JP4613597B2 - Analysis equipment - Google Patents

Description

The present invention relates to an analyzer for optically analyzing components contained in a test solution using a test piece that is subjected to chromatographic development by applying a test solution such as blood, and in particular, the test solution is tested. It belongs to an analyzer that improves measurement accuracy by changing the timing of analysis in accordance with the speed at which a piece is developed.

In recent years, with the improvement of home medical care and regional medical care such as clinics and clinics, as well as the increase in early diagnosis and urgent clinical tests, even non-clinical specialists can easily and quickly achieve high accuracy. An analyzer capable of performing measurement has come to be demanded, and an analyzer for POCT (Point of Care Testing), which can perform highly reliable measurement in a short time without complicated operation, is in the spotlight.
POCT is a general term for tests performed in “close to patients” such as general practitioners, specialists' examination rooms, wards, and clinics for outpatients. It is a method that has been attracting attention as it greatly helps to improve the quality of medical treatment by performing treatment and monitoring the treatment process and prognosis. Compared to testing in the central laboratory, it is said that the cost of transporting and installing specimens and the cost of unnecessary testing can be reduced, and the total cost of testing can be reduced. In the United States, where hospital management rationalization is progressing, it is expanding rapidly and is expected to become a growing market in Japan and other countries.
As an immunosensor, dry analytical elements such as chromatographic sensors do not require reagent adjustment, and only by simple operations such as dropping a liquid sample such as blood or urine to be measured onto the analytical element. Since it is possible to analyze an analysis object of a solution to be inspected and it is very useful for simple and rapid analysis, it is put into practical use as a representative of POCT today. In addition to being able to measure anyone anytime and anywhere from the market, higher accuracy is required with faster measurement time, and dedicated analyzers that optically read the above-described analytical elements have also been proposed (for example, , See Patent Document 1).

In FIG. 6, the structure of the conventional test piece 7a will be described. Formed by fixing a spotting portion 8a for spotting a solution to be tested, a channel 9z for developing the solution to be tested, and a reagent for a measurement object in the solution to be tested in a part of the channel 9z. The reagent immobilization unit 11a thus formed, the labeled reagent holding unit 10a formed by holding the labeling reagent that can be eluted by the development of the solution to be inspected in the other part of the channel 9z, and the reagent from the channel 9z. It is comprised from the material | dough which is a part except the fixing | fixed part 13a and the labeling reagent holding | maintenance part 10a.
In FIG. 6, a conventional apparatus configuration will be described. The light emitted from the semiconductor laser as the light source is converted into a parallel beam and irradiated onto the test piece 7a as a beam. 6z indicates the irradiation position of the beam. At this time, the light is received by the first photodiode 4a as the reference light 2a. On the other hand, scattered light 3a is generated from the surface of the test piece 7, and is received by the second photodiode 5a. Log conversion is performed on the outputs received by the first photodiode 4a and the second photodiode 5a, and the Log conversion value of the second photodiode 5 is subtracted from the Log conversion value of the first photodiode 4. Output as an optical signal level absorbance value.
In FIG. 7, a specific operation method will be described. FIG. 7A shows the relationship between the development of the test piece and the solution to be inspected, and FIG. 7B shows the absorbance value (reagent immobilization) in the reagent immobilization unit that changes when the test solution is chromatographed. It is the figure which showed the change of the fixed amount of the labeling reagent of a part.
In FIG. 7A, when the test solution 12e is spotted on the spotting portion 8a of the test piece 7a, the test solution 12e starts chromatographic development. In the process of chromatographic development, the labeling reagent also develops the test piece 7a together with the test solution 12e by passing through the labeling reagent holding unit 10a that holds the labeling drug that binds to the analyte of the test solution 12e. At this time, the analyte and the labeling reagent are combined. The labeled reagent combined with the analysis object is fixed to the reagent fixing part 11a in the middle of the test piece 7a. The labeling reagent that has not been bound to the analysis target is developed downstream without being fixed to the reagent immobilization unit 11a.
The time for completing the development of all the solutions to be tested 12e to the most downstream side of the test piece 7a, that is, the time required for stabilizing the absorbance value shown in FIG. After reaching the predetermined position 24 in 9z, it waits for a predetermined time 21a (irradiation start time). After waiting for a predetermined time 21a, the reagent immobilization unit 11a is irradiated with a beam, the colored absorbance value is measured, and the analyte concentration is displayed.
Japanese Patent Laid-Open No. 2003-4743

  By the way, in the above-described conventional analysis apparatus, after the solution 12e to be inspected reaches the predetermined position 24, all the predetermined times for waiting until the solution 12e to be inspected reaches the most downstream is a certain time (predetermined time 21a). It was adjusted.

