JP4986487B2 - Blood clotting time measurement device - Google Patents

Description

  The present invention relates to a blood coagulation time measurement apparatus, and more particularly to a blood coagulation time measurement apparatus that optically analyzes a coagulation time measurement sample prepared by mixing a blood sample and a coagulation time measurement reagent.

  Conventionally, before performing this measurement (for example, biochemical analysis), measurement of interfering substances (hemoglobin, bilirubin, chyle, etc.) in the sample has been performed to evaluate the quality of the sample (serum, etc.). (See, for example, Patent Document 1, Patent Document 2, and Patent Document 3). The interference substance is a substance that coexists in a sample together with a target substance (for example, fibrinogen) to be inspected and interferes with optical measurement of the target substance.

  In the method for measuring chyle, jaundice, and hemolysis in serum disclosed in Patent Document 1, the serum is irradiated with light of four wavelengths, and firstly, a short wavelength in the visible range ( For example, the absorbance is measured by using light of 410 nm), and the serum having the absorbance of a certain value or more is determined as abnormal serum due to chyle, jaundice, and hemolysis. Secondly, for serum determined to be abnormal serum, by comparing the absorbance measured using four wavelengths with several preset criteria, chyle, jaundice and The degree of hemolysis is determined.

  In the chromogen (interfering substance) measurement method disclosed in Patent Document 2, a blank reagent is prepared by mixing a blank reaction reagent with a specimen in which suspended substances (hemoglobin, bilirubin, chyle, etc.) are mixed. Then, the specimen blank solution is irradiated with light of four types of wavelengths including those having absorption of chyle and substantially no absorption of hemoglobin and bilirubin, thereby measuring the degree of the interference substance. Yes. Specifically, regarding chyle, the degree of chyle is calculated by obtaining a regression curve of wavelength-absorbance assuming that the absorbance is expressed by an exponential function of wavelength. As for hemoglobin and bilirubin, it is assumed that there is a fixed relationship between absorbances at different wavelengths. Is calculated.

  Further, in the analyzer for determining whether hemolysis, jaundice, and lipemia are present in the serum sample disclosed in Patent Document 3, first, suction is performed on a needle tube disposed in a transparent portion provided in the probe. The absorbance of the serum sample in the needle tube is measured by irradiating the emitted serum sample with light emitted from the light emitting diode. Then, a serum sample determined to be measurable based on the absorbance is transferred to a clinical analyzer, and the measurement is performed.

JP-A-57-59151 JP-A-6-66808 JP-A-10-153597

  However, in Patent Document 1 and Patent Document 3 described above, before performing this measurement (such as biochemical analysis), a sample such as serum is used at its original concentration to measure the interference substance in the sample. There is a problem that it is necessary to provide an optical measurement structure (for example, an optical detection unit and a probe) for measuring an original concentration sample separately from the main measurement unit.

  Further, the above-mentioned Patent Document 2 has a disadvantage that it is necessary to perform measurement of an interference substance by optical measurement using a sample blank solution that cannot be used in the main measurement (original measurement). Therefore, this interfering substance must be measured separately from this measurement. In addition, in order to adjust the specimen blank solution, it is necessary to prepare a sample such as serum separately from the main measurement, and there is a problem that the consumption of the sample increases until the result of the main measurement is obtained.

  The present invention has been made to solve the above problems, and one object of the present invention is that it is not necessary to measure an interfering substance separately from the measurement of the blood coagulation time, and It is an object of the present invention to provide a blood coagulation time measuring device capable of suppressing consumption.

Means for Solving the Problems and Effects of the Invention

  In order to achieve the above object, a blood coagulation time measurement apparatus according to the first aspect of the present invention comprises a sample preparation unit for preparing a coagulation time measurement sample by mixing a blood sample with a coagulation time measurement reagent, A light irradiating unit for irradiating light to the coagulation time measurement sample, and receiving light of a plurality of wavelengths over time from the coagulation time measurement sample irradiated with light, and acquiring optical information over time A first light-receiving unit; and a measurement unit that measures a coagulation time of the sample for measuring the coagulation time based on optical information acquired by the first light-receiving unit, wherein the measurement unit includes the first light-receiving unit. The coagulation time of the interfering substance that interferes with the optical measurement of the coagulation time measurement sample based on the optical information at the time before the coagulation time measurement sample exhibits a coagulation reaction among the optical information acquired by Degree of content in sample for measurement It is configured to measure.

  In the blood coagulation time measuring apparatus according to the first aspect, as described above, the light having a plurality of wavelengths is received over time from the sample for measuring the coagulation time irradiated with light, and optical information over time is acquired. By providing one light receiving portion, optical information used for measuring the content of the interference substance in the coagulation time measurement sample by the first light receiving portion (the optical information at the time before the coagulation time measurement sample shows a coagulation reaction). Information) and optical information (a plurality of optical information over time) used for measurement of the coagulation time (main measurement) can be acquired. The clotting reaction is a reaction in which blood coagulation occurs through the conversion of fibrinogen in plasma into fibrin through a number of endogenous or extrinsic reactions. That is, even if a blood coagulation reagent is mixed with plasma, blood coagulation does not start immediately, usually after about 7 seconds in the extrinsic system (PT measurement reagent), and usually about 14 seconds in the intrinsic system (APTT measurement reagent). A coagulation reaction takes place. The present invention focuses on the fact that the optical information at the time point before this coagulation reaction (referred to as lag phase) is the same optical information as in the state in which the specimen is diluted. In other words, with the above configuration, the measurement unit not only measures the coagulation time using a plurality of optical information over time, but also at a time point (lag phase) before the coagulation time measurement sample shows a coagulation reaction. The content of the interference substance can be measured using optical information. As a result, the measurement unit can measure the content of the interference substance in the coagulation time measurement sample without performing measurement only for the interference substance separately from the main measurement. At this time, in the first light receiving unit, optical information (a plurality of data over time) used for measurement of the coagulation time (main measurement) is obtained from one coagulation time measurement sample in which a blood sample is mixed with a reagent for coagulation time measurement. And the optical information used for measuring the content of the interference substance (optical information at the time point before the coagulation time measurement sample shows the coagulation reaction) can be acquired. As a result, it is not necessary to separately prepare the sample used for the main measurement and the sample used for the measurement of the content of the interference substance, so that consumption of the blood sample can be suppressed.

  In the first aspect, a first light receiving unit is provided for receiving light from a coagulation time measurement sample in which a blood sample is mixed with a coagulation time measurement reagent and acquiring optical information over time. Thus, optical information can be acquired from a blood sample diluted with a reagent for measuring the clotting time. Thereby, even if it is difficult to detect optical information because the concentration of the blood sample is high, the first light receiving unit acquires optical information from the diluted blood sample (coagulation time measurement sample). Therefore, the measurement range in which optical information can be acquired can be expanded.

  In the blood coagulation time measurement apparatus according to the first aspect, preferably, the measurement unit measures the contents of the plurality of interfering substances based on the optical information at the plurality of wavelengths acquired by the first light receiving unit. It is configured as follows. If comprised in this way, by using the several optical information acquired by the light of the several wavelength irradiated from a light irradiation part, it will be easy to utilize that the wavelength which each interference substance absorbs differs. Each of the contents of the plurality of interfering substances can be measured.

  In the blood coagulation time measuring apparatus for measuring the content of the plurality of interfering substances, the first light receiving unit is preferably configured to acquire at least optical information at the first wavelength, the second wavelength, and the third wavelength. And the measurement unit is configured to provide at least one of bilirubin, hemoglobin, and chyle in the blood sample based on optical information in at least one of the first wavelength, the second wavelength, and the third wavelength acquired by the first light receiving unit. It is comprised so that any content may be measured. If comprised in this way, a bilirubin, hemoglobin, and a chyle will absorb by using the some optical information acquired by the light of the 1st wavelength, 2nd wavelength, and 3rd wavelength irradiated from a light irradiation part. Utilizing the fact that the wavelengths are different, the contents of bilirubin, hemoglobin and chyle can be measured respectively.

  In the blood coagulation time measuring apparatus for measuring the content of bilirubin, hemoglobin, and chyle, preferably, the first wavelength is a wavelength that bilirubin and hemoglobin do not substantially absorb and chyle absorbs, The wavelength is a wavelength that bilirubin does not substantially absorb and is absorbed by hemoglobin and chyle, a third wavelength is a wavelength that bilirubin, hemoglobin, and chyle absorb, and the measurement unit is at least at the first wavelength. A first estimating means for estimating an influence of chyle on the optical information at the second wavelength and the third wavelength based on the optical information; an influence of the chyle at the estimated second wavelength; and Second estimation means for estimating the influence of hemoglobin on the optical information at the third wavelength based on the optical information, and the second light receiving section The optical information at the first wavelength, the second wavelength and the third wavelength, the influence of chyle on the optical information at the second wavelength and the third wavelength estimated by the first estimating means, and the second estimating means Is configured to measure the content of bilirubin, hemoglobin and chyle in the blood sample based on the influence of hemoglobin on the optical information estimated at the third wavelength. If comprised in this way, based on the optical information in the 1st wavelength which is a wavelength which only a chyle absorbs, the content degree of the chyle in a blood sample can be measured easily. Further, based on the optical information at the second wavelength, which is the wavelength absorbed by hemoglobin and chyle, and the influence of chyle on the optical information at the second wavelength estimated by the first estimating means, The content of hemoglobin in the blood sample can be measured. Further, optical information at the third wavelength, which is a wavelength absorbed by all of bilirubin, hemoglobin, and chyle, the influence of chyle on the optical information at the third wavelength estimated by the first estimating means, 2 Based on the influence of hemoglobin on the optical information at the third wavelength estimated by the estimation means, the content of bilirubin in the blood sample can be easily measured. As described above, the contents of bilirubin, hemoglobin, and chyle can be easily measured.

  In this case, it is preferable that the first light receiving unit is configured to further acquire optical information at a fourth wavelength which is not substantially absorbed by bilirubin and hemoglobin and is absorbed by chyle. Is configured to estimate the effect of chyle on the optical information at the second and third wavelengths based on the optical information at the first and fourth wavelengths. If comprised in this way, bilirubin and hemoglobin will not absorb substantially, and based on the optical information in a 4th wavelength in addition to the 1st wavelength which a chyle absorbs, other wavelengths (2nd wavelength and 3rd wavelength) The effect of chyle on the optical information at the wavelength) can be estimated. Thereby, based on the optical information at one type of wavelength, based on the two pieces of optical information at the two types of wavelengths, compared to estimating the effect of chyle on the optical information at other wavelengths, It is more accurate to estimate the effect of chyle on the optical information at other wavelengths. As a result, the influence of bilirubin and hemoglobin can be estimated using the accurately estimated influence of chyle, so that the influence of interfering substances (chyle, hemoglobin and bilirubin) can be accurately estimated.

  In the blood coagulation time measurement apparatus according to the first aspect, preferably, the first light receiving unit does not substantially absorb bilirubin and hemoglobin, and does not substantially absorb bilirubin, the first wavelength absorbed by chyle. The optical information at the second wavelength absorbed by hemoglobin and chyle and the third wavelength absorbed by bilirubin, hemoglobin and chyle, and the measuring unit is at least a first light receiving unit. The first acquisition means for acquiring the influence of chyle on the optical information based on the optical information at the first wavelength acquired by the method, and the influence of chyle on the optical information acquired by the first acquisition means And second acquisition means for acquiring the influence of hemoglobin on the optical information based on the optical information at the second wavelength acquired by the first light receiving unit, and the first acquisition means The influence of chyle on the optical information acquired more, the influence of hemoglobin on the optical information acquired by the second acquisition means, and the optical information at the third wavelength acquired by the first light receiving unit Based on the third acquisition means for acquiring the influence of bilirubin on the optical information, the influence of chyle on the optical information acquired by the first acquisition means, and the optical acquired by the second acquisition means And an output unit that outputs the influence of hemoglobin on the target information and the influence of bilirubin on the optical information acquired by the third acquisition unit. Thereby, the influence of the chyle acquired by the first acquisition means, the influence of the hemoglobin acquired by the second acquisition means, and the influence of the bilirubin acquired by the third acquisition means can be easily output to the output means. Can do.

