Abstract:
An automatic analysis apparatus with a liquid level detection function includes a pipetting device for pipetting a liquid sample from a sample cup to a reaction container by using a pipetting probe that serves as a first capacitor electrode. A sample cup holding means serves as a second capacitor electrode having a ground potential. The conductor material is arranged along a direction in which the pipetting probe moves down for pipetting and is separate from the pipetting device. The conductor material has the same ground potential as that of the sample cup holding means and also serves as a second electrode whereby at any one time either of the sample cup holding means and the conductive material serves as a second capacitor electrode in combination with the first capacitor electrode. An a electrical detector is provided for detecting a change of electrode static capacitance between the pipetting probe and the sample cup holding means and between the pipetting probe and the conductive material as of level detection of the liquid sample. Measurement means are also provided for measuring an ingredient of the reaction container.

Description:
BACKGROUND OF THE INVENTION 
     The present invention relates to an automatic analysis apparatus having a function for pipetting a liquid sample from one container to another container by using a pipetting probe that serves as an electrode for detecting liquid level. 
     In a conventional automatic analysis apparatus, the liquid sample of a living body such as blood or urine is pipetted from a sample cup to a reaction container on a reaction line, a reagent is pipetted from a reagent bottle to the reaction container corresponding to analysis items of measurement objects, and the mixture of the sample and the reagent is measured by a measuring means such as a photometer. 
     In the pipetting operation, the tip of the pipetting probe is dipped in the sample liquid of the pipetting object, but the deeper that the tip of the pipetting probe is dipped, the greater than the quantity of the sample liquid adhered to an outer wall of the probe increases, and the contamination becomes significant. 
     Then, in order to reduce the dipping depth of the pipetting probe as much as possible, a liquid level of the container is detected, and at a position where the tip of the probe reaches a little beneath the liquid level, the probe stops to move down, and the probe is controlled to withdraw a predetermined amount of the sample liquid. 
     A pipetting probe serves as an electrode for detecting liquid level, and a liquid container holding means serves as the other electrode for detecting liquid level; the liquid level in the container is detected by a change of an electrostatic capacitance between the pipetting probe and the liquid container holding means, as shown in Japanese Patent Laid-open No. 62-289769 (1987) bulletin and Japanese Patent publication No. 6-7112 bulletin (corresponding to U.S. Pat. No. 4,897,244). 
     In these documents, the pipetting probe is connected to an electric liquid level detecting circuit, and the liquid container holding means is electrically connected to the ground. 
     Furthermore, relating to the pipetting probe having a metal inner tube and a metal outer tube, Japanese Patent Laid-open No. 7-43369 bulletin is disclosed, in which insulation resistance between the metal inner tube and the metal outer tube is kept in a good condition, whereby the electrostatic capacitance corresponding to the liquid level of the sample is surely detected. 
     Further relating to a pipetting nozzle serving as one electrode to detect the liquid level of the sample, Japanese Patent Laid-open No. 8-258661 bulletin is disclosed. 
     SUMMARY OF THE INVENTION 
     In the automatic analysis apparatus stated above, the sample cup pipetted with the sample liquid corresponding to the pipetting object is mounted on a sample disc as one embodiment of the container holding means. 
     When all of the sample cups are set to the sample disc, a detecting signal on the basis of the change of the electrostatic capacitance between the pipetting probe and the sample disc is a big value, and the liquid level detection error is very small. 
     On the other hand, several kinds of the sample cups having different size are used usually. An especially small sample cup may be set on the sample disc directly, and other containers or supporting holding tools are set on the container loading region of the sample disc, or the small sample cup may be mounted indirectly on the top of the other containers or the supporting holding tools. 
     When a small-sized sample cup having a short overall length is set on the sample disc indirectly, the spatial distance between the sample liquid in the sample cup and the sample disc serving as the electrode for detecting liquid level becomes large, and it becomes impossible to obtain a sufficient detecting signal to recognize the liquid level with which the pipetting probe contacts, such that the liquid level detection is not executed surely. 
     An object of the present invention is to provide an automatic analysis apparatus which is capable to surely detect a liquid level of the sample liquid of the sample cup, even if the height of the sample cup is different from the height location arranged for the sample cup holding means. 
