DE102023119098A1 - Method for setting a total density of a solid-state separator and set of solid-state separators - Google Patents

Abstract

The application relates to a method for setting a total density (ρ _total ) of a solid separator (1) for separating at least two components (2, 3) of a body fluid (4), wherein the first component (2) has a first density (p ₁ ) and the second component (3) has a second density (ρ ₂ ) and wherein a target value of the total density (ρ _total ) of the solid separator (1) lies between a value of the first and a value of the second density (ρ ₁ , ρ ₂ ), the solid separator (1) comprising
- a first material (5) and
- a second material (6), wherein both materials (5, 6) are present separately from one another in the solid-state separator (1).
In order to provide a method for setting a total density (ρ _total ) of a solid-state separator (1) which can be carried out particularly simply and quickly and at the same time eliminates the disadvantages of the prior art, the invention provides that an inserted volume (V ₁ , V ₂ ) of at least one of the materials (5, 6) of the solid-state separator (1) is adjusted depending on the determined current densities (ρ ₁ , ρ ₂ ) of the two materials (5, 6) so that the value of the total density (ρ _total ) of the solid-state separator (1) corresponds to the target value.
Furthermore, the application relates to a set comprising at least two solid-state separators (1).

Description

The present application relates to a method for adjusting a total density of a solid-state separator for separating at least two components of a body fluid according to the preamble of claim 1. Furthermore, the present invention relates to a set comprising at least two solid-state separators, with the features according to claim 14.

Solid-state separators are used to separate components of a body fluid from one another. A first component of the body fluid has a first density and a second component of the body fluid has a second density. The body fluid can be blood in particular, with the components to be separated being the blood serum and blood plasma as well as the leukocyte film (buffy coat). However, any other body fluid can also be broken down into its components and kept in a separate state using the solid-state separator. For example, the solid-state separator can be used to separate urine, saliva, amniotic fluid and intestinal fluid into their respective components.

The solid-state separator typically comprises a first material and a second material, with the two materials being present separately from one another in the solid-state separator.

A solid separator is generally used in conjunction with a centrifuge to separate the components of a body fluid. The solid separator is placed in a sample container, typically a tube, together with a body fluid and then centrifuged. As a result of the centrifugal force acting on the body fluid and the different densities of the two components of the body fluid, the components separate from one another. Since this state only lasts as long as the centrifugal force acts on the body fluid, the solid separator is required. A target value for the overall density of the solid separator lies between the densities of the two components, so that the solid separator positions itself between the two components during centrifugation. The solid separator is typically designed in such a way that an exchange of components is possible during the centrifugation process, but is prevented if the centrifugal force is removed. In this way, the components of the body fluid remain separated from one another in the sample container even after the centrifugation process, i.e. after the centrifugal force has ceased.

One problem with known solid separators has been that the materials used to manufacture the solid separator are subject to batch-related fluctuations. However, since the overall density of the solid separator is tailored to the body fluid to be separated, the fluctuations in the densities of the materials mean that the solid separator does not position itself optimally between the components during centrifugation. The result can be an unwanted mixing of the components after the centrifugation process has ended or the receipt of an insufficient sample volume for an analysis of the body fluid.

State of the art

To solve the above-mentioned problem, methods for adjusting the overall density of a solid-state separator are known. For example, the WO 2016/069613 A1 The solid-state separator shown there is impermeable to liquids after insertion into a sample container, but has a ball in an interior which, when subjected to a centrifugal force, moves from a rest position against a spring and thus opens up a passage opening for the body fluid. When the centrifugal force is removed, the ball is moved to the rest position due to the force provided by the spring and thus closes the passage opening. The solid-state separator also has cavities in the interior which can be filled with a fluid depending on the densities of the components of the body fluid to be separated in order to be able to set an overall density of the solid-state separator. For example, the cavities can be filled with a liquid or gaseous composition during a manufacturing process. It can also be provided that the cavities enclose a vacuum.

However, the disadvantage of the known methods for setting the overall density of a solid-state separator has been that the manufacture of such solid-state separators is particularly complex. In particular, it cannot be ruled out that the composition that is filled into the cavities is also subject to fluctuations that would have to be taken into account.

Task

The object of the present invention is therefore to provide a method for adjusting the total density of a solid-state separator, which is particularly simple and quick to carry out and thereby eliminating the disadvantages of the state of the art.

Solution

Based on the method mentioned above, the above object is achieved by adjusting the volume used of at least one of the materials of the solid-state separator depending on the determined current densities of the two materials.

In the context of the present invention, the "total density" of the solid separator is understood to be the quotient of a total mass and a total volume of the solid separator. The total mass is made up of at least the masses of the two materials, the total volume is made up of at least the volumes of the two materials.

In the context of the present invention, the "target value" of the total density does not necessarily mean a single value. Rather, the target value can also be a range in which the total density should lie.

