JP2012103150A - Analysis method and apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To improve performance of an analysis apparatus successively analyzing samples dotted on reaction vessels with the reaction vessels exchanged one by one.SOLUTION: In an analysis method, an analysis apparatus 1 into which reaction vessels 20 may be introduced and from which the reaction vessels 20 may be ejected is used for analysis, and time Ta necessary from dotting of a sample on each reaction vessel to introduction of the reaction vessel and time Tb necessary from the introduction to completion of the analysis are precedently known. After a sample is dotted on one reaction vessel 20, when a request for subsequent analysis using a next reaction vessel 20 to be exchanged with the former reaction vessel 20 is issued, information corresponding to time T=Ta1+Tb1-Tc-Ta2, wherein Ta1 and Tb1 are the time Ta and Tb of the former reaction vessel respectively, Ta2 is the time Ta of the next reaction vessel and Tc is time elapsing from dotting on the former reaction vessel 20 to the issue of the request, is created.

Description

  The present invention relates to an analyzer, and more particularly to an analyzer that analyzes a sample using a reaction vessel in which the sample is spotted on a reagent portion.

  The present invention also relates to an analysis method performed using such an analysis apparatus.

  In recent years, a large number of assay devices have been developed that hold a test substance (sample) that may contain a test substance on a carrier, and that can easily and quickly test this test substance using an assay such as immunological measurement. Various devices for in-vitro diagnostics, toxic substances, and the like are also commercially available. As an example of such a device, one utilizing an immunochromatographic method as shown in Patent Document 1 can be cited. In the case of using a device utilizing the immunochromatography method, the test result can be obtained by holding the sample solution on a carrier and then allowing it to stand for about 5 to 10 minutes. For this reason, a test method using an assay method such as an immunological test is widely adopted as a simple and quick test method, for example, in a clinical test in a hospital or a test test in a laboratory.

  In particular, in clinical settings such as clinics, clinics, and home medical care, immunochromatographic analyzers (immunochromatography readers) are used as point-of-care testing (POCT) clinical analyzers that perform simple tests regardless of clinical laboratory specialists. ) Is often used. This immunochromatographic analyzer measures the coloration state of the reagent of the loaded device with high sensitivity, and enables high-sensitivity and highly reliable inspection even in a low coloration state where visual judgment is difficult. . Patent Document 2 shows an example of this type of analyzer.

  In the analysis method as described above, it is required to detect a very small amount of a test substance with high sensitivity. As an analysis method that meets such a requirement, for example, a method that performs amplification (sensitization) processing shown in Patent Document 3 is known. In this method, after developing a test substance on a carrier, a washing solution is fed to wash away the labeling substance captured by specific binding to the reaction site on the carrier, and then the sensitizing solution is put on the carrier. By sending the solution and sensitizing it, a minute amount of the test substance can be detected with high sensitivity.

  The sensitization process can be performed as necessary. That is, if the coloration state of the reagent can be measured by normal processing, the measurement ends there. If the coloration state cannot be measured by normal processing, the coloration is performed after further sensitization processing. The state may be measured.

  The carrier described above is often used by being held in a reaction container generally called a cartridge, a package, a test kit, etc., and Patent Document 4 shows an example of such a reaction container. .

  In addition, as one of analyzers using this type of reaction vessel, as disclosed in Patent Document 5, the reaction vessel can be introduced and discharged, and the analysis of the sample in one received reaction vessel can be performed. It is widely known that once completed, it is drained and another reaction vessel is accepted for further analysis.

JP 2008-139297 A JP 2009-13381 A JP 2009-287952 A JP 2007-101364 A JP 2007-175005 A

  As described above, the configuration in which the reaction vessels are received one by one while being exchanged one by one and the analysis is sequentially performed can also be applied to an immunochromatographic analyzer using the reaction vessel to which the above-described sensitization processing is performed.

  However, when performing sensitization processing, the time required from the spotting to completion of analysis is longer than when not performing it. Then, it becomes difficult to increase the throughput, that is, the number of analysis processes per hour.

  The present invention has been made in view of the above circumstances, and can increase the number of analysis processes per hour in an analyzer configured to receive and sequentially analyze reaction vessels while exchanging reaction vessels one by one. The purpose is to provide an analysis method.

  Another object of the present invention is to provide an analyzer that can carry out such an analysis method.

  In the analysis method according to the present invention, when performing analysis sequentially by replacing reaction vessels one by one, the reaction vessels are arranged in the analysis device only for the last fixed time from the point of sample application to the completion of analysis. In such a case, spotting is performed outside the analyzer, and the optimum spotting timing that can maximize throughput is obtained. It is intended to be understood by the operator.

That is, the analysis method according to the present invention more specifically,
While using an analyzer that can introduce and discharge reaction vessels holding reagents,
As the reaction vessel, a reaction container in which the necessary time Ta from the sample spotting to the reagent made outside the analyzer to the introduction and the necessary time Tb from the introduction to the completion of analysis are known in advance,
After the sample is spotted on the reagent outside the analyzer, the reaction container is introduced into the analyzer,
In an analysis method for detecting a reaction state between a sample and a reagent in an analyzer and analyzing the sample based on the reaction state,
When a new analysis request is made using the next reaction vessel that can be replaced with the reaction vessel after spotting one reaction vessel, the time T = Ta1 + Tb1-Tc-Ta2
(However, Ta1 and Tb1 are the times Ta, Tb,
Ta2 is the time Ta for the next reaction vessel,
Tc is the elapsed time from the spotting to the request in the one reaction vessel)
It is characterized by generating a notification indicating.

