JP2002522746A - Method and apparatus for online test samples - Google Patents

Abstract

  (57) [Summary] A method of serologically testing a sample such as blood, wherein at least one, and preferably a series of subsamples are separated, wherein at least one subsample is subjected to at least one serological test. Wherein at least one test is performed online.

Description

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a method for serologically testing a sample such as blood.

For example, in the meat processing industry, it is very important to be able to determine whether an animal processing meat meets general health standards, at least during feeding, lactation and / or slaughter. To that end, for example, blood or other body fluids of the animal are serologically tested, for example, to demonstrate their bacterial or viral infection. It is known to perform such tests by drawing blood from live animals, which blood is accurately examined in the laboratory. The blood sample is divided into a number of different parts, each of which is subjected to a special serological test. The results found are combined and the health of the animal in question is determined based on it. Such data is returned to the farm where the animal of interest is located, so that the animal, its same group of animals and / or the same breeding animal at least later for human or animal consumption can be slaughtered, Or not served.

Furthermore, it is known in the meat processing industry to take a random blood sample from a slaughtered animal, which sample is serologically tested in a laboratory in the manner described above. Based on such data, all batches of meat from a plurality of slaughtered animals are or are not slaughtered for human or animal consumption at least later.

In such a known method, in each case the sample is sent to a laboratory, where the various serologic tests are performed by different humans, at least at different stages and by different means. This is expensive, time consuming, and inefficient. There is also a risk of losing the direct link between the animal from which the sample was taken and the test results.
In addition, the animal in question will often be further processed before the relevant results are fully available. In addition, testing live animal samples carries the risk that such samples are no longer quite accurate at slaughter.

[0005] Hospitals, blood banks and the like test (blood) samples in a similar manner.

It is thus an object of the present invention to provide a method of the kind described in the introduction, which avoids the stated disadvantages of the known methods, while retaining their advantages. You. For this purpose, the method according to the invention is characterized by the features of claim 1.

Performing serologic tests online offers the advantage that the desired results can be obtained relatively quickly, while at the same time a good connection between the animal from which the sample is taken and the relevant sample to be processed is maintained. . Furthermore, a large number of tests can be performed in a rapid and simple manner, while tests on different animals or at least parts thereof can be performed sequentially as well as in parallel. Thus, based on the results found, further processing of the tested meat or treatment of the tested animal can be adjusted. Based on the achievement of a series of parallel, rapid, accurate and relatively inexpensive serological tests, and on the basis of the measurements found, thanks to the precise adjustment of further processing or treatment, humans or animals consuming meat and And / or the health of the tested animals is more effectively protected than before, and if not all animals are sacrificed, not scheduled to be sacrificed or not treated, the serum of many animals is instead Allow immediate examination.

The term “on-line” should be understood to mean at least the testing of a sample, in particular a blood sample drawn from an animal or human on site. In this context, "on-site" includes a space suitable for conducting serological tests located some distance from the location where the sample is taken to the space where the collected blood sample is quickly transported. Should be understood. Thus, for example, pneumatic transport can be used for transport, whereby the sample is available for serological testing within minutes.

In an advantageous embodiment, the method according to the invention is characterized by the features of claim 2.

[0010] In an advantageous embodiment, a relatively large number of serological tests are performed on-line on sub-samples separated from the sample taken. To that end, the separated subsamples are pretreated and introduced into the matrix of the receiving cavities, while different serological reactions occur in different receiving cavities. To this end, different sub-samples are preferably mixed with various first processing media, and the subsequently formed mixture of sub-samples is processed using a different or the same further processing medium. Thus, different receiving cavities of one matrix result in parallel and / or successively different mixtures of subsamples, first and further processing media, resulting in the coupling of various reactions or active ingredients. The subsample in the receiving cavity of the matrix can then be further processed and analyzed, and a complete view of the resulting measurements can be obtained for the animal in question or at least a portion thereof. Each receiving cavity that is filled after the serological test has been completed gives the results of the serological test performed therein, which for each receiving cavity in question in the matrix rows and / or columns. Different tests can be. This allows a simple comparison of this matrix with other known matrices, so that the results found for a number of different tests can be analyzed at once, for example through pattern recognition.

In this context, the term “matrix of receiving cavities” should be understood to mean at least a number of columns and rows of receiving cavities, wherein for two or more rows and / or columns, each row And / or the number of receiving cavities in a column may be different from the number of receiving cavities in an adjacent row or column. The location of each receiving cavity in the matrix can be established by a coordinate system (eg, the number of columns and columns of the receiving cavity) in the matrix to further process the measurements. This is possible and whenever relevant, is referred to herein as a series of receiving cavities, where a portion of the same subsample is provided. Thus, when multiple subsamples are processed simultaneously, the separated subsamples can be inserted into different columns of the receiving cavity. However, it is also conceivable that the random distribution of each subsample, ie, not distributed in rows or columns, may be possible. Therefore, depending on the selected coordinate system,
Each subsample can establish a receiving cavity or cavity into which it is inserted.

In a particularly advantageous manner, the method according to the invention is characterized by the features of claim 4.

[0013] By using a mixture of at least two conjugates, with at least one as the processing medium, the different sub-samples can be loaded into the various receiving cavities in a column of a matrix of receiving cavities, Special advantages are achieved in that serological tests can be performed. This allows the receiving cavity to be packed in a particularly simple manner, while ensuring a simple manner in which all tests in the column of the selected receiving cavity are performed with identically processed subsamples. , Which allows for better comparisons. In each receiving cavity, for example, a further different processing medium can be added. Also, each receiving cavity of a row of the matrix can for example be further processed with the same processing medium, while the interrelated rows are processed with different processing media. At each receiving cavity, a specific combination of bound or unbound antibodies, antigens, etc. is obtained, which may or may not be labeled with a label detectable by the assay used.

In this context, the term “conjugate” should be understood to mean at least an element, whereby in a serologic test an antigen such as, for example, a virus or other foreign substance, or Antibodies specifically raised thereto can be indicated.
In particular, this should be understood to mean a labeled immunoreactant. The sign may consist of at least one or more of the following elements: For example, horseradish peroxidase (HRPO), alkaline phosphatase,
1. enzymes such as urease, glucose oxidase, dehydrogenase, β-D-galactosidase; 2. a fluorescent dye; ^3. Radioactive elements such as H ³ , C ¹⁴ , I ¹³¹ ; 4. biotin; Gold ball 6. 6. carbon spheres; or europium.

[0015] Modifications or alternatives so far will be readily apparent to those skilled in the art.

In a further advantageous embodiment, the method of the invention is further characterized by the features of claim 6.

[0017] Coating the matrix of the receiving cavity, preferably with various further processing media such as specific antibodies or antigens, is sufficient to allow the receiving cavity to be pre-treated before performing a series of serological tests. It offers the advantage that processing can be performed under controlled conditions. For a specific series of serologic tests and the like, the matrix plate is always present during the test, since the matrix multiplicity in the receiving cavity, called the matrix plate, can be adjusted in a suitable and well-defined manner. Thus, sequencing of serological tests can be performed at high speed, with high accuracy and reproducibility, and at relatively low cost. Especially when such matrix plates are used in the on-line method of the present invention, the desired number of serologic tests are supplied and unloaded in meat, blood or (semi) continuously in a (semi) continuous process. This provides the advantage that it can be performed on other types of samples.

In this context, the term “coating” should be understood to mean at least the elements used for serological tests, whereby antigens such as, for example, viruses or foreign substance types, or Antibodies specifically raised against this, in particular immunoreactants, can be indicated. Such coatings include, for example: 1. Complete virus particles, or specific parts thereof; 2. whole antibodies, or specific parts thereof; 4. peptides; proteins other than those mentioned in 4.1-3; or It consists of residues or combinations thereof.

[0019] Other coatings applicable to the present invention will be readily apparent to those skilled in the art.

More particularly, the method of the invention is characterized by the features of claim 7.

In the method, a portion of the subsample is introduced into an associated receiving cavity (s) through a smearing movement of a pickup part across one or more receiving cavities. That is, a relatively small receiving cavity can be filled, which is difficult, if not otherwise impossible, to fill due to the surface tension of the subsample. Furthermore, due to the application movement of the pick-up part, an equal amount of subsample is introduced into the associated receiving cavity each time. In fact, the excess is smeared on the upper edge of the receiving cavity by the pick-up part.
f). In each case, it is possible in a particularly simple manner to fill the receiving cavities in exactly the same amount each time, and even with small receiving cavities. In this manner, individual receiving cavities can be filled, but also a matrix of receiving cavities as used by the method of the invention, for example, a series of receiving cavities in a column.

In particular, a relatively small receiving cavity can be filled without problems, without loss of subsamples, and all subsamples from the same subsample are available,
And since it can be used for one or more tests according to the method of the present invention, a particularly small amount of subsample is sufficient and can be used for a wide range of tests. This is particularly advantageous when only a small amount of the sample or medium required for the test is available, or when the sample or processing medium is expensive or dangerous.

The application operation for inserting the sub-samples into different receiving cavities can of course be performed in different ways and by different means, but the sub-samples may be received in the relevant pick-up part before application. Direct contact between the pick-up part and the receiving cavity is not necessary, as transport already takes place through adhesion. The advantage achieved by avoiding direct bonding is that the pickup part can be used repeatedly, since there is no contamination of the pickup part by at least partially received cavities and vice versa. In fact, different pickup portions may be used for different columns of the receiving cavity or combinations thereof.

In a preferred embodiment, the method of the invention is characterized by the features of claim 8.

By simultaneously submitting the different receiving cavities to a suitable assay, a complete picture of the serologic test results is given, so that, for example, viral or bacterial bias in a sample can be obtained very quickly. . This involves the incorporation of analytical instrument (s), so that multiple matrices of the receiving cavity can be analyzed quickly one after the other, so that non-invasive methods, such as radiometric measurements, are used. It is.

More particularly, the method of the invention is characterized by the features of claim 9, in particular of claims 9 and 10.

The use of radiation measurements allows for quick and non-invasive measurements. Light measurement is particularly suitable for this, even more so, for example, those images which are comparable to the corresponding images of a known sample are immediately recorded and analyzed. By recording the relevant measurements of such known samples, such as color, median, X-irradiation, etc., or a combination thereof, as an overall image in a databank, from the expected pattern for each receiving cavity Can be established through mere comparison of an unknown sample to such a known image, which provides an indication as to the results of a particular serological test. As a result, in parallel with the serologic test, such as a control test, such as a measurement of the acidity of the sample or a serologic test value or other non-serologic test values that can affect at least the interpretation thereof, It is considered that reference tests can be performed.

The advantage that by supplementing the databank with a reference image taken from a sample that is known as far as the relevant value is concerned, that is to say a self-learning system is obtained which always links the sample to a serologically optimal test I will provide a. The use of an algorithm for a suitable computing device for this offers the advantage that it is possible in a particularly simple and automatic manner.

In a further preferred embodiment, the method according to the invention is characterized by the features of claim 11.

By serologically testing a large number of separate samples simultaneously, the diversity of a sample can be tested in a relatively short time for a number of aspects, while the samples are being run in parallel and / or serially. Can be tested. The advantage achieved in this way is that the test is performed quickly, preferably online, on a number of variables. The results can be fed directly to a meat processing device to coordinate further processing.

The invention further relates to an apparatus for on-line serological testing of a sample, such as a blood sample, characterized by the features of claim 12.