     In the automatic analysis apparatus comprising a pipetting device for pipetting a sample liquid from a sample cup to a reaction container by using a pipetting probe that serves as an electrode for detecting a liquid level of the liquid sample, the sample cup holding means serving as another electrode for detecting the liquid level, an electric detecting element for detecting a change of an electrostatic capacitance between said pipetting probe and said sample cup holding means and a measurement means for measuring the contents of the reaction container, the present invention is characterized by comprising a construction such that a conductive material is arranged along a direction to which the pipetting probe is disposed, and said conductive material has an isopotential to the other electrode. 
     In a desirable embodiment of the present invention, said sample cup holding means are driven so as to transfer said sample cup being held to an aspiration location by said pipetting probe, and said conductive material is arranged apart from said sample cup holding means and in the neighborhood of said sample aspiration location. 
     This conductive material includes a pair of plate portions which oppose each other, keeping a gap through which said sample cup on said sample cup holding means is able to pass. 
     Said sample cup holding means and said conductive material are contacted to ground electrically. 
     In a desirable embodiment of the present invention, a control part is provided for controlling moving down operation of the pipetting probe according to the output of the liquid level detecting signal supplied from an electric circuit based on change of an electrostatic capacitance between the pipetting probe and the conductive material. 
     The conductive material is arranged in a region between a height location that is lower than a bottom end of the probe when the pipetting probe moves to a horizontal direction and a height location that is higher than the upper end of sample cup holding means. 
     This conductive material has a part extended in parallel to a direction to which the pipetting probe moves down. 
     Moreover, the sample cup holding means has an electrical conduction body as another electrode which surrounds the outer wall of the sample cup. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a schematic diagram, which shows a total construction of the automatic analysis apparatus of the present invention. 
     FIG. 2 is an explanatory view of a liquid level detection system in the analysis apparatus of FIG.  1 . 
     FIG. 3 shows an embodiment of a conductive material used in a pipetting location of the sample. 
     FIG. 4 is an explanatory view of the liquid level detection operation when setting a sample cup directly. 
     FIG. 5 is an explanatory view of the liquid level detection operation when setting a sample cup indirectly. 
     FIG. 6 is an explanaory view of the liquid level detection operation when not applying the present invention. 
     FIG. 7 is an explanaory view of the liquid level detection operation when applying the present invention. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     FIG. 1 is a schematic diagram of the total construction of the automatic analysis apparatus in the present invention. 
     In FIG. 1, the reaction disc  109  is arranged so as to be intermittently rotatable on a water tank kept at a constant temperature. 
     On the reaction disc  109 , a plurality of reaction containers  106  are arranged keeping a circle state, rotation and stopping of the reaction disc  109  are performed at predetermined times, and a line of the reaction container is transferred the retroaction line top. 
     On a movable arm  2  that is moved vertically and horizontally by a driving department (not shown in the figure), a sample pipetting probe  105  to aspirate and eject the sample is installed. 
     The sample pipetting probe  105  pipettes the sample from the sample cup  101  to the reaction container  106  on the reaction disc  109  which is mounted on the sample disc  102  top as the sample cup holding means. 
     Referring to FIG. 2, the construction of a liquid level detection unit will be explained. In FIG. 2, an AC signal output from an AC oscillation circuit  8  is input into a liquid level detecting circuit  9 . 
     As for the AC signal, a sine wave is reasonable, but a square wave or a triangle wave may be replaced. 
     The liquid level detecting circuit  9  has a detecting circuit  93  to detect a change of an electrostatic capacitance produced between the sample disc  102  connected to ground and the sample pipetting probe  105 . 
     The detecting circuit  93  for detecting the electrostatic capacitance change has a conventional circuit bridge circuit. 
     The liquid level detecting circuit  9  amplifies the change of the detected electrostatic capacitance, and the AC amplified signal is input into a rectifier circuit  10 . 
     The input AC signal is converted into a direct current signal in the rectifier circuit  10 , and is input into a comparator  11 . 
     The comparator  11  compares a change of the input electrostatic capacitance signal with a value before being changed, whereby a detecting signal  12  showing the presence of contact of the pipetting probe  105  with a liquid level in a container, in other words, presence of liquid level detection is provided. 
     A pair of discharge elements  91   a  and  91   b  formed with an electroconductive material on a printed circuit board are disposed to face each other keeping a gap of around 0.1 mm. 
     Both discharge elements facing each other have peaked tips inside thereof so as to concentrate static electricity thereon and to permit easy discharge of the electricity. 
     One discharge element  91   a  of a pair of the discharge elements is contacted to ground electrically. 
     The other discharge element  91   b  is electrically connected with the pipetting probe  105  and with the detecting circuit  93  for detecting the electrostatic capacitance change. 