Meanwhile, one analyzer according to the present invention is:
An analyzer having a structure capable of introducing and discharging a reaction container holding a reagent,
As the reaction container, a container in which the required time Ta from the sample spotting to the reagent made outside the analyzer to the introduction and the necessary time Tb from the introduction to the completion of the analysis are known in advance is applied,
In an analyzer for detecting a reaction state between a sample and a reagent with respect to a reaction vessel introduced after spotting a sample on the reagent outside the analyzer, and analyzing the sample based on the reaction state,
A spotting timing input means for inputting a point in time when the reaction container is spotted;
An analysis request input means for inputting an analysis request;
Time measuring means for measuring an elapsed time Tc from the spotting in the one reaction vessel to the input of the request;
A calculation means for obtaining a time T = Ta1 + Tb1-Tc-Ta2 when the analysis request is input;
(However, Ta1 and Tb1 are the times Ta, Tb,
Ta2 is the time Ta for the next reaction vessel,
Tc is the elapsed time from the spotting to the request in the one reaction vessel)
Notification means for generating a notification indicating the time T is provided.

  In the analyzer of the present invention, as described above, one reaction vessel in the analyzer is replaced with the next reaction vessel, and analysis is performed successively using these reaction vessels. The part to be performed is not limited to one place, and two or more similar parts may be provided and the parts may be configured to perform the analysis in parallel.

  The analysis request input means is a general switch for inputting an electric signal in response to an operation of the apparatus operator, or when receiving a voice such as an apparatus operator's voice, converting it into an electric signal and inputting it. It is possible to apply voice input means or the like.

  Further, the calculation means and the notification means may be provided in the analyzer main body, or may be provided separately from the analyzer main body.

  As the notification means, it is desirable to use display means for indicating the time T in numbers. Such display means is preferably configured to indicate the time T by a number and then gradually count down the number. The countdown is usually preferably in units of 1 second, but may be in other units such as 1 minute or even in units of time smaller than 1 second.

  Further, as the notification means, a means for issuing a display or warning indicating that the time T has elapsed can be applied. Furthermore, instead of directly indicating the time T, the hour and minute of the spotting time of the next reaction vessel may be indicated based on the calculated time T and the current time.

  On the other hand, in the analysis apparatus of the present invention, it is preferable that a condition input means for inputting information indicating at least one of the times Ta1, Tb1, and Ta2 is provided.

  Furthermore, in the analyzer of the present invention, it is preferable that a condition reading means for reading the information on the time Ta and Tb indicated in the introduced reaction vessel is provided.

Another analysis apparatus according to the present invention is as follows.
An analyzer having a structure capable of introducing and discharging a reaction container holding a reagent spotted with a sample, and performing sensitization processing of the introduced reaction container,
The spotting time of the sample in the introduced first reaction container,
Time required from the spotting time to the start of sensitization processing,
The time required from the time of spotting the sample in the second reaction container introduced into the analyzer next to the first reaction container to the start of sensitization,
And the time required for sensitization in the first reaction vessel,
, The sensitization process in the first reaction container and the sensitization process in the second reaction container are continuously performed, the calculation means for obtaining the spotting point of the specimen in the second reaction container,
Notification means for generating notification information based on the spotting time determined by the calculation means;
It is characterized by comprising.

  Note that the above-mentioned “continuously performed” means that the sensitization process in the second reaction container following the sensitization process in the first reaction container has no time lag or does not significantly affect the measurement time. It is meant to be done after a slight time lag.

  Further, the notification information may be information indicating how many minutes and seconds after the spotting time, or information indicating the time after what minutes and seconds.

  FIG. 8 is a time chart showing the flow of processing when the reaction vessels are replaced one after another and analysis is sequentially performed using them. In this chart, the portion indicated by a thin arrow is the time Ta in the present invention, that is, the required time from the sample spotting to the introduction of the reaction vessel into the analyzer, and the portion indicated by a thick arrow is the time Tb in the present invention, that is, the reaction vessel. This is the time required from introduction to completion of analysis.

  Here, when the nth reaction vessel in the order of use is considered as one reaction vessel in the present invention, the (n + 1) th reaction vessel in the order of use replaced with it becomes the next reaction vessel in the present invention. As can be seen from this chart, the time T = Ta1 + Tb1-Tc-Ta2 is spotted on the (n + 1) th reaction vessel after this time T since the request for a new analysis using the (n + 1) th reaction vessel is made. For example, the time when the end of time Tb1 and the start of time Tb2 coincide. This means that the time point at which the analysis for the nth reaction vessel ends is exactly the time point at which the (n + 1) th reaction vessel should be introduced into the analyzer.

  Therefore, when a new analysis request using the next reaction container to be replaced with the reaction container is made after spotting one reaction container, if the notification indicating the time T is generated, the time The apparatus user will know that the next reaction vessel should be spotted after T. Therefore, if the next reaction vessel is spotted after that time T, the reaction vessel can be unnecessarily long in the analyzer, as can be seen from the fact that all the thick arrows in FIG. It will be possible to maximize the analysis throughput.

