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Title:
ROD PROVIDED WITH CHANNEL
Document Type and Number:
WIPO Patent Application WO/2002/075282
Kind Code:
A1
Abstract:
A rod for use in an apparatus for measuring viscoelastic properties of a fluid sample, which apparatus comprises a movable cup and a stationary rod, is disclosed. Several embodiments of the rod, all of which comprise at least one channel for supplying or removing fluid sample(s) or reagent(s) into or out of the cup are disclosed. Further, a rod and cup assembly is described, wherein the rod and cup are suitably together as an engaged unit.

Inventors:
RAANBY MATS (SE)
Application Number:
PCT/SE2002/000460
Publication Date:
September 26, 2002
Filing Date:
March 13, 2002
Export Citation:
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Assignee:
GLOBAL HEMOSTASIS INST MGR AB (SE)
RAANBY MATS (SE)
International Classes:
G01N11/16; (IPC1-7): G01N11/16
Domestic Patent References:
WO1997039332A11997-10-23
Foreign References:
US4154093A1979-05-15
US4602501A1986-07-29
US5327778A1994-07-12
Attorney, Agent or Firm:
ZACCO SWEDEN AB (P.O. Box 23101 Sveavägen 170 Stockholm, SE)
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Claims:
Claims
1. A rod for use in an apparatus for measuring viscoelastic properties of a fluid sample, which apparatus comprises a movable cup and a stationary rod, having a first end and a second end, the second end being intended for insertion into the cup, wherein the rod is provided with at least one channel for supplying or removing fluid sample (s) or reagent (s) into or out of the cup.
2. A rod according to claim 1, wherein at least one channel extends from an inlet/outlet on the rod that is positioned at a distance from the second end of the rod, through the rod and to an outlet/inlet the second end of the rod.
3. A rod according to any one of claims 1 or 2, wherein at least one channel extends to the bottom of said second end of the rod.
4. A rod according to any one of claims 13, wherein an inlet/outletof at least one channel is situated at said first end of the rod.
5. A rod according to any one of claims 14, wherein at least one channel has an extension parallel to the longitudinal axis of the rod.
6. A rod according to claim 5, wherein one channel has an extension, which coincides with the longitudinal axis of the rod.
7. A rod according to any one of claims 16, wherein at least one channel is adapted to embrace a syringe with which fluid sample (s) or reagent (s) can be supplied to or removed from the cup.
8. A rod according to claim 7, wherein a section of at least one channel facing the first end of the rod has dimensions adapted to embrace the barrel of the syringe, whereas a section of said channel facing the second end is tapered to fit the narrow end of the syringe.
9. A rod according to any one of claims 18, provided with at least two channels wherein a first channel extends to a point at the second end of the rod, which point is intended to be below the desired surface level of the fluid sample in the cup during measuring, and wherein a second channel extends to a point at the second end of the rod that equals the desired surface level of fluid sample in the cup.
10. A rod according to any one of claims 19, wherein at least one channel consists of a main channel with an outlet/inlet at the second end of the rod and at least two inlets/outlets at the first end of the rod.
11. A rod according to any one of claims 110 consisting of a shaft and a bob.
12. A rod according to claim 11, wherein the bob is detachable.
13. A rod and cup assembly, wherein the rod is according to any one of claims 112.
14. A rod and cup assembly according to claim 13, wherein the rod and cup are together as an engaged unit.
15. A rod and cup assembly according to claim 14, wherein the engagement is provided by protruding edges extending from the periphery of the rod and/or the upper part of the cup.
Description:
Rod provided with channel The present invention relates to a rod, especially for use in an apparatus for measuring viscoelastic properties of fluid samples, which apparatus comprises a movable cup and a stationary rod. The present invention also relates to a rod and cup assembly. The assembly is particularly suitable as a disposable article.

Background There are several techniques with which viscoelastic properties can be measured.