The adjustment is made in such a way that the value of the total density of the solid separator corresponds to a target value. The target value depends on the densities of the components of the body fluid to be separated. In the event that the body fluid to be separated is blood, the target value for the total density of the solid separator is in a range between 1.040 and 1.045 g/cm ³ . The materials used to manufacture the solid separator have different densities, and the densities of the materials can be subject to batch-related fluctuations. If a volume of material with a fluctuating density is maintained regardless of the fluctuation, it cannot be guaranteed that the total density of the solid separator corresponds to the target value. Rather, the total density of the solid separator also fluctuates in such a case. This is because the total density of the solid separator is determined from the quotient of a total mass and a total volume of the solid separator. The total mass is determined from the sum of the masses of the materials used, the total volume from the sum of the volumes of the materials used. If the solid separator is made of two materials, the total density of the solid separator can be determined as follows: $${\rho }_{Gesamt}=\frac{\mathrm{<figure-callout\; id="1"\; label="m"\; filenames="DE102023119098A1\_0005.png,DE102023119098A1\_0010.png"\; state="\{\{state\}\}">m</figure-callout>}1+m2}{{\mathrm{<figure-callout\; id="1"\; label="V"\; filenames="DE102023119098A1\_0005.png,DE102023119098A1\_0010.png"\; state="\{\{state\}\}">V</figure-callout>}}_1+{\mathrm{<figure-callout\; id="2"\; label="V"\; filenames="DE102023119098A1\_0015.png"\; state="\{\{state\}\}">V</figure-callout>}}_2}=\frac{{\rho }_1\cdot {\mathrm{<figure-callout\; id="1"\; label="V"\; filenames="DE102023119098A1\_0005.png,DE102023119098A1\_0010.png"\; state="\{\{state\}\}">V</figure-callout>}}_1+{\rho }_2\cdot V_2}{{\mathrm{<figure-callout\; id="1"\; label="V"\; filenames="DE102023119098A1\_0005.png,DE102023119098A1\_0010.png"\; state="\{\{state\}\}">V</figure-callout>}}_1+{\mathrm{<figure-callout\; id="2"\; label="V"\; filenames="DE102023119098A1\_0015.png"\; state="\{\{state\}\}">V</figure-callout>}}_2}$$

Here, m ₁ describes the mass of the first material used, m ₂ the mass of the second material used, V ₁ the volume of the first material used and V ₂ the volume of the second material used. The densities of the materials can be determined from the quotient of mass and volume, where ρ ₁ describes the density of the first material and ρ ₂ the density of the second material.

In order to prevent the overall density from fluctuating, the invention provides for the densities of the materials to be determined first. The densities can then preferably be compared with a respective target density of the materials. If deviations are found between the determined densities of the materials to be used and the respective target density, a volume of the material or materials with a different density is adjusted during the manufacture of the solid-state separator.

For example, if the density of the second material matches the target density, while the density of the first material deviates from the target density, the volume of the first material to be used can be determined as follows: $${\mathrm{<figure-callout\; id="1"\; label="V"\; filenames="DE102023119098A1\_0005.png,DE102023119098A1\_0010.png"\; state="\{\{state\}\}">V</figure-callout>}}_1=\frac{V_2\left({\rho }_{gesamt}-{\rho }_2\right)}{{\mathrm{<figure-callout\; id="1"\; label="\rho "\; filenames="DE102023119098A1\_0005.png,DE102023119098A1\_0010.png"\; state="\{\{state\}\}">\rho </figure-callout>}}_1-{\rho }_{gesamt}}$$

The volume of the first material can be determined depending on the volume of the second material V ₂ , the total density ρ _total of the solid separator and the determined densities ρ ₁ , ρ ₂ of the materials, whereby the total density is predetermined and the determined densities of the materials are unchangeable. The volume of the first material to be used can thus be adjusted depending on the volume of the second material to be used.

If the determined density of the first material is lower than the target density, the volume of the first material used must be adjusted accordingly, i.e. increased, in order to adjust the overall density to the target value. Due to the difference in density between the first material and the target density and the resulting adjusted volume of the first material, the mass used of the material with the adjusted volume is also changed. If the density of the first material is increased compared to a target density, for example, the volume used of the first material must be adjusted by reducing the volume to compensate for the increased density. During the adjustment, the mass used of the first material can also change. Conversely, the volume used must be increased if the density deviates downwards from the target density.

If both the first material and the second material differ in their density, the volumes of both materials must be adjusted. Here, too, the masses used for the two materials can change.

The method according to the invention has many advantages. In particular, the method ensures that the overall density of the solid separator does not change regardless of batch-related fluctuations in the densities of the materials used. This is made possible in particular by determining the densities of the materials used before the solid separator is manufactured. In this way, the overall density of the solid separator can be easily adjusted by adjusting the volume of the material with a different density. The adjustment is advantageously carried out during the manufacture of the solid separator, so that no further adjustments need to be made to the solid separator as the end product.

A particular advantage of the method is that the overall density of the solid-state separator can be easily and quickly adjusted. In contrast to the methods known from the prior art, the laborious filling of a cavity is not necessary. Instead, the overall density can be easily adjusted by adjusting the volume of at least one material used.

It is also conceivable that the solid-state separator comprises at least one further component. For example, it is conceivable that the solid-state separator has three components.

According to a preferred embodiment of the invention, it is provided that the first material forms a first component and the second material forms a second component, wherein the components are connected to one another, preferably interlocking with one another.

For the purposes of the present application, a "component" is understood to mean a part of the solid-state separator. The component does not necessarily have to be designed separately from another component or other elements of the solid-state separator. Rather, the component can also be designed integrally with other components and/or elements of the solid-state separator.

It can be provided that the solid-state separator comprises at least two components, wherein a first component is made of or comprises the first material and a second component is made of or comprises the second material. The two components are connected to one another, wherein it can preferably be provided that the components close a through opening of the solid-state separator when the solid-state separator is at rest. Under the influence of a centrifugal force, in particular when the solid-state separator is centrifuged, the components move in the sample container due to the different densities of the materials used and preferably open the through opening. For example, it can be provided that the through opening is closed due to another component of the solid-state separator when the solid-state separator is at rest. The components are connected to one another to ensure that the solid-state separator closes the through opening again automatically once the centrifugal force has ceased. It can preferably be provided that the components are connected to one another in a form-fitting manner. In particular, it can be provided that the solid-state separator comprises at least one floating body and at least one ballast body, wherein the ballast body is formed predominantly from the first material and the floating body is formed predominantly from the second material.