  Specifically, for example, when Ta and Tb are common in all the reaction vessels and Ta: Tb = 2: 1, according to the present invention, the reaction vessel is introduced into the analyzer immediately after spotting and the analysis is completed. As compared with the case where the reaction vessel is taken out, the throughput is increased up to about three times. This is based on the premise that the number of analyzes is somewhat large and the time Ta in the first analysis is very short with respect to the time required for the entire analysis.

  In addition, as described above, the analyzer according to the present invention includes a spotting timing input means for inputting a point in time when the reaction container is spotted, an analysis request input means for inputting a request for analysis, A time measuring means for measuring an elapsed time Tc from the spotting in one reaction vessel until the request is inputted; a computing means for obtaining a time T = Ta1 + Tb1-Tc-Ta2 when the analysis request is inputted; Since the notification means for generating the notification indicating the time T is provided, the analysis method of the present invention described above can be performed according to this analysis apparatus.

  In the analyzer of the present invention, in particular, as the notification means, when the display means for indicating the time T in numbers and then gradually counting down the numbers is used, the apparatus operator next observes the display. It becomes possible to clearly grasp the timing of spotting on the reaction vessel.

  Moreover, in the analyzer of the present invention, in particular, when a condition input means for inputting information indicating at least one of the times Ta1, Tb1 and Ta2 is provided, is the reaction vessel introduced into the analyzer? Regardless, the time value can be used to determine the T value.

  On the other hand, in the analyzer of the present invention, in particular, when condition reading means for reading the information on the time Ta and Tb shown in the introduced reaction vessel is provided, the value of these times is set to the value of T. Be available to ask. However, when Ta and Tb are not obtained by a method other than the condition reading means and Ta and Tb in the introduced reaction vessel are used as Ta and Tb in a reaction vessel other than the introduced reaction vessel, the time Ta It is assumed that the values of Tb and Tb are common to reaction vessels other than the introduced reaction vessel.

  Note that the present invention is not limited to the case where the sensitization process is performed in the analyzer as described above, and the reaction container is arranged outside the analyzer from the spotting to the start of the sensitization process. During the period until completion, the reaction container was placed outside the analyzer for a predetermined period immediately after the spotting, and when the predetermined period passed, the reaction container was introduced into the analyzer for analysis. The case is generally applicable.

The perspective view which shows the analyzer by one Embodiment of this invention Partially broken side view of the analyzer Block diagram showing the electrical configuration of the analyzer Front view showing part of the analyzer The partially broken top view which shows one state of the cartridge used for the said analyzer Partially cutaway plan view showing another state of the cartridge Partially cutaway plan view showing still another state of the cartridge Explanatory drawing explaining the effect of this invention The top view which shows the operation part of the said analyzer

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. FIG. 1 is a perspective view of a chromatographic analyzer 1 according to an embodiment of the present invention, FIG. 2 is a partially broken side view thereof, and FIG. 3 is an electrical configuration thereof. First, the basic configuration of the present apparatus will be described with reference to FIGS.

  As shown in these drawings, the chromatographic analyzer 1 includes a housing 10 having an opening 10a on the front surface, a display unit 11 disposed on the top surface of the housing 10, and a menu displayed on the display unit 11. An operation unit 12 for performing an operation, a power switch 13, and a cartridge loading unit 14 for introducing and loading an immunochromatographic cartridge (inspection reaction container) 20 into the apparatus are provided. Further, inside the housing 10, a rail 15 that guides the cartridge loading unit 14 so as to be movable in the left-right direction in FIG. 2, and a pressing unit 30 for crushing a cleaning liquid pot 27 and a sensitizing liquid pot 28 described later, respectively. , 34 and a first measurement unit 40 and a second measurement unit 50 that acquire information from the cartridge 20.

  The cartridge loading unit 14 is movable along the rail 15 automatically or manually. When most of the cartridge passes through the opening 10a and is taken out of the housing 10, the cartridge 20 supplied with the test solution (sample) is placed thereon as described below. Thereafter, the cartridge loading unit 14 is pushed into the housing 10 as shown in FIG. 2, whereby the cartridge 20 is taken into the chromatographic analyzer 1.

  FIG. 4 is a front view showing a state where the pressing portions 30 and 34 are viewed from the left side in FIG. Here, the cartridge 20 is shown broken away. Hereinafter, the pressing portions 30 and 34 will be described with reference to FIG. The pressing portion 30 includes an arm 31 that is rotatable around a shaft 31 a like a seesaw, a pressing piece 32 that is fixed to a lower end of the arm 31, and a cam that is disposed below the rear end of the arm 31. 33. The cam 33 is connected to a drive shaft 39 rotated by a motor 38 so as to be freely connected and disconnected via an electromagnetic clutch (not shown), for example. When the cam 33 rotates, the rear end of the arm 31 is pushed up, and the pressing piece 32 at the tip moves downward. The other pressing portion 34 also has an arm 35, a pressing piece 36, and a cam 37 and is configured in the same manner as the pressing portion 30.

  Here, the pressing piece 32 of the pressing portion 30 and the pressing piece 36 of the pressing portion 34 are respectively the cleaning liquid pot 27 disposed inside the cartridge when the cartridge 20 is disposed at a predetermined position in the housing 10. It arrange | positions so that it may come to the position right above the liquid sensitive pot 28. FIG.