Such a device allows for on-line serological testing for sample diversity in a simple manner in a fast, efficient and accurate manner and in a relatively short time. Further, the apparatus allows for processing of each of the multiple sub-samples with the first processing medium, and subsequently distributing them to multiple receiving cavities, while pre-processing the second processing medium in each receiving cavity. Can be added to the sample. As a result, for each receiving cavity, it can be determined which combination of the subsample, the first pretreatment medium and the second pretreatment medium is included. This means providing in a simple manner the possibility of performing different serological tests in each receiving cavity, optionally starting from the same sample. In this way, a diagram of the diversity of different sample values is obtained at the same time. Further, the device of the present invention allows for the proper and accurate addition of samples, subsamples, first and second processing media, and as a result of this means for analyzing the contents of the filled receiving cavity. Alternatively, absolute or relative measurements that can be compared to previously performed serological tests can be selectively represented. The use of the device according to the invention therefore offers a high reproducibility.

In a first advantageous embodiment, the device according to the invention is characterized by the features of claim 14, in particular by the features of claims 14 and 15.

Preferably, prior to inserting the relevant portion of the sub-sample into each receiving cavity, providing a second (and any additional) processing medium allows the receiving cavity to be separated from the device, optionally before the test cycle. This provides the advantage of being able to be prepared by This allows for a quick and efficient treatment, especially when the receiving cavity is housed in a replaceable unit. Providing a second processing medium in the coating-like receiving cavity allows the second (and any further) processing medium to be fixedly connected to the receiving cavity and deliberately detached therefrom. it can. In addition, this provides a suitable bond between the coating and the sample-derived element maintained from the relevant portion of the processed sub-sample in the receiving cavity, for example, even during a subsequent subsequent rinse. Each of the receiving cavities may include a special second processing medium, for example, an antigen or antibody specific for serologic tests performed in the at least partially associated receiving cavities.

In a further aspect, the device according to the invention is characterized by the features of claim 16.

The use of a matrix plate provided with receiving cavities offers the advantage of easy exchangeability and processability, while the receiving cavities always have a fixed position relative to each other. By using a second pick-up means, which can introduce the pretreated sub-samples into different receiving cavities via a spreading motion, a relatively small receiving cavity can be easily filled with the correct amount of sub-samples. At the same time, one flow movement can, for example, fill a column of receiving cavities. In this connection,
"Applying motion" refers to at least one receiving cavity or at a distance such that at least a portion of the sample present flows to or through the receiving cavity over at least the associated second pickup portion. It should be understood to include the relative movement of the pickup portion along it. During the application movement, the distance between the second pick-up means and the receiving cavity is preferably slightly greater than 0 mm, so that direct contact is avoided and contamination is prevented.

The present invention further relates to a matrix plate, in particular a matrix plate according to claim 25, which is suitable for use in the method or the device according to the invention.

In this context, a “matrix plate” refers to a multiple series and columns of receiving locations, in particular a portion of the sample and preferably one or more processing media to be tested in or on each receiving location during use. It is to be understood that a receiving cavity is provided for receiving a fixed amount of the mixture, while at the same time the position of the respective receiving position on the carrier is determined, and that the carrier is clearly fixed. Furthermore, the advantage is achieved that the arrangement and addition can be performed in a quick and simple manner. By providing at least a large number of receiving locations, especially in the receiving cavity containing the processing medium for the mixture contained in the relevant cavity, their addition is easily possible while at the same time the relevant serum is used before the matrix plate is used. The advantage is that relatively large samples can be processed relatively quickly because they can be prepared for biological testing.

In an advantageous embodiment, the matrix plate according to the invention is characterized by the features of claim 26.

Providing the processing medium in or on a number of receiving locations of the matrix plate provides the advantage of fixedly binding the relevant processing medium to the matrix plate as a coating, which is advantageous for the use of the matrix plate and The advantage of simplifying the process, while at the same time providing at least a portion of the coating derived from the mixture arranged in or on the receiving location, suitably for further processing, such as a buffer, a rinsing medium, etc. I will provide a. By providing different receiving cavities containing different processing media, the matrix plate of the present invention allows multiple tests, particularly serologic tests, to be performed simultaneously on a single matrix plate while still providing different test results. It achieves the advantage that it can be made available quickly.

The present invention further relates to an analyzer according to claim 28.

Such an analyzer has the advantage that a diagram of the test results of a series of receptive positions, ie the sequence of the tests performed, can be obtained at the same time, this result being simply compared with the test results of a known sample. can do. Preferably, the results of all tests performed are analyzed simultaneously and can be compared to the results of known samples. In this regard, non-invasive analytical methods have the advantage of being free of contamination by the sample, so that interim cleaning can be omitted.

The invention further relates to a method for processing meat products according to claim 30.

Testing samples online from animals sacrificed or to be sacrificed can be done relatively quickly, for example, within 70 minutes, preferably 45 minutes
Within minutes, and more particularly within 30 minutes, and in a preferred embodiment within 2 minutes of the sample being taken, while at the same time providing a good, clear definition between the sample, animal and test results. Maintain good associations. In this way, an optimal slaughter and further processing route can be established for each animal.

The present invention further relates to a processing medium according to claim 32.

The use of a treatment comprising at least two specific conjugates allows a sample treated with this treatment medium to be used for at least two specific tests, in particular serologic tests, each conjugate being tested. It has the advantage of being specific.

To clarify the present invention, exemplary embodiments of the method and apparatus of the present invention will now be further described with reference to the accompanying drawings.

In the description of this drawing, corresponding parts have corresponding reference numerals.

FIG. 1 schematically shows a top plan view of an apparatus for serologically and on-line testing of a sample such as a blood sample according to the invention. The device 1 comprises a supply means 2 for supplying a container 3 each containing a sample 4, a pre-holding means 5, a first holding means 6 and a second holding means 7, and an analyzing means 8, which comprises: We'll look at everything further.

Each container 3 contains a sample 4, for example blood taken from a human or animal, which can be identified and tracked for the individual or human concerned.
The front-retaining means 5 comprises a substantially cubic shaped block 9 lowered into bearings 12 for rotation about an axis 11 extending through the centers of two end faces 10 located on opposite sides. (FIG. 2). The other four sides 13
Are each provided with a receiving cavity 14 which is slightly cup-shaped and has, for example, an annular circumference. By means of a drive 15, for example a stepper motor and suitable coupling means, the block 9 can be rotated about the axis 11 such that in each case the front receiving cavity extends horizontally and overlaps the plane 16. To this end, the block can be rotated 90 ° or a multiple thereof each time. Further, the driving means 15
For reasons which will be described further below, they are arranged to be able to move back-and-forward to some extent at a relatively small angle from the indicated center position.

The first holding means likewise comprises a cubic shaped block 17 lowered on the bearing 12 for rotation about a second axis of rotation 19 extending through two opposite end faces 18. (FIG. 2). The other four side faces 21 each have a main direction which is located substantially parallel to the axis 19, for example, in a slightly concave top view, and each has a central axis 24 (of this (A central axis extends at right angles to the axis 19) is provided a five-grooved first receiving cavity 22 having a first end 23 disposed adjacent thereto. Successively, first, third and fifth first receiving cavities 22 are provided at the first end 2 located next to the first end face 18A.
5A, and the second and fourth first receiving cavities 22 have a second end 25B located adjacent the opposite second end face 18B. Adjacent to the first end 23, the first receiving cavity has a greater depth than the adjacent second end. As a result, the liquid inserted next to the second end flows in the direction of the first end of the associated first receiving cavity,
The advantages are described below.

The second holding means 7 comprises a plate portion 26 provided with a number of series R of receiving cavities 27 and a column K having a relatively small volume, for example a few μl or ml. Each receiving cavity is substantially in the shape of a cup, as can be seen in particular in FIGS. The second holding means 7 in the form of a matrix plate may be of a disposable type or may be reused after cleaning. The matrix plate 7 and the receiving cavities 27 are described further below.

The analysis means 28 is designed for analyzing the contents of at least one, preferably more, in particular all the filled receiving cavities 27 in the matrix plate 7. To that end, the analysis means 8 preferably comprises a so-called CCD camera (“charge-coupled device”), whereby in each case at least one of the receiving cavities 27
One row and / or column image can be taken, and preferably all of the receiving cavities 27 can be recorded at the same time, and the recording (s) can be further analyzed in the manner described below. it can.

Adjacent to the supply means 2 is provided a front-pickup means 28 comprising a suction needle 30 mounted on a movable arm 29, which needle of the container 3 for picking up an amount of the sample 4. Into which the filled needle 30 can be pivoted by the arm 29 to a position above the pre-receiving cavity 14, where the picked-up sample is dispensed from the needle 30 and the pre-receiving cavity Received at 14. The needle 30 can then be swiveled away and rinsed, after which it is ready to pick up a new sample from the next container 3. This needle 30 will be described in a more preferred manner with reference to FIGS. 8A-D.

Next to the front pick-up means 28, a sample partially filled in the front-receiving cavity 14,
On an arm 32 which can be moved over the pre-reception cavity 14 for inserting an amount of pretreatment medium, for example a solvent and / or blood anticoagulant (if it has not already been added to the sample during the blood draw). A pre-addition means 31 comprising an addition needle 33 attached to the front end. By driving the drive means 15 in the manner described above, the mixing block 9 makes a backward-and-forward movement through the slight angle, and a proper mixing of the sample in the receiving cavity 14 with the pretreatment medium. Is obtained. Needle 33 is used only for the pretreatment medium, so there is no need to rinse this needle.

Instead of using the pre-addition means 31, one or each pretreatment medium can also be introduced into the pre-receiving cavity 14 via the needle 30, rinsing the needle 30 and its supply passage directly. .

Next to the pre-addition means 31, a pick-up needle 36 (the number of the pick-up needles corresponds to the column K of the receiving cavity 27 on the second holding means 7) mounted on the movable arm 35. A first pick-up means 34 is provided. In the embodiment shown, five pickup needles 36 are provided and arranged in rows having a pattern corresponding to the pattern of the first receiving cavities 22 on the first holding means 6. With the pick-up needle 36, five sub-samples can be taken from the anterior-receiving cavity 14, which can be dispensed to the first end 23 of the first receiving cavity 22 (FIG. 5).
B). The pickup needles 36 are then swiveled away and cleaned so they are ready to be used for the next sample.

Next to the first pick-up means 34, it comprises an addition needle 39 mounted on a movable arm 38 and in a pattern corresponding to the position of the second end 25 A, 25 B of the first receiving cavity 22. An arranged first addition means 37 is provided. With five dosing needles 39, a first processing medium can be added to each subsample received in the associated receiving cavity (FIG. 5A), but a first processing introduced into a separate first receiving cavity 22. The media may be different from each other. Each first processing medium can include, for example, one or more conjugates, the purpose of which will be further described. The arrangement of the addition needles 39 prevents such needles from coming into contact with the sample, ie prevents contamination.

By the driving of the second driving means 40, the first holding means 6 is driven around the axis 19 by the backward and forward movements according to the above-mentioned backward- and forward movements of the front-holding means 5. obtain. Due to this backward-and-forward oscillating movement, the sub-samples that flowed together at the first end of the first receiving cavity 22 and the first added to these sub-samples
Proper mixing with the processing medium is obtained. Advantageously, the first receiving cavity 22 inclined downwards towards the first end 23 allows at least the processing medium to be introduced into the first receiving cavity 22 in a simple manner without the addition needle 39 contacting the sub-sample. This eliminates the need for cleaning the associated addition needle 39 after each addition. The relatively deep first ends 23 provide the advantage that the suction of the mixture from each first receiving cavity 22 can be made easier in this way.