  In the blood coagulation time measurement apparatus provided with the first acquisition means for acquiring the influence of chyle on the optical information, preferably the first acquisition means measures the coagulation time in addition to the optical information at the first wavelength. The influence of chyle on the optical information is acquired based on the optical information derived from the coagulation time measuring reagent acquired by irradiating the reagent for light. If comprised in this way, even when the optical information in a 1st wavelength contains the optical information derived from the sample for coagulation time measurement, it easily derives from the sample for coagulation time measurement to optical information It is possible to acquire the influence of only chyle that does not contain optical information.

  In the blood coagulation time measuring apparatus according to the first aspect, preferably, the light irradiation unit is configured to irradiate light having a plurality of different wavelengths in a time division manner. If comprised in this way, the light which has a some wavelength can be irradiated to the sample for coagulation time measurement of a measurement part by a time division. As a result, the sample for coagulation time measurement can be sequentially irradiated with light having a plurality of wavelengths, so that a plurality of pieces of optical information necessary for measuring the content of the interference substance can be easily obtained. In addition, depending on the type of clotting time measurement reagent added to the blood sample, even if the wavelength suitable for measuring the clotting time is different, light with a wavelength suitable for measurement is easily used for clotting time measurement. The reagent can be irradiated.

  The blood coagulation time measurement apparatus according to the first aspect preferably further includes a second light receiving unit that receives light from a blood sample before the coagulation time measurement reagent is mixed and acquires optical information, and the measurement unit Is configured to measure the content of the interfering substance in the blood sample that optically interferes with the optical measurement of the blood sample, based on the optical information acquired by the second light receiving unit. If comprised in this way, the content degree of the interfering substance in a blood sample can be measured in the stage before the reagent for coagulation time measurement is mixed. Thereby, when the content of the interfering substance in the blood sample measured by the second light receiving unit is large, it is determined that it is difficult to measure a reliable coagulation time, and the measurement can be stopped. it can. As a result, since the coagulation time measurement reagent can be stopped from being mixed with the blood sample to be measured, it is possible to suppress wasteful consumption of the coagulation time measurement reagent. Further, in this case, since the main measurement by the first light receiving unit is not performed on a blood sample for which it is difficult to obtain a highly reliable measurement result (coagulation time), the measurement efficiency of the apparatus can be improved. it can.

  In this case, it is preferable that the information processing apparatus further includes a determination unit that determines whether or not optical information with time is acquired by the first light receiving unit based on the optical information acquired by the second light receiving unit. If comprised in this way, it can be judged easily whether this measurement by a 1st light-receiving part is performed.

  In the blood coagulation time measurement apparatus including the second light receiving unit, preferably, the content of the interference substance in the blood sample measured based on the optical information acquired by the first light receiving unit, and the second light receiving unit The image processing apparatus further includes a selection unit that selects one of the interference substances in the sample for measuring the coagulation time measured based on the acquired optical information. According to this configuration, the content of the interference substance in the blood sample of the original concentration that is not diluted with the clotting time measurement sample, and the interference substance in the clotting time measurement sample diluted with the clotting time measurement sample, etc. The content level can be easily selected.

  A blood coagulation time measurement apparatus according to a second aspect of the present invention includes a sample preparation unit for preparing a coagulation time measurement sample by mixing a blood sample with a coagulation time measurement reagent, and the prepared coagulation time measurement sample. A light irradiating unit that irradiates light; a first light receiving unit that receives light of a plurality of wavelengths over time from a sample for measurement of coagulation time irradiated with light; and a first light receiving unit that acquires optical information over time And a measurement unit for measuring the coagulation time of the sample for coagulation time measurement based on the optical information acquired by the measurement unit, the measurement unit for measuring the coagulation time among the optical information acquired by the first light receiving unit. Based on the optical information at the time point before the sample shows a coagulation reaction, the interference substance included in the coagulation time measurement sample and interfering substances that interfere with the optical measurement of the coagulation time measurement sample are specified.

  In the blood coagulation time measuring apparatus according to the second aspect, as described above, the light having a plurality of wavelengths is received over time from the sample for measuring the coagulation time irradiated with light, and optical information over time is acquired. By providing one light-receiving unit, the first light-receiving unit allows the optical information used to identify the interfering substance contained in the coagulation time measurement sample (optical information before the coagulation time measurement sample exhibits a coagulation reaction). ) And optical information (multiple optical information over time) used for measurement of the coagulation time (main measurement) can be acquired. As a result, the measurement unit not only measures the coagulation time using a plurality of optical information over time, but also measures the coagulation time using the optical information at the time before the coagulation time measurement sample shows a coagulation reaction. Interfering substances contained in the sample for use can be specified. As a result, the measurement unit can specify the interference substance contained in the coagulation time measurement sample without performing measurement only for the interference substance separately from the main measurement. At this time, in the first light receiving unit, optical information (a plurality of data over time) used for measurement of the coagulation time (main measurement) is obtained from one coagulation time measurement sample in which a blood sample is mixed with a reagent for coagulation time measurement. And the optical information used to specify the interference substance (optical information at the time point before the sample for coagulation time measurement shows a coagulation reaction) can be acquired. As a result, it is not necessary to separately prepare the sample used for the main measurement and the sample used for specifying the interference substance, so that consumption of the blood sample can be suppressed.

  In the second aspect, a first light receiving unit is provided for receiving light from a coagulation time measurement sample in which a blood sample is mixed with a coagulation time measurement reagent and acquiring optical information over time. Thus, optical information can be acquired from a blood sample diluted with a reagent for measuring the clotting time. Thereby, even if it is difficult to detect optical information because the concentration of the blood sample is high, the first light receiving unit acquires optical information from the diluted blood sample (coagulation time measurement sample). Therefore, the measurement range in which optical information can be acquired can be expanded.

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

(First embodiment)
FIG. 1 is a perspective view showing the entire configuration of a blood coagulation time measuring apparatus according to a first embodiment of the present invention, and FIG. 2 is a detection mechanism of the blood coagulation time measuring apparatus according to the first embodiment shown in FIG. It is the top view which showed the part and the conveyance mechanism part. 3-14 is a figure for demonstrating the structure of the blood coagulation time measuring apparatus by 1st Embodiment shown in FIG. First, with reference to FIGS. 1-14, the whole structure of the blood coagulation time measuring apparatus 1 by 1st Embodiment of this invention is demonstrated.

  The blood coagulation time measuring apparatus 1 according to the first embodiment of the present invention is an apparatus for optically measuring and analyzing the amount and activity level of a specific substance related to blood coagulation / fibrinolysis function, Plasma is used as a blood sample. In the blood coagulation time measurement apparatus 1 according to the present embodiment, the blood sample is optically measured using the coagulation time method, the synthetic substrate method, and the immunoturbidimetric method, thereby measuring the coagulation time of the blood sample. Measurement items include PT (prothrombin time), APTT (activated partial thromboplastin time), and Fbg (fibrinogen amount). In addition, measurement items of the synthetic substrate method include ATIII and the like, and measurement items of the immunoturbidimetric method include D dimer, FDP and the like.

  As shown in FIG. 1, the blood coagulation time measuring apparatus 1 is electrically connected to the detection mechanism unit 2, the transport mechanism unit 3 disposed on the front side of the detection mechanism unit 2, and the detection mechanism unit 2. And the control device 4.

  In order to supply the blood sample to the detection mechanism unit 2, the transport mechanism unit 3 uses the detection mechanism unit 2 as a rack 151 on which a plurality of (in this embodiment, ten) test tubes 150 containing the blood sample are placed. It has the function to convey to the suction position 2a (see FIG. 2). In addition, the transport mechanism unit 3 stores a rack set region 3a for setting a rack 151 in which a test tube 150 that stores an unprocessed blood sample is stored, and a test tube 150 that stores a processed blood sample. And a rack housing area 3b for housing the rack 151.

  The detection mechanism unit 2 is configured to be able to acquire optical information about the supplied blood sample by performing optical measurement on the blood sample supplied from the transport mechanism unit 3. Yes. In the present embodiment, optical measurement is performed on a blood sample dispensed from the test tube 150 placed on the rack 151 of the transport mechanism unit 3 into the cuvette 152 (see FIG. 2) of the detection mechanism unit 2. Is called. 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, and a lamp unit 50. And two reagent dispensing arms 60, a cuvette transfer section 70, a second optical information acquisition section 80, an emergency sample setting section 90, a cuvette disposal section 100, and a fluid section 110.

  The cuvette supply unit 10 is configured to be able to sequentially supply a plurality of cuvettes 152 (see FIGS. 3 and 4) that are randomly inserted by the user 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. In addition, the support base 14 has a function of rotating and transferring the cuvette 152 that has moved by sliding down the guide plate 13 to a position where the supply catcher unit 15 can grip it. The supply catcher unit 15 is provided to supply the cuvette 152 rotated and transferred by the support base 14 to the rotary conveyance unit 20.

  The rotary transport unit 20 is provided to transport the cuvette 152 supplied from the cuvette supply unit 10 and a reagent container (not shown) containing a coagulation time measurement reagent for coagulating the blood sample in the rotation direction. Yes. As shown in FIG. 2, the rotary transport unit 20 includes a circular reagent table 21, an annular reagent table 22 arranged outside the circular reagent table 21, and an annular reagent table 22. Are formed by an annular secondary dispensing table 23 arranged on the outer side of the annular ring, and an annular primary dispensing table 24 arranged on the outer side of the annular secondary dispensing table 23. 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.

  As shown in FIG. 2, each of the reagent tables 21 and 22 includes a plurality of holes 21a and 22a provided at predetermined intervals along the circumferential direction. The holes 21a and 22a of the reagent tables 21 and 22 are provided for placing a plurality of reagent containers (not shown) containing a clotting time measuring reagent for coagulating blood. The primary dispensing table 24 and the secondary dispensing table 23 each include a plurality of cylindrical holding portions 24a and 23a provided at predetermined intervals along the circumferential direction. The holding parts 24 a and 23 a are provided to hold the cuvette 152 supplied from the cuvette supply part 10. In the cuvette 152 held in the holding unit 24a of the primary dispensing table 24, a blood sample accommodated in the test tube 150 of the transport mechanism unit 3 is dispensed during the primary dispensing process. Further, in the cuvette 152 held in the holding unit 23a of the secondary dispensing table 23, the blood sample accommodated in the cuvette 152 held in the primary dispensing table 24 is dispensed during the secondary dispensing process. Is done. 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 a branch optical fiber 58 of the lamp unit 50 described later to pass therethrough.

  The sample dispensing arm 30 aspirates the blood sample accommodated in the test tube 150 conveyed to the aspiration position 2a by the conveyance mechanism unit 3 and in the cuvette 152 transferred to the rotary conveyance unit 20. Has the function of dispensing.

  The first optical information acquisition unit 40 is configured to measure the presence and concentration of interfering substances (chyle, hemoglobin, and bilirubin) in the blood sample before adding the coagulation time measurement reagent or diluent. Optical information is obtained from (an original sample to which a diluent, a coagulation time measurement reagent, etc. are not added). Specifically, interference is performed using four types of light (405 nm, 575 nm, 660 nm, and 800 nm) among five types of light (340 nm, 405 nm, 575 nm, 660 nm, and 800 nm) emitted from the lamp unit 50 described later. The presence of substance and its concentration are measured.

  The acquisition of the optical information of the blood sample by the first optical information acquisition unit 40 is performed before the optical measurement (main measurement) of the coagulation time measurement sample by the second optical information acquisition unit 80. As shown in FIGS. 2 and 3, the first optical information acquisition unit 40 acquires optical information from the blood sample in the cuvette 152 held in the holding unit 24 a of the primary dispensing table 24. 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.

  As shown in FIG. 4, the light receiving side holder 43 is attached to the light emitting side holder 41 via a bracket 44 (see FIG. 3), and can accommodate the substrate 45 on which the photoelectric conversion element 42 is mounted. It is formed in a simple shape. The light receiving side holder 43 is attached with a lid member 43a provided with a slit 43b at a predetermined position. Light from a later-described branch optical fiber 58 that has passed through the cuvette 152 held by the holding portion 24 a of the primary dispensing table 24 is photoelectrically transmitted through a pair of small holes 24 b of the holding portion 24 a and a slit 43 b of the light receiving side holder 43. It is detected by the conversion element 42.

