Pipette tip having a receiving space that tapers in a curved manner

Abstract

Proposed is an exchangeable pipette tip (10; 110; 210), wherein the pipette tip (10; 110; 210) extends along a channel axis (K), wherein the channel axis (K) defines an axial direction (a) running along the channel axis (K), radial directions (r) orthogonal with respect to the channel axis (K), and a circumferential direction (u) encircling the channel axis (K), wherein the pipette tip (10; 110; 210), at one axial longitudinal end thereof forming a coupling longitudinal end (12), has a coupling formation (40) which is designed for coupling to a counterpart coupling formation of a pipette device, wherein the pipette tip (10; 110; 210), at the longitudinal end thereof situated axially opposite the coupling longitudinal end (12) and forming a dosing longitudinal end (14), has a pipette opening (34) that is communicatively connected to a receiving space (36) designed for receiving liquid that is to be dosed, wherein the receiving space (36) of the pipette tip (10; 110; 210) is designed to taper toward the pipette opening (34), characterized in that at least one axial portion of the receiving space (36) is concave and forms a concave axial portion (26), such that an inner wall (11b) of the pipette tip (10; 110; 210) that radially delimits said portion is curved about at least one curvature axis (K3) running transversely with respect to the channel axis (K).

Description

[0001] Pipette tip with curved tapered receiving chamber

[0002] Description

[0003] The present invention relates to an interchangeable pipette tip for pipette devices, in particular for pipette robots. The pipette tip extends along a channel axis.

[0004] The channel axis defines an axial direction running along the channel axis, radial directions orthogonal to the channel axis and a circumferential direction running around the channel axis.

[0005] The pipetting tip has a coupling formation at its one axial longitudinal end, hereinafter referred to as the "coupling longitudinal end", which is designed for coupling with a coupling counter-formation of a pipetting device.

[0006] At its longitudinal end axially opposite the coupling longitudinal end, hereinafter referred to as the "dosing longitudinal end," the pipette tip has a pipette opening that communicates with a receiving chamber designed to receive the liquid to be dispensed. Thus, liquid can flow through the pipette opening from the external environment of the pipette tip into the receiving chamber and from the receiving chamber into the external environment.

[0007] The receiving space of the pipette tip is tapered towards the pipette opening.

[0008] Such pipette tips are well known in the art. They are used, for example, by the applicant under the trade name "CO-RE®." As with the preferred embodiments of the present invention, these are plastic components manufactured by injection molding. Such pipette tips are disposable and, for hygienic reasons to avoid cross-contamination, are disposed of after a single use. Therefore, the interchangeable pipette tips can be temporarily coupled to a pipetting device for pipetting operations. The coupling formation of the pipette tip allows the pipette tip to be coupled to and subsequently released from a coupling counter-formation of a pipetting device.

[0009] The trade name "CO-RE®" is an acronym for "Compressed O-Ring Expansion," which refers to the locking of a pipette tip to a pipette device through axial compression and the resulting radial expansion of an O-ring. The O-ring, which can be deformed in this manner, is arranged on the coupling counter-formation of the pipette device and, through radial expansion, can engage a concave locking recess formed in the coupling formation and circumferentially surrounding the channel axis. This allows the O-ring to not only hold the pipette tip positively to the coupling counter-formation, but also simultaneously create a gas-tight seal between the coupling formation and the external environment.

[0010] The concave locking recess, like the O-ring engaging in it by deformation to achieve the described sealing effect, is designed to be rotationally symmetrical with respect to the channel axis and forms a recess in the inner wall along an axial region of the coupling formation which dents the inner wall of the coupling formation radially outwards.

[0011] Such a pipette tip is known, for example, from EP 1 171 240 A1.

[0012] A further development of this pipette tip is known from WO 2017 / 218032 A1. In this further development, the O-ring on the coupling counterformation of the pipette device that locks the pipette tip to the coupling counterformation is replaced by a segmented spring ring with convex projections projecting radially outward. The convex projections can be displaced radially outward against their spring preload by an axially displaceable clamping cone into engagement with the locking recess still present in the coupling formation of the pipette tip, thus securely holding the pipette tip to the coupling counterformation of the pipette device. However, due to the segmentation of the convex projections, the sealing effect provided by the O-ring is no longer present.The further development of the pipette tip therefore has a separate contact surface, usually conical, or more precisely: negatively conical, at an axial distance from the locking recess, for a seal arranged on the coupling counter-formation to seal the coupled pipette tip against the external environment.

[0013] The advantage of this design is, among other things, that the seal or seal contact surface located axially closer to the dispensing end also shields the radially outwardly projecting convex projections from contamination by the dispensing liquid. Furthermore, the seal provided on the coupling counterformation can be deformed solely by the coupling movement of the pipette tip or its coupling formation relative to the coupling counterformation and, unlike the aforementioned O-ring, does not require a deformation actuator.

[0014] The pipette tips of the present application are suitable and intended for dosing liquid in a pipetting operation in which a working gas is present in a pipetting channel of a pipetting device coupled to the pipette tip. The pressure of the working gas is manipulated by the pipetting device relative to the ambient pressure in order to aspirate the liquid to be dosed into the receiving space of the pipette tip and dispense it from the receiving space of the pipette tip. During pipetting operation, working gas is generally also constantly present in the pipette tip, as it is usually not completely filled with the liquid to be dosed (hereinafter referred to as "dosage liquid").During pipetting, the dosing liquid held in the pipette tip is located closer to the pipette opening due to gravity, while the working gas that transmits pressure changes to the dosing liquid generally occupies a volume that is axially further away from the pipette opening than the dosing liquid held in the pipette tip. Thus, the pipette tip coupled to a pipette device extends the pipette channel assigned by the coupling for the duration of the coupling. Dispensing is always the task of a pipette tip discussed here. Aspiration is a preferred method for holding dosing liquid in the holding chamber. Alternatively, the holding chamber can also be filled with dosing liquid from the pipette device via filling channels.

[0015] Manufacturers and users of pipette tips are constantly striving to increase the accuracy of a pipetting process, especially a dispensing process, while also reducing the minimum possible repeatable dispensable liquid quantity. The pipette tips discussed here are often used on pipetting robots for so-called "screening" with very expensive liquids, often available only in very small quantities. The smaller the quantities of such valuable liquids that can be repeatedly dispensed, the more cost-effective the screening process can be, to name just one possible example.

[0016] Limits to the accuracy of a dispensing and the minimum possible repeatable dispensable amount of liquid are set by the effects of the wetting of the surfaces of the pipette tip by the dispensing liquid, as well as by splashes that may occur during dispensing. Splashes cause the actual dispensed amount to be dispensed not as a single drop of liquid, but as a series of drops with satellite drops.

[0017] With the pipetting tips discussed in the present application, dispensing can be performed quasi-synchronously by displacing the working gas, and asynchronously by momentum transfer. In the quasi-synchronous process by displacing the working gas, the dispensed liquid quantity essentially follows the movement of a pipetting piston of the pipetting device, which is displaced towards the pipetting opening to displace the working gas in its pipetting channel, increasing the pressure of the working gas. The movement of the pipetting piston and the dispensing liquid through the pipetting opening of the pipetting tip occurs simultaneously and in the same direction. The pipetting piston displaces the working gas, which in turn displaces the dispensing liquid held in the receiving chamber. The volume of the working gas displaced during the piston movement usually corresponds approximately to the dispensed liquid quantity.

