Patent Application
20090317303
The present application claims the benefit of EP Appl. No. 08104530.4 filed Jun. 24, 2008, the content of which is hereby incorporated herein by reference in its entirety.
The present invention relates to a disposable pipette tip for releasably connecting with a pipette shaft.
Disposable pipette tips are used to receive and dispense liquids. Such pipette tips are particularly useful for receiving and dispensing small volumes of liquid. For pipetting, the shaft of a pipette is connected to an elongated rigid tubular interface of the pipette tip. Following pipetting, the pipette tip is released from the shaft of the pipette and discarded.
Disposable pipette tips are well known in the art. Usually, pipette tips are produced with injection molding techniques using thermoplastic materials. Such thermoplastic materials have a limited elasticity. They commonly have a rigid interface for connecting with the pipette shaft.
U.S. Pat. No. 4,072,330 discloses a pipette tip interface with a deformable conical sealing zone which is obtained by reduction of the wall thickness. This renders the pipette tip more fragile and prone to damage.
In particular in automated systems, it is difficult to achieve precision of the orientation of the pipette shaft and the pipette tip with respect to the vessel comprising the sample using pipette tips known in the art. If the shaft does not correctly align with the rigid pipette tip interface, the connection may not be leak tight, leading to imprecision when pipetting a liquid.
In a first aspect, the invention relates to a disposable pipette tip for releasably connecting with a pipette shaft, comprising an elongated flexible tubular interface having a central axis for connecting the pipette tip to the pipette shaft, and an elongated tubular part extending from a distal tip opening to said tubular interface, wherein said elongated flexible tubular interface comprises at least one section having a geometry providing a horizontal strain of said section of said elongated flexible tubular interface of more than about 20% and wherein the extensibility of said section of said elongated flexible tubular interface is reversible, and wherein said disposable pipette tip is made of polypropylene.
In a second aspect, the invention relates to a rack for storing pipette tips, wherein said rack comprises pipette tips according to the invention.
In a third aspect, the invention relates to a method of producing a disposable pipette tip according to the invention, comprising the step of 1-compound injection molding using a mold which is of a shape that protrusions are formed on the inside surface of an elongated flexible tubular interface of said pipette tip.
In a fourth aspect, the invention relates to a system for pipetting liquid samples, comprising a disposable pipette tip according to the invention, and a pipette comprising a pipette shaft for connecting to a pipette tip, wherein said pipette shaft is connected to said pipette tip to pipette liquid samples.
In a fifth aspect, the invention relates to a process of connecting a pipette to a pipette tip, comprising the steps of
In a sixth aspect, the invention relates to a process for pipetting liquid samples, comprising the steps of:
In a seventh aspect, the invention relates to an analytical system comprising at least one module which comprises the pipette tips of the invention.
a-b show perspective views of one embodiment of a flexible interface of a disposable pipette tip in a relaxed (
a-c show top views (T) of different embodiments (
a-b show the interaction of pipette shaft and pipette tip interface (
a-c schematically show a comparison of strain of the basic material of the pipette tip (
a-b show two embodiments of pipette tips with interfaces comprising section with material with and without a flexible geometry either perpendicular (
As mentioned hereinabove, the present invention provides a disposable pipette tip for releasably connecting with a pipette shaft which comprises an elongated flexible tubular interface having a central axis for connecting said pipette tip to the pipette shaft. Said disposable pipette tip additionally comprises an elongated tubular part extending from a distal tip opening to said tubular interface. The elongated flexible tubular interface of said disposable pipette tip comprises at least one section which has a geometry which provides a strain of said section of said elongated flexible tubular interface of more than about 20% and wherein the extensibility of said section of said elongated flexible tubular interface is reversible. In a certain embodiment, said strain is more than 30%. In another embodiment, said strain is more than 40%.
According to the present invention, an “analyte” is understood to be a substance of interest, e.g. a nucleic acid of interest or a protein of interest which is investigated and its presence or absence, or its concentration in a biological sample is determined as its presence or absence is indicative of a certain condition or disease of a human or animal. In a certain embodiment, said analyte is a biological analyte, for example a nucleic acid. Said nucleic acid may be RNA or DNA or any derivative thereof.