  The substrate 45 has a function of amplifying an electrical signal corresponding to the transmitted light amount detected by the photoelectric conversion element 42 and transmitting the amplified signal to the control unit 4 a of the control device 4. As shown in FIG. 5, 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 detected by 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 adjusts the gain (amplification factor) of the amplifier 45e in accordance with a periodic change in the wavelength (340 nm, 405 nm, 575 nm, 660 nm, and 800 nm) of light emitted from a branch optical fiber 58 of the lamp unit 50 described later. It is configured to change. Further, as shown in FIG. 5, the controller 45 d is electrically connected to the control unit 4 a of the control device 4, and digital signal data corresponding to the transmitted light amount acquired by the first optical information acquisition unit 40. Is transmitted to the control unit 4a of the control device 4.

  As shown in FIG. 2, the lamp unit 50 is provided to supply light used for optical measurement performed by the first optical information acquisition unit 40 and the second optical information acquisition unit 80. That is, one lamp unit 50 is configured to be used in common for the first optical information acquisition unit 40 and the second optical information acquisition unit 80. As shown in FIGS. 6 and 7, the lamp unit 50 includes a halogen lamp 51 as a light source, condenser lenses 52 a to 52 c, a disk-shaped filter unit 53, a motor 54, and a light transmission type sensor 55. And an optical fiber coupler 56, eleven branch optical fibers 57 (see FIG. 7), and one branch optical fiber 58 (see FIG. 7).

  As shown in FIG. 6, the halogen lamp 51 is accommodated in a lamp case 51 a having a plurality of fins for cooling the air heated by the halogen lamp 51 generating heat. The condensing lenses 52 a to 52 c have a function of condensing the light emitted from the halogen lamp 51. The condensing lenses 52 a to 52 c are arranged on an optical path that guides the light emitted from the halogen lamp 51 to the optical fiber coupler 56. The light emitted from the halogen lamp 51 and collected by the condensing lenses 52a to 52c passes through any one of optical filters 53b to 53f of the filter unit 53 described later and is guided to the optical fiber coupler 56. .

  Further, as shown in FIG. 8, the filter unit 53 of the lamp unit 50 is attached to be rotatable around a motor shaft (not shown) of the motor 54. The filter unit 53 includes a filter plate 53a on which five optical filters 53b to 53f having different light transmission characteristics (transmission wavelengths) are provided. The filter plate 53a is provided with five holes 53g for attaching the optical filters 53b to 53f and a hole 53h that is blocked so as not to transmit light. In the five holes 53g, five optical filters 53b, 53c, 53d, 53e, and 53f having different light transmission characteristics (transmission wavelengths) are respectively installed. The holes 53g and 53h are provided at a predetermined angular interval (equal interval of 60 ° in the present embodiment) along the rotation direction of the filter portion 53. The hole 53h is a spare hole, and a filter is attached when a filter needs to be added.

  The optical filters 53b, 53c, 53d, 53e, and 53f transmit light having wavelengths of 340 nm, 405 nm, 575 nm, 660 nm, and 800 nm, respectively, and do not transmit light of other wavelengths. Accordingly, light transmitted through the optical filters 53b, 53c, 53d, 53e, and 53f has wavelength characteristics of 340 nm, 405 nm, 575 nm, 660 nm, and 800 nm, respectively.

  Further, the filter plate 53a is provided with six slits at predetermined angular intervals (equal intervals of 60 ° in the present embodiment) along the circumferential direction. One of the six slits is an origin slit 53j having a larger slit width in the rotation direction of the filter plate 53a than the other five normal slits 53i. The origin slit 53j and the normal slit 53i are formed at a predetermined angular interval (equal interval of 60 ° in the present embodiment) at an intermediate angular position between the adjacent holes 53g and 53h.

  In addition, when light is irradiated from the lamp unit 50 to the cuvette 152 of the primary dispensing table 24 and the cuvette 152 of the cuvette placement unit 81 described later, the filter unit 53 is configured to continuously rotate. . Accordingly, with the rotation of the filter plate 53a, five optical filters 53b to 53f having different light transmission characteristics and one light shield are provided on the optical path of the light collected by the condenser lenses 52a to 52c (see FIG. 4). The holes 53h (see FIG. 5) are intermittently arranged sequentially. For this reason, five types of light having different wavelength characteristics are sequentially and sequentially irradiated. In the present embodiment, the filter unit 53 is configured to rotate once per 0.1 second. Accordingly, the cuvette 152 of the primary dispensing table 24 and the cuvette 152 of the cuvette placement unit 81 described later are sequentially irradiated with five types of light having different wavelength characteristics in 0.1 seconds. In the first optical information acquisition unit 40, the photoelectric conversion element 42 acquires five electrical signals corresponding to five types of wavelengths every 0.1 second, and the second optical information acquisition unit 80. Then, five electric signals corresponding to five kinds of wavelengths are acquired every 0.1 second by the photoelectric conversion element 82b (photoelectric conversion element 82e for reference light).

  Further, as shown in FIG. 8, the light transmission type sensor 55 is provided to detect passage of the origin slit 53j and the normal slit 53i accompanying the rotation of the filter unit 53. When the origin slit 53j and the normal slit 53i pass through the sensor 55, the light receiving unit detects light from the light source through the slit and outputs a detection signal. Since the origin slit 53j has a larger slit width than the normal slit 53i, when the origin slit 53j passes, the detection signal output from the sensor 55 is more than the detection signal when the normal slit 53i passes. The output period is long. Therefore, based on the detection signal from the sensor 55, it is possible to monitor whether the filter unit 53 is rotating normally.

  In addition, the optical fiber coupler 56 has a function of causing the light that has passed through the optical filters 53b to 53f to enter each of the eleven branch optical fibers 57 and the one branch optical fiber 58. That is, the optical fiber coupler 56 simultaneously guides the same quality of light to the 11 branch optical fibers 57 and the one branch optical fiber 58. Further, as shown in FIG. 2, the tips of the eleven branch optical fibers 57 are connected to the second optical information acquisition unit 80, and the light from the lamp unit 50 is sent to the second optical information acquisition unit 80. It leads to the sample for measuring the coagulation time in the set cuvette 152. Specifically, as shown in FIG. 9, the eleven branch optical fibers 57 are respectively inserted into ten insertion holes 81a and one reference light measurement hole 81b, which will be described later, of the second optical information acquisition unit 80. It is arranged to supply light. Further, as shown in FIGS. 2 and 3, the tip of one branch optical fiber 58 is connected to the first optical information acquisition unit 40, unlike the eleven branch optical fiber 57, and the lamp unit. The light from 50 is guided to the blood sample in the cuvette 152 held in the holding portion 24a of the primary dispensing table 24. Therefore, the five types of light having different wavelength characteristics that intermittently pass through the optical filters 53b to 53f pass through the branch optical fibers 57 and 58, and the first optical information acquisition unit 40 and the second optical information acquisition unit 80. Are supplied to each.

  As shown in FIGS. 1 and 2, the reagent dispensing arm 60 is a cuvette in which a coagulation time measurement reagent in a reagent container (not shown) placed on the rotary transport unit 20 is held by the rotary transport unit 20. It is provided for mixing the blood sample in the cuvette 152 with the reagent for measuring the clotting time by dispensing into the cuvette 152. Thereby, the coagulation time measurement reagent is prepared by adding the coagulation time measurement reagent to the blood sample for which the optical measurement by the first optical information acquisition unit 40 has been completed. The cuvette transfer unit 70 is provided to transfer the cuvette 152 between the rotary conveyance unit 20 and the second optical information acquisition unit 80.

  Here, in the first embodiment, the second optical information acquisition unit 80 heats the coagulation time measurement sample prepared by mixing the blood sample with the coagulation time measurement reagent, and the lamp unit 50 performs the heating. It is provided to receive light over time from a sample for coagulation time measurement irradiated with light of a plurality of wavelengths, and to acquire optical information over time for each wavelength. Specifically, the second optical information acquisition unit 80 includes three types of light (405 nm, 660 nm, and 800 nm) among the five types of light (340 nm, 405 nm, 575 nm, 660 nm, and 800 nm) emitted from the lamp unit 50. ) To obtain the transmitted light amount for each elapsed time. The light having a wavelength of 660 nm irradiated from the branch optical fiber 57 is a main wavelength used when measuring Fbg (fibrinogen amount), PT (prothrombin time), and APTT (activated partial thromboplastin time). In addition, light having a wavelength of 800 nm is a sub-wavelength used when measuring Fbg, PT, and APTT. The measurement wavelength of ATIII which is a measurement item of the synthetic substrate method is 405 nm, and the measurement wavelength of D dimer and FDP which are measurement items of the immunoturbidimetric method is 800 nm. The measurement wavelength of platelet aggregation is 575 nm. As described above, the sample analyzer 1 according to this embodiment obtains light of a plurality of wavelengths by passing the light emitted from the halogen lamp 51 as one light source through the optical filters 53b to 53f of the filter unit 53. Measurement of various measurement items is performed using the light.

  That is, in the second optical information acquisition unit 80 of the first embodiment, the main wavelength is less than the sub-wavelength by utilizing the fact that the light of low wavelength can catch the coagulation reaction more significantly than the light of high wavelength. Is set to be smaller. Specifically, when the measurement items are Fbg (fibrinogen amount), PT (prothrombin time) and APTT (activated partial thromboplastin time), the main wavelength of 660 nm is set to be smaller than the sub-wavelength of 800 nm. ing.

  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. As shown in FIG. 9, the cuvette placement portion 81 has ten insertion holes 81a for inserting the cuvette 152 (see FIG. 2), and 1 for measuring the reference light without inserting the cuvette 152. Two reference light measurement holes 81b are provided. 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.

  The reference light measurement hole 81 b is provided to monitor the characteristics of the light emitted from the branch optical fiber 57. Specifically, the light radiated from the branched optical fiber 57 is directly received by the photoelectric conversion element 82e for reference light of the detection unit 82, thereby causing fluctuations derived from the halogen lamp 51 (see FIG. 6) of the lamp unit 50. Is detected as an electrical signal. Then, the detected light characteristic (electric signal) is subtracted from the signal corresponding to the transmitted light of the coagulation time measurement sample in the cuvette 152 inserted in the insertion hole 81a, thereby transmitting the transmitted light of the coagulation time measurement sample. The signal corresponding to is corrected. Thereby, it is possible to suppress the occurrence of a slight difference due to the characteristics of the light every time optical information is measured.

  In addition, the detection unit 82 of the second optical information acquisition unit 80 performs optical measurement (main measurement) on the coagulation time measurement sample in the cuvette 152 inserted into the insertion hole 81a under a plurality of conditions. It is configured to be possible. As shown in FIGS. 7 and 8, the detection unit 82 is provided with a collimator lens 82a, a photoelectric conversion element 82b, and a preamplifier 82c corresponding to each insertion hole 81a into which the cuvette 152 is inserted. Corresponding to the measurement hole 81b (see FIG. 1), a reference light collimator lens 82d, a reference light photoelectric conversion element 82e, and a reference light preamplifier 82f are provided.

  As shown in FIGS. 9 and 10, the collimator lens 82a is installed between the end of the branch optical fiber 57 that guides light from the lamp unit 50 (see FIG. 6) and the corresponding insertion hole 81a. Yes. The collimator lens 82a is provided to make the light emitted from the branch optical fiber 57 into parallel light. The photoelectric conversion element 82b is attached to the surface on the insertion hole 81a side of the substrate 83 installed so as to face the end of the branch optical fiber 57 with the insertion hole 81a interposed therebetween. The photoelectric conversion element 82b detects light (hereinafter referred to as transmitted light) that passes through the coagulation time measurement sample when light is applied to the coagulation time measurement sample in the cuvette 152 inserted into the insertion hole 81a. In addition, it has a function of outputting an electrical signal (analog signal) corresponding to the detected transmitted light. The photoelectric conversion element 82b is arranged to receive five types of light emitted from the branch optical fiber 57 of the lamp unit 50.

  The preamplifier 82c is attached to the surface of the substrate 83 opposite to the insertion hole 81a, and is provided to amplify an electrical signal (analog signal) from the photoelectric conversion element 82b.

  In addition to the photoelectric conversion element 82b (reference light photoelectric conversion element 82e) and preamplifier 82c (reference light preamplifier 82f), the substrate 83 includes an amplifying unit 82g and an A / A as shown in FIG. A D converter 82h, a logger 82i, and a controller 82j are provided. The amplifier 82g includes an amplifier (L) 82k having a predetermined gain (amplification factor), an amplifier (H) 82l having a gain (amplification factor) higher than that of the amplifier (L) 82k, and a changeover switch 82m. Have. In the present embodiment, the electrical signal from the preamplifier 82c is input to both the amplifier (L) 82k and the amplifier (H) 82l. The amplifier (L) 82k and the amplifier (H) 82l are provided to further amplify the electric signal from the preamplifier 82c. The changeover switch 82m selects whether to output the electrical signal from the amplifier (L) 82k to the A / D converter 82h or to output the electrical signal from the amplifier (H) 82l to the A / D converter 82h. Is provided to do. The changeover switch 82m is configured to perform a changeover operation when a control signal from the controller 82j is input.

