JP2006300814A - Dispensing apparatus, suction abnormality determination method in the same, and method for setting threshold value for suction abnormality determination - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To highly sensitively detect suction abnormalities by setting a threshold along a suction pressure curve and eliminate problems such as mismatches with an actual suction pressure curve. <P>SOLUTION: Prior to the suction of blood serum 201 by a nozzle tip 102, a pressure value P<SB>R0</SB>before suction is measured by a pressure sensor 107. A threshold information (a threshold PL (t) of suction pressure) for blood serum corresponding to the nozzle tip 102 in use is acquired from a threshold information storage part 113. The threshold PL (t) of suction pressure which changes according to time since the start of suction of the blood serum 201 by the nozzle tip 102 is set through the use of the measured pressure value P<SB>R0</SB>before suction. Then the suction of the blood serum 201 is started, and the threshold PL (t) of suction pressure is compared with suction pressure detected by the pressure sensor 107 at each time since the start of suction. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to, for example, a dispensing device that dispenses serum separated from blood, a suction abnormality determination method in the dispensing device, and a threshold setting method for determining suction abnormality, and in particular, a suction abnormality such as clogging of a nozzle tip is determined. This is suitable for use.

  For example, in the field of examining blood collected from a human body, serum (liquid sample) separated from blood is dispensed into a test container by an automatic dispensing device. In the automatic dispensing device, the nozzle is moved to the position of the liquid sample, and the pump is driven to decompress the inside of the nozzle and suck the liquid sample with the nozzle tip. Then, the nozzle is moved to the position of the cuvette while the liquid sample is sucked, and the sucked liquid sample is discharged to the cuvette.

  By the way, when serum is dispensed, the nozzle tip may be clogged by fibrin contained in the serum, or the nozzle tip may be clogged when the nozzle tip contacts the separating agent and sucks the separating agent. There is a risk. When a suction abnormality such as clogging of the nozzle tip occurs as described above, the amount of liquid sample dispensed varies, and the analysis accuracy decreases. Further, in the case of clogging due to contact with the separating agent, other substances (separating agent) are mixed in the liquid sample (serum). Therefore, it is extremely important to detect suction abnormalities such as clogged nozzle tips and take appropriate measures.

  Here, as shown by the solid line in FIG. 10, the suction pressure when the liquid sample is sucked by the nozzle tip continuously changes from the start of the suction of the liquid sample, and is shown by the dotted line A and the dotted line B when the suction abnormality occurs. It is known that the suction pressure changes. Up to now, as indicated by a two-dot chain line in FIG. 10, when a certain pressure value is set as a threshold value, and the suction pressure exceeds the threshold value (becomes below), suction abnormalities such as nozzle tip clogging have occurred. It was determined that it occurred.

  However, since the suction pressure gradually decreases even during normal operation, when a constant pressure value is set as a threshold value, it is necessary that the threshold value does not exceed the minimum value of the suction pressure. For this reason, in particular, when a suction abnormality occurs at an early stage after the start of suction and a pressure change occurs, detection of the pressure change may be delayed (in the case indicated by the dotted line A) or may not be detected at all (dotted line). (In the case of B), there is a risk that the suction abnormality cannot be detected reliably.

JP 2000-121649 A

  In Patent Document 1, as described above, a constant pressure value is not used as a threshold value, but when a predetermined amount of sample is dispensed, a suction pressure curve is based on a dispensing parameter that affects a change in suction pressure. It is disclosed that data is obtained by calculation, and a region having a predetermined vertical width along the curve of the suction pressure curve data is set as a determination region.

However, when the suction pressure curve data is calculated based on only the dispensing parameters as disclosed in Patent Document 1, when the actual phenomenon deviates from the theory, the calculated suction pressure curve is It will not match the suction pressure curve. For example, Patent Document 1 considers pressure loss (viscous loss) proportional to the flow velocity, but pressure loss proportional to the square of the flow velocity (dynamic pressure 1/2 · ρ · v ² generated at the tip of the nozzle tip). (Pressure loss of a rapidly contracting tube and a expanding tube proportional to the above) is not considered. When the flow velocity is large, the effect proportional to the square of the flow velocity cannot be ignored and does not match the actual suction pressure characteristics. Patent Document 1 considers only the case where the pump speed is constant. For example, it does not support trapezoidal driving (acceleration from a small initial speed and finally decelerate and stop). It will not match the suction pressure characteristics.

  The present invention has been made in view of the above points, and detects a suction abnormality with high sensitivity by setting a threshold value related to a suction pressure that changes according to the time from the start of suction of a liquid sample by a nozzle tip. The purpose is to eliminate the inconvenience that does not match the actual suction pressure characteristics.