  FIG. 5 is a plan view showing the upper surface of the cartridge 20 in a cutaway manner. Hereinafter, the cartridge 20 will be described with reference to FIG. The cartridge 20 is formed on the upper surface of the case for spotting the sample solution on the insoluble carrier 21, the insoluble carrier 21 having the test line A, the test line B, and the control line C, the cartridge case 22 for containing the insoluble carrier 21. And an observation window 24 for observing the inspection site of the insoluble carrier 21 (the portions of the test lines A and B and the control line C). An information display unit 25 is provided on the upper surface of the cartridge case 22. The cartridge loading unit 14 is also provided with an observation window 14a that is substantially aligned with the observation window 24.

  The insoluble carrier 21 has an immobilized labeling substance. Test lines A and B each have a specific binding substance to the test substance immobilized as a reagent, and control line C is used to determine the end of measurement. In addition, the cartridge 20 in this embodiment is for analyzing positive / negative for influenza as an example.

  Further, an insoluble carrier 72 for liquid feeding and an insoluble carrier 73 for absorption are disposed inside the cartridge 20 with the insoluble carrier 21 sandwiched therebetween. The cleaning liquid pot 27 is fixed above the insoluble carrier 72 for feeding liquid, and the sensitizing liquid pot 28 is fixed above the end of the insoluble carrier 21 on the control line C side.

  The first measuring unit 40 measures the coloration state of the inspection site (the test lines A and B and the control line C) through the observation window 24 of the cartridge 20. As shown in FIG. 2, the first measurement unit 40 includes a camera 42 and a light source 44, and when the cartridge 20 is loaded in the analyzer 1, these are opposed to the observation window 24 from below the cartridge 20. It is configured. Then, based on the optical information on the examination site acquired by the first measurement unit 40, the optical density and chromaticity are calculated as the coloration state of the examination site (this will be described later).

Note the optical density, the intensity of light incident on the test site of the cartridge 20 I, when the intensity of the reflected light from the test site was a I _r, is defined by the following equation.

Optical density = −log ₁₀ (I _r / I)
The chromaticity is a numerical display of hue and saturation, and is calculated from RGB luminance signals read by the camera. As a chromaticity color system, a general CIE color system can be used.

  The camera 42 has, for example, a configuration in which a plurality of photodiodes are arranged in a line or an image sensor including an area sensor, and generates an output corresponding to the amount of received light. The light receiving range of the camera 42 is a belt-like range extending in the longitudinal direction of the cartridge 20. The light source 44 is a module in which, for example, an LED is built, and is configured to emit white light. The light source 44 may emit, for example, monochromatic light as long as the chromaticity before and after the sensitization process described later can be distinguished. When the light source 44 is composed of a plurality of modules, the light source 44 can also be composed of a plurality of modules that emit monochromatic light of different wavelengths. The light emitted from the light source 44 can illuminate a predetermined range in the longitudinal direction of the cartridge 20.

  On the other hand, the second measurement unit 50 irradiates the information display unit 25 of the cartridge 20 with illumination light and acquires information displayed on the information display unit 25. The information display unit 25 displays information related to the inspection by handwriting or sticker attachment. Information related to testing includes, for example, information related to the patient from whom the test substance was collected (name, age, gender, etc.) and information related to the sample / reagent used in the test (test substance, cleaning solution, sensitizing solution, etc. to be tested) Name, required time from sample spotting to reagent to introduction of analyzer, required time from introduction to analyzer to completion of analysis, etc.). The method for acquiring information is not particularly limited, and the information display unit 25 can be imaged as it is or read from bar-coded information.

  As shown in FIG. 2, the second measuring unit 50 includes a camera 52 and a light source 54, and when the cartridge 20 is loaded into the analyzer 1, they face the information display unit 25 from above the cartridge 20. It is configured as follows. And the information regarding the test | inspection acquired by the 2nd measurement part 50 and a test result are linked | related and managed. Specific configurations of the camera 52 and the light source 54 are the same as those of the camera 42 and the light source 44 described above, respectively.

  Next, the electrical configuration of this apparatus will be described with reference to FIG. The operations of the pressing mechanisms 30 and 34 and the cameras 42 and 52 (including the light sources 44 and 54, respectively) including the display unit 11, the operation unit 12, and the motor 38 described above are controlled by the control unit 80 shown in FIG. The The analyzer 1 can be operated using, for example, a commercial power source of 100 to 240V, and the power source unit 100 that receives the commercial power source and converts it into a direct current of 12V, and the direct current of 12V are input. Switching unit 101. In addition, the analyzer 1 can be driven by a battery 102 as a secondary battery, and the battery 102 is also connected to the switching unit 101. The switching unit 101 receives a 12V DC current supplied from the power supply unit 100 when the commercial power supply is connected, and a 12V DC current supplied from the battery 102 when the commercial power supply is not connected. Switch to use in parts.

  In addition, a battery capacity monitoring unit 103 is connected to the switching unit 101 as battery remaining amount detecting means for detecting the remaining power amount of the battery 102. In general, because of its chemical characteristics, a battery has a characteristic that when the capacity decreases, the internal resistance increases and the terminal voltage decreases. Therefore, the residual power can be detected by measuring the terminal voltage. The battery capacity monitoring unit 103 thus continues to detect the remaining power amount of the battery 102 and inputs a signal indicating the remaining power amount to the control unit 80.