However, in reality, when blood is used as the solution to be inspected, the viscosity of blood varies depending on the individual due to the influence of blood components. Accordingly, when the same amount of blood is spotted on the test piece, the blood development speed is different. The deployment speed is faster when the viscosity is lower than when the viscosity is higher. Therefore, it was found that the following problems occur when the waiting time for developing the test piece is constant.

The problem will be described with reference to FIG.

FIG. 8 shows a development waiting time after blood passes through the predetermined position 24 in FIG. 7A in the case where three types of blood having different analytes and having different concentrations are chromatographed in advance. It is the figure which showed the change of the light absorbency value in the reagent fixed part which can be obtained according to progress of this.

The three types of viscosity are mainly due to differences in red blood cells (hematocrit value) and proteins in blood, and are viscosity A, viscosity B, and viscosity C in order of increasing viscosity.

In the conventional analyzer, a waiting time 21a according to the viscosity B is set. Here, the low-viscosity viscosity A is already developed in the waiting time 22a and the color reaction is stable. However, waiting until the waiting time 21a for the blood of viscosity B causes the unnecessary waiting time 25 to occur, and the analysis time becomes longer. Specifically, when the waiting time 21a hematocrit value of 40% of the blood and 240 seconds at a temperature of 25 ° C., the Te blood smell to deploy earlier is assumed that a delay of approximately 60 seconds occurs.

Next, the viscosity C, which has the next highest viscosity, is not completely developed in the waiting time 21a because the blood deployment speed is slow. The deployment is actually completed in the waiting time 23a. Therefore, when measured at the waiting time 21a, an error 26 of about 5% is generated in the absorbance value, and there is a problem that analysis accuracy is lowered.

Further, the above-described problem occurs when the amount of the solution to be inspected that is spotted on the test piece does not satisfy the prescribed amount of measurement even when the viscosity of the solution to be inspected is the same. This is because the amount of the solution to be inspected that develops in the flow path is small, the amount of the sample to be inspected supplied to the front of the development is small, and the development speed is slower than the prescribed amount. For this reason, as in the case of high viscosity (viscosity C), there is a problem of performing measurement when the development is not completed.

In addition to the above problems, as a result of intensive studies by the present inventors, it is a value after the waiting time 21a that has been conventionally regarded as a stabilization region of the absorbance value. When the absorbance value is measured in more detail, it is within a certain period of time. I understood that it was only stable.

The problem will be described with reference to FIG.

FIG. 9 is a diagram obtained by removing the change in the viscosity C from FIG. 8, and FIG. 9B is a diagram further enlarging a part thereof. In the viscosity A, after the elapse of time 22, the development of the solution to be inspected is completed and becomes a stable absorbance value 20a. However, as shown in FIG. 9B in which the portion 27 of FIG. 9A is enlarged, the absorbance value 20a changes when the accuracy of the unit of the absorbance value is increased. Therefore, if the measurement is performed after the common waiting time 21a has elapsed, there is a problem that the difference 28 becomes a measurement error of about 5 to 10% when high accuracy is obtained.

As described above, when performing absorbance measurement in the conventional analyzer, there is a problem that the measurement value includes a large error due to the difference in the deployment speed, and an error due to the absorbance value being unstable after the deployment is completed. Existed.

In order to solve the conventional problems, the analyzer of the present invention, the analysis light to the reagent immobilization part is provided a reagent immobilization part that fixes the inspection target solution developed on the test piece inspection target solution is spotted in reaction analyzer which optically analyzes the the irradiated the inspection target solution and the analyzing light, and detecting means for detecting the deployment speed of the inspection target solution is developed in the specimen, said detecting means detects And setting means for setting the irradiation start time of the analysis light based on the development speed and the performance of the test piece .