In the context of the present application, a "floating body" is understood to mean a component of the solid-state separator that is made of a material whose density is lower than the density of the component of the body fluid that has the higher density. During the centrifugation process, the floating body therefore "floats" on the component of the body fluid that has the higher density. Under the influence of a centrifugal force, the floating body experiences a force that is lower than that of the ballast body.

In the context of the present application, a "ballast body" is understood to mean a component of the solid-state separator that is made of a material whose density is greater than the density of the component of the body fluid that has the lower density. During the centrifugation process, the ballast body is therefore arranged below the component of the body fluid that has the lower density. Under the influence of the centrifugal force, the ballast body experiences a greater force than the floating body.

It has proven to be useful to separate the floating body and the ballast body from each other, also with regard to the choice of material. In other words, it can be particularly advantageous if the ballast body is completely is made of the first material, while the floating body is completely made of the second material.

Furthermore, it can be provided that the solid-state separator comprises three components. A first component can be designed as a floating body. A second component can be a hard component that encloses a third component. The second and third components form a ballast body.

A preferred embodiment of the invention further provides that the first material is hard, at least after the solid separator has been manufactured. For the purposes of the present application, a "hard" material is understood to mean a material that is not soft or elastic and hardly or not at all yields under the influence of force. The hardness of the material ensures that the solid separator does not deform or only slightly deforms under the influence of centrifugal force. The choice of a hard material has proven to be particularly advantageous, particularly in the case where the solid separator is adapted to a sample container due to an external geometry to form a sealing insert.

According to a further preferred embodiment of the invention, it is provided that the first material and/or the second material is/are a plastic material. The use of plastic materials has also proven to be particularly advantageous from an economic point of view, since the solid separator can thus be produced particularly easily and inexpensively. Since the solid separator is generally only used once, the use of plastic material is particularly advantageous. In particular - if plastic materials are used - according to a preferred embodiment of the invention, it can be provided that the solid separator is produced by means of an injection molding process, wherein the adjustment of the volume used takes place during the injection molding process, preferably by changing the geometry of a mold. The production of the solid separator by means of the injection molding process has proven to be particularly economical. In addition, a geometry of the solid separator can be adjusted particularly easily and quickly by changing the geometry of the mold used. In particular, a volume of the material with a different density can be easily adjusted. It is conceivable that only a mold for producing the solid separator needs to be adjusted in order to be able to adjust the volume of the material.

According to a preferred embodiment of the invention, it is provided that the total volume of the solid separator remains the same and only a ratio of the volume of the first material used to the volume of the second material used is changed. In other words, to adapt the solid separator, a volume of the first material is reduced or increased compared to a volume of the second material. The reverse case is also conceivable. In the event that the density of the first material is lower than the predetermined target density, it can preferably be provided that the volume of the second material used is reduced while the volume of the first material used is increased in order to compensate for the fluctuation in density while the total volume remains the same.

A preferred embodiment provides that the total volume of the solid separator is changed. If the volume of at least one material used is changed, the total volume is also indirectly changed without any further measures. The total volume can be increased or reduced compared to a "standard" solid separator, whose materials match the target densities in terms of their densities.

A further preferred embodiment of the invention provides that an external shape of the solid separator is not changed. In other words, the adjustment of the volume of at least one material used cannot be seen from the outside of the solid separator. This is particularly advantageous if an external shape of the solid separator is adapted to a standardized or normed sample container. In particular, if the solid separator is designed in such a way that the solid separator is to fit tightly in the solid separator, it is even necessary that the external shape remains unchanged at least in a sealing area of the solid separator even after the volume has been adjusted.

A particularly preferred further development of the solid-state separator according to the invention provides that the body fluid to be separated is blood, with the components to be separated being the blood plasma and the blood serum of the blood. In a centrifugation process, a leukocyte film (buffy coat) is also formed, which is arranged between the blood plasma and the blood serum. When separating blood, it can be provided that the target density of the first material is in the range from 1.3 g/cm ³ to 1.5 g/cm ³ , while the target density of the second material is in the range from 0.8 g/cm ³ to 1.0 g/cm ^3. The total density of the solid-state separator should therefore be between a density of blood plasma, which is approximately 1.03 g/cm ³ , and a density of blood serum, which is approximately 1.11 g/cm ³ .

Preferably, the floating body and the ballast body can together form a valve, wherein the ballast body or the floating body preferably has a pin that can be inserted into a through-opening of the floating body or the ballast body, wherein the overall density of the solid separator is preferably adjusted by changing a geometry of the pin. Preferably, it can be provided that the ballast body and the floating body move away from each other when the centrifugal force acts due to their different densities. In this process, the pin is removed from the through-opening. It can be particularly advantageous if the pin is assigned to the ballast body, while the floating body has the through-opening. The opposite case, in which the ballast body has the through-opening and the floating body has the pin, is also conceivable. Furthermore, in this case it is particularly preferred if an external shape of the solid separator is adjusted in such a way that the solid separator lies sealingly against a wall of the sample container when at rest and after separation of the components. During the centrifugation process, the solid separator can be designed to move within the sample container in order to position itself between the components of the body fluid to be separated. An exchange of the components is possible in particular through the through-opening.

Preferably, it can be provided that the ballast body is made of the first material or contains it. The volume of the ballast body can preferably be adjusted by adjusting the geometry of the pin. In this way, the volume can advantageously be adjusted without changing the external shape of the solid-state separator.