Next, the operation of the analyzer 1 of the present embodiment will be described. First, a specific measurement operation procedure will be described.
<< First stage >>
In this first stage, first, as shown in FIG. 5, for example, the sample solution 90 is spotted from the solution inlet 23 of the cartridge 20 outside the analyzer 1 and developed on the insoluble carrier 21. Thereafter, the cartridge 20 is disposed outside the analyzer 1 for a predetermined time, and then introduced and loaded into the analyzer 1 as described above.
<< Second stage >>
Here, first, the pressing portion 30 shown in FIGS. 2 and 4 is driven, the tip of the arm 31 is moved downward, and the pressing piece 32 crushes the cleaning liquid pot 27 in the cartridge 20 from the outside. As a result, as shown in FIG. 6, the cleaning liquid 91 stored in the cleaning liquid pot 27 cleans the inspection site of the insoluble carrier 21. At this time, the washing liquid 91 is sufficiently spread by the insoluble carrier 72 for liquid feeding, and then fed in the order of the insoluble carrier 21 and the insoluble carrier 73 for absorption.

  Next, the pressing portion 34 shown in FIGS. 2 and 4 is driven, the tip of the arm 35 is moved downward, and the pressing piece 36 crushes the sensitizing liquid pot 28 in the cartridge 20 from the outside. As a result, as shown in FIG. 7, the sensitizing solution 92 stored in the sensitizing solution pot 28 is sent to the inspection site of the insoluble carrier 21 to be sensitized. The sensitizing liquid 92 and the cleaning liquid 91 are disclosed in detail in the above-mentioned Patent Document 3, and can be applied to the present invention.

  After this sensitization processing, an image of the inspection site of the cartridge 20 is acquired by the camera 42 shown in FIG. The control unit 80 shown in the figure calculates the optical density and chromaticity of the image thus obtained, and displays the values, or the test results such as the presence or absence of a disease determined from these values, on the display unit 11. Let Thereafter, the cartridge 20 is taken out from the analyzer 1.

  Next, the point that the analysis throughput is increased will be described. First, the operation unit 12 shown in FIGS. 1 and 3 will be described with reference to FIG. The operation unit 12 includes a test button 12a, a mode button 12b, a next button 12c, a spotting button 12d, an input button 12e, and an up / down button 12f. In addition to these buttons, the operation unit 12 is appropriately provided with a lamp or the like indicating that an error has been detected, an analysis result has been output, the apparatus is ready for analysis, and the like. Detailed description is omitted.

  The test button 12a is a button for instructing the start of the analysis operation. The mode button 12b is a button for selecting several analysis modes, for example, a mode for accepting only a cartridge 20 dedicated to a certain analysis or a mode for accepting a cartridge 20 for performing another analysis, and the up and down buttons 12f are these modes. The input button 12e sets the selected mode.

  As described above, the cartridge 20 in this embodiment is for analyzing positive / negative for influenza. In order to determine this negative, 15 minutes are required, but the above-described sensitization process performed by introducing the cartridge 20 into the analyzer 1 only requires 5 minutes. In other words, the 10 minutes before that is only the time for monitoring the test lines A and B. Even so, if the cartridge 20 is introduced into the analyzer 1 immediately after being spotted and analyzed, the analyzer 1 is used for 15 minutes per sample, so that only 4 samples can be analyzed per hour. become.

  The significance of using the analyzer 1 as in the present embodiment to determine positive / negative for influenza includes shortening the time required for analysis in addition to ensuring the objectivity of the analysis result by automatic determination. However, in actual hospitals, there are often 10 to 20 inspection requests per hour, and in clinics there are 5 to 10 inspection requests per hour. Can not respond to. Therefore, in order to respond to such an inspection request, for example, about 2 to 7 same analyzers are required in a hospital and about 2 to 3 in a clinic.

  On the other hand, according to the present embodiment, it is possible to respond to the inspection request as described above by using only one analyzer 1. This will be described below. In the present embodiment, the cartridge 20 is placed outside the analyzer 1 for 10 minutes after the sample is spotted outside the analyzer 1. That is, in this embodiment, the required time Ta from the sample spotting to the introduction of the cartridge 20 into the apparatus is 10 minutes, and therefore the required time Tb from the introduction to the completion of the analysis is 5 minutes. In the present embodiment, as an example, the same cartridge 20 is used in a series of influenza tests, so the above Ta = 10 minutes and Tb = 5 minutes are common in all analyses.

  When the apparatus user who performs the influenza test performs sample spotting on one cartridge 20, the user presses the spotting button 12d in FIG. 9 and inputs the time point when spotting is performed. That is, in this embodiment, the spotting button 12d constitutes spotting timing input means. When the cartridge 20 is first subjected to analysis, the cartridge 20 is introduced into the analyzer 1 after 10 minutes have elapsed since the spotting.

  Thereafter, when a new analysis is to be performed using the next cartridge 20, the apparatus user presses the next button 12 c and inputs that there is a request to the analyzer 1. That is, in this embodiment, the next button 12c constitutes an analysis request input means for inputting an analysis request.

  The control unit 80 shown in FIG. 3 also constitutes the time measuring means in the present invention, and measures the time Tc from when the spotting button 12d is pressed until the next button 12c is pressed. The control unit 80 also constitutes a calculation unit in the present invention. When the next button 12c is pressed, the control unit 80 obtains the above-described time T = Ta1 + Tb1-Tc-Ta2. Here, in this embodiment, since Ta1 = Ta2 = 10 minutes and Tb1 = 5 minutes, T = 5 minutes−Tc.

