JP2548383B2 - Method and apparatus for detecting bubbles in liquid sample - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial field of application] The present invention detects air bubbles in a liquid sample in an automatic dispensing device used for analysis and inspection (specimen inspection) of liquid samples such as serum, urine and reagents. A method and an apparatus thereof.

[Conventional technology]

In the conventional automatic dispensing device of this type, a liquid sample (hereinafter, abbreviated as a sample) is put in a container having a desired shape for analysis and inspection.

[Problems to be Solved by the Invention]

According to the above-mentioned conventional automatic dispensing device, even if bubbles are generated in the sample contained in the container, no consideration has been given to detecting the bubbles. Therefore, even if air bubbles are generated when air is mixed when the sample is put in the container, the dispensing is performed as it is and an error occurs in the dispensing amount. This error has a considerable influence on the analysis value (at the time of inspection), and there is a problem in that the influence is great especially when a small amount of aliquot is dispensed.

OBJECT OF THE INVENTION The present invention has been made to solve the above problems, and an object thereof is to provide a method and an apparatus for detecting bubbles generated in a sample.

[Means for solving the problem]

In order to achieve the above object, the method for detecting bubbles in a liquid sample according to the invention of claim (1) is such that a liquid sample is automatically separated by a nozzle tip having a non-tapered portion and a tapered tapered portion. In an automatic pipetting device for pouring, a method for detecting bubbles in a liquid sample sucked into the nozzle tip, which allows the beam-shaped light to pass while intersecting the nozzle tip and transmitting the light. Is moved in one direction at a constant speed along the nozzle tip,
Detecting a change in the amount of transmitted light along the nozzle tip,
By observing the rate of change in the amount of light passing through the nozzle tip by performing time differentiation on the detected change in the amount of light, the liquid sample in the nozzle tip is eliminated while eliminating the detection of the tapered portion of the nozzle tip. Is detected, and the bubbles in the nozzle tip are detected based on the detected boundary.

Further, a method for detecting bubbles in a liquid sample according to a second aspect of the present invention is the same as the method for detecting bubbles in a liquid sample according to the first aspect, in which detection of a tapered portion of the nozzle tip is excluded. However, in the step of detecting the boundary between the liquid sample and the air in the nozzle tip, the beam-shaped light is moved from the non-tapered portion through the tapered tapered portion toward the tip. In the state in which the nozzle tip is moving, it is a step of detecting a place having a polarity opposite to the differential value of the boundary between the non-tapered portion and the tapered portion as the boundary between the liquid sample and the bubble. Characterize.

Furthermore, in the device for detecting bubbles in a liquid sample according to the invention described in claim (3), an automatic dispenser for automatically dispensing a liquid sample by a nozzle tip having a non-tapered portion and a tapered tapered portion. A method for detecting bubbles in a liquid sample sucked into the nozzle tip in a pouring device, which is an optical system in which light emitted from a light-emitting body is formed into a beam,
Nozzle tip moving means for moving the nozzle tip containing a liquid sample in one direction at a constant speed by intersecting the beam-shaped light, a photodetector for detecting the light transmitted through the nozzle tip, and the photodetection Differentiating circuit to detect the rate of change of the amount of transmitted light occurring at the boundary between the liquid sample and the air in the nozzle tip by differentiating the detection signal of the vessel, and processing the output signal of the differentiating circuit to obtain the nozzle tip A signal processing circuit that detects the boundary between the liquid sample and the air in the nozzle tip while eliminating the detection of the tapered portion, and detects the bubbles in the nozzle tip based on the detected boundary. It is characterized by having.

[Action]

According to the method for detecting air bubbles in a liquid sample according to the invention having the above-mentioned configuration, the beam-shaped light is transmitted while intersecting the nozzle chip, and the transmission position thereof is the nozzle. Light that moves through the nozzle at a constant speed and in one direction, detects a change in the amount of transmitted light along the nozzle chip, and performs time differentiation on the detected change in the amount of light to pass through the nozzle chip. Bubbles in the liquid sample sucked into the nozzle tip are detected by observing the rate of change of the light amount. In this case, since the time differentiation is performed to observe the rate of change in the amount of light transmitted through the tip, the boundary between the liquid sample and the air in the nozzle tip is eliminated while eliminating the detection of the tapered portion of the nozzle tip. Can be detected, and the bubbles in the nozzle tip can be detected based on the detected boundary.

