GB2635360A

GB2635360A - Haematology apparatus

Info

Publication number: GB2635360A
Application number: GB2317178.8A
Authority: GB
Inventors: Christopher Turpin Mark
Original assignee: Analytical Tech And Control Ltd; Analytical Technology and Control Ltd
Current assignee: Analytical Tech And Control Ltd; Analytical Technology and Control Ltd
Priority date: 2023-11-09
Filing date: 2023-11-09
Publication date: 2025-05-14
Also published as: GB202317178D0

Abstract

A blood sampling and viscosity measuring container comprises a body having a blood sample chamber 12 with an inlet, e.g., a septum 44. At least a portion of the chamber comprises a parallel walled tube which may be under vacuum. A bob 30 is located within the tube with a 0.05-1mm blood flow annular gap and has a portion e.g., shaft 32 extending outside the chamber which is sealed to a container guide end 54 prior to use by an O-ring 56 and secured by a clip 52. In use, the tube is filled with blood under vacuum to 90% via a needle, the tube is placed in a measurement unit (Fig. 10) and the clip 52 removed to release the bob which is driven to reciprocate in the chamber by magnetic engagement of the measurement unit head with a shaft ferromagnetic ball 50. Reciprocation force is measured to provide viscosity and coagulation point. Following measurement, the bob may be moved to a disposal configuration where a second O-ring 58 and the shaft end 38 seals the chamber against the guide end.

Description

Haematology Apparatus The present invention relates to a haematology apparatus for the determination of macro physical properties of blood and in particular viscosity. Sample Tube for the Measurement of Blood Viscosity and Clotting Parameters

Background

Haematology is the branch of medicine that deals with the study, diagnosis, treatment, and prevention of blood-related disorders. This includes diseases and conditions that affect the blood cells (red and white blood cells, and platelets), blood proteins, blood vessels, bone marrow, lymph nodes, and spleen. One aspect of haematology is determination of the viscosity of blood and obvious clotting characteristics.

Blood viscosity is a measurement creating much interest within the medical profession, but with little by way of practical measurement techniques suitable for a clinical environment.

Blood is a complex rheological fluid with properties that change rapidly with both time, shear rate and physiology. The rheological properties of blood have been reviewed recently by Nader et al (Nader. (2019). Blood Rheology: Key Parameters, Impact on Blood Flow, Role in Sickle Cell Disease and Effects of Exercise. Front. Physiol., 17 October 2019).

Whilst the underlying mechanisms are complex biochemical pathways the present invention is concerned with the macro physical properties. Specifically, blood is a complex fluid being a suspension of solid components in a liquid base of plasma. The solid components principally comprise red blood cells white blood cells and platelets: Plasma is the liquid component of blood that makes up about 55% of the total blood volume.

Red blood cells (RBCs): Red blood cells, also called erythrocytes, are the most abundant cells in the blood, making up about 45% of the total blood volume.

White blood cells (WBCs): White blood cells, also called leukocytes, make up less than 1% of the total Platelets: Platelets, also called thrombocytes, are small cell fragments that help to form blood clots. They make up less than 1% of the total blood volume and are essential for stopping bleeding after an injury.

As a consequence of its complex structure blood is a non-Newtonian fluid, meaning that its viscosity (resistance to flow) is not constant and varies depending on the shearing force applied to it. The viscosity of blood changes in response to shear stress, which is the force applied to the fluid as it flows through blood vessels.

At low shear rates (i.e., when blood is flowing slowly), blood behaves like a Newtonian fluid, with a relatively constant viscosity. However, at higher shear rates (i.e., when blood is flowing more quickly), the viscosity of blood decreases, allowing it to flow more easily.

This non-Newtonian behaviour is due to the presence of red blood cells, which can align and form aggregates in response to shear stress, changing the fluid's overall behaviour. Additionally, the plasma proteins and other components of blood can interact with each other in complex ways, further contributing to its non-Newtonian properties.