Next to the first addition means 37, there is provided a second pickup means 41 mounted on the movable arm 42 and comprising a second pickup needle 43 in which the needles are arranged substantially linearly. However, the second pickup needles 43 are distributed along the first end 23 of the first receiving cavity 22. By means of the second pick-up needle 43, the quantity of the mixture of the sub-sample and the associated first processing medium, preferably measured correctly, is picked up from each first receiving cavity 22 and the receiving cavity 27 on the second holding means 7 (FIG. 5B). The procedure for this is as follows.

The second pickup needles 43 filled with the amount of the mixture of the sub-sample and the first processing medium are opened in such a way that each second pickup needle 43 is located at the beginning of the column of the receiving cavity 27. The distal end 44 is moved to a position above the surface 45 of the plate-shaped second holding means 7. Next, five second pickup needles 43 are moved to the positions shown in FIG.
It is moved in a direction parallel to the upper surface 45 and parallel to the column 45 as indicated by the arrow P in FIGS. Since the distance between the free end 44 of the needle 43 and the upper surface 45 of the matrix plate 7 is relatively small, the mixture of sub-samples and processing medium is filled such that the receiving cavity is completely filled as shown in FIG. Receiving cavity 2 from associated needle 43
7 would be extruded through application. The application movement of the needle 43, in particular the mixture, entails the risk of air bubbles entering the associated receiving cavity 27 (so that one or more receiving cavities 27 cannot be filled or not completely filled). Of the receiving cavity 27 is filled with an appropriate addition volume. Thus, a relatively small receiving cavity can be filled in a suitable manner regardless of the tension of the liquid.

As shown in more detail in FIG. 4, at least some, and preferably all, receiving cavities 27 are provided with a second processing medium in the form of a coating 44 on which the sub-samples and the first A mixture of processing media 45 is provided. In a general sense, the coating 44 in question is arranged for reaction with at least one component present in the mixture 45, this component being, for example, an antigen, antibody, serum or antibody, such as for a customary Elisa test. It can be said that serum, enzymes and the like are sufficient. The different receiving cavities 27 on the matrix plate 7 each have a specific coating 4
4, but the receiving cavities 27 of different columns K and / or rows R can have the same or different coatings 44. Therefore, in each receiving cavity 27 there is always the same sub-sample, a specific first processing medium and a specific second processing medium.
A special combination of a mixture of processing media (ie, coatings 44) is formed. Thus, a specific reaction occurs in each receiving cavity 27, which will indicate the presence of a component that is specifically detected in the subsample. As an illustration, a matrix plate 7 with 5 columns K and 5 rows R, ie 25 receiving cavities 27
Thus, at least 25 different detections can occur in principle in one operation. Through a specific combination of the active ingredient, in particular the various conjugates in each first processing medium and its adjusted coating 44 in each receiving cavity 27 in the column K covered by the associated dosing needle 43, the same mixture 45 Thereby, a different test can be performed in each column K more easily.

After filling the different receiving cavities 27 with the relevant mixture 45, the matrix plate is treated in the same known and customary manner, for example by rinsing with a buffer and further treated with a medium, after which the matrix plate 7 is treated. Exposure to analysis means 8. As mentioned, the analyzing means 8 preferably comprises a CCD camera, whereby a record of all receiving cavities 27 can be made at once. The analysis means 8 is connected to a computer, such as a computer 46, where records can be created and analyzed.
To this end, the computer 46 is provided with an algorithm for comparing the record with a standardized record stored in a data bank of the computer 46. Since each of the standardized records is made with samples of known composition, such records are referred to to know which components were included and which were not in the relevant samples. Based on the comparisons thus made by the algorithm, it is possible to establish at a time what components were present in sample 4 and, if appropriate, their extent, and to make this determination, for example, of the human or animal taken from which the relevant sample was taken. It can be used, for example, for medical procedures, slaughter, etc. to determine the processing route. Indeed, of course, it is also possible to apply other types of analytical means 8 known per se, while at the same time per receiving cavity 27 or per row R or column of receiving cavity 27 for further comparison by the algorithm. It is also possible to create one record for each K.

Using the first driving means 15 and the second driving means 40, respectively, the blocks 9 and 17 in addition to the back-and-forward movements have a 90 ° angle around their respective axes of rotation 11 and 19. You can also rotate through. That is, the next series of pre-reception cavities 14 and the first reception cavities 22 are in each case in overlapping horizontal positions, while the pre-reception cavities 14 respectively filled with the sample or mixture used.
Alternatively, the first receiving cavity 22 rotates toward a vertical side. Block 9 is followed by a first spray nozzle 47, and block 17 is followed by a second spray nozzle 48, both spray nozzles being connected to a pressurizing means 49 for spraying the cleaning medium, This allows the front-receiving cavity 14 and the first receiving cavity 22 to be rinsed against the side of the respective block 9, 17 facing the associated spray nozzle 47, 48 respectively to clean it. . More preferably, a third spray nozzle 49 is arranged adjacent to the bottom side of block 9 and a fourth spray nozzle 50
Are arranged adjacent to the bottom side of the block 17 and the spray nozzles 49 and 50
In order to dry the front receiving cavity 14 and the first receiving cavity 22 located on the bottom surface, respectively, it is connected to a second pressing means 51 for blowing air against the bottom surface of the blocks 9 and 17. It is always cleaned during use, and a series of dried pre-receiving cavities 14 or first receiving cavities 22 can be rotated to the top for use, which is then automatically cleaned and dried. , For this purpose, 2
This means that one block 9, 17 always rotates 90 ° in the same direction.

The device 1 can be controlled by a computer 46. To do this,
Driving means 15 and 40, supply means 2, front-pickup means 28, front-addition means 31, first pickup means 34, first addition means 37, second pickup means 41, first pressurization means 49 and second addition means. The drive means 52 for the pressure means 51 is connected to a computer 46 designed for control. Further, the processing of the matrix plate 7 and the control of the analyzing means 8 can be controlled by the computer 46.

FIG. 3 shows a cross section of the matrix plate 7, showing the receiving cavities 27 of each column K. Included between the columns K of the receiving cavities 27 are ribs 53, whereby during the filling of the receiving cavities 27 by the application means, one mixture 45 of the columns K
From mixing with one mixture of another column K. FIG. 3A shows another embodiment in which grooves 54 are provided instead of ribs 53, while in the embodiment shown in FIG.
Seven juxtaposed columns K are arranged at different heights. In the latter two embodiments, the mixture 45 in one column K is effectively prevented from being mixed with the mixture 45 in the adjacent column K.

With the device according to the invention, a large number of samples can be automatically analyzed at a relatively high speed and in a relatively short time, which makes it possible to analyze the samples in a (semi) continuous manner. Shall be remarkably suitable for

In the device 1 according to the invention, the or each second processing medium and / or the further processing medium is placed in the receiving cavity 27 on the matrix plate by a further adding means 27, not shown in the drawing, but in the receiving cavity on the matrix plate. 27 can be inserted. For this purpose, the outlet openings can be provided in a pattern corresponding to the pattern of the receiving cavities 27, the outlet openings being individually controllable, for example, by a computer 46. In another embodiment, the additional loading means comprises a further series of loading needles movable on the matrix plate 7, at least a series and / or column of receiving cavities 27, parallel to, perpendicular to direction P shown in FIG. 6B, or At the same time comprising the various angles, the associated second or further processing medium can be inserted into the receiving cavity 27, preferably by the application movement described for the second pick-up means 41. In this way, any desired combination of mixture 45, second processing medium and optionally further processing medium can be obtained.

FIG. 7 schematically shows an advantageous arrangement of the addition means, which is particularly suitable for adding a substrate to the cavities 27 in the matrix plate 7. Preferably, a number of such loading devices are arranged in the matrix plate 7 in a matrix corresponding to the RxC matrix. The dosing device 60 of the present invention comprises a chamber 61 having a bottom 62 and a top surface 63. Extending through the bottom 62 is a hollow needle 64 having a chamfered first end 65 located outside the chamber and a second end 66 located on the bottom 62 at a distance B within the chamber. Furthermore, this supply opening 68, in which the drainage line 67 passes through the bottom 62 and is located in the chamber, is located on the bottom 62 at a distance S, which is at least shorter than the distance D and may be zero. Upper surface 6
Extending into the chamber through 3 is an exhaust line 69 and a vent line 7
0, which is relatively larger than the sections of the exhaust line 69, the needle 64, and the drainage line 67. The vent line 70 is provided with a valve 71, which can close or open the vent line. Drainage line 67 is provided with shut-off means, in particular pumping means (not shown in the drawings) for draining liquid through the drainage line, as will be described in more detail below. Connected to the vent line 69 are suction means (not shown in the drawings), the purpose of which will be described in more detail hereinafter.

The device 60 of FIG. 7 can be used as follows.

The first end 65 of the needle 64 is located in a liquid that is picked up in a container 72 as shown in FIG. 7A. Next, when valve 71 and drain line 67 are closed and air is exhausted from chamber 61 through exhaust line 69, FIGS.
Liquid is drawn into the chamber via the needle 64 as shown in FIG. When the drain line 67 is closed, the liquid level in the chamber 61 is set to the needle 6 as shown in FIG. 7D.
4 can be raised above the second end 66. The evacuation means is then turned off and when the drain line 67 is opened, the liquid flows out of the chamber 61, as shown in FIG. 7E, and possibly by suitable pump means. Drain line 67
The drainage of liquid through will end when the liquid level in the chamber is flowed at the supply opening 68 as shown in FIG. 7F. During such steps 7A-7F, the first end 65 of the needle 64 is maintained in the liquid in the container 72. The first end 65 of the needle 64 then moves into the cavity 27 of the matrix plate 7 in such a way that the bottom of the cavity 27 is less contacted as shown in FIG. 7G. The valve 7 is then opened and relatively more air is relatively quickly introduced into the chamber 61 via the vent line 70, while the exhaust line 69 and the drain line 67 are closed. During the discharge of the liquid from the chamber 61, the liquid that was behind in the needle 64 is pushed out of the needle 64 into the cavity 27 by air pressure, as shown in FIG. 7H, as shown in FIGS. 7E and 7F. Here, the chamfered end 65 of the needle 64 has the advantage of flushing air from the cavity 27 so as to prevent air bubbles from forming in the cavity 27. In this manner, splashing of the liquid, mixing of the cavity into the environment, and the like are easily prevented, and at the same time, the liquid is removed from the cavity 2.
7 can be introduced relatively quickly. When the cavity 27 is completely filled, the needle 6
4 can be pulled slightly upward and blow air from the chamber through the space between the opening in the hollow end 65 of the needle and the upper surface of the matrix plate 7 without affecting the liquid in the cavity. You can leave.

The device according to FIG. 7 has the advantage of allowing particularly precise dosing in a particularly simple manner, since the same amount of liquid always remains behind the needle 64. Thus, this amount of liquid is the amount to be added, which is always equal. Therefore, the internal volume of the needle is the added amount and can be accurately adjusted to the internal volume of the cavity 27. Moreover, such devices can be easily applied without the need for complex systems such as pistons, valves and the like. An advantage achieved by arranging such an addition device in the matrix according to the cavities 27 of the matrix plate 7 is that each cavity 27 can be supplied with exactly the desired amount of processing medium, such as a substrate, in one operation.

FIGS. 8A-D show a particularly suitable pickup and dosing device for picking up a sample such as blood, optionally with the addition of a pretreatment medium, such as a solvent, to the pre-holding means 5. . The dosing device is described as pre-pickup and pre-dosing means.

