JPH0155417B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a serum fractionating device, and more particularly to a device that automatically fractionates only serum, which is a supernatant, from a centrifuged blood sample and dispenses it into a sample cup.

When blood is injected into a specimen container such as a test tube and left undisturbed or centrifuged, translucent serum precipitates in the upper layer, and red blood clots recede in the lower layer. Then, in an analyzer or the like, only the upper layer of serum is fractionated and dispensed into a sample cup. In this case, the suction nozzle is positioned by detecting the interface between the serum and the blood clot in advance, thereby preventing the blood clot from being mixed into the serum. This is as disclosed in Japanese Patent Application Laid-Open No. 55-90857 filed by the present applicant. However, even with such accurate positioning, due to negative suction pressure, etc.
Accidentally aspirating blood clots may occur. In such a case, it is necessary to detect this, immediately stop the fractionation operation, and avoid contaminating the fractionated serum.

Furthermore, the serum dispensed into the sample cup is subjected to various analyzes by an analyzer. In such analysis, there are test items that are significantly affected by chyle and hemolysis. Therefore, conventionally, such chyle, hemolysis, etc. have been determined by visual inspection by the operator.

In this way, conventional equipment relied on human judgment, which not only resulted in poor work efficiency, but also resulted in a large amount of impurities mixed in with the sample itself, making it difficult to obtain good samples. There is.

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide a serum fractionating device that monitors serum transported for fractionation during its transport route, thereby allowing a good sample to be obtained and high operational efficiency.

The present invention will be described in detail below along with embodiments shown in the drawings.

FIG. 1 is a schematic configuration diagram showing the configuration of an embodiment of the present invention. Blood in a test tube 1 serving as a sample container has already been separated into blood 3 in the lower layer and serum 5 in the upper layer by a method such as centrifugation. This test tube 1 is held substantially vertically by a holding means (not shown). A nozzle head 7 is arranged above the test tube 1, and the nozzle head 7 includes a lifting platform 702.

This nozzle head will now be described in detail with reference to FIG. The lifting table 702 has a nozzle 704 for sucking the serum 5 in the test tube 1.
and an optical fiber 706 are mounted substantially parallel to each other so as to be able to move up and down integrally. optical fiber 7
06 is utilized to perform two functions.
That is, one of them is to detect the boundary between the blood clot 3 and the serum 5, and the other is to obtain serum information (chyle) within the serum 5. For that purpose,
This optical fiber 706 has a reciprocating optical path, and its tip 706a faces into the test tube 1. A light emitting means 710 such as a light emitting diode and a light receiving means 712 such as a phototransistor are optically coupled to the other ends 706b and 706c of the optical fiber 706, respectively. These light emitting means, ie, light emitting diode 710 and light emitting means, ie, phototransistor 712 cooperate with each other to detect light detector 70.
8. The light from the light emitting diode 710 enters into the optical fiber from one end 706b of the optical fiber 706, and is emitted from its tip 706a. This irradiation light is reflected at the boundary between the chyle or blood clot 3 contained in the serum 5 and the serum 5, and passes through the optical fiber 706 again to the other end 70.
6C is received by the phototransistor 712. The output of this phototransistor 712 is sent to one contact 212 of the switch 21 as an analog signal.
(Figure 1).

Note that, as shown in FIG. 2, this optical fiber 706 is fitted with a sheath 706'.
As will be described later, it is possible to detect that the serum has entered the liquid surface by the change in resistance (current) between the sheath 706' and the ground potential (GND).

Connected to the other end of the suction nozzle 704 is a tube 716 for transporting the aspirated serum and made of a light-transparent material such as Teflon. An electrode pair 714 for detecting air bubbles is provided in the middle of this tube 716. This electrode pair 714 is an electrode 714a connected to the ground level.
and an electrode 714b separated from the electrode 714a by a predetermined distance. These electrodes 714a, 714b
are both connected to the input of the bubble detector circuit 19. Furthermore, a photodetector 718, which is one feature of the present invention, is provided in the middle of the tube 716. This photodetector 718 includes a light emitting means 720 such as a light emitting diode, and a light receiving means 722 such as a phototransistor that faces the light emitting diode with the tube 716 in between. This photodetector 718 is provided to accurately determine the degree of hemolysis by eliminating the influence of bilirubin contained in serum, as will be described later. The light emitting diode 720 of the photodetector 718 has a peak emission wavelength of, for example, 565 nm, and the phototransistor 722 has high sensitivity from the visible region to the near-infrared region. The output of this phototransistor 722 is applied to the other contact 211 of the analog switch 21. Note that the light emitting diode 710 included in the photodetector 708
The light emitting diode 720 included in this photodetector 718 both receives AC power from the light emitting power source 33 for AC lighting.