The non-Newtonian behaviour of blood is an important factor in understanding its flow characteristics in the body and can have implications for the diagnosis and treatment of certain blood disorders.

The determination of the viscosity of non-Newtonian fluids is complex and the geometry of the shear field and the shear rate are important factors in accurately determining viscosity.

The viscosity of blood can be measured in medicine using various techniques, including viscometry and rheometry.

Viscometry involves measuring the resistance to flow of blood under standardized conditions in one of a number of measurement systems designed so that the shear rate can be estimated and kept constant. This technique provides a measure of the resistance of the blood to flow, which is related to its viscosity.

Rheometry involves subjecting blood to controlled shear stress or strain rate using a rotating or oscillating device. By measuring the torque required to rotate the device and the resulting deformation of the blood, the viscosity and other rheological properties of the blood can be determined.

Another technique used to assess blood viscosity is haematocrit, which measures the percentage of red blood cells in the blood. Since red blood cells are the primary determinant of blood viscosity, an increase in haematocrit can lead to an increase in blood viscosity.

Blood viscosity can also be estimated indirectly through the use of surrogate markers, such as erythrocyte sedimentation rate (ESR) or plasma viscosity. These markers reflect changes in the concentration of blood cells or proteins that can affect blood viscosity.

Overall, the measurement of blood viscosity can provide valuable information about the hemodynamic properties of blood flow and can be used help to diagnose and manage various cardiovascular and haematological conditions.

For practical measurement of blood viscosity most measurements are made by either a falling body viscometer, a capillary viscometer or via a cone and plate viscometer.

In a falling body viscometer, the viscosity is evaluated in terms of the time taken for a body, typically a ball or a rod, and having a density considerably greater than the blood, to fall a fixed distance through the sample under the effect of gravity. Whilst this method is technically simple, the method has no control over shear rate and is effectively a single point measurement.

In a capillary viscometer the blood is forced under pressure through a narrow tube and the flow rate measured. The flow rate is a measure of viscosity in this situation but is again a single point measurement.

In a cone and plate viscometer a small quantity of blood is sheared between a rotating conical element and a flat plate, the torque generated is measured and is proportional to the viscosity. This instrument offers a well-defined shear rate but is difficult to apply to blood as the torque generated is very small due to the low viscosity of the blood.

Specifically, the viscosity of blood can change over time in vitro (outside the body) due to a number of factors, such as temperature, shear stress, and exposure to anticoagulants.

Further, when blood is removed from the body and placed in a test tube or other container, it begins to coagulate, or clot, due to the activation of the clotting cascade. This process can cause the viscosity of the blood to increase over time as the clotting factors interact with each other and form a fibrin network.

In addition, the temperature of the blood can affect its viscosity, as warmer temperatures can decrease the viscosity by reducing the viscosity of the plasma. Conversely, lower temperatures can increase the viscosity of blood by increasing the viscosity of the plasma.

The shear stress applied to the blood during testing can also affect its viscosity, as higher shear rates can cause the red blood cells to deform and change shape, leading to changes in the overall viscosity of the blood.

As can be seen the measurement of blood viscosity is both complex and important.

By further example treatment with anticoagulants, such as heparin or EDTA, can also affect the viscosity of blood in vitro. These agents can interfere with the clotting cascade and prevent blood from coagulating, leading to changes in the rheological properties of the blood. The ability to measure blood viscosity is therefore an important tool in evaluating treatments.

The changes between in vitro and in vivo blood viscosity mean that it is important to carefully control the testing conditions and minimize the time between blood collection and testing to obtain accurate measurements of blood viscosity in vitro.

A standard method for determining blood viscosity in vitro is the, a falling body viscometer method.

Attempts have been made to automate and increase the utility of a falling body viscometer method, such as that disclosed in European Patents EP4083600A1 whereby numerous balls can be released in a timed fashion to measure the viscosity change over a short time period.

The cone and plate method, a measurement system commonly used for the measurement of industrial products, is adapted for the measurement of blood by enclosing the cone and plate geometry in a well. Such a method is disclosed in US Patent u52003/036711A1.