Further, the irradiation start time set by the setting means is a time for measuring the time after the solution to be inspected passes through a predetermined position on the test piece.

Further, the developing speed detected by the detecting means is based on a difference in arrival time of the solution to be inspected at two different points arrived by developing the solution to be inspected.

Further, the developing speed detected by the detecting means is based on a distance that the solution to be inspected is developed within a predetermined time.

Furthermore, the test piece is made of a strip-shaped porous carrier, and blood is developed by chromatography.

Further, the test piece is provided with a labeling reagent, characterized by optically analyzing the color of the labeled reagent.

Further, a scanning means for detecting the arrival position of the irradiated specimen solution analysis light to the deployment direction of the inspection target solution in the specimen, the specimen solution is spotted specimens mounted or after the deployment speed detection A first prohibiting means for prohibiting the detection of the development speed or the irradiation of the analysis light to the reagent immobilization unit when the scanning means previously irradiates the analysis light and the solution to be inspected has reached a predetermined position; It is characterized by having.

Further, a scanning means for detecting the arrival position of the irradiated specimen solution analysis light to the deployment direction of the inspection target solution in the specimen, the specimen solution is spotted specimens mounted or after the deployment speed detection A second prohibiting unit for prohibiting the detection of the development speed or the irradiation of the analysis light to the reagent immobilization unit when the scanning unit previously irradiates the analysis light and the arrival position of the solution to be inspected cannot be detected; It is characterized by that.

Furthermore, the irradiation direction of the analysis light used by the scanning means for detecting the arrival position of the solution to be inspected is from the downstream to the upstream of the solution to be inspected for developing the test piece.

Furthermore, when the expansion | deployment speed | velocity which the said detection means detects does not satisfy | fill predetermined speed, the 3rd prohibition means which prohibits irradiation of the analysis light to the said reagent fixing | fixed part is provided.

As described above, the present invention provides a reagent immobilization unit for immobilizing the test solution developed on the test piece on which the test solution is spotted, and irradiates the reagent immobilization unit with analysis light to thereby provide the test solution. In the analyzer for optically analyzing the reaction between the analysis light and the analyzing light, a detecting means for detecting a developing speed at which the solution to be inspected is developed on the test piece, a developing speed detected by the detecting means, and the test piece And setting means for setting the irradiation start time of the analysis light based on the performance.Therefore, when performing the absorbance measurement, there is a large error in the measurement value due to the difference in the development speed and the performance of the test piece. In other words, the absorbance value is not stabilized after the completion of the development, and as a result, the detection accuracy can be improved.

Hereinafter, embodiments of the analyzer according to the present invention will be described in detail with reference to the drawings.
Example 1
FIG. 1 is a diagram showing a schematic configuration of an analyzer according to the present invention.

In FIG. 1, when the solution to be inspected is spotted on the spotted portion 8 of the solution to be inspected of the test piece 7, the solution to be inspected develops in the channel 9 having a width indicated by the arrow 9a of the test piece 7. The deployment direction is developed toward the downstream side on the opposite side, with the spotted portion 8 side of the test piece 7 as the upstream side. While the solution to be inspected develops, the labeling reagent also develops together with the solution to be inspected by first passing through the labeling reagent holding unit 10. The developed labeling reagent is fixed to the reagent immobilization unit 11 in the flow path 9 in accordance with the concentration of the analyte in the test solution. In addition, the test piece 7 can be removed from the apparatus, and the test solution is spotted with the test piece 7 removed, and the measurement is started by detecting that the test piece 7 is attached to the apparatus. The signal is

In FIG. 1, light emitted from a semiconductor laser as a light source is converted into a parallel beam and irradiated onto the test piece 7 as a beam. An irradiation position 6 indicates a beam irradiation position. At this time, light is received by the first photodiode 4 as reference light 2. On the other hand, scattered light 3 (reflected light) is generated from the surface of the test piece 7 and is received by the second photodiode 5. Alternatively, instead of receiving the scattered light 3 from the surface of the test piece 7, the transmitted light that has passed through the test piece 7 may be received by a photodiode. Log conversion is performed on the outputs received by the first photodiode 4 and the second photodiode 5, and the Log conversion value of the second photodiode 5 is subtracted from the Log conversion value of the first photodiode 4, Output as an optical signal level absorbance value. Since light is absorbed by the labeling reagent and the test solution, the absorbance value of the portion where the labeling reagent and the test solution are developed is higher than that of the portion where the labeling reagent and the test solution are not developed. Further, the absorbance value of the reagent immobilization unit is used as the absorbance value of the analyte in the test solution.