Returning to FIG. 1, the sheath 7 of the optical fiber 706
06' and the ground electrode 714a are connected to the input of the serum level detection circuit 17. The operations of this serum level detection circuit 17 and the air bubble detection circuit 19 will be described later, and their outputs are respectively given to the microprocessor 31.

Output from phototransistor 712 or 722 switched by analog switch 21
The output from the multiplexer 27 is given to one input of the multiplexer 27 via a common preamplifier 23 and amplifier 25. This multiplexer 27 also receives outputs from other similar amplifiers. The output of the multiplexer 27 is then converted into digital data by the A/D converter 29, and this digital data is provided to the microprocessor 31.

A tank 13 is connected to the output side of the Teflon tube 716 via a dispensing valve 11 . This tank 13 is connected to a compressed air source 37 through a pneumatic circuit 39 . Therefore, the compressed air source 37 and the pneumatic circuit 39 provide a negative pressure for suction by the nozzle 704 and pressurize the erroneously aspirated blood to return it into the test tube 1. The dispensing valve 11 is controlled to open and close by an electromagnetic mechanism 15 operating under the control of the microprocessor 31. Therefore, dispensing valve 1
1 is configured as a solenoid valve.

Next, the principle of detecting the degree of hemolysis in this embodiment will be explained with reference to FIGS. 3 and 4. The spectrum of chyle, hemolysis and bilirubin in serum is known to have unique absorption characteristics, as shown by lines A, B and C in FIG. In this embodiment, the degree of hemolysis is determined by a photodetector 718 based on a change in the amount of light transmitted through the tube 716. For that purpose, a light emitting diode 720 is used as described above.
is selected to have a peak emission wavelength of 550 to 585 nm. As can be seen from lines B and C, in this wavelength region, if there is no influence of chyle,
It will be appreciated that this is a wavelength range that is sensitive to hemolysis, or hemoglobin, but not bilirubin. FIG. 4 shows an experimentally determined relationship between the degree of hemolysis and the rate of decrease in the amount of transmitted light when water is used as a reference (ie, 0). From this figure 4, if there is no influence of chyle,
The degree of hemolysis can be determined directly from the rate of decrease in the amount of transmitted light. In this way, photodetector 718
is used to detect the degree of hemolysis in serum.

FIG. 5 shows the tip 706a of the optical fiber 706 when the optical fiber 706 is introduced into the serum and descended into the serum for many samples such as normal serum to strong chyle serum, and the blood clot 3 and serum. 5 shows the relationship between the output V of the phototransistor 712 and the distance between it and the interface with the phototransistor 712. and,
In FIG. 5, normal serum is shown by line S0, and weak chyle serum and strong chyle serum are shown by lines S1 and S2, respectively. As can be seen from FIG. 5, the output V of the phototransistor 712
shows a nearly constant value at positions far from the boundary, and gradually increases as it approaches the boundary. This tendency is the same for normal serum, weak chyle serum, and strong chyle serum, and in all cases, the output V at the boundary shows a constant value. The influence of light reflected from the fat particles in the chyle serum becomes more pronounced as the degree of chyle increases. Therefore, when compared over the same distance, the output V shows a higher value in the order of strong chyle serum, weak chyle serum, and normal serum. Therefore, in this embodiment, the above
Similar to No. 90857, when controlling the level of the output V of the phototransistor 712 to be discriminated by a certain threshold to stop the nozzle from descending, the initial value V0 of the output V is measured, and the above-mentioned procedure is performed according to this initial value. The threshold hold (Sh) is determined. Note that details will be described later.

FIG. 6 is a flow diagram for explaining the operation of the embodiment shown in FIG. The operation of the embodiment shown in FIG. 1 will be explained below with reference to FIG.

