JP4758793B2 - Sample analysis method and sample analyzer - Google Patents

Description

  The present invention relates to a sample analysis method and a sample analysis device, and more particularly to a sample analysis method and a sample analysis device for measuring a sample containing an interfering substance.

  Conventionally, a clinical analyzer is used as an example of a sample analyzer in the field of clinical examination. Prior to examination with a clinical analyzer, measurement of interfering substances (hemoglobin, bilirubin, chyle, etc.) in the sample is performed in order to evaluate the quality of the sample. An interfering substance is a substance that coexists in a sample together with a target substance to be inspected and adversely affects the measurement of the target substance. When such an interfering substance exists in the sample, the optical information of the sample may change, and the optical measurement of the target substance may not be performed accurately. The concentration of these interfering substances can be determined by measuring the absorbance at different wavelengths specific to the interfering substances. However, when measuring hemoglobin or bilirubin in a sample, if chyle is present in the sample, an increase in the baseline due to chyle is observed in the absorbance at each wavelength. It was difficult. On the other hand, it is desired to measure hemoglobin and bilirubin without being affected by chyle in the measurement of interfering substances for sample quality evaluation.

Thus, conventionally, by utilizing the fact that the absorbance of chyle is represented by an exponential function of wavelength, the absorbance at a predetermined wavelength is estimated, and by subtracting the estimated absorbance from the actually measured absorbance at that wavelength, A measuring method for removing the influence of chyle has been proposed. (For example, refer to Patent Document 1). In the measurement method disclosed in Patent Document 1, the absorbance obtained at a wavelength (660 nm) at which there is substantially no absorption of hemoglobin and bilirubin and absorption of chyle is obtained by using the absorbance of the chyle and the wavelength. By substituting into an exponential function (A = α · λ ^β (A: absorbance, α: constant due to particles, β: constant due to average particle diameter, λ: wavelength)) indicating the relationship, a predetermined wavelength λ The absorbance A at is estimated.

JP-A-6-66808

In the measurement method disclosed in Patent Document 1, since there is substantially no absorption of hemoglobin and bilirubin and there is only one absorbance obtained at a wavelength where chyle absorption is present, absorbance at a predetermined wavelength λ. An approximate expression is used to determine the unknowns α (a constant due to particles) and β (a constant due to the average particle diameter) of the equation for estimating A (A = α · λ ^β ). Therefore, it is difficult to calculate an accurate estimated value (absorbance) at a predetermined wavelength from the absorbance estimation formula determined using the approximate formula. As a result, there is a problem that it is difficult to obtain an accurate measurement result in which the influence of chyle is removed from the actually measured value.

  The present invention has been made to solve the above-described problems, and one object of the present invention is to provide a sample analysis method and a sample analysis apparatus capable of acquiring accurate optical information. For the purpose.

Means for Solving the Problems and Effects of the Invention

In order to achieve the above object, the sample analysis method according to the first aspect of the present invention provides a first absorbance at a first wavelength and a second wavelength , respectively, which are wavelengths that hemoglobin does not substantially absorb and chyle absorbs. And acquiring the second absorbance, obtaining the third absorbance at the third wavelength, which is the wavelength absorbed by hemoglobin and chyle, and containing chyle contained in the sample based on the first absorbance or the second absorbance A step of obtaining the degree, and a step of obtaining the unknowns α and β in the relational expression A = α · λ ^β for obtaining the absorbance A of chyle at an arbitrary wavelength λ based on the first absorbance and the second absorbance. Substituting the third wavelength into λ in the equation to estimate the absorbance of the chyle at the third wavelength, and subtracting the absorbance of the chyle at the third wavelength from the third absorbance, It is comprising a step of determining the content degree of hemoglobin.

In the sample analysis method according to the first aspect, the first wavelength, the second wavelength, and the third wavelength are wavelengths that bilirubin does not substantially absorb, and the fourth wavelength that is absorbed by hemoglobin, chyle, and bilirubin. In step 4, the fourth wavelength is obtained by substituting the fourth wavelength for λ in the relational expression to estimate the absorbance of chyle at the fourth wavelength, and by multiplying the degree of hemoglobin content by a constant. A step of estimating the absorbance of hemoglobin at the wavelength, and a step of determining the content of bilirubin contained in the sample by subtracting the absorbance of chyle at the fourth wavelength and the absorbance of hemoglobin at the fourth wavelength from the fourth absorbance. Further included. Hemoglobin and chyle are substances that interfere with the optical measurement of the target substance contained in the sample. After measuring the first absorbance, the second absorbance, and the third absorbance from the sample, a reagent is added to the sample. The method further includes a step of preparing a measurement sample, a step of optically measuring the measurement sample, and a step of analyzing a target substance contained in the sample based on optical information obtained by optical measurement. In addition, it further includes an output step of outputting the analysis result of the target substance together with information on the content of hemoglobin and chyle obtained from the sample. The target substance is a substance related to blood coagulation function, and the sample is plasma.

The sample analyzer according to the second aspect of the present invention acquires the first absorbance and the second absorbance at the first wavelength and the second wavelength , respectively, which are wavelengths that are absorbed substantially by hemoglobin but are not absorbed by chyle. A measurement unit for obtaining a third absorbance at a third wavelength, which is a wavelength absorbed by hemoglobin and chyle, and a degree of chyle contained in the sample based on the first absorbance or the second absorbance. and based on the second absorbance, with determining the unknowns alpha and beta in the equation a = α · λ ^β for determining the absorbance a of chyle in the arbitrary wavelength lambda, and substituting the third wavelength to the equation lambda Then, the absorbance of the chyle at the third wavelength is estimated, and the absorbance of the chyle at the third wavelength is subtracted from the third absorbance, thereby obtaining the content of hemoglobin contained in the sample. And a resulting means.

In the sample analyzer according to the second aspect, the first wavelength and the second wavelength are wavelengths that are not substantially absorbed by bilirubin, and the measurement unit is the fourth wavelength that is a wavelength that is absorbed by hemoglobin, chyle, and bilirubin. Obtaining the fourth absorbance, the obtaining means substitutes the fourth wavelength into λ of the relational expression, estimates the absorbance of the chyle at the fourth wavelength, and multiplies the degree of hemoglobin content by a constant, thereby obtaining the fourth wavelength. The absorbance of hemoglobin in the sample is estimated, and the content of bilirubin contained in the sample is obtained by subtracting the absorbance of chyle at the fourth wavelength and the absorbance of hemoglobin at the fourth wavelength from the fourth absorbance. In addition, output means for outputting information on the content of hemoglobin and chyle is further provided.

In the sample analyzer according to the second aspect, preferably, hemoglobin and chyle are substances that interfere with optical measurement of a target substance contained in the sample, and the measurement unit adds the reagent to the sample, thereby the target substance. And a preparation means for preparing a measurement sample used for optical measurement of the first, measuring the first absorbance, the second absorbance, and the third absorbance from the sample before the reagent is added, and preparing the measurement sample from the sample. The measurement sample is optically measured, and the target substance contained in the sample is analyzed based on optical information obtained by the optical measurement . In addition, output means for outputting the analysis result of the target substance together with information on the content of hemoglobin and chyle obtained from the sample is further provided.

In the sample analyzer according to the second aspect, preferably, the measurement unit includes a light source that selectively irradiates light having the first wavelength, light having the second wavelength, and light having the third wavelength, light having the first wavelength, A light receiving unit that receives light of the second wavelength and light of the third wavelength. If comprised in this way, while being able to irradiate a sample with the light of the 1st wavelength, the light of the 2nd wavelength, and the light of the 3rd wavelength with a light source easily, the light of three kinds of wavelengths which passed the sample is easy Can be received by the light receiving unit. In addition, it further includes a table for holding a plurality of light-transmitting containers containing samples in an annular shape, and the plurality of containers held by the table are sequentially arranged between the light source and the light receiving unit by rotating the table. It is configured to be.

In the sample analyzer according to the second aspect, preferably, the first wavelength and the second wavelength are wavelengths of 590 nm to 900 nm. As described above, if the first wavelength and the second wavelength are selected from the range of 590 nm to 900 nm, the wavelength that the second substance absorbs without being substantially absorbed by the first substance can be selected.