The term “fluid” as used herein relates to any kind of solution used in analytical tests. A fluid may include fluid biological samples such as blood, serum, sputum, cerebral fluid, urine, or any type of soluble reagent used for preparing or processing said analyte.
The term “biological sample” as used herein relates to any sample derived from a biological organism. In an embodiment of the invention, the biological sample comprises viruses or bacterial cells, as well as isolated cells from multicellular organisms as e.g. human and animal cells such as leucocytes, and immunologically active low and high molecular chemical compounds such as haptens, antigens, antibodies and nucleic acids, blood plasma, cerebral fluid, sputum, stool, biopsy specimens, bone marrow, oral rinses, blood serum, tissues, urine or mixtures thereof. Thus, the biological sample may be either solid or fluid. In a certain embodiment of the invention the biological sample is a fluid from the human or animal body. A biological sample which is a fluid is also called a sample fluid. In a certain embodiment the biological sample is blood, blood plasma, blood serum or urine. The blood plasma is for example EDTA-, heparin- or citrate-treated blood plasma. In an embodiment of the invention the biological sample comprises bacterial cells, eukaryotic cells, viruses or mixtures thereof. In a certain embodiment of the invention, the virus is the hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), the human immunodeficiency virus (HIV), the human papilloma virus (HPV) or parvovirus B19. The biological sample can also be of a type used for environmental analysis, food analysis or molecular biology research, e.g. from bacterial cultures or phage lysates.
The term “releasably” as used herein relates to the interaction between pipette tip and pipette shaft being releasable, i.e. the pipette tip, after connecting to the pipette shaft, may be released again.
The term “elongated flexible tubular interface” as used herein relates to the part of the pipette tip which is brought into direct contact with a pipette shaft when the pipette tip is connected to the pipette shaft. The term “tubular” is meant to describe a conical or cylindrical shaped structure with an empty interior through which liquid or air can pass. The term “elongated” relates to the fact that the interface extends over a distance sufficient to properly connect with a pipette shaft. The terms “elongated flexible tubular interface” and “interface” are used interchangeably herein.
The term “pipette shaft” relates to the part of a pipette for transferring liquids capable of connecting directly with a pipette tip. Said connection with the interface can be either from the inside or the outside of the interface. Thus, in a certain embodiment, when connecting with the interface, the pipette shaft enters the inside of the flexible tubular interface of the pipette tip and causes the interface to extend. In another embodiment, the pipette shaft grips the interface from the outside. In yet another embodiment of the pipette shaft hereinbefore described, said pipette shaft forms part of a robotic pipetting system. Said robotic pipetting system may comprise more than one pipette shafts which can interact with a pipette interface hereinbefore described.
The term “strain” as used herein relates to a measure of the flexibility of an object. The relative strain, ε, is given by the formula:
ε=(l−l0)/l0
where ε is the relative strain in measured direction, l0 is the original length of the material and l is the current length of the material. The strain εF∞ of a material is, therefore, understood to be the elastic limit. This limit defines the transition between fully reversible elastic deformation of a material and plastic deformation which is not reversible. For common polymers, strain or εF∞ is <5%. e.g. for PVC (polyvinyl-chloride), εF∞ is 0.8%; for polycarbonate (PC), εF∞ is 0.4%, and for polypropylene (PP), εF∞ is between 2.0 and 2.5%.
The term “geometry” as used herein relates to the three-dimensional structure of the interface. The extensibility or strain of the pipette tip is, thus, not achieved by using an elastic material for making the interface, but by the structure of the interface itself. However, it is within the scope of the present invention that parts of the interface or all of the interface may comprise an elastic material, such as rubber, which has a geometry which produces an increased strain compared to just the strain of the elastic material itself. Non-limiting examples for geometries of the interface are protrusions, or a net-like structure of the interface.
In a certain embodiment, the strain is a horizontal strain.
The term “reversible” as used herein relates to the reversibility of strain of the interface. When interacting with a pipette shaft, the flexible interface of the pipette tip is extended. When, subsequently, the pipette tip is released from the pipette shaft, the interface returns into its original relaxed state, and can be reused. This means that a pipette shaft can be connected to and released from one pipette tip repeatedly. This allows reusing the pipette tips at least once.