Next, FIG. 2 is a diagram showing the relationship between the arrival position of the solution to be inspected and the measurement end condition.

The predetermined position 14 which is a range in which the development speed of the test solution 12 is detected is set 8 mm upstream from the downstream test piece edge, and the predetermined position 13 is set 4 mm upstream from the predetermined position 14.

  Further, by making the predetermined position 14 and the predetermined predetermined position for starting unfolding waiting (starting counting until the laser irradiation start time) the same position, it is not necessary to move from the predetermined position 14, so that the processing efficiency is improved. Become. The predetermined position 14 is desirably set on the downstream side where the difference in the deployment speed becomes large. The reason why the difference in the development speed becomes large on the downstream side is that the amount supplied up to the head of the solution 12 to be inspected varies depending on the difference in viscosity and the amount of the deposited sample.

After detecting the measurement start signal, the absorbance value is acquired while moving the beam 6a from the predetermined position 14 toward the upstream side, and the current arrival position of the solution 12 to be inspected is scanned. A stepping motor is used for movement.

The determination of the arrival of the solution to be inspected 12 is made when the absorbance value obtained by adding a predetermined threshold value to the absorbance value in the portion where the solution to be inspected 12 is not developed exceeds.

For example, when it is detected that the test solution 12 has reached the position 15 while scanning from the predetermined position 14 to the predetermined position 13 in FIG. 2A, the test solution 12 is already downstream of the predetermined position 13. Since the expansion speed cannot be obtained, the measurement is terminated. This indicates that it took time until the test piece was attached to the apparatus after the user spotted the test solution on the test piece.

Therefore, if the predetermined position 13 is further set on the upstream side and the distance from the predetermined position 14 is increased, the distance for measuring the development speed is increased, so that the accuracy is improved, but the solution to be tested is spotted. After that, the time required for attaching the test piece to the apparatus is shortened, and the operability for the user is deteriorated. Therefore, in consideration of the accuracy of the deployment speed and the user operability, it is desirable that the set position of the predetermined position 13 is within 4 to 6 mm upstream from the predetermined position 14.

If the arrival of the solution to be inspected 12 is not detected even after scanning up to the most upstream position 16 of the flow path 9 shown in FIG. 2B, the measurement is terminated as the solution to be inspected 12 is not spotted. . When the arrival of the solution to be inspected 12 is detected between the predetermined position 13 and the most upstream position 16, the beam irradiation position is moved to the predetermined position 13 to prepare for the next operation.

Next, FIG. 3 is a diagram showing the relationship between the development of the solution to be inspected and the measurement range of the development speed.

  The arrival of the solution to be inspected 12a is detected by irradiating the beam 6b to a predetermined position 13a located upstream in the range 17 in which the development speed of the solution to be inspected 12a is detected (FIG. 3 (a)). When arrival is detected, the beam irradiation position is moved to a predetermined position 14a indicated by the beam 6c. Simultaneously with the start of movement, the CPU provided in the apparatus starts counting up the time counter A from zero. Next, when arrival of the solution to be inspected 12b is detected at the predetermined position 14a (FIG. 3B), the time counter A stops counting up.

In consideration of the case where the solution to be inspected does not reach the predetermined position 13a or the predetermined position 14a, a time limit for executing the arrival detection is provided. The time limit is set so that when the beam 6b is moved to the predetermined position 13a, the time counter A and another time counter B start counting up from 0 and reach a predetermined counter value. If the arrival of the solution to be inspected is not detected within the time limit, the measurement is terminated because the amount of the solution to be inspected necessary for development is insufficient. Next, the development speed of the solution to be inspected is calculated from the calculated counter value A and the distance between the range 17. The calculation method is set to range 17 ÷ counter value A = deployment speed (mm / s).