[0018] In the asynchronous method using pulse transfer, the movement of a pipetting piston and the resulting dispensing of a drop of liquid do not occur simultaneously and in the same direction. Due to the nature of the method, dispensing always follows a piston movement in the dispensing direction. The dispensing liquid flows through the pipetting opening either while the pipetting piston is moving in the aspiration direction or when the pipetting piston is stationary. Furthermore, the volume swept by a pipetting piston surface wetted by the working gas during the piston movement is not directly proportional to the amount of liquid dispensed.Rather, the pipetting piston is moved at very high acceleration in a short time in the dispensing direction and then in the aspiration direction to generate a pressure pulse in the working gas, which propagates along the channel axis and ultimately impinges on the dosing liquid surface facing the working gas in the receiving chamber. According to a currently accepted theory, the pressure pulse transferred from the working gas to the dosing liquid propagates further along the channel axis in the direction of the pipetting orifice and leads to the detachment of a liquid droplet at the meniscus of the dosing liquid held in the pipetting tip, which is closer to the pipetting orifice.

[0019] The movement of a pipetting piston is just one, albeit the most common, way to change the pressure in the working gas. A pressure reservoir can also be used, which can be temporarily connected and disconnected from the working gas in the pipetting channel via at least one valve arrangement.

[0020] With a displacement-based dispensing method, liquid droplets down to the single-digit microliter range can be dispensed repeatedly. With a pulse-based dispensing method, liquid droplets of less than 1 pl can be dispensed with sufficient repeatability. Therefore, the object of the present invention is to improve the interchangeable pipette tips known from the prior art so that they can pipette the smallest possible liquid volumes in the single-digit microliter range or below with greater accuracy.

[0021] The present application uses the term "pipetting" as a generic term for aspirating liquid through the pipetting opening into the receiving space of the pipetting tip and for dispensing liquid from the receiving space of the pipetting tip through its pipetting opening.

[0022] The present invention achieves the stated object in that at least one axial section of the receiving space is designed as a concave axial section in such a way that an inner wall of the pipette tip radially delimiting it is curved about at least one axis of curvature running transversely to the channel axis.

[0023] Known prior-art pipette tips generally have a conical receiving space, whereby the receiving space can have more than one cone angle along the channel axis. For example, the conical receiving space of the above-mentioned "CO-RE®" pipette tips has a first, smaller cone angle in a section extending from and containing the pipette opening, and a larger cone angle in a second section axially adjacent to the first section. Due to the conical design of the receiving space, the inner wall radially delimiting it is concave around the channel axis as the axis of curvature. However, the inner wall of the known pipette tip does not have any further curvature.

[0024] Tests and computer-aided simulations conducted by the applicant have now shown that significant improvements in dispensing accuracy can be achieved by at least partially abandoning the conical shape of the receiving chamber in favor of a receiving chamber whose inner wall is curved around at least one axis of curvature running transversely to the channel axis. This particularly applies to pulse-based dispensing, which is preferred for smaller liquid quantities. Without wishing to be limited to the theory expressed below, the described concave design of the receiving chamber appears to favorably influence the propagation of the pressure pulse introduced into the dosing liquid by the working gas toward the pipetting opening, compared to the previously used conical receiving chamber.

[0025] The concave configuration of the receiving space in the concave axial section is preferably based on an inner wall of the pipette tip that is curved along the channel axis without jumps or kinks and radially outwardly delimits the receiving space. However, it should not be ruled out that the concave configuration of the receiving space in the concave axial section is formed by an axial polyhedral sequence of inner wall surfaces, each of which has no curvature about a curvature axis running transversely to the channel axis, but which overall lead to a concave configuration of the inner wall about a curvature axis running transversely to the channel axis.For example, a correspondingly concavely curved receiving space in the concave axial section can be achieved by an axial sequence of coaxial negatively conical inner wall sections, of which the negatively conical section following in the direction of the pipetting opening of the pipetting tip has a larger cone opening angle than an axially immediately preceding conical section which is located further away from the pipetting opening.

[0026] If the pipette tip, as preferred by the present invention, has a rotationally symmetrical inner wall for radially delimiting the receiving space, the receiving space has an infinite number of axes of curvature running transversely to the channel axis, around which the inner wall is locally curved. The inner wall can then be thought of as formed by rotating a generating curve around the channel axis. The generating curve is curved around at least one axis of curvature running transversely to the channel axis. With the rotation of the generating curve around the channel axis, the at least one axis of curvature of the generating curve also rotates around the channel axis, which ultimately leads to the infinitely large number of axes of curvature running transversely to the channel axis of the entire rotationally symmetrical inner wall.

[0027] However, it should not be ruled out that the inner wall of the pipette tip delimiting the receiving space is formed by a plurality of surfaces that adjoin one another in the circumferential direction and of which at least one is not a surface of revolution with locally constant distances from the channel axis over its angular extent. At least one of the mentioned surfaces, preferably each one, can be curved only about the at least one axis of curvature running transversely to the channel axis. Such a polyhedral boundary of the receiving space is preferably constructed symmetrically with respect to the channel axis such that the entire inner wall is formed by a certain number of identical surface regions adjoining one another in the circumferential direction.In principle, however, even a single surface area that is concave in an angular sector around the channel axis according to the above description can bring about an improvement in the pulse propagation in the dosing liquid in the receiving space, while the remaining surface areas of the inner wall do not have a concave curvature in the above sense.

[0028] Due to the tapering of the pipette tip along the channel axis, the at least one axis of curvature for forming the concavely curved inner wall of the pipette tip is preferably oriented orthogonally to the channel axis. An inner wall section curved around an axis of curvature orthogonal to the channel axis directly affects the tapering of the receiving space in the axial direction toward the pipette opening, without any peripheral components.

[0029] To avoid any misunderstandings, it should be clarified that the inner wall of the pipette tip points towards the virtual channel axis. The pipette tip is essentially a channel component that is completely axially penetrated by a channel. The channel can have locally different inside widths, in particular diameters, and thus different cross-sectional areas along the channel axis. The channel can even have locally different cross-sectional shapes along the channel axis, although this is not preferred. At least one filter element can be provided in the channel. For the purposes of transport and storage, one or both longitudinal ends of the pipette tip can be closed by a lid or a plug.

[0030] Since the inner wall extends continuously around the channel axis, it is concave with respect to the channel axis. Due to the preferably at least partial, particularly preferably complete, rotationally symmetrical design of the inner wall with respect to the channel axis as the axis of rotational symmetry, according to a preferred embodiment of the present invention, the inner wall is curved in the concave axial section about the at least one axis of curvature running transversely to the axis of curvature, and the inner wall is further curved around the channel axis as a second axis of curvature. The present invention does not relate to the curvature about the second axis of curvature, but delimits the inventive curvature that may be added to this curvature to avoid misunderstandings.

[0031] A design of the inner wall that is only partially rotationally symmetrical can refer to a completely circumferentially encircling rotationally symmetrical design in only at least one axial section, while at least one further axial section of the inner wall or of the receiving space is not rotationally symmetrical, as well as a design that is rotationally symmetrical in the circumferential direction only along a partially encircling circumferential section, while a complementary circumferential section is not rotationally symmetrical.

[0032] Since, according to current assessment of available development results, the concave axial section improves the propagation of a pressure pulse transmitted from the working gas to the dosing liquid in the dosing liquid, the concave axial section is preferably formed where dosing liquid is received during pipetting operation to achieve the identified technical advantages. As a rule, dosing liquid does not reach the axial section of the pipette tip having the coupling formation. Furthermore, a meniscus of the dosing liquid received in the receiving space, which is closer to the coupling formation, is usually not brought closer to the coupling formation than a predetermined minimum axial distance. Therefore, the concave axial section is preferably located in an axial region of the pipette tip which, starting from the pipette opening, extends over 50% of the total axial extension length of the pipette tip.Further optionally, the concave axial section can be formed only in this axial area.