     In accordance with this construction, the external noise signal caused by electrification of static electricity detected by the pipetting probe  105 , is electricity discharged through a pair of discharge elements  91   a ,  91   b  to the arm, whereby transmission of the noise signal to the detecting circuit  93  of the electrostatic capacitance change is restrained. 
     An inductance  92  is mounted between the other discharge element  91   b  and the electrostatic capacitance change detecting circuit  93  furthermore. 
     This inductance  92  shows a high impedance characteristic corresponding to high frequency. Therefore, the discharging to the ground of the noise signal is promoted. 
     The output signal of the detecting circuit  93  for the electrostatic capacitance change goes through an operational amplifier  94 . 
     The amplification factor of the operational amplifier  94  is different corresponding to the smallest detection capacity of the device, however it is several 108-several 100 times generally. 
     The output AC signal of operational amplifier  94  is converted to a direct current signal by a rectifier circuit  10 . 
     Because, in the example of FIG. 2, the alternating output of the operational amplifier  94  is clamped by Zener diode  95 , a sudden signal such as the static electricity noise or other disturbance noise, that is, a useless signal is not transmitted to the rectifier circuit  10 , and is not integrated. 
     Accordingly, a bad affect by the external noise is extremely small. 
     In the analysis apparatus shown in FIG. 1, the metal pipetting probe  105  which is one electrode for liquid level detection is connected to the liquid level detecting circuit  9 , and is electrically contacted with the metal sample disc  102  serving as the other electrode for the liquid level detection. 
     However, being connected reversibly, that is, in the case that the sample disc is connected to the liquid level detecting circuit, and is contacted with the pipetting probe, a change of the electrostatic capacitance may be detected too. 
     In the example shown in FIG. 1, the whole body of the sample disc  102  is electrically conductive, however, instead of the above, most of the sample disc  102  may be constituted with a non-electrically conductive matter such as a plastic, and the electrically conductive matter functioning as the electrode for the liquid level detection may be provided in the region which directly contacts a sample cup or closely approaches it, that is, only in the region surrounding the outer wall of the sample cup. 
     In any event, a holding location of each container in the sample disc  102  is formed as an electrode for detecting the liquid level having a shape to surround the outer wall of the container. Construction of the automatic analysis apparatus shown in FIG. 1 will be explained further. 
     On a reagent disc  125 , which is freely rotatable, a bottle  112  of the reagent is arranged corresponding to plural analysis items as analysis objects. 
     A reagent pipetting probe  110  installed on the movable arm pipettes the predetermined amount of the reagent from the reagent bottle  112  to a reaction container  106 . 
     The sample pipetting probe  105  executes an aspiration behavior of the sample and a discharge behavior according to the operation of a sample pump  107  for the sample. 
     Reagent pipetting probe  110  executes an aspiration behavior of the reagent and a discharge behavior with an operation of the syringe pump  111  for the reagent. 
     The analysis item that should be analyzed for each sample is input from a keyboard  121  or an input unit as a display of CRT  118 . 
     The computer  103  controls an operation of each unit in this automatic analysis apparatus. The sample cup  101  is transferred to a sample aspiration location according to an intermittent rotation of the sample disc  102 , the descent of the sample pipetting probe  105  in the sample cup being stopped. 
     When the tip of the pipetting probe  105  contacts with the liquid level of the sample according to a drop operation thereof, a detecting signal is output from the liquid level detecting circuit  9 , whereby the computer  103  controls the drop operation of the drive department of the movable arm  2  to stop. 
     Subsequently after having aspirated the predetermined amount of the sample in the pipetting probe  105 , the pipetting probe  105  rises to top dead center, the mobile arm  2  having the pipetting probe  105  is turned in a horizontal plane, and the sample pipetting probe  105  moves down in a location of the reaction container  106  on the reaction disc  109  and discharges the sample stored in the reaction container  106 . 
     When the reaction container  106  then moves to a position where the reagent should be added, the reagent corresponding to the analysis item is added from the reagent pipetting probe  110 . Corresponding to the pipetting of the sample and the reagent, the liquid level of the sample in the sample cup  101  and the reagent in reagent bottle  112  is detected. 
     The mixture in the reaction container to which the sample and the reagent are added, is stirred by a stirring device  113 . 
     Plural reaction containers cross a light beam from a light source  114  during passage of a line of the reaction container, and an absorbance of each mixture is measured by a photometer  115  as a measurement means. 
     The absorbance signal goes by way of an analog-to-digital converter  116  and through interface  104 , and is transmitted to the computer  103 , where the concentration of the analysis item is calculated. 