The dispensing device according to the present invention is a dispensing device that sucks a liquid sample with a nozzle tip, and includes threshold information including a predetermined parameter, and the predetermined parameter value when the liquid sample is sucked with the nozzle tip. And a threshold value setting means for setting a threshold value for a suction pressure that changes according to the time from the start of suction of the liquid sample by the nozzle tip, and a suction pressure when the liquid sample is sucked by the nozzle tip. The suction pressure detection means for comparing the suction pressure itself detected by the suction pressure detection means or a value obtained from the suction pressure with the threshold set by the threshold setting means to determine the suction abnormality Threshold value information including the predetermined parameter is obtained in advance using a nozzle tip equivalent to the nozzle tip. The acquired suction pressure curve by drawing a reference sample that has been prepared in accordance with the liquid sample, having the feature that those obtained by utilizing the suction pressure curve.
A suction abnormality determination method in a dispensing apparatus according to the present invention is a suction abnormality determination method in a dispensing apparatus that sucks a liquid sample with a nozzle tip, and includes threshold information including predetermined parameters, and the liquid sample with the nozzle tip. A threshold setting procedure for setting a threshold for a suction pressure that changes according to the time from the start of suction of the liquid sample by the nozzle tip using the predetermined parameter value at the time of suction, and the liquid by the nozzle tip A suction pressure detection procedure for detecting a suction pressure when the sample is sucked, a value of the suction pressure itself detected by the suction pressure detection procedure or a value obtained from the suction pressure, and a threshold value set by the threshold setting procedure The threshold information including the predetermined parameter is a pre-determined procedure. A suction pressure curve is obtained by sucking a reference sample prepared in accordance with the liquid sample using a nozzle tip equivalent to the nozzle tip, and obtained using the suction pressure curve. Characterized by points.
A threshold setting method for determining suction abnormality according to the present invention is a threshold setting method for determining suction abnormality for setting a threshold for suction pressure for determining suction abnormality when a liquid sample is sucked by a nozzle tip, A suction pressure curve acquisition procedure for acquiring a suction pressure curve by sucking a reference sample prepared according to the liquid sample at a maximum suction set amount using a nozzle tip equivalent to the nozzle tip, and the suction pressure Using the approximate curve acquisition procedure for obtaining an approximate curve of the suction pressure curve itself acquired by the acquisition procedure or at least a part of the curve obtained from the suction pressure curve, and the approximate curve determined by the approximate curve acquisition procedure It has a feature in that it has a threshold information determination procedure for determining threshold information regarding suction pressure for abnormality determination.

  According to the present invention, since the threshold value related to the suction pressure that changes according to the time from the start of suction of the liquid sample by the nozzle tip is set, the suction pressure curve itself or a curve obtained from the suction pressure curve is used. A threshold value can be set, and abnormal suction can be detected with high sensitivity.

  Moreover, the threshold information including predetermined parameters is obtained by sucking a reference sample prepared according to the liquid sample using a nozzle tip equivalent to the nozzle tip to be used, and the suction pressure curve Therefore, inconveniences that do not match the actual suction pressure characteristics can be eliminated.

  Furthermore, since the threshold value is set using the threshold information including the predetermined parameter and the predetermined parameter when the liquid sample is sucked by the nozzle tip, the reference parameter is used for the predetermined parameter. Even if the value is different from the value when the pressure is acquired, there is no need to acquire the suction pressure curve again.

Preferred embodiments of the present invention will be described below with reference to the accompanying drawings.
(First embodiment)
FIG. 1 is a diagram showing a schematic configuration of an automatic dispensing apparatus to which the present invention is applied. In the present embodiment, an example will be described in which blood is separated into a serum 201, a separating agent 202, and a blood clot 203 in a blood collection tube 200 by centrifugation, and the serum 201 is dispensed as a liquid sample.

  Reference numeral 101 denotes a nozzle having a tapered shape. Reference numeral 102 denotes a nozzle tip for aspirating the serum 201. In this embodiment, a disposable tip that is detachably attached to the tip of the nozzle 101 is used. Reference numeral 103 denotes an XYZ-axis drive unit realized by a stepping motor or the like, which moves the nozzle 101 in the X-axis, Y-axis, and Z-axis directions according to a control signal from the control unit 108.

  A pipe 104 connects the nozzle 101 and the syringe pump 105. A syringe pump 105 changes the air pressure in the nozzle 101, the nozzle tip 102, and the pipe 104 by moving the piston 105b in the cylinder 105a. A syringe pump driving unit 106 moves the piston 105 b of the syringe pump 105 in accordance with a control signal from the control unit 108.

  Reference numeral 107 denotes a pressure sensor that detects the air pressure in the nozzle 101, the nozzle tip 102, and the pipe 104, and outputs the detected pressure as a current signal.