Alternatively, as another method for obtaining the development speed, FIG. 4 is a diagram showing the relationship between the development of the solution to be tested and the measurement range of the development speed, as in FIG.

The predetermined position 18 is set 12 mm upstream from the downstream test piece edge. If it is set upstream, the time from when the solution to be inspected is applied to when the test piece is attached to the apparatus is shortened, which is inconvenient when handled by the user.

  First, the beam 6d is irradiated to the predetermined position 18 to detect the arrival of the solution to be inspected 12c (FIG. 4A). When arrival is detected, the irradiation position of the beam 6d is moved downstream by a minimum moving distance (0.0125 mm) at which the beam can move. The minimum moving distance is the stepping motor control 1 STEP, which is proportional to the pitch width of the lead screw.

At this time, the beam movement must be faster than the developing speed of the solution to be inspected. When the arrival of the solution to be inspected is detected at the position where the beam has moved, the beam is moved again. The above operation is repeated until a predetermined time elapses after the solution 12c to be inspected reaches the predetermined position 18. After a certain time elapses, the development distance 19 from the predetermined position 18 to the current position of the beam 6e is calculated, and the development speed of the solution 12d to be inspected is calculated from the constant time and the development distance 19. The calculation method is: deployment distance 19 ÷ constant time = deployment speed (mm / s).

If the development speed calculated by the above method does not fall within the predetermined speed determined in advance, the measurement is terminated because there is an abnormality in the solution to be inspected. As the abnormal content of the solution to be inspected, if the development speed is slower than the predetermined speed, the amount of the solution to be inspected having a high viscosity that is not assumed by the analyzer or the amount of the solution to be inspected necessary for development is insufficient. There may be. Further, when the development speed is higher than a predetermined speed, the solution to be inspected has a low viscosity that is not assumed by the analyzer.

Next, the waiting time A necessary for the development is obtained by correcting the reference waiting time B using the calculated development speed. The waiting time at this time becomes the laser irradiation start time.

The waiting time B is a waiting time required for completion of the development obtained by an experiment using the average viscosity of the solution to be inspected. When the test solution is blood, the hematocrit is 40%.

The correction formula is
Waiting time A = waiting time B ÷ {1 + PalaA × Log (development speed) + PalaB} = waiting time B + adjustment time, and ParaA and PalaB can be changed according to the performance of the test piece. The waiting time in the performance of the test piece with respect to the deployment speed is adjusted with PalaA, and the adjustment value is offset and finely adjusted with PalaB.

  Alternatively, the waiting time corresponding to the development speed may be determined using a table that has been facilitated in advance from the calculated development speed. Even in this case, the table can be changed according to the performance of the test piece.

  Next, after waiting for the calculated waiting time A, the absorbance value colored on the reagent immobilization part of the test piece is obtained, and the concentration of the analyte in the solution to be examined is obtained.

  The effect by the above invention is demonstrated using FIG.

  FIG. 5 is a graph showing changes in absorbance values at three different viscosities having the same concentration of the analyte in the test solution.

  The viscosity A, the viscosity B, and the viscosity C are in descending order of the viscosity of the solution to be inspected, and the waiting time A obtained from the developing speed of the viscosity B and the correction formula is set as the waiting time 21. The waiting time 21 is equal to the reference waiting time B, and is further assumed to be equal to the constant waiting time of the conventional invention. In addition, the waiting time obtained from the developing speed of the viscosity A and the viscosity C and the correction formula are referred to as a waiting time 22 and a waiting time 23, respectively.

By correcting the waiting time according to the viscosity, the viscosity A having a low viscosity has a waiting time 22 shorter than that of the conventional invention, and the measurement time can be shortened. Further, a stable absorbance value 20 at each viscosity (a value when the binding between the labeling reagent and the reagent immobilization part is completed) can be acquired.

The analyzer according to the present invention has a function of removing the influence on the measurement due to the viscosity of the solution to be inspected, and is useful in a technical field where a highly accurate measurement result is required.