Many of these techniques will encompass at least two surfaces, which move relative to each other. The type of relative motion may vary, but typically it can be described as unidirectional rotations or oscillations, the latter of which can be either rotational or lateral. A rheometer typically consists of a cup or container with holds the sample, and a rod, bob or plate that is inserted into the sample but without physical contact with the cup or container. In the following, the parts of the rheometer that are outside and inside the sample are referred to as cup and rod, respectively, and this regardless of their physical shape and number, unless otherwise specified. In rheometers with parts that move relative to each other, the rheological properties, also called viscoelastic properties, of the sample are deduced from the forces that are displayed when the sample is strained, i. e. forces that are displayed when parts of the sample move or have been moved relative to each other. Movement between cup and rod is one way of inducing strain in the sample. In some rheometers forces are registered by either the cup or the rod, and the strain induced by the other. In other rheometers both strain induction and registration are restricted to one of the two, the second being passive, i. e. neither inducing strain nor registering forces.

The present invention pertains to rheometers with passive rods. In the following, more detailed information on one type of free oscillation rheometer (FOR) will be given and used to describe the invention. This, however, does not limit the scope of the invention as the invention is applicable to any rheometer, which has a passive rod. Depending on the physical shape of the cup and the rod and on their relative movements, such other rheometers with a passive rod are characterized by concepts like plate-cone, Couette, parallel plate, lateral movement, parallel movement, rotation, pumping, forced oscillation and forced resonance oscillation.

Free oscillation rheometry (FOR) may be selected in advance of other rheometric techniques because it requires small sample volumes, allows low-cost disposables, determines viscosity of the magnitude displayed by water and can deliver correct viscoelastic information for biological gels, such as jams, creams, cheeses and coagulated blood and plasma. In FOR the

sample (in practice the cup with sample inside) is set into free oscillation and the damping and frequency of the oscillation are measured. In its advanced form, which includes precise determinations of viscoelastic properties, the method was invented by Leif Bohlin (Bohlin, L.

Method for measuring rheological properties and rheometer for carrying out the method. WO 94/08222.1994 14.04.) A convenient way to practice the method according to Bohlin is a torsion pendulum where the sample is set into oscillation around its axis. The frequency and damping of the oscillation are influenced by the rheological properties of the sample. By repeated initiations of the oscillation, rheological and rapid calculations rheological changes in the sample, the sample can be studied and displayed in real-time on a computer screen.

A torsion pendulum FOR can encompass a passive rod, which, if cylindrical in shape and placed in the center of the sample, will create a concentric tube of sample, the thickness of which is referred to as a gap. At some conditions, and if the level of liquid is adjusted to be unchanged, this passive rod has no influence on the determination. At these conditions, oscillations in liquid, initiated by oscillations of the cup, will only penetrate some distance into the sample, which is small in comparison to the gap. Such conditions are referred to as surface loading. At other conditions, the presence of a passive rod will influence the determination. At such conditions the oscillations in the sample penetrate the gap and are referred to as gap loading. At gap loading conditions the passive rod will impose a node in the oscillation of the sample at the surface of the rod. An almost infinitive thin film of sample in contact with the passive rod will remain stationary. Viscoelastic properties of samples with low viscosity and low elasticity tend to give surface loading conditions whereas samples with high viscosity and/or high elasticity tend to give gap loading.

FOR has been shown to perform well for the monitoring of blood plasma coagulation (Ranby, M., Gustafsson, K. M. and Lindahl, T. L., 1999. Laboratory diagnosis of thrombophilia by endothelial cell modulated coagulation. Blood Coagul Fibrinolysis 10,173- 179.) and whole blood coagulation (Ramstrom, S., Ranby, M. and Lindahl, T., 1999. Iso- citrate is a more gentle anticoagulant than citrate. Thromb Haemost 82 suppl., 292-293.). Both of these studies employed a ReoRox FOR from Global Hemostasis Institute MGR AB, Linkoping, Sweden, with an oscillation frequency of about 10 Hz and a cylindrical plastic sample cup with an inner diameter of 12 mm.

Until now, when performing a rheological analysis with an instrument with a passive rod, the sample has been supplied into the cup before bringing the rod in position.

Alternatively, the sample has been supplied into the gap between the cup and the rod.

