|Número de publicación||WO2011095798 A1|
|Tipo de publicación||Solicitud|
|Número de solicitud||PCT/GB2011/050154|
|Fecha de publicación||11 Ago 2011|
|Fecha de presentación||31 Ene 2011|
|Fecha de prioridad||8 Feb 2010|
|Número de publicación||PCT/2011/50154, PCT/GB/11/050154, PCT/GB/11/50154, PCT/GB/2011/050154, PCT/GB/2011/50154, PCT/GB11/050154, PCT/GB11/50154, PCT/GB11050154, PCT/GB1150154, PCT/GB2011/050154, PCT/GB2011/50154, PCT/GB2011050154, PCT/GB201150154, WO 2011/095798 A1, WO 2011095798 A1, WO 2011095798A1, WO-A1-2011095798, WO2011/095798A1, WO2011095798 A1, WO2011095798A1|
|Solicitante||The Secretary Of State For Environment, Food & Rural Affairs|
|Exportar cita||BiBTeX, EndNote, RefMan|
|Citas de patentes (10), Clasificaciones (6), Eventos legales (3)|
|Enlaces externos: Patentscope, Espacenet|
Liquid Extraction Apparatus
Field of invention
The invention relates to apparatus to extract liquid from a sample in a closed container, particularly from a mixed liquid and non-liquid sample, such as a clotted blood sample.
The use of blood samples is a common way of screening for diseases, to confirm the presence of a disease and/or to detect abnormal blood content in both human medicine and veterinary analysis. For example, in the United Kingdom, the Veterinary Laboratories Agency (VLA) co-ordinates statutory government surveillance programs for a number of diseases which may involve processing millions of blood samples per year, particularly during a disease outbreak. Similar programmes are carried out by equivalent authorities in most other countries. On the human medicine side, major hospitals typically include a pathology department responsible for conducting analysis of various tissue and fluid samples, including blood. Such a department would typically process several hundreds to several thousands of samples per day.
Blood samples are often extracted, in both the human and animal context, using proprietary evacuated blood collection tubes such as the Vacutainer® system, available from BD (Becton, Dickinson & Company, Oxford, UK). Similar tubes are available from other manufacturers. Each Vacutainer® tube is manufactured to contain a partial vacuum and having a removable lid. The person taking the blood sample inserts a needle into the vein of the patient or animal, the needle being connected to another needle which can be used to pierce the lid of the Vacutainer® tube. The vacuum in the tube then causes blood to be extracted into the tube, which can then be disconnected from the system. If necessary, further samples may be extracted into additional tubes which can be connected to the system while the needle remains in the vein. Once sample collection is complete, the needle is withdrawn from the vein. This system allows multiple samples to be taken at minimal risk to the person taking the blood and also reduces discomfort to the patient, since manipulation of a syringe in the vein or multiple needle insertions are not required. Different Vacutainer® tubes may contain different additives, such as anticoagulants or clot activators, depending on the type of test to which the sample is to be subjected. As mentioned above, other similar sample tube ranges are available and are used according to the preference of a particular institution and/or the requirements of a particular screening programme.
Some tests must be carried out on the serum portion of a blood sample, so the sample is collected in a tube which does not include anticoagulants and the blood is allowed to clot. Currently, before a test such as an ELISA test for diagnosis of a disease and/or detection of antibodies can be carried out, the clot must first be removed, since the presence of red blood cells and other elements of the clot would interfere with the test. Clot removal is typically achieved either by opening the tube and manually removing the clot, or by centrifuging the sample so that the clot collects at the base of the tube, at which time the tube is opened and the upper serum layer removed by hand or by a robot. In either case, the step of opening the tube represents a safety risk to the user and/or (even if the process is fully automated), increases the overall time required to process each sample. One method of overcoming such problems is provided by EP0898977, which discloses a centrifuge-based device which is capable of separating blood cells from the liquid part of a blood sample. The device is reusable and is small enough to be included as a component of a clinical analyser. The present invention provides an alternative and simpler solution to the problem of separating a liquid component of a sample from a mixed liquid and non-liquid sample, so that the liquid can be processed for analysis, diagnostic and/or detection purposes.
Summary of Invention
According to a first aspect of the invention, there is provided apparatus to extract liquid from a mixed liquid and non-liquid sample in a closed sample container, comprising:
a) a liquid extraction location;
b) a conveying device to convey the sample container to and from the extraction location;
c) a positioning device to position the container at the extraction location such that the liquid collects under gravity in a region of the container where the non-liquid does not; and d) an extractor for extracting the liquid from the region without opening the container.
The apparatus may also comprise a liquid receiving location and a system for transferring the extracted liquid to the receiving location. Advantageously, the invention provides a system for separating a liquid component from a mixed liquid/non-liquid sample (such as a serum/blood clot sample) from the sample container and moving it to a second receiving container placed at the receiving location, which second container may then be used in further activities such as analytical tests. This is achieved without any need to open the sample container, which is a particular advantage in the case of blood samples which may expose a person opening the sample to infection. In addition, the apparatus is preferably automated, comprising a controller configured to operate the apparatus, so that a person is only required to handle samples before and after, but not during, the operation of the apparatus. The term "the liquid collects under gravity in a region of the container where the non- liquid does not" indicates that the liquid component moves, due to the force of gravity, to a region of the container simply as a result of the position to which the container is moved, with the non-liquid component not moving to that region. Therefore, the liquid is substantially separated from the non-liquid. No other force need be exerted in order to move the liquid and non-liquid components of the sample to different regions, i.e., additional actions such as centrifugation or use of physical separation barriers are not required.
The non-liquid part of the sample may be a solid, or another non-liquid structure such as a gel, mucus, or other component having a greater viscosity than the liquid part of the sample. An example is a clotted blood sample, where the liquid part is serum and the non-liquid part is one or more blood clots. However, the sample could also be biological sample such as a faecal sample, a tissue sample in liquid, a cell culture, or an environmental sample such as river water or a mixed water/mud or water/sand sample. None of these examples should be considered to be limiting, but are given merely to indicate the range of samples for which the apparatus would be useful. In addition, the apparatus may be used to enable collection of liquid from a wholly liquid sample, providing the advantage that there is no requirement for the sample container to be opened.
In an embodiment, the sample container is an elongate container having a first end and a second end and the positioning device positions the container so that the liquid collects under gravity in an end region of the container adjacent the first end. This means that a portion, for example most or all, of the liquid part of the sample collects at the end region at or adjacent the first end, in the absence of any substantial amount of the non-liquid part of the sample. Ideally, none of the non-liquid portion collects at this end region, or the non-liquid part only collects at the end region a period of time after the liquid part has collected there, e.g., a period of time sufficient for at least some of the liquid to be extracted from the sample, prior to the collection in the region of any non- liquid part, such as 1-20 seconds, for example 2-10 or 2-5 seconds. Typical time periods are non-limiting and will depend on the nature of the sample being considered. This system is, therefore, distinguished from systems which require layering of different parts of the sample, for example after a centrifugation step, with the layers optionally separated by a physical separation barrier. Variations on such systems are described, for example, in JP59210343 and US2005/0186119, both of which depend on use of at least one centrifugation step to achieve sample separation.
For example, when the sample container is at the extraction location, it may be positioned such that the longitudinal axis of the container is angled between 0° and 20° from the horizontal, the first end being lower than the second end when the axis is not horizontal. A suitable angle may be determined by the skilled person, taking into account factors including the viscosity of the liquid portion of the sample and the relative density of the solid and liquid parts. The angle of the longitudinal axis may be about 1°, about 2°, about 3°, about 4°, about 5°, about 6°, about 7°, about 8°, about 9° or about 10° from the horizontal, with the first end lower than the second end of the container. About 1°, about 2°, about 3°, about 4° or about 5° are most typical suitable angles, particularly for clotted blood samples. Such an inclination has the result that the liquid component of the sample moves, under the force of gravity, to one end of the elongate container. The non-liquid component does not move in this way, because the degree of inclination is not sufficient for the force of gravity to overcome the force of friction and/or surface tension which tends to keep the non-liquid part in the same place.
The second end of the container may be lower than the first end when the sample container is not at the extraction location, so that the force of gravity acts to encourage the non-liquid part of the sample towards one end of the tube, prior to the conveying of the sample container to the liquid extraction location and the inclination of the sample container described in the previous paragraph, allowing the liquid component to move under gravity to a different region of the tube, from where it can be extracted.
The extractor may comprise a needle (typically having a sharp and a non-sharp end) which can pierce the sample container, the position of the needle preferably being moveable between an extraction position and a dispensing position. The dispensing position of the needle may then be such that liquid contained in the needle can be transferred to the receiving location by being expelled from the needle. Alternatively, a connection from the non-sharp end of the needle may enable the liquid to be aspirated directly to the receiving location without being ejected via the needle.
In one embodiment, an elongate sample container has a lid at the first end. For example, the elongate sample chamber may be a tube having a lid at one end, for example (by way of example only) a Vacutainer® blood sampling tube or other such tube, a lidded test tube for storing tissue samples or for culturing a cell sample, or a lidded tube for taking environmental samples.
In the extraction position, the needle may extend into the sample container at the end region adjacent the first end, for example, through the lid of the container when present, and is positioned at an acute angle relative to a lower side of the sample container in the end region adjacent the first end. An appropriate angle may be, for example, between 10° and 60°, for example, between 20° and 50°, for example, between 30° and 40°. The needle may be retractable, the apparatus being configured to initially position the needle outside the sample container, subsequently causing the needle to extend so that it pierces the sample container, the sharp end of the needle contacting (especially being submerged in) the liquid; finally the needle is retracted from the sample after the liquid has been extracted into and through the needle. The longitudinal axis of the needle is positioned at an acute angle relative to the lower side of the sample container, providing the additional benefit that, should the non-liquid part of the sample start to move under gravity into the region of the container occupied by the liquid sample, it will tend to slide over the top of the needle without impeding the extraction of the liquid sample. This is particularly the case since most needles are formed with an angled tip with the material of the needle forming a point, rather than a blunt end. The aperture of the needle is typically formed at an angle across the cross-section of the needle.
The apparatus may further comprise a sample identification location, which may comprise an identity detector for detecting the identity of a sample container positioned at the identification location. This is particularly important where the samples are being processed for some analysis purpose such as environmental monitoring, disease screening or antibody or drug screening trials. In such a case, each sample has a unique identifiable label applied to it, the label being associated with the sample through the testing and results analysis stages. In one embodiment, the label comprises a barcode and the identity detector comprises a barcode reader, connected to a recordal and/or data processing device so that the location of that sample within the apparatus may be identified and stored. The sample identification location may comprise one or more mirrors, to enable the reading of the barcode even if the sample is not positioned within the apparatus such that the barcode on the sample is directly readable by the barcode reader. A system incorporating an example of a mirror system is, for example, disclosed in US6,588,669.
In one embodiment of the invention, the apparatus comprises a guide system configured to convey the sample container from the identification location to the extraction location. Therefore, the container is engaged with the apparatus via the guide system, configured to move the container sequentially through the identification location (where the identification of the sample can be logged) and then on to the extraction location where the liquid portion of the sample can be extracted and moved to a container at the receiving location. The apparatus may also be arranged so that the container may be moved sequentially to the extraction location and then on to the identification location. Alternatively, the identity detector can be located so that the identity can be determined when the container is at the extraction location. Therefore, the extraction location and the identification location may be the same. The identity of the receiving container can be related to the initial identity of the sample container, whether by application of a further corresponding identification label (e.g., a barcode) or by location within an array system such a 96-well plate. Software to track the identity and location of samples in such a system is readily obtainable and/or can be prepared by the skilled person.
The invention encompasses apparatus comprising a computer or other controller (e.g., microcontroller-based electronic circuitry) configured to convey the sample container to and from the extraction location and to position the container at the extraction location such that the liquid collects in a region of the container where the non-liquid does not. The computer may also be configured to identify a sample and to relate the identity to a particular receiving container into which liquid from the sample container is transferred.
The apparatus may comprise a guide system configured to convey more than one sample container sequentially to and from the extraction location. Therefore, the apparatus may comprise a sample support which comprises a succession of sample container engagement devices linked sequentially to form a chain. This might take the form of a rigid or flexible sample rack, or a succession of clips each of which can engage with a sample container and with each other, or be joined to each other in some other way, so as to form a chain. The chain may be continuous, for example forming a continuous loop structure within the apparatus, with sample containers being added and removed directly on the apparatus. Alternatively, batches of samples may be engaged with the apparatus in the form of a non-infinite/non-continuous chain such as a rack. The sample support may be integral with the apparatus or removable from it. The apparatus may also be configured to accommodate more than one container simultaneously at the extraction location, in which case the apparatus may comprise more than one extractor, such that liquid may be extracted from more than one sample container simultaneously. Therefore, a group of samples may be brought into position in the extraction location, a different extractor extracting liquid from each sample simultaneously with other extractors operating on other samples. This may enable the processing of more samples in a given time period than would be otherwise possible. The apparatus may be configured to transfer the liquid extracted from one sample container to a receiving container located at the receiving location, and further configured to transfer the liquid extracted from another sample container to a separate receiving container also located at the receiving location, so that the liquid extracted from each sample container is kept separate from the liquid extracted from other sample containers. A separate identification location may be associated with the position of each sample within the extraction location, so that the identity of each of the samples within the extraction location may be logged and linked with the liquid sample retained in the separate receiving containers at the receiving location. The apparatus may further comprise a loading location and/or a removing location. A loading location is a position within the apparatus where one or more sample containers can be engaged with the apparatus (e.g., via the guide system), for example by engaging a pre-loaded rack or chain of samples with the apparatus, or by engaging sample containers one-by-one with a sample support already in position in the apparatus. This may be achieved manually or by use of an automated system. A removing location is the converse of this, where samples are removed from the apparatus. The removing location, in particular, may not require external intervention for disengagement of the sample containers with the apparatus; for example, containers may "tip off the end of a conveyor system into, for example, a disposal container, or a clip device engaging the sample with the apparatus may be released so as to "drop" the sample from the apparatus.
The removed sample containers need not be stored, since the useful liquid part of the sample can be stored in the receiving container located at the receiving location. This container is subsequently removed from the apparatus and used in downstream procedures, such as ELISA analysis for disease diagnosis or antibody detection, or other procedures. When multiple samples are processed by the apparatus, multiple receiving containers may be collected together as, for example, a 96-well plate. This plate can then be stored as a precaution in case confirmatory testing of any sample(s) is required. Advantageously, the space required to store a 96 well plate is significantly less than the space required to store 96 sample containers such as Vacutainer® tubes. This also provides an advantage over the centrifugal system disclosed in the aforementioned EP0898977, which does not allow for storage of a portion of the original sample or of the liquid component which is processed by a clinical analyser.
In one embodiment of the apparatus, it may be configured to inject a small quantity of air into the sample container, through the needle, immediately prior to extraction of liquid from the container. This may be particularly useful when the sample container was manufactured with a partial vacuum, such as a Vacutainer® tube. Injection of some air into the sample container can act to equalise the vacuum, with the result that subsequent extraction of liquid from the sample is facilitated. The volume of air to be injected will vary depending on the sample container being used but, in the context of a 6ml Vacutainer® tube, a suitable volume might be around 0.5-0.8ml, preferably about 0.75ml.
The apparatus may comprise a cleaning system for cleaning the extractor after a liquid sample has been extracted and before a subsequent liquid sample is extracted. For example, where the extractor is a needle, it may be connected at a non-sharp end to a first connection between the needle and an extraction pump and also to a second connection between the needle and a wash fluid supply. The first and second connections may be joined to one another via a valve, with a third connection then extending from the valve to engage directly with the non-sharp end of the needle. The valve may operate or switch to enable the extraction pump to extract liquid from the sample via the needle, or to enable the wash fluid supply to connect to the needle, for example to be ejected through the needle so as to wash it. The wash fluid may be, for example, water or a liquid detergent and/or antimicrobial solution.
In an alternative embodiment, the needle may be disposable, in which case the apparatus is configured to disengage from a needle after it has been used to extract a liquid sample from a container and to transfer the liquid to a receiving container. The apparatus is configured then to engage with a replacement needle prior to extraction of a subsequent liquid sample.
The apparatus according to the invention may comprise a controller configured to cycle the apparatus through the following steps:
a) moving the needle to the extraction position wherein the unconnected sharp end of the needle contacts (i.e., may be submerged in) liquid in the sample; b) activating the extraction pump to extract the liquid from the sample container; c) moving the needle to the dispensing position;
d) transferring the liquid to the receiving location;
e) moving the needle to a washing position; and
f) activating the wash fluid supply to flush wash fluid through the needle.
There may be a subsequent step (g) in which the extraction pump is activated to draw air into the needle and, optionally, the first or third connection, depending on which is directly engaged with the non-sharp end of the needle. This provides an advantage of providing a bubble of air in the needle and/or first or third connection, between the liquid sample being drawn through the needle and the wash fluid, creating a physical barrier between the liquid and the wash fluid. This prevents any dilution of the liquid sample by liquid wash fluid which might otherwise contact the sample.
The controller may additionally cause the apparatus to move the sample container into the identification location (where present) and subsequently into the extraction location before step (a) above is carried out. The sample container is also moved from the extraction location after the completion of at least steps (a), (b) and (c). Where more than one sample is to be sequentially processed by the apparatus, the subsequent sample may be moved into the extraction location while one or more of steps (d), (e), (f) and (where present) (g) is completed for the preceding sample.
As mentioned above, in an embodiment the mixed liquid and non-liquid sample is a coagulated blood sample, the liquid being serum and the non-liquid being at least one blood clot. In that case, the apparatus may further comprise a clot detector for detecting the attachment of a blood clot to a lid of an elongate container such as a tube. Depending on the orientation of a blood sample during transport from the collection site to the analysis site, blood clots can form in association with the lid of the container, such that they do not move away from the lid even when the container is in an upright position with the lid uppermost. When this situation occurs, tilting of the sample so that the lid end is slightly lower than the base end of the tube, as described above, will not serve to separate the liquid from the clot in the way required for the present apparatus to operate as envisaged. Therefore, it is preferable for the apparatus to include a clot detector for detecting a sample where a clot has formed on the lid, so as to allow for the removal of that sample from the apparatus. Such a sample is most appropriately processed by hand. Such samples represent a small minority of clotted blood samples obtained. The detection may be by use of an optical detection system.
Such a detector may suitably be positioned close to the identity detector, or be located in a position such that, for example, a lid-associated clot is detected prior to the step of identification of the sample and particularly before the sample is moved to the extraction location.
Such an obstruction detection system may also be appropriate in conjunction with samples other than clotted blood samples and the skilled person will readily be able to determine whether inclusion of this feature in the apparatus is appropriate in a given context.
The apparatus according to the invention may be included within an analyser device, capable of conducting one or more analysis method(s) on the liquid sample contained in the receiving container(s). In the context of a blood sample, this may be a device for counting types of blood cells and/or for detecting/quantifying other blood components and/or chemical compounds.
According to a second aspect of the invention, there is provided a method of extracting liquid from a sample in a closed sample container without opening the container, comprising use of the apparatus according to the first aspect of the invention. Preferably, the sample is a mixed liquid and non-liquid sample.
According to a related aspect of the invention, there is provided a method of extracting liquid from a mixed liquid and non-liquid sample in a closed elongate sample container having a first end and a second end, without opening the container, comprising
a) positioning a longitudinal axis of the container at an angle so that it is horizontal or so that the first end is lower than the second end when the axis is not horizontal;
b) inserting a needle into the container so that the sharp end is positioned at an end region adjacent the first end and the needle is positioned at an acute angle relative to a lower side of the sample container in the end region adjacent the first end; and c) extracting liquid from the sample by aspiration through the needle.
The longitudinal axis may be at an angle sufficient to cause the liquid to collect under gravity in a region of the container where the non-liquid does not so collect, or collects after a period of time sufficient for extraction of liquid in step (c) to take place. An angle of, for example, between 0° and 20° from the horizontal may be suitable. A suitable angle may be determined by the skilled person, taking into account factors including the viscosity of the liquid portion of the sample and the relative density of the solid and liquid parts. The angle of the longitudinal axis may be about 1°, about 2°, about 3°, about 4°, about 5°, about 6°, about 7°, about 8°, about 9° or about 10° from the horizontal, with the first end lower than the second end of the container. About 1°, about 2°, about 3°, about 4° or about 5° are typical suitable angles, particularly for clotted blood samples.
The method may be carried out using apparatus according to the first aspect of the invention. Brief Description of Figures
Embodiments of the invention will now be described, by way of example only, with reference to the following Figures 1 to 9 in which:
Figure 1 shows the principle of positioning a sample tube so as to enable extraction of serum from a blood sample containing a blood clot; Figure 2 is a view of apparatus according to the invention;
Figure 3 is a plan view of the apparatus of Figure 2;
Figure 4 shows a needle housing positioning the needle in the extraction position;
Figure 5 shows a needle housing positioning the needle in a dispensing position;
Figure 6 is a close-up view of a sample container at the extraction location; Figure 7 shows a sample support arrangement;
Figure 8 shows the sample support arrangement of Figure 7 in use to position sample containers at the extraction location; and Figure 9 shows an uncovered (A) and an exploded (B) view of the interior of a needle apparatus to be used as an extractor in the apparatus.
During a large scale screening program by VLA for the bovine disease brucellosis, it was found that there were significant inefficiencies in a system which was required to process as many as 8000 samples per day. Samples were collected on farms by veterinary staff using the Vacutainer® system and tubes labelled with a unique barcode label, so that results derived from the sample could be allocated to the correct site and animal. The samples for a whole herd were then posted to the VLA along with accompanying documentation. Upon receipt they were unpacked and logged into a testing database by manually entering the data included in the paperwork and by use of a barcode scanner. The Vacutainer® tubes were then placed into linear containers called "spools", which were loaded onto a machine which unwound the spool from one side and passed it through a "de-bunging" mechanism to remove the lids of the tubes carried on the spool. The spool was then rewound it onto an empty carousel on the other side. This method only removed around 90% of the lids (also known as bungs) and so an operator manually removed those that remained before unloading the spool and moving the open tubes to the next process.
The original Vacutainer® tubes did not contain an anticoagulant, so the blood clotted to form two phases consisting of a soft but solid and resilient clot surrounded by liquid serum. Later on in the testing process, some of this serum was required to be aspirated from the tube using processing robots which, although designed to cope with the clots in situ, often malfunctioned if the clot blocked the probe.
It had, therefore, been found necessary to introduce an extra process before testing to remove these clots and this was achieved manually, using wooden applicator sticks similar to "chop-sticks" that were discarded with the clots to prevent cross- contamination. Each test-tube was picked up manually from the spool, tilted and then the two wooden sticks were used to "slide" the clot out of the tube into a bin.
A time-and-motion study was carried out on this process, with the findings shown in Table 1 below. In Table 1, actions which are underlined are those which were fully manual and which, collectively, took up a signification portion of the time needed to process a batch of 240 samples. There is, therefore, a need to reduce the number of steps required in the process and to reduce the time taken to process samples from the point of receipt in the laboratory to the points of obtaining results.
As shown in Figure 1A, experimentation with sample tubes showed that a slight tilting of the tube 1 so that the lid end 5 was lower than the other end had the result that, under gravity, the serum part of the sample moved towards the lid end whilst the clot 10 remained at the other end. The upper surface of the liquid serum is shown in Figure 1A by the dotted line 12. A needle 15 could then be inserted through the tube so that the serum could be extracted. Even if the clot 10 moved towards the lid end 5, this occurred more slowly than the movement of the serum and so the serum could be removed. As shown in Figure IB, positioning the needle at an acute angle 20 relative to the lower side of the tube, with the open face 25 of the sharp end of the needle positioned towards the lower side of the tube, has the result that a clot 10 which moves towards the lid end 5 tends to slide up and over the needle 15, so that serum can still be removed and separated from the clot.
An automated apparatus, to utilise this principle in a scaled-up laboratory setting, was then developed and is shown in Figures 2 and 3. Several samples, grouped as 30, are placed in a sample spool 35 which forms a part of the apparatus. The spool conveys the samples through the apparatus in the direction of the arrow "Z" and, at the end of the apparatus, the samples fall from the spool into the bucket 40, from where they can be discarded. The sample tube 45 is the tube which is in the extraction location and its identity is determined by scanning the barcode on the tube using the barcode reader 50, positioned over the extraction location. The sample extractor is a needle housed in case 55, which is shown in Figures 2 and 3 in a position for washing. In use, the case 55 can rotate into an extraction position (see Figure 4 and further discussion below) and to a dispensing position (see Figure 5) and a washing position. The needle in case 55 is connected to a pump 60 which can actuate to suck liquid into the needle when the case and needle are in the extraction position.
The apparatus also carries a 96-well rack 65 which engages with and can be moved along the apparatus by the conveyor 70. The movement of the sample containers and the 96-well rack, as well as of the needle in the case 55, are controlled by a computer which ensures that liquid sample removed from a particular sample container is transferred to a particular well in the 96-well rack, ensuring that results obtained from analysing the content of each well can be related to the identity of a particular sample provided to the laboratory.
Figure 4 shows the needle case 55 in the extraction position. The case 55 contains the needle on a mounting block driven by a screw (see discussion below and Figure 9). The orientation of the case 55 shown in Figure 4 positions the needle so that it can be extended through the lid of the sample container 45, which is at the extraction location and inclined as shown in Figure 6 (see discussion below). The serum is aspirated into the needle by the action of the pump 60 shown in Figure 2, the needle is retracted and the needle case 55 then rotates so that the needle 100 is positioned over the appropriate well 67 in the 96-well rack 65, as shown in Figure 5 and as directed by the computer controlling the apparatus. The liquid sample is then dispensed into the well 67, at which time the needle case 55 can rotate to the wash position shown in Figures 2 and 3 and water flushed through the needle. Figure 6 shows a closer view of the tube 45 in the extraction location. The lid end 45b is positioned to be lower than the non-lid end 45a as the result of a block 75 which is located at the extraction location so that a tube moving into the extraction location is pushed up over the block. The lid end of the tube does not change position as a result of the grip of the sample spool. As the Figure shows, this has the effect of raising one end 45a of the tube 45 so that serum contained in the tube moves to the lid end 45b, from where it can be extracted. Samples which are not at the extraction location are inclined so that the lid end of the tube is level with, or higher than, the non-lid end, so that the contents of the tube remain at the non-lid end.
Figures 7 and 8 show an alternative sample container spool and system for positioning a sample at the extraction location. As shown in Figure 7, sample tubes 1 are engaged with clips 80 which are linked together in a chain and positioned on a guide wire 85 which drives the clips and, therefore, the tubes through the apparatus. The lower end of the tubes can run against a second guide wire or rail 87, the position of which can change so as to force the non-lid ends of the tubes 1 to be positioned so that the non- lid end of the tube is slightly higher than the lid end, i.e., the position of tube 45 in Figures 4 and 5. The changing orientation of the tubes is shown in Figure 8, where the guide wire 85 and sample clips 80 act to move the samples in the direction of the arrow "Y". As the samples approach the extraction position, the non-lid ends of the tubes are forced upwards by the second guide wire 87 so that sample 95 is in the correct position for liquid extraction.
Figure 9 shows an uncovered (Figure 9 A) and an exploded (Figure 9B) view of the interior of the needle case 55. The needle 100 is mounted on a mounting block 105 supported by guide rails 110. The block is attached to a lead screw 115 which is connected to and reversibly rotatable by a motor 120. Mounting the needle 100 on a screw 115 in this way provides the advantage that the longitudinal force required for the needle to puncture a lid of a sample tube can be provided. The components of the needle case are held together with bolts 125 and the whole mechanism is mounted to a rotational platform 130. This is also controlled by a motor and enables the needle case 55 to be moved to the various required positions.
Together, the features of the apparatus enable the extraction of liquid from a mixed liquid and non-liquid sample in a closed container, without needing to open the container. In addition, the overall number of containers required to process a sample from the text site, through extraction, sample analysis and storage, is reduced, as well as the time and the number of people required to process large numbers of samples.
|Patente citada||Fecha de presentación||Fecha de publicación||Solicitante||Título|
|EP0898977A2||24 Ago 1998||3 Mar 1999||Beckman Coulter, Inc.||Blood separation device and method|
|JPS59210343A||Título no disponible|
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|Clasificación internacional||G01N35/10, G01N1/40, A61M1/02|
|Clasificación cooperativa||B01L3/0293, G01N35/1079|
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