  The A / D converter 82h is provided to convert an electrical signal (analog signal) from the amplification unit 82g into a digital signal. The logger 82i has a function for temporarily storing digital signal data from the A / D converter 82h. The logger 82 i is electrically connected to the control unit 4 a of the control device 4, and transmits the digital signal data acquired by the second optical information acquisition unit 80 to the control unit 4 a of the control device 4.

  As shown in FIGS. 1 and 2, the emergency sample setting unit 90 is provided for performing a sample analysis process on a blood 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 a blood sample supplied from the transport mechanism unit 3. 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 fluid part 110 is provided to supply a liquid such as a cleaning liquid to the nozzles provided in each dispensing arm during the shutdown process of the blood coagulation time measuring apparatus 1.

  The control device 4 (see FIG. 1) includes a personal computer (PC) and the like, and includes a control unit 4a including a CPU, ROM, RAM, and the like, a display unit 4b, and a keyboard 4c. In addition, the display unit 4b analyzes information on interference substances (hemoglobin, chyle (lipid) and bilirubin) present in the blood sample and data of the digital signal transmitted from the second optical information acquisition unit 80. It is provided to display the obtained analysis result (coagulation time) and the like.

  Next, the configuration of the control device 4 will be described. As shown in FIG. 12, the control device 4 is configured by a computer 401 mainly composed of a control unit 4a, a display unit 4b, and a keyboard 4c. The control unit 4a mainly includes a CPU 401a, a ROM 401b, a RAM 401c, a hard disk 401d, a reading device 401e, an input / output interface 401f, a communication interface 401g, and an image output interface 401h. The CPU 401a, ROM 401b, RAM 401c, hard disk 401d, reading device 401e, input / output interface 401f, communication interface 401g, and image output interface 401h are connected by a bus 401i.

  The CPU 401a can execute computer programs stored in the ROM 401b and computer programs loaded in the RAM 401c. The computer 401 functions as the control device 4 when the CPU 401a executes an application program 404a as will be described later.

  The ROM 401b is configured by a mask ROM, PROM, EPROM, EEPROM, or the like, in which computer programs executed by the CPU 401a and data used for the same are recorded.

  The RAM 401c is configured by SRAM, DRAM, or the like. The RAM 401c is used to read out computer programs recorded in the ROM 401b and the hard disk 401d. Further, when these computer programs are executed, they are used as a work area of the CPU 401a.

  The hard disc 401d is installed with various computer programs to be executed by the CPU 401a, such as an operating system and application programs, and data used for executing the computer programs. An application program 404a for measuring blood coagulation time according to the present embodiment is also installed in the hard disk 401d.

  The reading device 401e is configured by a flexible disk drive, a CD-ROM drive, a DVD-ROM drive, or the like, and can read a computer program or data recorded on the portable recording medium 404. The portable recording medium 404 stores an application program 404a for measuring blood coagulation time. The computer 401 reads the application program 404a from the portable recording medium 404 and installs the application program 404a on the hard disk 401d. Is possible.

  Note that the application program 404a is not only provided by the portable recording medium 404, but also from an external device communicatively connected to the computer 401 by an electric communication line (whether wired or wireless). It is also possible to provide through. For example, the application program 404a is stored in a hard disk of a server computer on the Internet, and the computer 401 can access the server computer to download the application program 404a and install it on the hard disk 401d. It is.

  In addition, an operating system that provides a graphical user interface environment such as Windows (registered trademark) manufactured and sold by US Microsoft Corporation is installed in the hard disc 401d. In the following description, it is assumed that the application program 404a according to the present embodiment operates on the operating system.

  The output interface 401f includes, for example, a serial interface such as USB, IEEE 1394, and RS-232C, a parallel interface such as SCSI, IDE, and IEEE1284, and an analog interface including a D / A converter and an A / D converter. ing. A keyboard 4c is connected to the input / output interface 401f, and the user can input data to the computer 401 by using the keyboard 4c.

  The communication interface 401g is, for example, an Ethernet (registered trademark) interface. The computer 401 can transmit and receive data to and from the detection mechanism unit 2 using a predetermined communication protocol through the communication interface 401g.

  The image output interface 401h is connected to a display unit 4b configured by an LCD or a CRT, and outputs a video signal corresponding to image data given from the CPU 401a to the display unit 4b. The display unit 4b displays an image (screen) according to the input video signal.

  In addition, the blood coagulation time measurement application program 404a installed in the hard disk 401d of the control unit 4a is a transmitted light amount (digital) of the coagulation time measurement sample transmitted from the second optical information acquisition unit 80 of the detection mechanism unit 2. Signal data) is used to measure the coagulation time of the sample for coagulation time measurement. This coagulation time is from the time when a coagulation time measurement reagent for coagulating the blood sample in the cuvette 152 is added until the coagulation time measurement sample (blood sample added with the coagulation time measurement reagent) loses fluidity. (Coagulation time). The coagulation reaction in which the coagulation time measurement sample loses fluidity is a reaction in which fibrinogen in the blood sample is changed to fibrin by the added coagulation time measurement reagent. In the blood coagulation time measuring apparatus 1 according to the first embodiment, this coagulation reaction that reacts depending on the amount of fibrinogen in the blood sample is changed in the amount of transmitted light of the sample for measuring the coagulation time shown in FIGS. This is confirmed by the amount (difference between the transmitted light amount before reaction and the transmitted light amount after reaction).

  Here, in the first embodiment, the blood coagulation time measurement application program 404a transmits the transmitted light amount data (digital signal data) over time of the coagulation time measurement sample transmitted from the second optical information acquisition unit 80. ), The amount of transmitted light detected during the period before the clotting time measurement sample shows a clotting reaction (the hatched area in FIG. 13), and interfering substances (chyle, hemoglobin and It has the function of measuring the presence and concentration of bilirubin). Specifically, the application program 404a performs transmission measured from 3.0 sec to 4.0 sec after the addition of the coagulation time measurement reagent from the received amount of transmitted light (digital signal data) with time. The light quantity data (digital signal data) is selected, and the average value of the selected plurality of transmitted light quantities is calculated. Therefore, in the present embodiment, the filter unit 53 (see FIG. 8) of the lamp unit 50 is configured to rotate once per 0.1 second, so that the application program 404a is 3.0 sec to 4.0 sec. The average value of the 10 transmitted light amounts acquired in the meantime is calculated.

  Furthermore, in the first embodiment, the blood coagulation time measurement application program 404a uses the data on the amount of transmitted light over time (digital signal data) of the blood sample transmitted from the first optical information acquisition unit 40. It also has a function of measuring the presence and concentration of interfering substances (chyle, hemoglobin and bilirubin) in the blood sample.

  Here, with reference to FIG. 13 and FIG. 14, the coagulation reaction (coagulation time) of the coagulation time measurement sample obtained by adding the coagulation time measurement reagent to the blood sample will be described in detail.

  When a blood sample mixed with an interference substance (chyle) is measured by the blood coagulation time measurement apparatus 1, as shown in FIG. 13, the measurement result measured at the main wavelength (660 nm) on the low wavelength side is an interference substance (milk). And the amount of transmitted light is about 190 to about 220. In addition, when the main wavelength is used, the amount of change ΔH1 of the transmitted light amount indicating the blood coagulation reaction (difference between the transmitted light amount before the reaction and the transmitted light amount after the reaction) is also affected by the interference substance (chyle). Tend to be smaller. On the other hand, the measurement result measured at the sub-wavelength (800 nm) on the high wavelength side is not easily affected by the interference substance (chyle) as will be described later, and the transmitted light amount (about 190 to about 220) measured at the main wavelength. ) And becomes a transmitted light amount of about 350 to about 390. In addition, when the sub-wavelength is used, the amount of change ΔH2 (> ΔH1) in the amount of transmitted light that indicates the blood coagulation reaction is also less likely to be affected by the interfering substance and less likely to decrease. Therefore, when measuring a blood sample contaminated with interfering substances (chyle), the measurement at the sub-wavelength on the high wavelength side can capture the coagulation reaction larger than the measurement at the main wavelength on the low wavelength side. Is possible.

  On the other hand, when a normal blood sample in which no interfering substance is mixed is measured, as shown in FIG. 14, the amount of change ΔH3 in the amount of transmitted light measured at the main wavelength (660 nm) on the low wavelength side (= about 980 (= before reaction) Transmitted light amount (about 2440) −transmitted light amount after reaction (about 1460))) is a change amount ΔH4 (= approximately 720 (= transmitted light amount before reaction) (measured at the sub-wavelength on the higher wavelength side). About 2630)-greater than the amount of transmitted light after reaction (about 1910))). Therefore, when measuring a normal blood sample, it is possible to capture the coagulation reaction larger when measuring at the main wavelength on the lower wavelength side than when measuring at the sub wavelength on the higher wavelength side.

  15 to 20 are graphs showing the absorbance spectrum of the interference substance. Next, referring to FIGS. 15 to 20, the four types of light emitted from the branched optical fiber 58 guided to the first optical information acquisition unit 40 and the branched optical fiber 57 guided to the second optical information acquisition unit 80 are used. The light having wavelengths of 405 nm, 405 nm, 575 nm, 660 nm, and 800 nm will be described in detail.

  Light having a wavelength of 660 nm and 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. And as shown in FIG. 17, it turns out that the chyle absorbs the light of the wavelength from 405 nm of a low wavelength region to 800 nm of a high wavelength region. Therefore, when chyle is added to hemoglobin, as shown in FIG. 18, 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. Also, when chyle is added to bilirubin, as shown in FIG. 19, 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, as shown in FIG. 17, light having a wavelength of 660 nm is more absorbed by chyle than light having a wavelength of 800 nm, and thus optical information measured with light having a wavelength of 800 nm. It can be seen that the influence of chyle is smaller in the case of optical information measured with light having a wavelength of 660 nm.

  In this way, the wavelength of large absorption differs for each interfering substance (milky, hemoglobin, and bilirubin), so analysis is performed according to the results of qualitative judgment described later and the type of interfering substances contained in the blood sample. It is possible to determine the selection of the wavelength used for the measurement and the cancellation of this measurement. Further, without performing qualitative determination for each interfering substance, it may be qualitatively determined whether or not there is an influence of the interfering substance for each measurement wavelength. In this case, the wavelength determined to have substantially no influence of the interference substance may be used for the analysis, and the wavelength determined to have the influence of the interference substance may not be used for the analysis.

  The blood sample (plasma) to be measured by the blood coagulation time measuring apparatus 1 according to the present embodiment may contain interference substances (chyle, hemoglobin, and bilirubin), and uses light having a wavelength of 405 nm. The absorbance of the blood sample measured in this way is attributed to the absorbance of chyle, the absorbance of hemoglobin, and the absorbance of bilirubin. In addition, the absorbance of blood samples 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 blood samples 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 blood sample measured using light having a wavelength of 660 nm and / or 800 nm, it is determined whether the content of chyle in the blood sample is an amount that adversely affects the measurement. It becomes possible to do. Whether the hemoglobin content in the blood sample has an adverse effect on the measurement by removing the influence (absorbance) of chyle from the absorbance of the blood sample measured using light having a wavelength of 575 nm It becomes possible to determine whether or not. Then, by removing the influence of chyle (absorbance) and the influence of hemoglobin (absorbance) from the absorbance of the blood sample measured using light having a wavelength of 405 nm, the content of bilirubin in the blood sample is measured. It is possible to determine whether the amount has an adverse effect.

In addition, when the absorbance spectrum of chyle shown in FIG. 17 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)

  FIG. 21 is a flowchart showing the procedure of the sample analysis operation of the blood coagulation time measuring apparatus according to the first embodiment shown in FIG. FIG. 22 is a view showing a sample analysis list output to the display unit of the control device of the blood coagulation time measuring apparatus according to the first embodiment shown in FIG. Next, the blood sample measurement operation of the blood coagulation time measurement apparatus 1 will be described in detail with reference to FIGS. 1 to 5, 8 to 13, 21, and 22.