  The values Ta1 = Ta2 = 10 minutes and Tb1 = 5 minutes, for example, once the cartridge 20 before use is introduced into the analyzer 1, and the information display unit 25 of the cartridge 20 is displayed by the second measuring unit 50 shown in FIG. Can be input to the control unit 80. When doing so, the measurement part 50 becomes a condition reading means in the present invention. Alternatively, an external barcode reader or the like may be provided as condition reading means, and the values of Ta and Tb may be read from the used cartridge 20 one by one and input to the control unit 80. This latter method can be used even when the values of Ta1 and Ta2 are different from each other. When the latter method is adopted, it is desirable to display on the display unit 11 such as “Please read the reagent code with an external reader.”

  The control unit 80 causes the display unit 11 to display the value of T = 5 minutes−Tc. In other words, in the present embodiment, the control unit 80 and the display unit 11 constitute notification means in the present invention. At this time, first, for example, “remaining time: X minutes Y seconds next spotting: A minutes B seconds” is displayed on the display unit 11. Here, “next spotting: A minute B seconds” is the value of T, and “remaining time: X minutes Y seconds” ends the analysis on the cartridge 20 that has already been spotted at that time. It shows the time until.

  Thereafter, the control unit 80 counts down the value of the A minute B seconds, for example, by 1 second, and causes the display unit 11 to display the value. Then, when the counted down value becomes zero, that is, when the time T has elapsed since the next analysis request is made, the control unit 80 displays, for example, “Remaining time: X minutes Y seconds. “Arrive: 0 min 0 sec.”, And a buzzer (not shown) is sounded to prompt the user of the device.

  As a result, the user of the apparatus places a sample on the next cartridge 20 and presses the spotting button 12d to cause the control unit 80 to input a spotting timing. The spotting timing input in this way is used to obtain the time T in the same manner as described above when another cartridge 20 is used.

  When the analysis of the cartridge 20 in the analyzer 1 is completed, that is, when the display of “X minute Y second” becomes “0 minute 0 second”, the control unit 80 displays, for example, “processing completed” on the display unit 11. "Print now. Replace cartridge." Is displayed and the buzzer sounds to prompt replacement of the cartridge 20. As a result, the user of the apparatus causes the cartridge 20 that has been analyzed to be discharged from the analyzer 1, and instead, introduces the next cartridge 20 into the analyzer 1. The introduction and discharge of the cartridge 20 is performed by operating the cartridge loading unit 14 described above. If the analyzer 1 is provided with printing means, the analysis result is printed out.

  By performing sample spotting on each cartridge 20 as described above and sequentially exchanging the cartridges 20, the time that the cartridges 20 are in the analyzer 1 is basically continuous as shown in FIG. (Ignore the short time required for cartridge replacement). Thereby, the throughput of influenza testing and the like is increased. Specifically, in the present embodiment, if the number of times of analysis is somewhat large and the time Ta in the first analysis is so small that it can be ignored with respect to the time required for the entire analysis, the cartridge 20 is removed from the analyzer 1 throughout the entire analysis process. The throughput can be increased up to about three times as compared with the case where it is placed inside.

  As described above, the analysis apparatus 1 configured to receive the cartridge 20 at only one position has been described. However, the present invention is configured to receive the cartridge 20 at a plurality of positions and perform analysis on the plurality of cartridges 20 in parallel. The present invention can be similarly applied to the analyzed apparatus. That is, even in such a configuration, if the cartridge 20 is replaced and received one by one at each location where the cartridge 20 is received, the throughput can be improved by applying the present invention.

  The items related to the measurement will be briefly described below.

(Sample solution)
The sample solution that can be analyzed using the analyzer of the present invention is as long as it may contain a test substance (natural products, toxins, hormones, physiologically active substances such as agricultural chemicals, environmental pollutants, etc.). For example, biological samples, especially animal (especially human) body fluids (eg blood, serum, plasma, spinal fluid, tears, sweat, urine, pus, runny nose or sputum) ) Or excrement (for example, feces), organs, tissues, mucous membranes and skin, overwhelmed specimens (swabs), gargles, or animals and plants themselves or their dried bodies, which are considered to contain them, are diluted with a diluent described below. Can be mentioned.

  Leave the sample solution as it is, or in the form of an extract obtained by extracting the sample solution with an appropriate extraction solvent, and further dilute this extract with an appropriate diluent. It can be used in the form or the extract concentrated by an appropriate method.

(Labeling substance)
As a labeling substance that can be used in the present invention, metal fine particles (or metal colloids), colored latex particles, enzymes, etc., which are used in general immunochromatography, can be visually confirmed or can be inspected by reaction. It can be used without any particular limitation as long as it is a labeled substance, but when a signal is sensitized by metal deposition on the labeling substance by a reduction reaction of metal ions using the labeling substance as a catalyst, From the viewpoint of catalytic activity, metal fine particles are preferred.