In the sample analyzer according to the second aspect, preferably, the third wavelength is a wavelength of not less than 500 nm and less than 590 nm. Thus, if the third wavelength is selected from the range of 500 nm or more and less than 590 nm, the absorption wavelength of the first substance can be selected.

In the configuration for measuring the fourth absorbance at the fourth wavelength, the fourth wavelength is preferably a wavelength of 300 nm or more and less than 500 nm. Thus, if the fourth wavelength is selected from the range of 300 nm or more and less than 500 nm, the absorption wavelength of the third substance can be selected.

  DESCRIPTION OF THE PREFERRED EMBODIMENTS Embodiments embodying the present invention will be described below with reference to the drawings.

  FIG. 1 is a perspective view showing an overall configuration of a sample analyzer according to an embodiment of the present invention. FIG. 2 shows a detection mechanism unit and a transport mechanism unit of the sample analyzer according to the embodiment shown in FIG. It is the shown top view. 3 to 9 are diagrams for explaining details of the configuration of the sample analyzer according to the embodiment shown in FIG. 10 to 15 are graphs showing the absorbance spectrum of the interference substance. First, with reference to FIGS. 1-15, the whole structure of the sample analyzer 1 by one Embodiment of this invention is demonstrated.

  A sample analyzer 1 according to an embodiment of the present invention is an apparatus for optically measuring and analyzing the amount and the degree of activity of a specific substance related to blood coagulation / fibrinolysis functions. Plasma is used. In the sample analyzer 1 according to the present embodiment, the sample is optically measured using a coagulation time method, a synthetic substrate method, and an immunoturbidimetric method. The coagulation time method is a measurement method for detecting the process of coagulation of a specimen as a change in transmitted light or scattered light. The synthetic substrate method is a measurement method that detects a change in absorbance in the process of color development of a chromogenic synthetic substrate added to a specimen based on a change in transmitted light. The immunoturbidimetric method is a measurement method for detecting a change in absorbance due to an antigen-antibody reaction of an antibody sensitizing reagent such as a latex reagent added to a specimen based on a change in transmitted light. As shown in FIG. 1, the sample analyzer 1 includes a detection mechanism unit 2, a transport mechanism unit 3 disposed on the front side of the detection mechanism unit 2, and a control device 4 electrically connected to the detection mechanism unit 2. It is comprised by.

  The transport mechanism unit 3 corresponds to the suction dispensing position 2a (see FIG. 2) of the detection mechanism unit 2 with the rack 151 on which a plurality of (in this embodiment, ten) test tubes 150 containing specimens are placed. By transporting to the position, the specimen is automatically supplied to the detection mechanism unit 2. In the transport mechanism unit 3, a rack set region 3a for setting a rack 151 on which a test tube 150 containing an unprocessed sample is placed, and a test tube 150 containing a treated sample are placed. A rack housing area 3b for housing the rack 151. That is, the rack 151 set in the rack setting area 3a is transported to a position corresponding to the suction dispensing position 2a of the detection mechanism unit 2 as shown in FIG. Then, after the sample dispensing (primary dispensing) process in the test tube 150 by the detection mechanism unit 2 is performed, the detection mechanism unit 2 transports and stores the sample in the rack storage region 3b. A plurality of racks 151 can be set in the rack setting area 3 a of the transport mechanism unit 3.

  The control device 4 includes a personal computer (PC) and the like, and includes a control unit 4a, a display unit 4b, and a keyboard 4c as shown in FIG. As shown in FIG. 5, the control unit 4a mainly includes a CPU 4d, a ROM 4e, a RAM 4f, a hard disk 4g, an input / output interface 4h, an image output interface 4i, and a communication interface 4j. The ROM 4e, the RAM 4f, the hard disk 4g, the input / output interface 4h, the image output interface 4i, and the communication interface 4j are connected to each other via a bus 4k so that data communication is possible.

  The CPU 4d can execute computer programs stored in the ROM 4e and the hard disk 4g and computer programs read out to the RAM 4f.

  The ROM 4e stores a computer program to be executed by the CPU 4d and data used for executing the computer program.

  The RAM 4f is used as a work area for the CPU 4d when reading out the computer program stored in the ROM 4e and the hard disk 4g and executing the computer program.

  The hard disk 4g stores a computer program to be executed by the CPU 4d, data used for executing the computer program, and the like. This computer program has a function for analyzing optical information measured by the detection mechanism unit 2 and outputting an analysis result.

  An input unit including a keyboard 4c, a mouse (not shown), and the like is connected to the input / output interface 4h. The input unit (keyboard 4c, mouse, etc.) is provided for performing operations on the screen of the display unit 4b. The image output interface 4i is connected to a display unit 4b composed of a liquid crystal display. The display unit 4b is provided to display information on interfering substances (hemoglobin, chyle (lipid) and bilirubin) present in the specimen and the analysis result obtained by the control unit 4a. The communication interface 4j is connected to the detection mechanism unit 2 and has a function for receiving optical information measured by the detection mechanism unit 2.

  The detection mechanism unit 2 is configured to be able to acquire optical information related to the sample by performing optical measurement on the sample supplied from the transport mechanism unit 3. In the sample analyzer 1 according to the present embodiment, optical measurement is performed on the sample dispensed from the test tube 150 of the transport mechanism unit 3 into the cuvette 152 (see FIG. 2) of the detection mechanism unit 2. As shown in FIGS. 1 and 2, the detection mechanism unit 2 includes a cuvette supply unit 10, a rotary transport unit 20, a sample dispensing arm 30, a first optical information acquisition unit 40, a lamp unit 50, Two reagent dispensing arms 60, a cuvette transfer unit 70, a second optical information acquisition unit 80, an emergency sample setting unit 90, a cuvette disposal unit 100, and a fluid unit 110 are provided.

  The cuvette supply unit 10 is configured to be able to sequentially supply a plurality of cuvettes 152 to the rotary conveyance unit 20. As shown in FIG. 2, the cuvette supply unit 10 includes a hopper 12 attached to the apparatus main body via a bracket 11 (see FIG. 1), two guide plates 13 provided below the hopper 12, A support base 14 disposed at the lower ends of the two guide plates 13 and a supply catcher portion 15 provided at a predetermined interval from the support base 14 are included. The two guide plates 13 are smaller than the diameter of the flange portion 152a (see FIG. 4) of the cuvette 152 and larger than the diameter of the trunk portion 152b (see FIG. 4) of the cuvette 152. They are arranged in parallel. The cuvette 152 supplied into the hopper 12 is configured to move while sliding down toward the support base 14 with the collar portion 152a engaged with the upper surfaces of the two guide plates 13.

  As shown in FIG. 2, the support base 14 includes a rotating portion 14 a provided so as to be rotatable with respect to the support base 14, and a concave portion 14 b formed adjacent to the rotating portion 14 a. Four cutouts 14c are formed at a predetermined angle (90 degrees) on the outer peripheral portion of the rotating portion 14a. These four cutouts 14c are provided to accommodate the cuvettes 152 guided by the two guide plates 13 one by one. The recess 14b is configured to receive the cuvette 152 in the notch 14c of the rotating portion 14a, and supply starts when the cuvette 152 is supplied to the rotary conveying unit 20 by the supply catcher unit 15. It is provided as a position.

  The supply catcher unit 15 is provided to supply the cuvette 152 of the cuvette supply unit 10 to the rotary conveyance unit 20. The supply catcher 15 includes a drive motor 15a, a pulley 15b connected to the drive motor 15a, a pulley 15c provided at a predetermined interval from the pulley 15b, and a drive transmission mounted on the pulleys 15b and 15c. It has a belt 15d, an arm portion 15f attached to the pulley 15c via a shaft 15e, and a drive portion 15g for moving the arm portion 15f in the vertical direction. The drive motor 15a has a function as a drive source for rotating the arm portion 15f about the shaft 15e between the support base 14 and the rotary conveyance unit 20. A chuck portion 15h for sandwiching and gripping the cuvette 152 is provided at the tip of the arm portion 15f.

  The rotary transport unit 20 is provided to transport the cuvette 152 supplied from the cuvette supply unit 10 and the reagent container (not shown) containing the reagent added to the specimen in the cuvette 152 in the rotation direction. Yes. The rotary transport unit 20 includes a circular reagent table 21, an annular reagent table 22 disposed outside the circular reagent table 21, and a circle disposed outside the annular reagent table 22. An annular secondary dispensing table 23 and an annular primary dispensing table 24 disposed outside the annular secondary dispensing table 23 are configured. The primary dispensing table 24, the secondary dispensing table 23, the reagent table 21, and the reagent table 22 can be rotated in both the clockwise direction and the counterclockwise direction, and the respective tables are independent of each other. And can be rotated.