  Reference numeral 108 denotes a control unit that controls each part of the automatic dispensing apparatus, and is configured by a CPU of a computer, for example. Reference numeral 109 denotes an input unit for an operator to perform various settings and the like, and is configured by, for example, a keyboard or a mouse. Reference numeral 110 denotes a display unit for displaying various types of information, and is configured by a liquid crystal display, for example.

  Reference numeral 111 denotes an I / V conversion circuit that converts a current signal output from the pressure sensor 107 into a voltage signal. Reference numeral 112 denotes an AD converter that converts a voltage signal of an analog signal output from the I / V conversion circuit 111 into a digital signal.

  Reference numeral 113 denotes a threshold information storage unit that stores suction pressure threshold information including a pressure value before suction as a parameter, and outputs the threshold information to the threshold setting unit 114. Although the threshold information stored in the threshold information storage unit 113 will be described in detail later, a reference sample (physical properties equivalent to the serum 201) prepared according to the serum 201 using a nozzle tip equivalent to the nozzle tip 102 to be used. The suction pressure curve is obtained by sucking the reference sample having a maximum suction set amount, and is obtained using the suction pressure curve.

  Reference numeral 114 denotes a threshold setting unit that uses the threshold information acquired from the threshold information storage unit 113 and the pressure value before suction when the serum 201 is sucked by the nozzle tip 102 to suck the serum 201 by the nozzle tip 102. A threshold value of the suction pressure that changes according to the time from the start is set.

  Reference numeral 115 denotes a determination unit, which compares the suction pressure detected by the pressure sensor 107 with the threshold value of the suction pressure set by the threshold setting unit 114 when the serum 201 is sucked by the nozzle chip 102, and determines the suction pressure. When the threshold is exceeded, it is determined that the nozzle tip 102 is clogged.

  Here, how to obtain the threshold information stored in the threshold information storage unit 113 will be described.

  As a first step, prior to actually dispensing serum 201, a reference sample having physical properties equivalent to serum 201 is aspirated at a maximum aspiration setting amount using a nozzle tip equivalent to nozzle tip 102 to be used. Thus, the suction pressure curve P (t) (reference waveform) is acquired.

Next, as a second step, an approximate curve P _a (t) of the suction pressure curve P (t) acquired in the first step is obtained by fitting processing. That is, in the second step, the pressure value P ₀ before suction, the liquid level height h when sucking the maximum liquid amount in the nozzle tip, the minimum pressure value P _min , the minimum from the start of suction (start of the syringe pump 105) time T _min until the pressure value P _min, a density of the reference sample [rho, using a gravitational acceleration g, the time constant tau, approximate curves P _a a (t), the following equation suction pressure curve P (t) (1 )
P _a (t) = P ₀ − (P ₀ −P _min −ρgh) · (1−exp (−t / τ)) − ρgh · t / T _min
... Formula (1)
(T is the time when the time when suction is started is 0)
The time constant τ is determined so that the actually measured suction pressure curve P (t) and the approximate curve P _a (t) substantially coincide with each other.

Specifically, as shown in FIG. 2A, after the pressure value P ₀ before suction is measured by the pressure sensor 107, the reference sample is sucked to obtain the suction pressure curve P (t), and the minimum pressure is obtained. to obtain the time T _min of from the value P _min and the suction start (start of the syringe pump 105) until the minimum pressure value P _min. The time T _min can be calculated from the operating parameters of the syringe pump 105. For example, in the case of trapezoidal driving (acceleration from a small initial speed, and finally decelerating and stopping), as shown in FIG. Time until just before. As described above, trapezoidal driving other than the constant speed can be dealt with. Then, the pressure value at the time T _min is measured from the actually measured suction pressure curve P (t) and set as the minimum pressure value P _min .

  Further, the liquid level height h at the time of maximum liquid volume suction in the nozzle tip is acquired, and the maximum water head pressure ρgh is taken in as shown in FIG.

Then, as shown in FIG. 2C, the time constant τ is sequentially increased from 0, and the time constant τ is determined so that the approximate curve P _a (t) substantially matches the actually measured suction pressure curve P (t). .

Next, as a third step, as shown in FIG. 2D, the suction pressure threshold value PL () using the approximate curve P _a (t) obtained as described above and the constant PL ₀ is used. t) with the following formula (2)
PL (t) = P _a (t) −PL ₀ Formula (2)
Determine as. If the value of the constant PL ₀ is reduced, the detection sensitivity of the suction abnormality can be increased. The constant PL ₀ is set to an appropriate value in consideration of noise and the like.