The front-pickup means 28 comprises a hollow needle 30 provided with a chamfered first open end 80 as previously described. Provided around the free end of the needle 30 is a sleeve-shaped jacket 81, closed at its upper end 82. For example, a bottom end 83 flush with the top of the open end 80 of the needle 30 is open to the bottom. Since the jacket 81 preferably sandwiches the needle, no air or liquid can pass upwardly between the jacket 81 and the needle 30. Such a device can be used, for example, as follows.

The needle 30 with the jacket 81 moves into the liquid 84 in the container 85 as illustrated in FIG. 8 where the liquid is obliquely parallel and shaded. Jacket 81 and needle 3
Since 0 is closed, air is trapped in the needle and in the needle and jacket 81 when introduced into the liquid. This prevents liquid from entering the closed space 86 between the needle 30 and the jacket 81 (FIG. 8B). Next, a volume of liquid 84 is withdrawn into the needle (FIG. 8C). Here, needle 30 is withdrawn from the liquid, along with jacket 81, while liquid 84 remains behind needle 30 (FIG. 8D). Since no liquid enters the space 86, mixing outside the needle 30 is prevented in a simple manner,
In addition, liquid 84 is prevented from being carried over the outside of the needle and is dispensed unintentionally. Thus, with such a device, the addition can be carried out particularly accurately. In practice, the amount added is completely determined by the amount of liquid taken up in the needle 30. A further advantage is that such an addition device can be maintained and cleaned in a particularly simple manner. In order to dispense the liquid 84 from the needle 30, the jacket 81 is preferably pulled over the needle 30, which prevents any liquid that may be entrained along the jacket 81 during the addition. To this end, the jacket 81 can be mounted, for example, on a needle 30 so that it can slide in a simple manner. Jacket 81 can also be designed to replace its top surface. Numerous changes that are readily apparent to those skilled in the art are possible in this regard.

Those skilled in the art will appreciate that the processing medium (s), such as a substrate, after the necessary steps, such as washing,
Is added to the cavity of the matrix plate 7, it will be immediately understood that different further steps, usually including washing steps, coloring steps, incubation steps, etc., are carried out before the matrix is subjected to analytical means. .

It will be appreciated that many modifications are possible. For example, the front holding block and / or
Alternatively, the first holding means may be of a different design, for example having a triangular or polygonal cross section perpendicular to the axis of rotation 11 or 14, while at the same time one or more series of front-receiving cavities or first receiving cavities on each side. Can be included. Series R of the second holding means 7
And / or the number of columns K can be adjusted depending on, for example, the number of tests to be performed and the possible combinations of processing media used, in particular the mixture of conjugates, but the first receiving cavity on the first holding means Can be adjusted to the number of columns K. The means for cleaning and drying the different receiving cavities can be designed in various suitable ways, for example as contact-cleaning means. Also, instead of the driving means, other means can be used to set the oscillations of the blocks 9 and 17, but additionally stirring means etc. can be used to mix the sample and sub-sample with the various treatment media. Is also good. Still other pickup means and addition means can be applied to transport between different phases during processing of samples, subsamples and mixtures. Also, the supply means and the pre-holding means, the pre-processing means and the first holding means, the first holding means and the second
Additional processing means can be provided for adding additional processing media such as, for example, anticoagulants, solvents, buffer means, reagents, etc. between the holding means and / or the second holding means and the analysis means.

[Brief description of the drawings]

FIG. 1 schematically shows a top plan view of the device of the invention.

2 schematically shows the device of FIG. 1 from the side.

FIG. 3 shows a front sectional view of the matrix plate taken from line III-III in FIG. 1;

3A and 3B show, in a side section taken from line III-III in FIG.
2 represents two alternative embodiments.

FIG. 4 shows the receiving cavity of the matrix plate in an enlarged side section taken from line III-III in FIG. 1;

5A is a top plan view of FIG. 2 showing the position of the sample transport means.

5B is a top plan view of FIG. 2 showing the location of the receiving means for the sample mixed with the conjugate.

FIG. 6A is a top plan view showing the addition means for inserting the sample / conjugate mixture into the receiving cavity of the matrix plate.

FIG. 6B is a side cross-section taken from line VIB-VIB of FIG. 6A, depicting the means during insertion of the mixture into the receiving cavity.

7A-I schematically show devices for addition to specific substrates.

8A-D schematically show devices for picking up and adding liquids.

[Procedural Amendment] Submission of translation of Article 34 Amendment of the Patent Cooperation Treaty

[Submission date] February 1, 2000 (2000.2.1)

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] Full text

[Correction method] Change

[Correction contents]

Title: Method and apparatus for on-line test samples

[Claims]

1. A device for sample testing serologically the online such as blood; - several sub-sample from the sample to be tested, preferably for picking up at least two sub-samples First pickup means; first holding means for storing subsamples carried by the first pickup means; first addition means for adding a first processing medium to each subsample in the first holding means; First mixing means for mixing the or each subsample with an associated first processing medium added thereto; second pickup means for separately picking up each subsample from the first holding means; -Second holding means for separately storing the processed sub-samples carried therein by the second pick-up means; Said second holding means comprising a predetermined number of rows and columns of cavities, preferably a matrix of receiving cavities; a second pick-up means, for supplying the relevant picked-up pretreatment subsamples to separate columns of the receiving cavities. And means arranged for distributing them therein; means are provided for adding a second processing medium to the relevant portion of the processed subsample in the receiving cavity; and Means for analyzing at least some, and preferably all, of the contents.

2. Pre-pickup means for picking up samples from a sample stock;-Pre-holding means for samples carried therein by the pre-pickup means;-Samples in the pre-holding means. Pre-adding means for adding the pre-treatment medium to the sample; pre-mixing means for mixing the sample with the pre-treatment medium; wherein the first pickup means picks up the sub-sample from the pre-holding means. The device of claim 1, wherein the device is arranged to:

3. A method according to claim 1, wherein a second processing medium is provided in at least some or preferably each of the receiving cavities, preferably prior to introducing a part of the subsample associated therewith. 3. The device according to 2.

4. Apparatus according to claim 3, wherein some, preferably each, receiving cavity to be filled is coated with at least a second processing medium.

5. The receiving cavity is contained in at least one plate part, preferably a matrix plate, and the second pick-up means has associated pre-treatment by movement of the or each surface of the associated plate part. 5. A method according to claim 1, wherein the subsample is arranged to transfer a portion of the subsample to a receiving cavity.
The device according to item.

6. The front-holding means comprises at least one of the front-mixing blocks.
Wherein the front-mixing means comprises: a front-mixing block which is swiveled relative to each other at a relatively small first angle; or a front-mixing block which is relatively large. Apparatus according to any one of the preceding claims, wherein the apparatus is arranged to selectively tilt in one direction at an angle about a substantially horizontally arranged axis of rotation.

7. The front-mixing block is provided with at least two, preferably on all sides, a front-mixing cavity, the front-pickup means for supplying the sample at least temporarily to the front-mixing cavity. 7. The apparatus according to claim 6, wherein the cleaning means is arranged for carrying, in particular, cleaning the or each pre-mixing cavity at least partially simultaneously.

8. The method of claim 1, wherein the first holding means comprises a series of first mixing cavities, and wherein the first mixing means comprises vibration means for providing vibration to the first mixing cavities. The apparatus according to claim 1.

9. Apparatus according to claim 8, wherein the first pick-up means comprises a series of pick-up elements arranged at interrelated positions corresponding to the positions of the first series of mixing cavities.

10. Apparatus according to claim 9, wherein the pick-up elements are arranged in rows corresponding to the positions of the receiving cavities in the rows in the second holding means.

11. A series of first mixing cavity is included in at least one side of the first mixing block, wherein in the first mixing means - or pivoted to each other at a relatively small first angle of the first mixing block Or tilting the first mixing block in one direction at a relatively large second angle about a substantially horizontally arranged axis of rotation. An apparatus according to claim 1.

12. The first mixing block is provided with a series of first mixing cavities on at least two, preferably all sides, wherein the first pickup means disposes the sub-samples at least temporarily in a first upward direction. 12. The arrangement according to claim 11, arranged for carrying into one mixing cavity, wherein the cleaning means is provided for at least partially simultaneously treating, in particular cleaning, the or each further series of first mixing cavities. Equipment.

13. A first mixing cavity has a bottom surfaces inclined and slightly larger internal volume than the volume of the sub-sample is delivered therein, the first addition means each next to the highest end of the bottom surface 13. A method as claimed in any one of claims 6 to 12, wherein the associated first processing medium is arranged to deliver at a horizontal and vertical distance from the processed subsample contained in the associated first mixing cavity. Equipment.

14. A matrix plate particularly suitable for use in an apparatus according to any one of claims 1 to 13, comprising a matrix of a receiving cavity, wherein the sample or sample is introduced into the receiving cavity. At least some receiving cavities comprising a processing medium for some of them are provided, in at least some of the receiving cavity columns, in the associated receiving cavity column, at least one other receiving cavity processing medium. The matrix plate as described above, wherein at least one receiving cavity is provided which is coated with a different processing medium.

15. Apparatus according to any one of the preceding claims, wherein the method is for processing meat products, wherein the processed meat products such as carcasses or parts thereof are continuously supplied. A blood sample is taken from at least some, and preferably each, of the meat products to be supplied, and is serologically tested, at least in part based on the measurements found by the analytical method used. The above processing method in which it is determined whether or not each meat product is further processed.

16. A meat processing device comprising a device according to any one of claims 1 to 13 and comprising means for continuously supplying a meat product,
A pick-up means is arranged for each sample of body fluid from the supplied meat product, preferably each time blood is drawn, and a device is arranged for serological testing of each of the collected samples, wherein the discharge for the meat product is performed. A meat processing apparatus as described above, wherein control means are provided for controlling the means and the discharge means based on the serological test results.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to an apparatus for serologically testing a sample such as blood.

For example, in the meat processing industry, it is very important to be able to determine whether an animal processing meat meets general health standards, at least during feeding, lactation and / or slaughter. To that end, for example, blood or other body fluids of the animal are serologically tested, for example, to demonstrate their bacterial or viral infection. It is known to perform such tests by drawing blood from live animals, which blood is accurately examined in the laboratory. The blood sample is divided into a number of different parts, each of which is subjected to a special serological test. The results found are combined and the health of the animal in question is determined based on it. Such data is returned to the farm where the animal of interest is located, so that the animal, its same group of animals and / or the same breeding animal at least later for human or animal consumption can be slaughtered, Or not served.

Furthermore, it is known in the meat processing industry to take a random blood sample from a slaughtered animal, which sample is serologically tested in a laboratory in the manner described above. Based on such data, all batches of meat from a plurality of slaughtered animals are or are not slaughtered for human or animal consumption at least later.

In such a known method, in each case the sample is sent to a laboratory, where the various serologic tests are performed by different humans, at least at different stages and by different means. This is expensive, time consuming, and inefficient. There is also a risk of losing the direct link between the animal from which the sample was taken and the test results.
In addition, the animal in question will often be further processed before the relevant results are fully available. In addition, testing live animal samples carries the risk that such samples are no longer quite accurate at slaughter.

[0005] Hospitals, blood banks and the like test (blood) samples in a similar manner.

[0006] It is thus an object of the present invention to provide a device of the kind described in the introduction, which avoids the stated disadvantages of the known method, while retaining their advantages. You. For this purpose, the device according to the invention is characterized by the features of claim 1.