  Each of the reagent tables 21 and 22 includes a plurality of holes 21a and 22a provided at predetermined intervals. The holes 21a and 22a of the reagent tables 21 and 22 are provided for placing a plurality of reagent containers (not shown) containing various reagents added when preparing a measurement sample from a specimen. Yes. Further, the primary dispensing table 24 and the secondary dispensing table 23 include a plurality of cylindrical holding portions 24a and 23a provided at predetermined intervals, respectively. The holding parts 24 a and 23 a are provided to hold the cuvette 152 supplied from the cuvette supply part 10. A sample from the test tube 150 of the transport mechanism unit 3 is dispensed to the cuvette 152 held in the holding unit 24a of the primary dispensing table 24 during the primary dispensing process. In addition, the sample from the cuvette 152 held in the primary dispensing table 24 is dispensed to the cuvette 152 held in the holding unit 23a of the secondary dispensing table 23 during the secondary dispensing process. Further, as shown in FIG. 4, the holding portion 24a has a pair of small holes 24b formed at positions facing each other on the side of the holding portion 24a. The pair of small holes 24b is provided to allow light emitted from the optical fiber 55 of the first optical information acquisition unit 40 described later to pass therethrough.

  The sample dispensing arm 30 shown in FIG. 2 transfers the sample in the test tube 150 conveyed by the conveyance mechanism unit 3 to the suction dispensing position 2a of the detection mechanism unit 2 in the primary dispensing table 24 of the rotary conveyance unit 20. It has a function for dispensing into the cuvette 152 held by the holding part 24a. The sample dispensing arm 30 holds the sample in the cuvette 152 held by the holding unit 24 a of the primary dispensing table 24 of the rotary conveyance unit 20 in the holding unit 23 a of the secondary dispensing table 23. It also has a function for dispensing in the cuvette 152. The sample dispensing arm 30 includes a drive motor 31, a drive transmission unit 32 connected to the drive motor 31, and an arm unit 34 attached to the drive transmission unit 32 via a shaft 33 (see FIG. 1). It is out. The drive transmission unit 32 is configured to be capable of rotating the arm unit 34 about the shaft 33 and moving the arm unit 34 in the vertical direction by the driving force from the drive motor 31. A nozzle 35 (see FIG. 1) for aspirating and discharging the specimen is attached to the distal end of the arm portion 34.

  The first optical information acquisition unit 40 detects optical information from the sample in order to detect the presence, type, and content of interference substances (chyle, hemoglobin, and bilirubin) in the sample before adding the reagent. (Absorbance) is acquired. The acquisition of the optical information (absorbance) of the sample by the first optical information acquisition unit 40 is performed before the optical measurement of the sample by the second optical information acquisition unit 80. As shown in FIGS. 2 and 3, the first optical information acquisition unit 40 is disposed above the primary dispensing table 24 of the rotary conveyance unit 20 and is held by the holding unit 24 a of the primary dispensing table 24. Optical information is acquired from the specimen in the cuvette 152. As shown in FIGS. 3 and 4, the first optical information acquisition unit 40 includes a light emitting side holder 41, a photoelectric conversion element 42 (see FIG. 4), a light receiving side holder 43, a bracket 44, and a photoelectric conversion element. And a substrate 45 on which 42 is mounted.

  The substrate 45 has a function of amplifying an electrical signal from the photoelectric conversion element 42 and transmitting the amplified signal to the control unit 4a of the control device 4. As shown in FIG. 6, the substrate 45 includes a preamplifier 45a, an amplification unit 45b, an A / D converter 45c, and a controller 45d. The amplification unit 45b includes an amplifier 45e and an electronic volume 45f. The preamplifier 45a and the amplifier 45e are provided to amplify the electric signal from the photoelectric conversion element 42. The amplifier 45e of the amplifying unit 45b is configured to be able to adjust the gain (amplification factor) of the amplifier 45e by inputting a control signal from the controller 45d to the electronic volume 45f. The A / D converter 45c is provided to convert the electric signal (analog signal) amplified by the amplifier 45e into a digital signal.

  The controller 45d changes the gain (amplification factor) of the amplifier 45e in accordance with a periodic change in the wavelength (405 nm, 575 nm, 660 nm, and 800 nm) of light emitted from the optical fiber 55 of the lamp unit 50 described later. It is configured. Further, as shown in FIG. 6, the controller 45 d is electrically connected to the control unit 4 a of the control device 4, and the digital signal data acquired by the first optical information acquisition unit 40 is transmitted to the control device 4. It transmits to the control part 4a. Thereby, in the control device 4, the digital signal data from the first optical information acquisition unit 40 is analyzed (analyzed), whereby the specimen in the cuvette 152 for the four types of light emitted from the optical fiber 55 is obtained. And the presence / absence and type of interfering substances in the sample, the degree of inclusion, and the like are analyzed. Based on the analysis result, it is determined whether or not the sample is measured by the second optical information acquisition unit 80, and the detection result analysis method and analysis result from the second optical information acquisition unit 80 are determined. Display method is controlled.

  As shown in FIG. 7, the lamp unit 50 includes a halogen lamp 51, three condenser lenses 52, a disk-shaped filter member 53, an optical fiber coupler 54, and optical fibers 55 and 56. Yes. The three condenser lenses 52 are provided for condensing the light from the halogen lamp 51 on the filter member 53. The two optical fibers 55 and 56 extending from the optical fiber coupler 54 are led to the first optical information acquisition unit 40 and the second optical information acquisition unit 80, respectively.

  Further, as shown in FIGS. 7 and 8, the filter member 53 is provided to be rotatable around a shaft 53a. As shown in FIG. 8, the filter member 53 is provided with a plurality of filters 53 b having different transmission wavelengths at predetermined angular intervals (45 degrees in the present embodiment) along the rotation direction of the filter member 53. . As described above, by configuring the filter member 53 having the plurality of filters 53b having different transmission wavelengths to be rotatable, the light from the halogen lamp 51 can sequentially pass through the plurality of filters 53b having different transmission wavelengths. Therefore, it is possible to sequentially supply light having a plurality of different wavelengths to the optical fibers 55 and 56. In the present embodiment, the filter member 53 supplies light having four different wavelengths of 405 nm, 575 nm, 660 nm, and 800 nm to the optical fiber 55, and five different values of 340 nm, 405 nm, 575 nm, 660 nm, and 800 nm. Light having a wavelength is supplied to the optical fiber 56.

  3 to 6, the optical fiber 55 is a cuvette in which light having four different wavelengths supplied from the optical fiber coupler 54 (see FIG. 7) is held in the holding unit 24a of the primary dispensing table 24. 152 is provided to irradiate. The light emission side holder 41 is provided in order to support the optical fiber 55 as shown in FIG. The photoelectric conversion element 42 has a function for detecting light from the optical fiber 55 that has passed through the cuvette 152 and converting it into an electrical signal. As shown in FIG. 3, the light-receiving side holder 43 is attached to the light-emitting side holder 41 via a bracket 44, and is formed in a shape that can accommodate the photoelectric conversion element 42 (see FIG. 4). The light receiving side holder 43 is attached with a lid member 43a provided with a slit 43b at a predetermined position. The light from the optical fiber 55 that has passed through the cuvette 152 held by the holding portion 24a of the primary dispensing table 24 is detected by the photoelectric conversion element 42 through the slit 43b of the lid member 43a.

  As shown in FIG. 9, the optical fiber 56 has a cuvette placement portion 81 (see FIG. 7) of the second optical information acquisition portion 80 to be described later with light having five different wavelengths supplied from the optical fiber coupler 54 (see FIG. 7). It is provided to irradiate the cuvette 152 held in (see FIG. 2).

