Patent Application
20090148345
1. Field of the Invention
The present invention relates to automated analyzers that qualitatively and quantitatively analyze biological samples such as blood and urine and more particularly to an automated analyzer with a sample pretreatment mechanism that performs pretreatments, such as dilution or the like, on a sample before analysis.
2. Description of the Related Art
Automated analyzers that qualitatively and quantitatively analyze biological samples such as blood and urine may be unable to accurately measure the samples when the concentrations of the samples are high enough to exceed the measurable ranges of measurement instruments of the analyzers. In such a case, those samples are diluted for re-measurement. There are two methods associated with such sample dilution. One is to dilute a sample in a reaction vessel; the other is to dilute a sample in a vessel other than the reaction vessel which is exclusively used for the dilution purpose. As one of the latter methods, JP-A-05-80059 discloses an automated analyzer with a pretreatment disk that performs a pretreatment on a sample before
The pretreatment disk of the automated analyzer disclosed in JP-A-05-80059 rotates such that the operations performed for a particular pretreatment vessel placed on the pretreatment disk proceed in the following order: rinsing a pretreatment vessel (hereinafter also referred to as a dilution vessel); dispensing a sample into the pretreatment vessel; dispensing a diluent into the pretreatment vessel; and dispensing the diluted sample into a reaction vessel. Also, during one cycle of the pretreatment disk which spans 6 seconds, the pretreatment disk rotates 360 degrees plus N degrees, wherein N is the number obtained by dividing one by the total number of pretreatment vessels.
Such an automated analyzer has the following two drawbacks.
The first is decrease in the processing capability of the automated analyzer. Although the pretreatment disk rotates during each cycle, it has to stop at a certain position when a diluted sample needs to be dispensed into multiple reaction vessels for multiple-attribute analysis of the sample. During this period, the pretreatment disk stays at that position until all the dispensing operations are complete. No dilution and rinsing operation can be performed for other pretreatment vessels during the period, which may result in a decrease in the processing capability of the automated analyzer.
The second is the inability of the analyzer to control its pretreatment time. When such attributes of a sample as its enzymes and proteins are to be analyzed, that analysis can be made as soon as the sample is diluted at a particular rate. In contrast, measurement of glycosylated hemoglobin (HbAlc), which is contained in red blood cells in a blood sample, requires the sample, after diluted, to be left untreated for a certain amount of time or heated at a fixed temperature. Specifically, the sample has to be put on standby for measurement until its red blood cells are hemolyzed (broken down due to osmosis) to free hemoglobin and the like from the blood cells. Because the pretreatment disk of the automated analyzer disclosed in JP-A-05-80059 always rotates cyclically, this is efficient when the same pretreatment time is required for each sample. However, when there are samples with different pretreatment-times, the analysis efficiency of the automated analyzer may decrease.
An object of the present invention is thus to provide an automated analyzer with a sample pretreatment device which can operates smoothly under various analysis conditions.
To achieve the above object, the present invention is configured as follows:
An automated analyzer comprises:
a reaction vessel in which a sample is reacted with a reagent;
a pretreatment mechanism for performing the pretreatments when necessary on a sample before the sample is transferred from the sample vessel to the reaction vessel, the pretreatment mechanism having a pretreatment-vessel transfer mechanism for circulating the plurality of pretreatment vessels on a closed track, wherein while circulating the plurality of pretreatment vessels on the closed track, the pretreatment-vessel transfer mechanism alternates a first cycle during which a sample is transferred from the sample vessel to one of the plurality of pretreatment vessels and a second cycle during which a sample that completed the pretreatments is transferred from one of the plurality of pretreatment vessels to the reaction vessel; and
control means for controlling the pretreatment-vessel transfer mechanism such that the pretreatment-vessel transfer mechanism transfers a predetermined number of the plurality of pretreatment vessels on the closed track during the first cycle and such that the pretreatment-vessel transfer mechanism operates the second cycle when a sample that completed the pretreatments is in one of the plurality of pretreatment vessels.