     Analysis result prints are output by a printer  117  through the interface  104 , or displayed on the CRT  118 , and are stored in the hard disk  122  as a memory device. 
     The reaction container  106  is then washed in a location of the washing mechanism  119 . 
     A pump  120  for washing supplies washing liquid to the reaction container and the disposed waste is drained from the reaction container. 
     According to the example of FIG. 1, the container holding department is formed on three lines of concentric circles of the sample disc  102  so as to set three lines of the sample cups. A sample aspiration location by the sample pipetting probe  105  is established on each line. 
     A conductive material shown in FIG. 3 is arranged so as to correspond to that sample aspiration location. 
     This conductive material is arranged in a height region which is lower than a probe bottom end of a height location before the sample pipetting probe starts to move down in the sample aspiration location, or a height location just before the sample pipetting probe moves to a horizontal direction. 
     Further, this conductive material is arranged at the height region higher than the upper end of the sample disc  102  serving as one of the electrodes for the liquid level detection. 
     The conductive material  14  shown in FIG. 3, is constituted by a metal electrically-conductive plastic or non-electroconductivity electrically-conductive plastic, treated by a metal plating, and is kept to be an isopotential with the sample disc  102 . 
     That is, the conductive material  14  is contacted with ground when the sample disc is electrically contacted with ground. 
     If the sample disc is a type connected with the liquid level detecting circuit  9  electrically, the conductive material  14  is connected to the liquid level detecting circuit  9  electrically, too. 
     This conductive material  14  is arranged along a direction to which the sample pipetting probe  105  moves down and up vertically in the sample aspiration location. 
     The conductive material  14  in FIG. 3 has a pair of plates  14   a  and  14   b  arranged to face each other, and is installed and held by a guard or support member  13  that is a part for installation. 
     A through hole  13   a  through which the sample pipetting probe  105  may move freely in and out in a vertical direction is formed in the guard  13  and the conductive material  14 . The guard  13  is installed to or mounted on a base  20  of the analysis apparatus as shown in FIGS. 4 and 5. 
     Plates  14   a  and  14   b  face each other in parallel, and the gap of them is a distance through which the sample cup  101  on the sample disc  102  may pass, and a distance that may have a function as an electrode for the liquid level detection. 
     In a circumstance explained in an example of FIG. 3, both plates  14   a ,  14   b  are arranged to be parallel, however when being arranged upwards of the sample disc as shown in FIG. 1, they become a shape curved along a transfer locus of the sample cup  101  on each line. 
     The plates  14   a ,  14   b  are extended in a vertical direction so that they are made parallel to the moving up and down direction of the sample pipetting probe  105 . 
     The overall length of the top and bottom direction of plates  14   a , 14   b , is about half of the overall distance that the sample pipetting probe  105  is capable of moving downward, and is changed depending on the size of the sample cup. 
     The guard  13  that is a component for installation may be constituted by plastic or the metal. 
     The guard department  13  is used to prevent a foreign article from approaching the probe during an operation of the sample pipetting probe  105 , and especially, to prevent a hand of the operator from contacting the pipetting probe. 
     FIG. 4 shows a case in which a small-sized sample cup  5  is set in the sample disc  102 , and FIG. 5 shows a case in which the sample cup  5  is set in the sample disc  102  intermediately through an auxiliary holding tool. 
     In the example of FIG. 5, a test tube  6  of 100 mm in overall length is used as the auxiliary holding tool. 
     When being set as shown in FIG. 5, as the liquid level of the sample  7  in the sample cup  5  leaves from the sample disc  102  physically, it becomes difficult to detect a change of the electrostatic capacitance between the sample disc  102  as an electrode for the liquid level detection and the sample pipetting probe  105 . 
     The conductive material  14  contacted electrically so as to be an isopotential with the sample disc  102  is provided corresponding to the sample aspiration location. 
     This conductive material  14  is arranged to leave or be spaced from the sample disc  102  and from the sample pipetting probe  105 . 
     The conductive material  14  has a function as an electrode for detecting liquid level, which is similar to the sample disc  102 . 
     In a state that a sample cup is set as shown in FIG. 4, when the liquid level of the sample  7  in the sample cup  5  is detected without applying the present invention, that is, when the conductive material  14  is not used, the electrostatic capacitance value between the sample pipetting probe  105  and the sample disc  102  changes as shown by a broken line in FIG.  6 . 
