JPS5845541A - Measuring apparatus of bilirubin in blood - Google Patents

Abstract

PURPOSE:To determine directly ad sutomatically bilirubin in blood, by irradiating serums with a light of four kinds of wavelength and measuring the absorbance of the light of each wavelength. CONSTITUTION:To a cell holder 17, a capillary contg. zero-point setting liquid (distilled water) is set, and a light of wavelength of 455nm, 575nm, 440nm and 415nm is respectively radiated from a optical part 1 through interference filters 2a-2d which are capable of switching by a driving apparatus. Then the output voltage from a photoreceptor 4 at each wavelength is outputted as the differential voltage between said output voltage and the output voltage held at zero- point compensating circuits 7a-7d, to make the output from a logarithm converting circuit 6 to zero. Subsequently, the capillary of which the inside wall is coated with a solution of 8.3pH, and containing serums, is held at a cell holder 17, and a light of four kinds of wavelength is radiated from the optical part 1 in a same manner. The zero-point compensating voltage at each wavelength from the photoreceptor 4 is converted to a frequency signal at a V-F converting circuit 9, and stored at storage circuits 11a-11d. From these stored values the amount of bilirubin is computed at a computing part 14, and the re- sult is displayed at the display part 15 and printed at a printer 16.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a method for determining total bilirubin in blood by spectral absorption.
The present invention relates to a blood bilirubin measuring device capable of measuring the concentration of direct bilirubin and indirect bilirubin.

The amount of bilirubin in the serum of a normal person is 0.2 to 1.0.

/d+, but jaundice and bile method appear in 21
0/d+ (overt yellow pox), 1 to 2 +
11 (+/No jaundice or bilious urine appears with the old dose increase)
+? , (II yellowtail Im). Also, the type of bilirubin that increases during hemolytic stress is not excreted in the urine. Therefore, it is not possible to detect subclinical or hemolytic jaundice by examining yellowing of the skin or bile urine.

Bilirubin is mainly produced in the reticuloendothelial system, taken up by hepatocytes, conjugated with curcuronic acid, and excreted as a component of bile. Of these, the free bilirubin that reaches the hepatocytes exhibits an indirect reaction, while the bilirubin that passes through the hepatocytes changes to conjugated bilirubin and exhibits a direct reaction. An increase in the amount of direct bilirubin is seen in cases of increased biliary pressure and destruction of hepatocyte cords, and an increase in the amount of indirect bilirubin is seen in cases of excessive bilirubin production and impaired excretory function of hepatocytes.

Therefore, in the case of hepatocellular burden, an indirect reaction occurs in the early stage (during the period of hepatocellular excretory dysfunction), but as hepatocellular rupture progresses, a direct reaction occurs. In obstructive jaundo, the amount of bilirubin increases primarily directly in the early stages, but the amount increases secondary to hepatocyte excretory dysfunction. Hemolytic burden primarily increases indirect bilirubin.

Most of the bilirubin in the blood of healthy people is of the indirect type. Therefore, the qualitative and quantitative determination of direct and indirect bilirubin is an important basis for differentiating the types of jaundice.

For these reasons, quantifying blood bilirubin is extremely important for early diagnosis and differential diagnosis of the burden.Measurement of serum bilirubin concentration includes measurement of total bilirubin concentration as well as direct dolirupin concentration and indirect bilirubin concentration. It is important to also measure the concentration.

Conventionally, E and M are used to measure direct bilirubin, indirect bilirubin, and total bilirubin in blood.

Act or A, A, B, Act. This is a method in which the direct bilirubin is fractionated from serum bilirubin using an analytical reagent, the absorbance of total bilirubin and direct bilirubin is measured, and indirect bilirubin is then calculated from the results of both measurements. Therefore, total bilirubin,
The measurement of direct bilirubin and indirect bilirubin is extremely complicated, inefficient, and time-consuming, and it has been difficult to urgently measure large volumes of serum.

The present invention corrects the above-mentioned drawbacks and makes it possible to automatically measure total bilirubin, direct bilirubin, and indirect bilirubin directly from blood without the need for fractionation using analytical reagents. The purpose is to provide equipment.

Total bilirubin (T
B), direct bilirubin (DB>, indirect bilirubin (ID)
B) is shown to be calculated by the following calculation by multiplying the measured absorbance of serum at four wavelengths by a predetermined coefficient in order to remove the influence of hemoglobin.

TB -ax7+11+ bXAL υ A = aX A1+ CxA3+ dx A4
Io-k /-10 meters ≦ I DB-TBX I D DB-TB-[DB (However, TB: Total bilirubin concentration, IDB: Indirect bilirubin concentration, DB: Direct bilirubin concentration, A□,
A2, A1, A,: Absorbance of serum measured at each of the four wavelengths transmitted by the interference filter, alb, c,
d, e, f, g: coefficients)
Four wavelengths: 455nm, 575nm, 440nm,
415ns, coefficients a=4.2, b--4,2, c
--4,2, d-0,5, e--3,2, f-4,3,
It has been confirmed through experiments that the best calculated value is obtained when a--0.6.