The word ‘sample’ as used herein is also referred to as an analyte or specimen and refers to biological samples such as blood and urine. The ‘sample vessels’ can be of any form including test tubes, cuvettes, and small cups as long as it is capable of containing a sample. The sample vessels can be placed on the circumference of a circular sample disk or on a sample rack that can place thereon one or more sample vessels. The ‘reaction vessels’ refer to vessels in which a sample and reagent are mixed for analysis. Representative analyses include colorimetric analysis, in which a reaction is detected by a change in the color of liquid, and immunoanalysis and gene analysis, in which a sample to be analyzed is reacted with a reagent that bonds specifically to the sample, and a labeled substance in the resultant bonded substance is measured in terms of luminance. The automated analyzer of the present invention can be applied to the above analyses and to any kind of analysis other than the above.
Means for transferring a sample from a sample vessel into a pretreatment vessel and means for transferring a pretreated sample from a pretreatment vessel into a reaction vessel can be pressure generating devices such as a syringe, diaphragm, and vacuum pump. Any widely-used liquid dispensing probe, which changes the pressure inside its nozzle to suction a liquid into the nozzle and dispense it out from the nozzle, can be used for those means as long as it is capable of transferring a liquid.
The ‘pretreatment-vessel transfer mechanism’ can be of any form as long as pretreatment vessels can be transferred on a closed or endless track. A representative example is a disk-shaped rotating mechanism. The pretreatment-vessel transfer mechanism can also be a circular carousel having a closed moving belt for transferring pretreatment vessels thereon.
The ‘first and second cycles’ refer to periods during which the pretreatment-vessel transfer mechanism, or the pretreatment disk, rotates to transfer pretreatment vessels. For example, during each of the first cycle, the pretreatment disk rotates such that five pretreatment vessels are transferred unidirectionally (clockwise or counterclockwise). In contrast, during each of the second cycle, the pretreatment disk rotates seemingly randomly. Since the second cycle is a period during which a pretreated sample in a pretreatment vessel placed on the pretreatment disk is transferred to a reaction vessel, it can be a period during which no operation is performed when there is no pretreated sample to be transferred. Also, a pretreated sample in a pretreatment vessel may be transferred to several reaction vessels during several second cycles in the case of multiple-attribute biochemical analysis. The present invention is distinctive in the above respect: that is, regular and (seemingly) random rotational movements of the pretreatment disk are repeated. The repetition can be an alternation of regular movement and random movement or an alternation in which a regular movement is repeated several times and then followed by a repetition of a random movement several times.
The effects produced by the present invention are the following:
1) The automated analyzer of the invention is less subject to decrease in its processing capability due to pretreatments. This is because the automated analyzer is capable of continuing analysis while keeping on the pretreatment (dilution) disk a particular sample that is put on standby for re-analysis,
2) When samples, after diluted, need be left untreated for a certain amount of time or heated at a fixed temperature for a certain amount of time as a pretreatment, that amount of time can be changed as desired. Therefore, the automated analyzer can analyze samples smoothly also when they need hemolytic treatment as a pretreatment.
Other objects and advantages of the invention will become apparent from the following description of embodiments with reference to the accompanying drawings in which:
The features of the present invention are briefly described below.
Configuring the system control of an automated analyzer based on sample dilution cycles affects the processing capability of the automated analyzer during re-sampling. To avoid this, the automated analyzer according to the present invention adopts two-cycle system control in which one cycle is a sample dilution cycle (hereinafter referred to as a cycle A), and the other is a sample re-sampling cycle (hereinafter referred to as a cycle B). These cycles A and B are designed to operate alternately. Hereinafter, the automated analyzer of the present invention is described in which the analyzer performs sample dilution as a pretreatment. However, the automated analyzer according to the invention can be applied to any pretreatment-automated analyzer as long as it analyzes biological samples.
Performed during cycles A are a series of dilution operations including: rinsing a dilution vessel; dispensing an original sample into a dilution vessel; dispensing a diluent into a dilution vessel; and stirring a sample and diluent in a dilution vessel. These operations are concurrently performed on some of the dilution vessels placed on the dilution disk of the analyzer during one cycle A, and each of the operations is performed by respective mechanisms, such as a sampling probe and a diluent dispensing probe, disposed at particular positions around the dilution disk.
Performed during cycles Bis the operation of moving a dilution vessel containing a diluted sample into a re-sampling position, where the sample is re-sampled (dispensed) into a reaction vessel.