  Here, with reference to FIG. 10 to FIG. 15, the light of the four wavelengths (405 nm, 575 nm, 660 nm, and 800 nm) emitted from the optical fiber 55 guided to the first optical information acquisition unit 40 will be described in detail. To do. The light having a wavelength of 660 nm and the light having a wavelength of 800 nm are light that hemoglobin and bilirubin do not substantially absorb and chyle absorbs, as shown in FIGS. Moreover, the light which has a wavelength of 575 nm is light which bilirubin does not absorb substantially and hemoglobin and chyle absorb. Moreover, the light which has a wavelength of 405 nm is light which all of hemoglobin, bilirubin, and chyle absorb. Then, as shown in FIG. 12, the chyle absorbs light having a wavelength from 405 nm in the low wavelength region to 800 nm in the high wavelength region. Therefore, when chyle is added to hemoglobin, as shown in FIG. 13, the absorbance spectrum of hemoglobin is equal to the absorbance (absorbing light) of chyle compared to the absorbance spectrum of hemoglobin shown in FIG. It can be seen that the baseline is rising. In addition, when chyle is added to bilirubin, as shown in FIG. 14, the baseline of the absorbance spectrum of bilirubin increases by the amount of absorbance of chyle compared to the absorbance spectrum of bilirubin shown in FIG. You can see that

Further, when the absorbance spectrum of chyle shown in FIG. 12 is plotted on a log-log graph, it is known that the absorbance spectrum of chyle is substantially a linear expression (straight line) as shown in FIG. It has been. That is, the linear expression (straight line) can be expressed as the following expression (1) using the constants a and b.
log ₁₀ Y = alog ₁₀ X + b (1) (Y: absorbance, X: wavelength)

  Since the sample (plasma) to be measured by the sample analyzer 1 according to the present embodiment includes interference substances (chyle, hemoglobin, and bilirubin), the sample measured using light having a wavelength of 405 nm is used. The absorbance is attributed to the absorbance of chyle, the absorbance of hemoglobin, and the absorbance of bilirubin. In addition, the absorbance of the specimen measured using light having a wavelength of 575 nm is attributed to the absorbance of chyle and hemoglobin, and not to the absorbance of bilirubin. In addition, the absorbance of the specimen measured using light having wavelengths of 660 nm and 800 nm contributes only to the absorbance of chyle, and does not contribute to the absorbance of hemoglobin and the absorbance of bilirubin. Therefore, by analyzing the absorbance of the sample measured using light having a wavelength of 660 nm and / or 800 nm, it is determined whether the content of chyle in the sample is an amount that adversely affects the measurement. Is possible. Whether or not the hemoglobin content in the sample has an adverse effect on the measurement by removing the influence (absorbance) of chyle from the absorbance of the sample measured using light having a wavelength of 575 nm. Can be determined. Then, by removing the influence of chyle (absorbance) and the influence of hemoglobin (absorbance) from the absorbance of the specimen measured using light having a wavelength of 405 nm, the content of bilirubin in the specimen has an adverse effect on the measurement. It is possible to determine whether the amount is given.

  Further, the two reagent dispensing arms 60 shown in FIG. 2 are configured so that the reagents in the reagent containers (not shown) placed in the holes 21 a and 22 a of the reagent tables 21 and 22 are transferred to the secondary dispensing table 23. The cuvette 152 is provided for dispensing. By these two reagent dispensing arms 60, a reagent is added to the specimen in the cuvette 152 of the secondary dispensing table 23 to prepare a measurement sample. As shown in FIG. 2, each of the two reagent dispensing arms 60 includes a drive motor 61, a drive transmission unit 62 connected to the drive motor 61, and a shaft 63 (see FIG. 1) connected to the drive transmission unit 62. And an arm portion 64 attached thereto. The drive transmission unit 62 is configured to be able to rotate the arm unit 64 about the shaft 63 and to move in the vertical direction by the driving force from the drive motor 61. A nozzle 65 (see FIG. 1) for aspirating and discharging the reagent is attached to the distal end portion of the arm portion 64.

  The cuvette transfer unit 70 is provided to transfer the cuvette 152 containing the measurement sample between the secondary dispensing table 23 of the rotary conveyance unit 20 and the cuvette placement unit 81 of the second optical information acquisition unit 80. It has been. As shown in FIG. 2, the cuvette transfer unit 70 includes a chuck unit 71 for sandwiching and gripping the cuvette 152, and a chuck unit 71 for moving the chuck unit 71 in the X direction, the Y direction, and the Z direction (see FIG. 1). Drive mechanism 72. In addition, the drive mechanism unit 72 has a function for vibrating the chuck unit 71. Thus, the measurement sample accommodated in the cuvette 152 can be easily stirred by vibrating the chuck portion 71 while holding the cuvette 152.

  The second optical information acquisition unit 80 has a function of heating a measurement sample prepared by adding a reagent to a specimen and optically measuring the measurement sample. As shown in FIG. 2, the second optical information acquisition unit 80 includes a cuvette placement unit 81 and a detection unit 82 disposed below the cuvette placement unit 81. The cuvette placement portion 81 is provided with a plurality of insertion holes 81 a for inserting the cuvette 152. The cuvette placement portion 81 incorporates a heating mechanism (not shown) for heating the cuvette 152 inserted into the insertion hole 81a to a predetermined temperature.

  Further, the detection unit 82 of the second optical information acquisition unit 80 can perform optical measurement on the measurement sample in the cuvette 152 inserted into the insertion hole 81a under a plurality of conditions. It is configured. As shown in FIG. 9, the detection unit 82 includes a photoelectric conversion element 83, a preamplifier 84, an amplification unit 85, an A / D converter 86, a logger 87, and a controller 88.

  The photoelectric conversion element 83 shown in FIG. 9 detects light from the lamp unit 50 that has passed through the measurement sample in the cuvette 152 inserted into the insertion hole 81a of the cuvette placement unit 81 and converts it into an electrical signal. It has a function to do. The photoelectric conversion element 83 is arranged to receive five types of light emitted from the optical fiber 56 of the lamp unit 50. Note that light having wavelengths of 340 nm and 405 nm irradiated from the optical fiber 56 is used for measurement by the synthetic substrate method, respectively. Moreover, the light which has a wavelength of 575 nm and 800 nm is each used for the measurement by an immunoturbidimetric method. In addition, light having a wavelength of 660 nm is used for measurement by a coagulation time method.

  The preamplifier 84 is provided to amplify the electric signal from the photoelectric conversion element 83. Then, as shown in FIG. 9, the amplifying unit 85 includes an amplifier (L) 85a having a predetermined gain (amplification factor) and an amplifier (H) 85b having a gain (amplification factor) higher than that of the amplifier (L) 85a. And a changeover switch 85c. In the present embodiment, the electrical signal from the preamplifier 84 is input to both the amplifier (L) 85a and the amplifier (H) 85b. The amplifier (L) 85a and the amplifier (H) 85b are provided to further amplify the electric signal from the preamplifier 84. The changeover switch 85c selects whether to output the electrical signal from the amplifier (L) 85a to the A / D converter 86 or to output the electrical signal from the amplifier (H) 85b to the A / D converter 86. Is provided to do. The changeover switch 85c is configured to perform a changeover operation when a control signal from the controller 88 is input.

  The A / D converter 86 is provided for converting the electrical signal (analog signal) from the amplification unit 85 into a digital signal. The logger 87 has a function for temporarily storing digital signal data from the A / D converter 86. The logger 87 is electrically connected to the control unit 4 a of the control device 4, and transmits digital signal data acquired by the second optical information acquisition unit 80 to the control unit 4 a of the control device 4. Thereby, in the control device 4, based on the analysis result of the digital signal data from the first optical information acquisition unit 40 acquired in advance, the data of the digital signal transmitted from the second optical information acquisition unit 80 is obtained. Analyzed and displayed on the display unit 4b.

  The emergency sample setting unit 90 shown in FIG. 2 is provided for performing a sample analysis process on a sample that requires an emergency. The emergency sample setting unit 90 is configured to allow an emergency sample to be interrupted when a sample analysis process is performed on the sample supplied from the transport mechanism unit 3. The emergency sample setting unit 90 includes a rail 91 provided so as to extend in the X direction, and an emergency sample rack 92 movable along the rail 91. In this emergency sample rack 92, a test tube insertion hole 92a for inserting a test tube (not shown) containing an emergency sample and a reagent container (not shown) containing a reagent are inserted. A reagent container insertion hole 92b is provided.

