suppressed by applying a blocking agent to the entire reaction area in advance. Further, by defining the inside of the flow-out prevention wall <NUM> as the reaction area, it is possible to more easily discharge the specimen or the like as a side effect of applying the blocking agent.

Further, as the blocking agent, a synthetic polymer not originating from animals and plants, such as polyethylene glycol, can be used in general technique, and it can be appropriately selected and used according to the properties of the material of the reaction plate <NUM>, a target substance such as an antigen, a specimen such as blood, and a reagent such as a cleaning solution.

As shown in <FIG>, the storage container <NUM> may have a reaction plate storing portion <NUM> and an absorber storing portion <NUM> formed therein. Further, the storage container <NUM> is a bottomed box-shaped member having an open end on the upper side, and when a rib <NUM> is formed on the inner wall of the absorber storing portion <NUM>, it becomes possible to hold the absorber <NUM> more reliably. Further, it is preferable that the reaction plate storing portion <NUM> has an opening portion <NUM> formed at a position corresponding to the reaction area <NUM> when the reaction plate <NUM> is placed thereon. Further, the storage container <NUM> can directly heat the reaction area <NUM> from outside of the biochemical reaction substrate <NUM> through the opening portion <NUM>.

Further, the reaction plate storing portion <NUM> and the absorber storing portion <NUM> are made in communication with each other through the storage portion groove <NUM>, and even if the specimen or the like leaks out of the flow-out prevention wall <NUM> due to stirring or the like, configured is made such that the specimen or the like can be guided from the reaction plate storing portion <NUM> to the absorber storing portion <NUM>.

As shown in <FIG>, the cover <NUM>, which is a member that closes the open end of the storage container <NUM> described above and constitutes an outer shell of the biochemical reaction substrate <NUM>, has a side wall portion 36a that hangs down and extends from the outer peripheral edge of the top side <NUM>. Further, an inner wall portion <NUM> is formed so at to hang down to the top side <NUM> at a position corresponding to the flow-out prevention wall <NUM> of the reaction plate <NUM>, and when the reaction plate <NUM> is stored in the biochemical reaction substrate <NUM>, the inner wall portion <NUM> is in abutment with the flow-out prevention wall <NUM>.

Further, a defining wall <NUM> extending downward from the top side <NUM> is formed at a position corresponding to a continuous portion between the reaction plate storing portion <NUM> and the absorber storing portion <NUM> of the storage container <NUM>. The defining wall <NUM> separates the reaction area <NUM> of the reaction plate <NUM> from the absorber <NUM>. Note that the inner wall portion <NUM> and the defining wall <NUM> are formed discontinuously with each other via a missing portion <NUM>. If the inner wall portion <NUM> is extended to a part of the missing portion <NUM>, a minute gap is generated between the outer periphery of the flow passage <NUM> and the inner wall portion <NUM>, and there is a risk of leakage to the outside seen from the reaction area of the flow-out prevention wall <NUM> by a capillary phenomenon due to the presence of the gap, or there is a risk that the specimen or the like absorbed by the absorber <NUM> may flow back to the reaction area <NUM> side; therefore, the missing portion <NUM> is provided to prevent this.

Further, the inner wall portion <NUM> may have a missing portion for adjustment <NUM> formed at an end portion in the longitudinal direction of the cover <NUM>. Forming a part of the inner wall portion <NUM> as an inner wall of the side wall portion 36a enables space saving and cost reduction of material cost and the like.

In addition, the side wall portion of the outer periphery of the cover <NUM> is configured to have a rugged-shaped slip prevention device <NUM> so that the examiner can surely grasp the biochemical reaction substrate <NUM> by the slip prevention device <NUM>. Further, a rib <NUM> may be formed on the inner wall of the side wall portion 36a corresponding to the absorber storing portion <NUM> as in the absorber storing portion <NUM>.

Note that as shown in <FIG>, a plurality of sets (for example, <NUM> spots/one set) of antigens <NUM> are arranged in a predetermined number of sets (for example, <NUM> spots/<NUM> sets) in the reaction area <NUM> of the reaction plate <NUM>. Arranging in this way makes it possible to increase the amount of the antigen <NUM> placed on the reaction area <NUM>, and to detect a plurality of allergic reactions by one test. This can be achieved by making the type of the antigen the same for each set, and setting a distance between the sets to eliminate the influence during measurement. The distance between the sets is preferably <NUM> or more, more preferably <NUM> to <NUM>, further preferably <NUM> to <NUM>, and suitably about <NUM>. This makes it possible to perform, for example, the test of IgE antibody in a blood sample against different types of antigens (allergens) all at once. Therefore, this test can reduce the amount of specimen, and reduce the time and the number of steps.