However, neither procedure is convenient and requires manipulative precision as to avoid

damage to the instrument by physical force or by spilled sample. Furthermore, as can be needed for other analysis, removal of some portion of the sample is inconvenient. And, as may be necessary in some analysis, addition of reagent to the sample and mixing is inconvenient as well. The inconveniences are sometimes so large that the required manipulations are deemed impossible. In addition, it can be required that the surface level of sample present in the cup is well defined and that the sample shall be continuously added to and removed from the cup. Also, if sample (s) and/or reagent (s) are toxic, there is a need to minimize the exposure of these to laboratory staff.

In all, there is a need for equipment that allows better and safer supply, removal and mixing of sample and reagent (s) when performing viscoelastic analysis with rheometers encompassing a passive rod.

Moreover, there is a desire of disposal equipment to further simplify the handling and to reduce health hazards of the staff. Disposal equipment is also suitable if the analysis irreversibly alters the surfaces of, or in other ways destroys, the rod and/or the cup.

Description of the drawings Figure 1 shows a cross-sectional view of a first embodiment of a rod according to the invention in a cup.

Figure 2 shows a cross-sectional view of a second embodiment of a rod according to the invention in a cup.

Figure 3 shows a cross-sectional view of a rod and cup assembly according to the invention..

Figure 4 shows a cross-sectional view of a third embodiment of a rod according to the invention in a cup.

Figure 5 shows a cross-sectional view of a fourth embodiment of a rod according to the invention.

Description of the invention The present invention provides an improved rod for use in an apparatus for viscoelastic measurements. The rod is provided with one ore more channels for supplying or removing liquid samples or reagents to the measuring cup of the apparatus.

More precisely, one aspect of the invention relates to a rod for use in an apparatus for measuring viscoelastic properties of fluid samples, which apparatus comprises a movable cup (1) and a stationary rod (2), having a first end (3) and a second end (4), the second end being intended for insertion into the cup (1), wherein the rod is provided with at least one channel (5) for supplying or removing fluid sample (s) or reagent (s) into or out of the cup.

The term"rod"is used to cover any suitable device that is used for immersion into a fluid sample placed in a cup in an apparatus for elastic measurements, and the rod is e. g. in. the form of a stick or a bob on a bob-shaft.

The term"cup"is used to cover any suitable vessel that is used for a fluid sample in an apparatus for viscoelastic measurements.

The second end (4) of the rod (2) will be inserted into the cup (1) prior to supplying samples and/or reagents. The samples and/or reagents are thereafter supplied through one or more channels (5) of the rod into the cup. Channels in the rod (2) can also be used for removal of sample from the cup (1), before, during or after the measuring operation. The supply and/or removal of samples and/or reagents to or from the cup through a channel in the rod essentially simplifies the handling, since the supply/removal does not require such a great precision. It further reduces the drawback of the staff being exposed to hazardous samples and/or reagents, since the staff need not come into direct contact with the sample and/or reagent.

To render the passage through the channel possible, the sample or reagent must be fluid, i. e. liquid, gas, powder, emulsion or suspension. One or more samples and/or reagents might be supplied or removed through the rod channel (s).

In one embodiment at least one channel (5) extends from an inlet/outlet (7) on the rod that is positioned at a distance from the second end (4) of the rod, through the rod and to an outlet/inlet (11) at the second end (4) of the rod. The distance between the openings of the channel is preferably exceeding the depth of the cup.

In a further embodiment at least one channel extends to the bottom (6) of said second end (4) of the rod. This end of the channel will be inserted into the cup before supplying samples and/or reagents.

In another embodiment the inletloutlet of at least one channel is situated at said first end (3) of the rod, i. e. at or near the top of the rod when it is an upright position.

In yet another embodiment at least one channel has an extension parallel to the longitudinal axis of the rod. In a specific example one channel has an extension, which coincides with the longitudinal axis of the rod.

In a presently most preferred embodiment at least one channel (5) is adapted to embrace a syringe (51) with which fluid sample (s) or reagent (s) can be supplied to or removed from the cup. More specifically a section (8) of at least one channel (5) facing the first end (3) of the rod (2) has dimensions adapted to embrace the barrel (52) of the syringe, whereas a section (9) of said channel facing the second end (4) is tapered to fit the narrow end (53) of the syringe. This implies that the cross-section of the channel is about the same as the

cross-section of the syringe, so that the barrel of the syringe can be fully inserted into the channel of the rod, thus leading to a very easy and safe supply of the sample and/or reagent. to the cup. Since the syringe exactly fits into the channel, unintentional use of a larger syringe is avoided thus giving no risk for supplying too much sample to the cup. This is a great advantage since overflow of sample would flow out into the interior of the apparatus and in the worst case damage the apparatus. In addition, insertion of the syringe into the bob can facilitate temperature equilibration the content of the syringe since it is submerged into the bob which in turn can be temperature controlled The syringe should preferably be of a standard type, such as those normally used in medical applications.