  As the material of the metal fine particles, a metal simple substance, metal sulfide, other metal alloy, or polymer particle label containing metal can be used. The average particle size of the particles (or colloid) is preferably in the range of 1 nm to 10 μm. Here, the average particle diameter is an average value of the diameters of the plurality of particles (the longest diameter of the particles) measured by a transmission electron microscope (TEM). More specifically, gold colloids, silver colloids, platinum colloids, iron colloids, aluminum hydroxide colloids, composite colloids thereof, and the like are preferable. Gold colloids, silver colloids, platinum colloids, and composite composite colloids thereof are preferable. It is desirable to be. In particular, gold colloid and silver colloid are suitable in terms of appropriate particle diameters, and gold colloid is red and silver colloid is yellow, which is more preferable in view of high visibility. By using a gold colloid, the sensitization process using a silver ion-containing compound changes the chromaticity of the label before and after the sensitization (the gold colloid is colored red, and after the sensitization, the reduced silver Since the ions are deposited on the gold colloid and become black), this change can be used for error determination of the inspection as will be described later. The average particle size of the metal colloid is preferably about 1 to 500 nm, more preferably 1 to 100 nm.

(Specific binding substance)
The specific binding substance is not particularly limited as long as it has affinity for the test substance. For example, when the test substance is an antigen, an antibody against the antigen, the test substance is a protein, a metal ion Alternatively, aptamers for low molecular weight organic compounds, and when the test substance is a nucleic acid such as DNA or RNA, nucleic acid molecules such as DNA or RNA having a sequence complementary thereto, or the test substance is avidin. In some cases, biotin, and in the case where the test substance is a specific peptide, a complex that specifically binds to this can be used. In the above example, the relationship between the specific binding substance and the test substance can be exchanged. For example, when the test substance is an antibody, an antigen against the antibody can be used as the specific binding substance. Furthermore, a compound or the like partially containing a substance having affinity for the test substance as described above can also be used as the specific binding substance.

  Specific examples of the antibody include antiserum prepared from the serum of an animal immunized with the test substance, an immunoglobulin fraction purified from the antiserum, and cell fusion using spleen cells of the animal immunized with the test substance Or a fragment thereof [for example, F (ab ′) 2, Fab, Fab ′, or Fv] can be used. These antibodies can be prepared by a conventional method.

(Insoluble carrier)
The material of the insoluble carrier 21 is preferably porous, for example, a nitrocellulose membrane, a cellulose membrane, an acetylcellulose membrane, a polysulfone membrane, a polyethersulfone membrane, a nylon membrane, glass fiber, a nonwoven fabric, a cloth, or a thread. Preferably mentioned.

  On the chromatographic carrier, a specific binding substance for the test substance is immobilized, and a test site or a control site is produced if desired. The specific binding substance may be directly immobilized on a part of the chromatographic carrier by physical or chemical binding, or the specific binding substance may be physically or chemically attached to fine particles such as latex particles. The fine particles may be trapped on a part of the chromatographic carrier and immobilized.

(Sensitizer)
The sensitizing solution is a solution capable of causing a signal sensitization by producing a colored or luminescent compound or the like when a contained drug reacts by a catalytic action of a labeling substance or a test substance. For example, a silver ion solution that causes metal silver to be deposited by physical development on a metal label. Details include general books in the field of photographic chemistry (for example, “Basics of Revised Photo Engineering-Silver Salt Photo Edition” (Japan Photographic Society, Corona), “Photochemistry” (Akira Sakurai, Photo Industry Publishing) ), “Latest Prescription Handbook” (Shinichi Kikuchi et al., Amico Publishing Co., Ltd.)), so-called developers can be used. For example, when a physical developer containing a silver ion-containing compound is used as a sensitizer, silver ions in the solution can be reduced mainly by a metal colloid or the like that serves as a development nucleus by a silver ion reducing agent. .

As another example, an enzyme reaction is used. For example, a solution of a phenylenediamine compound and a naphthol compound, which becomes a dye by the action of a peroxidase label and hydrogen peroxide, can be used. Further, it may be a chromogenic substrate for detecting horseradish peroxidase as described in the non-patent document “Staining using clinical test Vol. 41 no. 9 p. 1020 H ₂ O ₂ -POD system”. In addition, the chromogenic substrate described in JP2009-156612A can be particularly preferably used. A system using a metal catalyst such as platinum fine particles instead of the enzyme may be used.

  As an example using another enzyme, there is a system in which alkaline phosphatase is used as a label and color is developed using 5-bromo-4chloro-3-indolyl-phosphate disodium salt (BCIP) as a substrate. As described above, the reaction that gives a color is given as a representative, but any combination of enzyme and substrate, such as those generally used in enzyme immunoassays, may be used, and even a chemiluminescent substrate is a substrate that emits fluorescence. May be.

(Silver ion-containing compound)
As the silver ion-containing compound, an organic silver salt, an inorganic silver salt, or a silver complex can be used. Preferably, it is a silver ion-containing compound having high solubility in a solvent such as water, and examples thereof include silver nitrate, silver acetate, silver lactate, silver butyrate, and silver thiosulfate. Particularly preferred is silver nitrate. The silver complex is preferably a silver complex coordinated to a ligand having a water-soluble group such as a hydroxyl group or a sulfone group, and examples thereof include hydroxythioether silver. The inorganic silver salt or silver complex is generally contained as silver in an amount of 0.001 mol / m ^{2 to} 0.2 mol / m ² , preferably 0.01 mol / m ^{2 to} 0.05 mol / m ^2. preferable.

(Silver ion reducing agent)
As the silver ion reducing agent, any inorganic or organic material or a mixture thereof can be used as long as it can reduce silver ions to silver.