It can also preferably be provided that the pin of the ballast body has at least one inner pin. In such a case, it is particularly preferred if the overall density of the solid-state separator is adjusted by changing a length of the inner pin of the pin. It is conceivable that the pin has a cavity and the inner pin protrudes into the cavity of the pin. It can preferably be provided that a length of the inner pin in a target state differs from a length of the pin. In particular, it can be provided that the inner pin is shorter than the pin when the target state is present. The target state is present precisely when the densities of the materials match the target densities. Due to the difference in the lengths when the target state is present, an adjustment of the length of the inner pin, in particular an extension of the inner pin, can advantageously be carried out if the densities of the materials deviate from the target densities - i.e. the target state is not present at the moment. The volume of the material can be adjusted by adjusting the length of the inner pin. If the inner pin is already shorter than the pin when the target state is present, it can be ensured that the inner pin can be extended to adjust the volume of the material without the inner pin exceeding the length of the hollow space of the pin. Advantageously, the adjustment of the volume used is therefore not visible to an observer of the solid-state separator. It can also be ensured that the external shape of the solid-state separator can be retained.

The object mentioned at the outset is further achieved by means of a set with the features according to claim 14. The set comprises two solid separators. A first solid separator has a first material with a first density and a second material with a second density, while a second solid separator also has the first and second materials, but the first material has a third density and the second material has a fourth density. The first and third densities and/or the second and fourth densities differ from one another. The total densities of the solid separators, however, match. In other words, the two solid separators have the same materials, but differ in the densities of the materials. While the density of the first material in the first solid separator has a first value, the density of the first material in the second solid separator has a second value. The same applies to the second material. Due to the deviations, however, it is still possible for the total densities of the solid separators to match. This is made possible in particular by adjusting the volumes of the materials used in such a way that the overall densities correspond to a target value.

For the purposes of the present invention, when comparing a material with a first density with the same material with a second density, the second-mentioned material is understood to be a material that has the same material base as the material to be compared. The materials that differ in density are therefore not necessarily chemically identical in all respects, but fall under the same material master.

The set according to the invention has many advantages. In particular, the two solid separators in the set have identical overall densities, although the densities of the individual materials differ at least in part. Due to the identical overall densities, both solid separators in the set can therefore be used to separate the same body fluid, although the densities of the materials used differ from one another.

A further embodiment of the invention provides that each of the solid-state separators comprises at least one floating body and at least one ballast body, wherein each of the ballast bodies is predominantly made of the first material and each of the floating bodies is predominantly made of the second material. The advantages mentioned in relation to the solid-state separator with the features according to claim 3 apply analogously to the set.

According to a preferred embodiment of the invention, it is further provided that a total volume of the two solid separators is identical. In this case, the solid separators are constructed identically. Due to the identical total volumes and the identical total densities, the total masses of the two solid separators are also identical.

An alternative preferred embodiment of the invention provides that a total volume of the solid separators differs from one another. In such a case, the total densities of the two solid separators are identical, but the total volumes and thus also the total masses of the solid separators differ.

Nevertheless, in this case it can preferably be provided that the solid separators are identical in their external shape. Viewed from the outside, it is therefore not apparent that the solid separators have different total volumes. This can be made possible in particular by one shape of the solid separator differing from the shape of the other solid separator only in an interior. For example, it can be provided that each solid has a pin, which in turn has an inner pin. A length of the inner pins of the two solid separators can differ in such a way that the total volumes differ from one another. At the same time, a geometry of the inner pin is adapted in such a way that the total densities match.

implementation examples

• 1: Einen vertikalen Schnitt durch einen Probenbehälter, wobei sich ein gemäß dem erfindungsgemäßen Verfahren hergestellter Festkörpertrenner in einer Ausgangsstellung in dem Probenbehälter befindet.
• 2: Eine perspektivische Ansicht eines Schwimmkörpers des Festkörpertrenners aus 1.
• 3: Eine perspektivische Ansicht eines Ballastkörpers des erfindungsgemäßen Festkörpertrenners aus 1.
• 4: Eine weitere perspektivische Ansicht des Ballastkörpers aus 3 in einem vertikalen Schnitt.
• 5: Eine perspektivische Ansicht des Festkörpertrenners aus 1.
• 6: Einen vertikalen Schnitt durch den Festkörpertrenner aus 1.
• 7: Wie 6, wobei eine Zentrifugalkraft auf den Festkörpertrenner wirkt.
• 8: Einen horizontalen Schnitt durch einen Probenbehälter, wobei sich der Festkörpertrenner aus 1 in einer Ausgangsstellung in dem Probenbehälter befindet.
• 9: Wie 1, wobei verschiedene Bewegungsstadien des Festkörpertrenners gezeigt sind.
• 10: Eine Detailansicht des Festkörpertrenners während eines Zentrifugationsvorgangs.
• 11: Den Probenbehälter mit dem Festkörpertrenner aus 1 in einem Endzustand des Festkörpertrenners nach dem Zentrifugationsvorgang.
• 12: Den Ballastkörper des Festkörpertrenners aus 1 während eines Herstellungsverfahrens.
• 13: Den Festkörpertrenner aus 1 während eines Herstellungsverfahrens.
• 14: Eine weitere Ansicht des Festkörpertrenners aus 1 während eines Herstellungsverfahrens.
• 15: Einen weiteren erfindungsgemäßen Festkörpertrenner während eines Herstellungsverfahrens.

The invention is explained in more detail below using an embodiment shown in the figures. It shows:

• 1 : A vertical section through a sample container, wherein a solid-state separator manufactured according to the method according to the invention is in an initial position in the sample container.
• 2 : A perspective view of a floating body of the solid-state separator from 1 .
• 3 : A perspective view of a ballast body of the solid state separator according to the invention from 1 .
• 4 : Another perspective view of the ballast body from 3 in a vertical section.
• 5 : A perspective view of the solid state separator from 1 .
• 6 : A vertical section through the solid state separator from 1 .
• 7 : How 6 , whereby a centrifugal force acts on the solid separator.
• 8 : A horizontal section through a sample container, with the solid separator consisting of 1 in an initial position in the sample container.
• 9 : How 1 , showing different stages of motion of the solid-state separator.
• 10 : A detailed view of the solid separator during a centrifugation process.
• 11 : Remove the sample container with the solid separator from 1 in a final state of the solid separator after the centrifugation process.
• 12 : The ballast body of the solid state separator from 1 during a manufacturing process.
• 13 : The solid state separator from 1 during a manufacturing process.
• 14 : Another view of the solid state separator from 1 during a manufacturing process.
• 15 : Another solid separator according to the invention during a manufacturing process.