[0033] Since the amount of dosing liquid in the receiving chamber constantly decreases, especially during aliquoting operation, the concave axial section is preferably formed in at least one axial region which, starting from the pipetting opening, extends over 35%, more preferably over 25%, even more preferably over 10%, particularly strongly preferably over 5%, of the entire axial extension length of the pipetting tip. This ensures that even with only a small amount of dosing liquid received in the receiving chamber, the technical advantages of the above-described concave design of the receiving chamber can be used. This preferably does not mean that the concave axial section is only formed in the aforementioned axial regions of the pipetting tip, but that the concave axial section is at least also formed in the aforementioned axial regions of the pipetting tip.In principle, the entire receiving space between the coupling formation and the pipetting opening can be the concave axial section.

[0034] According to a preferred embodiment of the invention, the concave axial section achieves a particularly advantageous effect with regard to accuracy and the smallest possible repeatable dispensing quantity in that the receiving space tapers in the concave axial section towards the pipetting opening in such a way that, along the entire concave axial section, of two clear cross-sections of the receiving space viewed at any different axial locations along the channel axis, the cross-sectional area of ​​the cross-section closer to the pipetting opening is not larger than the cross-sectional area of ​​the cross-section further away from the pipetting opening. This preferred embodiment excludes a radial widening of the receiving space that is locally limited to an axial region. Such a widening could lead to undesired diffusion of a pressure pulse propagating in the dispensing liquid towards the pipetting opening.Nevertheless, the above definition allows for local cylindrical axial regions. However, experiments have shown that the concentration of the pressure pulse propagating within the dosing liquid toward the pipetting orifice in the receiving space can be advantageously influenced by ensuring that, of two clear cross-sections of the receiving space viewed at any different axial locations along the channel axis, the cross-sectional area of ​​the cross-section closer to the pipetting orifice is smaller than the cross-sectional area of ​​the cross-section farther away from the pipetting orifice.

[0035] Preferably, the receiving space tapers continuously, at least in the concave axial section toward the pipetting opening. Particularly preferably, the entire receiving space tapers continuously along the channel axis.

[0036] Furthermore, when reference is made to a "cylindrical" shape in this application, this refers to a cylindrical shape in its most general form, i.e., a shape generated by a closed, circumferential planar curve that, as the shape generator, is displaced orthogonally to its plane of extension. Only preferably, the cylindrical shape is a circular cylindrical shape.

[0037] As explained above, the receiving space, or the inner wall of the pipette tip that radially delimits it, is designed with symmetry with respect to the channel axis as the axis of symmetry. In a preferred case, this symmetry can be rotational symmetry with the channel axis as the axis of rotational symmetry. In another case, this symmetry can consist in the inner wall being formed by a number of surface sections, at least two of which can be converted into one another by rotation about the channel axis. The concave curvature of the inner wall that is of interest here can then be particularly advantageously observed in the contour line that the inner wall has in a sectional view in a longitudinal section plane containing the channel axis. In the above-mentioned case of a polyhedral-concave receiving space, the contour line in the concave-axial section is a polygon. However, the contour line in the concave-axial section is preferably curved, in particular curved without jumps or steps.In principle, a concave axial section is sufficient to achieve the desired effect. In a single longitudinal section of a longitudinal section plane containing the channel axis, the contour line of the inner wall of the pipette tip bordering the concave axial section has exactly one radius of curvature. The concavely curved contour line is then a partial circle. A rotationally symmetrical inner wall section formed from this has the shape of a spherical cap section.

[0038] However, for the most effective concentration of a pressure pulse propagating in the dosing liquid held in the receiving space in the direction of the pipetting opening, it has proven advantageous if the contour line of the inner wall in the concave axial section has more than one radius of curvature along its axial extent. Preferably, for a longitudinal sectional view in at least one longitudinal sectional plane containing the channel axis, the curvature of a contour line of the inner wall of the pipetting tip radially delimiting the concave axial section does not become smaller or weaker as the pipetting opening is approached. Decreasing curvature means increasing radii of curvature. Particularly preferably, the curvature of the contour line becomes steadily larger or stronger as the pipetting opening is approached, i.e. the local radii of curvature of the contour line particularly preferably become steadily smaller as the pipetting opening is approached.

[0039] With regard to the above-mentioned preferred symmetry cases, what has been said above regarding the curvature of the contour line preferably applies in longitudinal sectional views in several longitudinal sectional planes containing the channel axis, particularly preferably in all such longitudinal sectional planes.

[0040] A preferred contour line of the inner wall of the pipette tip radially delimiting the concave axial section with a curvature that steadily increases towards the pipette opening can be obtained by a hyperbolic contour line.

[0041] Conversely, with distance from the pipette opening, the curvature of the contour line in the designated at least one longitudinal section plane containing the channel axis preferably decreases continuously. If h denotes a coordinate along the channel axis whose origin is located at the end of the concave axial section closer to the pipette opening and which increases in magnitude linearly proportional to the distance with increasing distance from the pipette opening, then the contour line M, specified by the radial distance M(h) of the contour line from the channel axis at the axial coordinate h, can have a course of the following hyperbolic structure:

[0042] Ki, K2, and K3 are constants. Each of the three constants Ki, K2, and K3 can be negative. K1 is preferably a function of the radial distance of the contour line from the channel axis at the longitudinal end of the contour line or the concave axial section closest to the pipetting opening, or is this radial distance. K1 is therefore preferably a positive value. K1, K2, and K3 are different from zero in terms of magnitude.

[0043] K2 and K3 are preferably each functions of the distance of the contour line from the channel axis at the longitudinal end of the contour line or the concave axial section closer to the pipetting opening, at the longitudinal end of the contour line or the concave axial section farther from the pipetting opening, the axial length of the concave axial section, and the angle of inclination of the contour line at the longitudinal end of the contour line closer to the pipetting opening. K2 is preferably also a function of K3.

[0044] With r nas the radial distance of the contour line from the channel axis at the longitudinal end of the concave axial section closer to the pipetting opening (h = 0), n as the radial distance of the contour line from the channel axis at the longitudinal end of the concave axial section farther from the pipetting opening (h = hend), and with IKA as the axial length of the concave axial section, equation 1 can be written in an advantageous embodiment: where for K3 in a preferred embodiment: with a being the angle of inclination of the contour line at the longitudinal end of the concave axial section closer to the pipetting opening.

[0045] In principle, the concave axial section can extend across the entire receiving chamber. However, as already explained above, it is sufficient to design only one axial section of the receiving chamber closer to the pipetting opening as the concave axial section.

[0046] Therefore, it can be provided that a second axial section of the receiving space is formed in an axial region located between the coupling formation and the concave axial section of the pipette tip, the radially delimiting inner wall of which differs from the inner wall in the concave axial section with respect to at least one parameter consisting of inclination relative to the channel axis and curvature about an axis of curvature running transversely to the channel axis. For reasons of ease of manufacture, this second axial section is preferably a conical section with at least one, preferably exactly one, cone angle constant along its axial extent. This cone angle is preferably between 3.5° and 4.5°. In the present application, the term "cone angle" always refers to the full cone angle, not half the cone angle, between the cone axis and a straight line on the cone surface.

[0047] This second axial section allows an axial region of the receiving chamber to be designed to store a relatively larger volume of liquid per axial length than in the concave axial section. This allows the pipette tip, despite its ability to dose liquid volumes in the range of less than 1 pl with repeatable accuracy, to hold a relatively large volume of liquid in the tens or even three-digit microliter range in the receiving chamber and keep it ready for dispensing. For example, the pipette tip can have a nominal capacity of at least 10 pl or at least 50 pl, including the aforementioned limits. For particularly extensive pipetting tasks, the pipette tip can have a nominal capacity of at least 90 pl or, preferably, at least 130 pl.The pipette tip discussed here can be used for both positive displacement and pulse-based pipetting, although the advantage of the concave axial section is particularly useful for pulse-based pipetting. Therefore, a pipette tip discussed here can also have a nominal capacity of at least 150 pl, even though the pulse-based dispensing method often only dispenses single doses of 50 to 120 nl.