  The suction pressure threshold value PL (t) obtained as described above is stored in the threshold value information storage unit 113 as threshold value information. In this case, if a plurality of types of nozzle chips are used as the nozzle chip 102, the first to third steps are performed on the nozzle chips equivalent to the nozzle chips to obtain the suction pressure threshold value PL (t). . If a liquid sample other than serum 201 is to be aspirated, the first to third steps are similarly performed on the reference sample of each liquid sample, and the threshold value PL (t) of the aspiration pressure is obtained.

  Next, with reference to the flowchart of FIG. 4, the dispensing operation in the automatic dispensing apparatus of the present embodiment will be described. First, the nozzle 101 to which the nozzle tip 102 is attached is moved to the suction position by the XYZ axis driving unit 103, and the tip of the nozzle tip 102 is inserted into the blood collection tube 200 and immersed in the serum 201 (step S401).

In this state, the pressure value P _R0 before suction is measured by the pressure sensor 107 (step S402).

Subsequently, the threshold information for serum (threshold pressure threshold PL (t)) corresponding to the nozzle chip 102 being used is acquired from the threshold information storage unit 113, and the pressure value P before suction measured in step S402. By using _R0 , a threshold value of the suction pressure that changes according to the time from the start of the suction of the serum 201 by the nozzle tip 102 is set (step S403).

That is, even if the pressure value P _R0 before suction is different from the pressure value P ₀ before suction when the reference sample is sucked, other parameters (liquid level height h, time T _min , density ρ, Since gravity acceleration g and time constant τ) do not change, the suction pressure curve has the same shape as shown in FIG. Accordingly, in the above equation (2), pressure values P _R0 and P _Rmin (P _Rmin can be obtained by using the difference between the pressure value P _R0 and the pressure value P ₀ ) are substituted for the pressure values P ₀ and P _min. This is set as the suction pressure threshold value PL (t).

  Thereafter, when the piston 105b of the syringe pump 105 is pulled, the air pressure in the nozzle 101, the nozzle tip 102, and the pipe 104 is reduced (aspiration pressure), and the suction of the serum 201 by the nozzle tip 102 is started (step S404). ).

  When the suction of the serum 201 is started by the nozzle chip 102, the suction pressure threshold PL (t) and the suction pressure detected by the pressure sensor 107 at each time from the start of suction based on the timer signal from the control unit 108. Are compared (step S405). That is, as shown in FIG. 6, a suction pressure threshold value (two-dot chain line in the figure) that changes according to the time from the start of suction is set along the suction pressure curve (solid line in the figure). . By setting a threshold value along the suction pressure curve in this way, detection of pressure changes due to suction abnormalities will not be delayed or cannot be detected at all, and suction abnormalities will be detected with high sensitivity. Can do.

  If the suction pressure exceeds the threshold value for a certain time in step S405, it is determined that the nozzle tip 102 is clogged (step S406). In this case, for example, the syringe pump 105 is stopped, and a predetermined process such as discharging the serum 201 sucked up to that time or replacing the nozzle tip 102 with a new one is performed (step S407).

  On the other hand, when the suction of the serum 201 by the nozzle tip 102 is completed without the suction pressure exceeding the threshold value in step S405 (step S408), the nozzle 101 is pulled up by the XYZ axis driving unit 103, and the test container (not shown) Move upward. Then, by pushing in the piston 105b of the syringe pump 105, the serum 201 in the nozzle tip 102 is discharged into the test container (step S409), and a series of dispensing operations is completed.

As described above, the suction pressure curve (reference waveform) is obtained by sucking the reference sample prepared according to the liquid sample (serum or the like) to be sucked using the nozzle tip equivalent to the nozzle tip 102 to be used. ) And using the reference waveform to obtain parameters such as a time constant τ and a pressure value P ₀ before suction to obtain threshold information, compared to obtaining suction pressure curve data by calculation, A threshold value that matches the actual suction pressure curve can be set, and inconveniences that do not match the actual suction pressure curve can be eliminated.

Moreover, even if the pressure value P _R0 before suction is different from the pressure value P ₀ before suction when the reference waveform is acquired, the threshold value PL (t) at the pressure value P ₀ before suction is used. be able to. Therefore, there is no need to newly acquire a reference waveform as the pressure value P _R0 before suction, and the work load can be reduced.

  Further, the reference waveform is acquired by aspirating the reference sample with the maximum aspiration setting amount, but even when the aspiration setting amount is changed when the serum 201 is aspirated, the threshold value PL (t) at the maximum aspiration setting amount is obtained. Can be used. That is, when only the suction set amount is changed, as shown by the two-dot chain line in FIG. 5, it matches the reference waveform at the maximum suction set amount until halfway, so the suction pressure curve at the maximum suction set amount is used. The threshold value PL (t) can be used as it is.