  First, the user turns on the power of the detection mechanism unit 2 and the control device 4 of the blood coagulation time measuring device 1 shown in FIGS. 1 and 2 to activate the blood coagulation time measuring device 1, Thereby, the initial setting of the blood coagulation time measuring apparatus 1 is performed. In the initial setting described above, 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 of the control device 4 is performed. The register of the unit 4a is initialized. 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. 22) output to the display unit 4b of the control device 4. Do. The control unit 4a receives the input of the sample analysis information, and the 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. 22 will be described. In the sample number column, a number (such as “000101”) for identifying each sample is input. In addition, a symbol (“PT”, “APTT”, etc.) indicating an item of measurement of the coagulation time performed on the sample is input in the measurement item column associated with the sample number. 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. 22 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. When the wavelength change flag is on, optical information acquired using light of a sub wavelength (for example, 800 nm) different from light of the main wavelength (for example, 660 nm) is analyzed for the measurement item. It shows that. 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. Then, when the user inputs the start of analysis processing, data for instructing the start of measurement is transmitted to the detection mechanism unit 2, and the test tube 150 containing the sample is transferred by the transport mechanism unit 3 shown in FIG. 2. The mounted rack 151 is transported. 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. In step S1, a predetermined amount of blood sample is aspirated from the test tube 150 by the sample dispensing arm 30 (see FIG. 2). Then, the specimen dispensing arm 30 is moved above the cuvette 152 held by the primary dispensing table 24 of the rotary transport unit 20. Thereafter, the blood sample is dispensed into the cuvette 152 by discharging the blood sample from 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 blood sample has been dispensed is conveyed to a position where measurement by the first optical information acquisition unit 40 is possible. Thereby, in step S2, the first optical information acquisition unit 40 performs optical measurement on a blood sample (original sample before addition of a coagulation time measurement reagent, etc.) in the cuvette 152 under a plurality of conditions. Is performed, a plurality of (five types) transmitted light amounts are acquired from the blood sample. Specifically, five types (340 nm, 405 nm, 575 nm, 660 nm, and 800 nm) of the branch optical fiber 58 of the lamp unit 50 are transferred to the cuvette 152 held in the holding unit 24a (see FIG. 4) of the primary dispensing table 24. Light of different wavelengths is irradiated. Light transmitted from the branch optical fiber 58 and transmitted through the cuvette 152 and the blood sample in the cuvette 152 are sequentially detected by the photoelectric conversion element 42. Then, the electric signal of the transmitted light amount detected by the photoelectric conversion element 42 is amplified by the preamplifier 45a (see FIG. 5) and the amplifier 45e, and converted into a digital signal by the A / D converter 45c. Thereafter, digital signal data corresponding to the transmitted light amount is transmitted to the control unit 4a of the control device 4 by the controller 45d. Thereby, the acquisition of the transmitted light amount (digital signal data) for the blood sample by the first optical information acquisition unit 40 is completed. In the control unit 4a of the control device 4, the absorbance is calculated for each wavelength from the received transmitted light amount data.

  In step S3, the CPU 401a (see FIG. 12) of the control device 4 uses the transmitted light amount data (digital signal data) transmitted from the first optical information acquisition unit 40 (see FIG. 3) to generate blood. The concentration and presence / absence of interfering substances (chyle, hemoglobin, and bilirubin) contained in the specimen (original specimen) are estimated, and then, in step S4, qualitative determination regarding the interfering substance is executed. In this qualitative determination, for each interfering substance, strong positive (contained in a large amount in the specimen), weak positive (contained in a predetermined amount in the specimen), and negative (substantially not contained in the specimen) It is determined which of the following is true. Here, the process of step S3 and step S4 is demonstrated in detail. The CPU 401a calculates the absorbance of the blood sample using the received digital signal data, and also calculates the presence and concentration of interfering substances (chyle, hemoglobin, bilirubin) in the blood sample. Specifically, the CPU 401a calculates the absorbance of the blood sample using the transmitted light amount data acquired using the four types (405 nm, 575 nm, 660 nm, and 800 nm) of light emitted from the lamp unit 50. Calculate the presence and concentration of interfering substances (chyle, hemoglobin and bilirubin). Then, the CPU 401a performs qualitative determination of the interference substance based on the calculated presence / absence of the interference substance in the blood sample and the concentration thereof. As this qualitative determination, a negative “−” indicating that the sample does not substantially contain an interfering substance, a weak positive “+” indicating that a predetermined amount of the interfering substance is included in the sample, and There is a strong positive “++” indicating that the sample contains a large amount of interfering substances. The result of such qualitative determination is displayed on the display unit 4b of the control device 4 together with the analysis result such as the coagulation time obtained in step S13 in step S15 described later.

  In step S5, the CPU 401a determines whether the main measurement is possible based on the result of the qualitative determination in step S4. Here, the process of step S5 will be described in detail. As shown in FIGS. 15 to 17, the wavelength that affects each interfering substance is different. That is, hemoglobin does not substantially absorb light at wavelengths of 660 nm and 800 nm, but absorbs light at 405 nm and 575 nm. Thus, it can be seen that hemoglobin does not substantially affect analysis using 660 nm or 800 nm light, but does affect analysis using 405 nm or 575 nm light. Similarly, bilirubin does not substantially affect analysis using 575 nm, 660 nm or 800 nm light, but does affect analysis using 405 nm light. In addition, chyle affects the analysis at all wavelengths (405 nm, 575 nm, 660 nm and 800 nm). As described above, when a large amount of hemoglobin is contained in the specimen as a result of the qualitative determination regarding the interfering substance (strong positive), the test item having the measurement wavelength of 405 nm or 575 nm has a normal blood coagulation time. The analysis cannot be performed. When a large amount of bilirubin is contained in the sample (strongly positive), the analysis of the blood coagulation time cannot be performed normally for the test item whose measurement wavelength is 405 nm. On the other hand, when chyle is contained in a large amount in the sample (strongly positive), it is strongly influenced at any measurement wavelength, and thus the blood coagulation time cannot be normally analyzed. Therefore, as a result of the qualitative determination, when hemoglobin is strongly positive and the measurement wavelength is a measurement item of 405 nm or 575 nm, bilirubin is strongly positive and the measurement wavelength is a measurement item of 405 nm, or chyle If is strongly positive, it can be determined that this measurement is impossible. If it is determined in step S5 that the main measurement is impossible, a flag is added to the measurement result in step S6, resulting in a measurement error. Thereafter, in step S15, which will be described later, “measurement error” and an error code are displayed on the display unit 4b of the control device 4. As a result, the user can check the error content by comparing the error code displayed on the display unit 4b with the error code described in the instruction manual or the like.

  If it is determined in step S5 that the main measurement is possible, the wavelength used for analysis is selected by the CPU 401a in step S7. As described above, as a result of the qualitative determination, when the chyle is negative, the main wavelength (660 nm) is selected, and when the chyle is weakly positive, the sub wavelength (800 nm) is selected. Then, when the length is selected for the main, the wavelength change flag is kept off, and when the sub wavelength is selected, the wavelength change flag is set on.

  In step S8, the light is irradiated from the branch optical fiber 57 by the photoelectric conversion element 82b (see FIG. 9) corresponding to the insertion hole 81a into which a cuvette 152 in which a coagulation time measurement sample to be described later is accommodated is inserted. Light is received. As a result, it is possible to detect, as an electrical signal, optical characteristics such as fluctuation inherent to the branched optical fiber 57 corresponding to the insertion hole 81a into which the predetermined cuvette 152 is to be inserted. As a result, by subtracting the electrical signal detected without inserting the cuvette 152 into the insertion hole 81a from the electrical signal acquired from the coagulation time measurement sample in the cuvette 152 inserted into the insertion hole 81a. It is possible to correct the signal corresponding to the transmitted light of the sample for coagulation time measurement. Thereby, it is possible to suppress the occurrence of a slight difference in the acquired electrical signal depending on the position where the cuvette 152 is inserted. In the present embodiment, the electrical signal specific to the branch optical fiber 57 is detected for 3 seconds after the reagent for clotting time is added to the blood sample by the reagent dispensing arm 60 until the cuvette 152 is inserted. Is done.

  Thereafter, in step S9, a predetermined amount of blood sample is aspirated from the cuvette 152 held by the holding unit 24a of the primary dispensing table 24 by the sample dispensing arm 30. Then, a predetermined amount of blood sample is discharged from the sample 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 a coagulation time measurement reagent for coagulating blood in a reagent container (not shown) placed on the reagent tables 21 and 22 is cuvette 152 of the secondary dispensing table 23. Add to the blood sample. Thereby, the sample for coagulation time measurement is prepared. In step S10, using the cuvette transfer unit 70, the cuvette 152 of the secondary dispensing table 23 in which the sample for coagulation time measurement is accommodated is inserted into the insertion hole of the cuvette placement unit 81 of the second optical information acquisition unit 80. Move to 81a. After the cuvette 152 containing the coagulation time measurement sample is inserted into the insertion hole 81a of the cuvette placement unit 81, the detection unit 82 of the second optical information acquisition unit 80 converts the cuvette 152 into the clot time measurement sample. On the other hand, by performing optical measurement (main measurement) under a plurality of conditions, a plurality (ten types) of transmitted light amounts are obtained from the coagulation time measurement sample. 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). After that, as shown in FIG. 10, light is irradiated from the branch optical fiber 57 of the lamp unit 50 to the cuvette 152 of the cuvette mounting portion 81. The branched optical fiber 57 periodically irradiates light of five different wavelengths (340 nm, 405 nm, 575 nm, 660 nm, and 800 nm) by the rotation of the filter unit 53 (see FIG. 8). The light of each wavelength irradiated from the branch optical fiber 57 and transmitted through the cuvette 152 and the coagulation time measurement sample in the cuvette 152 is sequentially detected by the photoelectric conversion element 82b. Then, an electric signal having a transmitted light amount corresponding to light of five different wavelengths converted by the photoelectric conversion element 82b is amplified by the preamplifier 82c and then sequentially input to the amplifying unit 82g.

  In the amplifying unit 82g, electric signals having transmitted light amounts corresponding to light of five different wavelengths from the preamplifier 82c (see FIG. 11) are converted into an amplifier (H) 82l having a high amplification factor and an amplifier (L) 82k having a normal amplification factor. Respectively. Then, by controlling the changeover switch 82m by the controller 82j, the electric signal amplified by the amplifier (H) 82l is output to the A / D converter 82h, and then the electric signal amplified by the amplifier (L) 82k is changed. It is output to the A / D converter 82h. Here, the changeover switch 82m is repeatedly switched according to the rotation timing of the filter unit 53 (see FIG. 8) in the lamp unit 50. As a result, in the amplifying unit 82g, electric signals having transmitted light amounts 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 82h. Is done. The ten types of electrical signals are converted into digital signals by the A / D converter 82h, temporarily stored in the logger 82i, and then sequentially transmitted to the control unit 4a of the control device 4.

  Then, from the time when the cuvette 152 containing the coagulation time measurement sample is inserted into the insertion hole 81a (3.0 seconds after the addition of the coagulation time measurement reagent) to the time when the coagulation reaction ends. During the period, an electrical signal corresponding to the transmitted light amount is detected by the photoelectric conversion element 82b and sequentially transmitted to the control unit 4a of the control device 4. Thereby, the CPU 401a of the control device 4 calculates the amount of change in the transmitted light amount for each wavelength (= transmitted light amount before reaction−transmitted light amount after reaction) using the received transmitted light amount data with time.

  Then, after acquisition of the transmitted light amount data (main measurement) by the second optical information acquisition unit 80, in step S11, the CPU 401a determines that the lag phase (4.0 seconds have elapsed since the addition of the coagulation time measurement reagent). ) Is used to estimate the concentration and presence of interfering substances (chyle, hemoglobin, and bilirubin) contained in the clotting time measurement sample. The clotting reaction is a reaction in which blood coagulation occurs through the conversion of fibrinogen in plasma into fibrin through a number of endogenous or extrinsic reactions. That is, even if a blood coagulation reagent is mixed with plasma, blood coagulation does not start immediately, usually after about 7 seconds in the extrinsic system (PT measurement reagent), and usually about 14 seconds in the intrinsic system (APTT measurement reagent). A coagulation reaction takes place. Therefore, the optical information at the time point before the coagulation reaction (referred to as the lag phase) is before the optical change caused by the coagulation reaction, and can be said to be the same optical information as the state in which the specimen is diluted. Therefore, the concentration and presence / absence of the interference substance can be estimated from the specimen diluted with the coagulation time measurement reagent.