In operation, first, in step 601, the microprocessor 31 performs an initialization operation in response to, for example, turning on a power switch (not shown). Continued step 603
In the microprocessor 31, the control signal a
is generated, and the nozzle elevating mechanism 35 starts lowering the elevating table 702 at high speed. Therefore, both the nozzle 704 and the optical fiber 706, which are integrally attached to the lifting table 702, descend at high speed into the blood sample container, ie, the test tube 1, which has already been centrifuged. At this time, the serum level detection circuit 17 detects a change in the resistance value between the nozzle 704 and the sheath 706' of the optical fiber 706.
It is detected whether the tip of the nozzle 704 enters the serum 5. If a large change occurs in the above-mentioned resistance value, the serum level detection circuit 17 outputs a detection signal b.
occurs. In the microprocessor 31, in response to the detection signal b from the serum level detection circuit 17,
While generating the control signal c, the amount of reflected light at the entry position, ie, the output of the A/D converter 29, is read, and this output value is set as the initial value _V0 (steps 607, 609). In response to the control signal c, the nozzle elevating mechanism 35 switches the elevating table 702 to low-speed lowering. This is to improve positioning accuracy. Since the peak emission wavelength of the light emitting diode 710 is 940 nm, the above-mentioned initial value of the amount of reflected light detects only the presence or absence of chyle (see FIG. 3). Then, from this read initial value, the microprocessor 31 calculates the degree of chyle S,
It is stored in a memory (not shown). This is for later correction of the degree of hemolysis. At the same time, in step 611, the microprocessor 31 sets a threshold level (Sh) for boundary surface detection based on the initial value _V0 read in step 609. In this embodiment, three levels of thresholds are prepared in advance, the initial values measured as described above are level-discriminated into three levels, and the three thresholds (Sh0, Sh0, Selectively set either Sh1 or Sh2 (Fig. 5). Initial value V0
is smaller than A1 in FIG. 5, that is, V
If 0<A1, threshold Sh0 is set. Also, the initial value V0 is A1≦V0<A2
If so, set threshold Sh1.
Further, if the initial value V0 is A2≦V0, a threshold Sh2 is set. To set such thresholds, reference values A1, A2, Sh0 and Sh1, Sh2 are stored in a predetermined storage area in the memory (not shown) of the microprocessor.
is stored in advance.

After that, the microprocessor 31 converts the A/D converter 2
Based on the digital data from step 9, the output V of the phototransistor 712 is read (step 6).
13). At this time, the lifting platform 702 and therefore the nozzle 704 can be seen descending at a low speed. and,
In step 615, the microprocessor 31 generates the control signal d when the reflected light level V reaches the set threshold, that is, when the noise stop position is reached (step 615).
17). In response to this control signal d, the lowering operation of the lifting platform 702 by the nozzle lifting mechanism 35 is stopped.

Subsequently, the microprocessor 31 receives the control signal e
is generated and applied to the analog switch 21. Therefore, the analog switch 21 was previously switched to the contact 212 side, but the other contact 2
It can be switched to the 11 side. In this way, A/D
The conversion system is shared by two photodetectors 708 and 718. Therefore, after this control signal e is issued, the output of the A/D converter 29 receives the output Vh of the phototransistor 722.

Next, the microprocessor 31 performs step 6.
At 21, a control signal f is generated and applied to the pneumatic circuit 39, and a control signal g is generated and applied to the electromagnetic mechanism 15. By that,
The pneumatic circuit 39 brings the tank 13 into a negative pressure state, the tank is connected to the tube 716 by the dispensing valve 11, and the serum 5 begins to be aspirated from the nozzle 704.

The microprocessor 31 reads the degree of hemolysis H from the A/D converter 29 during the serum suction operation, that is, the output Vh of the phototransistor 722 (step 623). The degree of hemolysis H is determined by the rate of decrease in the amount of light transmitted from the light emitting diode 720 to the phototransistor 722 via the tube 716 (see FIG. 4) when serum is flowing. Then, in the following step 625, the microprocessor 31 determines whether or not the read degree of hemolysis H exceeds a preset value.
Note that the set value used in step 625 is selected to be a value that corresponds to the case where the blood smear 3 is erroneously sucked into the nozzle. And the degree of hemolysis H
exceeds the set value, the microprocessor 31
immediately generates control signals h and i (steps 627 and 629). In response to the control signal h, the tank 13 is switched from a negative pressure state to a pressurized state. At the same time, in response to the control signal i, the electromagnetic mechanism 15
closes the injection valve 11 after a certain period of time. Therefore, the suction operation by the nozzle 704 is stopped, and the erroneously aspirated blood is returned to the sample container, that is, the test tube 1.

If, in step 625, the degree of hemolysis H has not reached such a set value, microprocessor 31 subsequently tests for the presence of an output from bubble detection circuit 19 in step 631. In the bubble detection circuit 19, the nozzle 704 and the tube 7
Due to the change in resistance between the electrodes separated by 16,
Detects the presence or absence of air bubbles. That is, the suction nozzle 7
When the serum reaches the level of the tip of the tube 716, this nozzle sucks in outside air, causing air bubbles to enter the tube 716, causing the pair of electrodes 714
The resistance value, that is, the current value between a and 714b (FIG. 2) changes rapidly due to the passage of this bubble. The bubble detection circuit 19 detects such changes and generates a detection signal j. The microprocessor 31 generates a control signal h in response to this detection signal j,
The suction operation is stopped as in the previous step 627 (step 633).