[0048] A nominal capacity of more than 500 pl is generally possible, but is no longer preferred due to the relatively large working gas volume between the piston surface of a piston of a pipetting channel coupling the pipetting tip, closer to the pipetting opening, and the pipetting opening. Therefore, the pipetting tip preferably has a nominal capacity of no more than 500 pl, particularly preferably no more than 350 pl, and even more preferably no more than 300 pl. In an advantageous embodiment, the pipetting tip therefore has a nominal capacity of no more than 265 pl.

[0049] The second axial section, which preferably has a greater axial length than the concave axial section, can be tapered in the direction from the coupling longitudinal end to the metering longitudinal end or can extend over an axial length with a predetermined taper such that its second clear width orthogonal to the channel axis at its end closer to the metering longitudinal end is between 40% and 60% of a first clear width parallel to the second clear width at its end closer to the coupling longitudinal end. The second clear width is preferably 50% of the first clear width. With a square cross-section of the receiving space, the clear width can be an edge length or a diagonal. Due to the preferred design of the receiving space as a rotationally symmetrical receiving space, the clear width is preferably a diameter.The first clear width can preferably be between 3 mm and 7 mm, particularly preferably between 3.5 mm and 5.5 mm, and most preferably between 3.8 mm and 4.2 mm. In a particularly preferred advantageous embodiment, the first clear width is exactly 4 mm.

[0050] In principle, it can be provided that the concave axial section ends at the pipetting opening. However, tests have shown that this is good for the formation of the dispensed drops of dosing liquid, but not optimal, especially with pulse-based dispensing. According to a preferred development of the present invention, a better pipetting tip, which dispenses a single drop without satellite drops, is obtained in that a third section of the receiving space is formed axially between the concave axial section and the pipetting opening as an opening line section, the radially delimiting inner wall of which differs from the inner wall in the concave axial section and in the second axial section with regard to at least one parameter: inclination relative to the channel axis and curvature about a curvature axis running transversely to the channel axis and clear width orthogonal to the channel axis.

[0051] The opening line section preferably comprises i.) a conical section with a cone angle of not more than 6°, wherein the channel axis is preferably the cone axis of the conical section, or / and ii.) a curved section running around the channel axis in the form of a concave section or a convex section with a radius of curvature which is at least ten times the axial length of the curved section, or / and iii.) a cylindrical section, wherein the channel axis is preferably the cylinder axis of the cylindrical section.

[0052] A circular-cylindrical section is preferred as the opening line section of the receiving chamber. Because the opening line section is preferably very short compared to the other axial sections mentioned, it can also have the circumferentially curved surface with a large radius of curvature mentioned under ii.), although iii.) and within iii.) the circular-cylindrical design is preferred. The cylindrical design allows for advantageous preconditioning of the dosing liquid received in the receiving chamber, as known from WO 2018 / 108825 A of the applicant, with regard to the shape of its meniscus closest to the pipette opening and its distance from the pipette opening itself. This not only enables the dispensing of very small quantities of liquid with high repeatability, but also the targeted, pulse-based dispensing of these small quantities of dosing liquid along the virtual channel axis.

[0053] In a very short axial transition region between the concave axial section and the opening line section, the inner wall can have an edge or a transition axial section that is convexly curved with respect to a curvature axis running transversely, preferably orthogonally, to the channel axis. The radius of curvature of the convex curvature of the inner wall in the transition axial section is preferably less than 0.6 mm, particularly preferably less than 0.4 mm, and even more preferably less than 0.3 mm. In a preferred embodiment, the radius of curvature is 0.2 mm.

[0054] The pipetting opening preferably has a clear width, in particular a diameter, orthogonal to the channel axis, with a dimension of less than 0.38 mm. This is smaller than the known and proven "CO-RE®" pipetting tip, which has a pipetting opening diameter of 0.4 mm with a nominal capacity of 50 pl. The clear width of the pipetting opening, in particular the diameter, is preferably less than 0.3 mm; more preferably, the clear width, in particular the diameter, is 0.275 mm.

[0055] Preferably, the dimension of the clear width, in particular as diameter, of the pipetting opening is greater than 0.2 mm, particularly preferably greater than 0.25 mm.

[0056] So far, only the internal shape of the pipette tip defined by the inner wall of the pipette tip has been described. According to a preferred embodiment of the invention, a radially outward-facing outer wall of the pipette tip in an extension section axially overlapping the opening line section can i.) have a concave curvature, viewed from the outside, about at least one curvature axis running transversely to the channel axis, or / and ii.) have a convex curvature, viewed from the outside, about at least one curvature axis running transversely to the channel axis, or / and iii.) be tapered toward the pipette opening, in particular conically tapered, or / and iv.) be cylindrical.

[0057] The outer wall of the pipette tip in an extension section axially overlapping the opening line section is preferably rotationally symmetrical, with the channel axis as the axis of rotational symmetry. The axis of curvature of the outer wall, which runs transversely to the channel axis, preferably runs orthogonally to the channel axis.

[0058] Preferably, the extension section axially overlapping the opening line section starts from the dosing longitudinal end of the pipette tip.

[0059] From the perspective of the desired lowest possible wetting of the outer wall of the pipette tip near the pipette opening, case ii.) is preferred, wherein the outer wall is particularly preferably formed starting from the dosing longitudinal end continuously into the concave axial section, particularly preferably up to the end of the concave axial section further away from the pipette opening according to ii.), i.e. with a convex curvature with respect to the axis of curvature. In this particularly preferred case, the outer wall is therefore convexly curved around the channel axis and is additionally convexly curved around axes of curvature orthogonal to the channel axis. There are preferably no further curvatures of the outer wall. This means that the contour of the outer wall of the pipette tip in the region of the opening line section does not follow the contour of the opening line section.

[0060] Preferably, the convex curvature of the outer wall, particularly starting from the pipette opening, does not become stronger, particularly preferably weaker, and even more preferably continuously weaker as it progresses in the direction away from the dosing longitudinal end. This particularly preferably applies up to the longitudinal end of the concave axial section furthest from the pipette opening.

[0061] The generatrix of a rotationally symmetrical outer wall of the pipette tip can also have a fundamentally hyperbolic profile in at least one, preferably in several, particularly preferably in all longitudinal sectional views in a longitudinal sectional plane containing the channel axis, particularly preferably directly starting from the dosing longitudinal end due to the advantageous wetting behavior. This also particularly preferably applies up to the longitudinal end of the concave axial section farthest from the pipette opening.

[0062] However, it should not be ruled out that the pipette tip has a cylindrical or conical collar in the region of the opening line section, meaning that the outer wall of the pipette tip is conical or cylindrical, in particular circularly cylindrical, in the region of the opening line section and only transitions into a convex shape at a distance from the pipette tip, for example in the region of a transition from the opening line section to the concave axial section, which is preferably spaced from the concave shape of the inner wall by the material thickness of the pipette tip, which in this case is to be measured orthogonally to the channel axis. The shape of the outer wall in the concave axial section then preferably follows the shape of the inner wall.The wall thickness can change in magnitude along the axial extension of the pipette tip, and in particular of the concave axial section or also of the second axial section, so that the shape sequence of the outer wall relative to the inner wall is preferably a qualitative shape sequence. In particular, according to one design option, the wall thickness can decrease in the axial direction, at least in the concave axial section, toward its longitudinal end closest to the pipette opening, preferably continuously, i.e., without kinks or jumps. Such a decreasing wall thickness can locally reduce the stiffness of the pipette tip, which in turn can influence the propagation of a pressure pulse into the absorbed dispensing liquid.By reducing the stiffness of the pipette tip in the area of ​​the concave axial section, for example, unwanted post-oscillation of the pipette tip in the concave axial section, caused by the propagation of a pressure pulse, can be reduced in amount or even completely eliminated. A lower stiffness of the pipette tip made of plastic is generally accompanied by higher internal damping of the pipette tip. Due to the preferred production of the pipette tip by injection molding, the plastic is preferably a thermoplastic. Among these, polyolefins are preferred, with polypropylene being preferred among the polyolefins, which has somewhat higher temperature stability than polyethylene. The pipette tip is preferably made of at least 90% by weight, more preferably 95% by weight, one and the same material in order to enable recycling orto enable the pipette tip to be reused in a single recycling stream. Therefore, the pipette tip is most preferably made of 100% by weight of the same material, disregarding unavoidable impurities.