During cycles A, the dilution disk rotates regularly such that when a particular dilution vessel completes the above series of dilution operations during cycles A, the next dilution vessel to be subjected to the series of dilution operations is either of the dilution vessels counterclockwise-adjacent or clockwise-adjacent to that dilution vessel.
During cycles B, the dilution disk rotates such that a dilution vessel containing a diluted sample is transferred to a particular position for re-sampling.
As stated above, cycles A and B operate alternately. During the transition from a cycle A to a cycle B, a dilution vessel that contains a diluted sample and is to be subjected to a re-sampling operation next is moved to the re-sampling position wherever on the dilution disk that dilution vessel is located. In such a case, the dilution disk is to select a clockwise or counterclockwise rotation, whereby the transfer of the dilution vessel takes the shortest route from the position of that vessel to the re-sampling position.
Described next is the transition from a cycle B to a cycle A.
As stated above, during cycles A, a series of dilution operations are regularly performed. During the transition from a cycle B to a cycle A, the dilution disk rotates such that a particular dilution vessel that completed a certain dilution operation during the preceding cycle A is subjected to the next dilution operation during the next cycle A. Assume, for example, that an original sample is dispensed into a particular dilution vessel during the preceding cycle A, and a cycle B begins. Then, that particular dilution vessel moves to a diluent dispensing position in the next cycle A.
In the automated analyzer of the present invention, during cycles A, dilution vessels placed on the dilution disk are sequentially subjected to a series of dilution operations with the dilution disk rotated, and cycles A and B are independent of each other. Therefore, re-sampling a diluted sample from a dilution vessel on the dilution disk into a reaction vessel on a reaction disk can be performed without stopping the series of dilution operations. Further, also in a multiple-attribute biochemical analysis in which a diluted sample is re-sampled several times into reaction vessels, dilution operations can be performed sequentially during cycles A although the dilution disk stays at one position during cycles B. In the case of a biochemical analysis in which samples, after diluted, need be left untreated for a certain amount of time or heated at a fixed temperature, cycles B are controlled not to operate until a predetermined amount of time passes. Also in cycles A during this period, dilution operations can be performed on dilution vessels one after another.
A preferred embodiment of the present invention is described below with reference to the accompanying drawings.
A biological sample is first dispensed into the sample vessels 2, and the sample rack 1 containing the sample vessels 2 is moved closer to the sampling probe 3. The biological sample is then dispensed into one of the dilution vessels 5 on the dilution disk 4 by the sampling probe 3. After diluted, the sample is moved to the re-sampling position 8, where it is sampled again into one of the reaction vessels 12 on the reaction disk 11 by the re-sampling probe 10.
Since the invention pertains to increased efficiency in pretreatments from sampling to re-sampling, described hereinafter is the operation of the automated analyzer (specifically, the operation of the dilution disk 4) during the pretreatments from sampling up to re-sampling.
During each cycle A, the following steps are concurrently performed on dilution vessels 5 placed on the dilution disk 4: sampling an original sample into a dilution vessel; dispensing a diluent into a dilution vessel; stirring a sample and diluent in a dilution vessel; and rinsing a dilution vessel. During each cycle B, only the step of dispensing a diluted sample into a reaction vessel is performed. Cycles A and B are controlled independently of each other and operate alternately. Note that the operations performed for a particular dilution vessel on the dilution disk 4 proceed in the following order.
Sampling-+Diluent dispensing->Stirring-*Re-sampling-*Standby for reanalysis-+Rinsing
[In the case of single-attribute biochemical analysis in which samples, after diluted, need not be left untreated for a certain amount of time or need not be heated at a fixed temperature as a pretreatment, i.e., samples need only be diluted as a pretreatment]
As stated above, performed during each cycle A are the steps of sampling an original sample into a dilution vessel, dispensing a diluent into a dilution vessel, stirring a sample and diluent in a dilution vessel, etc. However, performed during each cycle B is only the step of dispensing a diluted sample into a reaction vessel, and a cycle B does not operate until the first sample dispensed into a dilution vessel is mixed with a diluent and becomes ready for re-sampling; that is, a cycle B operates only when there is a sample available for re-sampling. When a sample, after diluted, need not be left untreated for a certain amount of time or need not be heated at a fixed temperature, that sample is re-sampled into a reaction vessel during the next cycle B immediately after that sample is stirred. As shown in
The following example is based on the assumption that twenty dilution vessels are on the dilution disk 4, and during cycles A, the dilution disk 4 rotates such that pretreatments are performed on every third dilution vessel, which means, with reference to
Referring to
As stated above, during cycles A, the dilution disk 4 rotates such that pretreatments are performed on every third dilution vessel. This means that after the dilution disk 4 completes a 360-degree rotation, alternating cycles A and B, the next dilution vessel into which the original sample is sampled is dilution vessel #20, which is clockwise-adjacent to dilution vessel #1, or the vessel into which the original sample is dispensed first.