The term “section” as used herein relates to a segment or part of the tubular interface which has a geometry and strain as described herein before. This means that the tubular interface may comprise parts with said geometry and parts without said geometry. In a certain embodiment, the parts without said geometry lack the flexibility defined by the geometry. Said sections may be arranged axially (i.e. in parallel with the axis of the tubular interface) or they may be for example arranged perpendicular to said axis. Thus, the tubular interface may, in a certain embodiment, comprise parts which are more solid, and parts which are flexible. In another embodiment, the entire tubular interface has a geometry as described herein.
In a certain embodiment, said tubular interface has a constant wall thickness.
The term “constant wall thickness” relates to the thickness of the wall of the interface described herein above and below. “Constant” means that the wall thickness is substantially identical over the whole interface. In a certain embodiment, said wall thickness is identical over the whole interface. “Identical” includes some variability due to production processes.
In another embodiment, the interface hereinbefore described has a sealing zone and a gripping zone, wherein said gripping zone has at least one section which has a geometry which provides a strain as hereinbefore described. The sealing zone is deprived of such a geometry as hereinbefore described. Thus, when strained, the sealing zone is irreversibly deformable.
When interacting a pipette shaft with a disposable pipette tip comprising an elongated flexible tubular interface according to the present invention, the connection between pipette tip and interface is leak-tight, even if the orientation of the shaft and the interface is not optimal, due to the flexibility of the interface. The flexibility of the interface of the pipette tip according to the present invention further prevents the pipette shaft from interacting too tightly with the interface and facilitates the removal of the pipette tip following pipetting. This also prevents damaging the tip material, thus also allowing reuse of the pipette tip.
Said pipette shaft can be a cannula through which the liquid is aspirated, or it can be a pipette shaft which exerts pneumatic pressure for aspirating liquid into the pipette tip according to the invention, and for subsequently dispensing said liquid into a vessel.
In a certain embodiment of the pipette tip hereinbefore described, said elongated flexible tubular interface comprises protrusions on the inside surface. In another embodiment, said elongated flexible tubular interface additionally comprises protrusions on the outside surface. In another embodiment of the pipette tip hereinbefore described, said protrusions are arranged in a one- or two-dimensional pattern. One- or two dimensional patterns can be selected from ribs, undulated protrusions or a two-dimensional rhomboid shape.
Thus, the term “protrusions” as used herein relates to ribbed or undulated surfaces of the interface which are protrusions relative to a virtual cylindrical or conical surface of said interface.
In a certain embodiment the elongated flexible tubular interface of the pipette tip comprises protrusions on the inside surface, and sometimes additionally on the outside surface. The protrusions are arranged as one- or two-dimensional ribs. In a certain embodiment, the orientation of the one- or two-dimensional ribs is radial. In another embodiment, the orientation of the ribs is axial. In yet another embodiment, said protrusions may be snap-fits extending from the surface of the pipette tip towards its axis.
In a certain embodiment of the disposable pipette tip hereinbefore described, said elongated flexible tubular interface is connected to said elongated tubular part by a ring-shaped planar sealing surface. This ring-shaped planar sealing surface extends from the opening of the elongated flexible tubular interface which is in a proximal location relative to the elongated part to the opening of the elongated tubular part proximal to said elongated flexible tubular interface. Furthermore, proximal to said ring-shaped planar sealing surface, the radius of said elongated flexible tubular interface is larger than the radius of said elongated tubular part. Thus, the ring-shaped planar sealing surface is a connection between the tubular interface and the elongated tubular lower part of the pipette tip. When the pipette shaft is connected to the pipette tip, the bottom surface of the shaft is pressed against the ring-shaped surface described hereinbefore, providing liquid-tightness. Consequently, this allows for a separation of the functions of gripping and providing liquid-tightness. Gripping is achieved by the interaction between the pipette shaft and the interface, while liquid-tightness is achieved by interacting the bottom of the shaft with said ring-shaped planar sealing surface hereinbefore described. This has the advantage that the functions of holding and of liquid-tightness between pipette shaft and pipette tip can be optimized separately.
The elongated flexible tubular interface and the elongated tubular part of the pipette tip of the present invention may be made of different materials.
In a certain embodiment of the disposable pipette tip hereinbefore described, said elongated flexible tubular interface is made of the same material as the elongated tubular part. In another embodiment, said pipette tip is a 1-compound injection molded pipette tip.
