WO2013064562A2

WO2013064562A2 - Method of sample transportation in a biochemical analyser and a biochemical analyser realizing this method

Info

Publication number: WO2013064562A2
Application number: PCT/EP2012/071606
Authority: WO
Inventors: Wojciech PRZYBECKI; Miroslaw OSTROWSKI; Andre Chojnacki; Eric CHARAVEL; Jan GROSZYNSKI
Original assignee: Pz Cormay S.A.
Priority date: 2011-10-31
Filing date: 2012-10-31
Publication date: 2013-05-10
Also published as: PL396829A1

Abstract

The object of the invention is the method of sample transportation in a biochemical analyser along a trajectory leading from the initial area through the pipetting area to the parking area, characterized in that, the trajectory passes through the pipetting area (3, 5) at least two times, and the time of sample transportation along the trajectory from the first pass through the pipetting area (3) to the second pass through the pipetting area (5) is not shorter than the time for performing a single determination by the biochemical analyser. The invention also includes a biochemical analyser realizing this method of sample transportation.

Description

Method of Sample Transportation in a Biochemical Analyser and a Biochemical Analyser Realizing this Method

The object of the invention is the method of sample transportation in a biochemical analyser along the trajectory leading from an initial area through a pipetting area to a parking area and the biochemical analyser realizing this method. The invention is applicable in modern medical diagnostics.

Biochemical analysers are advanced automated devices for testing chemical composition in blood serum and other body fluids (plasma, cerebrospinal fluid, urine). For example, in this manner, the contents of the following is determined in blood serum: glucose, lipids (e.g. cholesterol, triglycerides), enzymes (amylase, transaminases and phosphatases), ions (sodium, potassium, lithium, etc.) etc.

The central module of the analyser is constituted by a photometer, comprising a light source and a detector, by means of which a colour change of the reaction mixture, placed in a transparent cuvette, can be measured. In a typical, known in the art, analyser, reaction cuvettes are placed on a rotating rack (rotor). In its neighbourhood, there is another rotating rack, which stores reagents used in the test reactions. Firstly, a preheated portion of the reagent is placed in the cuvette, typically a volume of approximately 100-300 microliters, and in the said photometric module, the absorbance measurement of the pure reagent is made, thereby indicating a so-called background level for subsequent measurements. After the incubation time (typically about 1-2 minutes in order to stabilize the temperature at 37°C) a small amount of test blood serum is added to the reagent (typically - about a few microliters). Blood serum is collected from the third rotor, or other holder intended for the test samples. An addition of blood serum to the reagent is followed by mixing, and, in the cuvette, the chemical reaction takes place. This is usually a colour reaction (colorimetric), sometimes a turbid (immunoturbidimetric) reaction. After a few minutes, the chemical reaction is completed and the colour of the liquid in the cuvette stabilizes. Then, once again, the sample is overexposed in said photometric module, and then by subtracting the background and using the prior calibration of the device, the concentration of the test substance in the blood serum sample is calculated. For the determination of certain substances, two or more reagents are used. If the reaction of the first reagent with a sample of blood serum is not a colour reaction, additionally, another reagent containing a so-called chromogen is used, which causes a colour change of the test solution so as to perform a photometric measurement. The types of reagents as used and their concentrations are chosen so as to be able to carry out the test reactions in the volumes from 100 to several hundred microliters.

Biochemical analysers constructed in the above-mentioned way and carrying out the above-described test procedure are available in the market, e.g. flexor XL analysers of ELITech), and are subject of numerous patents and patent applications (e.g. JP 8211072 A, JP 10132735 A, JP 2010 33924 A, US 2004 0185549 Al, US 2005 0014274 Al, US 4808380, US 6162399 or US 2007 0065945 Al publications).

Typically, samples - that is, tubes with fluids intended for tests (e.g. with blood serum, cerebrospinal fluid, other body fluids) are placed in a special holder. Usually, rotating holders in the form of carousels, in which tubes form a circle or circles, are used (e.g. US 4808380 A). Less frequently, linear holders (usually more expensive solution) in which the tubes are arranged in a straight line, in one or several rows, (e.g. CN101806809 A, US 2005 014274 Al, US 6162399 A) are used.