Note that as shown in <FIG>, the defining wall portion 37a, the inner wall portion <NUM> and the side wall portion 36a may be formed discontinuously, by forming a defining wall portion 37a in a substantially L shape such that the inner wall portion <NUM> and the defining wall <NUM> are continuous like the shape of the missing portion of the cover 30a, and forming the inner wall missing portion 33a in the inner wall portion <NUM> and the defining wall missing portion 33b in the defining wall, respectively. Since there is a risk that leakage occurs to the outside as seen from the reaction area of the flow-out prevention wall <NUM> due to the capillary phenomenon, or the specimen or the like absorbed by the absorber <NUM> flows back to the reaction area <NUM> side, this is prevented by forming the inner wall missing portion 33a and the defining wall missing portion 33b in this manner.

Further, as shown in <FIG>, it is preferable to form a slope 15a formed in the flow passage portion 12a of the reaction plate 10a such that the specimen or the like can be discharged more easily. As shown in <FIG>, the slope 15a is smoothly formed in a continuous portion with the reaction area <NUM> such that the specimen or the like can be discharged without waste, thus preventing the specimen or the like from staying in the continuous portion between the reaction area <NUM> and the slope 15a. Further, as shown in <FIG>, the cross-sectional shape of the slope 15a itself is also configured to have a smooth curve, thereby preventing the specimen and the like from staying on the slope 15a.

Further, it is preferable that the antigens <NUM> arranged in the reaction area <NUM> are arranged such that they are concentrated in the middle of the reaction plate <NUM> as shown in <FIG>. By adjusting the arrangement position of the antigens <NUM> in this way, it is possible to reduce the time for converting the antigens <NUM> into a solid phase on the reaction plate <NUM>.

Next, with reference to <FIG>, the operation of an analyzer for performing an allergy test using the biochemical reaction substrate <NUM> according to the present embodiment will be described.

As shown in <FIG>, an analyzer <NUM> according to the present embodiment includes a housing <NUM> having an operating panel <NUM>, and a loading section <NUM> for installing a reagent cartridge <NUM> to be described later and the biochemical reaction substrate <NUM>. The loading section <NUM> can be opened and closed by an installation door (not shown).

As shown in <FIG>, the inside of the analyzer <NUM> is defined into the installation area <NUM>, a barcode reading area <NUM>, a dispensing area <NUM>, a stirring area <NUM>, a detection area <NUM>, and a drainage area <NUM> which are arranged on the same straight line. Further, a moving table <NUM> guided by a guide device <NUM> arranged on the same straight line is movably mounted in a range from the installation area <NUM> to the drainage area <NUM>. Further, adjacent areas may be configured to overlap with each other in such a way as that in the stirring area <NUM> and the dispensing area <NUM>, an overlapping portion may occur in these areas.

As shown in <FIG>, the moving table <NUM> includes a substrate holding portion 116a on which the reagent cartridge <NUM> is placed and also the biochemical reaction substrate <NUM> is placed. Further, a driving section <NUM> extending substantially in parallel with the guide device <NUM> is attached thereto, and the driving section <NUM> is wound around with a ring-shaped band, which is rotated by a drive source such as a motor (not shown), and is configured to be able to move the moving table <NUM> along the guide device <NUM> by transmitting the driving force of the band to the moving table <NUM>.

Next, each area of the installation area <NUM>, the barcode reading area <NUM>, the dispensing area <NUM>, the stirring area <NUM>, the detection area <NUM>, and the drainage area <NUM> will be described.