Preferred examples of the inorganic reducing agent include reducible metal salts and reducible metal complex salts whose valence can be changed by metal ions such as Fe ²⁺ , V ²⁺ , and Ti ³⁺ . When using an inorganic reducing agent, it is necessary to complex or reduce the oxidized ions to remove or render them harmless. For example, in a system using Fe ²⁺ as a reducing agent, a complex of Fe ³⁺ that is an oxide can be formed using citric acid or EDTA, and can be rendered harmless. In this system, it is preferable to use such an inorganic reducing agent, and more preferable is a metal salt of Fe ²⁺ .

  In the above-described embodiment, a method of sensitizing a labeling substance by reducing a silver ion-containing compound with a reducing agent is used as a sensitizing method in a colored state, but the sensitizing method in the present invention is limited to this. Not. The sensitizing solution may be any solution that can cause a signal sensitization by generating a colored or luminescent compound by reacting the contained drug by the catalytic action of a labeling substance or a test substance. And liquids using such enzymes.

  Moreover, in the said embodiment, although the immunochromatography method was demonstrated as an assay method, the assay method applied by this invention is not limited to this. A system that does not use a so-called immune reaction may be used, for example, a system that captures a test substance with a nucleic acid such as DNA or RNA without using an antibody, or another small molecule or peptide that has an affinity for the test substance, A system in which a test substance is captured by a protein, a complex-forming substance, or the like may be used.

DESCRIPTION OF SYMBOLS 1 Chromatographic analyzer 10 Case 11 Display part 12 Operation part 13 Power switch 14 Cartridge loading part 20 Immunochromatography cartridge 21 Insoluble carrier 22 Cartridge case 23 Solution inlet 26 Sheet material 27 Washing liquid pot 28 Sensitizing liquid pots 30 and 34 Press unit 32, 36 Press piece 33, 37 Cam 38 Motor 40, 50 Measuring unit 87, 88 Blade 80 Control unit 90 Sample solution 91 Cleaning solution 92 Sensitizing solution 102 Battery 103 Battery capacity monitoring unit A, B Test line C Control line

Claims (8)

While using an analyzer that can introduce and discharge reaction vessels holding reagents,
As the reaction vessel, a reaction container in which the necessary time Ta from the sample spotting to the reagent made outside the analyzer to the introduction and the necessary time Tb from the introduction to the completion of analysis are known in advance,
After the sample is spotted on the reagent outside the analyzer, the reaction container is introduced into the analyzer,
In an analysis method for detecting a reaction state between a sample and a reagent in an analyzer and analyzing the sample based on the reaction state,
When a request for a new analysis using the next reaction vessel that is replaced with the reaction vessel is made after a reaction vessel is spotted, a notification indicating the time T = Ta1 + Tb1-Tc-Ta2 is generated. Characteristic analysis method.
(However, Ta1 and Tb1 are the times Ta, Tb,
Ta2 is the time Ta for the next reaction vessel,
Tc is the elapsed time from the spotting to the request in the one reaction vessel) An analyzer having a structure capable of introducing and discharging a reaction container holding a reagent,
As the reaction container, a container in which the required time Ta from the sample spotting to the reagent made outside the analyzer to the introduction and the necessary time Tb from the introduction to the completion of the analysis are known in advance is applied,
In an analyzer for detecting a reaction state between a sample and a reagent with respect to a reaction container introduced after spotting the sample on the reagent outside the analyzer, and analyzing the sample based on the reaction state,
A spotting timing input means for inputting a point in time when the reaction container is spotted;
An analysis request input means for inputting an analysis request;
Time measuring means for measuring an elapsed time Tc from the spotting in the one reaction vessel to the input of the request;
A calculation means for obtaining a time T = Ta1 + Tb1-Tc-Ta2 when the analysis request is input;
An analysis device comprising a notification means for generating a notification indicating the time T.
(However, Ta1 and Tb1 are the times Ta, Tb,
Ta2 is the time Ta for the next reaction vessel,
Tc is the elapsed time from the spotting to the request in the one reaction vessel)   3. The analysis apparatus according to claim 2, wherein a display means for indicating the time T as a number is provided as the notification means.   4. The analyzer according to claim 3, wherein the display means displays the time T by a numeral and then counts down the numeral gradually.   The analyzer according to any one of claims 2 to 4, wherein means for issuing a display or an alarm indicating that the time T has passed is provided as the notification means.   6. The analyzer according to claim 2, further comprising a condition input unit that inputs information indicating at least one of the times Ta1, Tb1, and Ta2.   The analyzer according to any one of claims 2 to 6, further comprising a condition reading means for reading information of the times Ta and Tb indicated in the introduced reaction vessel. An analyzer having a structure capable of introducing and discharging a reaction container holding a reagent spotted with a sample, and performing sensitization processing of the introduced reaction container,
The spotting time of the sample in the introduced first reaction container,
Time required from the spotting time to the start of sensitization processing,
The time required from the time of spotting the sample in the second reaction container introduced into the analyzer next to the first reaction container to the start of sensitization,
And the time required for sensitization in the first reaction vessel,
, The sensitization process in the first reaction container and the sensitization process in the second reaction container are continuously performed, the calculation means for obtaining the spotting point of the specimen in the second reaction container,
Notification means for generating notification information based on the spotting time determined by the calculation means;
An analysis apparatus comprising:

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