In the case of linear holders, the holders together with the tubes are transported within the biochemical analyser along the substantially straight sections of the track. The holders begin their route in the fixed initial area, onto which they are loaded by the operator or automatically. Then, the holder is transported to the so-called pipetting point, that is, to the area in which the pipettes or needles of the biochemical analyser draw a given amount of test material from a sample placed in the holder. This material is then precisely dosed into the cuvette with the reagent and mixed, in order to perform the required determination, as described above. Finally, the holders with samples reach the end of their route within the biochemical analyser - to the so-called parking area. Transporting the linear holders with samples takes place - as mentioned above - substantially along straight lines and is realized by various known methods - e.g. using rollers, a conveyor belt, a chain, a set of strands, etc. Solutions of this type are known e.g. from the above-mentioned publications CN101806809 A, US 2005 014274 Al, US 6162399 A.

If the rotating holders, in the form of carousels (e.g. US 4808380 A), are used, then the sample transportation within the biochemical analyser is realized by an appropriate rotation of the holder (e.g. by means of a stepping motor). As in the case of linear holders - for a certain setting (a specific angle of rotation) of the holder, the samples placed therein reach the pipetting point, where the pipettes or needles of the biochemical analyser draw the test material from the sample. After pipetting, the rotation of the holder is continued, so that in the pipetting area, another sample appear.

Unfortunately, it happens that the requested test (determination) fails and has to be repeated. This may happen due to various types of errors in the operation of the biochemical analyser (e.g. invalid collection of the reagent due to the appearance of air bubbles or foam). The need to repeat the test also appears when the concentration of the test substance in the sample is outside the possible-to-determine scope by means of the used reagent (the so-called linearity end). Then, the determination has to be repeated using diluted sample, diluted reagent or other reagent. Whether the determination needs to be repeated or not - is known only after the receipt of the result of the first determination, which, in typical prior art biochemical analysers, lasts from a few to several minutes. During this time, the corresponding holder with the sample is transported, and therefore, at the time when it is considered necessary to repeat the test, the sample is not in the pipetting area. Therefore, in the art, complicated mechanisms which find and return the appropriate sample for retesting are used.

On the other hand, according to Japanese Patent Application No. JP 61107161 A, on the material taken from a single sample, a few (e.g. three) such determinations are performed right away, in case any of the determinations fail. However, this is a very uneconomical method: in this case, the sample material is very quickly consumed (or: the samples must be appropriately greater), and also an appropriate multiplication of systems performing determinations is required.

Another problem is associated with the samples, for which the determination should be performed immediately, in addition to the normal sequence for performing determinations by the analyser (the so-called cito samples, related to emergencies, life-threatening states, etc.). When using circular holders (carousels) - determinations performed on the set sequence of samples has to be stopped, a cito sample or samples has to be added to the device, the requested tests has to be performed on them, and then the regular determinations has to be resumed on the said sequence of samples. This process is time consuming and requires the use of special mechanical solutions regarding loading of the samples. For example, U.S. patent application No. U.S. 2011112683 Al discloses a solution, according to which the appropriately determined samples are placed in the holder, then in the validation process, urgent samples from the other ("normal") samples are distinguished by the said determination, and finally "normal" samples are unloaded from the holder onto the waiting area, while, for urgent samples, the requested determinations are performed.

On the other hand, according to the international patent application No. WO 2010 087303 Al, in the biochemical analyser, in which the samples placed in holders are substantially transported along straight lines, there are two initial areas, to which holders with samples can be added: a "normal" area and an initial area intended for urgent samples. In normal operating mode, the biochemical analyser collects samples from the "normal" area unless the samples are loaded to the other initial area intended for urgent samples. In such a case, at first, the samples from this area are collected, and the test is performed for them.

Japanese Application No. JP 2007322287 A discloses a solution, according to which, by means of special levers and pushrods, the order of holders with samples waiting in the queue for pipetting can be changed. This allows for the addition of holders with cito samples into appropriate places in the queue so that the tests on these samples could be quickly performed.

Therefore, the object of the present invention is to propose a method of transporting samples, which is deprived of the above drawbacks.

Another object of the invention is to propose a biochemical analyser realizing this method of sample transportation.