As shown in <FIG> and <FIG>, the installation area <NUM> is located at one end side (left end in <FIG>) of the guide device <NUM>. Further, as shown in <FIG>, configuration is made such that when the moving table <NUM> is located in the installation area <NUM>, the reagent cartridge <NUM> and the biochemical reaction substrate <NUM> can be installed from the outside of the housing <NUM> to the moving table <NUM> via the loading section <NUM>. The reagent cartridge <NUM> is configured to be able to store a specimen <NUM>, a reaction reagent 112a, a cleaning solution 112b, and a chip <NUM>. Note that in the description of the present application, the reaction reagent 112a and the cleaning solution 112b are collectively referred to as a "reagent <NUM>" hereinafter. The biochemical reaction substrate <NUM> includes an injection hole <NUM> opening toward the reaction area <NUM> for dispensing the specimen <NUM> and the reagent <NUM> as described above, and the absorber storing portion <NUM> for draining the excessive specimen <NUM> and reagent <NUM> after stirring the biochemical reaction substrate <NUM> after dispensing the specimen <NUM> and the reagent <NUM>. An absorber not shown is stored in the absorber storing portion <NUM>, and excessive specimen <NUM> and reagent <NUM> are held by the absorber so as not to flow to the outside. Note that the reaction reagent is a reagent for a reaction necessary for detection, and refers to, for example, a labeled antibody and a luminescent substrate. The reaction reagent may be any reagent necessary for the reaction and is not particularly limited to these specific examples. Moreover, the positions for disposing the reaction reagent 112a and the cleaning solution 112b may be appropriately determined, and are not limited to the positions shown in <FIG>.

Further, a heating section <NUM> is attached to the substrate holding portion 116a, on which the biochemical reaction substrate <NUM> is installed, so as to correspond to the reaction area <NUM> of the biochemical reaction substrate <NUM> so that attempt is made to reduce the reaction time by heating the reaction area to a body temperature (for example, about <NUM>) with the heating section <NUM>.

Next, as shown in <FIG>, the moving table <NUM> is moved to the barcode reading area <NUM> along the guide device <NUM>. A barcode reader <NUM> is attached to the barcode reading area <NUM> so that the analyzer <NUM> reads reagent information such as a reagent, reagent expiration date and lot, calibration curve knowledge information, etc. by reading the barcodes respectively printed or affixed on the side walls of the reagent cartridge <NUM> and the biochemical reaction substrate <NUM> with the barcode reader <NUM>.

As shown in <FIG>, the dispensing area <NUM> includes a dispensing nozzle <NUM> that is attached so as to be movable in a direction substantially perpendicular to the guide device <NUM>. The dispensing nozzle <NUM> is a member that sucks and ejects the specimen <NUM> and the reagent <NUM> stored in the reagent cartridge <NUM> and dispenses the specimen <NUM> and the reagent <NUM> to the biochemical reaction substrate <NUM>. In this dispensing, first, in order to fit a chip <NUM> stored in the reagent cartridge <NUM> to the distal end of the dispensing nozzle <NUM>, the moving table <NUM> is moved such that the position of the chip <NUM> stored in the reagent cartridge <NUM> is located directly below the dispensing nozzle <NUM>, and thereafter, the dispensing nozzle <NUM> is lowered to fit the chip <NUM> to the distal end of the dispensing nozzle <NUM>.

Next, in order to suck the specimen <NUM> and the reagent <NUM> or the like of the moving table <NUM> from the reagent cartridge <NUM>, the moving table <NUM> is moved such that the position where the specimen <NUM> or the reagent <NUM> or the like of the moving table <NUM> is located directly below the dispensing nozzle <NUM>, and the specimen <NUM> or the reagent <NUM> is sucked respectively. Similarly, after the specimen <NUM> or the reagent <NUM> is sucked, the moving table <NUM> is moved such that the injection hole <NUM> of the biochemical reaction substrate <NUM> is located directly below the dispensing nozzle <NUM>, and the sucked specimen <NUM> and reagent <NUM> or the like is dispensed into the reaction area <NUM> through the injection hole <NUM> of the biochemical reaction substrate <NUM>.

The used chip <NUM> is separated from the dispensing nozzle <NUM> and returned to a predetermined position of the reagent cartridge <NUM>. At this time, since it is made unnecessary to provide a position for collecting the used chip <NUM> by returning the used chip <NUM> to the original position, the size of the reagent cartridge <NUM> can be reduced and the used chip <NUM> can be reliably collected.