[0007] Such a device makes it possible to carry out on-line serological tests for sample diversity in a simple manner in a fast, efficient and accurate manner and in a relatively short time. Further, the apparatus allows for processing of each of the multiple sub-samples with the first processing medium, and subsequently distributing them to multiple receiving cavities, while pre-processing the second processing medium in each receiving cavity. Can be added to the sample. As a result, for each receiving cavity, it can be determined which combination of the subsample, the first pretreatment medium and the second pretreatment medium is included. This means providing in a simple manner the possibility of performing different serological tests in each receiving cavity, optionally starting from the same sample. In this way, a diagram of the diversity of different sample values is obtained at the same time. Further, the device of the present invention allows for the proper and accurate addition of samples, subsamples, first and second processing media, and as a result of this means for analyzing the contents of the filled receiving cavity. Alternatively, absolute or relative measurements that can be compared to previously performed serological tests can be selectively represented. The use of the device according to the invention therefore offers a high reproducibility.

In a first advantageous embodiment, the device according to the invention has the form of claim 3 , in particular claim 3
And 4 are the features.

Preferably, by providing a second (and any further) processing medium prior to inserting the relevant portion of the sub-sample into each receiving cavity, the receiving cavity may be separated from the device prior to a test cycle. This provides the advantage of being able to be prepared by This allows for a quick and efficient treatment, especially when the receiving cavity is housed in a replaceable unit. Providing a second processing medium in the coating-like receiving cavity allows the second (and any further) processing medium to be fixedly connected to the receiving cavity and deliberately detached therefrom. it can. In addition, this provides a suitable bond between the coating and the sample-derived element maintained from the relevant portion of the processed sub-sample in the receiving cavity, for example, even during a subsequent subsequent rinse. Each of the receiving cavities may include a special second processing medium, for example, an antigen or antibody specific for serologic tests performed in the at least partially associated receiving cavities.

In a further aspect, the device according to the invention is characterized by the features of claim 5 .

The use of a matrix plate provided with receiving cavities offers the advantage of easy exchangeability and processability, while the receiving cavities always have a fixed position relative to each other. By using a second pick-up means, which can introduce the pretreated sub-samples into different receiving cavities via a spreading motion, a relatively small receiving cavity can be easily filled with the correct amount of sub-samples. At the same time, one flow movement can, for example, fill a column of receiving cavities. In this connection,
"Applying motion" refers to at least one receiving cavity or at a distance such that at least a portion of the sample present flows to or through the receiving cavity over at least the associated second pickup portion. It should be understood to include the relative movement of the pickup portion along it. During the application movement, the distance between the second pick-up means and the receiving cavity is preferably slightly greater than 0 mm, so that direct contact is avoided and contamination is prevented.

The invention further relates to a matrix plate, in particular a matrix plate according to claim 14 , which is suitable for use in the method or the device of the invention.

In this context, a “matrix plate” refers to a large series of receiving locations and columns, in particular a portion of the sample preferably tested in or on each receiving location during use and one or more processing media. It is to be understood that a receiving cavity is provided for receiving a fixed amount of the mixture, while at the same time the position of the respective receiving position on the carrier is determined and clearly defined carrier. Furthermore, the advantage is achieved that the arrangement and addition can be performed in a quick and simple manner. By providing at least a large number of receiving locations, especially in the receiving cavity containing the processing medium for the mixture contained in the relevant cavity, their addition is easily possible while at the same time the relevant serum is used before the matrix plate is used. The advantage is that relatively large samples can be processed relatively quickly because they can be prepared for biological testing.

[0014] Providing the processing medium in or on a number of receiving locations of the matrix plate provides the advantage of fixedly binding the relevant processing medium to the matrix plate as a coating, which is advantageous for the use of the matrix plate and The advantage of simplifying the process, while at the same time providing at least a portion of the coating derived from the mixture arranged in or on the receiving location, suitably for further processing, such as a buffer, a rinsing medium, etc. I will provide a. By providing different receiving cavities containing different processing media, the matrix plate of the present invention allows multiple tests, particularly serologic tests, to be performed simultaneously on a single matrix plate while still providing different test results. It achieves the advantage that it can be made available quickly.

The invention furthermore relates to a method for processing meat products according to claim 15 .

Testing on-line samples taken from animals that have been or will be sacrificed requires that the test results be relatively quick, eg within 70 minutes, preferably 45 minutes.
Within minutes, and more particularly within 30 minutes, and in a preferred embodiment within 2 minutes of the sample being taken, while at the same time providing a good, clear definition between the sample, animal and test results. Maintain good associations. In this way, an optimal slaughter and further processing route can be established for each animal.

The present invention further relates to a processing medium according to claim 17 .

The use of a treatment comprising at least two specific conjugates allows a sample treated with this treatment medium to be used for at least two specific tests, in particular serologic tests, each conjugate being tested. It has the advantage of being specific.

The present invention also relates to a method according to claim 18 .

Performing serologic tests online provides the advantage that the desired results can be obtained relatively quickly, while maintaining a good connection between the animal from which the sample is taken and the relevant sample to be processed. . Furthermore, a large number of tests can be performed in a rapid and simple manner, while tests on different animals or at least parts thereof can be performed sequentially as well as in parallel. Thus, based on the results found, further processing of the tested meat or treatment of the tested animal can be adjusted. Based on the achievement of a series of parallel, rapid, accurate and relatively inexpensive serological tests, and on the basis of the measurements found, thanks to the precise adjustment of further processing or treatment, humans or animals consuming meat and And / or the health of the tested animals is more effectively protected than before, and if not all animals are sacrificed, not scheduled to be sacrificed or not treated, the serum of many animals is instead Allow immediate examination.

The term “on-line” should be understood to mean at least the testing of a sample, in particular a blood sample taken from an animal or human on site. In this context, "on-site" includes a space suitable for conducting serological tests located some distance from the location where the sample is taken to the space where the collected blood sample is quickly transported. Should be understood. Thus, for example, pneumatic transport can be used for transport, whereby the sample is available for serological testing within minutes.

In the method, a portion of the subsample is introduced into an associated receiving cavity (s) through a smearing movement of a pickup part across one or more receiving cavities. That is, a relatively small receiving cavity can be filled, which is difficult, if not otherwise impossible, to fill due to the surface tension of the subsample. Furthermore, due to the application movement of the pick-up part, an equal amount of subsample is introduced into the associated receiving cavity each time. In fact, the excess is smeared on the upper edge of the receiving cavity by the pick-up part.
f). In each case, it is possible in a particularly simple manner to fill the receiving cavities in exactly the same amount each time, and even with small receiving cavities. In this manner, individual receiving cavities can be filled, but also a matrix of receiving cavities as used by the method of the invention, for example, a series of receiving cavities in a column.

In particular, a relatively small receiving cavity can be filled without problems and without loss of subsamples, and all subsamples from the same subsample are available,
And since it can be used for one or more tests according to the method of the present invention, a particularly small amount of subsample is sufficient and can be used for a wide range of tests. This is particularly advantageous when only a small amount of the sample or medium required for the test is available, or when the sample or processing medium is expensive or dangerous.

The application operation for inserting the sub-samples into different receiving cavities can of course be carried out in different ways and by different means, but the sub-samples may be received in the relevant pick-up part before application. Direct contact between the pick-up part and the receiving cavity is not necessary, as transport already takes place through adhesion. The advantage achieved by avoiding direct bonding is that the pickup part can be used repeatedly, since there is no contamination of the pickup part by at least partially received cavities and vice versa. In fact, different pickup portions may be used for different columns of the receiving cavity or combinations thereof.

In an advantageous embodiment, a relatively large number of serological tests are performed on-line on sub-samples separated from the sample taken. To that end, the separated subsamples are pretreated and introduced into the matrix of the receiving cavities, while different serological reactions occur in different receiving cavities. To this end, different sub-samples are preferably mixed with various first processing media, and the subsequently formed mixture of sub-samples is processed using a different or the same further processing medium. Thus, different receiving cavities of one matrix result in parallel and / or successively different mixtures of subsamples, first and further processing media, resulting in the coupling of various reactions or active ingredients. The subsample in the receiving cavity of the matrix can then be further processed and analyzed, and a complete view of the resulting measurements can be obtained for the animal in question or at least a portion thereof. Each receiving cavity that is filled after the serological test has been completed gives the results of the serological test performed therein, which for each receiving cavity in question in the matrix rows and / or columns. Different tests can be. This allows a simple comparison of this matrix with other known matrices, so that the results found for a number of different tests can be analyzed at once, for example through pattern recognition.

In this context, a “matrix of receiving cavities” should be understood to mean at least a number of columns and rows of receiving cavities, wherein for two or more rows and / or columns, each row And / or the number of receiving cavities in a column may be different from the number of receiving cavities in an adjacent row or column. The location of each receiving cavity in the matrix can be established by a coordinate system (eg, the number of columns and columns of the receiving cavity) in the matrix to further process the measurements. This is possible and whenever relevant, is referred to herein as a series of receiving cavities, where a portion of the same subsample is provided. Thus, when multiple subsamples are processed simultaneously, the separated subsamples can be inserted into different columns of the receiving cavity. However, it is also conceivable that the random distribution of each subsample, ie, not distributed in rows or columns, may be possible. Therefore, depending on the selected coordinate system,
Each subsample can establish a receiving cavity or cavity into which it is inserted.

By using a mixture of at least two conjugates, with at least one as a processing medium, the different sub-samples can be loaded into the various receiving cavities in a column of a matrix of receiving cavities. Special advantages are achieved in that serological tests can be performed. This allows the receiving cavity to be packed in a particularly simple manner, while ensuring a simple manner in which all tests in the column of the selected receiving cavity are performed with identically processed subsamples. , Which allows for better comparisons. In each receiving cavity, for example, a further different processing medium can be added. Also, each receiving cavity of a row of the matrix can for example be further processed with the same processing medium, while the interrelated rows are processed with different processing media. At each receiving cavity, a specific combination of bound or unbound antibodies, antigens, etc. is obtained, which may or may not be labeled with a label detectable by the assay used.

In this context, the term “conjugate” should be understood to mean at least an element, whereby in a serologic test an antigen such as a virus or other foreign substance, or Antibodies specifically raised thereto can be indicated.
In particular, this should be understood to mean a labeled immunoreactant. The sign may consist of at least one or more of the following elements: For example, horseradish peroxidase (HRPO), alkaline phosphatase,
1. enzymes such as urease, glucose oxidase, dehydrogenase, β-D-galactosidase; 2. a fluorescent dye; ^3. Radioactive elements such as H ³ , C ¹⁴ , I ¹³¹ ; 4. biotin; Gold ball 6. 6. carbon spheres; or europium.

[0029] Modifications or alternatives so far will be readily apparent to those skilled in the art.

Coating the matrix of the receiving cavity, preferably with various further processing media such as specific antibodies or antigens, is sufficient to allow the receiving cavity to be pre-treated before performing a series of serological tests. It offers the advantage that processing can be performed under controlled conditions. For a specific series of serologic tests and the like, the matrix plate is always present during the test, since the matrix multiplicity in the receiving cavity, called the matrix plate, can be adjusted in a suitable and well-defined manner. Thus, sequencing of serological tests can be performed at high speed, with high accuracy and reproducibility, and at relatively low cost. Especially when such matrix plates are used in the on-line method of the present invention, the desired number of serologic tests are supplied and unloaded in meat, blood or (semi) continuously in a (semi) continuous process. This provides the advantage that it can be performed on other types of samples.

The term “coating” in this context should be understood to mean at least the elements used for serological tests, whereby antigens such as, for example, viruses or foreign substance types, or Antibodies specifically raised against this, in particular immunoreactants, can be indicated. Such coatings include, for example: 1. Complete virus particles, or specific parts thereof; 2. whole antibodies, or specific parts thereof; 4. peptides; proteins other than those mentioned in 4.1-3; or It consists of residues or combinations thereof.