In another embodiment the rod is provided with at least two channels (5,10) wherein a first channel (5) extends to a point (11) at the second end (4) of the rod, which point is intended to be situated below the desired surface level (12) of the fluid sample (13) in the cup (1) during measuring, and wherein a second channel (10) extends to a point (14) at the second end (4) of the rod that equals the desired surface level (12) of fluid sample in the cup. Thus, by supplying samples and/or reagents through the first channel (5) and removing them through the second channel (10), precise adjustment of the surface level (12) of the sample can be achieved or as another advantage, continuous measuring of samples can be performed.

It is within the scope of the invention that one or more of the inlets/outlets can be provided with membranes of elastic material so that the supplying and/or removal of sample and/or reagent is accomplished with a hypodermic needle pierced through the membrane.

In a further embodiment at least one channel consists of a main channel with an outlet/inlet at the second end (4) of the rod and at least two inletsloutlets (22,23; 42,43) at the first end (3) of the rod. This means that two or more samples and/or reagents can be supplied simultaneously. As another possibility samples and/or reagents can be supplied to the cup through the main channel via an inlet, and be removed from the cup through an outlet via the same main channel.

In a preferred embodiment the rod consists of a shaft (31) and a bob (32). Preferably the bob is detachable. The bob is thus exchangeable, indicating that different types of bobs can be used together with the same shaft or that disposable bobs can be used, while the shaft is recycled. Another advantage with a detachable bob appears if a surface modification is required for the surfaces, which are to be in contact with the fluid sample, for example a bob coated with noble metal. When a rod with a detachable bob is used, there is an opportunity to perform a surface modification on only the bob, in a surface modifying chamber or vessel,

without having to treat the shaft. The surface modified bob can then be attached to the shaft, to form a rod according to the invention, and be used in performing the viscoelastic analysis.

Another aspect of the invention relates to a rod and cup assembly comprising a rod according to the invention. In a preferred embodiment the rod and/or the cup is provided with means for attaching a cup to the second end of the rod. This leads to the opportunity of inserting the rod and cup as one assembly into the measuring apparatus, which simplifies the handling of the equipment. It might also be especially advantageous in cases where extraordinary high level of cleanliness is required to avoid contamination of the sample.

Providing the rod and cup as an engaged assembly also decreases the contact between sample and operator, which is important when handling infectious samples. A disposable rod-cup assembly may, after the analysis, be removed from the instrument and disposed with a minimum of risk. It is emphasized that there has been practically no possibility to use an engaged rod-cup assembly, according to prior art, since no convenient means of supplying the sample to the cup has been available.

The attaching means specifically involves protruding edges (33,34) extending from the cup and/or the rod. This indicates that a cup can be attached, loosely hanging, to the rod.

When such an assembly is inserted into a measuring apparatus, the cup will be lifted off the protruding edges and will thus be free to move in relation to the rod. Such rod and cup assemblies can be delivered as disposal articles, which simplifies the handling and is especially advantageous when performing measurements on hazardous samples. Moreover, disposal equipment is advantageous when performing measurements on samples, which destroy the cup and/or the rod.

The described rod and cup assembly is particularly suitable for measuring changes of the viscoelastic properties of a sample during a reaction, e. g. polymerization or curing of polymers, curing of two-component adhesives or coagulation of blood. For reactions requiring two or more reactants a rod provided with two or more channels is especially suitable.

The rod can be made of any suitable material, such as thermoplastic material, thermosetting plastics, rubber or metal. It can be formed by molding or turning or any other suitable forming method. As an example, injection molding of thermoplastic material would be appropriate for the manufacture of rods. The rod might also be provided with a surface coating if desired.