The stirring area <NUM> is located between the dispensing area <NUM> and the barcode reading area <NUM>. As shown in <FIG>, the moving table <NUM> is moved reciprocally in the stirring area <NUM> along the guide device <NUM> to appropriately stir the dispensed specimen <NUM> and reagent <NUM>. At this time, the dispensing nozzle <NUM> and a detection camera <NUM> to be described later are configured to retract upward so as not to interfere with the moving table <NUM> during stirring. Further, while the stirring may be performed at any speed as long as the specimen <NUM> and the reagent <NUM> can be stirred reliably, for example, the stirring is preferably performed at a speed at which the moving table <NUM> can be moved about <NUM> to <NUM> times per minute with an amplitude of <NUM>; more preferably, the moving table is stirred at a stirring speed of about <NUM> to <NUM> times a minute; furthermore preferably, the moving table is stirred at a stirring speed of about <NUM> to <NUM> times a minute; and optimally, the moving table is stirred at a stirring speed of about <NUM> times a minute.

Next, as shown in <FIG>, the moving table <NUM> is moved to the drainage area <NUM>, and drainage is performed by causing excessive specimen <NUM> and reagent <NUM> to be absorbed by the absorber <NUM> stored in the absorber storing portion <NUM> of the biochemical reaction substrate <NUM>. The drainage area <NUM> is disposed at the other end portion of the guide device <NUM>, and a stopper <NUM> is attached to the end portion of the guide device <NUM> as shown in <FIG>. In addition, the moving table <NUM> includes a tilting mechanism by which the substrate holding portion 116a is tilted at a predetermined angle when the moving table <NUM> reaches the drainage area <NUM>. Such tilting of the substrate holding portion 116a by this tilting mechanism allows the specimen <NUM> and the reagent <NUM> to be smoothly drained from the reaction area <NUM> of the biochemical reaction substrate <NUM> to the absorber storing portion <NUM>. Note that while the tilting angle by the tilting mechanism may be formed to any extent as long as smooth drainage can be performed and, for example, the tilting angle may be usable in a range of <NUM>° from the same angle as that of the slope <NUM> formed between the reaction area <NUM> in the biochemical reaction substrate <NUM> and the absorber storing portion <NUM>, the tilting mechanism is preferably configured to be tilted at <NUM>° or more; more preferably configured to be tilted at <NUM>° to <NUM>°; further preferably, configured to be tilted at <NUM>° to <NUM>°; and optimally, configured to be tilted at <NUM>°.

Next, the operation of the tilting mechanism will be described with reference to <FIG>. A tilting cam <NUM> is attached to the substrate holding portion 116a, and as shown in <FIG>, when the moving table <NUM> moves to the drainage area <NUM>, the tilting cam <NUM> comes into abutment with the stopper <NUM> attached to the end portion of the guide device <NUM>. Then, as shown in <FIG>, when the moving table <NUM> is further moved to the stopper <NUM> side, the tilting cam <NUM> pivots about the pivot shaft <NUM>, and the roller <NUM> attached to the distal end of the tilting cam <NUM> moves in such a way as to be lifted up. This movement of the roller <NUM> causes the substrate holding portion 116a to be lifted up with the rotary shaft <NUM> as a fulcrum as shown in <FIG>. Thus, since the roller <NUM> is attached to the distal end of the tilting cam <NUM>, it becomes possible to smoothly tilt the substrate holding portion 116a. Moreover, when the drainage is finished, while the moving table <NUM> is moved to a detection area <NUM> to be described later, since at this time, the abutment between the stopper <NUM> and the tilting cam <NUM> is released, the tilting of the substrate holding portion 116a is also released at the same time, and thus, the upper surface of the moving table <NUM> and the substrate holding portion 116a return to a substantially horizontal state.