  Next, in step S12, the CPU 401a uses the blood sample (original sample) to estimate the interference substance estimated in step S3 and the interference estimated in step S11 using the coagulation time measurement sample. It is determined whether the difference from the substance estimation result is within a predetermined threshold. That is, in step S12, it is monitored that variations occur in both estimation results acquired from the same blood sample.

  If the difference between the two estimation results is within the threshold value in step S12, the main wavelength and the sub wavelength are selected from the plurality of transmitted light amount data measured in the second optical information acquisition unit 80 in step S13. Among these, the CPU 401a analyzes the blood coagulation time using the transmitted light amount data of the coagulation time measurement sample measured at the wavelength selected in step S7. For example, when the test item of the blood sample is “PT” and the wavelength change flag is OFF, the transmitted light amount data measured by irradiating light having the main wavelength of “PT” of 660 nm is analyzed. Used for. Thereafter, in step S15, the CPU 401a outputs analysis results such as blood coagulation time and various flags.

  On the other hand, if the CPU 401a of the control device 4 determines that the difference between the two estimation results is larger than the threshold value in step S12, a flag is added to the measurement result in step S14, resulting in a measurement error. Thereafter, in step S15, “measurement error” and an error code are displayed on the display unit 4b of the control device 4. As a result, the user can check the error content by comparing the error code displayed on the display unit 4b with the error code described in the instruction manual or the like. In this way, the blood sample analysis operation of the blood coagulation time measuring apparatus 1 is completed.

  23 to 26 are flowcharts for explaining the details (subroutine) of the interference substance concentration estimation processing in step S11 of FIG. Next, the interference substance concentration estimation processing in step S11 of FIG. 21 will be described in detail with reference to FIGS.

Based on the transmitted light amount data of the sample for coagulation time measurement in the lag phase acquired by the second optical information acquisition unit 80, in step S31 shown in FIG. 23, the light of each wavelength (405 nm, 575 nm, 660 nm, and 800 nm) is received. The absorbance of the clotting time measurement sample in the lag phase is calculated. Specifically, the CPU 401a starts the coagulation reaction from the time when the cuvette 152 containing the coagulation time measurement sample is inserted into the insertion hole 81a (3.0 seconds after the addition of the coagulation time measurement reagent). Absorbance was calculated using the average value of the total 10 transmitted light intensity data acquired during the period before the start of time (4.0 seconds after the addition of the coagulation time measurement reagent). Yes. Here, the absorbance A is a value obtained by the following equation (2) using the light transmittance T (%) of the sample for coagulation time measurement.
A = −log ₁₀ (T / 100) (2)

  In step S32, chyle is checked. Specifically, as shown in FIG. 24, in step S32a, it is determined whether or not the absorbance (Abs. 660) of the sample for coagulation time measurement with respect to light having a wavelength of 660 nm is larger than a predetermined value. If it is determined in step S32a that the absorbance (Abs. 660) of the clotting time measurement sample with respect to light having a wavelength of 660 nm is greater than a predetermined value, the chyle in the clotting time measurement sample is determined in step S32b. And the item of the chyle flag in the sample analysis list (see FIG. 22) is changed from off (“0” in the table) to on (“1” in the table). . On the other hand, if it is determined in step S32a that the absorbance (Abs. 660) of the coagulation time measurement sample with respect to light having a wavelength of 660 nm is equal to or less than a predetermined value, the chyle in the coagulation time measurement sample. Therefore, the item of the chyle flag in the sample analysis list is maintained in an off state (“0” in the table). In the first embodiment, the content of chyle in the coagulation time measurement sample was measured using light having a wavelength of 660 nm, but the light in the coagulation time measurement sample was measured using light having a wavelength of 800 nm. The content of chyle may be measured.

And in 1st Embodiment, the correction | amendment formula of chyle is calculated | required in step S32c using the light absorbency (Abs.660) of the sample for coagulation time measurement with respect to the light of a wavelength of 660 nm. Specifically, the following standard formula (3) for the absorbance of chyle is determined in advance.
Y = 10 ^b0 · X ^a0 (3)

This standard equation is a relational expression between the absorbance Y and the wavelength X of a standard chyle. In other words, a0 and b0 are defined as unknowns a and b in the above equation (1), and the equation is modified so that the absorbance equation is obtained (the left side is Y). Then, the difference between the measured absorbance (Abs. 660) and the absorbance at 660 nm according to the standard formula (Abs. 660 standard) (the absorbance obtained by substituting the wavelength 660 into the standard formula) {(Abs. 660) − (Abs .660 standard)} is added to the right side of this standard expression. Thus, the following chyle correction formula (4) is obtained.
y = 10 ^b0 · x ^a0 + {(Abs.660) − (Abs.660 standard)} (4)

  In step S32d, an estimated value of the absorbance of the chyle with respect to light having a wavelength of 575 nm (Abs. 575 chyle estimated value) is calculated from the chyle correction formula obtained in step S32c. That is, by substituting the wavelength (x = 575 nm) into the correction formula (4), 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 (4) in the same manner as in step S32d described above. . That is, by substituting the wavelength (x = 405 nm) into the correction formula (4), 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. 23, hemoglobin is checked. Specifically, as shown in FIG. 25, in step S33a, the 575 nm calculated in step S32d (see FIG. 20) described above from the absorbance (Abs. 575) of the coagulation time measurement sample with respect to light having a wavelength of 575 nm. The absorbance (Abs. 575) of the clotting time measurement sample for light at a wavelength of 575 nm was corrected by subtracting the estimated value of the absorbance of the chyle (Abs. Estimate the absorbance of hemoglobin to light of the wavelength. 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, hemoglobin is present in the sample for measuring the clotting time in step S33b. Therefore, the item of the hemoglobin flag in the sample analysis list (see FIG. 22) is changed from off (“0” in the table) to on (“1” in the table). On the other hand, if it is determined in step S33a that ((Abs.575) − (Abs.575 chyle estimated value)) is equal to or less than a predetermined value, the hemoglobin content in the coagulation time measurement sample is determined. It is determined that the amount does not affect the actual measurement, and 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 described above. ) Is calculated. Specifically, as shown in the following equation (5), (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)} (5)

  Next, bilirubin is checked in step S34 shown in FIG. Specifically, as shown in FIG. 26, in step S34a, the 405 nm calculated in step S32e (see FIG. 24) described above from the absorbance (Abs. 405) of the coagulation time measurement sample with respect to light having a wavelength of 405 nm. Estimated value of absorbance of chyle (Abs. 405 estimated value of chyle) with respect to light of a wavelength of λ and estimated value of absorbance of hemoglobin (Abs. 405 estimated value of chyle) calculated at step S33c (see FIG. 25) described above. By subtracting (405 Hgb estimated value), the absorbance (Abs. 405) of the sample for coagulation time measurement with respect to light with a wavelength of 405 nm is corrected, and the absorbance of bilirubin with respect to light with 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 coagulation time is determined. Since the bilirubin content in the measurement sample is judged to have an adverse effect on this measurement, the item of the bilirubin flag in the sample analysis list (see FIG. 22) is off (“0” in the table). It is changed to ON (“1” in the table). 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 coagulation time It is determined that the content of bilirubin in the measurement sample has an adverse effect on this measurement, and the item of the bilirubin flag in the sample analysis list is maintained in an off state (“0” in the table). In this manner, the interference substance concentration estimation using the coagulation time measurement sample is completed.

  The interference substance concentration estimation using the blood sample (original sample) in step S3 of FIG. 21 is the same as that described above except that the data used is the transmitted light amount data acquired by the first optical information acquisition unit 40. Since this is the same as the concentration estimation of the interference substance using the sample for measuring the coagulation time, the description thereof is omitted.

(Second Embodiment)
The configuration of the blood coagulation time measurement device according to the second embodiment is not provided with the first optical information acquisition unit 40 of the blood coagulation time measurement device of the first embodiment. Therefore, prior to the acquisition of the optical information by the second optical information acquisition unit 80, the optical information is acquired by the first optical information acquisition unit 40, and based on this, the concentration of the interference substance is estimated and the qualitative information about the interference substance is obtained. The configuration is not configured to perform the determination, and based on only the optical information in the lag phase obtained by the second optical information acquisition unit 80, the concentration estimation of the interference substance and the qualitative determination regarding the interference substance are performed. ing. In addition, about the structure similar to the structure of the blood coagulation time measuring apparatus by 1st Embodiment, the same code | symbol is attached | subjected and the description is abbreviate | omitted.

  FIG. 27 is a flowchart showing the procedure of the sample analysis operation of the blood coagulation time measuring apparatus according to the second embodiment. First, the user turns on the power of the detection mechanism unit 2 and the control device 4 of the blood coagulation time measuring device 1 shown in FIGS. 1 and 2 to activate the blood coagulation time measuring device 1, Thereby, the initial setting of the blood coagulation time measuring apparatus 1 is performed. Thereafter, the user inputs sample analysis information and analysis processing start. After the input to start the analysis process, the blood sample is collected in step S201 shown in FIG. Note that the initial setting of the blood coagulation time measurement apparatus 1, the input of sample analysis information, and the primary dispensing process in step S201 are the same as the process in step S1 (see FIG. 21) of the first embodiment, and therefore description thereof will be given. Is omitted.

  After the primary dispensing process in step S201, an air blank measurement process is performed in step S202, and then a secondary dispensing process is performed in step S203. In step S204, optical measurement is performed on the coagulation time measurement sample under a plurality of conditions, and transmission light amount data is acquired by the second optical information acquisition unit 80. In addition, since the process of these step S202, step S203, and step S204 is respectively the same as the process of step S8 of 1st Embodiment, step S9, and step S10, the description is abbreviate | omitted.

  Next, in step S205, the CPU 401a uses the transmitted light amount data in the lag phase (4.0 seconds after the addition of the coagulation time measurement reagent) to interfering substances contained in the coagulation time measurement sample. Estimate the concentration and presence of (chyle, hemoglobin and bilirubin). In step S206, the CPU 401a performs qualitative determination regarding the interference substance based on the estimated concentration of the interference substance. Thereafter, in step S207, the CPU 401a selects a wavelength to be used for analysis. Then, in step S208, for the coagulation time measurement measured at the wavelength selected in step S207 out of the main wavelength and the sub wavelength among the plurality of transmitted light amount data measured in the second optical information acquisition unit 80. The CPU 401a analyzes the blood coagulation time using the transmitted light amount data of the sample. Thereafter, in step S209, the CPU 401a outputs analysis results such as blood coagulation time and various flags, and ends the process. In addition, since the process of these steps S206, S207, S208, and S209 is the same as the process of step S4, step S7, step S13, and step S15 in 1st Embodiment, respectively, the description is abbreviate | omitted.

  Next, concentration estimation using the coagulation time measurement sample in step S205 will be described. In this case, since the measurement target is a coagulation time measurement sample obtained by adding a coagulation time measurement reagent to a blood sample, the acquired transmitted light amount data includes not only the influence of the concentration of the interference substance but also the coagulation time measurement reagent. The effect of turbidity is also included. Therefore, in the concentration estimation using the coagulation time measurement sample, unlike the concentration estimation process in step S10 in the first embodiment described above, it is more preferable to perform a process in consideration of the turbidity of the coagulation time measurement reagent. Therefore, in the concentration estimation using the coagulation time measurement sample in this embodiment, processing is performed in consideration of the turbidity of the coagulation time measurement reagent.

  28 to 31 are flowcharts for explaining details (subroutine) of the interference substance concentration estimation processing in step S205 of FIG. First, in step S131 shown in FIG. 28, the absorbance of the coagulation time measurement sample with respect to light of each wavelength (405 nm, 575 nm, 660 nm, and 800 nm) is calculated. Specifically, the CPU 401a starts the coagulation reaction from the time when the cuvette 152 containing the coagulation time measurement sample is inserted into the insertion hole 81a (3.0 seconds after the addition of the coagulation time measurement reagent). Absorbance was calculated using the average value of the total 10 transmitted light intensity data acquired during the period before the start of time (4.0 seconds after the addition of the coagulation time measurement reagent). Yes.