[In the case of multiple-attribute biochemical analysis in which samples, after diluted, need not be left untreated for a certain amount of time or need not be heated at a fixed temperature as a pretreatment, i.e., samples need only be diluted as a pretreatment]
As stated above, performed during each cycle A are the steps of sampling an original sample into a dilution vessel, dispensing a diluent into a dilution vessel, stirring a sample and diluent in a dilution vessel, etc. However, performed during each cycle B is only the step of dispensing a diluted sample into a reaction vessel, and a cycle B does not operate until the first sample dispensed into a dilution vessel is mixed with a diluent and becomes ready for re-sampling; that is, a cycle B operates only when there is a sample available for re-sampling. When a sample, after diluted, need not be left untreated for a certain amount of time or need not be heated at a fixed temperature, that sample is re-sampled into a reaction vessel during the next cycle B immediately after that sample is stirred. When multiple attributes of a sample is to be analyzed, that is, when that sample needs to be re-sampled several times, that sample is re-sampled in as many cycles B as necessary, as shown in
Similar to the single-attribute biochemical analysis described above, the following example of multiple-attribute biochemical analysis is also based on the assumption that twenty dilution vessels are on the dilution disk 4, and during cycles A, the dilution disk 4 rotates such that pretreatments are performed on every third dilution vessel.
The multiple-attribute analysis of a sample is the same as the single-attribute analysis except for the subsequent operations performed after the operation in
[In the case of biochemical analysis in which samples, after diluted, need be left untreated for a certain amount of time or heated at a fixed temperature as a pretreatment, e.g., analysis of HbPd, (glycosylated hemoglobin) in which samples needs hemolytic treatment as a pretreatment]
In such a case, the operations performed for a particular dilution vessel placed on the dilution disk 4 proceed in the following order.
Sampling-3 Diluent dispensing-*Stirring-3 Leaving the sample untouched or heating it-*Re-sampling-*Standby for reanalysis-*Rinsing
When a sample diluted in cycle A needs to be left untreated or heated at a fixed temperature for a certain amount of time, that sample is re-sampled into a reaction vessel in the next cycle B that comes right after the passage of that amount of time.
Wherever on the dilution disk 4 the diluted sample is located, it is transferred to the re-sampling position d during the above cycle B. This movement of the sample is prompted by software which controls the time to be allocated to the sample up until re-sampling.
As shown in
For example, after the sample dispensed into dilution vessel #1 is subjected to a stirring operation, it is heated at a fixed temperature for a certain amount of time. If that amount of time is two minutes, the sample is re-sampled in the next cycle B that comes immediately after the passage of two minutes (two minutes might include several cycles A and B). Until this cycle B, no operation is performed during the preceding cycles B.
1-2. Movement of Dilution Vessels During cycle A
As shown in
1-3. Movement of Dilution Vessels During cycle B
The dilution disk 4 during cycles B does not rotate until a sample is diluted and becomes ready for re-sampling. When the sample is ready, it is transferred during the next cycle B to the re-sampling position d, as shown in
As stated above, the dilution disk 4 does not rotate during cycles B until a sample is available for re-sampling. In such a case, a dilution vessel can also be rinsed.
In a biochemical analysis in which samples, after diluted, need to be left untreated for a certain amount of time or heated at a fixed temperature, a particular dilution vessel undergoes the following treatments in the following order, as is also shown in
While the invention has been described in its preferred embodiments, it is to be understood that the words which have been used are words of description rather than limitation and that changes within the purview of the appended claims may be made without departing from the true scope and spirit of the invention in its broader aspects.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2007-316506 | Dec 2007 | JP | national |