According to the invention, the method of sample transportation in the biochemical analyser along a trajectory leading from the initial area through the pipetting area to the parking area, is characterized in that the trajectory passes through the pipetting area at least two times, and the time of sample transportation along the trajectory from the first pass through the pipetting area to the second pass through the pipetting area is not shorter than the time for performing a single determination by the biochemical analyser.

Preferably, the said trajectory passes through the pipetting area exactly two times. Preferably, the time of sample transportation along a trajectory from the first pass through the pipetting area to the second pass through the pipetting area is equal to the time for performing a single determination by the biochemical analyser.

Preferably, the said sample is placed in a holder.

In a preferred embodiment of the invention, the said trajectory comprises two substantially parallel sections, each of which passes through the pipetting area.

Preferably, the maximum speed of the sample transportation along the trajectory is about 200 mm/sec.

Preferably, the sample transportation along the trajectory is carried out by a method selected from the group comprising: a pulling mechanism with an electromagnet-controlled latch moving along a guide, a transporting mechanism equipped with a toothed belt with hooks, a conveyor belt, a chain, rollers.

In the most favourable embodiment of the invention, the inventive method is carried out in a biochemical analyser, equipped with transporting means for transporting samples from an initial area through a pipetting area to a parking area, pipetting means for pipetting a portion of the sample for analysis while the sample is in the pipetting area and analysing means for performing biochemical analysis of said portion of the sample.

The invention also includes a biochemical analyser realizing this method of sample transportation.

Because, in the solution according to the invention, all the samples pass through the pipetting area within the time period which is higher or equal to the time for performing a single determination - it is very easy to repeat the test, if necessary, for a particular sample. Any additional mechanisms searching for the sample and delivering it again into the pipetting area are not necessary for this purpose.

Secondly, due to the fact that the cito (urgent) samples are placed in a separate, dedicated rotor, it is possible to add these samples at any time. After inserting the cito samples and introducing orders for performing urgent tests, the analyser automatically stops collecting the routine samples (linear holders with samples stop for this time), collects the cito samples and then immediately resumes collecting the routine samples. The invention will now be further described in a preferred embodiment, with referenceccompanying drawings, in which:

Figure 1 shows an overall view of the biochemical analyser according to the invention,

Figure 2 shows schematically the construction of the biochemical analyser according to the invention with an indication of the sample trajectory (straight arrows show the transportation direction of the holders with samples, curved arrows show the rotation of the sample collection arm) and

Figure 3 shows schematically the construction of the linear sample feeder with an indication of operating areas.

The following indications were used in the drawings:

1 beginning of the holder trajectory (external track - holder validation area),

2 waiting area,

3 sample collection area for the primary measurement,

4 waiting area for the results of the primary measurement,

5 sample collection area for the repeated measurement,

6 position of the sample collection arm for the primary measurement,

7 position of the sample collection arm for the repeated measurement,

8 parking area (end of the sample feeding track, end of the holder trajectory),

9 holder,

10 external track (external guide),

11 internal track (internal guide). Preferred embodiment of the invention

Figure 1 shows an overall view of the preferred embodiment of the biochemical analyser according to the present invention. On the other hand, Figure 2 shows schematically the construction of the biochemical analyser, and Figure 3 shows schematically the construction of the linear sample feeder with an indication of operating areas according to the invention in the embodiment.

In a preferred but non-limiting embodiment, the sample transportation in the biochemical analyser is as follows:

Samples in holder 9 made of aluminium and PTFE, measuring 40 x 116mm and 62mm of height, will be placed in the initial area 1 of the trajectory. The holder 9 with samples is collected therefrom, after prior sample validation by means of the barcode scanner, and is transported along the external guide 10 (to the right in Figure 3). Transportation of the holder 9 is realized by the pulling mechanism with an electromagnet-controlled latch moving along the guide located on the side, and in parallel to the track for holder 9 transportation. The length of this section is 540mm. Because the transportation speed of the holder 9 with samples along the trajectory is about 100 mm/sec. - the samples reach the pipetting area 3 after 5.4 seconds since the beginning of the route. After passing this section, the holder 9 is taken over by a transporting mechanism equipped with a toothed belt with hooks. This mechanism precisely moves the holder 9 in the primary pipetting area 3, setting the successive samples in the sample collection position. In the pipetting area 3, the analyser pipette collects the required amount of material from the sample. This material is then delivered to the reaction cuvette of the analyser (not shown in the drawing), mixed with a suitable reagent and used for the photometric determination, according to the known in the art method, described in the introduction. In the case of the described analyser, the time for performing the determination is constant and amounts to 12 minutes. During this time, the holder 9 with samples is transported further, from the pipetting area 3 to the end of the external guide 10. Having reached this position, the holder 9 is transported to the internal guide 11 by means of a special mechanism, and then, by means of another toothed belt with hooks moving in the opposite direction, is transported to the pipetting area 5 for the repeated measurements. After a period not shorter than 12 minutes since the time of the first pipetting, the holder 9 with samples is located in the pipetting area 5 for the repeated measurement. Then, the result of the test, which is the result of the first pipetting, is known. If it is invalid (e.g. linear range for the measurement has been exceeded) - the test can be easily repeated, by performing another pipetting. If it is not necessary (the result of the test, which is the result of the first pipette is correct) - the second pipetting and retesting are not performed. Then, the holder 9 with samples is transported further along the internal track 11 (to the left in Figure 3), by another pulling mechanism with an electromagnet-controlled latch moving along the guide located on the side, in parallel to the track, till it reaches the parking area 8.

The indicated period of 12 minutes is only an example, and is usually longer, depending on the number of tests commissioned to be performed in the subsequent samples. According to the invention, it is essential that the length of the trajectory of the holder 9 with samples from the first pass through the pipetting area 3 to the second pass through the pipetting area 5 and the transportation speed of the holder 9 with samples along the trajectory be selected in such a way that the transportation time of the sample from the first pass through the pipetting area 3 to the second pass through the pipetting area 5 was not shorter, and preferably equal or slightly longer than the time required to perform the determination.

During this time (simultaneously), along the trajectory, successive holders 9 with samples are transported. They may be continuously added to the initial area 1, they successively enter the pipetting area 3, they are transported further along the trajectory 4 and successively re-enter the pipetting area 5. Finally, they successively reach the parking area 8.

The cito samples are inserted into a separate rotor, independent of the linear feeder. At any moment, the performance of the tests on samples from the linear feeder can be stopped and a sample from the cito rotor can be collected. The test results of the cito sample will be issued by the device after the period of about 12 minutes since the sample collection.

Claims

1. A method of sample transportation in a biochemical analyser along a trajectory leading from an initial area through a pipetting area to a parking area, characterized in that the trajectory passes through the pipetting area (3, 5) at least two times, and the time of sample transportation along the trajectory from the first pass through the pipetting area (3) to the second pass through the pipetting area (5) is not shorter than the time for performing a single determination by the biochemical analyser.

2. The method according to claim 1, characterized in that the said trajectory passes through the pipetting area (3, 5) exactly two times.

3. The method according to any one of the preceding claims, characterized in that the time of sample transportation along the trajectory from the first pass through the pipetting area (3) to the second pass through the pipetting area (5) is equal to the time for performing a single determination by the biochemical analyser.

4. The method according to any one of the preceding claims, characterized in that the said sample is placed in the holder (9).

5. The method according to any one of the preceding claims, characterized in that the said trajectory comprises two substantially parallel sections (10, 11), each of which passes through the pipetting area.

6. The method according to any one of the preceding claims, characterized in that, the maximum speed of sample transportation along the trajectory is about 200 mm/sec.

7. The method according to any one of the preceding claims, characterized in that the sample transportation along the trajectory is realized by a method selected from the group comprising: a pulling mechanism with an electromagnet-controlled latch moving along a guide, a transporting mechanism equipped with a toothed belt with hooks, a conveyor belt, a chain, rollers.

8. The method according to any one of the preceding claims, characterized in that it is carried out in a biochemical analyser, equipped with transporting means (10, 11) for transporting samples from an initial area (1) through a pipetting area (3, 5) to a parking area (8), pipetting means (6, 7) for pipetting a portion of the sample for analysis while the sample is in the pipetting area (3, 5) and analysing means for performing biochemical analysis of said portion of the sample.

9. The biochemical analyser realizing the method of sample transportation according to any one of the preceding claims.