  The cuvette discarding unit 100 is provided for discarding the cuvette 152 of the rotary conveyance unit 20. As shown in FIG. 2, the cuvette disposal unit 100 includes a disposal catcher unit 101, a disposal hole 102 (see FIG. 1) provided at a predetermined interval from the disposal catcher unit 101, and a disposal hole 102. And a disposal box 103 installed below the screen. The disposal catcher unit 101 is provided to move the cuvette 152 of the rotary transport unit 20 to the disposal box 103 through the disposal hole 102 (see FIG. 1). The discard catcher unit 101 includes a drive motor 101a, a pulley 101b connected to the drive motor 101a, a pulley 101c provided at a predetermined interval from the pulley 101b, and a drive transmission attached to the pulleys 101b and 101c. The belt 101d has an arm portion 101f attached to the pulley 101c via a shaft 101e, and a drive portion 101g for moving the arm portion 101f in the vertical direction. The drive motor 101a has a function as a drive source for rotating the arm portion 101f between the rotary conveyance portion 20 and the disposal hole 102 about the shaft 101e. A chuck portion 101h for sandwiching and gripping the cuvette 152 is provided at the tip of the arm portion 101f. The disposal box 103 is provided with a grip portion 103a for gripping the user when the user pulls the disposal box 103 to the front side of the apparatus.

  The fluid section 110 shown in FIG. 1 is provided to supply a liquid such as a cleaning liquid to the nozzles 35 and 65 provided in each dispensing arm when the sample analyzer 1 is shut down.

  FIG. 16 is a flowchart showing a control flow of the control unit of the control device of the sample analyzer according to the embodiment shown in FIG. FIG. 17 is a diagram showing a sample analysis list output to the display unit of the control device of the sample analyzer according to the embodiment shown in FIG. Next, with reference to FIG. 1, FIG. 16, and FIG. 17, a sample analysis process of the sample analyzer 1 according to the embodiment of the present invention will be described.

  First, when the user turns on the power of the detection mechanism unit 2 and the control device 4 of the sample analyzer 1 shown in FIG. 1, the sample analyzer 1 is activated, whereby the sample analyzer 1 is activated. Is initialized. In the above-described initial setting, an operation for returning the mechanism for moving the cuvette 152 and each dispensing arm to the initial position is performed, whereby the detection mechanism unit 2 is initialized and the control device 4 The register of the control unit 4a is initialized (step S1). Then, sample analysis information is input by the user. That is, the user uses the keyboard 4c of the control device 4 to input information in the sample number and measurement item columns in the sample analysis list (see FIG. 17) output to the display unit 4b of the control device 4. Do. The control unit 4a accepts input of these sample analysis information (step S2), and these sample analysis information is stored in the control unit 4a.

  The user does not input the sample analysis information using the keyboard 4c, but a bar code label or the like is pasted on the test tube 150 containing the sample in advance and is read by a bar code reader or the like. The unit 4a may be configured to acquire the sample analysis information. In this case, when the barcode label data is read, the control unit 4a can access the host computer that manages the sample analysis information and the like, and acquire the sample analysis information corresponding to the data read from the barcode. . Thereby, the control part 4a can acquire sample analysis information, without a user inputting sample analysis information.

  Here, the sample analysis list shown in FIG. 17 will be described. In the sample number column, a number (such as “000101”) for identifying each sample is input. In addition, a symbol (“PT”, “ATIII” or the like) indicating an item of measurement performed on the sample is input in the measurement item column associated with the sample number. Measurement items “PT” (prothrombin time) and “APTT” (activated partial thromboplastin time) are items to be measured using a coagulation time method. The measurement item “ATIII” (antithrombin III) is an item to be measured using the synthetic substrate method. The measurement item “FDP” (fibrin degradation product) is an item to be measured using an immunoturbidimetric method (hereinafter, optical measurement performed using a clotting time method, a synthetic substrate method, or an immunoturbidimetric method). To “main measurement”).

  The sample analysis list also includes an item of secondary dispensing flag, an interference substance flag item including three small items of bilirubin, hemoglobin, and chyle, an item of wavelength change flag, and an item of high gain flag. And are provided. Each of these items is set to OFF (indicated by “0” in the table) in the initial setting of step S1, but according to the analysis result of the optical information from the first optical information acquisition unit 40, Changed to on (displayed as “1” in the table). FIG. 17 shows a state in which all items are off. The state in which the secondary dispensing flag is on indicates that the sample is the subject of secondary dispensing for the measurement item. When the interfering substance flag bilirubin, hemoglobin, or chyle flag is on, it is likely that the specimen is highly influenced by bilirubin, hemoglobin, or chyle for the measurement item. The state in which the wavelength change flag is on indicates that optical information acquired using light having a wavelength (800 nm) different from light having a normal wavelength (660 nm) is to be analyzed for the measurement item. The state in which the High gain flag is on indicates that optical information acquired with a gain (amplification factor) higher than the gain (amplification factor) of the normal amplifier 45e is to be analyzed.

  After the sample number and the measurement item are input, a reagent container (not shown) containing a reagent necessary for preparing a measurement sample and a test tube 150 containing the sample are set at predetermined positions. In this state, the user inputs an analysis process start. Thereby, in step S3, the sample analysis process is started. Then, after the predetermined sample analysis process is completed, it is determined in step S4 whether or not an instruction for shutting down the sample analyzer 1 has been input. If it is determined in step S4 that an instruction to shut down the sample analyzer 1 has not been input, the process returns to step S2, and other sample analysis information is input by the user. On the other hand, if it is determined in step S4 that an instruction to shut down the sample analyzer 1 has been input, a shutdown process is performed in step S5. Thereby, after the nozzle 35 and the nozzle 65 provided in each dispensing arm shown in FIG. 1 are cleaned, the power of the detection mechanism unit 2 and the control device 4 of the sample analyzer 1 is automatically turned off. The sample analysis process of the sample analyzer 1 is completed.

  FIG. 18 is a flowchart showing details (subroutine) of analysis processing by the control unit 4a according to the embodiment shown in step S3 of FIG. Next, with reference to FIG. 1, FIG. 2, FIG. 4 to FIG. 8 and FIG. 18, the analysis processing by the control device 4 in step S3 of FIG. When the user inputs the start of analysis processing, data instructing measurement of the first optical information is transmitted to the detection mechanism unit 2, and the measurement is instructed (step S11). As described above, when the measurement of the first optical information is instructed, first, the transport mechanism unit 3 shown in FIG. 2 transports the rack 151 on which the test tube 150 containing the sample is placed. . Thereby, the rack 151 in the rack setting area 3a is transported to a position corresponding to the suction dispensing position 2a of the detection mechanism section 2. Then, a predetermined amount of sample is aspirated from the test tube 150 by the nozzle 35 (see FIG. 1) of the sample dispensing arm 30. Then, the drive motor 31 of the sample dispensing arm 30 is driven to move the nozzle 35 of the sample dispensing arm 30 above the cuvette 152 held on the primary dispensing table 24 of the rotary conveyance unit 20. Then, the primary dispensing process is performed by discharging the sample from the nozzle 35 of the sample dispensing arm 30 into the cuvette 152 of the primary dispensing table 24.

  Then, the primary dispensing table 24 is rotated, and the cuvette 152 into which the sample is dispensed is transported to a position where measurement by the first optical information acquisition unit 40 is possible. Thereby, the optical measurement with respect to the sample is performed by the first optical information acquisition unit 40, and optical information is acquired from the sample. Specifically, first, four different wavelengths (405 nm, 575 nm, 660 nm, and 800 nm) from the optical fiber 55 that has passed through the specimen in the cuvette 152 held in the holding unit 24a (see FIG. 4) of the primary dispensing table 24. ) Are sequentially detected by the photoelectric conversion element 42. Then, the electric signal converted by the photoelectric conversion element 42 is amplified by the preamplifier 45a (see FIG. 6) and the amplifier 45e, and converted into a digital signal by the A / D converter 45c. Thereafter, the digital signal data is input to the controller 4a of the controller 4 by the controller 45d, and the controller 4a receives the first optical information (step S12). In step S13, the control unit 4a of the control device 4 analyzes (analyzes) the first optical information of the specimen.