  In step S132, a check for chyle is performed. Specifically, as shown in FIG. 29, in step S132a, the absorbance (reagent turbidity) specific to the reagent derived from the coagulation time measurement reagent from the absorbance (Abs. 660) of the coagulation time measurement sample with respect to light having a wavelength of 660 nm. The absorbance (Abs. 660) of the sample for measuring the coagulation time with respect to light having a wavelength of 660 nm is corrected by subtracting the degree (Abs. 660). Thereby, it is possible to obtain the corrected absorbance ((Abs. 660) − (reagent turbidity Abs. 660)) from which the turbidity of the coagulation time measurement reagent is removed. In the second embodiment, the absorbance specific to the reagent at 660 nm (reagent turbidity Abs. 660) derived from the coagulation time measurement reagent and the absorbance at 800 nm (reagent turbidity Abs. 800) described later, the absorbance at 575 nm (reagent) Turbidity Abs. 575) and absorbance at 405 nm (reagent turbidity Abs. 405) are fixed values set for each type of reagent, and are obtained in advance by mixing a coagulation time measurement reagent and water. . Then, it is determined whether or not the corrected absorbance ((Abs. 660) − (reagent turbidity Abs. 660)) is larger than a predetermined value. If it is determined in step S132a that the above-described corrected absorbance ((Abs.660) − (reagent turbidity Abs.660)) is greater than a predetermined value, in step S132b, the coagulation time measurement sample contains It is determined that chyle is present, and the chyle flag item in the sample analysis list (see FIG. 22) is changed from off (“0” in the table) to on (“1” in the table). Is done. On the other hand, if it is determined in step S132a that the corrected absorbance ((Abs. 660) − (reagent turbidity Abs. 660)) is not more than a predetermined value, in step S132b, the sample for coagulation time measurement. It is determined that the content of the chyle in the stage 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 clotting time measurement sample was measured using light having a wavelength of 660 nm. However, the milk in the clotting time measurement sample was measured using light having a wavelength of 800 nm. May be measured.

In the second embodiment, in step S132c, as in the case of light having a wavelength of 660 nm in step S132a described above, corrected absorbance ((Abs) obtained by removing the turbidity of the coagulation time measurement reagent in light having a wavelength of 800 nm is used. .800)-(Reagent Turbidity Abs.800)). The corrected absorbance at (660 nm) ((Abs. 660) − (reagent turbidity Abs. 660)) and the corrected absorbance at 800 nm ((Abs. 800) − (reagent turbidity Abs. 800)) are used. Find the correction formula for chyle. Specifically, the wavelength (X = 660) and the corrected absorbance (Y = (Abs. 660) − (reagent turbidity Abs. 660)) are substituted into the above formula (1) to derive the following formula (1a). At the same time, the wavelength (X = 800) and the corrected absorbance (Y = (Abs. 800) − (reagent turbidity Abs. 800)) are substituted into the above formula (1) to derive the following formula (1b).
log ₁₀ {(Abs.660) - (reagent Turbidity _{Abs.660)} = alog 10 660 +} b ··· (1a)
log ₁₀ {(Abs. 800) − (reagent turbidity Abs. 800)} = allog ₁₀ 800 + b (1b)

Then, the above equations (1a) and (1b) are combined to calculate the constants a and b, and the chyle correction equation (6) for deriving the absorbance y of the chyle at a predetermined wavelength x is derived.
log ₁₀ y = alog ₁₀ x + b (6)

  In step S132d, 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 (6) obtained in step S132c described above. That is, by substituting the wavelength (x = 575 nm) into the correction formula (6), the estimated value of the absorbance of the chyle with respect to the light having the wavelength of 575 nm (y = Abs.575 chyle estimated value) is calculated.

  Then, in step S132e, an estimated value (Abs. 405 chyle estimated value) of chyle absorbance with respect to light having a wavelength of 405 nm is calculated from the chyle correction formula (6) in the same manner as in step S132d described above. . That is, by substituting the wavelength (x = 405 nm) into the correction formula (6), 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 S133 shown in FIG. 28, hemoglobin is checked. Specifically, as shown in FIG. 30, in step S133a, the turbidity of the coagulation time measurement reagent in light having a wavelength of 575 nm is removed in the same manner as in the case of light having a wavelength of 660 nm in step S132a described above. Absorbance ((Abs.575)-(Reagent turbidity Abs.575)) is obtained. Then, the absorbance of the chyle is estimated for the light of the wavelength of 575 nm calculated in the above-described step S132d (see FIG. 29) from the corrected absorbance of the wavelength of 575 nm ((Abs.575) − (reagent turbidity Abs.575)). The corrected absorbance at 575 nm ((Abs.575) − (reagent turbidity Abs.575)) was corrected by subtracting the value (Abs.575 chyle estimate) to obtain the absorbance of hemoglobin for light at a wavelength of 575 nm. presume. Whether or not the absorbance of hemoglobin (((Abs.575)-(reagent turbidity Abs.575))-(Abs.575 chyle estimated value)) with respect to the estimated light having a wavelength of 575 nm is larger than a predetermined value. Is judged. If it is determined in step S133a that (((Abs.575) − (reagent turbidity Abs.575)) − (Abs.575 chyle estimated value)) is greater than a predetermined value, in step S133b It is determined that hemoglobin is present in the clotting time measurement sample, and the hemoglobin flag item in the sample analysis list (see FIG. 22) is changed from off (“0” in the table) to on (in the table). “1”). On the other hand, when it is determined in step S133a that (((Abs.575) − (reagent turbidity Abs.575)) − (Abs.575 chyle estimated value)) is not more than a predetermined value The hemoglobin flag in the sample analysis list is kept off ("0" in the table) because it is judged that the hemoglobin content in the clotting time measurement sample does not affect the measurement. Is done.

In step S133c, hemoglobin for light having a wavelength of 405 nm is calculated from “((Abs.575) − (reagent turbidity Abs.575)) − (Abs.575 chyle estimated value)” calculated in step S133a. The estimated value of the absorbance (Abs. 405Hgb estimated value) is calculated. Specifically, as shown in the following formula (7), (Abs.405Hgb estimated value) is calculated in step S133a (((Abs.575) − (reagent turbidity Abs.575)) − ( Abs. 575 (chile estimated value)) is multiplied by a constant H (6.5 to 7.5 (preferably 6.8)).
(Abs.405 Hgb estimated value) = H × {((Abs.575) − (reagent turbidity Abs.575)) − (Abs.575 chyle estimated value)} (7)

  Next, in step S134 shown in FIG. 28, bilirubin is checked. Specifically, as shown in FIG. 31, in step S134a, the turbidity of the coagulation time measurement reagent in light having a wavelength of 405 nm is removed as in the case of light having a wavelength of 660 nm in step S132a described above. Absorbance ((Abs.405)-(reagent turbidity Abs.405)) is obtained. Then, from the corrected absorbance at the wavelength of 405 nm ((Abs. 405) − (reagent turbidity Abs. 405)), the absorbance of the chyle with respect to the light of the wavelength of 405 nm calculated in the above-described step S132e (see FIG. 29). By subtracting the estimated value (Abs. 405 Hgb estimated value) and the estimated value of the absorbance of hemoglobin (Abs. 405 Hgb estimated value) for the light having the wavelength of 405 nm calculated in step S133c (see FIG. 30) described above, 405 nm The corrected absorbance ((Abs. 405)-(reagent turbidity Abs. 405)) is further corrected to estimate the absorbance of bilirubin with respect to light having a wavelength of 405 nm. Then, the absorbance (((Abs.405)-(reagent turbidity Abs.405))-(Abs.405 chyle estimated value)-(Abs.405 Hgb estimated value)) of bilirubin with respect to the estimated light having a wavelength of 405 nm is obtained. It is determined whether or not it is greater than a predetermined value. In step S134a, it is determined that ((((Abs.405) − (reagent turbidity Abs.405)) − (Abs.405 chyle estimated value) − (Abs.405Hgb estimated value)) is greater than a predetermined value. In step S134b, it is determined that the content of bilirubin in the clotting time measurement sample has an adverse effect on the measurement, and the item of the bilirubin flag in the sample analysis list (see FIG. 22) is determined. It is changed from off (“0” in the table) to on (“1” in the table). On the other hand, in step S134a, ((((Abs.405)-(Reagent turbidity Abs.405))-(Abs.405 chyle estimated value)-(Abs.405Hgb estimated value)) is not more than a predetermined value. If it is determined that the bilirubin content in the sample for clotting time measurement has an adverse effect on the measurement, the bilirubin flag item in the sample analysis list is off (in the table “0”) state. In this way, concentration estimation using the coagulation time measurement sample is completed.

  In the first and second embodiments described above, the coagulation reaction used for estimating the concentration and presence of the interfering substance in the coagulation time measurement sample by providing the second optical information acquisition unit 80 as described above. The amount of transmitted light at a point before the time (from 3.0 seconds to 4.0 seconds after the addition of the coagulation time measurement reagent) and a plurality of time-dependent data used for measurement of the coagulation time (main measurement) Both the transmitted light amount data and the transmitted light amount data can be acquired. As a result, the application program 404a of the control device 4 not only measures the coagulation time by using the change in the transmitted light amount data with time, but also before the time point indicating the coagulation reaction (the hatched area in FIG. 13). ), The presence / absence and concentration of the interference substance can be measured.

  In the first and second embodiments, a plurality of transmitted light quantities over time used for measurement of the coagulation time (main measurement) are obtained from one coagulation time measurement sample in which a blood sample is mixed with a coagulation time measurement reagent. It is possible to acquire the change and the amount of transmitted light before a coagulation reaction used for estimating the concentration and presence / absence of the interfering substance. The clotting reaction is a reaction in which blood coagulation occurs through the conversion of fibrinogen in plasma into fibrin through a number of endogenous or extrinsic reactions. That is, even if a blood coagulation reagent is mixed with plasma, blood coagulation does not start immediately, usually after about 7 seconds in the extrinsic system (PT measurement reagent), and usually about 14 seconds in the intrinsic system (APTT measurement reagent). A coagulation reaction takes place. In the present embodiment, attention is paid to the fact that the optical information at a time point before the coagulation reaction (referred to as a lag phase) is the same optical information as that in which the specimen is diluted. That is, with the above-described configuration, it is not necessary to separately prepare a sample used for the main measurement and a sample used for estimating the concentration and presence / absence of the interfering substance, so that consumption of a blood sample can be suppressed.

  In the first and second embodiments, the second optical system receives light from a coagulation time measurement sample in which a blood sample is mixed with a coagulation time measurement reagent over time, and acquires a change in the amount of transmitted light with time. By providing the target information acquisition unit 80, the transmitted light amount data can be acquired from the coagulation time measurement sample diluted with the coagulation time measurement reagent. As a result, the second optical information acquisition unit 80 acquires the transmitted light amount data from the diluted coagulation time measurement sample even when it is difficult to detect the transmitted light amount data due to the high blood sample concentration. Therefore, the measurement range in which transmitted light amount data can be acquired can be expanded.

  Also, in the second embodiment, the bilirubin and hemoglobin are substantially made by constructing the application program 404a to estimate the effect of chyle on the optical information at 575 nm and 405 nm based on the absorbance at 660 nm and 800 nm. The effect of chyle on the absorbance at other wavelengths (second wavelength and third wavelength) can be estimated based on the absorbance at the two wavelengths absorbed by the chyle. Thus, based on the absorbance at one type of wavelength, compared to estimating the effect of chyle on the absorbance at other wavelengths, the absorbance at other wavelengths is based on the two absorbances at two types of wavelengths. It is possible to accurately estimate the effect of chyle by estimating the effect of chyle. As a result, the influence of bilirubin and hemoglobin can be estimated using the accurately estimated influence of chyle, so that the influence of interfering substances (chyle, hemoglobin and bilirubin) can be accurately estimated.

  In addition, in the first embodiment, in addition to the second optical information acquisition unit 80 for performing the main measurement, the transmitted light amount is acquired by receiving light from the blood sample before the coagulation time measurement reagent is mixed. By providing the one optical information acquisition unit 40, it is difficult to measure a reliable coagulation time when the concentration of the interfering substance in the blood sample measured by the first optical information acquisition unit 40 is high. Judging that there is, the measurement can be stopped. As a result, since the coagulation time measurement reagent can be stopped from being mixed with the blood sample to be measured, it is possible to suppress wasteful consumption of the coagulation time measurement reagent. Further, in this case, since the main measurement by the second optical information acquisition unit 80 is not performed on a blood sample for which it is difficult to obtain a reliable measurement result (coagulation time), the measurement efficiency of the apparatus is improved. It can also be improved.