[0063] The thermoplastic can be conventional or made from renewable raw materials. It can be used filled or unfilled, with the thermoplastic used to form the pipette tip preferably being colorless, more preferably translucent, and even more preferably transparent. Particles and / or fibers selected from graphite, flax, hemp, sugar cane, and the like, to name just a few possible fillers, can be considered as fillers.

[0064] The axial length of the concave axial section can preferably be between 15% and 60% of the total length of the pipette tip. The axial length of the second axial section can be between 35% and 70% of the total length of the pipette tip. The axial length of the orifice line section can be between 0.8% and 3% of the total length of the pipette tip. The total sum of the percentage lengths of the axial sections is less than 100%, since the coupling axial section also contributes to the total length of the pipette tip, but does not contribute to the axial sections: orifice line section, concave axial section, and second axial section. With the coupling axial section, the sum of the axial dimensions of the orifice line section, concave axial section, and second axial section is 100% of the total axial length of the pipette tip.

[0065] Regardless of the total length of the pipette tip, for fluid mechanics reasons, the opening line section has a length of at least 0.35 mm, preferably at least 0.4 mm, and particularly preferably exactly 0.5 mm. Likewise, the opening line section is preferably no longer than 0.8 mm, preferably no longer than 0.7 mm, and particularly preferably no longer than 0.6 mm.

[0066] The pipette tip preferably has a total length of at least 35 mm, preferably at least 45 mm, particularly preferably at least 50 mm, and even more preferably exactly 52.5 mm. Likewise, the pipette tip preferably has a total length of no more than 90 mm, preferably no more than 75 mm, particularly preferably no more than 65 mm.

[0067] The concave axial section preferably has a length of at least 7 mm, particularly preferably at least 8.5 mm, and more preferably at least 9 mm. Most preferably, the concave axial section has a length of exactly 10 mm. Likewise, the concave axial section preferably has a length of no more than 20 mm, particularly preferably no more than 16 mm, and more preferably no more than 13 mm.

[0068] The second axial section preferably has a length of at least 20 mm, particularly preferably at least 25 mm, more preferably at least 28 mm, and most preferably exactly 30 mm. Likewise, the second axial section preferably has a length of no more than 50 mm, particularly preferably no more than 40 mm, and more preferably no more than 35 mm.

[0069] The coupling axial section preferably amounts to approximately 15% to 35% of the total length of the pipette tip. In absolute terms, the coupling axial section, including a transition section to the axially adjoining second axial section, is preferably at least 7 mm long, particularly preferably at least 9 mm long, more preferably at least 11 mm long, and most preferably exactly 12 mm long. Likewise, the axial length of the coupling axial section is preferably no greater than 20 mm, particularly preferably no greater than 16 mm, and even more preferably no greater than 14 mm.

[0070] The coupling formation is preferably a shape of an inner wall of the pipette tip facing the channel axis, into which a coupling counter-formation axially penetrates in order to temporarily secure the pipette tip to the coupling counter-formation. Preferably, the inner wall of the coupling formation has a circumferential locking recess that bulges radially outward and is designed to engage with a radially expanding elastic element, in particular the O-ring mentioned above. The coupling formation is preferably designed like the coupling formation of the known CO-RE® pipette tips in order to ensure the use of the pipette tips according to the invention on the pipette devices previously using the applicant's CO-RE® pipette tips.The locking recess, which is preferably rotationally symmetrical with respect to the channel axis as the axis of rotation, has, in a longitudinal sectional view containing the channel axis, a contour line curved about an axis of curvature orthogonal to the channel axis, which contour line moves away from the channel axis along its axial extent and approaches the channel axis again.

[0071] Likewise, the coupling formation preferably has a radial shoulder as a stop surface for engagement with a counter-coupling formation. Accordingly, the inner diameter of the pipette tip decreases abruptly from an axial coordinate starting at the longitudinal end of the coupling. This axial coordinate is preferably between 3.5 and 6.5 mm starting from the longitudinal end of the coupling.

[0072] The axial sections described here are directly axial sections of the receiving space of the pipette tip or of a channel axially penetrating the pipette tip. The axial sections are also used as location or area specifications of the pipette tip as a whole. In accordance with the above explanations, it should be clarified that the present invention also relates to the use of a pipette tip as described and further developed above for the pulse-based dispensing of a dosing liquid received in the pipette tip together with a working gas.

[0073] The present invention is explained in more detail below with reference to the accompanying drawings. It shows:

[0074] Fig. 1 is an elevational view of a first embodiment of a pipette tip according to the invention,

[0075] Fig. 2 is a longitudinal sectional view of the pipette tip of the first embodiment in the longitudinal sectional plane II-II of Figure 1 containing the channel axis,

[0076] Fig. 3 is an enlarged view of the dosing longitudinal end of the first embodiment in longitudinal section,

[0077] Fig. 4 is an enlarged view of a dosing longitudinal end of a second embodiment of a pipette tip according to the invention in longitudinal section, and

[0078] Fig. 5 is an enlarged view of a dosing longitudinal end of a third embodiment of a pipette tip according to the invention in longitudinal section.

[0079] In Figure 1, an elevational view of a first embodiment of a pipette tip according to the invention is generally designated 10. The pipette tip 10 extends along a rectilinear channel axis K, which runs parallel to the plane of the drawing in Figure 1. The channel axis K defines an axial direction a running along the channel axis K, radial directions r running orthogonal to the channel axis K, and a circumferential direction u running around the channel axis K.

[0080] The pipetting tip 10 is oriented in Figure 1 according to its arrangement in a pipetting operation, ie the upper end in Figure 1 is designed as a coupling longitudinal end 12 for coupling to a pipetting channel of a pipetting device and the lower end in Figure 1 is designed as a dosing longitudinal end 14 for receiving dosing liquid into a receiving space 36 of the pipetting tip 10 and for dispensing dosing liquid from this.

[0081] The pipette tip 10 has, at its coupling longitudinal end 12, a coupling axial section 16, which is generally not reached by dosing liquid, which preferably rises in the axial direction from the dosing longitudinal end 14 by aspiration and is taken up into the pipette tip 10. The maximum nominal fill height of the pipette tip 10 is indicated in Figures 1 and 2 by the dashed line FL.

[0082] In the coupling axial section 16, on the outer side 10a of the pipette tip 10, support ridges 20 are formed in the axial direction a from an end-side cylindrical or slightly inclined conical annular section 18 toward the dosing longitudinal end 14, on whose end face 20a, facing in the axial direction a, the pipette tip 10 can be provided resting in a carrier container (not shown) for reception by a pipetting device. The support ridges 20 are arranged equidistantly in the circumferential direction u. Instead of the support ridges 20, the annular section 18 could also be formed axially extended, so that instead of individual end faces 20a, a closed, circumferential annular end face could serve as the support surface for the pipette tip 10.However, for a pipetting device to more securely pick up a pipette tip 10 from a carrier providing the pipette tip 10, it is advantageous if the support surface of the pipette tip 10 resting on a carrier surface is as small as possible to avoid undesirable adhesion effects between the pipette tip and the carrier. Such adhesion effects could make it difficult to lift the pipette tip 10 out of the carrier. Furthermore, the formation of support ridges 20 can save material compared to a solid ring section.