  In step S14, the control unit 4a (see FIG. 1) of the control device 4 causes the sample in the cuvette 152 held in the holding unit 24a of the primary dispensing table 24 to be secondary based on the analysis result in step S13. It is determined whether or not it is a target for dispensing. If it is determined in step S14 that the sample in the cuvette 152 held in the primary dispensing table 24 is not a target for secondary dispensing, the control unit 4a is contained in the sample in step S15. Interfering substances (at least one substance selected from the group consisting of bilirubin, hemoglobin, and chyle (including cases where it is difficult to identify the interfering substances)) are highly affected, making it difficult to perform highly reliable analysis. A message having a certain content is output to the display unit 4b (see FIG. 1) of the control device 4. On the other hand, if it is determined in step S14 that the sample in the cuvette 152 held in the holding unit 24a of the primary dispensing table 24 is the subject of the secondary dispensing, the second optical information is obtained in step S16. Is transmitted to the detection mechanism unit 2 to instruct the measurement. A predetermined amount of sample is aspirated from the cuvette 152 held in the holding unit 24 a of the primary dispensing table 24 by the nozzle 35 of the sample dispensing arm 30. Thereafter, a predetermined amount of specimen is discharged from the nozzle 35 of the specimen dispensing arm 30 to the plurality of cuvettes 152 of the secondary dispensing table 23, whereby the secondary dispensing process is performed.

  Then, the reagent dispensing arm 60 is driven, and the reagent in the reagent container (not shown) placed on the reagent tables 21 and 22 is added to the specimen in the cuvette 152 of the secondary dispensing table 23. . Thereby, the sample for a measurement is prepared. Then, by using the chuck portion 71 of the cuvette transfer portion 70, the cuvette 152 of the secondary dispensing table 23 in which the measurement sample is accommodated is inserted into the insertion hole 81a of the cuvette placement portion 81 of the second optical information acquisition portion 80. Move.

  Then, the detection unit 82 of the second optical information acquisition unit 80 performs optical measurement on the measurement sample in the cuvette 152 under a plurality of conditions, so that a plurality (10 types) of measurement samples can be obtained. Optical information is acquired. Specifically, first, the cuvette 152 inserted into the insertion hole 81a of the cuvette placement portion 81 is heated to a predetermined temperature by a heating mechanism (not shown). Thereafter, light is applied to the cuvette 152 of the cuvette placement unit 81 from the optical fiber 56 (see FIG. 7) of the lamp unit 50. The optical fiber 56 is periodically irradiated with light of five different wavelengths (340 nm, 405 nm, 575 nm, 660 nm, and 800 nm) by the rotation of the filter member 53 (see FIG. 8). The light of each wavelength irradiated from the optical fiber 56 and transmitted through the cuvette 152 and the measurement sample in the cuvette 152 is sequentially detected by the photoelectric conversion element 83 as shown in FIG. Then, electrical signals corresponding to light of five different wavelengths converted by the photoelectric conversion element 83 are amplified by the preamplifier 84 and then sequentially input to the amplifying unit 85.

  In the amplifying unit 85, electric signals corresponding to light of five different wavelengths from the preamplifier 84 are respectively input to the amplifier (H) 85b having a high gain and the amplifier (L) 85a having a normal gain. Then, by controlling the changeover switch 85c by the controller 88, the electrical signal amplified by the amplifier (H) 85b is output to the A / D converter 86, and then the electrical signal amplified by the amplifier (L) 85a The data is output to the A / D converter 86. Here, the changeover switch 85 c is repeatedly changed over according to the rotation timing of the filter member 53 in the lamp unit 50. Thereby, in the amplifying unit 85, electric signals corresponding to light of five different wavelengths are respectively amplified at two different amplification factors, and a total of ten types of electric signals are repeatedly output to the A / D converter 86. The 10 types of electrical signals are converted into digital signals by the A / D converter 86, temporarily stored in the logger 87, and then sequentially transmitted to the control unit 4 a of the control device 4. The control unit 4a receives the second optical information (step S17).

  In step S18, the second optical information is obtained based on the analysis result of the optical information (digital signal data) from the first optical information acquisition unit 40 acquired in advance by the control unit 4a of the control device 4. Analysis (analysis) of the optical information determined to be suitable for analysis among a plurality (ten types) of optical information with respect to the measurement sample from the acquisition unit 80 is performed. In step S19, the control unit 4a of the control device 4 determines whether or not the analysis result of the measurement sample in step S19 can be output. In step S19, if it is determined that the analysis result of the measurement sample in step S18 cannot be output, it is difficult to perform highly reliable analysis in step S15. The message is output to the display unit 4b (see FIG. 1) of the control device 4. In addition, as a case where judgment from above-mentioned step S19 to step S15 is performed, in this embodiment, in the measurement item performed using a coagulation time method, the analysis result of the data of the electrical signal corresponding to the light of a wavelength of 800 nm is used. The case where it cannot output is mentioned. On the other hand, if it is determined in step S19 that the analysis result of the measurement sample in step S18 can be output, the analysis result of the measurement sample is output to the display unit 4b of the control device 4 in step S20. To do.

  In step S14, if it is determined from the analysis result of the first optical information that a reliable measurement result cannot be obtained at the default wavelength, measurement is performed at a wavelength different from the default wavelength. You may make a judgment. When measurement is performed at different wavelengths, it is determined whether or not the analysis result can be output after performing measurement (main measurement) and analysis of the second optical information. If it is determined that output is possible, the analysis result is output to the display unit 4b (step S20). If it is determined that output is not possible, it is difficult to perform highly reliable analysis in step S15. A message indicating that there is a message is output to the display unit 4b (step S15).

  19 to 22 are flowcharts for explaining the details (subroutine) of the optical information analysis processing from the first optical information acquisition unit according to the embodiment shown in step S13 of FIG. Next, the first optical information analysis processing method in step S13 of FIG. 18 will be described in detail with reference to FIGS. 1 and 17 to 22.

Here, in the present embodiment, the optical information (light transmittance) of the specimen acquired by the first optical information acquisition unit 40 is input to the control unit 4a of the control device 4 as shown in FIG. In step S31, the absorbance of the specimen for light of each wavelength (405 nm, 575 nm, 660 nm, and 800 nm) is calculated. Here, the absorbance A is a value obtained by the following equation (2) using the light transmittance T (%) of the specimen.
A = −log ₁₀ (T / 100) (2)

  In step S32, chyle is checked. Specifically, as shown in FIG. 20, in step S32a, it is determined whether or not the absorbance (Abs. 660) of the specimen with respect to light having a wavelength of 660 nm is greater than a predetermined value. If it is determined in step S32a that the absorbance (Abs. 660) of the sample with respect to light having a wavelength of 660 nm is greater than a predetermined value, it is determined in step S32b that chyle exists in the sample. Thus, the item of the chyle flag in the sample analysis list (see FIG. 17) is changed from off (“0” in the table) to on (“1” in the table). On the other hand, when it is determined in step S32a that the absorbance (Abs. It is determined that the level does not affect the measurement, and the item of the chyle flag in the sample analysis list is maintained in an off state (“0” in the table). In this embodiment, the content of chyle in the sample is measured using light with a wavelength of 660 nm. However, the content of chyle in the sample is measured using light with a wavelength of 800 nm. Also good.

In the present embodiment, correction of chyle in step S32c is performed using the absorbance of the specimen (Abs. 660) with respect to light having a wavelength of 660 nm and the absorbance of the specimen (Abs. 800) with respect to light having a wavelength of 800 nm. Find the formula. Specifically, the wavelength (X = 660) and the absorbance (Y = Abs. 660) are substituted into the above formula (1) to derive the following formula (1a), and the wavelength (X = 800) and absorbance (Y = Abs. 800) are substituted to derive the following formula (1b).
log ₁₀ Abs. 660 = alog ₁₀ 660 + b (1a)
log ₁₀ Abs. 800 = alog ₁₀ 800 + b (1b)

Then, the equations (1a) and (1b) are combined to calculate the constants a and b, and the chyle correction equation (3) for deriving the absorbance y of the chyle at a predetermined wavelength x is derived.
log ₁₀ y = alog ₁₀ x + b (3)

  In step S32d, an estimated value (Abs. 575 chyle estimated value) of chyle absorbance with respect to light having a wavelength of 575 nm is calculated from the chyle correction formula (3) obtained in step S32c. That is, by substituting the wavelength (x = 575 nm) into the correction formula (3), an estimated value of the absorbance of the chyle with respect to light having a wavelength of 575 nm (y = Abs.575 chyle estimated value) is calculated.