  In the first embodiment, the first optical information acquisition unit 40 that receives light from the blood sample before the coagulation time measurement reagent is mixed and acquires the transmitted light amount, and the second optical measurement are performed. By providing the optical information acquisition unit 80, it is possible to perform concentration estimation using a clotting time measurement sample in addition to concentration estimation using an original sample (blood sample). Thereby, it is possible to confirm whether or not an accurate estimation result is obtained by comparing the concentration estimation using the original sample (blood sample) and the concentration estimation using the clotting time measurement sample. As a result, a more accurate measurement result of the concentration and presence of the interfering substance can be obtained. In addition, when the compared estimation result values are far from each other, an apparatus error such as a dispensing error of the coagulation time measuring reagent can be monitored.

  Further, in the second embodiment, the first optical acquisition unit is not provided, and only the second optical information acquisition unit is used to estimate the concentration of the interference substance, which is dedicated for measuring the interference substance. Since it is not necessary to provide a device (first optical information acquisition unit) separately from the main measurement unit (second optical information acquisition unit), the blood coagulation time measurement device can be prevented from becoming complicated. It is possible to suppress the device itself from becoming large. Moreover, it is not necessary to perform optical measurement of a blood sample (original sample), and the operation of the blood coagulation time measuring device can be prevented from becoming complicated.

  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 first embodiment and the second embodiment, the main wavelength is set to a low wavelength and the sub wavelength is set to a high wavelength. However, the present invention is not limited to this, and the main wavelength is set to a high wavelength. In addition to setting the wavelength, the sub-wavelength may be set to a low wavelength. As a result, even when the amount of fibrinogen in the blood sample is small and the clotting reaction cannot be captured largely, if the subwavelength of the low wavelength is selected, the clotting reaction can be captured even for the low fibrinogen blood sample.

  In the first embodiment and the second embodiment, the detection mechanism unit and the control device are separately provided. However, the present invention is not limited to this, and the function of the control device is provided in the detection mechanism unit. Also good.

  Moreover, in the said 1st Embodiment and 2nd Embodiment, although the example which performs the optical measurement (main measurement) of the sample for coagulation time measurement using the coagulation time method was shown, this invention is not limited to this, Optical measurement of a sample for coagulation time measurement may be performed using a synthetic substrate method or immunoturbidimetric method other than the coagulation time method.

It is the perspective view which showed the whole structure of the blood coagulation time measuring apparatus by 1st Embodiment of this invention. It is the top view which showed the detection mechanism part and conveyance mechanism part of the blood coagulation time measuring apparatus by 1st Embodiment shown in FIG. It is the perspective view which showed the 1st optical information acquisition part of the blood coagulation time measuring device by 1st Embodiment shown in FIG. It is a schematic diagram for demonstrating the structure of the 1st optical information acquisition part of the blood coagulation time measuring device by 1st Embodiment shown in FIG. It is a block diagram of the 1st optical information acquisition part of the blood coagulation time measuring device by 1st Embodiment shown in FIG. It is the perspective view which showed the lamp unit of the blood coagulation time measuring apparatus by 1st Embodiment shown in FIG. It is a schematic diagram for demonstrating the structure of the lamp unit of the blood coagulation time measuring apparatus by 1st Embodiment shown in FIG. FIG. 7 is an enlarged perspective view showing a filter portion of the lamp unit shown in FIG. 6. It is the schematic for demonstrating the internal structure of the detection part of the 2nd optical information acquisition part of the blood coagulation time measuring device by 1st Embodiment shown in FIG. It is sectional drawing for demonstrating the structure of the detection part of the 2nd optical information acquisition part of the blood coagulation time measuring device by 1st Embodiment shown in FIG. It is a block diagram of the 2nd optical information acquisition part of the blood coagulation time measuring device by 1st Embodiment shown in FIG. It is a block diagram of the control apparatus of the blood coagulation time measuring apparatus by 1st Embodiment shown in FIG. It is a measurement result of the blood sample mixed with the interference substance measured by the 2nd optical information acquisition part of the blood coagulation time measuring apparatus by 1st Embodiment shown in FIG. It is a measurement result of the normal blood sample measured by the 2nd optical information acquisition part of the blood coagulation time measuring apparatus by 1st Embodiment shown in FIG. It is the graph which showed the light absorbency spectrum of the interference substance (hemoglobin). It is the graph which showed the light absorbency spectrum of interference substance (bilirubin). It is the graph which showed the light absorbency spectrum of the interference substance (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 the chyle shown in FIG. 17 on the log-log graph. It is the flowchart which showed the procedure of the analysis operation | movement of the blood coagulation time measuring apparatus by 1st Embodiment shown in FIG. It is the figure which showed the sample analysis list output to the display part of the control apparatus of the blood coagulation time measuring device by 1st Embodiment shown in FIG. 5 is a flowchart for explaining details (subroutine) of interference substance concentration estimation processing by the control device of the blood coagulation time measurement device according to the first embodiment shown in FIG. 1; It is the flowchart which showed the subroutine of the check of the interference substance (chyle) shown in FIG. It is the flowchart which showed the subroutine of the check of the interference substance (hemoglobin) shown in FIG. It is the flowchart which showed the subroutine of the check of the interference substance (bilirubin) shown in FIG. It is the flowchart which showed the procedure of the analysis operation | movement of the blood coagulation time measuring device by 2nd Embodiment of this invention. It is a flowchart for demonstrating the detail (subroutine) of the density | concentration estimation process of the interference substance by the control apparatus of the blood coagulation time measuring apparatus of 2nd Embodiment of this invention. It is the flowchart which showed the subroutine of the check of the interference substance (chyle) shown in FIG. It is the flowchart which showed the subroutine of the check of the interference substance (hemoglobin) shown in FIG. It is the flowchart which showed the subroutine of the check of the interference substance (bilirubin) shown in FIG.

Explanation of symbols

1 Blood coagulation time measurement device 4 Control device (measurement unit)
4a Control unit (first estimation means, second estimation means, first acquisition means, second acquisition means, third acquisition means, determination means, selection means)
4b Display unit (output unit)
40 1st optical information acquisition part (2nd light-receiving part)
50 Lamp unit (light irradiation part)
60 Reagent dispensing arm (sample preparation unit)
80 Second optical information acquisition unit (first light receiving unit)

Claims (12)

A sample preparation unit for preparing a sample for coagulation time measurement by mixing a blood sample with a reagent for coagulation time measurement;
A light irradiation part for irradiating light to the prepared sample for measuring the coagulation time;
A first light-receiving unit that receives light of a plurality of wavelengths over time from the sample for measuring the coagulation time irradiated with light, and acquires optical information over time;
A measurement unit that measures the coagulation time of the sample for coagulation time measurement based on the optical information acquired by the first light receiving unit;
The measuring unit is configured to perform optical measurement of the coagulation time measurement sample based on optical information obtained before the coagulation time measurement sample exhibits a coagulation reaction among the optical information acquired by the first light receiving unit. A blood coagulation time measurement apparatus configured to measure the content of an interference substance that interferes with measurement in the coagulation time measurement sample.   2. The measurement unit according to claim 1, wherein the measurement unit is configured to measure the contents of the plurality of interference substances based on optical information at a plurality of wavelengths acquired by the first light receiving unit. Blood clotting time measurement device. The first light receiving unit is configured to obtain at least optical information at a first wavelength, a second wavelength, and a third wavelength,
The measurement unit is configured to transmit bilirubin, hemoglobin, and milk in the blood sample based on optical information in at least one of the first wavelength, the second wavelength, and the third wavelength acquired by the first light receiving unit. The blood coagulation time measuring device according to claim 2, wherein the blood coagulation time measuring device is configured to measure a content degree of at least one of the two. The first wavelength is a wavelength that bilirubin and hemoglobin do not substantially absorb and chyle absorbs,
The second wavelength is a wavelength that bilirubin does not substantially absorb and hemoglobin and chyle absorb,
The third wavelength is a wavelength absorbed by bilirubin, hemoglobin and chyle,
The measuring unit is
First estimating means for estimating an influence of chyle on the optical information at the second wavelength and the third wavelength based on at least the optical information at the first wavelength;
Second estimation means for estimating the influence of hemoglobin on the optical information at the third wavelength based on the estimated influence of chyle at the second wavelength and the optical information at the second wavelength. With
Optical information at the first wavelength, the second wavelength, and the third wavelength acquired by the first light receiving unit, and optical information at the second wavelength and the third wavelength estimated by the first estimation unit. The content of bilirubin, hemoglobin and chyle in the blood sample is measured based on the effect of chyle on the blood and the effect of hemoglobin on the optical information at the third wavelength estimated by the second estimating means The blood coagulation time measuring device according to claim 3, wherein the blood coagulation time measuring device is configured to do so. The first light-receiving unit is configured to further acquire optical information at a fourth wavelength that bilirubin and hemoglobin do not substantially absorb and that chyle absorbs,
The first estimating means is configured to estimate an influence of chyle on optical information at the second wavelength and the third wavelength based on optical information at the first wavelength and the fourth wavelength. The blood coagulation time measuring device according to claim 4. The first light receiving unit includes a first wavelength that bilirubin and hemoglobin do not substantially absorb and absorbs chyle, a second wavelength that bilirubin does not substantially absorb and hemoglobin and chyle absorb, and bilirubin Is configured to obtain at least optical information at a third wavelength absorbed by hemoglobin and chyle,
The measuring unit is
First acquisition means for acquiring the influence of chyle on the optical information based on at least the optical information at the first wavelength acquired by the first light receiving unit;
The influence of hemoglobin on the optical information based on the influence of chyle on the optical information acquired by the first acquisition means and the optical information at the second wavelength acquired by the first light receiving unit. Second acquisition means for acquiring
The influence of chyle on the optical information acquired by the first acquisition unit, the influence of hemoglobin on the optical information acquired by the second acquisition unit, and the first acquired by the first light receiving unit. 3rd acquisition means which acquires the influence of bilirubin on optical information based on optical information in three wavelengths,
The influence of chyle on the optical information acquired by the first acquisition means, the influence of hemoglobin on the optical information acquired by the second acquisition means, and the third acquisition means The blood coagulation time measurement apparatus according to claim 1, further comprising an output unit that outputs the influence of bilirubin on the optical information. The first acquisition means includes
Based on the optical information derived from the coagulation time measurement reagent obtained by irradiating light to the coagulation time measurement reagent in addition to the optical information at the first wavelength, milk to the optical information is obtained. The blood coagulation time measurement device according to claim 6, wherein the influence of the blood flow is acquired.   The blood coagulation time measurement apparatus according to any one of claims 1 to 7, wherein the light irradiation unit is configured to irradiate light having a plurality of different wavelengths in a time-sharing manner. A second light receiving unit that receives light from the blood sample before the coagulation time measurement reagent is mixed to obtain optical information;
The measurement unit is configured to measure the content of the interfering substance in the blood sample that optically interferes with the optical measurement of the blood sample based on the optical information acquired by the second light receiving unit. The blood coagulation time measuring device according to any one of claims 1 to 8.   The blood according to claim 9, further comprising: a determination unit that determines whether or not optical information with time is acquired by the first light receiving unit based on the optical information acquired by the second light receiving unit. Coagulation time measuring device.   The content of the interfering substance in the blood sample measured based on the optical information acquired by the first light receiving unit, and the interference measured based on the optical information acquired by the second light receiving unit. The blood coagulation time measurement apparatus according to claim 9 or 10, further comprising a selection means for selecting any one of the content of the substance in the coagulation time measurement sample. A sample preparation unit for preparing a sample for coagulation time measurement by mixing a blood sample with a reagent for coagulation time measurement;
A light irradiation part for irradiating light to the prepared sample for measuring the coagulation time;
A first light-receiving unit that receives light of a plurality of wavelengths over time from the sample for measuring the coagulation time irradiated with light, and acquires optical information over time;
A measurement unit that measures the coagulation time of the sample for coagulation time measurement based on the optical information acquired by the first light receiving unit;
The measurement unit is included in the coagulation time measurement sample based on optical information obtained before the coagulation time measurement sample exhibits a coagulation reaction among the optical information acquired by the first light receiving unit. And a blood coagulation time measurement device configured to identify an interfering substance that interferes with optical measurement of the sample for coagulation time measurement.

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