The blood bilirubin measuring device according to the present invention measures the absorbance of the serum by transmitting the collected serum with light of the above-mentioned four wavelengths, calculates the absorbance of the serum using the above-mentioned coefficients based on the measured value, calculates total bilirubin, direct bilirubin, etc. , the concentration of indirect bilirubin can be obtained automatically.

An embodiment of the present invention will be described below based on the same song.

FIG. 1 schematically shows the configuration of a blood bilirubin measuring device according to an embodiment of the present invention.

In the figure, 1 is an optical section, 2 is 455 nm,
Four interference filters 28 to 2d that transmit light having wavelengths of 575 nm, 440 nm, and 415 nm are connected to the driving device 3.
This is a filter section in which the interference filters 2a to 2d are sequentially switched by the following steps.

4 is a light receiver that receives light transmitted through serum or distilled water in a capillary tube; 5 is a DC amplifier that amplifies the light receiving output of the light receiver 4; and 6 is a logarithmic conversion circuit that logarithmically converts the output of the DC amplifier 5.

7 is a zero point correction circuit that corrects the zero point of the output of the logarithmic conversion circuit 6 each time the interference filters 28 to 2d of the filter section 2 is switched, and 8 is a zero point correction circuit of the zero point correction circuits 78 to 7d corresponding to the switching of the interference filters 28 to 2d. A switching circuit that switches to either
9 is V-F! which converts the voltage output signal of the logarithmic conversion circuit 6 into a frequency signal. The l conversion circuit 10 is an arithmetic circuit that performs calculations based on the output of the V-F conversion circuit 9.

The arithmetic circuits 10 each have a wavelength of 455n-1575r.
v, 44Qns, 415nm interference filter 28~2d
The output A of the V-F conversion circuit 9 in the case of ! ”i and A+a
Memory circuit 118 for storing each sA44o1A samurai
11d, and the values A6, Ah'+t, and A440SA+1S stored in the memory circuits 11a to 11d, respectively, to multipliers 12a to 12d that multiply the coefficients set in the coefficient setters 138 to 13d (however, the coefficients are set as described above). to 4.2
, -4.2, -4.2.0.5, -3.2.4.3, -
0.6>, and based on the outputs of the multipliers 12a to 12d, T B = 4.2 x A-4,2 x 1A = 4.
2XA4st 4.2XA44o +0.5xA4I
rIe--3,2x A45t+ 4.3 x A+4
．． -0.6 x At, +rIDB-TBxIDDB=TB-IDB.

15 are calculation results TB and IDB by the calculation unit 14;

A display section 16 displays the DB, and 16 is a printer that prints the TB, IDB, and DB.

In addition, 17 is a capillary tube containing serum or a liquid for setting the zero point (
It is a cell holder that holds a capillary tube containing water (that is, distilled water).

Next, the operation of the above embodiment will be explained.

First, a capillary tube containing distilled water is set in the cell holder 17.

Next, the four interference filters 28 to 2d are sequentially switched by the drive device 3, and the zero point correction circuits 78 to 7d are
Switching is performed by the switching circuit 8 in correspondence with the interference filters 28 to 2d. In the case of the interference filter 2a that transmits the wavelength of 455 ns, the wavelength of 455 ns of the light from the optical section 1 is transmitted through the interference filter 2a.
- Only the light passes through the interference filter 2d, passes through the distilled water in the capillary tube held in the cell holder 17, and is received by the light receiver 4. Since the output voltage from the light receiver 4 is output as a differential voltage with the voltage held in the zero point correction circuit 7a, the output of the logarithmic conversion circuit 6 becomes zero. Similarly 575+
Each interference filter 2b of v, 440+v, 415n-
, 2c, '2d are held in the zero point correction circuits 7b, 7C, 7d, respectively,
The output of the logarithmic conversion circuit 6 when distilled water is irradiated with light of each wavelength is made zero.

Next, the capillary tube containing distilled water is removed from the cell holder 17, and the capillary tube containing the serum to be measured is removed from the cell holder 1.
Hold it at 7. The inner wall of the capillary for measurement was filled with I) H83 solution (corrected with phosphate buffer and peasant soda).
This is coated with a substrate liquid. When the collected blood is put into a capillary tube and the capillary tube is rotated at high speed in a centrifuge, the blood is separated into red parts (blood cells) and yellow parts (serum). Conditions are set to obtain an absorption curve.

Of the light from the optical section 1, only the light with a wavelength of 455 nl is first irradiated onto the serum in the capillary tube by the interference filter 2a.