Here, as shown in FIG. 4, when the nozzle tip is moving upward (the beam light is moving toward the tip of the nozzle tip), the beam light moves from the non-tapered portion. The differential value becomes positive when moving to the two-way portion, but becomes negative when bubbles are present. Therefore, in such a movement mode, by detecting a place having a polarity opposite to the differential value of the boundary between the non-tapered portion and the tapered portion as the boundary between the liquid sample and the bubbles, the liquid sample in the nozzle tip and the air are separated from each other. When the boundary is detected (claim (2)), since the change in the light amount that occurs when the beam-shaped light transits from the non-tapered portion to the tapered portion is not counted, the taper of the nozzle tip is substantially reduced. It becomes possible to detect the boundary between the liquid sample and the air while eliminating the detection of the striped portion.

As described above, the method for detecting bubbles in a liquid sample according to the present invention is an automatic dispensing device for automatically dispensing a liquid sample with an existing nozzle tip having a non-tapered portion and a tapered tapered portion. In this case, it is possible to properly detect bubbles.

Further, according to the device for detecting bubbles in the liquid sample according to the invention described in claim (3), the bubbles mixed in the sample can be detected with high accuracy by a simple configuration.

〔Example〕

FIG. 1 is a schematic view of an apparatus suitable for carrying out the method for detecting bubbles in a liquid sample according to the present invention, and FIG. 2 is a plan view of the apparatus.

In FIGS. 1 and 2, 10 (hereinafter, abbreviated as a chip) that transmits near-infrared light is made of an optically transparent or translucent material such as plastic, and a sample (eg, serum) 12 is put in and is fed in one direction at a constant speed by the chip moving means 36 in the direction of the arrow, that is, upward in the illustrated example.

The near-infrared light emitting diode 14 as a light emitter is 700 nm
It emits near-infrared light having a wavelength of up to 1000 nm, and this near-infrared light passes through the optical system of the lens 16 and the cylindrical lens 18, and has a constant width and a constant thickness so as to intersect with the chip 10. Beam 20.

The beam 20 that has passed through the chip 10 passes through an optical filter 22 that transmits only light having a wavelength in the near infrared region, and reaches a photodetector 24.

To the output side of the photodetector 24, a differentiation circuit 26 that differentiates the detection signal of the photodetector 24 and a signal circuit 28 that processes the output signal of the differentiation circuit are sequentially connected.

FIG. 3 is a characteristic diagram of the amount of transmitted light with respect to the movement of the chip 10 that intersects near infrared light, and FIG. 4 is a characteristic diagram showing the relationship between the amount of light received by the photodetector 24 and the output signal of the differentiating circuit 26. is there.

 Next, the bubble detection method of the present invention will be specifically described.

The near-infrared light emitted from the near-infrared light emitting diode 14 is converted into a parallel beam by the lens 16, and the cylindrical lens 18
Thus, the tip 10 is narrowed down to a certain size at the position of the tip in the axial direction. The squeezed size is determined by the minimum volume of bubbles generated in the sample to be detected.

Further, the beam width in the direction perpendicular to the axis of the chip 10 is larger than the width determined by the intersection of the positions of the chips, so that the beam 20 always irradiates the chip 10 even if the position accuracy of the tip of the chip 10 is poor. Has become.

The light transmitted through the chip 10 passes through the optical filter 22 and is detected so that other light in the visible region such as illumination light does not enter the photodetector 24.

Now, bubbles 30 are generated in the sample put in the chip 10 and the first
Suppose that the situation is as shown in the figure.

When the chip 10 in such a state is irradiated with the beam 20 as shown in FIG. 2, the amount of transmitted light has a characteristic as shown in FIG. 3 with respect to the beam irradiation position on the chip 10.
That is, in the place where the sample 12 exists, the amount of transmitted light is larger than that in the place where the sample 12 does not exist (air layer).
At the boundary between the and air, a stepwise change occurs in the amount of transmitted light.

With such a tip 10 crossing the beam 20,
When the chip moving means 36 is moved at a constant speed in the direction of the arrow, the characteristic shown in FIG.

The amount of received light increases with time because the shape of the chip 10 is tapered.

In order to detect this stepwise change in the amount of received light, the output signal of the photodetector 24 is input to the differentiating circuit 26 to perform time differentiation. From the differentiating circuit 26, as shown in FIG. Output signal can be obtained. That is, when the chip 10 is moved upward from the position shown in the figure, a negative polarity differential pulse 32 is obtained at the location of the bubble 30 in the specimen 12.