Next, the microprocessor executes the previous step 6.
The degree of hemolysis H read in step 23 is transferred to step 60.
9 and temporarily stored, and corrected with the degree of chyle S (step 635).
Note that correction of the degree of hemolysis due to chyle is performed as follows. That is, the microprocessor 31 uses a correction calculation formula obtained in advance through experiments.
Store it in ROM and use the S and H obtained above.
The corrected degree of hemolysis H' is obtained by: The greater the degree of chyle S, the greater the degree of hemolysis after correction.
H' becomes larger than the actually measured value H.

When the suction operation is stopped in response to air bubble detection, the microprocessor 31 generates control signals k and l (steps 637 and 639). In response, the nozzle elevating mechanism 35 raises the elevating table 702 and stops it at a predetermined value.

The degree of chyle S read in step 609 described above may be notified to the operator by a printer, display device, etc. (not shown). The same applies to the exact degree of hemolysis after correction in step 635.

As described above, according to the present invention, a signal for immediately stopping the suction operation is generated when blood clot is erroneously aspirated, so that the present invention is particularly effective for automatic dispensing analyzers and the like.

Furthermore, as in the above embodiment, if the degree of hemolysis is corrected based on the influence of chyle, it is possible to know the degree of hemolysis more accurately, which is very beneficial.

[Brief explanation of drawings]

FIG. 1 is a schematic diagram showing an embodiment of the present invention. FIG. 2 is an illustrative view showing the nozzle head in detail, FIG. 2 a is a top view, FIG. 2 b is a sectional view taken along line B-B in FIG. 2 a, and FIG. It is a left side view. FIG. 3 is a graph showing the spectrum of chyle, hemoglobin and bilirubin in serum. FIG. 4 is a graph showing the relationship between the degree of hemolysis and the rate of decrease in the amount of transmitted light. FIG. 5 is a graph for explaining the threshold for boundary surface detection. FIG. 6 is a flow diagram for explaining the operation of the embodiment shown in FIG. In the figure, 1 is a test tube, 7 is a nozzle head,
704 is a nozzle, 706 is an optical fiber, 708,
718 is a photodetector, 716 is a tube, 17 is a serum level detection circuit, 19 is a bubble detection circuit, 21 is an analog switch, 29 is an A/D converter, 31 is a microprocessor, and 39 is a pneumatic circuit.

Claims (1)

[Scope of Claims] 1. A specimen container containing blood and serum; a nozzle for aspirating the serum from the specimen container; a tube made of a light-transmitting material for transporting the serum from the nozzle; Hemolysis degree detection means for detecting the degree of hemolysis of serum transported within the tube, the hemolysis degree detection means comprising: a light emitting means provided in a part of the length direction of the tube; a light receiving means for receiving transmitted light; and a calculation means for calculating a degree of hemolysis based on the output of the light receiving means, and the wavelength of the light from the light emitting means is determined by the amount of bilirubin contained in the serum. 550 to 585 nm, which is not sensitive to hemoglobin but is sensitive to hemoglobin; and signal generating means for generating a stop signal for stopping suction from the nozzle in response to the determination by the means that the degree of hemolysis exceeds a predetermined value. 2. A reciprocating optical path means inserted into the serum of the sample container, and a second reciprocating optical path means for allowing light to enter the reciprocating optical path means.
The serum fractionating device according to claim 1, comprising a light emitting means and a second light receiving means for receiving reflected light from the reciprocating optical path means. 3. Claim 2, further comprising a correction means for correcting the influence of chyle contained in the serum on the degree of hemolysis detected by the degree of hemolysis detection means according to the output of the second light receiving means. The serum fractionation device described. 4. Conversion means for converting the outputs of the light receiving means and the second light receiving means into digital data, and a switching means for switching the light receiving means output or the second light receiving means output and providing it to the converting means, A serum fractionating device according to claim 2. 5. The serum fractionating device according to claim 4, wherein the conversion means includes amplifier means for amplifying the analog signal. 6. The serum fractionating device according to claim 2, further comprising a holding means for holding the reciprocating optical path means and the nozzle integrally so as to be movable up and down with respect to the sample container.