Device and method for separating a liquid component of a blood sample, and analyzer apparatus comprising such a device

A device for separating at least part of the liquid component of a blood sample and methods thereof are disclosed. Generally, the device includes a container body for receiving the blood sample, a layer of retaining porous material, a layer of separating permeable material. The retaining porous material retains non-liquid components of the blood sample after the non-liquid components have been subjected to centrifugal force which forces them through the separating permeable material into the retaining porous material.

TECHNICAL FIELD

Embodiments of the invention concerns a device and a method for separating at least part of a liquid component of a blood sample, and an analyzer apparatus comprising a device of the above mentioned kind.

BACKGROUND

The separation of liquid components of blood samples, e.g. plasma and serum, is a necessary and important pre-analytical step in clinical diagnostics.

Known methods for performing the above mentioned separation require a considerable amount of manual work and time. The automation of that manual work, both in terms of throughput, workflow and reliability, becomes essential.

An important parameter is the time required for plasma or serum separation during centrifugation. This time could be substantially reduced by centrifugation of the sample tube around its axis of symmetry instead of using the conventional swing bucket method. This is because the length of the motion path followed by cell components of blood sample during centrifugation of the sample container about its symmetry axis is much shorter than in a conventional swing bucket centrifugation of a primary sample tube. When swing bucket centrifugation of a sample tube containing a blood sample is performed the rotation axis is perpendicular to the length axis of the sample tube and the motion path followed by cell components of blood sample during the centrifugation is much longer because the cell components move along the length axis of the sample tube towards the bottom of this tube.

If a primary sample tube is used for example as a sample container for centrifugation around its axis of symmetry, the length of the motion path followed by cell components of blood sample during centrifugation is less than the length of the radius of the primary sample tube, e.g. between 1 and 4 mm.

A problem associated with primary sample tube centrifugation around its axis of symmetry is the maintenance of the separation after centrifugation is stopped. The separated non liquid components are only temporary stuck against the internal wall of the sample tube and will mix again with the liquid component to then slowly sediment at the bottom of the tube.

In U.S. Pat. No. 4,509,941 a sample tube is disclosed comprising a porous material for entrapping blood cells when the tube is centrifuged along its vertical axis. A particularly designed cap helps to keep the porous material in place against the interior wall of the tube. A problem however remains, as the blood cells are not steadily trapped in the porous material. The same document discloses that plasma itself can be used to release the red blood cells from said material. This means that if the separated plasma is not removed quickly, it will be contaminated again by the blood cells.

SUMMARY

Embodiments of the present invention provide a device for separating at least part of the liquid component of a blood sample and prevent the non-liquid components of the blood sample from returning into the separated part of liquid component. This is achieved by means of a layer of a suitable separating permeable material, acting as a barrier for the passive leaking of blood cells from a retaining porous material, while allowing blood cells to pass through when subjected to centrifugal force.

Embodiments of the present invention also increase the processing throughput and provide more than one volume of plasma by providing a device for simultaneously separating at least part of the liquid components of different blood samples. This is achieved by dividing the inventive device into a plurality of sections and respective sample compartments, separated by partition walls.

Another advantage of the embodiments of the present invention is the enablement of tests like quality checks already in the separation device. This is achieved by integrating a photometric chamber for collecting part of the separated liquid component at the bottom of the inventive device.

In one embodiment, a separation device for separating at least part of the liquid component of a blood sample is disclosed. The separation device comprises a container body, at least one sample compartment for receiving the blood sample and retaining at least part of the separated liquid component after separation, at least one layer of a retaining porous material, and at least one layer of a separating permeable material. The retaining porous material retains non-liquid components of the blood sample, after the non-liquid components have been subjected to centrifugal force which forces them through the layer of separating permeable material into the retaining porous material.

In another embodiment, a separation device for separating at least part of the liquid component of a blood sample is disclosed. The device comprises a container body, at least one sample compartment for receiving the blood sample and retaining at least part of the separated liquid component after separation, at least one layer of retaining porous material for retaining non-liquid components of the blood sample, and at least one photometric chamber, which is fluidically connected with at least one sample compartment. The photometric chamber collects at least a part of the separated liquid component and is configured and dimensioned for enabling photometric measurement of the liquid component therein collected.

In still another embodiment, a separation device for separating at least part of the liquid component of at least one blood sample is disclosed. The device comprises a container body being divided into a plurality of sections by partition walls, and a plurality of sample compartments for receiving a plurality of the blood samples and retaining at least part of the separated liquid component after separation, wherein at least one of the sections comprises a layer of retaining porous material for retaining non-liquid components of the blood sample after separation.

The subject invention will now be described in terms of its preferred embodiments with reference to the accompanying drawings. These embodiments are set forth to aid the understanding of the invention, but are not to be construed as limiting.

REFERENCE NUMERALS USED IN DRAWINGS

11single compartment container body or sample tube13axis of rotation for axial centrifugation of container body1114upper portion of container body1115side wall of container body1116upper opening of container body1117lower portion of container body1118bottom region of container body1119bottom wall of container body1121cap of container body1122photometric chamber connected with the interior of container body1123opening in the bottom wall16of container body1124layer of retaining porous material24aouter annular portion of layer2424binner annular portion of layer2425inner surface of cylindrical side wall1526layer of permeable separating material27air30sample compartment of container body1131blood sample32non-liquid components of blood sample3133liquid component of blood sample3141multi-compartment container body43axis of rotation for axial centrifugation of container body4144upper portion of container body4145side wall of container body46upper opening of container body4147lower portion of container body4148inclined side wall of container body4149bottom wall of container body4150arrow51-58sample compartment of container body4161-68partition wall of container body4172bottom region of compartment5276bottom region of compartment5682cover of upper opening46of container body4184layer of retaining porous material84aouter portion of layer8484binner portion of layer8485inner surface of side wall4586layer of permeable separating material87air88pipetting opening/pierceable pipetting opening89pipetting opening/pierceable pipetting opening92opening in the bottom wall of compartment5296opening in the bottom wall of compartment56102photometric chamber connected with compartment52106photometric chamber connected with compartment56112mirror arranged within cup102116mirror arranged within cup106121incident light beam122reflected light beam123incident light beam124reflected light beam130arrow132photometric chamber connected with compartment52141mirror142mirror143incident light beam144reflected light beam145reflected light beam151—158section of container body41312blood sample in compartment52316blood sample in compartment56322non-liquid component of blood sample312326non-liquid component of blood sample316332liquid component of blood sample312336liquid component of blood sample316

DETAILED DESCRIPTION

Embodiments of the present invention refers to a separation device for separating at least part of the liquid component of a blood sample, said separation device comprising a container body, at least one sample compartment for receiving said blood sample and retaining at least part of said separated liquid component after separation, a layer of retaining porous material, a layer of separating permeable material, wherein said retaining porous material is retaining non-liquid components of said blood sample, after said non-liquid components have been subjected to centrifugal force, forcing them through said separating permeable material into said retaining porous material.

For non-liquid components of blood is intended particulate matter with a density such that separation by gravity or centrifugation can be allowed within a relatively short time. Examples are blood cells, cell aggregates, micro-clots, etc. This may not comprise very small components eventually present such as viruses.

A liquid component of blood is in the first place plasma or serum and its components such as proteins, electrolytes, etc. after the non-liquid components have been separated.

According to the present invention a separating permeable material is a material comprising a large number of closely-spaced holes sized for the passage of matter with a size typical of non-liquid components of a blood sample under centrifugation conditions but preventing passage under steady conditions. The separating permeable material may have the shape of a mesh or stent and is preferably made of a an inert polymer, preferably hydrophobic, preferably having a contact angle comprised between 90 and 140 degrees. The size of said holes or mesh opening is preferably comprised between 90 and 200 micrometers. Inert means, not interacting with the blood sample. Suitable materials are for example Nylon, Teflon or the like. An example of suitable material is Nitex Nylon 03-171 manufactured by Sefar, Switzerland. The function of said material is therefore more than simply structural. More than keeping the layer of retaining porous material in place, such materials ensure a better down flow of the separated liquid component of the blood sample after centrifugation and prevents the non-liquid components of the blood sample from returning into the separated part of liquid component.

A retaining porous material is a material in which non-liquid components of a blood sample can be accumulated when subjected to centrifugal force in direction of said material, so that the non-liquid components can be retained inside the pores. This material is preferably chosen from a group comprising an open cell foam, a foamed rubber, a fleece, a mat, a honeycomb-like material or the like, and has a volume preferably larger than the volume of the non-liquid components to be retained. An example of suitable material is the foam S6050HY by KOEPP Schaum GmbH, Germany, available in reticulated and non reticulated form.

According to a preferred embodiment said container body is divided into a plurality of sections by partition walls. A layer of said retaining porous material and a layer of said separating porous material are arranged in at least one of said sections.

A separation device according to the present invention may therefore comprise a single sample compartment, for separating at least part of the liquid component of a blood sample or a plurality of compartments for the simultaneous separation of at least part of the liquid components of a plurality of blood samples.

Both kinds of devices have:

a vertical axis of rotation,

at least one sample compartment for receiving said blood sample and retaining at least part of said separated liquid component after separation, said at least one sample compartment being located between said axis of rotation and a layer of separating permeable material, and

a layer of retaining porous material located between said layer of separating permeable material and the side wall of the container body.

It is recognizable that the separation conditions and thus the separation efficiency in case of a multi-compartment device are similar to those of a single-compartment device where separation is carried out by centrifugation around the axis of symmetry.

Centrifuges required for rotating said separation devices, around said vertical axis of rotation, can be small and thus suitable for being integrated as an automatically operated centrifuge into a clinical diagnostic analyzer apparatus. Such analyzer apparatus may comprise one or a few of such centrifuges for all of the samples in the analyzer apparatus. Such centrifuge, however, can also be a stand-alone device or can be integrated into another device as e.g. a sample preparation unit.

As these separation devices comprise one or a few compartments, preferably an even number of compartments as e.g. 2, 4, 6, 8, 12, 18, they are also well suitable for the fast processing of small batches.

Liquid component separated in a device according to the invention is preferably taken out before analysis by means of a pipetting needle. The pipetting needle is preferably part of an automatic pipetting unit of an analyzer apparatus. For sampling separated liquid component the pipetting needle may pierce a cover, which may close the device. This process is thus much simpler, faster and more convenient than the conventional methods, which require a conventional swing bucket centrifuge outside of the analyzer.

According to a preferred embodiment of the present invention, the separation device further comprises at least one photometric chamber, which is fluidically connected with said at least one sample compartment, said chamber collecting at least a part of the separated liquid component and being configured and dimensioned for enabling photometric or reflectometric measurements of said liquid component therein collected.

According to another embodiment, the present invention provides a separation device for separating at least part of the liquid component of at least one blood sample, said device comprising a container body, at least one sample compartment for receiving said blood sample and retaining at least part of said separated liquid component after separation, a layer of retaining porous material for retaining non-liquid components of said blood sample, and at least one photometric chamber which is fluidically connected with said at least one sample compartment, said photometric chamber collecting at least a part of the separated liquid component and being configured and dimensioned for enabling photometric measurement of said liquid component therein collected.

These embodiments make thus possible to perform sample integrity checks including measurement of serum indices. In this way, required integrity checks of the blood sample can be carried out automatically in the same separation device and by the same analyzer apparatus before the usual analysis of plasma or serum samples is carried out.

According to another embodiment, the present invention provides a separation device for separating at least part of the liquid component of at least one blood sample, said device comprising a container body being divided into a plurality of sections by partition walls, a plurality of sample compartments for receiving a plurality of said blood samples and retaining at least part of said separated liquid component after separation, wherein at least one of said sections comprises a layer of retaining porous material, for retaining non-liquid components of said blood sample after separation.

According to another embodiment, at least one of said sections further comprises a layer of separating permeable material, for preventing the non-liquid components of the blood sample from returning into the separated part of liquid component.

According to another embodiment said separation device further comprises at least one photometric chamber being fluidically connected with said at least one sample compartment through an opening in the bottom wall of the lower portion of said container body, said photometric chamber collecting at least a part of the separated liquid component and being configured and dimensioned for enabling a photometric measurement of said liquid component therein collected.

The present invention also refers to a method for separating at least part of the liquid component of at least one blood sample, said method comprising:(a) providing a separation device according to any of the favorite embodiments,(b) introducing a blood sample into the at least one sample compartment of said separation device,(c) rotating said device about an axis at a predetermined speed for separating the liquid component of the blood sample from the non-liquid components thereof, and(d) stopping said rotation, thereby allowing the separated liquid component of said at least one blood sample to flow towards the central and lower part of said at least one sample compartment, whereas the non-liquid components of the blood sample and a portion of the liquid component of the blood sample are retained by the layer of retaining porous material.

For the device embodiments comprising a photometric chamber, the method above may further comprise the step of effecting a photometric measurement of at least part of the liquid component collected in at least one photometric chamber of said device.

A clinical diagnostic analyzer apparatus according to the present invention may therefore comprise a device according to any of the embodiments, means for centrifuging said device about an axis, a detector for performing photometric or reflectometric measurements of the contents of a photometric chamber of said device.

The centrifugation time necessary for achieving plasma or serum separation with a device according to the invention is shorter than the centrifugation time required in the case of a conventional swing bucket centrifugation of a primary sample tube, because the cell components of the blood sample have to migrate along a shorter distance. In the embodiments shown byFIGS. 1 to 9, wherein the sample container is a sample tube, the migration distance of the cell components of the blood sample is less than half the length of the radius of the cross-section of the sample container. In the embodiments shown byFIGS. 10 to 17, the migration distance of the cell components of the blood sample is only about half the distance of the thickness of the layer of blood which is spun to the outer wall of the sample container.

First Example of a Device According to the Invention

A first example of a device according to the invention is described hereinafter with reference toFIG. 1.

The container body of the device is a sample tube11and a layer24of a retaining porous material is arranged within sample tube11.

Sample tube11has a symmetry axis13, a cylindrical side wall15, an upper opening16, a bottom region18, and a bottom wall19. The upper opening16of sample tube11is closed by a stopper or cap21which is pierceable by a pipetting needle. The interior of sample tube11comprises an upper portion14and a lower portion17. The container further has a sample compartment for receiving a blood sample and retaining the separated part of liquid component.

The outer surface of layer24is in contact with and covers at least partially the inner surface25of the cylindrical side wall15. In a preferred embodiment porous material layer24covers the entire inner surface25of the cylindrical side wall15.

Layer24of porous material is suitable for retaining non-liquid components32of the blood sample31.

Layer24of porous material is made of e.g. an open cell foam, a foamed rubber, a fleece, a mat, a honeycomb-like material or the like.

In a preferred embodiment the device comprises in addition a layer26of separating permeable material such as a mesh or stent, which is in contact with and extends at least partially over the inner surface of layer24of retaining porous material. In a preferred embodiment, layer26extends over the entire inner surface of layer24.

The separating permeable material layer26is made preferably of a plastic material, e.g. Nylon, Teflon or the like. Layer26keeps layer24in place, ensures a better down flow of the separated part of liquid component of the blood sample and prevents the separated non-liquid components from returning into the separated part of liquid component.

First Example of a Method According to the Invention

A first example of a method according to the invention for separating a liquid component from a blood sample makes use of the device described above with reference toFIG. 1and comprises the following steps illustrated byFIGS. 2 to 5:(a) introducing a blood sample31(shown inFIG. 2) into the sample compartment30of sample tube11,(b) rotating sample tube11about its symmetry axis13(as shown byFIGS. 3 and 5) at a predetermined speed for separating the liquid component of the blood sample from the non-liquid components thereof, and(c) stopping the rotating of sample tube11, thereby allowing the liquid component of the blood sample to flow towards the central and lower part of the sample compartment30, whereas the non-liquid components of the blood sample31and a portion of the liquid component of the blood sample are retained by layer24of the retaining porous material.

Step (b) is carried out with a rotation speed adjusted to a value in a range between 1000 and 20000 rpm. The time required for the separation depends from the rotation speed. A decrease of the time required for the separation is obtained by increasing the rotation speed. In the case of centrifugation of the sample tube11, the following are examples of rotation speeds used and of the values of the separation time achieved:

With a rotation speed of 20000 rpm, separation of platelet-free plasma (<1000 platelets per μL) of a blood sample is achieved in a separation time lying in a range from 30 to 60 seconds.

After step (c) a portion of the liquid component of the blood sample can be collected by pipetting through the cap21while the non-liquid components of the blood sample31and a portion of the liquid component of the blood sample are retained by layer24of the retaining porous material.

Layer26of separating permeable material is located between the sample compartment30and the layer24of retaining porous material. Non-liquid components32of blood sample31can pass through layer26of separating permeable material during centrifugation, while layer26of separating permeable material prevents the non-liquid components32from returning into the separated part of liquid component in the sample compartment30after separation is completed.

The cross-sectional view shown byFIG. 5shows the spatial distribution of the liquid component33and the non-liquid components32of blood sample31at the end of the axial centrifugation of sample tube11according to step (b) but before stopping the rotation of the above described method and as schematically represented byFIG. 3. As shown byFIG. 5, the non-liquid components32occupy an outer annular portion24aof layer24of retaining porous material, whereas a first portion of the liquid component33occupies an inner annular portion24bof layer24of retaining porous material and a second portion of the liquid component33occupies an annular space between layer26of separating permeable material and a space27occupied by air in the sample compartment30.

In one embodiment of the above described method, sample tube11is a blood collection tube, the inside of which is under vacuum. This tube contains a coagulation preventing agent, and the blood sample31is introduced into the blood collection tube by venipuncture. In this case the liquid component33separated by the above described method is blood plasma.

In another embodiment of the above described method, sample tube11is a blood collection tube, the inside of which is under vacuum. This tube contains no coagulation preventing agent or contains a coagulation promoting agent, and the blood sample31is introduced into the blood collection tube by venipuncture. In this case the liquid component33separated by the above described method is blood serum.

After step (c) sample tube11and the separated liquid component33contained therein are usually kept at a suitable temperature until sample tube11and its contents are transferred to a clinical diagnostic analyzer apparatus for analysis of the liquid component33. However, the entire process may be executed by the same clinical diagnostic analyzer apparatus. The liquid component33of the blood sample is then pipetted from sample tube11by means of a pipetting needle which pierces cap21, enters sample tube11and aspirates the liquid component33, which is transferred e.g. to a reaction cuvette of the clinical diagnostic analyzer apparatus.

Second Example of a Device According to the Invention

A second example of a device according to the invention is described hereinafter with reference toFIG. 6.

The structure of this second example is a variant of the structure of the example shown byFIG. 1. In this variant, sample tube11shown byFIG. 6comprises in addition a photometric chamber22, which is fluidically connected with sample compartment30through an opening23in the bottom wall19of sample tube11. Photometric chamber22is configured and dimensioned for enabling photometric measurement of a liquid contained therein.

Second Example of a Method According to the Invention

A second example of a method according to the invention for separating a liquid component from a blood sample makes use of the device described above with reference toFIG. 6and comprises the following steps illustrated byFIGS. 7 to 9:(a) introducing a blood sample31(shown inFIG. 7) into sample compartment30of sample tube11(shown inFIG. 6),(b) rotating sample tube11about its symmetry axis13at a predetermined speed for separating the liquid component of the blood sample31from the non-liquid components thereof (as shown byFIG. 8), and(c) stopping the rotating of sample tube11, thereby allowing the liquid component of the blood sample to flow towards the central and lower part of the sample compartment30and into photometric chamber22, whereas the non-liquid components32of the blood sample31and a portion of the liquid component33of the blood sample are retained by layer24of the retaining porous material.

Step (b) is carried out as in the first example.

After step (c) a portion of the separated liquid component of the blood sample can be collected by pipetting through the cap21while the non-liquid components of the blood sample31and a portion of the liquid component of the blood sample are retained by layer24of the porous material.

In this second example of a method according to the invention a portion of separated liquid component33is collected in photometric chamber22and is therein photometrically evaluated.

In one embodiment of the above described method, sample tube11is a blood collection tube, the inside of which is under vacuum. This tube contains a coagulation preventing agent, and the blood sample31is introduced into the blood collection tube by venipuncture. In this case the portion of the liquid component33separated by the above described method and contained in photometric chamber22is blood plasma.

In another embodiment of the above described method, sample tube11is a blood collection tube, the inside of which is under vacuum. This tube contains no coagulation preventing agent or contains a coagulation promoting agent, and the blood sample31is introduced into the blood collection tube by venipuncture. In this case the portion of the liquid component33separated by the above described method and contained in photometric chamber22is blood serum.

In this case, sample integrity checks including measurement of serum indices can be performed by photometric measurement of the serum sample contained in photometric chamber22.

The further processing of sample tube11after step (c) is e.g. as described above in the first example of a method according to the invention.

Third Example of a Device According to the Invention

A third example of a device according to the invention is described hereinafter with reference toFIGS. 10 to 12.

These figures refer to a multi-compartment device comprising a container body41which has a symmetry axis of rotation43. As shown byFIG. 12, the interior of container body41is divided into a plurality of sections51-58and respective sample compartments151-158by partition walls61-68. Each of compartments51to58is adapted for receiving a blood sample. All compartments51to58have preferably the same shape and the same size, and the number of compartments is preferably an even number. In a preferred embodiment the container is divided into12compartments. Each one of the sections151to158has a bottom region like72and76shown inFIG. 11. In a preferred embodiment container body41is a one-piece container body.

Container body41has an upper portion44and a lower portion47. The upper portion44of container body41has a cylindrical side wall45and an upper opening46. The lower portion47of container body41has the shape of a truncated cone and has a conical side wall48and a bottom wall49.

The device shown byFIGS. 10 to 12further comprises a layer84of a retaining porous material which is arranged within each of the sections151to158. The outer surface of layer84is in contact with and covers at least partially the inner surface85of the portion of the cylindrical side wall45which belongs to that compartment. In a preferred embodiment retaining porous material layer84covers the entire inner surface of the portion of the cylindrical side wall45which belongs to each section151to158.

The device shown byFIGS. 10 to 12further comprises a cover82of the upper opening46of container body41. Cover82is fixed to container body41. Cover82has at least one pipetting opening89for each of the sample compartments51to58. The at least one pipetting opening89allows passage of pipetting needle therethrough for pipetting a blood sample into or out of one of the sample compartments51-58. In a preferred embodiment cover82has a first pipetting opening88and a second pipetting opening89for each of the sample compartments51to58. First pipetting opening88allows passage of a pipetting needle therethrough for pipetting a blood sample into one of the compartments51-58. Second pipetting opening89allows passage of a pipetting needle therethrough for pipetting out of one of the compartments51-58a liquid component separated from that blood sample.

In a preferred embodiment, the device shown byFIGS. 10 to 12comprises in addition a layer of separating permeable material86which is in contact with and extend at least partially over the inner surface of layer84of retaining porous material. In a preferred embodiment, layer86extends over the entire inner surface of layer84.

Third Example of a Method According to the Invention

A third example of a method according to the invention for separating a liquid component from a blood sample makes use of the device described above with reference toFIGS. 10 to 12and comprises the following steps illustrated byFIGS. 13 to 15which show compartments52and56of container body41:(a) introducing blood samples312,316(shown inFIG. 13) into respective compartments52,56of the container body41of a device according to the above described third example of a device according to the invention,(b) rotating the container body41about its symmetry axis43(as shown byFIG. 14) at a predetermined speed and in a sense shown by arrow50for separating the liquid components332,336of the blood samples312,316from the non-liquid components322,326thereof, and(c) stopping the rotating of the container body41, thereby allowing the liquid components332,336of the blood samples312,316to flow towards the central and bottom regions72,76of the respective compartments52,56of the container body41, whereas the non-liquid components322,326of the blood samples312,316and portions of the liquid components332,336of the blood samples312,316are retained by layer84of the retaining porous material.

Step (b) is carried out with a rotation speed adjusted to a value in a range between 500 and 10000 rpm. The time required for the separation depends from the rotation speed. A decrease of the time required for the separation is obtained by increasing the rotation speed. In the case of centrifugation of the container body41the following are examples of rotation speeds used and of the values of the separation time achieved:

With a rotation speed of 10000 rpm, separation of platelet-free plasma (<1000 platelets per μL) of a blood sample is achieved in a separation time lying in a range from 30 to 60 seconds.

After step (c) portions of the liquid components332,336of the blood samples can be collected by means of a pipetting needle introduced through the pipetting openings89of cover82while the non-liquid components322,326of the blood samples312,316and portions of the liquid components332,336of the blood samples312,316are retained by layer84of the retaining porous material.

Layer86of separating permeable material is located between the sample compartment52,56and the layer of retaining porous material84. Non-liquid components of blood sample can pass through layer86of separating permeable material during centrifugation, while layer86of separating permeable material prevents the non-liquid components32from returning into the separated part of liquid component in the sample compartment52,56after separation is completed.

The spatial distribution of the liquid component332and the non-liquid components322of blood sample312during centrifugation of container body41according to step (b) of the above described method and as schematically represented byFIG. 14is similar to the spatial distribution shown byFIG. 5where container body is a sample tube11with the only difference that the interior of container body41is subdivided in sections151-158, whereas the interior of sample tube11is not. At the end of the centrifugation of container body41according to step (b), the non-liquid components322,326of the blood sample in any of sample compartments51-58occupy a segment of an outer portion84aof layer84of retaining porous material, whereas a first portion of the liquid components332,336of the blood sample occupies an inner portion84bof layer84of retaining porous material and a second portion of the liquid components occupy spaces each of which lies between layer86of separating permeable material and a space occupied by air87in the interior of a sample compartment51-58of container body41.

In one embodiment of the above described method, each of the blood samples312,316introduced into compartments52,56of container body41by pipetting through pipetting openings88of cover82is obtained by means of a blood collection tube, the inside of which is under vacuum. This tube contains a coagulation preventing agent, and the blood sample312,316is introduced into the blood collection tube by venipuncture. A coagulation preventing agent may be also or in alternative in sample compartments52,56of container body41. In this case the liquid components332,336separated by the above described method are blood plasma.

In another embodiment of the above described method, each of the blood samples312,316introduced into sample compartments52,56of container body41by pipetting through pipetting openings88of cover82is obtained by means of a blood collection tube, the inside of which is under vacuum. This tube contains no coagulation preventing agent or contains a coagulation promoting agent, and the blood sample312,316is introduced into the blood collection tube by venipuncture. A coagulation promoting agent may be also or in alternative in the sample compartments51-58of container body41. In this case the liquid component332,336separated by the above described method is blood serum.

After step (c) container body41and the separated liquid components332,336contained in the compartments52,56of container body41are usually kept at a suitable temperature until container body41and its contents are transferred to a clinical diagnostic analyzer apparatus for analysis of the liquid components332,336. However, the entire process may be executed by the same clinical diagnostic analyzer apparatus. The liquid components332,336of the blood samples are aspirated then from the interior of a sample compartment51-58of container body41by means of a pipetting needle which is introduced into the compartments of container body through the pipetting openings89and aspirates samples of the liquid components332,336, and transfers them e.g. to reaction cuvettes of the clinical diagnostic analyzer apparatus.

In a preferred embodiment, step (b) is carried out with a centrifuge which is part of a clinical diagnostic analyzer which has an automatic pipetting unit and the blood samples to be processed are introduced by the latter pipetting unit through openings88of cover82of container body41into sample compartments52,56of this container, and after the separation of the liquid and non-liquid components of the blood samples, the pipetting unit of the analyzer aspirates samples of the liquid components from the lower portions of sample compartments52,56of container body41, and this samples are analyzed in the clinical diagnostic analyzer.

In a preferred embodiment, in step (a) of the above described method a blood sample is loaded into each of the compartments51-58of container body41.

Fourth Example of a Device According to the Invention

A fourth example of a device according to the invention is described hereinafter with reference toFIG. 16.

The structure of this device is similar to the structure of the device described above with reference toFIGS. 10 to 12, but in this fourth example each of the compartments51-58of container body41comprises in addition a photometric chamber102,106, which is fluidically connected with the interior of that compartment52,56through an opening92,96in the bottom wall49of the container body41. Each of the photometric chambers102,106is configured and dimensioned for enabling photometric measurement of a liquid contained therein. As shown byFIG. 16, photometric chambers102,106have plane parallel side walls which extend downwards from opening92,96in the bottom wall of the corresponding compartment52,56.

FIG. 16shows how mirrors112,116can be integrated with the photometric chambers102,106, so that when an incident light beam121,123is transmitted towards that chamber, a light beam122,124is reflected by mirror112,116. The arrangement of a mirror112,116in chambers102,106enables a photometric measurement of a liquid contained in that chamber102,106.

Fifth Example of a Device According to the Invention

A fifth example of a device according to the invention is described hereinafter with reference toFIG. 17. This is a variant of the device shown inFIG. 16.FIG. 17shows a front view seen from the direction indicated by arrow130of only one of the compartments of the device and shows a photometric chamber132which is fluidically connected with compartment52and which is suitable for performing photometric measurements.

As shown byFIG. 17, the chamber132of the device has plane parallel side walls which extend downwards from opening92in the bottom wall of the corresponding compartment52.

FIG. 17, shows an example of how mirrors141and142may be arranged externally with respect to chamber132to guide light during photometric measurement of a liquid contained in that chamber. In this case an incident light beam143is transmitted towards mirror141, a corresponding light beam144is reflected by mirror141, passes through chamber132, and is reflected by mirror142which emits a corresponding reflected light beam145.

Fourth Example of a Method According to the Invention

A fourth example of a method according to the invention for separating a liquid component from a blood sample makes use of the device described above with reference toFIG. 16or a device described above with reference toFIG. 17and comprises the following steps:(a) introducing blood samples312,316(as shown inFIG. 13) into respective sample compartments52,56of the container body41of a device according to the above described third example of a device according to the invention,(b) rotating the container body41about its symmetry axis43(as shown byFIG. 14) at a predetermined speed and in a sense shown by arrow50for separating the liquid components332,336of the blood samples312,316from the non-liquid components322,326thereof, and(c) stopping the rotating of the container body41, thereby allowing the liquid components332,336of the blood samples312,316to flow towards the central and bottom regions72,76and into photometric chambers102,106,132of the respective sample compartments52,56of the container body41, whereas the non-liquid components322,326of the blood samples312,316and portions of the liquid components332,336of the blood samples312,316are retained by layer84of the retaining porous material.

Step (b) is carried out as in example three.

After step (c) a portion of the liquid components332,336of the blood sample can be collected by pipetting through the pipetting openings89of cover82while the non-liquid components322,326of the blood samples312,316and portions of the liquid components332,336of the blood samples312,316are retained by layer84of the retaining porous material.

A layer86of separating permeable material is located between the sample compartment52,56and the layer of retaining porous material84. Non-liquid components of blood sample can pass through layer86of separating permeable material during centrifugation, while layer86of separating permeable material prevents the non-liquid components32from returning into the separated part of liquid component in the sample compartment52,56after separation is completed.

In this fourth example of a method according to the invention a portion of the separated liquid component332,336is collected in photometric chamber102,106or132and therein photometrically determined.

Again, a coagulation preventing agent or a coagulation promoting agent may be used and plasma or serum respectively obtained.

In a preferred embodiment, in step (a) of the above described method a blood sample is loaded into each of the compartments51-58of container body41.

Sample integrity checks including measurement of serum indices can be performed by photometric measurement of the serum sample contained in photometric chamber102,106or132.

The further processing of the contents of container body41after step (c) is e.g. as described above in the third example of a method according to the invention.

First Example of an Analytical Apparatus According to the Invention

A first example of an analytical apparatus according to the invention is e.g. a clinical diagnostic analyzer apparatus comprising a device as described above with reference toFIG. 1and an arrangement for centrifuging the sample tube11of such a device about its symmetry axis13.

In a preferred embodiment, this apparatus comprises a device as described above with reference toFIG. 6and a detector comprising electro-optical means for performing photometric measurements of the contents of the photometric chamber22of that device.

Second Example of an Analytical Apparatus According to the Invention

A second example of an analytical apparatus according to the invention is e.g. a clinical diagnostic analyzer apparatus comprising a centrifuge to receive the device as described above with reference toFIGS. 10 to 12and an arrangement for centrifuging the container body41of such a device about its symmetry axis43.

In a preferred embodiment, this apparatus comprises a device as described above with reference toFIGS. 16 and 17and electro-optical means for performing photometric measurements of the contents of the photometric chamber (cup)102,106or132of that device.

Experimental Data

In a device of the type described above with reference toFIGS. 10 to 15, the container body41is made by injection molding of a suitable plastic material, has a diameter of 6.5 cm and comprises8compartments51-58having each a volume of 4.7 mL. In each compartment a layer of retaining porous material84and a layer of separating porous material86are arranged. The layer84has a volume of 0.95 mL and is foam S605oHY reticulated, by Koepp Schaum GmbH, Germany. Layer86is Nytex Nylon 03-171 by Sefar, Switzerland.

A volume of 1.5 mL of each blood sample from different patients contained in lithium heparin test tubes (Becton Dickinson Vacutainer®) are introduced in different compartments of container body41.

The device is then rotated at 14000 rpm for 35 seconds with a centrifuge Minispin® Plus by Eppendorf, Germany.

After centrifugation, a volume of 500 mL plasma is collected from the lower portion of each compartment of container body41.

The quality of these plasma samples is compared with the quality of reference plasma obtained from the same blood samples by a conventional method, centrifuging at 1900 g for 10 min with conventional centrifuge.

A measure of the quality of plasma is the measure of the number of platelets still present in the plasma. This was measured by an automated hematology analyzer KX-21N by Sysmex, Japan.

The average platelet number for the reference samples was about 25000 while the average platelet number for plasma obtained with the device of the present invention was about <1000.

It is thus clear that the device according to the present invention makes it possible to obtain plasma samples of high quality in a short time.