  In step S32e, the estimated value of the absorbance of the chyle with respect to light having a wavelength of 405 nm (Abs. 405 chyle estimated value) is calculated from the chyle correction formula (3) in the same manner as in step S32d described above. . That is, by substituting the wavelength (x = 405 nm) into the correction formula (3), the estimated value of the absorbance of the chyle with respect to the light having the wavelength of 405 nm (y = Abs.405 chyle estimated value) is calculated.

  Next, in step S33 shown in FIG. 19, the hemoglobin is checked. Specifically, as shown in FIG. 21, in step S33a, the light with a wavelength of 575 nm calculated in step S32d (see FIG. 20) described above from the absorbance (Abs. 575) of the specimen with respect to light with a wavelength of 575 nm. By subtracting the estimated absorbance of the chyle (Abs. 575 estimated chyle), the absorbance of the analyte (Abs. 575) for light at a wavelength of 575 nm was corrected to obtain the absorbance of hemoglobin for light at a wavelength of 575 nm. presume. And it is judged whether the light absorbency ((Abs.575)-(Abs.575 chyle estimated value)) of hemoglobin with respect to the light of the estimated wavelength of 575 nm is larger than a predetermined value. If it is determined in step S33a that ((Abs.575) − (Abs.575 chyle estimated value)) is greater than the predetermined value, it is determined in step S33b that hemoglobin is present in the sample. As a result, the hemoglobin flag item in the sample analysis list (see FIG. 17) is changed from off (“0” in the table) to on (“1” in the table). On the other hand, when it is determined in step S33a that ((Abs.575) − (Abs.575 chyle estimated value)) is equal to or less than a predetermined value, the content of hemoglobin in the sample is determined in this measurement. The hemoglobin flag item in the sample analysis list is maintained in the off state (“0” in the table).

Then, in step S33c, the estimated value of the absorbance of hemoglobin with respect to light having a wavelength of 405 nm (Abs.405Hgb estimated value) from “(Abs.575) − (Abs.575 chyle estimated value)” calculated in step S33a. ) Is calculated. Specifically, as shown in the following formula (4), (Abs.405Hgb estimated value) is a constant obtained by calculating ((Abs.575) − (Abs.575 milky estimate value)) in step S33a. It is calculated by multiplying by H (6.5 to 7.5 (preferably 6.8)).
(Abs.405 Hgb estimated value) = H × {(Abs.575) − (Abs.575 chyle estimated value)} (4)

  Next, bilirubin is checked in step S34 shown in FIG. Specifically, as shown in FIG. 22, in step S34a, light having a wavelength of 405 nm calculated in step S32e (see FIG. 20) described above from the absorbance (Abs. 405) of the specimen with respect to light having a wavelength of 405 nm. Estimated value (abs. 405 Hgb estimated value) of hemoglobin with respect to light having a wavelength of 405 nm calculated in step S33c (see FIG. 21) described above. Is corrected for the absorbance of the specimen (Abs. 405) with respect to light having a wavelength of 405 nm, and the absorbance of bilirubin with respect to light having a wavelength of 405 nm is estimated. Then, it is determined whether or not the absorbance ((Abs. 405) − (Abs. 405 chyle estimated value) − (Abs. 405Hgb estimated value)) of bilirubin with respect to the estimated light having a wavelength of 405 nm is larger than a predetermined value. The If it is determined in step S34a that ((Abs.405)-(Abs.405 chyle estimated value)-(Abs.405Hgb estimated value)) is greater than a predetermined value, in step S34b, The bilirubin content in the sample analysis table (see FIG. 17) is judged to have an adverse effect on this measurement, and the item of the bilirubin flag in the sample analysis list (see FIG. 17) is changed from “0” in the table to on (in the table Then, it is changed to “1”). On the other hand, if it is determined in step S34a that ((Abs.405) − (Abs.405 chyle estimated value) − (Abs.405Hgb estimated value)) is equal to or less than a predetermined value, The bilirubin content in the sample analysis table is determined to have an adverse effect on the measurement, and the item of the bilirubin flag in the sample analysis list is maintained in the off state (“0” in the table). In this way, the optical information analysis process acquired by the first optical information acquisition unit 40 is completed.

  In the present embodiment, as described above, in step S31, hemoglobin is not substantially absorbed, and specimens for light of each wavelength (405 nm, 575 nm, 660 nm, and 800 nm) including wavelengths of 660 nm and 800 nm that are absorbed by chyle The absorbance of chyle (Abs. 660 and Abs. 800) at two wavelengths (660 nm and 800 nm), which are absorption wavelengths of chyle only, can be obtained. Thus, in step S32c, the effect of chyle on the absorbance at a predetermined wavelength is estimated based on the absorbance of chyle at two wavelengths (660 nm and 800 nm) (Abs. 660 and Abs. 800). The correction formula (3) can be obtained. Therefore, based on this correction formula (3), an estimated value (Abs. Chyle estimated value) of chyle absorbance at a wavelength of 575 nm can be calculated. That is, the absorbance of chyle at 575 nm can be estimated more accurately than when estimating the absorbance of chyle at a predetermined (575 nm) wavelength using a correction formula obtained from one type of wavelength. As a result, in step S33a, the hemoglobin content can be accurately estimated. If it is determined that the hemoglobin content in the sample has an adverse effect on the main measurement, the main measurement described above becomes difficult depending on the measurement item, and this can be interrupted. Therefore, it is possible to avoid wasting the reagent used for the main measurement. In this case, the specimen containing a large amount of hemoglobin as described above is considered to be a specimen in which red blood cells are hemolyzed (hemolyzed specimen) when purifying plasma from whole blood. Can be used for remeasurement.

  In the present embodiment, in step S31, by calculating the absorbance of the specimen with respect to light of each wavelength (405 nm, 575 nm, 660 nm, and 800 nm) including the wavelength of 405 nm that is the absorption wavelength of bilirubin, in step S32c, the predetermined absorbance is obtained. The above correction equation (3) for estimating the influence of chyle on the absorbance at the wavelength of can be obtained. Therefore, based on this correction formula (3), an estimated value (Abs. 405 chyle estimated value) of chyle absorbance at a wavelength of 405 nm can be calculated. That is, the absorbance of chyle at 405 nm can be estimated more accurately than the case where the absorbance of chyle at a predetermined (405 nm) wavelength is estimated using a correction formula obtained from one type of wavelength. If it is determined from the estimated absorbance of chyle that the content of chyle in the sample has an adverse effect on this measurement, this measurement may be difficult depending on the measurement item. Can be interrupted. Therefore, it is possible to avoid wasting the reagent used for the main measurement. In addition, re-measurement can be performed after filtering the chyle contained in this specimen.

  In the present embodiment, in step S34a, the estimated absorbance (Abs. 405) of the chyle to light having the wavelength of 405 nm calculated in step S32e is calculated from the absorbance (Abs. 405) of the sample with respect to light having the wavelength of 405 nm. The estimated effect of chyle (Abs. 405 milk) by subtracting the estimated value of hemoglobin absorbance (Abs. 405 Hgb estimate) for the light of 405 nm wavelength calculated in step S33c. And an accurate absorbance at a wavelength of 405 nm from which the influence of hemoglobin (Abs. 405Hgb estimated value) has been removed. As a result, the content of bilirubin can be accurately estimated in step S34a. When it is determined that the content of bilirubin in the sample is an extent that adversely affects the main measurement, the main measurement described above becomes difficult depending on the measurement item, and this can be interrupted. Therefore, it is possible to avoid wasting the reagent used for the main measurement. In addition, this sample can be used for remeasurement with another apparatus.

  The embodiment disclosed this time should be considered as illustrative in all points and not restrictive. The scope of the present invention is shown not by the above description of the embodiments but by the scope of claims for patent, and further includes all modifications within the meaning and scope equivalent to the scope of claims for patent.

  For example, in the above-described embodiment, the example in which the present invention is applied to the sample analyzer in which the detection mechanism unit and the control device are electrically connected has been described. You may give the function of.