[0032] Other coatings applicable to the present invention will be readily apparent to those skilled in the art.

By simultaneously submitting the different receiving cavities to an appropriate assay, a complete picture of the serologic test results is obtained, so that, for example, viral or bacterial bias in a sample can be obtained very quickly. . This involves the incorporation of analytical instrument (s), so that multiple matrices of the receiving cavity can be analyzed quickly one after the other, so that non-invasive methods, such as radiometric measurements, are used. It is.

The use of radiation measurements allows for quick and non-invasive measurements. Light measurement is particularly suitable for this, even more so, for example, those images which are comparable to the corresponding images of a known sample are immediately recorded and analyzed. By recording the relevant measurements of such known samples, such as color, median, X-irradiation, etc., or a combination thereof, as an overall image in a databank, from the expected pattern for each receiving cavity Can be established through mere comparison of an unknown sample to such a known image, which provides an indication as to the results of a particular serological test. As a result, in parallel with the serologic test, such as a control test, such as a measurement of the acidity of the sample or a serologic test value or other non-serologic test values that can affect at least the interpretation thereof, It is considered that reference tests can be performed.

The advantage of providing a self-learning system by supplementing the databank with a reference image taken from a sample that is known as far as the relevant value is concerned, ie that the sample is always connected with optimal serological testing I will provide a. The use of an algorithm for a suitable computing device for this offers the advantage that it is possible in a particularly simple and automatic manner.

By serologically testing a large number of separate samples simultaneously, the diversity of a sample can be tested in a relatively short time for a number of aspects, while the samples are being run in parallel and / or serially. Can be tested. The advantage achieved in this way is that the test is performed quickly, preferably online, on a number of variables. The results can be fed directly to a meat processing device to coordinate further processing.

To clarify the present invention, exemplary embodiments of the method and apparatus of the present invention will now be further described with reference to the accompanying drawings.

In the description of the figures, corresponding parts have corresponding reference numerals.

FIG. 1 schematically shows a top plan view of an apparatus for serologically and on-line testing of a sample such as a blood sample according to the invention. The device 1 comprises a supply means 2 for supplying a container 3 each containing a sample 4, a pre-holding means 5, a first holding means 6 and a second holding means 7, and an analyzing means 8, which comprises: We'll look at everything further.

Each container 3 contains a sample 4, for example blood taken from a human or animal, which can be identified and tracked for the individual or human concerned.
The front-retaining means 5 comprises a substantially cubic shaped block 9 lowered into bearings 12 for rotation about an axis 11 extending through the centers of two end faces 10 located on opposite sides. (FIG. 2). The other four sides 13
Are each provided with a receiving cavity 14 which is slightly cup-shaped and has, for example, an annular circumference. By means of a drive 15, for example a stepper motor and suitable coupling means, the block 9 can be rotated about the axis 11 such that in each case the front receiving cavity extends horizontally and overlaps the plane 16. To this end, the block can be rotated 90 ° or a multiple thereof each time. Further, the driving means 15
For reasons which will be described further below, they are arranged to be able to move back-and-forward to some extent at a relatively small angle from the indicated center position.

The first holding means likewise comprises a cubic shaped block 17 lowered on the bearing 12 for rotation about a second axis of rotation 19 extending through two opposite end faces 18. (FIG. 2). The other four side faces 21 each have a main direction which is located substantially parallel to the axis 19, for example, in a slightly concave top view, and each has a central axis 24 (of this (A central axis extends at right angles to the axis 19) is provided a five-grooved first receiving cavity 22 having a first end 23 disposed adjacent thereto. Successively, first, third and fifth first receiving cavities 22 are provided at the first end 2 located next to the first end face 18A.
5A, and the second and fourth first receiving cavities 22 have a second end 25B located adjacent the opposite second end face 18B. Adjacent to the first end 23, the first receiving cavity has a greater depth than the adjacent second end. As a result, the liquid inserted next to the second end flows in the direction of the first end of the associated first receiving cavity,
The advantages are described below.

The second holding means 7 comprises a plate portion 26 provided with a number of series R of receiving cavities 27 and a column K having a relatively small volume, for example a few μl or ml. Each receiving cavity is substantially in the shape of a cup, as can be seen in particular in FIGS. The second holding means 7 in the form of a matrix plate may be of a disposable type or may be reused after cleaning. The matrix plate 7 and the receiving cavities 27 are described further below.

The analysis means 28 is designed for analyzing the contents of at least one, preferably more, in particular all the filled receiving cavities 27 in the matrix plate 7. To that end, the analysis means 8 preferably comprises a so-called CCD camera (“charge-coupled device”), whereby in each case at least one of the receiving cavities 27
One row and / or column image can be taken, and preferably all of the receiving cavities 27 can be recorded at the same time, and the recording (s) can be further analyzed in the manner described below. it can.

Next to the supply means 2, there is provided a front-pickup means 28 comprising a suction needle 30 mounted on a movable arm 29, which needle of the container 3 for picking up an amount of the sample 4. Into which the filled needle 30 can be pivoted by the arm 29 to a position above the pre-receiving cavity 14, where the picked-up sample is dispensed from the needle 30 and the pre-receiving cavity Received at 14. The needle 30 can then be swiveled away and rinsed, after which it is ready to pick up a new sample from the next container 3. This needle 30 will be described in a more preferred manner with reference to FIGS. 8A-D.

Next to the front pick-up means 28, a sample partially filled in the front-receiving cavity 14,
On an arm 32 which can be moved over the pre-reception cavity 14 for inserting an amount of pretreatment medium, for example a solvent and / or blood anticoagulant (if it has not already been added to the sample during the blood draw). A pre-addition means 31 comprising an addition needle 33 attached to the front end. By driving the drive means 15 in the manner described above, the mixing block 9 makes a backward-and-forward movement through the slight angle, and a proper mixing of the sample in the receiving cavity 14 with the pretreatment medium. Is obtained. Needle 33 is used only for the pretreatment medium, so there is no need to rinse this needle.

Instead of using the pre-addition means 31, one or each pretreatment medium can also be introduced into the pre-receiving cavity 14 via the needle 30, rinsing the needle 30 and its supply passage directly. .

Next to the pre-addition means 31, a pickup needle 36 (the number of the pickup needles corresponds to the column K of the receiving cavity 27 on the second holding means 7) mounted on the movable arm 35. A first pickup means 34 is provided. In the embodiment shown, five pickup needles 36 are provided and arranged in rows having a pattern corresponding to the pattern of the first receiving cavities 22 on the first holding means 6. With the pick-up needle 36, five sub-samples can be taken from the anterior-receiving cavity 14, which can be dispensed to the first end 23 of the first receiving cavity 22 (FIG. 5).
B). The pickup needles 36 are then swiveled away and cleaned so they are ready to be used for the next sample.

Next to the first pick-up means 34, it comprises an addition needle 39 mounted on a movable arm 38 and in a pattern corresponding to the position of the second end 25 A, 25 B of the first receiving cavity 22. An arranged first addition means 37 is provided. With five dosing needles 39, a first processing medium can be added to each subsample received in the associated receiving cavity (FIG. 5A), but a first processing introduced into a separate first receiving cavity 22. The media may be different from each other. Each first processing medium can include, for example, one or more conjugates, the purpose of which will be further described. The arrangement of the addition needles 39 prevents such needles from coming into contact with the sample, ie prevents contamination.

By the driving of the second driving means 40, the first holding means 6 is driven around the axis 19 by the backward and forward movements according to the above-mentioned backward and forward movements of the front-holding means 5. obtain. Due to this backward-and-forward oscillating movement, the sub-samples that flowed together at the first end of the first receiving cavity 22 and the first added to these sub-samples
Proper mixing with the processing medium is obtained. Advantageously, the first receiving cavity 22 inclined downwards towards the first end 23 allows at least the processing medium to be introduced into the first receiving cavity 22 in a simple manner without the addition needle 39 contacting the sub-sample. This eliminates the need for cleaning the associated addition needle 39 after each addition. The relatively deep first ends 23 provide the advantage that the suction of the mixture from each first receiving cavity 22 can be made easier in this way.

Next to the first addition means 37, there is provided a second pickup means 41 mounted on the movable arm 42 and comprising a second pickup needle 43 in which the needles are arranged substantially in a straight line. However, the second pickup needles 43 are distributed along the first end 23 of the first receiving cavity 22. By means of the second pick-up needle 43, the quantity of the mixture of the sub-sample and the associated first processing medium, preferably measured correctly, is picked up from each first receiving cavity 22 and the receiving cavity 27 on the second holding means 7 (FIG. 5B). The procedure for this is as follows.

The second pickup needles 43 filled with the amount of the mixture of the sub-sample and the first processing medium are opened in such a way that each second pickup needle 43 is located at the beginning of the column of the receiving cavity 27. The distal end 44 is moved to a position above the surface 45 of the plate-shaped second holding means 7. Next, five second pickup needles 43 are moved to the positions shown in FIG.
It is moved in a direction parallel to the upper surface 45 and parallel to the column 45 as indicated by the arrow P in FIGS. Since the distance between the free end 44 of the needle 43 and the upper surface 45 of the matrix plate 7 is relatively small, the mixture of sub-samples and processing medium is filled such that the receiving cavity is completely filled as shown in FIG. Receiving cavity 2 from associated needle 43
7 would be extruded through application. The application movement of the needle 43, in particular the mixture, entails the risk of air bubbles entering the associated receiving cavity 27 (so that one or more receiving cavities 27 cannot be filled or not completely filled). Of the receiving cavity 27 is filled with an appropriate addition volume. Thus, a relatively small receiving cavity can be filled in a suitable manner regardless of the tension of the liquid.

As shown in more detail in FIG. 4, at least some, and preferably all, of the receiving cavities 27 are provided with a second processing medium in the form of a coating 44 on which the sub-samples and the first A mixture of processing media 45 is provided. In a general sense, the coating 44 in question is arranged for reaction with at least one component present in the mixture 45, this component being, for example, an antigen, antibody, serum or antibody, such as for a customary Elisa test. It can be said that serum, enzymes and the like are sufficient. The different receiving cavities 27 on the matrix plate 7 each have a specific coating 4
4, but the receiving cavities 27 of different columns K and / or rows R can have the same or different coatings 44. Therefore, in each receiving cavity 27 there is always the same sub-sample, a specific first processing medium and a specific second processing medium.
A special combination of a mixture of processing media (ie, coatings 44) is formed. Thus, a specific reaction occurs in each receiving cavity 27, which will indicate the presence of a component that is specifically detected in the subsample. As an illustration, a matrix plate 7 with 5 columns K and 5 rows R, ie 25 receiving cavities 27
Thus, at least 25 different detections can occur in principle in one operation. Through a specific combination of the active ingredient, in particular the various conjugates in each first processing medium and its adjusted coating 44 in each receiving cavity 27 in the column K covered by the associated dosing needle 43, the same mixture 45 Thereby, a different test can be performed in each column K more easily.