The analysis apparatus according to the present invention has a function of correcting the measurement time corresponding to the viscosity of the solution to be inspected, and is useful in a technical field where a quick measurement time is required for measurement of an analysis object.

The schematic block diagram of the analyzer in this invention In the present invention, the relationship between the arrival position of the solution to be tested and the end of measurement In the present invention, the relationship between the development range of the solution to be tested and the measurement range of the development speed In the present invention, the relationship between the development range of the solution to be tested and the measurement range of the development speed In the present invention, changes in absorbance values at different viscosities Schematic configuration diagram of the analyzer in the conventional invention Changes in absorbance values during the development of the solution to be tested and the waiting time for development in the conventional invention Problem diagram of different viscosities in the conventional invention Problem diagram of different viscosities in the conventional invention

1, 1a Semiconductor laser (light source)
2, 2a Reference light 3, 3a Scattered light 4, 4a First photodiode 5, 5a Second photodiode 6, 6a, 6b, 6c, 6d, 6e Beam irradiation position 7, 7a Test piece 8, 8a Portions 9 and 9z Channel 9a Channel width 10, 10a Labeling agent holding portion 11, 11a Reagent immobilization portion 12, 12a, 12b, 12c, 12d Solution to be tested 13, 13a, 18 Upstream of measurement range of development speed Predetermined positions 14, 14a Predetermined positions downstream of the development speed measurement range 16 Uppermost stream positions 17, 19 of the flow path Measurement speed ranges 20, 20a Stable absorbance values 21, 21a, 22, 22a, 23 after deployment, 23a Deployment waiting time 24 Deployment waiting start position 25 Extra waiting time 26, 28 Error 27 Enlarged portion

Claims (10)

The reaction of the irradiated analysis light to the reagent immobilization part is provided a reagent immobilization part that fixes the inspection target solution developed on the test piece inspection target solution is spotted the inspection target solution and the analyzing light in the analyzer which optically analyzes the detection means for detecting the deployment speed of the inspection target solution is developed in the specimen, the analysis light based on the performance of the test piece and development speed detected by the detection means An analyzer comprising: setting means for setting an irradiation start time. 2. The analyzer according to claim 1, wherein the irradiation start time set by the setting means is a time measured after the solution to be inspected passes through a predetermined position on the test piece. 2. The analysis according to claim 1, wherein the developing speed detected by the detecting means is based on a difference in arrival time of the solution to be inspected at two different points arrived by developing the solution to be inspected. apparatus. 2. The analyzer according to claim 1, wherein the developing speed detected by the detecting means is based on a distance that the solution to be inspected is developed within a predetermined time. The analyzer according to claim 1, wherein the test piece is made of a strip-shaped porous carrier, and blood is developed by chromatography. The test strip comprises a labeled reagent, analyzer according to claim 1, wherein the optically analyzing a color of the labeled reagent. A scanning means for detecting the arrival position of the irradiated specimen solution analysis light to the deployment direction of the inspection target solution in the specimen, the prior detection of the inspection target solution is spotted specimens mounted or after the development speed A first prohibiting unit that prohibits detection of the development speed or irradiation of the analysis light to the reagent immobilization unit when the scanning unit irradiates analysis light and the solution to be inspected reaches a predetermined position; The analyzer according to claim 1. A scanning means for detecting the arrival position of the irradiated specimen solution analysis light to the deployment direction of the inspection target solution in the specimen, the prior detection of the inspection target solution is spotted specimens mounted or after the development speed A second prohibiting unit for prohibiting the detection of the development speed or the irradiation of the analysis light to the reagent immobilization unit when the scanning unit irradiates the analysis light and the arrival position of the solution to be tested cannot be detected. The analyzer according to claim 1, wherein 9. The irradiation direction of the analysis light used by the scanning means for detecting the arrival position of the solution to be inspected is from the downstream to the upstream of the solution to be inspected for developing the test piece. The analyzer in any one of. The analyzer according to claim 1, further comprising a third prohibiting unit that prohibits irradiation of the analysis light to the reagent immobilization unit when a deployment speed detected by the detection unit does not satisfy a predetermined speed.

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