     In FIGS. 4 to  7 , the height location A of the sample pipetting probe  105  is the height of the probe bottom end when the pipetting probe is in the greatest rise location (top dead center). 
     When the sample pipetting probe  105  moves to the reaction container  106  horizontally, it starts to move keeping a state of the height location A. 
     At the height location B, the bottom end of the pipetting probe  105  in at a height corresponding to the guard  13 . The height location C is a height of a liquid level of the sample in a state shown in FIG.  5 . 
     The height location D is in a height of a liquid level of the sample in a state shown in FIG.  4 . 
     Moreover, in FIGS. 6 and 7, the horizontal scale shows a dropping distance of the pipetting probe, and the vertical scale shows the electrostatic capacitance value Cx (pico farad). 
     According to the dropping distance from the greatest rise location of the sample pipetting probe  105 , a floating capacitance of the guard  13  and the sample disc  102  are added to the pipetting probe, and the electrostatic capacitance value added to the pipetting probe  105  changes as C 1 , C 2 , C 4  on a broken line shown in FIG.  6 . 
     The electrostatic capacitance value suddenly changes when it drops to the liquid level height location D. 
     On the contrary, when the sample cup  5  is set as shown in FIG. 5, and the conductive material  14  in the present invention is not used, the electrostatic capacitance value changes as C 1 , C 2 , C 5  on a solid line shown in FIG.  6 . 
     In other words, even if the bottom end of the sample pipetting probe  105  contacts with the liquid level of the sample  7  (it comes into contact with the height location C), the change of the electrostatic capacitance value is small. 
     This is because the sample cup  5  is physically separated from the sample disc  102  that is one of the electrodes used for detecting the liquid level, and it becomes difficult to detect the change, because the change of the electrostatic capacitance is small. 
     Furthermore, it is difficult to set up a threshold for the liquid level detection because a difference y of the electrostatic capacitance value of c 4  and c 5  is large. 
     Referring to FIGS. 4,  5  and  7 , the liquid level detection operation of the present invention will be explained in the next. 
     At first, in a state setting the sample cup  5  as shown in FIG. 4, the conductive material  14  does not participate in the liquid level detection, and the sample disc  102  participates in the liquid level detection as one electrode. 
     When the sample pipetting probe  105  moves down from the greatest height location A, the electrostatic capacitance value changes as shown by a broken line in FIG. 7, and when the tip of the probe contacts with the liquid level of the sample at the height location D, it becomes the electrostatic capacitance value C 4 . 
     Such a change is almost equal to the case shown by the broken line of FIG.  6 . 
     According to the output of the liquid level detecting signal  12 , the computer  103  that is a control part controls the drive department so as to stop the moving down of the movable arm  2 . 
     In a setting state of the sample cup  5  as shown in FIG. 5 next, the sample disc  102  does not participate in the liquid level detection substantially, and the change of the electrostatic capacitance between the conductive material  14  that is one electrode for detecting the liquid level and the sample pipetting probe  105  is detected by the liquid level detecting circuit  9 . 
     When the sample pipetting probe  105  gradually moves down from the greatest height location A, the electrostatic capacitance value changes as C 1 , C 2 , C 3  on a solid line shown in FIG.  7 . 
     When the tip of the sample pipetting probe  105  contacts with the liquid level of the sample  7  in the sample cup  5  mounted on the test tube  6 , the electrostatic capacitance value suddenly changes to become C 3  at the height location C. 
     This electrostatic capacitance value C 3  is almost the same as the value C 4  provided with the setting state shown in FIG. 4, and the threshold setting for the liquid level detection is easy. 
     The liquid level detecting signal  12  is output with the change of the electrostatic capacitance, and the computer  103  controls it so that the moving down operation of the movable arm  2  stops. 
     Subsequently, a predetermined amount of the sample is aspirated in the sample pipetting probe  105 . 
     When the sample cup  5  is indirectly set to the sample disc by using an auxiliary holding tool such as the test tube  6 , the setting height of the sample cup  5  changes according to the size of the auxiliary holding tool. 
     Moreover, the liquid level height of the sample  7  changes by repeating the pipette operation, too. 
     The conductive material  14  is arranged so as to be extended along the moving down direction of the pipetting probe, and it is constituted to almost exist along the overall length of the sample cup  5 . Further, even if the liquid level height changes, the liquid level may be detected surely. 
     According to the present invention, even if holding heights of sampling containers are different from each other, it becomes possible to detect the electrostatic capacitance change surely in the case when the pipetting probe contacts with the sample liquid level, whereby the liquid level detection may be performed with high accuracy.