After filling the different receiving cavities 27 with the relevant mixture 45, the matrix plate is treated in the same known and customary manner, for example by rinsing with a buffer and further treated with a medium, after which the matrix plate 7 is Exposure to analysis means 8. As mentioned, the analyzing means 8 preferably comprises a CCD camera, whereby a record of all receiving cavities 27 can be made at once. The analysis means 8 is connected to a computer, such as a computer 46, where records can be created and analyzed.
To this end, the computer 46 is provided with an algorithm for comparing the record with a standardized record stored in a data bank of the computer 46. Since each of the standardized records is made with samples of known composition, such records are referred to to know which components were included and which were not in the relevant samples. Based on the comparisons thus made by the algorithm, it is possible to establish at a time what components were present in sample 4 and, if appropriate, their extent, and to make this determination, for example, of the human or animal taken from which the relevant sample was taken. It can be used, for example, for medical procedures, slaughter, etc. to determine the processing route. Indeed, of course, it is also possible to apply other types of analytical means 8 known per se, while at the same time per receiving cavity 27 or per row R or column of receiving cavity 27 for further comparison by the algorithm. It is also possible to create one record for each K.

Using the first drive means 15 and the second drive means 40, respectively, the blocks 9 and 17 in addition to the rear-and-forward movement have an angle of 90 ° around their respective axes of rotation 11 and 19. You can also rotate through. That is, the next series of pre-reception cavities 14 and the first reception cavities 22 are in each case in overlapping horizontal positions, while the pre-reception cavities 14 respectively filled with the sample or mixture used.
Alternatively, the first receiving cavity 22 rotates toward a vertical side. Block 9 is followed by a first spray nozzle 47, and block 17 is followed by a second spray nozzle 48, both spray nozzles being connected to a pressurizing means 49 for spraying the cleaning medium, This allows the front-receiving cavity 14 and the first receiving cavity 22 to be rinsed against the side of the respective block 9, 17 facing the associated spray nozzle 47, 48 respectively to clean it. . More preferably, a third spray nozzle 49 is arranged adjacent to the bottom side of block 9 and a fourth spray nozzle 50
Are arranged adjacent to the bottom side of the block 17 and the spray nozzles 49 and 50
In order to dry the front receiving cavity 14 and the first receiving cavity 22 located on the bottom surface, respectively, it is connected to a second pressing means 51 for blowing air against the bottom surface of the blocks 9 and 17. It is always cleaned during use, and a series of dried pre-receiving cavities 14 or first receiving cavities 22 can be rotated to the top for use, which is then automatically cleaned and dried. , For this purpose, 2
This means that one block 9, 17 always rotates 90 ° in the same direction.

The device 1 can be controlled by a computer 46. To do this,
Driving means 15 and 40, supply means 2, front-pickup means 28, front-addition means 31, first pickup means 34, first addition means 37, second pickup means 41, first pressurization means 49 and second addition means. The drive means 52 for the pressure means 51 is connected to a computer 46 designed for control. Further, the processing of the matrix plate 7 and the control of the analyzing means 8 can be controlled by the computer 46.

FIG. 3 shows a cross section of the matrix plate 7, showing the receiving cavities 27 of each column K. Included between the columns K of the receiving cavities 27 are ribs 53, whereby during the filling of the receiving cavities 27 by the application means, one mixture 45 of the columns K
From mixing with one mixture of another column K. FIG. 3A shows another embodiment in which grooves 54 are provided instead of ribs 53, while in the embodiment shown in FIG.
Seven juxtaposed columns K are arranged at different heights. In the latter two embodiments, the mixture 45 in one column K is effectively prevented from being mixed with the mixture 45 in the adjacent column K.

With the device according to the invention, a large number of samples can be automatically analyzed at a relatively high speed and in a relatively short time, which makes it possible to analyze the samples in a (semi) continuous manner. Shall be remarkably suitable for

In the device 1 according to the invention, the or each second processing medium and / or the further processing medium is placed in the receiving cavity 27 on the matrix plate by a further addition means 27, not shown in the drawing, but in the receiving cavity on the matrix plate. 27 can be inserted. For this purpose, the outlet openings can be provided in a pattern corresponding to the pattern of the receiving cavities 27, the outlet openings being individually controllable, for example, by a computer 46. In another embodiment, the additional loading means comprises a further series of loading needles movable on the matrix plate 7, at least a series and / or column of receiving cavities 27, parallel to, perpendicular to direction P shown in FIG. 6B, or At the same time comprising the various angles, the associated second or further processing medium can be inserted into the receiving cavity 27, preferably by the application movement described for the second pick-up means 41. In this way, any desired combination of mixture 45, second processing medium and optionally further processing medium can be obtained.

FIG. 7 schematically illustrates an advantageous arrangement of the addition means, particularly suitable for adding a substrate to the cavities 27 in the matrix plate 7. Preferably, a number of such loading devices are arranged in the matrix plate 7 in a matrix corresponding to the RxC matrix. The dosing device 60 of the present invention comprises a chamber 61 having a bottom 62 and a top surface 63. Extending through the bottom 62 is a hollow needle 64 having a chamfered first end 65 located outside the chamber and a second end 66 located on the bottom 62 at a distance B within the chamber. Furthermore, this supply opening 68, in which the drainage line 67 passes through the bottom 62 and is located in the chamber, is located on the bottom 62 at a distance S, which is at least shorter than the distance D and may be zero. Upper surface 6
Extending into the chamber through 3 is an exhaust line 69 and a vent line 7
0, which is relatively larger than the sections of the exhaust line 69, the needle 64, and the drainage line 67. The vent line 70 is provided with a valve 71, which can close or open the vent line. Drainage line 67 is provided with shut-off means, in particular pumping means (not shown in the drawings) for draining liquid through the drainage line, as will be described in more detail below. Connected to the vent line 69 are suction means (not shown in the drawings), the purpose of which will be described in more detail hereinafter.

The device 60 of FIG. 7 can be used as follows.

The first end 65 of the needle 64 is disposed in a liquid that is picked up in a container 72 as shown in FIG. 7A. Next, when valve 71 and drain line 67 are closed and air is exhausted from chamber 61 through exhaust line 69, FIGS.
Liquid is drawn into the chamber via the needle 64 as shown in FIG. When the drain line 67 is closed, the liquid level in the chamber 61 is set to the needle 6 as shown in FIG. 7D.
4 can be raised above the second end 66. The evacuation means is then turned off and when the drain line 67 is opened, the liquid flows out of the chamber 61, as shown in FIG. 7E, and possibly by suitable pump means. Drain line 67
The drainage of liquid through will end when the liquid level in the chamber is flowed at the supply opening 68 as shown in FIG. 7F. During such steps 7A-7F, the first end 65 of the needle 64 is maintained in the liquid in the container 72. The first end 65 of the needle 64 then moves into the cavity 27 of the matrix plate 7 in such a way that the bottom of the cavity 27 is less contacted as shown in FIG. 7G. The valve 7 is then opened and relatively more air is relatively quickly introduced into the chamber 61 via the vent line 70, while the exhaust line 69 and the drain line 67 are closed. During the discharge of the liquid from the chamber 61, the liquid that was behind in the needle 64 is pushed out of the needle 64 into the cavity 27 by air pressure, as shown in FIG. 7H, as shown in FIGS. 7E and 7F. Here, the chamfered end 65 of the needle 64 has the advantage of flushing air from the cavity 27 so as to prevent air bubbles from forming in the cavity 27. In this manner, splashing of the liquid, mixing of the cavity into the environment, and the like are easily prevented, and at the same time, the liquid is removed from the cavity 2.
7 can be introduced relatively quickly. When the cavity 27 is completely filled, the needle 6
4 can be pulled slightly upward and blow air from the chamber through the space between the opening in the hollow end 65 of the needle and the upper surface of the matrix plate 7 without affecting the liquid in the cavity. You can leave.

The device according to FIG. 7 has the advantage that particularly accurate dosing is possible in a particularly simple manner, since the same amount of liquid always remains behind the needle 64. Thus, this amount of liquid is the amount to be added, which is always equal. Therefore, the internal volume of the needle is the added amount and can be accurately adjusted to the internal volume of the cavity 27. Moreover, such devices can be easily applied without the need for complex systems such as pistons, valves and the like. An advantage achieved by arranging such an addition device in the matrix according to the cavities 27 of the matrix plate 7 is that each cavity 27 can be supplied with exactly the desired amount of processing medium, such as a substrate, in one operation.

FIGS. 8A-D show a particularly suitable pickup and dosing device for picking up a sample such as blood, optionally with the addition of a pretreatment medium, such as a solvent, to the pre-holding means 5. . The dosing device is described as pre-pickup and pre-dosing means.

The front-pickup means 28 comprises a hollow needle 30 provided with a chamfered first open end 80 as previously described. Provided around the free end of the needle 30 is a sleeve-shaped jacket 81, closed at its upper end 82. For example, a bottom end 83 flush with the top of the open end 80 of the needle 30 is open to the bottom. Since the jacket 81 preferably sandwiches the needle, no air or liquid can pass upwardly between the jacket 81 and the needle 30. Such a device can be used, for example, as follows.

The needle 30 with the jacket 81 moves into the liquid 84 in the container 85 as shown schematically in FIG. 8, where the liquid is obliquely parallel and shaded. Jacket 81 and needle 3
Since 0 is closed, air is trapped in the needle and in the needle and jacket 81 when introduced into the liquid. This prevents liquid from entering the closed space 86 between the needle 30 and the jacket 81 (FIG. 8B). Next, a volume of liquid 84 is withdrawn into the needle (FIG. 8C). Here, needle 30 is withdrawn from the liquid, along with jacket 81, while liquid 84 remains behind needle 30 (FIG. 8D). Since no liquid enters the space 86, mixing outside the needle 30 is prevented in a simple manner,
In addition, liquid 84 is prevented from being carried over the outside of the needle and is dispensed unintentionally. Thus, with such a device, the addition can be carried out particularly accurately. In practice, the amount added is completely determined by the amount of liquid taken up in the needle 30. A further advantage is that such an addition device can be maintained and cleaned in a particularly simple manner. In order to dispense the liquid 84 from the needle 30, the jacket 81 is preferably pulled over the needle 30, which prevents any liquid that may be entrained along the jacket 81 during the addition. To this end, the jacket 81 can be mounted, for example, on a needle 30 so that it can slide in a simple manner. Jacket 81 can also be designed to replace its top surface. Numerous changes that are readily apparent to those skilled in the art are possible in this regard.

Those skilled in the art will recognize that the processing medium (s), such as a substrate, after necessary steps, such as washing,
Is added to the cavity of the matrix plate 7, it will be immediately understood that different further steps, usually including washing steps, coloring steps, incubation steps, etc., are carried out before the matrix is subjected to analytical means. .

It will be appreciated that many modifications are possible. For example, the front holding block and / or
Alternatively, the first holding means may be of a different design, for example having a triangular or polygonal cross section perpendicular to the axis of rotation 11 or 14, while at the same time one or more series of front-receiving cavities or first receiving cavities on each side. Can be included. Series R of the second holding means 7
And / or the number of columns K can be adjusted depending on, for example, the number of tests to be performed and the possible combinations of processing media used, in particular the mixture of conjugates, but the first receiving cavity on the first holding means Can be adjusted to the number of columns K. The means for cleaning and drying the different receiving cavities can be designed in various suitable ways, for example as contact-cleaning means. Also, instead of the driving means, other means can be used to set the oscillations of the blocks 9 and 17, but additionally stirring means etc. can be used to mix the sample and sub-sample with the various treatment media. Is also good. Still other pickup means and addition means can be applied to transport between different phases during processing of samples, subsamples and mixtures. Also, the supply means and the pre-holding means, the pre-processing means and the first holding means, the first holding means and the second
Additional processing means can be provided for adding additional processing media such as, for example, anticoagulants, solvents, buffer means, reagents, etc. between the holding means and / or the second holding means and the analysis means.

[Brief description of the drawings]

FIG. 1 schematically shows a top plan view of the device of the invention.