  Furthermore, as described below, even if the viscosity of the liquid sample to be aspirated and the suction speed at the time of dispensing differ from the viscosity of the reference sample or the suction speed when the reference sample is sucked, It is possible to use the threshold value PL (t) obtained based on the above.

(When the viscosity of the liquid sample to be aspirated is different from the viscosity of the reference sample)
Even when the viscosity of the liquid sample to be aspirated is different from the viscosity of the reference sample, the threshold value PL (t) obtained based on the reference sample can be used. FIG. 7A shows suction pressure curves P ₁ (t) to P ₅ (t) when the viscosity [cP] of the liquid sample changes in the range of 1 to 20 [cP].

For example, using a liquid sample having a minimum viscosity of 1 [cP] as a reference sample, an approximate curve P _a1 (t) is obtained by the above equation (1). For the other viscosities 2 [cP], 5 [cP], 10 [cP], and 20 [cP], only the minimum pressure value _Pmin is acquired from the reference waveform. The approximate curve P _a1 minimum pressure value P _min and another viscosity 2 (t) [cP], 5 [cP], 10 [cP], when replacing the minimum pressure value P _min at 20 [cP], FIG. Approximate curves P _a2 (t) to P _a5 (t) as shown in 7 (a) are obtained.

That is, if a fitting process is performed on a liquid sample having a minimum viscosity of 1 [cP] and only the minimum pressure value _Pmin is acquired for other viscosities, the respective viscosities of 1 [cP], 2 [cP], and 5 [ Threshold values at cP], 10 [cP], and 20 [cP] can be obtained (formula (2)). In this case, as shown in FIG. 7A, the deviation between the approximate curves P _a2 (t) to P _a5 (t) and the suction pressure curves P ₂ (t) to P ₅ (t) increases as the viscosity increases. The detection sensitivity decreases slightly as the viscosity increases and the viscosity increases, but the threshold value PL (t) at each viscosity can be easily obtained.

Further, when the viscosity of the liquid sample to be aspirated is different from the viscosity of the reference sample, if the time constant τ is changed, the threshold value PL (t obtained based on the reference sample can be obtained without reducing the detection sensitivity. ) Can be used. In FIG. 7B, as in FIG. 7A, the suction pressure curves P ₁ (t) to P ₅ (P) when the viscosity [cP] of the liquid sample changes in the range of 1 to 20 [cP]. t).

The liquid sample of the minimum viscosity 1 [cP] and a maximum viscosity 20 [cP], time as their approximate curve P _a (t) is the suction pressure curve P ₁ (t), respectively coincide substantially to P ₅ (t) The constant τ is determined, and from the result, the time constant τ is expressed by an expression in relation to the viscosity. For example, the following formula (3)
τ = 0.068 × viscosity [cP] +0.148 (3)
become that way. For the other viscosities 2 [cP], 5 [cP], and 10 [cP], only the minimum pressure value _Pmin is acquired from the reference waveform. Then, for example, the approximate curve P _a1 minimum pressure value P _min and another viscosity 2 (t) [cP], 5 [cP], as well as replacing the minimum pressure value P _min of 10 [cP], the above equation (3) Substituting with the time constant τ obtained in step (b), approximate curves P _a2 (t) to P _a4 (t) as shown in FIG. 7B are obtained.

That is, a fitting process is performed on a liquid sample having a minimum viscosity of 1 [cP] and a maximum viscosity of 20 [cP], and the time constant τ is expressed in relation to the viscosity. For other viscosities, only the minimum pressure value P _min is obtained. If acquired, the threshold values at the respective viscosities 1 [cP], 2 [cP], 5 [cP], 10 [cP], and 20 [cP] can be obtained (the above formula (2)). In this case, as shown in FIG. 7B, the deviation between the approximate curves P _a2 (t) to P _a4 (t) and the suction pressure curves P ₂ (t) to P ₄ (t) is small, and the detection sensitivity The threshold value PL (t) at each viscosity can be obtained without dropping the value.

(When the suction speed during dispensing is different from the suction speed when the reference sample is sucked)
Even when the suction speed at the time of dispensing is different from the suction speed when the reference sample is sucked, the threshold value PL (t) obtained based on the reference sample can be used as in the case of the viscosity. . FIG. 8A shows suction pressure curves P ₁ (t) to P ₆ (t) when the suction speed [kpps] changes in the range of 16 to 26 [kpps].