A solid state separator 1 manufactured according to the method of the invention is shown in the 1 to 15 shown. The solid separator 1 serves to separate components 2, 3 of a body fluid 4 with different densities from one another in the course of a centrifugation process. The centrifugation process is an essential component in the preanalytics of blood 11 for medical purposes. For this purpose, the blood 11 is taken from a patient and placed in a sample container 19 in the form of a blood collection tube 20. The blood collection tube 20 already contains - as can be seen from 1 visible - the solid-state separator 1, which was previously inserted into the blood collection tube 20. By means of the centrifugation process, the blood 11 is to be separated into its components 2, 3, namely blood plasma 12, blood serum 13 and a leukocyte film ("buffy coat"), whereby the aforementioned components 2, 3 of the blood 11 have different densities.

The solid body separator 1 has two relatively movable, interconnected components 7, 8: a floating body 9 and a ballast body 10. The floating body 9 is in 2 shown, the ballast body 10 in the 3 and 4 . A composite state of the solid state separator 1 is shown in the 5 to 7 shown. The ballast body 10 is made of a first material 5, while the floating body 9 is made of a second material 6. Both components 7, 8 are made of plastic. The first material 5 forming the ballast body 10 has a first density ρ ₁ that is greater than a density ρ ₂ of the second material forming the floating body 9. The second density ρ ₂ is less than the density of the blood serum 13, the first density ρ ₁ is greater than the density of the blood plasma 12. The total density ρ _total of the solid-state separator 1 lies between the density of the blood plasma 12 and the density of the blood serum 13.

Furthermore, the second material 6 is soft and supple and has recovery properties. The first material 5, on the other hand, has no recovery properties and is designed without elastic properties.

The ballast body 10 has a first, essentially hemispherical section 21 and a second section 22, the latter being in the form of a pin 15. The first section 21 of the ballast body 10 is provided with four grooves 23, which are arranged at an angle of 90° to one another. On an upper side, the first section 21 is provided with four connecting elements 24 in the form of webs 25. The webs 25 connect the areas of the first section 21 of the ballast body 10 which do not have a groove 23. The pin 15 of the ballast body 10 is - as can be seen from the 4 visible - hollow and has an inner pin 17 protruding into a cavity 27. A length 18 of the inner pin 17 is reduced compared to a length 26 of the cavity 27 of the pin 15, as can be seen in particular from the 6 is evident.

The floating body 9 is designed in the form of a funnel and has a sealing area 28 at an upper end. A circumferential sealing edge 29 is formed on the sealing area 28 for the circumferential sealing contact with an inner side of the blood collection tube 20. An outer diameter 30 of the sealing edge 29 is larger than an inner diameter 31 of the blood collection tube 20, so that the solid body separator 1, when in an initial position, which is particularly in 1 shown, is held in the blood collection tube 20 due to static friction of the sealing edge 29 on the wall 52. Furthermore, the floating body 9 has a through-opening 16 which extends through the floating body 9 along a longitudinal axis 32 of the floating body 9.

The through-opening 16 of the floating body 9 and the pin 15 of the ballast body 10 together form a valve 14 for opening or closing the through-opening 16 in the floating body 9. The pin 15 of the ballast body 10 is in a resting state of the solid-state separator 1, which in 5 shown, is inserted into the through opening 16 of the floating body 9 and closes it liquid-tight.

However, the floating body 9 and the ballast body 10 are movable relative to one another. When the centrifugal force acts on the solid-state separator 1, the ballast body 10 experiences a greater force than the floating body 9, so that the ballast body 10 moves relative to the floating body 9. In the process, the pin 15 is moved out of the through-opening 16. In order to prevent the two components 7, 8 from separating completely from one another and to ensure that the valve 14 closes automatically again when the centrifugal force ceases, the floating body 9 of the solid-state separator 1 has a connecting element 33. The connecting element 33 has four tab-shaped sections 48 which are made from the second material 6 and are each arranged at an angle of 90° to one another on an underside 29 of the floating body 9. The flap-shaped sections 48 are elastically deformable and create a force-transmitting connection between the floating body 9 and the ballast body 10, so that - starting from a resting state of the solid-state separator 1 - a force is required for a relative movement between the floating body 9 and the ballast body 10 to overcome a restoring force defined by the connecting element 33. This force wall is provided by the action of the centrifugal force on the solid separator 1.

Furthermore, the connecting element 33 overlaps the ballast body 10 in an overlapping area 35. In the overlapping area 35, the solid-state separator 1 has grooves 23 in the first section 21 of the ballast body 10. Furthermore, the connecting element 33 has four retaining brackets 36 that surround the ballast body 10. The grooves 23 serve to accommodate the retaining brackets 36. The retaining brackets 36 converge on an underside 51 of the solid-state separator 10. The retaining brackets 36 are also made of the second material 6.

The connecting element 33 is also connected to the ballast body 10 in four anchoring points 38 by means of four anchoring elements 24 in such a way that in the event of a relative movement, in particular as a result of the action of a centrifugal force on the solid-state separator 1, the respective retaining bracket 36 of the connecting element 33 is prevented from deforming in the overlap region 35. The webs 25 in the ballast body 10 serve as anchoring elements 24. The webs 25 are positively connected on the one hand to the retaining brackets 36 and on the other hand to the tab-shaped sections 48 of the connecting element 33 outside the overlap region 35.