2 schematically shows the device of FIG. 1 from the side.

FIG. 3 shows a front sectional view of the matrix plate taken from line III-III in FIG. 1;

3A and 3B show, in a side section taken from line III-III in FIG.
2 represents two alternative embodiments.

FIG. 4 shows the receiving cavity of the matrix plate in an enlarged side section taken from line III-III in FIG. 1;

5A is a top plan view of FIG. 2 showing the position of the sample transport means.

5B is a top plan view of FIG. 2 showing the location of the receiving means for the sample mixed with the conjugate.

FIG. 6A is a top plan view showing the addition means for inserting the sample / conjugate mixture into the receiving cavity of the matrix plate.

FIG. 6B is a side cross-section taken from line VIB-VIB of FIG. 6A, depicting the means during insertion of the mixture into the receiving cavity.

7A-I schematically show devices for addition to specific substrates.

8A-D schematically show devices for picking up and adding liquids.

[Procedural Amendment] Submission of translation of Article 34 Amendment of the Patent Cooperation Treaty

[Submission date] March 28, 2000 (2000.3.28)

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] Claims

[Correction method] Change

[Correction contents]

[Claims]

17. An apparatus for use in an apparatus according to claim 1.
Medium, comprising at least two specific binders.
The above treatment medium wherein each conjugate is test-specific for a different test.

18. Sample who tested serologically for such as blood samples, etc.
Separating at least one, and preferably a series of subsamples,
Subjecting at least one subsample to at least one serologic test;
One test is performed online and each subsample is
Or aspirated, preferably through their tubular ends, and then
The open end of the back-up area is the measured volume of the subsample associated with the receiving cavity.
The longitudinal edges on them so that they are at least filled under the influence of cohesion
A short distance over the receiving cavity in the relevant column of the matrix, where
The extra subsample is the long axis of the receiving cavity, which is more relevant by the preceding pickup part
The above method which is flush with the opposite edge.

──────────────────────────────────────────────────続 き Continuation of front page (81) Designated country EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE ), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, SD, SZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CU, CZ, DE, DK, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE , KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, UA, UG, US, UZ, VN, YU, ZW (72) Inventor Rigtoboat, Gierald Holland Nuel-1338 Geiti Almere Okapi Strat 29 (72) Inventor Puik, Wouter Cornelis N. Netherlands-8243 Buzett Le Restad Schioner 43-40 F term (reference) 2G058 AA09 BA08 CA04 CC02 EA11 ED03 ED11 ED12 ED16 FA03 FB03 GA02 GA20

Claims (32)

[Claims] 1. A method for serologically testing a sample, such as a blood sample, comprising separating at least one, and preferably a series of subsamples, and separating at least one subsample with at least one serology. Such a method, wherein the at least one test is conducted online, wherein the method is subject to a dynamic test. 2. In order to obtain a column of a matrix of receiving cavities filled with different sub-samples, some of the sub-samples are separated and each of the sub-samples is mixed with at least a first processing medium and then each sub-sample is mixed. At least a portion of the sample is introduced into a column of at least one receiving cavity in the matrix, wherein at least in each receiving cavity filled with the sub-sample, further processing medium is mixed with the associated sub-sample, and then at least The method of claim 1, wherein the contents of some filled receiving cavities are subjected to a suitable assay. 3. The method according to claim 1, wherein the sample is separated from the amount of the medium containing the sample and pretreated with at least a pre-treatment medium such as a solvent, after which the subsample is separated. . 4. The method according to any one of the preceding claims, wherein the at least one processing medium comprises a mixture of at least two conjugates. 5. The method of claim 1, wherein at least some of the receiving cavities are provided with an associated further processing medium before inserting a portion of the associated subsample therein. Method. 6. The method according to claim 5, wherein at least one further processing medium or a mixture of further processing media is provided by coating the associated receiving cavity. 7. Each subsample is received in or on a pickup portion,
Preferably aspirated through their tubular ends, after which the open ends of the pick-up portions are filled with their long axes such that the receiving cavity is filled at least under the influence of cohesion with the measured amount of the relevant subsample. A short distance from the directional edge over the receiving cavity in the associated column of the matrix, where the excess subsample is leveled by the preceding pickup portion with the longitudinal edge of the associated receiving cavity A method according to any one of the preceding claims. 8. The method according to claim 1, wherein the receiving cavity is simultaneously subjected to a suitable assay. 9. The method according to claim 1, wherein the radiation measurement, in particular the light measurement, is used as an analytical method, wherein an image of the matrix of the receiving cavity is recorded by a receiver, and this image is compared with a previously measured image stored in a data bank and associated. For each receiving cavity, the desired measurement of the sample in the image, at least the component detected therein, is known, and based on this comparison, the desired measurement is determined for each associated receiving cavity.
A method according to any one of the preceding claims. 10. The databank is filled with some images taken from a sample having a known composition, the databank is replenished with images of the sample to be inspected, and the algorithm of the computing device determines which image is measured. Determining whether it is suitable for inclusion in the bank depending on at least some measurement data of such a sample, the measurement data being measured externally and input to a calculation unit;
A method according to any one of the preceding claims. 11. The method according to claim 1, wherein several separated samples are processed simultaneously in one device. 12. An apparatus for on-line serological testing of a sample such as blood, etc. for picking up several sub-samples, preferably at least two sub-samples, from a sample to be tested. First pickup means; first holding means for storing the subsamples carried by the first pickup means; first addition means for adding a first processing medium to each subsample in the first holding means; First mixing means for mixing the or each subsample with an associated first processing medium added thereto; second pickup means for separately picking up each subsample from the first holding means; -Second holding means for separately storing the processed sub-samples carried therein by the second pick-up means; Said second holding means comprising a predetermined number of rows and columns of a matrix of receiving cavities, preferably of receiving cavities; the second pick-up means supplying the relevant picked-up pretreatment subsamples to separate columns of the receiving cavities. -Means for adding a second processing medium to the relevant portion of the processed subsample in the receiving cavity; and-a filled receiving cavity. Means for analyzing at least some, and preferably all, of the contents of the above. 13. A front-pickup means for picking up a sample from a stock of samples; a front-holding means for the sample carried therein by the front-pickup means; a sample in the front-holding means. Pre-adding means for adding a pre-treatment medium to the sample; pre-mixing means for mixing the sample with the pre-treatment medium; wherein the first pickup means picks up a subsample from the pre-holding means. 13. The apparatus of claim 12, wherein the apparatus is arranged to: 14. A method according to claim 12, wherein a second processing medium is provided in at least some or preferably each of the receiving cavities, preferably before introducing a part of the subsample associated therewith. Device according to claim 13. 15. The device according to claim 14, wherein some, preferably each, receiving cavity to be filled is coated with at least a second processing medium. 16. The receiving cavity is included in at least one plate part, preferably a matrix plate, and the second pick-up means is associated with the associated pre-treatment by movement of the or each surface of the associated plate part. 16. The device according to any one of claims 12 to 15, wherein the device is arranged to transfer a portion of the subsample to a receiving cavity. 17. The front-holding means comprises at least one front-mixing cavity contained in a front-mixing block, wherein the front-mixing means comprises: a front-mixing block having a relatively small first angle. Or front-tilting the mixing block in one direction at a relatively large second angle, about a substantially horizontally arranged axis of rotation; Apparatus according to any one of claims 12 to 16, wherein 18. The front-mixing block is provided with at least two, preferably on all sides, a front-mixing cavity, the front-pickup means for supplying the sample at least temporarily to the front-mixing cavity. 18. The apparatus according to claim 17, wherein the cleaning means is arranged to carry, in particular, clean, the or each pre-mixing cavity at least partially simultaneously. 19. The method of claim 1, wherein the first holding means comprises a series of first mixing cavities, and wherein the first mixing means comprises vibration means for providing vibration to the first mixing cavities.
Apparatus according to any one of 2 to 18. 20. The first pick-up means comprises a series of pick-up elements arranged at interrelated positions corresponding to the positions of the first series of mixing cavities.
The device according to claim 19. 21. The apparatus according to claim 20, wherein the pickup elements are arranged in a row corresponding to the location of the receiving cavities in the row in the second holding means. 22. A series of first mixing cavities is included on at least one side of the first mixing block, wherein the first mixing means comprises:-a first mixing block pivoted relative to each other at a relatively small first angle; 22. or tilting the first mixing block in one direction at a relatively large second angle about a substantially horizontally aligned axis of rotation. An apparatus according to claim 1. 23. The first mixing block is provided with a series of first mixing cavities on at least two, preferably all sides, wherein the first pickup means disposes the sub-sample at least temporarily in a first upward direction. 18. The arrangement according to claim 17, arranged for carrying into one mixing cavity, wherein the cleaning means is provided for at least partially simultaneously treating, in particular cleaning, the or each further series of first mixing cavities. Equipment. 24. The first mixing cavity has a sloped bottom surface, and an interior volume slightly greater than the volume of the subsample is delivered therein, and the first addition means includes a first addition means next to the highest end of the bottom surface. 24. The method according to any one of claims 19 to 23, wherein the first processing medium is arranged to be delivered at a horizontal and a vertical distance from the processed subsample contained in the first mixing cavity. Equipment. 25. A matrix plate particularly suitable for use in a method according to any one of claims 1 to 11, or an apparatus according to any one of claims 12 to 24, comprising a receiving plate. Such a matrix plate comprising a matrix of cavities, wherein at least some receiving cavities are provided comprising a processing medium for a sample or a part thereof introduced into the receiving cavities. 26. The matrix plate according to claim 25, wherein at least some of the receiving cavities are coated with a processing medium. 27. The column of at least some of the receiving cavities comprises, or preferably is coated with, a processing medium different from the processing medium in at least one of the other receiving cavities in the associated column of receiving cavities. 27. The matrix plate according to claim 25 or 26, wherein at least one receiving cavity is provided. 28. An analytical device for use in a method according to any one of claims 1 to 11, or an apparatus according to any one of claims 12 to 24, comprising at least some Means for measuring the radiation coming from the contents of the receiving cavity, the reflection thereby or the absorption thereby, provided means for comparing the measured values with the corresponding known sampled measurements, The analytical device, wherein the corresponding measured value is stored in a data bank of the measuring device. 29. The measuring device comprises an algorithm for making the comparison, based thereon, representing the relevant sample or at least a serologic test result of a part thereof, wherein the algorithm determines the relevant measurement value found. 29. The analysis device of claim 28, wherein the analysis device is arranged to add to the databank, the arrangement being such that the analysis device self-learns. 30. A method of processing a meat product, wherein the meat product to be processed, such as carcass or a part thereof, is continuously supplied, wherein the method comprises the steps of: Or at least some of the meat products to which a blood sample is supplied by means of an apparatus according to any one of claims 12 to 24, and preferably using an analysis device according to claims 28 or 29, And preferably the above processing, which is taken from each and tested serologically and determines in which manner each meat product is further processed, based at least in part on the measurements found by the analytical method used Law. 31. Means for continuously supplying meat products, comprising an apparatus according to any one of claims 13 to 24, and preferably an analytical device according to claim 28 or 29. A meat processing device comprising: a pick-up means arranged for each sample of bodily fluid, preferably blood, from the fed meat product, the device for serologically testing each of the collected samples. Wherein the meat processing apparatus is provided with a discharge means for the meat product and control means for controlling the discharge means based on the serological test results. 32. A processing medium for use in the method according to any one of claims 1 to 11 or the apparatus according to any one of claims 12 to 24, wherein the processing medium is used. Such a processing medium comprising at least two specific binders.