For example, the reference sample is sucked at the minimum suction speed of 16 [kpps], and the approximate curve P _a1 (t) is obtained by the above equation (1). For other speeds 18 [kpps], 20 [kpps], 22 [kpps], 24 [kpps], and 26 [kpps], only the minimum pressure value _Pmin is acquired from the reference waveform. The minimum pressure value P _min of the approximate curve P _a1 (t) is changed to the minimum pressure value P at other suction speeds 18 [kpps], 20 [kpps], 22 [kpps], 24 [kpps], and 26 [kpps]. _When replaced with _min , approximate curves P _a2 (t) to P _a6 (t) as shown in FIG. 8A are obtained.

That is, if the fitting process is performed for the minimum suction speed 16 [kpps] and only the minimum pressure value _Pmin is acquired for the other suction speeds, the suction speeds 16 [kpps], 18 [kpps], and 20 [kpps] are obtained. The threshold values at kpps], 22 [kpps], 24 [kpps], and 26 [kpps] can be obtained (the above formula (2)). In this case, as shown in FIG. 8A, the deviation between the approximate curves P _a2 (t) to P _a6 (t) and the suction pressure curves P ₂ (t) to P ₆ (t) increases as the speed increases. As the speed increases and the speed increases, the detection sensitivity slightly decreases, but the threshold value PL (t) at each viscosity can be easily obtained.

In addition, when the suction speed at the time of dispensing is different from the suction speed at the time of sucking the reference sample, if the time constant τ is changed, the threshold value PL obtained based on the reference sample can be obtained without reducing the detection sensitivity. It is possible to use (t). In FIG. 8B, similarly to FIG. 8A, the suction pressure curves P ₁ (t) to P ₆ (t) when the suction speed [kpps] changes in the range of 16 to 26 [kpps]. Indicates.

Reference samples are sucked at a minimum suction speed of 16 [kpps] and a maximum suction speed of 26 [kpps], and their approximate curves P _a (t) are approximately coincident with the suction pressure curves P ₁ (t) and P ₆ (t), respectively. Thus, the time constant τ is determined, and the time constant τ is expressed by a formula in relation to the viscosity from the result. For example, the following formula (4)
τ = 0.0009 × speed [kpps] −0.034 (4)
become that way. For the other suction speeds 18 [kpps], 20 [kpps], 22 [kpps], and 24 [kpps], only the minimum pressure value _Pmin is acquired from the reference waveform. Then, for example, the approximate curve P _a1 minimum pressure value P _min and another suction speed 18 (t) [kpps], 20 [kpps], 22 [kpps], as well as replacing the minimum pressure value P _min of 24 [kpps] Substituting with the time constant τ obtained by the above equation (4), approximate curves P _a2 (t) to P _a5 (t) as shown in FIG. 8B are obtained.

That is, the fitting process is performed for the minimum suction speed 16 [kpps] and the maximum suction speed 26 [kpps], the time constant τ is expressed in relation to the suction speed, and only the minimum pressure value P _min is obtained for other suction speeds. If acquired, the threshold value at each suction speed 16 [kpps], 18 [kpps], 20 [kpps], 22 [kpps], 24 [kpps], and 26 [kpps] can be obtained (the above formula ( 2)). In this case, as shown in FIG. 8B, the deviation between the approximate curves P _a2 (t) to P _a5 (t) and the suction pressure curves P ₂ (t) to P ₅ (t) is small, and the detection sensitivity The threshold value PL (t) at each suction speed can be obtained without dropping the value.

(Second Embodiment)
In the first embodiment, the threshold value along the suction pressure curve is set. However, in this embodiment, the difference in suction pressure at a predetermined interval T _d (for example, about 20 [ms]) at each time is calculated. This is an example in which a threshold value is set along a curve to be expressed. The configuration and the like of the automatic dispensing device are the same as those described in the first embodiment, and hereinafter, the description will focus on differences from the first embodiment.

In the present embodiment, the threshold information stored in the threshold information storage unit 113 is obtained as follows. As a first step, prior to actually dispensing serum 201, a reference sample having physical properties equivalent to serum 201 is aspirated at a maximum aspiration setting amount using a nozzle tip equivalent to nozzle tip 102 to be used. As a result, a suction pressure curve P (t) (reference waveform) is obtained, and a curve P ′ (t) = (dP (t) / dt) representing a difference in suction pressure at a predetermined interval T _d at each time. _Td = P (t) -P (t- _Td ) is obtained. Specifically, the curve P ′ (t) can be obtained by taking the difference between the pressure value at the current time and the pressure value before the time T _d from the current time.