Next, the moving table <NUM> is moved to the detection area <NUM> as shown in <FIG>. The detection area <NUM> includes a detection camera <NUM>, a moving mechanism <NUM> that moves the detection camera <NUM> up and down in a direction substantially perpendicular to the guide device <NUM>, and a first cylinder <NUM> and a second cylinder <NUM> that move up and down together with the detection camera <NUM>. A light shielding portion <NUM> is attached to the distal end of the second cylinder <NUM> and can cover the reaction area <NUM> so as to shield the injection hole <NUM> of the biochemical reaction substrate <NUM> from light when the detection camera <NUM> is moved to the lower end by the moving mechanism <NUM>. Further, the first cylinder <NUM> is attached with the detection camera <NUM> at the upper end, and is fitted to the second cylinder <NUM>. The fitting portion between the first cylinder <NUM> and the second cylinder <NUM> is assembled so as to be shielded from light via an O-ring (not shown) and the like, and held together by the elastic force of the O-ring. Note that the first cylinder <NUM> and the second cylinder <NUM> include an adjustment mechanism that allows them to be movable relative to each other to adjust the distance for focusing between the reaction area <NUM> of the biochemical reaction substrate <NUM> and the detection camera <NUM> when the detection camera <NUM> is lowered, and this adjustment mechanism is configured with the O-ring described above interposed therebetween. As described above, since the adjustment mechanism is configured such that the first cylinder <NUM> and the second cylinder <NUM> are attached to each other via the O-ring, the second cylinder <NUM> slides up and down on the contact surface of the O-ring, and thus can move up and down with respect to the first cylinder <NUM>.

In this manner, in the detection area <NUM>, after the drainage of the specimen or the like is finished, as shown in <FIG>, the detection camera <NUM> is lowered, and the light shielding portion <NUM> provided at the distal end thereof is brought into close contact with the biochemical reaction substrate <NUM> to perform light shielding such that no outside light enters from the outside of the biochemical reaction substrate <NUM> and the analyzer <NUM>. In this state, it is possible to detect the presence or absence of an allergic reaction by detecting the presence or absence of light emission of the labeled antibody after an elapse of a predetermined reaction time. Since a luminescent substrate which causes an labeled anti-IgE antibody to emit light and to be visualized has been dispensed as a reagent (reaction reagent), the light emission of the labeled antibody is performed by subjecting the luminescent substrate to biochemical reaction in the reaction area under a predetermined environmental condition for a predetermined time period, and the intensity of the emitted light is measured by the detection camera <NUM>.

In this way, by configuring the dispensing nozzle <NUM> and the detection camera <NUM> to be able to move up and down together with the second cylinder <NUM>, the first cylinder <NUM>, and the light shielding portion <NUM>, and by making the position of the biochemical reaction substrate <NUM> movable, it becomes possible to prevent the cover and the moving mechanism from becoming larger than a mechanism that moves the light shielding portion and the cover while the detection camera <NUM> is fixed, thereby contributing to the overall downsizing of the analyzer <NUM>. Properly speaking, although it is desirable that the distance between the biochemical reaction substrate <NUM>, in which a detection target is present, and the detection camera <NUM> is fixed to a certain distance to perform measurement accurately, when such a fixed scheme is adopted, it is necessary to move up and down the hood that constitutes a dark room structure so as to cover the detection camera and the biochemical reaction substrate <NUM> to shield light during measurement, resulting in upsizing of the hood. Further it is also necessary for the hood to shield light by covering the entire biochemical reaction substrate <NUM> and, to make such light shielding complete, a structure for causing the hood to come into close contact with a base on which the biochemical reaction substrate <NUM> is placed such as by attaching an elastic body to the bottom of the hood (non-movable) becomes necessary, and thus the analyzer <NUM> is difficult to be downsized. In contrast to this, the analyzer <NUM> according to the present embodiment moves the detection camera <NUM> itself up and down, and thereby suppresses the space of the dark room structure, enabling downsizing of the moving mechanism. Furthermore, since by arranging the second cylinder <NUM> inside the first cylinder <NUM>, and attaching the light shielding portion <NUM> at the distal end thereof, thus bringing the light shielding portion <NUM> into close contact with biochemical reaction substrate <NUM>, it becomes possible to shield the biochemical reaction substrate <NUM> from light, such light shielding becomes possible with a space a little larger than or substantially equivalent to cover the entire top plate area of the biochemical reaction substrate <NUM>, or with a smaller space sufficient to cover the injection hole <NUM>, and thus the moving mechanism can be downsized. Further, while moving mechanisms in various directions are required in the analyzer, such as for moving the dispensing nozzle <NUM>, tilting the substrate holding portion 116a, and moving the barcode reader <NUM> and the like in accordance with the biochemical reaction substrate <NUM>, providing a moving mechanism corresponding to each moving direction leads to an increase in the size of the analyzer. In contrast to this, the analyzer <NUM> according to the present embodiment achieves downsizing of the analyzer <NUM> by arranging the installation area <NUM>, the dispensing area <NUM>, the stirring area <NUM>, the drainage area <NUM>, and the detection area <NUM> in the same straight line, and integrating the moving mechanism of the biochemical reaction substrate <NUM> that moves between each areas into one axis.