Thus, the flexibility of the tubular interface can be achieved by the structure of the surface of the interface alone, even with the same material used commonly for the production of pipette tips with a rigid tubular interface. Commonly, pipette tips are produced with injection molding techniques using thermoplastic materials (polymers). One such material is polypropylene. Thermoplastic materials are, however, limited in elasticity. Typically, the yield strain of such materials is about 5-10%. The pipette tip interfaces according to the present invention which have an increased strain due to the geometry of the interface structure when using those same materials can, thus, still return to their original shape when exposed to higher strains. Furthermore, since this effect can be achieved with a pipette tip wherein the elongated flexible tubular interface is made of the same material as the elongated tubular part, it is not necessary to use more laborious 2-component molding to combine rigid and flexible materials.
The present invention also relates to a rack for storing pipette tips, wherein said rack comprises pipette tips hereinbefore described.
Furthermore, the present invention relates to a method of producing a disposable pipette tip hereinbefore described, comprising the step of compound injection molding using a mold which is of a shape that protrusions are formed on the inside surface and/or outside surface of an elongated flexible tubular interface of said pipette tip.
Compound injection molding techniques are well known in the art. Thus, the present invention allows the use of common and cost-efficient production methods as well as the use of materials compliant with regulatory requirements for diagnostic applications for the production of the pipette tips hereinbefore described.
In a certain embodiment, said protrusions have a geometry as described hereinbefore.
In certain embodiments pipette tips according to the present invention are pipette tips with an interface having a diameter of about 1 to about 20 mm and a volume of about 10 μl to about 5 ml.
The present invention further relates to a system for pipetting liquid samples, comprising:
Referring now to
a shows a relaxed elongated flexible tubular interface (2) with protrusions (7) which provide flexibility to the interface. A ring shaped planar sealing surface (6) extending from the opening of the elongated flexible tubular interface (2) proximal to the elongated part (4) to the opening of elongated tubular part (4) proximal to the elongated flexible tubular interface (2).
The analytical system according to the invention may further comprise a detection module. In a certain embodiment, said detection module is a combined nucleic acid amplification and detection module.
In a certain embodiment of said analytical system, said system comprises at least one robotic pipetting system. The robotic pipetting system comprises pipette shafts which can interact with the elongated flexible tubular interface of pipette tips hereinbefore described. The interaction of the pipette shafts with the interfaces according to the present invention in such a system leads to improved robotic tolerances and reliability. In addition, the interaction does not damage the interface of the pipette tips, and the pipette tips can, thus, be reused.
The present invention also relates to a process of connecting a pipette to a pipette tip. This process comprises connecting the pipette shaft of said pipette with a pipette tip hereinbefore described. When connecting the pipette shaft to the pipette tip, the pipette tip is being fitted to the pipette shaft by extending the diameter of the elongated flexible tubular interface of the pipette tip. This extension allows adapting the interface to the diameter of the pipette shaft. Furthermore, the process comprises the step of providing liquid tightness. Liquid tightness is achieved by pressing the bottom surface of the pipette shaft to a ring shaped planar sealing surface. This ring-shaped planar sealing surface connects the interface and the lower tubular part of the pipette tip. The ring-shaped planar sealing surface extends from the opening of said elongated flexible tubular interface proximal to said elongated part to the opening of said elongated tubular part proximal to said elongated flexible tubular interface. Thus, proximal to said ring-shaped planar sealing surface, the radius of said elongated flexible tubular interface is larger than the radius of said elongated tubular part.
Furthermore, the present invention provides a process for pipetting liquid samples, comprising:
It is understood that the examples and embodiments described herein are for illustrative purposes only and are not intended to limit the scope of the claimed invention. It is also understood that various modifications or changes in light the examples and embodiments described herein will be suggested to person skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims.
While the foregoing invention has been described in some detail for purposes of clarity and understanding, it will be clear to one skilled in the art from a reading of this disclosure that various changes in form and detail may be made without departing from the true scope of the invention. For example, the systems and methods described above may be used in various combinations. All publications cited in this application are incorporated by reference in their entirety for all purposes to the same extent as if each individual publications were individually indicated to be incorporated by reference for all purposes.
| Number | Date | Country | Kind |
|---|---|---|---|
| 08104530.4 | Jun 2008 | EP | regional |