[0083] The support ridges 20 project radially outward beyond a cylindrical or slightly inclined conical second annular section 22 of the outer wall 11a of the pipette tip 10. This second annular section 22 is adjoined by a relatively steep conical section 24 of the outer wall 11a. The coupling axial section 16, which is not reached by the dosing liquid during normal pipetting operation, is axially adjoined by those axial sections of the pipette tip 10 which at least partially receive the dosing liquid during pipetting operation.

[0084] The most relevant axial section for the present application is the concave axial section 26, which derives its name from the special design of the inner wall 11b on the inner side 10b of the pipette tip in the concave axial section 26. This will be explained in more detail below in connection with Figures 2 and 3.

[0085] In the first embodiment of the pipette tip 10 shown in Figure 1, the outer wall 11a, with the exception of the axial section forming the support ridges 20, is rotationally symmetrical with the channel axis K as the axis of rotational symmetry. The outer wall 11a is therefore convexly curved around the channel axis K.

[0086] However, in the first embodiment, the outer wall 11a of the pipette tip 10 is also convexly curved about at least one curvature axis K2 orthogonal to the channel axis K from the dosing longitudinal end 14 in the axial direction toward the coupling longitudinal end 12 up to the end of the concave axial section 26 remote from the dosing longitudinal end 14. Due to the rotationally symmetrical design of the outer wall 11a, the contour line of the outer wall 11a shows the curvature convex to the curvature axis K2 in Figure 1. The radii of curvature emanating from the axes of curvature K2i and K22 are symbolically represented by dashed lines. With the exception of the axial section in which the support ridges 20 are formed, which break the strict rotational symmetry of the rest of the pipette tip, the elevation view of the pipette tip 10 is invariant with respect to a rotation of the pipette tip 10 about the channel axis K.

[0087] Due to the circumferentially equidistant arrangement of the similarly designed support ridges 20, the axial section of the pipette tip 10 having the support ridges 20 is also symmetrical with respect to the channel axis K at least to the extent that an elevation view of this axial section is invariant with a number of k support ridges 20 with respect to a rotation of the pipette tip 10 by a rotation angle of 3607k.

[0088] In Figure 1, two axes of curvature K2 (as axes K2i and K22) are shown as examples for the contour line of the outer wall 11a located to the left of the channel axis K, with the axes of curvature K2 running orthogonally to the plane of the drawing in Figure 1. Figures 1 to 5 are not to scale, which is why the distance of the respective axes of curvature K2 only qualitatively, but not quantitatively, indicates the respective radius of curvature indicated by dashed lines as the distance of the outer wall 11a from the respective axis of curvature K2.

[0089] The convex curvature of the contour line and thus of the outer wall 11a of the pipette tip 10 in the concave axial section 26 with respect to the at least one curvature axis K2 running orthogonally to the channel axis K is not constant along the channel axis K, but decreases with increasing distance from the dosing longitudinal end 14. This means that the radii of curvature, which indicate the convex curvature about a curvature axis K2, become larger in the concave axial section 26 with increasing distance from the dosing longitudinal end 14. For this reason, the convex curvature of the outer wall 11 a of the pipette tip 10 in the concave axial section 26 is not determined by a single curvature axis K2 orthogonal to the channel axis K, but by a plurality of curvature axes K2 following one another along the channel axis K, each of which can be thought of as rotating with the contour line around the channel axis K.

[0090] Axially between the concave axial section 26 and the coupling axial section 16 is a second axial section 28, in which the outer wall 11a of the pipette tip 10 is conical. The cone angle of the outer wall 11a in this section, measured from contour line to contour line across the channel axis K, is between 3.75° and 3.85°.

[0091] Axially between the concave axial section 26 and the dosing longitudinal end 14 there is an opening line section 30 in which the outer wall 11 a of the pipetting tip 10 is conical with the channel axis K as the cone axis or convexly curved around at least one further curvature axis K2 (not shown) orthogonal to the channel axis K.

[0092] Figure 2 shows a longitudinal sectional view of the pipette tip 10 of Figure 1 along the sectional plane II-II of Figure 1 containing the channel axis K. A channel 32 extends axially through the pipette tip 10 completely from the coupling longitudinal end 12 to the dosing longitudinal end 14. A filter can be accommodated in the channel 32, although this is not the case in the illustrated embodiment. In the illustrated embodiment, the channel 32 is rotationally symmetrical over its entire axial length with respect to the channel axis K as the axis of rotational symmetry.

[0093] Cross sections of the channel 32 along the channel axis K in cross-sectional planes orthogonal to the channel axis K are therefore circles, whereby the diameter of the respective cross-sectional circle can be of different sizes at different axial positions of the cross section along the channel axis K.

[0094] The channel 32 comprises a receiving space 36 extending from the pipetting opening 34 at the dosing longitudinal end 14, which serves to receive dosing liquid in the pipetting tip 10, and comprises a coupling space 38, which serves to couple to a pipetting channel of a pipetting device.

[0095] Starting from the coupling longitudinal end 12 axially in the direction of the dosing longitudinal end 14, the inner wall 11 b on the inner side 10b of the pipette tip is formed as a coupling formation 40.

[0096] First, the coupling formation 40, which is already largely known from the prior art, is briefly described: starting from the coupling longitudinal end 12, the inner wall 11 b of the pipette tip initially has an insertion bevel 42, which supports an axial physical introduction of a coupling counter-formation into the coupling space 38.

[0097] The insertion bevel 42 is followed by a cylindrical wall section 44 or a wall section 44 which tapers slightly in the direction away from the longitudinal end of the coupling, approximately with a full cone angle of between 1° and 5°, in which, in an axial section, a locking recess 46 which runs completely around the channel axis K and is rotationally symmetrical and dents the inner wall 11b radially outwards is formed for a positive locking engagement with a radially movable locking element of the coupling counter-formation.

[0098] At the longitudinal end of the wall section 44 remote from the coupling longitudinal end 12, the coupling formation 40 has a circumferential radial shoulder 48 as an axial stop for the precise relative positioning of the coupling counter-formation and the coupling formation 40 in the axial direction. Formed even further axially from the coupling longitudinal end 12 than the radial shoulder 48 is a negatively conical contact surface 50 for a seal provided on the coupling counter-formation.

[0099] At a certain safety distance axially from the conical contact surface 50, in order to prevent dosing liquid received in the receiving space 36 from reaching the coupling formation 40 or the coupling counter-formation introduced therein, the second axial section begins at reference numeral 52, in which the inner wall 11b of the pipette tip 10 has an initial diameter D1. The full cone angle of the inclination of the inner wall 11b in the conical, actually: negatively conical, second axial section 28 is equal to the above-mentioned full cone angle of the outer wall 11a of the pipette tip in the same second axial section 28. The initial diameter can preferably be between 3 mm and 5 mm and is 4 mm in the particularly preferred embodiment shown.

[0100] The length of the second axial section 28 is preferably between six and nine times the initial diameter D1, preferably between seven and eight times the initial diameter D1. In the example shown, the length of the second axial section 28 is 7.5 times the initial diameter D1. The second axial section 28 ends at reference numeral 54, where the receiving space 36 has a diameter D2 which is between one third and two thirds, more preferably between 40% and 60%, of the dimension of the initial diameter D1. In the exemplary embodiment shown, the diameter D2 is half the size of the initial diameter D1. The concave axial section 26, which is of particular interest in the present case, is immediately adjacent axially to the second axial section 28.In this concave axial section 26, the contour line M, which has the inner wall 11 b of the pipette tip 10 with the longitudinal section plane 11-11, is concavely curved around at least one, preferably around several, axes of curvature K3 orthogonal to the channel axis K.

[0101] Since the shape of the inner wall 11 b essentially follows the outer wall 11 a of the pipetting tip 10 in the concave axial section 26, the axes of curvature K3, i.e. K3i and K32, shown as examples, are located radially away by the respective wall thickness from the axes of curvature K2, i.e. K2i and K22, which indicate the convex curvature of the outer wall 11 a. Also and especially for the inner wall 11 b in the concave axial section 26, the curvature of the contour line as the shape-generating line of the rotationally symmetrical inner wall 11 b preferably decreases continuously, i.e. the radii of curvature, again symbolically represented by dashed lines, become larger as one progresses along the axial longitudinal end of the concave axial section 26 closer to the pipetting opening 34.A position variable h begins at the axial longitudinal end of the concave axial section 26 closer to the pipetting opening 34 and assumes values ​​increasing along the channel axis K in the direction of the axial longitudinal end of the concave axial section 26 further from the pipetting opening 34, linearly proportional to the distance from the longitudinal end closer to the pipetting opening.

[0102] Preferably, the contour line M in the concave axial section 26 is a hyperbolic contour line, which is structurally specified by the above equation 1. Its curvature decreases continuously with increasing distance from the longitudinal end of the concave axial section 26 closer to the pipetting opening 34 in the direction of the longitudinal end of the concave axial section 26 farther from the pipetting opening 34, or increases continuously with approaching the longitudinal end of the concave axial section 26 closer to the pipetting opening 34, starting from the longitudinal end of the concave axial section 26 closer to the pipetting opening 34. Due to the rotationally symmetrical design of the inner wall 11b in the concave axial section 26, what was said for the contour line M applies to the entire inner wall 11b in the concave axial section 26.

[0103] Due to this physical design of the inner wall 11 b and thus of the receiving space 36 in the concave axial section 26, a pressure pulse generated in a working gas in the coupled pipetting channel of a pipetting device, which pressure pulse is generally generated in an axial region of the pipetting channel outside the pipetting tip 10, spreads along the channel axis K in the direction of the pipetting opening and strikes a boundary surface of a dosing liquid received in the receiving space 36, which boundary surface is located further away from the pipetting opening 34, can spread particularly advantageously in the dosing liquid along the channel axis K in the concavely curved concave axial section 26.If this pressure pulse reaches the interface of the dosing liquid being collected, which is closer to the pipetting opening 34, the pressure pulse overcomes the surface tension of the dosing liquid at the interface, whereby a dosing liquid droplet in the submicroliter range, preferably with a droplet volume of less than 500 nl, particularly preferably less than 100 nl, can be ejected with a repeatably precise dosing quantity. Depending on the viscosity and surface tension of the dosing liquid, dosing liquid drops with a droplet volume of no less than 30 nl, more reliably no less than 50 nl, and particularly reliably no less than 70 nl can be dispensed with repeatable precision using a pulse-based method.

[0104] However, the concave axial section 26 of the receiving space 36 does not end directly at the pipetting opening 34, although this would be possible in principle according to the present invention. Axially between the pipetting opening 34 and the longitudinal end of the concave axial section 26 closer to the pipetting opening 34 is a preferably cylindrical opening line section 30 of the channel 32 or of the receiving space 36. The opening line section 30 has a diameter of less than 10%, preferably less than 7%, of the initial diameter D1. In the illustrated embodiment, the opening line section 30 has a diameter of 0.275 mm. With regard to pulse-based dispensing, the opening line section 30 serves to provide a meniscus of the dosing liquid received in the receiving space 36 that is as defined as possible and closer to the pipetting opening.By targeted changes in the working gas pressure in the pipetting channel, and thus also at least in the end region of the receiving chamber 36 closer to the coupling longitudinal end 12, a flat meniscus can be formed in the opening line section 30, which also has an axial distance from the pipetting opening 34. If the pressure pulse propagating in the received dosing liquid during a pulse-based dispensing encounters the meniscus closer to the pipetting opening, which has been preconditioned in the manner just described, at the end of its propagation, pulse-based dosing liquid droplets in the submicroliter range can be dispensed with high dosing accuracy and also with high repeatability.Further basic information on the preconditioning of a dosing liquid held in a receiving chamber of a pipette tip and its meniscus near the pipette opening for pulse-based dispensing is disclosed in WO 2018 / 108825 A by the applicant. The pipette tip discussed here is particularly suitable for carrying out a pulse-based dispensing method as disclosed in WO 2018 / 108825 A by the applicant.

[0105] A transition section may be formed between the opening line section 30 and the concave axial section 26, which may be necessary for manufacturing purposes to transition from the cylindrical opening line section 30 to the concave axial section 26 of the channel 32 or the receiving space 36. A radius of curvature at the transition of the inner wall 11b of the pipette tip 10 axially between the opening line section 30 and the concave axial section 26 may be, for example, 0.2 mm.

[0106] Figure 3 shows an enlarged longitudinal sectional view of the dosing end 14 of the pipette tip 10 of Figure 2.

[0107] For the sake of clarification, it should be noted that due to the rotationally symmetrical design of the inner wall 11 b of the pipette tip 10 in the illustrated embodiment, each longitudinal sectional view whose longitudinal sectional plane contains the channel axis K shows the same contour line M as the intersection line of the inner wall 11 b with the longitudinal sectional plane.

[0108] At the longitudinal end of the concave axial section 26 closer to the pipetting opening 34, the contour line M and thus the inner wall 11 b has an inclination of the angle a with respect to the channel axis K. The angle a can preferably be between 35° and 50°, particularly preferably between 35° and 45°, even more preferably between 37.5° and 42.5°, and most preferably is exactly 40°.

[0109] An end face 11c of the pipette tip 10, which surrounds the pipette opening 34 in a closed, circumferential manner, is preferably flat, i.e., a flat annular surface. Alternatively, it can also have a convex curvature, preferably around at least one axis of curvature orthogonal to the channel axis K. For example, the end face 11c can be formed as part of a torus surface, which is obtained by intersecting a torus with a plane oriented orthogonally to the torus axis. Since a large part of the outer side 10a of the pipette tip 10 is rotationally symmetrical, the torus axis is also preferably the rotational symmetry axis of the torus.

[0110] Figure 4 shows an enlarged view of the dosing longitudinal end 114 of a second embodiment of a pipette tip 110, corresponding to Figure 3.

[0111] Identical and functionally equivalent components and component sections as in Figures 1 to 3 are provided with the same reference numerals in Figure 4, but in the number range 100 to 199.

[0112] The second embodiment of Figure 4 will be described below only insofar as it differs from the previously described first embodiment, to whose description reference is expressly made for the explanation of the following second embodiment.

[0113] The second embodiment of Figure 4 differs from the first embodiment of Figures 1 to 3 only in that a section 111 a1 of the outer wall 111 a of the pipette tip 110 surrounding the opening line section 130 is cylindrical or conical with a small full cone angle of 1° to 5°, in any case in a longitudinal section containing the channel axis K with a straight contour line.

[0114] Since the remaining outer wall 111a is convexly curved in the region of the concave axial section 126, as in the first embodiment, with respect to axes of curvature K2 orthogonal to the channel axis K (see Figure 1), a transition region 156 of the outer wall 111a between the cylindrical or conical outer wall section 111a1 and the outer wall 111a is concavely curved in the region of the concave axial section 126 about axes of curvature orthogonal to the channel axis K. The radius of curvature in the transition region 156 can be very small, so that the optical impression of a circumferential edge is created.

[0115] Figure 5 shows an enlarged view of the dosing longitudinal end 214 of a third embodiment of a pipette tip 210, corresponding to Figures 3 and 4.

[0116] Identical and functionally equivalent components and component sections as in Figures 1 to 4 are provided with the same reference numerals in Figure 5, but in the number range 200 to 299.

[0117] The third embodiment of Figure 5 will be described below only insofar as it differs from the previously described first two embodiments, to whose description express reference is also made for the explanation of the following third embodiment.

[0118] The third embodiment differs from the second embodiment only in that the concavely curved transition region 256 of the outer wall 211a of the pipette tip 210 begins at the dosing longitudinal end 212 and, in the end section of the concave axial section 226 closer to the pipette opening, transitions into the previously described convexly curved region of the outer wall 211a. Therefore, starting from the dosing longitudinal end 214 in the direction of the coupling longitudinal end 212, the contour line of the outer wall 211a is initially concavely curved in the axial region of the opening line section 230 and transitions, preferably without kinks, into a convex curvature, which the outer wall 211a qualitatively maintains with decreasing curvature up to the longitudinal end of the concave axial section 226 farther from the pipette opening.

[0119] In tests, the first embodiment has shown the lowest tendency to wetting by dosing liquid dispensed from the receiving space 36.

Claims

Claims 1. Interchangeable pipette tip (10; 110; 210), whereby the pipette tip (10; 110; 210) extends along a channel axis (K), wherein the channel axis (K) defines an axial direction (a) running along the channel axis (K), radial directions (r) orthogonal to the channel axis (K) and a circumferential direction (u) running around the channel axis (K), wherein the pipetting tip (10; 110; 210) has at its one axial longitudinal end, as a coupling longitudinal end (12), a coupling formation (40) which is designed for coupling to a coupling counter-formation of a pipetting device, wherein the pipetting tip (10; 110; 210) has at its longitudinal end axially opposite the coupling longitudinal end (12), as a dosing longitudinal end (14; 114; 214), a pipetting opening (34; 134; 234) which is provided with a formed receiving space (36; 136; 236), wherein the receiving space (36; 136; 236) of the pipette tip (10; 110; 210) extends towards the pipette opening (34; 134;234) is tapered, characterized in that at least one axial section of the receiving space (36; 136; 236) is designed as a concave axial section (26; 126; 226) in such a way that an inner wall (11 b; 111 b; 211 b) of the pipetting tip (10; 110; 210) radially delimiting it is curved about at least one axis of curvature (K3) running transversely to the channel axis (K).

2. Replaceable pipette tip (10; 110; 210) according to claim 1, characterized in that the inner wall (11 b; 111 b; 211 b) in the concave axial section (26; 126; 226) is curved about the at least one axis of curvature (K3) running transversely to the channel axis (K) and is curved about the channel axis (K) as a second axis of curvature.

3. Replaceable pipette tip (10; 110; 210) according to claim 1 or 2, characterized in that the concave axial section (26; 126; 226) is located in an axial region of the pipette tip (10; 110; 210) whichstarting from the pipetting opening (34; 134; 234) extends over 50% of the total axial extension length of the pipetting tip (10; 110; 210). Replaceable pipetting tip according to one of the preceding claims, characterized in that the concave axial section (26; 126; 226) tapers continuously in the direction of the pipetting opening (34; 134; 234) in such a way that along the entire concave axial section (26; 126; 226) it applies that of two clear cross-sections of the receiving space (36; 136; 236) viewed at different axial locations along the channel axis (K), the cross-sectional area of ​​the cross-section located closer to the pipetting opening (34; 134; 234) is not larger than the cross-sectional area of ​​the cross-section located further away from the pipetting opening (34; 134; 234).Replaceable pipetting tip (10; 110; 210) according to one of the preceding claims, characterized in that for a longitudinal sectional view in at least one longitudinal sectional plane containing the channel axis (K), the curvature of a contour line (M) of the inner wall (11 b; 111 b; 211 b) of the pipetting tip (10; 110; 210) radially delimiting the concave axial section (26; 126; 226) does not become smaller as the pipetting opening (34; 134; 234) is approached. Replaceable pipetting tip (10; 110; 210) according to claim 5, characterized in that for the longitudinal sectional view in the at least one longitudinal sectional plane containing the channel axis (K), the curvature of the contour line (M) of the inner wall (11 b; 111 b; 211 b) of the pipetting tip (10; 110; 210) radially delimiting the concave axial section (26; 126; 226) increases as the pipetting opening (34; 134; 234) is approached.Replaceable pipette tip according to claim 6, characterized in that the contour line (M) of the inner wall (11 b; 111 b; 211 b) of the pipette tip (10; 110; 210) radially delimiting the concave axial section (26; 126; 226) has a hyperbolic profile. Replaceable pipette tip (10; 110; 210) according to one of the preceding claims, characterized in that a second axial section (28; 128; 228) of the receiving space (36; 136; 236) is formed in an axial region located between the coupling formation (40) and the concave axial section (26; 126; 226) of the pipette tip (10; 110; 210), the radially delimiting inner wall (11 b; 111 b; 211 b) of which differs from the inner wall (11 b; 111 b; 211 b) in the concave axial section (26; 126; 226) with regard to at least one parameter consisting of inclination relative to the channel axis (K) and curvature about an axis of curvature (K2) running transversely to the channel axis (K).Replaceable pipetting tip (10; 110; 210) according to claim 8, characterized in that the second axial section (28; 128; 228) is tapered in the direction from the coupling longitudinal end (12) to the dosing longitudinal end (14; 114; 214) in such a way that its second clear width (D2) orthogonal to the channel axis (K) at its end closer to the dosing longitudinal end (14; 114; 214) is between 40% and 60% of a first clear width (D1) parallel to the second clear width (D2) at its end closer to the coupling longitudinal end (12; 112; 212).Replaceable pipetting tip (10; 110; 210) according to one of the preceding claims, characterized in that axially between the concave axial section (26; 126; 226) and the pipetting opening (34; 134; 234) a third section of the receiving space (36; 136; 236) is formed as an opening line section (30; 130; 230), the inner wall (11 b; 111 b; 211 b) radially delimiting it differing from the inner wall (11 b; 111 b; 211 b) in the concave axial section (26; 126; 226) and in the second axial section (28; 128; 228) with respect to at least one parameter from inclination relative to the channel axis (K) and curvature about a direction running transversely to the channel axis (K). Curvature axis and clear width orthogonal to the canal axis (K). Replaceable pipette tip (10; 110; 210) according to claim 10, characterized in that the opening line section (30; 130; 230) of the receiving space (36; 136; 236) i.) a conical section with a cone angle of not more than 6° and / or ii.) a curved section running around the channel axis (K) in the form of a concave section or a convex section with a radius of curvature which is at least ten times the axial length of the curved section, and / or iii.) a cylindrical section. Replaceable pipetting tip (10; 110; 210) according to claim 10 or 11, characterized in that a clear width of the pipetting opening (34; 134; 234) orthogonal to the channel axis (K) has a dimension of less than 0.38 mm.Replaceable pipetting tip (10; 110; 210) according to one of claims 10 to 12, characterized in that a radially outwardly pointing outer wall (11 a; 111 a; 211 a) of the pipetting tip (10) in an extension section axially overlapping the opening line section (30; 130; 230) i.) has a concave curvature, viewed from the outside, about at least one axis of curvature running transversely to the channel axis (K) or / and ii.) has a convex curvature, viewed from the outside, about at least one axis of curvature running transversely to the channel axis (K) or / and iii.) is tapered towards the pipetting opening (34; 134; 234) or / and iv.) is cylindrical. Replaceable pipette tip (10; 110; 210) according to one of the preceding claims, characterized in that the axial length of the concave axial section (26; 126; 226) is between 15% and 60% of the total length of the pipette tip (10; 110; 210), that the axial length of the second axial section (28; 128; 228) is between 35% and 70% of the total length of the pipette tip (10; 110; 210), and that the axial length of the opening line section (30; 130; 230) is between 0.8% and 3% of the total length of the pipette tip (10; 110; 210). Replaceable pipette tip (10; 110; 210) according to one of the preceding claims, characterized in that the coupling formation (40) extends over approximately 15% to 35% of the total length of the pipette tip (10; 110; 210).Use of a pipette tip (10; 110; 210) according to one of the preceding claims for the pulse-based dispensing of a dosing liquid held in the pipette tip (10; 110; 210) together with a working gas.

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