The floating body 9 and the connecting element 33 are made of the same material and are designed as one piece. The tab-shaped sections 48 of the connecting element 33 connect the retaining brackets 36 as one piece with the sealing area 28 of the solid-state separator 1, as can be seen particularly well from 2 is evident. It is also evident that a cross-sectional area of the retaining brackets 36 exceeds a cross-sectional area of the tab-shaped sections 48 of the connecting element 33. In other words, the retaining brackets 6 are thicker than the tab-shaped sections 48 of the connecting element 33.

The solid separator 1 under the influence of a centrifugal force is in the 7 shown. During the centrifugation process, the centrifugal force causes the ballast body 10 to separate from the floating body 9. The connecting element 33 ensures that the ballast body 10 does not completely separate from the floating body 9. The connecting element 33 is elastically deformed in the area outside the overlap area 35, namely in the area of the flap-shaped section 48. The retaining brackets 36, on the other hand, are not deformed due to the connection of the connecting element 33 via the anchoring elements 24.

At the same time, however, the ballast body 10 is moved away from the floating body 9 in such a way that contact between the flap-shaped sections 48 of the connecting element 33 and the first section 21 of the ballast body 10 outside the anchoring point 38 is eliminated during the duration of the centrifugation process, as can be seen in particular from 7 is evident. The contact between the tab-shaped sections 48 of the connecting element 33 and the anchoring elements 24 is also at least partially eliminated on one side. However, due to the one-piece connection between the tab-shaped sections 48 of the connecting element 33 and the retaining brackets 36 of the connecting element 33, they remain in contact even under the influence of centrifugal force.

The sealing area 28 of the floating body 9 is squeezed when inserted into the blood collection tube 20 in such a way that the solid-state separator 1 can be accommodated in the blood collection tube 20. For this purpose, the solid-state separator 1 is rotated with its longitudinal axis 39 relative to an initial position which is in the 2 to 7 shown, rotated by 90° so that the longitudinal axis 39 of the solid-state separator 1 is aligned perpendicular to a longitudinal axis 40 of the blood collection tube 20. An inserted state of the solid-state separator 1 is shown in the 8 shown. After inserting the solid-state separator 1 into the blood collection tube 20, the patient's blood 11 can be filled into the blood collection tube 20. The blood collection tube 20 with the solid-state separator 1 is then inserted into a centrifuge (not shown in the figures) and centrifuged. A direction of rotation 53 in which the blood collection tube 20 is rotated is shown in 9 shown.

Due to a centrifugal force acting on the solid separator 1, the solid separator 1 overcomes the static friction. The solid separator 1 moves towards a bottom 41 of the blood collection tube 20 and rotates in the process, since the centrifugal force acts more strongly on the ballast body 10 due to the increased density of the ballast body 10 compared to the density of the floating body 9. The solid separator 1 aligns itself in such a way that the longitudinal axis 39 of the solid separator 1 is aligned parallel to the longitudinal axis 40 of the blood collection tube 20. In this state, the sealing edge 29 lies sealingly against the inside of the blood collection tube 20.

At the same time, during centrifugation, the components 2, 3 of the body fluid 4 to be separated are also separated from one another due to the density differences. The separation of the components 2, 3 is made possible by the presence of the through-opening 16 in the floating body 9. During centrifugation, the rifuge, the pin 15 of the ballast body 10 is moved out of the through-opening 16, so that a flow path 42 is released for the components 2, 3 of the blood 11, as can be seen in particular from 10 In this way, the components 2, 3 can be arranged above and below the solid separator 1 depending on their density.

Since the total density ρ _total of the solid separator 1 lies between a density of the first component 2 and a density of the second component 3 of the body fluid 4, the solid separator 1 arranges itself at a boundary 43 between the two components 2, 3 after the separation of the two components 2, 3, as can be seen from the 10 is visible. The total density ρ _total of the solid separator 1 is preferably selected such that a lowest point of the through opening 16 of the solid separator 1 is arranged above the boundary 43 between the two components 2, 3. For example, it can be provided that a distance between the lowest point and the boundary 43 is approximately 1 mm. In this way, on the one hand, a safety distance can be selected which prevents the second component 3 from being able to arrange itself above the solid separator 1 when the centrifugal force decreases. At the same time, the distance is selected to be as small as possible so that a loss of sample material, in particular of the component 2, is minimized when the component 2 is poured out of the blood collection tube 20 after the centrifugation process has ended.

The different stages of the solid separator 1 during its movement are shown in the 9 shown. After the centrifugal force ceases due to the centrifugation process being terminated, the connecting element 33 closes the valve 14. The pin 15 of the ballast body 10 is then reinserted into the through-opening 16. In this way, the components 2, 3 of the body fluid 4 remain separated from one another even after the centrifugal force ceases.

The restoring force of the tab-shaped sections 48 of the connecting element 33 is selected such that the pin 15 of the ballast body 10 is already inserted back into the through-opening 16 when the centrifugal force is reduced and does not move back into the through-opening 16 until the centrifugal force is completely eliminated. Such a state is in the 7 shown.

The fact that the solid-state separator 1 arranges itself at the boundary 43 between the components 2, 3 even in the event of fluctuations in the density ρ ₁ , ρ ₂ of the two materials used is ensured in the course of the production of the solid-state separator 1 by means of the method according to the invention for adjusting the total density ρ _total of the solid-state separator 1.

The total density ρ _total of the solid separator 1 is calculated as follows: $${\rho }_{Gesamt}=\frac{\mathrm{<figure-callout\; id="1"\; label="m"\; filenames="DE102023119098A1\_0005.png,DE102023119098A1\_0010.png"\; state="\{\{state\}\}">m</figure-callout>}1+m2}{{\mathrm{<figure-callout\; id="1"\; label="V"\; filenames="DE102023119098A1\_0005.png,DE102023119098A1\_0010.png"\; state="\{\{state\}\}">V</figure-callout>}}_1+{\mathrm{<figure-callout\; id="2"\; label="V"\; filenames="DE102023119098A1\_0015.png"\; state="\{\{state\}\}">V</figure-callout>}}_2}=\frac{{\mathrm{<figure-callout\; id="1"\; label="\rho "\; filenames="DE102023119098A1\_0005.png,DE102023119098A1\_0010.png"\; state="\{\{state\}\}">\rho </figure-callout>}}_1\cdot {\mathrm{<figure-callout\; id="1"\; label="V"\; filenames="DE102023119098A1\_0005.png,DE102023119098A1\_0010.png"\; state="\{\{state\}\}">V</figure-callout>}}_1+{\mathrm{<figure-callout\; id="2"\; label="\rho "\; filenames="DE102023119098A1\_0015.png"\; state="\{\{state\}\}">\rho </figure-callout>}}_2\cdot V_2}{{\mathrm{<figure-callout\; id="1"\; label="V"\; filenames="DE102023119098A1\_0005.png,DE102023119098A1\_0010.png"\; state="\{\{state\}\}">V</figure-callout>}}_1+{\mathrm{<figure-callout\; id="2"\; label="V"\; filenames="DE102023119098A1\_0015.png"\; state="\{\{state\}\}">V</figure-callout>}}_2}$$

Due to fluctuations in the density ρ ₁ of the first material 5 and/or the density ρ ₂ of the second material 6, a value of the total density ρ _total of the solid separator 1 may deviate from a target value of the total density ρ _total of the solid separator 1 required for optimal separation of the components 2, 3 of the blood 11. To avoid this, the densities ρ ₁ , ρ ₂ of the two materials 5, 6 are determined in a first step and compared with the respective target densities. The target densities are the densities that the materials 5, 6 must have so that the value of the total density ρ _total of the solid separator 1 is optimally set. Depending on the material 5, 6 whose density ρ ₁ , ρ ₂ deviates from the target density, a volume V ₁ , V ₂ of the first material 5 and/or the second material 6 used is adjusted. The adjustment of the volume V ₁ , V ₂ is carried out, for example, by extending or shortening the inner pin 17 of the pin 15 of the ballast body 10 of the solid body separator 1, as shown in the 12 shown.

In the event that the density ρ ₁ of the first material 5 that forms the ballast body 10 is reduced compared to the target density, the value of the total density ρ _total can be adjusted by extending the inner pin 17. Conversely, the value of the total density ρ _total can be adjusted by shortening the inner pin 17 if the density ρ ₁ of the first material 5 is increased compared to the target density. The volume V ₁ of the first material 5 used to form the solid body separator 1 can be determined as follows: $${\mathrm{<figure-callout\; id="1"\; label="V"\; filenames="DE102023119098A1\_0005.png,DE102023119098A1\_0010.png"\; state="\{\{state\}\}">V</figure-callout>}}_1=\frac{V_2\left({\rho }_{gesamt}-{\rho }_2\right)}{\left({\mathrm{<figure-callout\; id="1"\; label="\rho "\; filenames="DE102023119098A1\_0005.png,DE102023119098A1\_0010.png"\; state="\{\{state\}\}">\rho </figure-callout>}}_1-{\rho }_{gesamt}\right)}$$

The solid state separator 1 is used as in 13 shown using the injection molding process. In a first process step, the first material 5 is injected into a first mold 55 and a first component 7 is formed. The first component 7 later forms the ballast body 10 of the solid-state separator 1. The inner pin 17 and a wall of the pin 15 do not touch each other, so that a cavity 44 in the pin 17 is formed. Furthermore, the pin 15 is provided on an upper side with an annular recess 49 - as can be seen in particular from 4 is clearly visible - whereby the recess 49 is closed at three connection points 50 between the inner pin 17 and the pin 15.

After the first material 5 has hardened, the mold 55 is transferred from a first mold position to a second mold position. An interior space enclosed by the mold 55 in the second mold position essentially corresponds to a final shape of the solid body separator 1. The second material 6 is finally let into the mold 55 in a second process step through the annular recess 49 of the ballast body 10 without entering into a material bond with the first material 5 or the first component 7 formed therefrom. The second material 6 flows as in the 14 and 15 shown starting from the annular recess 49 on the top side 45 of the first component 7, through the cavity 44 in the pin 15 to a bottom side 46 of the first component 7. The bottom side 46 forms a reversal region 47, from which the second material 6 flows around an outside of the first component 7 up to a top side 45 of the first component 7. In a final state, the second material 6 completely fills the cavity 44 that was present in the pin 15 of the first component 7. The second material 6 is finally also hardened. After the second material 6 has hardened, the two components 7, 8 are movable relative to one another, wherein complete removal of the floating body 9 from the ballast body 10 is prevented due to the force-fitting connection of the connecting element 33 in the anchoring points 38.

In order to be able to adjust a length 18 of the inner pin 17 during the manufacturing process and thus to change a volume of the first component 7, a further tool 54 can be used, which is inserted into the molding tool 55 before the first material 5 is introduced, as can be seen in particular from the 12 can be seen. The tool 54 limits a flow of the first material 5 in the direction of a bottom side 34 of the floating body 9. In this way, the inner pin 17 can be adjusted in its length 18. After curing and insertion of the first component 7 into the second molding tool 55 or after transferring the first molding tool 55 into the second mold position, the tool 54 can be removed.

The solid separator 1 produced in this way can thus have inner pins 17 of different lengths while maintaining the same total density ρ _total, as can be seen from the 14 and 15 is evident. In the 14 a solid-state separator 1 is shown, which has a short inner pin 17, while the one in the 15 The solid-state separator 1 shown has a significantly longer inner pin 17, wherein a length 18 of the inner pin 17 exceeds the length of the pin 15 and penetrates into the first section 21 of the ballast body 10.

list of reference symbols

1

solid-state separators

2

first component

3

second component

4

body fluid

5

first material

6

second material

7

first component

8

second component

9

floats

10

ballast body

11

blood

12

blood plasma

13

blood serum

14

valve

15

cones

16

passage opening

17

inner tenon

18

length of the inner tenon

19

sample container

20

blood collection tubes

21

First Section

22

Second Section

23

Nut

24

anchoring element

25

web

26

length of the tenon

27

cavity

28

sealing area

29

sealing edge

30

outer diameter of the sealing edge

31

inner diameter of the blood collection tube

32

longitudinal axis of the float

33

connecting element

34

bottom of the float

35

overlap area

36

handlebar

37

bottom of the ballast body

38

anchoring point

39

longitudinal axis of the solid-state separator

40

longitudinal axis of the blood collection tube

41

bottom of the blood collection tube

42

flow path

43

Border

44

cavity

45

top of the first component

46

bottom of the first component

47

reversal area

48

Section

49

recess

50

connection point

51

bottom of the solid-state separator

52

wall

53

direction of rotation

54

Tool

55

mold

ρ1

first density

ρ2

second density

ρTotal

total density

V1

first volume

V2

second volume

QUOTES INCLUDED IN THE DESCRIPTION

This list of documents listed by the applicant was generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions.

Cited patent literature

• WO 2016/069613 A1 [0006]

Claims (18)

Method for setting a total density of a solid separator (1) for separating at least two components (2, 3) of a body fluid (4), wherein the first component (2) has a first density (p ₁ ) and the second component (3) has a second density (ρ ₂ ) and wherein a target value of the total density (ρ _total ) of the solid separator (1) lies between a value of the first and a value of the second density (ρ ₁ , ρ ₂ ), the solid separator (1) comprising - a first material (5) and - a second material (6), wherein both materials (5, 6) are present separately from one another in the solid separator (1), characterized by the following method step: adaptation of an inserted volume (V ₁ , V ₂ ) of at least one of the materials (5, 6) of the solid separator (1) depending on the determined current densities (ρ ₁ , ρ ₂ ) of the two materials (5, 6), so that the value of the total density (ρ _total ) of the solid state separator (1) corresponds to the target value. procedure according to claim 1 , characterized in that the first material (5) forms a first component (7) and the second material (6) forms a second component (8), wherein the components (7, 8) are connected to one another, preferably interlocking with one another. procedure according to claim 1 or 2 , characterized in that the solid-state separator (1) comprises at least one floating body (9) and at least one ballast body (10), wherein the floating body (9) is formed predominantly from the second material (6) and the ballast body (10) is formed predominantly from the first material (5). Method according to one of the preceding claims, characterized in that the first material (5) is hard at least after production of the solid-state separator (1). Method according to one of the preceding claims, characterized in that the first material (5) and/or the second material (6) is/are a plastic material. Method according to one of the preceding claims, characterized in that the solid-state separator (1) is produced by means of an injection molding process, wherein the adjustment of the volume used (V ₁ , V ₂ ) takes place in the course of the injection molding process, preferably by changing a geometry of a molding tool (55). Method according to one of the preceding claims, characterized in that the total volume of the solid-state separator (1) remains the same and only a ratio of the volume used (V ₁ ) of the first material (5) to the volume used (V ₂ ) of the second material (6) is changed. Method according to one of the Claims 1 until 6 , characterized in that the total volume of the solid separator (1) is changed. Method according to one of the preceding claims, characterized in that an external shape of the solid-state separator (1) is not changed. Method according to one of the preceding claims, characterized in that the body fluid (4) to be separated is blood (11), wherein the components (2, 3) to be separated are the blood plasma (12) and the blood serum (13) of the blood (11). Method according to one of the Claims 3 until 10 , characterized in that the floating body (9) and the ballast body (10) together form a valve (14), wherein the ballast body (10) or the floating body (9) preferably has a pin (15) which can be inserted into a through opening (16) of the floating body (9) or the ballast body (10), wherein preferably the total density (ρ _total ) of the solid-state separator (1) is adapted by means of a change in a geometry of the pin (15). procedure according to claim 11 , characterized in that the pin (15) of the ballast body (10) has at least one inner pin (17). procedure according to claim 12 , characterized in that the total density (ρ _total ) of the solid-state separator (1) is adjusted by means of a change in a length (18) of the inner pin (17) of the pin (15). Set comprising at least two solid separators (1), wherein - a first solid separator (1) has a first material (5) with a first density (p ₁ ) and a second material (6) with a second density (ρ ₂ ) and - a second solid separator (1) has the first material (5) with a third density and the second material (6) with a fourth density, - wherein the first (p ₁ ) and the third density and/or the second (p ₁ ) and the fourth density differ from one another, - where the total densities (ρ _total ) of the two solid separators (1) are the same. Set after claim 14 , characterized in that each of the solid-state separators (1) comprises at least one floating body (9) and at least one ballast body (10), wherein each of the floating bodies (9) is formed predominantly from the second material (6) and each of the ballast bodies (10) is formed predominantly from the first material (5). Set after claim 14 or 15 , characterized in that a total volume of the two solid separators (1) is identical. Set after claim 14 or 15 , characterized in that a total volume of the solid separators (1) differs from one another. Set after one of the Claims 14 until 17 , characterized in that the solid-state separators (1) are identical in their external shape.

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