Next, as a second step, an approximate curve P _a ′ (t) of the curve P ′ (t) acquired in the first step is obtained by fitting processing. That is, in the second step, the pressure value P ₀ before suction, the liquid level height h when sucking the maximum liquid amount in the nozzle tip, the minimum pressure value P _min , the minimum from the start of suction (start of the syringe pump 105) Using the time T _min until the pressure value P _min reaches, the density ρ of the reference sample, the gravitational acceleration g, the time constant τ, and the time T _d , an approximate curve P _a ′ (t) of the curve P ′ (t) is obtained. The following formula (5)
P _a ′ (t) = {− (P ₀ −P _min −ρgh) · ((1 / τ) exp (−t / τ)) − ρgh / T _min } · T _d
... Formula (5)
The time constant τ is determined so that the curve P ′ (t) and the approximate curve P _a ′ (t) substantially coincide with each other by performing the fitting process in the same manner as described in the first embodiment. .

Next, as a third step, using the approximate curve P _a ′ (t) obtained as described above and the constant PL ₁ , the difference in suction pressure at a predetermined interval T _d at each time is calculated. The threshold value PL ′ (t) is expressed by the following equation (6)
PL ′ (t) = P _a ′ (t) −PL ₁ Formula (6)
Determine as.

The threshold value PL ′ (t) of the difference between the suction pressures at the predetermined interval _Td at each time obtained as described above is stored in the threshold information storage unit 113 as threshold information. In this case, if a plurality of types of nozzle chips are used as the nozzle chip 102, the first to third steps are performed for the nozzle chips equivalent to the nozzle chips, and the threshold value PL ′ (t) is obtained. If a liquid sample other than the serum 201 is to be aspirated, the first to third steps are similarly performed on the reference sample of each liquid sample to obtain the threshold value PL ′ (t).

The dispensing operation in the automatic dispensing apparatus of this embodiment is also basically as shown in the flowchart of FIG. 4. In step S405, the threshold value PL ′ (t) and the pressure sensor at each time from the start of suction. The difference is that the difference between the pressure value at the current time detected by 107 and the pressure value before the time _Td from the current time is compared.

FIG. 9A is a characteristic diagram showing an example of a normal suction pressure curve, a suction pressure curve when clogging occurs, and a threshold value PL (t) in the first embodiment. On the other hand, FIG. 9B shows the difference in suction pressure at a predetermined interval T _d at each normal time in the second embodiment under the same conditions as in FIG. 9A. It is a characteristic view which shows an example of the curve to represent, the curve when clogging arises, and threshold value PL '(t). By treating the difference in suction pressure at a predetermined interval _Td in each time as in this embodiment, the change in suction pressure is emphasized, so that the detection sensitivity of suction abnormality can be increased.

In the first embodiment, a comparison determination with a threshold value (clogging determination) is performed immediately after the start of suction during the dispensing operation (determination time t = 0 to T _min ). In the second embodiment, Since it is necessary to take a difference, the clogging determination immediately after the start of suction cannot be performed, and a dead time T _st (about several tens [ms]) is set (determination time t = T _{st to} T _min ). For example, as shown in FIG. 3, the dead time T _st may be a time until completion of acceleration (reaching the highest speed) in trapezoidal driving. Another reason for setting the dead time is that the normal waveform, that is, the waveform is exactly the same immediately after aspiration, and the shorter the time from the start of aspiration, the smaller the difference between the normal waveform, that is, the waveform. There is a reason to wait until.

  As mentioned above, although this invention was demonstrated with embodiment, this invention is not limited only to embodiment, A change etc. are possible within the scope of the present invention.

It is a figure which shows schematic structure of the automatic dispensing apparatus to which this invention is applied. To explain a procedure for obtaining a suction pressure curve by sucking a reference sample prepared according to a liquid sample using a nozzle tip equivalent to the nozzle tip, and obtaining threshold information using the suction pressure curve FIG. It is a figure for demonstrating the trapezoid drive of a pump. It is a flowchart for demonstrating the dispensing operation | movement in an automatic dispensing apparatus. It is a figure for demonstrating a suction pressure curve. It is a figure which shows the relationship between a suction pressure curve and a threshold value. It is a figure for demonstrating the case where the viscosity of the liquid sample made into the suction object differs from the viscosity of a reference | standard sample. It is a figure for demonstrating the case where the suction speed at the time of dispensing differs from the suction speed when sucking a reference sample. It is the characteristic view which compared the state when the clogging in 1st Embodiment and 2nd Embodiment produced. It is a figure which shows the relationship between the suction pressure curve and threshold value when making a fixed pressure value into a threshold value.