Therefore, the output signal of the differentiating circuit 26 is output to the signal processing circuit 28.
It is possible to know that the bubble 30 has been generated in the sample 12 by inputting to the above and detecting the negative differential pulse.

Further, by measuring the time T from the negative differential pulse 32 to the next positive differential pulse 34, the bubbles 30 in the sample 12 are measured.
It is also possible to know the volume of.

〔The invention's effect〕

As described above, according to the method for detecting air bubbles in a liquid sample of the present invention, when air bubbles are generated due to mixing of air when a sample is put into a chip, the air bubbles are detected to analyze and inspect the chip. Since this can be avoided, it is possible to prevent an error in the dispensed amount due to the generation of bubbles. As a result, there is an effect that a stable analytical inspection can be performed with high accuracy.

Further, this bubble detection device has an effect that it can be obtained at a low cost with a simple configuration including an optical system for irradiating a light beam, a photoelectric conversion circuit, and a chip moving means.

[Brief description of drawings]

FIG. 1 is a front view showing an outline of an apparatus for carrying out a method for detecting bubbles in a liquid sample according to an embodiment of the present invention, FIG. 2 is a plan view thereof, and FIG. 3 is a transmitted light amount with respect to movement of a chip. FIG. 4 is a characteristic diagram showing the relationship between the amount of light received by the photodetector and the output signal of the differentiating circuit. 10 …… Chip (vessel) 12 …… Sample (liquid sample) 14 …… Near infrared light emitting diode 16,18 …… Lens 20 …… Beam 24 …… Photodetector 26 …… Differentiation circuit 28 …… Signal processing Circuit 30 …… Bubbles 36 …… Tip moving means.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Masaaki Takeda 6-22-1, Mure, Mitaka City, Tokyo Aloka Co., Ltd. (72) Kosuke Araki 6-22-1 Mure, Mitaka City, Tokyo Aloka Incorporated (56) References JP 49-120664 (JP, A) JP 61-110034 (JP, A) Actual development 61-38584 (JP, U)

Claims (3)

(57) [Claims] 1. An automatic dispensing device for automatically dispensing a liquid sample by a nozzle tip having a non-tapered portion and a tapered tapered portion, wherein an air bubble in the liquid sample sucked into the nozzle tip. A beam-shaped light is made to cross the nozzle tip and transmitted, and the transmission position is moved along the nozzle tip at a constant speed in one direction to move along the nozzle tip. By detecting the change in the amount of transmitted light and performing the time differentiation on the detected change in the amount of light to see the rate of change in the amount of light passing through the nozzle tip, the detection of the tapered portion of the nozzle tip is eliminated. While detecting the boundary between the liquid sample and the air in the nozzle tip, and detecting the air bubbles in the nozzle tip based on the detected boundary. Method of detecting air bubbles in the postal. 2. A method for detecting bubbles in a liquid sample according to claim 1, wherein the liquid sample and air in the nozzle tip are separated from each other while eliminating detection of a tapered portion of the nozzle tip. In the step of detecting the boundary, in the state in which the nozzle tip is moved so that the beam-like light moves in the direction of the tip portion from the non-tapered portion through the tapered tapered portion, A method for detecting bubbles in a liquid sample, comprising a step of detecting a place having a polarity opposite to a differential value of a boundary between the tapered portion and the tapered portion as a boundary between the liquid sample and the bubbles. 3. An automatic dispensing device for automatically dispensing a liquid sample by a nozzle tip having a non-tapered portion and a tapered tapered portion, wherein an air bubble in the liquid sample sucked into the nozzle tip. An optical system for converting the light emitted from a light-emitting body into a beam, and the nozzle tip containing a liquid sample is moved in one direction at a constant speed by intersecting the beam-like light. Nozzle tip moving means, a photodetector for detecting light transmitted through the nozzle tip, and a transmitted light amount generated at a boundary between a liquid sample and air in the nozzle tip by differentiating a detection signal of the photodetector with time. A differential circuit that detects the rate of change and an output signal of the differential circuit are processed to eliminate the detection of the tapered portion of the nozzle tip, and the boundary between the liquid sample and the air in the nozzle tip is eliminated. A device for detecting bubbles in a liquid sample, comprising a signal processing circuit for detecting and detecting the bubbles in the nozzle tip based on the detected boundaries.