The light that has passed through the serum is received by the light receiving section 4. Although the light is absorbed when passing through the serum, the output voltage of the light receiving section 4 is corrected by the voltage held for zero point correction in the zero point correction circuit 7a corresponding to the wavelength of 455n, and The output of the logarithmic conversion circuit 6 is converted into a frequency signal by the V-F conversion circuit 9, and is stored in the storage circuit 11a.

Next, the interference filters are switched to 2b and 2c12d, and the wavelengths of the light irradiated to the serum are sequentially switched to 575rv, 440+v, and 415rvk, and the absorbance is measured and stored in the memory circuits 11b, 11c, and 11d. . Note that the interference filter is connected to the drive device 3 by 2a,
2b, 20.2d, the zero point correction circuit is changed to 7a17b, 7c by the switching circuit 8.
.

7d and perform zero point correction respectively.

The calculation unit 14 performs the above-described calculation based on the values stored in the storage circuits 11a to 11d multiplied by the coefficients set in the coefficient setters 13a to 13d by the multipliers 12a to 12d. The calculation result TB.

IDB and DB are displayed on the display unit 15, and the printer 1
6 is printed.

In this way, total bilirubin, direct bilirubin, and indirect bilirubin can be automatically measured from the serum in the capillary tube 1' placed in the cell holder 17 by irradiating the light from the optical section 1.

Therefore, it is also possible to continuously irradiate a large number of capillary tubes containing serum with light and perform continuous measurements.

Furthermore, Figure 2 shows the correlation between the measured values of the present invention and the measured values of the conventional EM method based on experiments conducted by the present inventor. FIG. 3 shows the correlation with measured values.

As explained above, according to the measuring device of the present invention, total bilirubin, total bilirubin, Since the concentration of direct bilirubin and indirect bilirubin can be measured automatically, it is possible to measure a large amount of serum at high speed.

[Brief explanation of the drawing]

FIG. 1 is a block diagram showing one embodiment of the present invention. FIG. 2 is a graph showing the correlation between the measured values according to the present invention and the measured values according to the conventional EM method. FIG. 3 is a graph showing the correlation between the measured values according to the present invention and the measured values according to the conventional AAB method. 1... Optical section, 2... Filter section, 2a, 2b12
012 d...Interference filter, 3...Drive device, 4
. . . Photodetector, 5. DC amplifier, 6. Logarithmic conversion circuit, 7 a. 7 b, 7 c, 7 d... zero point correction circuit, 8.
...Switching circuit, 9...V-F conversion circuit, 10...Arithmetic unit, 11a111b, 11C, 11d...Storage circuit, 12a, 12b, 120.12 d+++
Multipliers, 13a, 13b. 130.13d... Coefficient setter, 14... Arithmetic unit,
15...Display section, 16...Printer, 17...Cell holder 〇Patent applicant Yuji Kobayashi Agent Patent attorney Makoto Hayakawa Procedural amendment (voluntary) Commissioner of the Japan Patent Office Shima 1) Haruki Tono 1. Indication of the case 1982 Patent Application No. 144369 2. Name of the invention Blood bilirubin measuring device 3. Person making the amendment Relationship to the case Patent applicant name: Fu'hiran'Gayai 4, Agent: 151 Phone number 370-5459 Address Room 712, New State Mena, 2-23-1 Yoyogi, Shibuya-ku, Tokyo 6. Contents of correction,〈;;ma(
1) Correct "-83 solution" on page 10, line 6 of the specification to rpl (8J solution). (2) Correct "1M method" on page 12, line 4 of the specification. (8) In the 6th line of page 12 of the specification, the phrase "AAB method" is corrected to "A, A, B, method." ( 4) "lFtM method" in the third line from the bottom of page 12 of the specification.
Correct the text to "11M, Law." (6) In the last line of page 12 of the specification, "AAB method" is corrected to "Mu, Mu, B, method."

Claims (1)

[Scope of Claims] An optical section for irradiating light onto the serum or zero point setting liquid; means for receiving the light from the optical section that has passed through the serum or the zero point setting liquid and outputting an absorbance measurement value; four types of interference filters that are sequentially switched by a driving device so as to transmit only four wavelengths of light from the optical section; four zero point correction circuits that respectively store the absorbance and correct the absorbance of serum at each wavelength using the stored values; a switching circuit that switches the four zero point correction circuits in response to switching of the four types of interference filters; ;Memorize the absorbance measurements of l1hWi at the four wavelengths Aiv-A, %A3, A4, TB -axA1+ bX% A'= aX AL+ CX A3+ dX A7) I
DB=TBXID DB-TB-IDB (where TB: total bilirubin concentration, IDB: indirect bilirubin concentration, DB: direct bilirubin concentration, a,
b, cld, e, f, g: coefficient)
A blood bilirubin measuring device equipped with a computing device that computes: