HK1165752B - Method and device for providing blood constituents - Google Patents

Description

Method and device for providing blood components

Technical Field

The invention relates to a method for providing at least one defined volume of a target component of a sample, in particular a blood sample. The invention also relates to a metering capillary (Dosierkapillare) and a device for providing at least one defined volume of a target component of a sample. Such a method, metering capillary and device may be used in particular for obtaining a defined plasma volume from capillary blood.

Background

The testing of samples of body fluids, such as blood, often forms an essential component of medical diagnostics. Such tests can be used both in the outpatient field and in the point-of-care field or in the field of home monitoring. The invention described below is described in particular with respect to blood samples, but other types of samples, in particular liquid samples and preferably body fluids, can also be examined accordingly. The invention is described below primarily in relation to blood samples, but without limiting the other possible sample types.

The sample is generally supplied for at least one medical and/or diagnostic use. For diagnostic use, this may, for example, check at least one property, for example at least one physically and/or chemically or biologically measurable parameter. For example, the sample can be qualitatively and/or quantitatively detected for at least one analyte, in particular at least one metabolite. For this purpose, numerous detection methods are known from the prior art.

For example, glucose, cholesterol, triglycerides, heme, urea, alanine Aminotransferase (ALT), aspartate Aminotransferase (AST), glutamyl transpeptidase (GGT), Creatinine (CREA) or high density lipoprotein cholesterol (HDL-C) or combinations of said or other analytes may be detected. In addition, other properties of the blood, such as the proportion of corpuscular components (hematocrit value) can be determined.

A problem in the testing of, for example, blood samples, but also in the testing of other kinds of samples, is that the blood sample in many cases has to be processed before further use. In particular for a large number of applications, it is necessary to break down a blood sample into its components, for example to separate plasma from the corpuscular components of the blood sample. This separation of the blood sample into its components must generally be carried out very carefully, since for many measurements a high degree of purity, i.e. a high degree of separation, is required with simultaneously accurately defined sample quantities. The high requirements in terms of accuracy of sample provision in many cases prevent or hinder the analysis by non-professional persons, since sample provision must usually be performed by trained personnel in order to guarantee said requirements. For example, no or only few devices are available on the market to date which are capable of measuring the parameter HDL-C (high density lipoprotein cholesterol). The reason is based in particular on the fact that this parameter can only be measured in the plasma mixed with anticoagulant for a precisely defined sample volume (for example 31 ± 1.5 μ l) due to the coagulation occurring during the separation, i.e. only after a very careful sample supply.

One known method for obtaining plasma (e.g., capillary plasma) from a blood sample is to obtain capillary blood using subsequent centrifugation. For example, blood that has exited the body surface through the capillaries can be collected for subsequent centrifugation.

Devices for collecting and centrifuging capillary blood are basically known from the prior art. For example, document US 5,456,885 describes a tubular element for collecting, separating and delivering a two-phase liquid. Also commercially available are capillaries which break off after filling at predetermined breaking points in order to obtain an accurate sample volume. Such capillaries are commercially available, for example, from Dr. Mueller, Freital, D-01705, GermanyObtained by company Limited or described, for example, in the document DE 29520918U 1. The broken capillary portion with the amount of blood located therein is then transferred into a sample container, such as a tip-bottom container (cup). Such sample containers are then centrifuged in a corresponding centrifuge. Alternatively, a capillary plasma sample from capillary blood may also be obtained by collecting capillary blood directly in the sample container. After centrifugation (in which the corpuscular part of the blood sample is separated from the plasma), the excess from the plasma is then pipettedThe required amount of excess plasma is removed.

However, there is often a problem in pipetting out: this process must be carried out with extreme care, since there is this risk: when pipetted, the blood clot is contacted at the bottom of the container and thus the non-plasma components are pipetted together. The plasma fraction can thus become contaminated, thereby significantly affecting the measurement values.

This risk of contaminating the plasma fraction can only be reduced by taking an unnecessarily large amount of blood or plasma. For example, as capillary blood, it is generally necessary to collect about 5 to 7 times the required amount of plasma in order to be able to recover the required amount of plasma without the risk of contamination.

And the aspect of drawing a larger volume of blood creates significant difficulties. For example, for routine testing, for example, to quantitatively detect one or more of the above analytes, typically about 31 ± 1.5 μ l of clean plasma is required. According to the above method, which is premised on a high capillary blood flow rate of the available volume, this is not always satisfactory. For example, according to the above description, about 150-.

Capillaries with predetermined breaking points are also known from other documents of the prior art. A mixing device for testing blood or other liquids is known, for example, from document US 4,066,407. Furthermore, a pipette is described, which has the advantage of being a slit. After centrifugation, the pipette is cut along the slit.

DE 1598501 discloses a method and a device for measuring an exact sample quantity of a substance in a capillary. Also described herein are: the capillary-like member was closed with a cap and centrifuged after filling with the sample. The hematocrit dose may then be metered. The capillary element also has a score which enables the capillary element to be broken in order to check the amount of plasma of a well-defined volume.

Document DE 2217230 also describes a disposable device for separating exact quantities of liquid samples. Precision capillary elements with predetermined breaking points are used here.

In a similar manner, DE 2724465 a1 describes a disposable micropipette for volumetrically pipetting liquids, in particular for capillary blood withdrawal. This can be used, for example, to obtain accurate traces of plasma. The micropipette tube has a plurality of predetermined breaking points. The predetermined breaking point is arranged outside the micropipette tube.

Document DE 10106362 a1 describes a device and a method for collecting an aqueous liquid sample. In this case, a capillary tube and a closure element are used, wherein the closure element can be broken or broken by means of a predetermined breaking point comprising a capillary tube section surrounding it. The capillary tube also has a mixing element made of a ferromagnetic material and a holding element for holding the mixing element in its interior. However, the holding element acts in combination with the ferromagnetic mixing element, so that centrifugal separation of the capillary at high rotational speeds can lead to damage to the capillary channel. As a possible embodiment of the capillary end, a luer taper (Luerkonus), i.e. a conical reduction of the outer diameter in the region of the capillary end, is also described.

The devices and methods known from the prior art have a number of technical challenges and disadvantages in practice. A significant disadvantage lies in particular in the operational safety of the known device. In particular, the capillary with the predetermined breaking point must be operated manually or automatically a number of times until the desired target components of the sample can be provided. This operation naturally involves a large amount of vibration and positioning of the capillary tube at different positions and directions, which can lead to erroneous measurement results. This can lead to overflow of sample volume, undesired mixing of sample components or metering errors.

Disclosure of Invention

It is therefore an object of the present invention to provide a method and a device which at least largely avoid the disadvantages of the known methods and devices for providing a defined volume of target components of a sample. In particular, the proposed method and device should be capable of providing a volume of a target component of a sample, in particular a plasma component of a blood sample, operationally safe, constant and accurately, while having a high purity and without the risk of contaminating the target component by other sample components.

Disclosure of the invention

This object is achieved by a method and a device having the features of the independent claims. Advantageous developments of the invention, which can be realized individually or in combination, are indicated in the dependent claims. The method described below can be implemented in particular with one or more of the described devices, and the devices can be configured to carry out the method according to the invention in one or more of the described variants. Accordingly, reference may be made to the description of the apparatus for possible embodiments of the method and vice versa.

The invention is based on the recognition that: the methods known from the prior art, in which capillary blood is first drawn by means of a capillary tube, which is then broken off in order to produce a defined volume of blood and the blood is then centrifuged (if necessary after an optional further treatment), can be significantly simplified and improved thereby: no blood is drawn from the capillary prior to centrifugation. The invention relates to a corresponding method and device, which can be used in particular for obtaining and applying a precisely defined volume of plasma. A specially adapted metering capillary is used, which has a constriction (Konstriktion) at least one of its openings. Accordingly, the invention may include a combination of blood acquisition in a special capillary, plasma acquisition by means of centrifugal separation of the blood in the capillary and finally plasma application by volumetric metering by breaking off the end of the capillary with a well-defined internal volume and emptying of the defined plasma volume for subsequent testing (e.g. by coating on a test strip). The present invention significantly reduces the amount of blood required without the need for manual separation and pipetting steps. While the amount of plasma obtained is constant and precise in volume.

A method is generally provided for providing at least one defined volume of a target component of a sample. As already mentioned above, this sample can be, in particular, a blood sample (e.g. capillary blood) and/or another sample of a body fluid. But other samples may in principle also be used.

A target component is generally understood herein to be a component of the sample that is of interest for the provision, for example, for further use of the component. The target component may be, inter alia, blood plasma, as indicated above. Provision is here understood to mean the acquisition of the target component and/or the application of the target component, in particular in at least one medical and/or diagnostic use. By "defined" volume is understood a volume which can be reproducibly provided within a preset margin of error, for example within a range of not more than ± 5% of the margin of error, preferably not more than ± 1%.

The proposed method comprises the following method steps, which are preferably, but not necessarily, carried out in the order shown. Additional method steps not shown can also be carried out. Furthermore, individual or several method steps can be repeated, or performed in parallel in time or overlapping in time.

In a first method step, at least one metering capillary is provided, which has at least two openings. A metering capillary is understood here to mean a capillary with a capillary channel, the dimensions of which are basically known. At least the dimensions should be known or reproducible to that extent, i.e. such that the above-mentioned tolerances can be maintained. The metering capillary or the metering channel can preferably be designed to be substantially straight. However, other geometries are also possible in principle, for example a bent metering capillary, for example a U-shaped bent metering capillary.

The metering capillary has at least two openings. The opening can be arranged, for example, at or near the end of the metering capillary, for example at a distance from the end of not more than twenty times the outer diameter of the metering capillary. Alternatively or additionally, at least one of the openings may also be arranged at other locations of the metering capillary. For example, the metering capillary may have two openings situated opposite one another, for example at correspondingly opposite ends of at least one capillary channel of the metering capillary. The metering capillary is preferably configured as a double-sided open, preferably linear metering capillary. The at least two openings may, for example, comprise, as embodied further below, at least one distal opening and at least one proximal opening. The proximal opening is understood here to be the opening through which the filling takes place, whereas the distal opening is understood to be the other opening through which the filling does not take place.

At least one of the openings of the metering capillary has a constriction according to the invention. A constriction is generally understood within the scope of the present invention as a reduction of the inner diameter of the metering capillary compared to the inner diameter of the metering capillary around the constriction, for example viewed in the longitudinal extension direction of the metering capillary before and/or after the constriction. For example, the capillary channel may have a substantially constant inner diameter outside the constriction. However, other designs are also possible in principle, for example conical capillary channels. The constriction can in particular reduce the inner diameter of the metering capillary by half or less, in particular by a quarter or less.

Preferably, the constriction has a length along the longitudinal extension of the capillary channel which does not exceed twenty times, particularly preferably ten times or even five times or twice, the intermediate inner diameter of the capillary channel outside the constriction. Correspondingly, the constriction can be configured as a local constriction of the inner diameter of the capillary channel. Other designs are possible.

When the opening has such a constriction, this may mean within the scope of the invention that the constriction is arranged directly at the opening or directly adjacent to the opening. Directly adjacent is here understood to mean, for example, arranged at a distance from the opening which is not more than twenty times the diameter of the opening, preferably not more than ten times the diameter of the opening, and particularly preferably not more than five times the diameter of the opening, or even not more than two times the diameter of the opening. Since the opening, as described above, can be arranged in particular at or near the end of the metering capillary, the constriction can also be arranged in particular at or near the end. The constriction is a constriction which can be configured in particular as a tip.

The constriction may comprise, for example, at least one inwardly projecting, circumferential capillary edge. But other constrictions in other kinds of reduced forms of capillaries are also possible. In general, the constriction can be produced technically easily, for example by a corresponding drawing process of a capillary tube.

The constriction can be arranged in particular at the end of the metering capillary, which is also described below as the constriction end. The constriction can be configured, for example, in such a way that the inner diameter of the metering capillary is reduced by a constriction in the region of the constriction to a value of 10% to 80%, in particular to 20% to 60%, and particularly preferably to approximately 40% (e.g. 42%), of the value of the inner diameter in the region outside the constriction. In the region of the constriction, i.e. at the location of the metering capillary where it is most strongly constricted by the constriction, for example at the end of the constriction, the inner diameter of the metering capillary is preferably not greater than 1.0mm, particularly preferably not greater than 0.8mm, in particular not greater than 0.6mm, for example 0.5 ± 0.2 mm. For example, the inner diameter of the metering capillary in the region of the constriction may be between 0.2mm and 0.8mm, preferably between 0.3mm and 0.7mm, and particularly preferably 0.5mm ± 0.2 mm. The metering capillary may have an internal diameter of, for example, 0.5mm to 2.0mm, in particular 0.8mm to 1.6mm, preferably 1.0mm to 1.4mm, and particularly preferably 1.2mm, for example 1.20 ± 0.02mm, in the region outside the constriction. The metering capillary may, for example, have a wall thickness of 0.05mm to 3.0mm, for example 0.07mm to 0.5mm, and particularly preferably 0.1 to 0.2mm, for example 0.175mm ± 0.02 mm. In the undivided state, the metering capillary may have a length of, for example, 20mm to 200mm, preferably 30mm to 120mm, and particularly preferably between 70mm and 80mm, for example 75.0mm ± 0.5 mm. The metering capillary can be separated into two sections, for example, by a separation process, wherein the first section (which is preferably directed towards the constriction end) has a length of, for example, between 5mm and 60mm, in particular between 20mm and 40mm, and particularly preferably between 25mm and 30mm, for example 28.0 ± 0.9 mm. The volume contained in the first portion can be, for example, a fraction of 10% to 70%, preferably a fraction of 20% to 60%, and particularly preferably a fraction of 30% to 40%, for example a fraction of 37% ± 2%, of the total volume of the metering capillary.

The at least one constriction represents a significant advantage of the metering capillary according to the invention over the devices known from the prior art. As described, for example, in the document DE 2217230 cited above, special handling is required for handling the device proposed by it, in order to avoid blood spillage. According to DE 2217230, the operation of the disclosed device must be carried out with great care, while the capillary-like element must be forcibly held in a horizontal position.

These limitations in operation can be substantially completely avoided with the metering capillary according to the invention and the method according to the invention now proposed. In this way, it is now no longer mandatory to keep the metering capillary horizontal during sampling and phase separation, but an inclined setting and operating position and orientation can also be used via the constriction without the sample running out of risk, i.e. in which orientation the longitudinal extension of the metering capillary has an angle other than 0 °, for example an angle of at least 20 ° or even at least 50 °, with the horizontal, up to an at least approximately vertical orientation. This aspect improves the ease of use of the method and metering capillary. On the other hand, the error susceptibility to medical applications is also greatly reduced, since now user-induced errors (for example, errors caused by holding the metering capillary obliquely) no longer necessarily lead to sample acquisition errors and/or metering errors (for example, by an overflow of sample liquid and the resulting incomplete filling of the metering capillary) and correspondingly erroneous measurement results.

At the same time, the metering capillary proposed is suitable for a method described further below, which comprises a separation of the components in the metering capillary and a subsequent division of the metering capillary into sections, in contrast to the configuration described, for example, in the above-mentioned document DE 10106362 a 1. The metering capillary thus proposed can be centrifuged in particular without disturbing the mixing element and the holding element in this case, without the risk of damaging or mixing the sample components. The breaking method can also be carried out for separating the components, for example at predetermined breaking points, without the mixing element and/or the retaining element influencing the process. Further details of the method steps are set forth further below.

In a further method step, the metering capillary is at least partially filled with the sample. The filling takes place here, for example, via one or more of the at least two openings, i.e. the proximal opening. Preferably at least substantially completely filled, so that the capillary channel is preferably completely filled with sample. For this purpose, a smaller sample volume can flow out of the opening that is not used for filling, for example the distal opening mentioned above. The excess volume flowing out of the distal opening can be removed after filling, for example by simple wiping. But in principle it is also possible to not completely fill the metering capillary, as long as the relevant part of the capillary channel which then provides the defined volume is substantially completely filled.

Furthermore, the method comprises the implementation of a method step in which a component separation is carried out in order to at least partially separate at least two components of the sample within the metering capillary. In particular, the at least two components of the blood sample may comprise already mentioned plasma and corpuscular parts of the blood sample (clot). But alternatively also other kinds of separation, for example into more than two components. In this case, unlike the methods known from the prior art, the component separation takes place in the capillary itself, without the sample being removed from the metering capillary. The method proposed thereby differs, for example, from the known methods in which the broken-off part of the capillary is placed in a centrifugation container, in order to discharge its content there into the centrifugation container for subsequent centrifugation.

The separation of the components can be achieved in particular by applying a force to the metering capillary and/or to the sample contained in the metering capillary. In particular, it can be gravity and/or generalized force (Scheinkraft) here. Gravity can be used for component separation, for example, in the context of static separation or sedimentation. A generalized force may for example comprise a centrifugal force which acts on the metering capillary and/or the sample within the metering capillary, for example by means of a centrifuge, in particular a haemocytometer, etc.

In a further method step, the metering capillary is divided into at least two sections, wherein at least one of the sections contains a defined volume of the target component.

The division of the metering capillary into at least two sections can be achieved in different ways, which are preferably adapted to the component separation. For example, two segments can be provided, so that, for example, the metering capillary can be divided into exactly two segments, which each correspond to an end of the metering capillary. One of the sections may for example serve as a target section and may contain a defined volume of the target component. Instead, it is also possible to split the metering capillary into a plurality of segments, so that, for example, both ends of the metering capillary are broken off and only the middle segment serves as a target segment, which comprises a defined volume of the target component. Different designs are possible.

As indicated above, the method may further comprise providing a defined volume of the target component for at least one medical and/or diagnostic use. The providing may, for example, comprise providing an analytical method for detecting at least one analyte in the target component and/or other methods for determining at least one other characteristic of the target component. To provide, a defined volume of the target component may be output by the target segment, for example. Here again, for example capillary forces can be used, for example by opening a section of at least one of the sections (i.e. the target section with the defined volume of the target component accommodated therein) close to the test element and/or the sample carrier. This approach can be achieved, for example, by placing the segment opening on the sample carrier. The test element and/or the sample carrier can be designed flat, for example as a test strip or a flat microscope carrier. The section openings that achieve the output (i.e. provide a defined volume of the target component) may for example comprise openings that were already present in the metering capillary before, preferably distal or proximal openings. Alternatively, the section opening can also comprise at least one opening which is produced when the metering capillary is divided into at least two sections, for example an opening at the break-off edge. But preferably via an already existing opening, since this opening also remains defined at all times for the different segmentation processes.

For component separation, the corpuscular components of the blood sample can be separated at least partially from the plasma by means of centrifugal force and/or the action of gravity, in particular in the case of blood samples. The separation of the metering capillaries is then preferably effected by: the defined volume of the target component contains as much as possible only plasma. Contamination by other blood components within predetermined tolerance limits can be tolerated here if necessary. Alternatively or additionally, other target components can naturally also be selected. For example, the targeted blood cell component may be selected as the target component. The following does not limit the other possible embodiments, however, with regard to the selection of the target component from the plasma.

The selection of the at least one target component is effected, as indicated above, in that the metering capillary is divided in a targeted manner, in order to select the target component from the metering capillary after the separation of the components. This can be achieved in particular by separating the metering capillary into at least two sections. As is further carried out in the following exemplary manner, for example, at least one mechanical breaking method can be used for separating the metering capillaries. For example, the metering capillary may have at least one predetermined breaking point, for example in the form of a completely or partially circumferential slit. The concept of cracks is to be understood broadly here and in principle encompasses any local reduction in wall thickness. For example, a cut-out may also be included. The crack can be designed in particular such that it causes a smooth break when it breaks. A plurality of predetermined breaking points may also be provided. The predetermined breaking point can, for example, have a crack depth of between 10 μm and 100 μm, in particular between 35 μm and 50 μm, and a wall thickness of between 150 μm and 300 μm, in particular 175 μm or 200 μm. The ratio of crack depth to wall thickness may be, for example, between 1/4 and 1/6.

The metering capillary may further comprise one or more optically distinguishable markings. The predetermined breaking point can be marked in particular by a color, for example by providing one or more user-recognizable markings on the outside of the metering capillary in the region of the predetermined breaking point. For example, one or more annular markings can be provided on one or both sides of the predetermined breaking point, for example symmetrically to the predetermined breaking point. The color marking can facilitate the handling of the metering capillary and in particular the separation of the segments.

The division of the metering capillary, for example by corresponding breaking, can be carried out, for example, in such a way that the target volume comprises less than 50% of the capillary volume of the metering capillary, preferably a maximum of 45%, and particularly preferably 37%. For example, a capillary having a constant capillary diameter may be used. For example, the metering capillary may have a capillary volume of between 70 μ l and 150 μ l, preferably between 80 μ l and 90 μ l, and particularly preferably 84 μ l. When the total capillary volume is about 84 μ l, the volume of the target component may be, for example, 31 μ l for the segmentation.

In particular when a capillary with a constant capillary diameter is used as metering capillary, the metering capillary can be divided, for example, into two or more sections, for example by the breaking method described above. The metering capillary may be divided, for example, by a ratio x. This ratio x then corresponds, for example, to the partial length of the capillary in the section containing the defined volume of the target component compared to the total length of the metering capillary and/or the total length of the initially filled metering capillary. This preferred ratio results from typical, practically occurring, hematocrit values, which in most cases do not exceed 60%. In this way, it is possible, for example, to ensure that, when a blood sample is used, the division always takes place in the region of the metering capillary which is filled only with plasma, for example, by a proportion x of 37%, for example, by a corresponding selection of the position of the predetermined breaking point. The defined volume of the target component can then be extracted in particular from the smaller of the two sections, i.e. a section whose length is less than 50% of the total length of the metering capillary, or preferably a section which is at most 45%, in particular 37%, of the total length of the metering capillary.

Additional steps may be performed after performing the component separation and before segmenting the metering capillary, for example to determine other characteristics of the sample. In this way, for example, at least one intermediate analysis step can be carried out after the component separation and before the metering capillary is divided. In the at least one intermediate analysis step, at least one property of the sample can be derived, for example, from the separation of at least parts of at least two components of the sample, for example, a blood sample of plasma and a corpuscular component of the blood sample, in a metering capillary. For example, the proportion of the corpuscular components of the blood sample, in particular the hematocrit value, can be determined.

This intermediate analysis step can be carried out in a comparatively simple manner, for example by optical measurement and/or optical observation. This can be done fully automatically or also manually. For example, a metering capillary made of glass or another at least partially transparent material can be used, so that the separation of the components in the metering capillary can be observed optically. In this way, by determining the position of at least one separation line between at least two components, it is possible to derive, for example, at least one characteristic, such as a hematocrit value. For a constant capillary diameter of the metering capillary, this can be measured, for example, by measuring the length of the portion of the metering capillary filled with the corpuscular component, for example, using a simple ruler or other measuring instrument, and comparing this length to the total length of the metering capillary or to the total filling length of the metering capillary, in order to calculate the corpuscular density value.

The at least one provided metering capillary can, for example, be configured as a linear metering capillary, as described above, but other embodiments are also possible. The metering capillary may, for example, have a distal end and a proximal end, wherein the distal opening is arranged at the distal end and the proximal opening is arranged at the proximal end. The distal and proximal openings are preferably arranged at the ends of the metering capillary which lie opposite one another.

At least one of the openings of the metering capillary has a constriction according to the invention. Reference is made to the above description as to possible embodiments of the constriction. In particular, the at least one distal opening can be configured with such a constriction. The at least one proximal opening, i.e. the opening through which the filling of the metering capillary is effected, can be configured without such a constriction. Instead of or in addition to the constriction at the distal opening, other openings with such a constriction can naturally also be provided, for example a proximal opening.

The filling of the metering capillary can, as indicated above, be effected here in particular by the proximal opening. In this case, as indicated above, a quantity of sample can flow out at the distal opening during filling. In this way it is ensured that the metering capillary is completely filled. The amount of sample that flows out can be removed, for example, by wiping the metering capillary or by other cleaning steps, before component separation is performed and/or at other points in time in the method. If a metering capillary with a constriction is used, as proposed according to the invention, the outflow of the sample at the distal end of the metering capillary can generally be hindered or at least reduced.

As indicated above, the defined volume of the target component can be used, in particular, for at least one medical and/or diagnostic use after the division of the metering capillary and thus after the acquisition of the defined volume of the target component. The provision may for example be achieved by at least one of the openings. Thus, for example, openings assigned to the separation lines, for example at the break points after breaking off the metering capillary, can be used. Since the break-off edge may be undefined, it is particularly preferred to provide a defined volume of the target component for at least one medical and/or diagnostic use through the initially present opening, for example the distal opening.

The filling of the metering capillary, as indicated above, is preferably carried out such that it is substantially completely filled by the sample. This can be achieved, for example, by the very small amount of sample flowing out of the distal opening. Before performing the component separation, at least one of the openings should be closed, in particular by a centrifugal separation method. In particular, the proximal opening can be closed. Alternatively or additionally, other openings can also be closed, for example openings into which the sample is pressed during the separation of the components. This may again be a proximal opening, in particular. But other embodiments are also possible in principle.

The at least one opening can be closed in different ways. In particular, one or more of the following closures can be used: putty; a lid, in particular a plastic lid, preferably a silicone lid; waxes, especially, cytometric waxes; a resin; and (3) an adhesive.

For the at least one metering capillary, materials known from the prior art can in principle be used. For example, the at least one metering capillary may comprise at least one glass material and/or be made entirely of glass. But other materials are in principle also possible, such as quartz, ceramics, plastics, etc. The materials used can be adapted in particular to the separation method used. If a snap-off process is used, a hard, brittle material is preferably used. If other separation methods are used, such as shearing, it is preferred to use a material that is easily sheared, such as plastic. Transparent or at least partially transparent materials may be used in particular.

The metering capillary may in particular have a capillary inner diameter of between 0.5mm and 4mm, in particular between 1.0 and 1.2 mm. This capillary diameter has proven suitable in practice for the collection of, inter alia, blood samples. While other capillary diameters are in principle also possible.

The metering capillary may additionally comprise one or more active agents. The metering capillary can in particular have at least one anti-coagulation agent (Antikoagulanz-Wirkstoff), i.e. an agent which at least partially impedes the coagulation of the blood sample. The active agent may be introduced, for example, into the material of the metering capillary. It is particularly preferred, however, that the active agent is applied as a coating, in particular in the form of an anti-coagulation coating, as an alternative or in addition to the inside of the metering capillary. Conventional anticoagulants (anticoagulants) such as EDTA coatings (ethylenediaminetetraacetic acid) and/or heparin coatings, such as sodium-heparin and/or lithium-heparin and/or amino-heparin, may be used here. Other anticoagulants are also known and may be used instead or in addition.

In a further preferred embodiment of the metering capillary, the metering capillary is designed to be smooth and/or flat at the opening provided with the constriction, i.e. at the end of the constriction. The metering capillary can be designed to be flat or planar, in particular at the constriction end. In particular, sharp break-off edges can be avoided in this way. Smooth and/or flat designs can be produced, for example, by polishing and/or heat treatment, for example, by fire rounding (feuerardung). For example, the outer surface can extend approximately perpendicularly to the longitudinal extension axis of the metering capillary at the opening provided with the constriction, for example, deviating from 90 ° by no more than 5 ° from the longitudinal extension axis of the metering capillary. For example, "smooth" may mean here that the average roughness (RMS roughness) is less than 100 μm, preferably less than 50 μm, and particularly preferably even less than 20 μm or even less than 10 μm, less than 5 μm, or even less than 2 μm.

In this way, the constriction end can be a component of a first segment, for example, which is produced, for example, according to a breaking method and from which, after the component separation and subsequent division of the metering capillary into at least two segments, a defined volume of the target component is contained. The first section can, for example, be in contact with the at least one test element, for example with the test zone and/or the working zone of the test element, at the end of the constriction, as described further below. In this case, a movement of the constriction end can also be effected on the test element, for example a circular movement, which facilitates the distribution of the sample from the first section on the test element. Damage to the test element is avoided here due to the preferably smooth nature of the end of the constriction.

In addition to the method described in one of the described method variants, a metering capillary is also proposed, which can be used in particular in the method according to the preceding embodiment. The metering capillary includes at least two openings. At least one of the openings has at least one constriction. Furthermore, the metering capillary has at least one separation line between the openings, in particular at least one separation line with at least one predetermined breaking point. A separation line is understood here to mean a line, in particular a line running perpendicular to the longitudinal extent of the capillary, along which separation can take place (in particular optically recognizable to the user). Alternatively or in addition to this predetermined breaking point, the separation line can also be formed in another manner, for example with at least one separation mark, for example in the form of a ring mark or the like, which marks the position of separation of the metering capillary when it is divided into at least two sections. Reference may be made to the above description for additional possible details.

In addition to the method and metering capillary in one or more of the above-described embodiment variants, a device is also proposed for providing at least one defined volume of a sample target component, in particular a blood sample, in particular for providing a defined volume of plasma. The device can be provided in particular for carrying out a method according to one or more of the above-described embodiment variants. The device comprises at least one metering capillary, in particular of the type described previously. The metering capillary comprises at least two openings and at least one separation line, in particular a separation line with at least one predetermined breaking point and/or at least one separation mark. Furthermore, the device comprises at least one separation device for performing a component separation for at least partially separating at least two components of the blood sample within the metering capillary. The separation device may in particular comprise a centrifuge, for example a haemocytometer. For further alternative embodiments of the device, reference can be made to the above description, for example.

The device may furthermore comprise at least one support device which is provided for fixing the metering capillary in a defined position for at least partially filling the metering capillary with the sample. For this defined position, both the spatial position and the orientation can be included in the concept, in particular a substantially horizontal position. A substantially horizontal position is to be understood here as meaning that the metering capillary is at an angle of 0 ° to the horizontal, but slight deviations, for example deviations of not more than 20 °, preferably not more than 5 °, can also be tolerated. While other orientations are possible in principle. The support means may comprise, for example, a capillary mount, for example in the form of a simple capillary clamp. Alternatively or additionally, the support device can also be a component of a separation device for performing the separation of the components, for example, so that the above-described separation of the components can also be performed subsequently in the support device, for example.

The proposed method, the proposed metering capillary and the proposed device have a number of advantages over known methods and devices of this type. The method thus proposed allows, for example, to obtain an accurately defined capillary plasma sample in a very simple manner and independently of the actual hematocrit value, for example, to obtain exactly 31 μ l from 84 μ l of capillary blood. In particular, a metering capillary with at least one constriction (preferably at the distal end) proves advantageous. The constriction can in particular prevent plasma from escaping on the one hand when and after the metering capillary is detached, for example after the metering capillary has been broken off, and on the other hand can prevent the metering capillary from overfilling during the filling process by interrupting the capillary transport. In principle, such a constriction may prove advantageous, for example, also when the metering capillary is placed at an angle.

The filling of the metering capillary can in principle take place from one or more openings. Closure of the metering capillary is for example performed at the proximal end. Alternatively, a closed distal end is also possible in principle. In this case, it is an advantage that the closure (e.g. the putty slug) used to close the distal end of the metering capillary is less contaminated by the sample. The distal end can thus be closed with putty, which on its outside does not come into contact with a blood collection site, for example on a finger.

Drawings

Further details and features of the invention are given by the following description of preferred embodiments, in particular in connection with the dependent claims. The individual features can be realized individually or in a plurality in combination with one another. The invention is not limited to the embodiments. Embodiments are schematically shown in the figures. The same reference numbers in the various figures denote identical or functionally identical elements or elements which correspond to one another in terms of their function.

Wherein:

FIG. 1 shows an embodiment of a metering capillary according to the present invention; and

fig. 2A to 2F show method steps of an embodiment of the method according to the invention.

Detailed Description

Fig. 1 shows a simple embodiment of a metering capillary 110 according to the invention. The metering capillary 110 is configured, for example, as a glass capillary and has a wall thickness of, for example, between 0.05 and 5mm, in particular approximately 0.2 mm. The metering capillary has a length l of preferably between 50 and 150mm, in particular about 75 mm. The inner diameter of the metering capillary is, for example, between 1.1 and 1.2mm, while the outer diameter may be, for example, 1.6 mm. The outer diameter is here shown in fig. 1 as Φ_AMarked with an inner diameter of phi_IAnd (4) marking.

The metering capillary preferably has a substantially constant inner diameter Φ in the illustrated embodiment_ISo that the internal volume of the metering capillary 110 is evenly distributed over the length of the metering capillary 110.

The metering capillary 110 is configured in the illustrated embodiment as a straight, double-sided open metering capillary 110 with two openings 112,114 lying opposite one another. A first of these two openings 112,114 is referred to below as the distal opening 116, and the second of these openings 112,114 is referred to as the proximal opening 118. As can be seen from fig. 1, in the illustrated embodiment the distal opening 116 has a constriction 120. The constriction 120 measures the internal diameter Φ of the capillary 110_IFor example to half, in particular to a quarter or less.

Furthermore, the metering capillary 110 has a separation line 122. The separation line 122 may comprise, for example, optically identifiable indicia. And it is particularly preferred that the separation line 122 comprises, as shown in fig. 1, a predetermined break point 124, at which the metering capillary 110 breaks. The crack depth of the crack may be, for example, 1/20 to 1/2, in particular 1/4 to 1/6, of the wall thickness of the metering capillary 110. For example, for a wall thickness of about 0.2mm, a groove depth of, for example, 35 μm to 50 μm is preferred.

The separation line 122 is arranged at a distance l' from one of the two openings 112,114, preferably the distal opening 116. The ratio of l' to l is also referred to below as x. Preferably, x is < 50%, and especially maximally 45% or less, especially 37%. Accordingly, in the interior of the metering capillary 110, a volume V' is accommodated between the distal end 126 (with the distal opening 116 at the distal end 126) and the parting line 122, which (taking into account the possible slight deviation by the constriction 120 at the distal end 126) and the ratio of the total volume V between the distal end 126 and the proximal end 128 being x. For example, the total volume V may comprise about 84 μ l, while the defined volume V' (which is also denoted below with reference numeral 130) is preferably 31 μ l ± 1.5 μ l. But other volumes or segmentations are possible in principle. The defined volume 130 contains the target component in the method described below.

The metering capillary 110 may optionally be modified in different ways. The metering capillary 110 can, for example, as is also shown in fig. 1, have an anti-coagulation coating 132, for example an EDTA coating, on its inner side.

Fig. 2A to 2F show method steps of an embodiment of the method according to the invention for providing a defined volume of target components of the sample 134. The sample 134 is here a blood sample in the present example, which is decomposed, for example, into plasma and corpuscular components. Here, the sample 134 before and after processing is conceptually not distinguished, so that it is collectively denoted by reference numeral 134. At the same time, these figures illustrate the use of a metering capillary 110 for providing a defined volume of a target component of a sample 134 and, in part, a device 136 according to the present invention.

Fig. 2A first provides a metering capillary 110, which is an integral part of the device 136. For example, it may be a metering capillary 110 of the kind described with reference to fig. 1. For example, a metering capillary 110 containing approximately 84. mu.l of EDTA coating having a length l of 75mm and an internal diameter Φ of 1.2mm may be used_IWhich has a slight constriction 120 at its distal end 126. Furthermore, the metering capillary 110 may have a separation line 122, in particular a predetermined break point 124, at a suitable location, for example at a distance l' of about 27mm from the distal end 126.

Furthermore, fig. 2A shows a process in which the metering capillary 110 is filled with a sample 134 (for example in the form of capillary blood) from its openings 112, 114. In the illustrated embodiment, this filling takes place from opening 112, which is thus defined as proximal opening 118. Instead, filling can also take place from the other opening 114. Preferably at least nearly completely filled.

During filling, metering capillary 110 may be housed, for example, in support 138. The support device 138 can be designed, for example, as a clamping device. The support device 138, as indicated in fig. 2A by reference numeral 140, can also be a component of a separation device, such as a centrifuge, in particular a haemocytometer. While a separate support 138 is also conceivable in principle. The support device 138 may be provided, inter alia, for holding the metering capillary 110 in a horizontal position. Thereby enabling the metering capillary 110 to be filled by a drop of blood 142 on the patient's finger 144. Alternatively or additionally, other kinds of samples may also be provided, for example samples from a separate container which is filled with blood beforehand. The proposed filling directly from the blood drop 142 has a number of advantages.

After the filling of the metering capillary 110 shown in fig. 2A, at least one opening 112,114 of the metering capillary 110 is closed in the method step shown in fig. 2B. Here, the metering capillary 110 can also be accommodated in a support 138, which is not shown in fig. 2B. In the embodiment shown in fig. 2B, the opening 118 proximal thereto is closed. In general, it is possible in particular to close that one of the openings 112,114, which is located furthest away from the axis of rotation of the centrifuge in the separation step described below when using the centrifuge as separation device 140, so that the sample 134 is pressed against this closed opening 112, 114. In this example, this is the proximal opening 118.

The closure of the openings 112,114 may be achieved, for example, with a closure 146, which may include, for example, a silicone cap, a wax of a corpuscular density, a resin, or a suitable adhesive.

The constriction 120 has a particularly positive effect on the opposite distal end 126 of the metering capillary 110, already when the metering capillary 110 is filled as shown in fig. 2A, but also when the proximal opening 118 is closed with a closure 146. As such, constriction 120 may impede substantial spillage of sample 134 from distal opening 116, for example, during filling or also during placement of closure 146. As shown in fig. 2B, while a smaller amount of sample 134 may flow out of distal opening 116 and then be removed, for example, by simple wiping. This excess (ueberstan), which flows out of the distal opening 116, is marked in fig. 2B with reference numeral 148.

Fig. 2C finally shows the filled metering capillary 110 closed with a closure 146. It may still be accommodated in the support means 138, which is not shown again in fig. 2C. Other storage is in principle also possible and, alternatively or additionally, the transport of the metering capillary 110. For this purpose, the distal opening 116 may optionally also be closed, for example, by a cap and/or by gluing or by a similar closure.

Subsequently, a step of component separation, shown symbolically in fig. 2D (here shown perspectively from above), is carried out. In component separation, a first component of the sample 134 (which includes the corpuscular part 152 of the sample 134) is separated from a second component 154 (which in the example shown includes plasma 156) at least to a large extent. This is achieved, for example, by means of the above-described separating device 140, in particular a centrifuge. The centrifuge may be configured, for example, as a blood cell density centrifuge or the like. In particular, simple centrifuges can be used which have no adjustment possibilities, for example, have a fixedly predefined rotational speed and/or operating time. The separation of the two components 150, 154 is effected in this case by centrifugal force, wherein the denser, corpuscular fraction 152 is pushed towards the proximal end 128 of the metering capillary 110. The lighter plasma 156 components, in turn, accumulate to the distal end 126. Between the two components 150, 154, as shown in fig. 2D, a phase boundary 158 is configured. The location of the phase boundary 158 is determined by the actual hematocrit value. The separation line 122, for example a predetermined breaking point 124, is chosen such that its position: it is located within the area of the second component 154 as close as possible to the phase boundary 158 for commonly occurring hematocrit values. As mentioned above, it may in particular be arranged 30mm from the distal end 126.

During the separation step, air bubbles may accumulate in the metering capillary 110 at the distal end 126. If this is the case, they can be pressed out of the distal opening 116, for example, in a further optional method step, for example, by the putty of the closure 146 being pushed back into the proximal opening 118. For example, the proximal end 128 may be pressed back into a putty pad (Kittmatte) after the detachment step. This ensures that the defined volume 130 no longer contains bubbles.

After the separation step, the metering capillary 110 may be removed from the separation device 140 and separated into at least two sections 160, 162. This is illustrated in fig. 2E by a simple break of the metering capillary 110 along the predetermined break point 124. Instead, the metering capillary 110 may also be divided into more than two sections.

The target component 164 is selected by separating the metering capillary 110 into sections 160, 162. In the illustrated embodiment, the target component 164 is as large a fraction as possible of the plasma 156, the plasma 156 forming the second component 154 of the sample 134. The target component 164 has here, as has already been described with reference to fig. 1, a precisely defined volume V'.

The plasma 156 thus obtained in the target component 164 may be mixed with different anticoagulants, for example, depending on the coating 132 of the metering capillary 110. Plasma 156 can also be produced from non-anticoagulated blood, for example by correspondingly rapid processing.

The centrifuged off target volume of target component 164 may, for example, be exactly 31 μ l, as described above. The target component 164 may, for example, be applied to a test element 166. This is exemplarily shown in fig. 2F. Here, a test element 166 in the form of a test strip is shown by way of example, which has at least one test field 168. For example, the test zones 168 may include a corresponding test chemistry. As an example, the method for Reflotron can be usedHDL-C-reagent carriers for model analyzers. The application of the target component 164 in the first section 160 can be carried out, for example, by: the distal opening 116 with constriction 120 is in contact with the carrier web of test zone 168. Instead, the openings 170 assigned to the predetermined breaking points 124 (which are produced in the separation step of the two segments 160, 162 shown in fig. 2E) can also be placed on the carrier web. But preferably the variant shown, in which one of the openings 112,114 already present initially (preferably the opening 114 with the constriction 120) is placed on the test zone 168, because it provides a defined limit surface, for example a smooth, flattened or polished limit surface. After application to the test element 166, for example, a property of the sample 134, which is now a plasma sample, can be measured, for example, qualitatively and/or quantitatively detecting at least one analyte in the plasma sample. For example, high density lipoprotein-cholesterol can be examined.

The described method and the illustrated device 136 furthermore enable further properties of the capillary blood sample to be determined. One or more intermediate analyses may thus also be performed, for example after the separation step shown in fig. 2D, but before the step of separation of the two sections 162, 164 shown in fig. 2E. The position of the phase boundary 158 can thus be determined, for example, by means of a corresponding measuring device. In this way, for example, the proportion of the corpuscular component 152 can be determined directly and thusThe hematocrit value of the sample 134 is obtained. This can be done, for example, by determining the red blood cell column with the aid of a calibrated rulerIs achieved (i.e., the length of the fraction 152 of blood cells of the first component). Since the metering capillary 110 is always filled uniformly and preferably completely, no nomogramming (Nomogramm) is generally required, similar to that of a small blood cell density tubeThe density of the blood cells is determined.

After the measurement, the two sections 160, 162 of the metering capillary 110 can be discarded or supplied to further measurements. The techniques required for producing metering capillaries with suitable markings and/or predetermined breaking points 124 are known in principle to the skilled worker. The required accuracy with regard to the amount of target component 164 to be obtained, for example plasma, is not problematic with regard to the manufacturing technology.

The separating apparatus 140, such as a centrifuge, also typically has no requirement for accuracy of rotational speed and/or operating time. The centrifugal force generated should be selected to be as low as possible so as not to overly load the sealing site at closure 146 at proximal end 128 of metering capillary 110. For example, a relative centrifugal force (rcf) of 5.000g to 10.000g, in particular 7.000 to 9.000g, and particularly preferably 8.000g, can be used, where g is the acceleration due to gravity. The proposed capillary dimensions are sufficient, for example, for hematocrit values of up to 60%, in order to be able to obtain 31 μ l of plasma.

Other, defined amounts of plasma or other amounts of the target component 164 can also be obtained by suitably positioning the predetermined breaking point 124 at the distal end 126 of the metering capillary 110 or by varying the inner diameter 110 of the metering capillary. The principle method of operation is not changed accordingly.

It is noted that the described metering capillary 110 may also be applied without performing a separation step. In this way, for example, a predetermined amount of blood can be applied by means of the metering capillary 110 without centrifugation.

It is furthermore noted that the method in fig. 2A to 2F is only symbolically shown and can be modified at will within the scope of the invention. Thus, for example, the constriction 120 can also, alternatively or additionally, be provided at the further openings 112, 114. Filling can also take place from the other openings 112, 114. Different variants of the illustrated method are conceivable.

As described above, the constriction 120 furthermore significantly improves and simplifies the operation of the metering capillary 110. The operational safety is particularly improved by preventing undesired spillage. To determine this, different tests were performed.

In these tests, the metering capillary 110 is used with a sample in the form of fresh capillary blood (also labeled "K" below) or venous blood (also labeled "V" below). Metering capillary 110 is coated with EDTA and has constriction 120. The metering capillary 110 has a length of 75.00mm + -0.50 mm, an inner diameter of 1.20mm + -0.02 mm, an outer diameter of 1.55mm + -0.02 mm, and a length of the first section 160 of 28.00mm + -0.90 mm. In the region of the constriction 120, the metering capillary 110 has an inner diameter of 0.50mm ± 0.20 mm. The predetermined breaking point 124 is marked on both sides by black ring marks having a width of 0.80mm ± 0.10mm, which are respectively arranged at a distance of 1.0mm ± 0.20mm from the predetermined breaking point 124.

The metering capillary 110 is completely filled with the sample 134 and accordingly held at a preset inclination to the horizontal for 5s of tipping. In this case, the two tilting directions are measured in each case, namely one tilting is carried out in each case with the opening 114 with the constriction 120 facing downward (hereinafter also referred to as "constriction end down" or "KU"), and one tilting is carried out in each case with the opening 112 without the constriction 120 facing downward (hereinafter also referred to as "open end down" or "OU").

The results of this measurement are shown in table 1. The abbreviations "K", "V", "KU" and "OU" used in this Table 1 have been set forth above. Furthermore, in the column of Table 1, which is marked with an inclination, the corresponding pair of each test indicates whether the sample 134 remains in the metering capillary 110 during the test (marked with a "+") or overflows (marked with a "-").

As the results in table 1 show, with one exception (serial number 6), two blood types (capillary and vein) meet the test conditions up to an angle of 30 °. This provides sufficient spill safety when handling the metering capillary 110, for example when removing it from the support, when sealing with a wax of corpuscular density or similar handling procedures. A completely filled metering capillary 110 of this size without constriction 120 will already overflow with a tilting hold of about 5 °, which can also happen inadvertently during operation. Furthermore, the constriction 120 allows the metering capillary 110 to be quickly rotated by 180 °, which is likewise not possible without the constriction 120. Thus, the constriction 120 is an important safety feature when operating the metering capillary 110.

Table 1: test results for sample spillage at different tilt angles for a metering capillary with a constriction.

The 5s hold time used in the described experiments provides in practice sufficient time for the metering capillary 110 to be operated with an idle hand. Furthermore, the test shows that the operator operating the metering capillary 110 does not suffer from the unfortunate fact that the metering capillary 110 overflows during the test. This unfortunate, in practice, often occurs with a completely filled, open, hematocrit capillary. Furthermore, the test shows that the metering capillary 110 with the constriction 120 is protected or even completely protected against spillage after an optional, one-sided closure, for example with a haemoglobin wax, at least until the separation process is carried out.

The constriction 120 is preferably provided only on one side, as is also the case in the described test. Another important reason for installing the constriction 120 unilaterally is the overflow behavior of the broken-off portion of the metering capillary 110 (e.g., the first section 160 in fig. 2E). The contents of first section 160, e.g., its plasma contents, should be applied, e.g., completely, to test element 166, e.g., to the refletron HDL C-test carrier, after centrifugation. In many cases, this will only work if first section 160 is placed in test zone 168 and/or working zone (e.g., yellow-coated zone for Reflotron HDL C-test carrier) without pressure and placed in a slight swirling motion until it is completely emptied. The pinch end with the pinch 120 is in many cases smoothly cut or rounded, for example, pyrogenically rounded. Conversely, if the other end of the first section 160 is used for movement during coating, the test zone 168 is easily damaged and rendered unusable by the friction of the sharp-edged capillary ends of the first section 160 (e.g., on the cover fabric of the test zone 168). Particularly preferably, the constriction end thus ends flat.

The metering capillary 110 is furthermore preferably filled with the sample 134 via the constriction end. Accordingly, the metering capillary 110 is generally contaminated with the sample 134, for example blood, only on the side of the constriction end on the outside thereof after filling. While cleaning the metering capillary 110 from the outside is difficult and tricky in practice. Such wiping of, for example, the metering capillary 110 requires skill and speed for an open capillary so that a portion of the sample 134 (e.g., blood) is not carried out of the metering capillary 110 altogether, for example, by the suction of the fiber cloth used for wiping. If a constriction 120 is used, the cleaning process is generally not difficult at all in practice due to the constriction 120 and can also be carried out without problems by a novice. The increased capillary force in the constriction 120 reliably prevents the sample 134, for example blood, from being carried out by the wipe.

List of reference numerals

110 metering capillary

112 opening

114 opening

116 distal to the opening

118 proximal opening

120 constriction

122 separation line

124 predetermined breaking point

126 distal end

128 proximal end

130 volume defined by

132 anti-coagulation coating

134 sample

136 device for providing a target component of a blood sample

138 support device

140 separating device

142 blood drop

144 finger abdomen

146 closure

148 excess

150 first component

152 blood cell fraction

154 second component

156 plasma

158 phase boundary

160 first section

162 second section

164 target component

166 test element

168 test area

170 opening

Claims (1)

1. A method for providing at least one defined volume of a target component (164) of a sample (134), the method comprising the steps of:

-providing at least one metering capillary (110) with at least two openings (112,114), wherein the openings (112,114) are arranged at the ends of the metering capillary (110), wherein at least one of the openings (112,114) has a constriction (120), wherein the constriction (120) is arranged directly at the opening (112,114), wherein the constriction (120) comprises at least one inwardly projecting annular edge of the metering capillary (110), wherein the constriction (120) is designed in such a way that, by means of the constriction (120), the inner diameter of the metering capillary (110) is reduced in the region of the constriction (120) to a value of 10% to 80% of the value of the inner diameter in a region outside the constriction (120), wherein the metering capillary (110) is at the opening (112,114) At least one separation line (122) with at least one predetermined breaking point (124);

-at least partially filling the metering capillary (110) with the sample (134);

-performing a component separation to at least partially separate at least two components (150, 154) of the sample (134) within the metering capillary (110); and

-dividing the metering capillary (110) into at least two sections (160, 162), wherein at least one of the sections (160) contains the defined volume of the target component (164).

2. The method according to claim 1, further comprising providing the defined volume of target components (164) for at least one medical and/or diagnostic use, or an analytical method for detecting at least one analyte in the target components (164).

3. The method according to claim 2, characterized in that the provision of the defined volume of target components (164) is effected by bringing a segment opening (114, 118, 170) of at least one of the segments (160) into proximity with a test element (166) and/or a sample carrier.

4. The method according to any of the preceding claims 1 to 3, characterized in that the sample (134) comprises a blood sample, wherein the corpuscular components (152) of the sample (134) are at least partially separated from the plasma (156) in a component separation by means of centrifugal force and/or the effect of gravity, wherein the segmentation of the metering capillary (110) is carried out in such a way that the defined volume of the target component (164) contains only the plasma (156).

5. The method of any of the preceding claims 1-3, wherein the metering capillary (110) has a capillary volume, wherein the defined volume of target component (164) comprises less than 50% of the capillary volume.

6. The method according to any of the preceding claims 1-3, further comprising at least one intermediate analysis step performed after performing component separation and before segmenting the metering capillary (110), wherein at least one characteristic of the sample (134) is derived from at least partially separating the at least two components of the sample (134) within the metering capillary (110).

7. The method according to the preceding claim 6, the characteristic being the fraction of corpuscular components in the sample (134).

8. Method according to any of the preceding claims 1-3, characterized in that at least one of the openings (112,114) is closed before performing the component separation, wherein the closing is achieved by at least one of the following closures (146): a cover; and (3) an adhesive.

9. The method of claim 8, wherein the at least one of the openings (112,114) is a proximal opening (118).

10. Method according to claim 8, characterized in that the lid is a plastic lid.

11. Method according to claim 10, characterized in that the lid is a silicone lid.

12. Method according to any of the preceding claims 1-3, characterized in that at least one of the openings (112,114) is closed before performing the component separation, wherein the closing is achieved by at least one of the following closures (146): putty, wax or resin.

13. The method according to claim 12, wherein the wax is a cytometric wax.

14. Method according to any one of the preceding claims 1 to 3, characterized in that for dividing the metering capillary (110) at least one mechanical breaking method is used, wherein the metering capillary (110) has at least one predetermined breaking point (124).

15. The method of claim 1, wherein the at least one of the openings (112,114) is a distal opening (116).

16. A metering capillary (110) for providing at least one defined volume of a target component (164) of a sample (134) using the method of any one of the preceding claims 1 to 15, the metering capillary (110) comprising at least two openings (112,114), wherein the openings (112,114) are arranged at the ends of the metering capillary (110), wherein at least one of the openings (112,114) has at least one constriction (120), wherein the constriction (120) is arranged directly at the opening (112,114), wherein the constriction (120) comprises at least one inwardly projecting annular edge of the metering capillary (110), wherein the constriction (120) is designed in such a way that, by means of the constriction (120), the inner diameter of the metering capillary (110) decreases in the region of the constriction (120) to a region outside the constriction (120) Wherein the metering capillary (110) furthermore has at least one separation line (122) with at least one predetermined breaking point (124) between the openings (112, 114).

17. The metering capillary (110) of claim 16, wherein the metering capillary (110) has a capillary volume, wherein the defined volume of target component (164) comprises less than 50% of the capillary volume.

18. The metering capillary (110) according to any one of the preceding claims 16 to 17, characterised in that the metering capillary (110) has at least one anti-coagulation active agent which is introduced into the material of the metering capillary or is applied as a coating on the inside of the metering capillary.

19. The metering capillary (110) as claimed in claim 18, the metering capillary (110) having an anti-coagulation coating (132).

20. The metering capillary (110) according to the preceding claim 18, the metering capillary (110) having an EDTA coating.

21. The metering capillary (110) according to any one of the preceding claims 16 to 17, characterised in that the metering capillary (110) is configured to be smooth and/or flat at the opening (112,114) provided with the constriction (120).

22. The metering capillary (110) according to the preceding claim 21, characterised in that the metering capillary (110) is polished and/or rounded by heat treatment at the opening (112,114) provided with the constriction (120).

23. A device for providing at least one defined volume of target components (164) of a sample (134), the device comprising at least one metering capillary (110) according to any of the preceding claims 16-22, furthermore comprising at least one separation device (140) for performing a component separation for at least partially separating at least two components (150, 154) of the sample (134) within the metering capillary (110).

24. The device according to claim 23, further comprising a support device (138) arranged to fix the metering capillary (110) in a defined position in order to at least partially fill the metering capillary (110) with the sample (134).

25. The device according to claim 24, the support means (138) being arranged to fix the metering capillary (110) in a substantially horizontal position in order to at least partially fill the metering capillary (110) with the sample (134).