Explanation of symbols

DESCRIPTION OF SYMBOLS 101 Nozzle 102 Nozzle tip 103 XYZ axis drive part 104 Piping 105 Syringe pump 106 Syringe pump drive part 107 Pressure sensor 108 Control part 109 Input part 110 Display part 111 I / V conversion circuit 112 AD converter 113 Threshold information storage part 114 Threshold setting part 115 determination unit

Claims (7)

A dispensing device for sucking a liquid sample with a nozzle tip,
Using the threshold information including a predetermined parameter and the predetermined parameter value when the liquid sample is sucked by the nozzle tip, the suction that changes according to the time from the start of the suction of the liquid sample by the nozzle tip Threshold setting means for setting a threshold related to pressure;
A suction pressure detecting means for detecting a suction pressure when the liquid sample is sucked by the nozzle tip;
A determination means for comparing a value of the suction pressure itself detected by the suction pressure detection means or a value obtained from the suction pressure with a threshold set by the threshold setting means to determine suction abnormality;
The threshold information including the predetermined parameter is obtained by sucking a reference sample prepared according to the liquid sample in advance using a nozzle tip equivalent to the nozzle tip, and obtaining the suction pressure. A dispensing apparatus characterized by being obtained using a curve. A suction abnormality determination method in a dispensing device that sucks a liquid sample with a nozzle tip,
Using the threshold information including a predetermined parameter and the predetermined parameter value when the liquid sample is sucked by the nozzle tip, the suction that changes according to the time from the start of the suction of the liquid sample by the nozzle tip A threshold setting procedure for setting a threshold related to pressure;
A suction pressure detection procedure for detecting a suction pressure when the liquid sample is sucked by the nozzle tip;
A determination procedure for determining a suction abnormality by comparing a value of the suction pressure itself detected by the suction pressure detection procedure or a value obtained from the suction pressure with a threshold set by the threshold setting procedure. ,
The threshold information including the predetermined parameter is obtained by sucking a reference sample prepared according to the liquid sample in advance using a nozzle tip equivalent to the nozzle tip, and obtaining the suction pressure. A method for determining abnormal suction in a dispensing device, wherein the abnormality is determined using a curve. A threshold setting method for determining suction abnormality for setting a threshold for suction pressure for determining suction abnormality when a liquid sample is sucked by a nozzle tip,
A suction pressure curve acquisition procedure for acquiring a suction pressure curve by sucking a reference sample prepared in accordance with the liquid sample with a maximum suction setting amount using a nozzle tip equivalent to the nozzle tip;
An approximate curve acquisition procedure for obtaining an approximate curve of at least a part of the suction pressure curve itself acquired by the suction pressure acquisition procedure or a curve obtained from the suction pressure curve;
A threshold information determination procedure for determining suction abnormality, comprising: threshold information determination procedure for determining threshold information regarding suction pressure for suction abnormality determination using the approximate curve obtained by the approximate curve acquisition procedure . In the approximate curve acquisition procedure, the pressure value P ₀ before suction, the liquid level height h when sucking the maximum liquid amount in the nozzle tip, the minimum pressure value P _min , and the minimum pressure value P _min from the start of suction. Using the time T _min , the density ρ of the reference sample, the gravitational acceleration g, and the time constant τ, an approximate curve P _a (t) of the suction pressure curve is expressed by the following equation: P _a (t) = P ₀ − (P ₀ − P _min −ρgh) · (1−exp (−t / τ)) − ρgh · t / T _min
(T is the time when the time when suction is started is 0)
The threshold value setting method for determining suction abnormality according to claim 3, wherein In the threshold information determination procedure, the suction pressure threshold PL (t) for determining suction abnormality is reduced using the approximate curve P _a (t) obtained by the approximate curve acquisition procedure and the constant PL _0. Formula PL (t) = P _a (t) −PL ₀
The threshold value setting method for determining suction abnormality according to claim 4, wherein the threshold value setting method is used to determine a suction abnormality. In the approximate curve acquisition procedure, the pressure value P ₀ before suction, the liquid level height h when sucking the maximum liquid amount in the nozzle tip, the minimum pressure value P _min , and the minimum pressure value P _min from the start of suction. Using the time T _min , the density ρ of the reference sample, the gravitational acceleration g, the time constant τ, and the time T _d , an approximate curve of the curve P ′ (t) representing the difference in suction pressure at a predetermined interval T _d at each time. P _a ′ (t)
P _a ′ (t) = {− (P ₀ −P _min −ρgh) · ((1 / τ) exp (−t / τ)) − ρgh / T _min } · T _d
The threshold value setting method for determining suction abnormality according to claim 3, wherein In the threshold information determination procedure, the approximate curve P _a ′ (t) obtained by the approximate curve acquisition procedure and the constant PL ₁ are used, and a predetermined interval T _d at each time for suction abnormality determination is used. The threshold value PL ′ (t) for the difference in suction pressure is expressed by the following formula: PL ′ (t) = P _a ′ (t) −PL ₁
The threshold value setting method for determining suction abnormality according to claim 6, wherein the threshold value setting method is determined by:

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