According to such an analyzer, it is possible, in an allergy test, to achieve higher test sensitivity and shorter testing time, reduce a required amount of blood or the like needed as the specimen, and decrease the number of test steps, thereby facilitating performance of the test, and it is also possible to reduce the risk of infection of the test staff, and to perform all the steps by moving on only one axis by disposing the installation area, the dispensing area, the stirring area, the drainage area, and the detection area on the same straight line, thus enabling downsizing of the entire apparatus.

Next, detection results of the analyzer <NUM> according to the present embodiment will be described with reference to <FIG>. As shown in <FIG>, in the present example, test was carried out by arranging antigens A (Cockroach), B (Timothy) and C (Salmon) in the reaction area of the biochemical reaction substrate.

As shown in <FIG>, in a state in which <NUM> seconds of exposure had elapsed after stirring, the antigen A and the antigen B were emitting light, and the light emission was confirmed by the detection camera. In addition, regarding the antigen C, strong light emission was not confirmed, and it was confirmed that this specimen contained a minute amount of IgE antibody with respect to the antigen C.

Moreover, it was confirmed that light emission due to remaining drainage around the reaction area was suppressed. Note that, although some light emission was confirmed around the reaction area, it was also confirmed that the light emission was in a range that did not affect the analysis, and did not affect the detection performance of the analyzer.

Note that regarding the antigen B, the light emission was strong when the exposure time was <NUM> seconds. On the other hand, as shown in <FIG>, the analyzer <NUM> according to the present embodiment performed photographing at intervals of exposure time of <NUM> seconds, <NUM> seconds, and <NUM> seconds. From the result, while the light emission of antigen B strongly affected the detection performance after elapse of <NUM> seconds, when the exposure time was <NUM> seconds, the light emission of the antigen B was in a state of appropriate intensity as shown in <FIG>, the detection performance for the antigen B was ensured by using a detection result with an exposure time of <NUM> seconds. Furthermore, in the analyzer <NUM> in the present embodiment, although a state of exposure time of <NUM> seconds was also photographed as shown in <FIG>, for the antigens A to C of this time, the light emission was feeble in <NUM> seconds. However, for antigens with strong light emission, the detection performance of the analyzer <NUM> can be further improved by using a detection result with an exposure time of <NUM> seconds.

Note that although the biochemical reaction substrate <NUM> according to the above-described embodiment has been described on cases where the injection hole <NUM> and the reaction area <NUM> are formed into a circle, these shapes are not limited to a circle and can be formed into, for example, an elliptical shape.

Moreover, as the reaction plate <NUM> used for the biochemical reaction substrate <NUM> according to the present embodiment described above, a transparent or colored plate can be used, but by using black, it is possible to measure at higher sensitivity. Moreover, by setting the range of the blocking agent applied to the reaction plate <NUM> to the reaction area <NUM> including the inside of the flow-out prevention wall <NUM> and the slope <NUM>, as well as to the inside of the flow passage <NUM>, it is possible to suppress further non-specific adsorption.

Claim 1:
A biochemical reaction substrate (<NUM>), comprising:
a reaction plate (<NUM>); an absorber (<NUM>); a storage container (<NUM>) having a reaction plate storing portion (<NUM>) for storing the reaction plate (<NUM>), an absorber storing portion (<NUM>) for storing the absorber (<NUM>), and a heated portion (<NUM>); and a cover (<NUM>) assembled to the storage container (<NUM>) so as to cover at least a part of the reaction plate (<NUM>) and the absorber (<NUM>) stored in the storage container (<NUM>), wherein
the reaction plate (<NUM>) includes a reaction area (<NUM>) in which a specific binding substance that specifically reacts with a substance to be tested in a specimen is immobilized, and a flow passage (<NUM>) that connects the absorber (<NUM>) and the reaction area (<NUM>), and wherein
the cover (<NUM>) includes an injection hole (<NUM>) for injecting a specimen or the like into the reaction plate (<NUM>),
wherein the flow passage (<NUM>) has a slope (<NUM>) formed in such a way to climb up from the reaction area (<NUM>).