  Moreover, in the said embodiment, ten types of optical information are obtained from the 2nd optical information acquisition part containing the lamp part which irradiates the light of five different wavelengths, and the amplification part which amplifies an electric signal by two different amplification factors. Acquire all (digital signal data) and, based on the analysis of the first optical information acquisition unit (checking of interference substances), determine that it is suitable for analysis from the acquired ten types of second optical information However, the present invention is not limited to this, and based on the analysis of the first optical information acquisition unit, there are 10 types of measurement conditions (acquisition conditions). One of them may be selected, and the second optical information may be acquired under the selected condition.

1 is a perspective view showing an overall configuration of a sample analyzer according to an embodiment of the present invention. It is the top view which showed the detection mechanism part and conveyance mechanism part of the sample analyzer by one Embodiment shown in FIG. It is the perspective view which showed the 1st optical information acquisition part of the sample analyzer by one Embodiment shown in FIG. FIG. 4 is a cross-sectional view schematically illustrating a first optical information acquisition unit according to the embodiment illustrated in FIG. 3. It is a block diagram of the control part of the control apparatus of the sample analyzer by one Embodiment shown in FIG. FIG. 4 is a block diagram illustrating a configuration of a first optical information acquisition unit according to the embodiment illustrated in FIG. 3. It is the schematic which showed the structure of the lamp | ramp part of the sample analyzer by one Embodiment shown in FIG. It is the front view which showed the filter member of the lamp | ramp part by one Embodiment shown in FIG. It is the block diagram which showed the structure of the 2nd optical information acquisition part of the sample analyzer by one Embodiment shown in FIG. It is the graph which showed the absorbance spectrum of hemoglobin. It is the graph which showed the absorbance spectrum of bilirubin. It is the graph which showed the light absorbency spectrum of chyle. It is the graph which showed the light absorbency spectrum at the time of adding chyle to hemoglobin. It is the graph which showed the light absorbency spectrum at the time of adding chyle to bilirubin. It is the graph which plotted the absorbance spectrum of chyle in the log-log graph. 3 is a flowchart showing a control flow of a control unit of the control device of the sample analyzer according to the embodiment shown in FIG. 1. It is the figure which showed the sample analysis list output to the display part of the control apparatus of the sample analyzer by one Embodiment shown in FIG. 2 is a flowchart showing a procedure of a sample analysis operation of the sample analyzer according to the embodiment shown in FIG. 3 is a flowchart showing an analysis procedure in a first optical information acquisition unit of the sample analyzer according to the embodiment shown in FIG. 1. FIG. 20 is a flowchart showing a subroutine for checking an interfering substance (chyle) shown in FIG. 19. FIG. FIG. 20 is a flowchart showing a subroutine for checking an interfering substance (hemoglobin) shown in FIG. 19. FIG. FIG. 20 is a flowchart showing a subroutine for checking an interfering substance (bilirubin) shown in FIG. 19. FIG.

Explanation of symbols

1 Sample analyzer (sample analyzer)
2 Detection mechanism (measurement unit)
4a controller (acquired hand stage)
4b display unit (out Chikarate stage)
42 Photoelectric conversion element (light receiving part)
55 Optical fiber (light source)
60 Reagent dispensing arm (preparation means)

Claims (15)

Hemoglobin does not substantially absorbed, to obtain the first absorbance and the second absorbance, respectively, in first and second wavelengths chyle is wavelength absorbing, third hemoglobin and chyle are wavelength absorbing Obtaining a third absorbance at a wavelength ;
Determining the content of chyle contained in the sample based on the first absorbance or the second absorbance;
Determining unknowns α and β in the relational expression A = α · λ ^β for determining the absorbance A of chyle at an arbitrary wavelength λ based on the first absorbance and the second absorbance ;
Substituting the third wavelength into λ of the relational expression to estimate the absorbance of chyle at the third wavelength;
And subtracting the absorbance of chyle at the third wavelength from the third absorbance to determine the content of hemoglobin contained in the sample. The first wavelength, the second wavelength, and the third wavelength are wavelengths that bilirubin does not substantially absorb,
Obtaining a fourth absorbance at a fourth wavelength, which is a wavelength absorbed by hemoglobin, chyle and bilirubin;
Substituting the fourth wavelength into λ of the relational expression to estimate the absorbance of chyle at the fourth wavelength;
Estimating the absorbance of hemoglobin at the fourth wavelength by multiplying the content of hemoglobin by a constant, and
The method according to claim 1, further comprising the step of subtracting the absorbance of chyle at the fourth wavelength and the absorbance of hemoglobin at the fourth wavelength from the fourth absorbance to determine the content of bilirubin contained in the sample. The sample analysis method described. The hemoglobin and chyle are substances that interfere with the optical measurement of the target substance contained in the sample,
Measuring the first absorbance, the second absorbance, and the third absorbance from a sample, and then adding a reagent to the sample to prepare a measurement sample;
Optically measuring the measurement sample;
The sample analysis method according to claim 1, further comprising a step of analyzing a target substance contained in the sample based on optical information obtained by optical measurement. The sample analysis method according to claim 3, further comprising an output step of outputting an analysis result of the target substance together with information on the content of hemoglobin and chyle obtained from the sample. The target substance is a substance related to the coagulation function of blood,
The sample analysis method according to claim 4, wherein the sample is plasma. Hemoglobin does not substantially absorbed, to obtain the first absorbance and the second absorbance, respectively, in first and second wavelengths chyle is wavelength absorbing, third hemoglobin and chyle are wavelength absorbing A measurement unit for obtaining a third absorbance at a wavelength ;
To determine the content of chyle contained in the sample based on the first absorbance or the second absorbance, and to determine the absorbance A of chyle at an arbitrary wavelength λ based on the first absorbance and the second absorbance. The unknowns α and ^β in the relational expression A = α · λβ are calculated, and the third wavelength is substituted into λ in the relational expression to estimate the absorbance of chyle at the third wavelength, and the third wavelength A sample analyzer comprising: an acquisition unit that obtains the content of hemoglobin contained in the sample by subtracting the absorbance of chyle in the third absorbance . The first wavelength and the second wavelength are wavelengths that bilirubin does not substantially absorb,
The measurement unit obtains a fourth absorbance at a fourth wavelength which is a wavelength absorbed by hemoglobin, chyle and bilirubin,
The acquisition means substitutes the fourth wavelength for λ of the relational expression, estimates the absorbance of chyle at the fourth wavelength, and multiplies the content of hemoglobin by a constant, thereby obtaining hemoglobin at the fourth wavelength. The degree of bilirubin contained in the sample is obtained by subtracting the absorbance of chyle at the fourth wavelength and the absorbance of hemoglobin at the fourth wavelength from the fourth absorbance. The sample analyzer described in 1. The sample analyzer according to claim 6 or 7, further comprising output means for outputting information relating to the content of hemoglobin and chyle. The hemoglobin and chyle are substances that interfere with the optical measurement of the target substance contained in the sample,
The measuring unit is
The apparatus further includes a preparation means for preparing a measurement sample used for optical measurement of the target substance by adding a reagent to the sample, and the first absorbance, the second absorbance, and the third absorbance from the sample before the reagent is added. the absorbance was measured by preparing a measurement sample from the sample, the sample for measurement was optically measured, so as to analyze the target substance contained in the sample based on the optical information obtained by the optical measurement The sample analyzer according to any one of claims 6 to 8 , which is configured . The sample analyzer according to claim 9, further comprising output means for outputting an analysis result of the target substance together with information on the content of hemoglobin and chyle obtained from the sample. The measuring unit is
A light source that selectively emits light of the first wavelength, light of the second wavelength, and light of the third wavelength;
11. The sample analyzer according to claim 6 , further comprising: a light receiving unit that receives the light of the first wavelength, the light of the second wavelength, and the light of the third wavelength. It further comprises a table for holding a plurality of translucent containers containing samples in an annular shape,
The sample analyzer according to claim 11, wherein the plurality of containers held on the table are sequentially arranged between the light source and the light receiving unit by rotating the table. The sample analyzer according to any one of claims 6 to 12 , wherein the first wavelength and the second wavelength are wavelengths of 590 nm to 900 nm. The sample analyzer according to any one of claims 6 to 13 , wherein the third wavelength is a wavelength of 500 nm or more and less than 590 nm. The sample analyzer according to claim 7 , wherein the fourth wavelength is a wavelength of 300 nm or more and less than 500 nm.

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