Other methods that have been used for blood viscosity include capillary viscosity measurement, such as the Benson Viscometer which is largely used for plasma viscosity measurements and cannot study coagulation processed due to the capillary becoming blocked.

Current methods of determining the viscosity of blood are complex, expensive, time consuming, in some circumstances be inaccurate. There is therefore a need for an alternative or improved method of determining blood viscosity.

As mentioned, the viscosity of blood in vitro changes over time and the determination of this phenomena is also of great importance. Specifically, blood taken from the body for processing prior to return, such as in extracorporeal membrane oxygenation (ECMO) or dialysis. ECMO is a life-support technique that uses a pump to circulate blood outside the body through an oxygenator, which adds oxygen and removes carbon dioxide, before returning the blood to the body. Dialysis is a procedure used in the treatment of patients with kidney failure whereby the blood is treated to remove waste products.

During ECMO, a catheter is inserted into a large vein, such as the jugular or femoral vein, to access the patient's blood. The blood is then pumped through a circuit that includes the oxygenator and a heat exchanger to maintain the blood at a normal temperature. The oxygenator removes carbon dioxide and adds oxygen, mimicking the function of the lungs.

ECMO is used in patients with severe respiratory or cardiac failure who are not responding to conventional treatments. It can provide temporary support while the underlying condition is treated or can be used as a bridge to transplant or other therapies.

ECM() is a complex and invasive procedure that requires specialized equipment and a highly trained medical team. It is typically used in critical care settings, such as intensive care units, and is reserved for patients with life-threatening conditions.

Hence, the ability to accurately measure clotting time is very significant in the use of such equipment and a rapid and effective means for doing so is required.

In addition, the transfer of blood from a subject to a measurement apparatus can provide a significant source of error. Specifically, blood in vitro not only clots over time but also in response to shear conditions. Hence each successive operation between extracting and measuring viscosity is a source of disturbing the clotting system and this makes measurement, such as measurements suitable for a comparison between patients, specific medical environments and sampling procedures problematic. There is therefore a need to simplify and improve sampling techniques and specifically to provide apparatus to enable this to be achieved.

A significant source of error can arise from the conventional means of obtaining a blood sample.

One such method is the evacuated tube system, a representative apparatus being the Vacutainer® the system is a convenient and efficient method for collecting blood samples and is widely used in healthcare settings for diagnostic and therapeutic purposes. The Vacutainer system was developed in 1947 by Joseph Kleiner and subsequently developed and marketed by Becton, Dickinson and Company.

The evacuated tube system consists of a sterile, evacuated plastic tube that is pre-coated with an anticoagulant or clot activator, depending on the type of sample being collected. The tube also contains a coloured rubber stopper that indicates the type of additive present in the tube.

Whilst this coating provides longevity of a sample, it also greatly disturbs the clotting characteristics and the viscosity characteristics over time.

To collect a blood sample using evacuated tube system collection, a healthcare provider first selects an appropriate vein and prepares the site using an antiseptic solution. A hollow needle is then inserted into the vein, the end of the needle remote from that inserted in the vein is then connected to an evacuated tube by inserting the needle through a septum sealing the tube and blood is drawn into the evacuated container, such that the tube is automatically filled with a predetermined volume of blood, as the vacuum in the tube draws blood into the tube and is thereby dissipated. Once the tube is filled, the tube is removed from the needle and further evacuated tubes may be used to take further samples. When sampling is finished the needle is removed, and pressure is applied to the puncture site to promote clotting and reduce the risk of bleeding.

Vacuum tube collection apparatus, such as Vacutainer tubes, are available in a variety of sizes and configurations, with different additives and clot activators designed for specific types of samples. For example, a Vacutainer with a green stopper contains sodium heparin and is commonly used for collecting plasma for chemistry and immunochemistry testing. A Vacutainer with a lavender stopper contains EDTA and is used for collecting whole blood for haematology testing.

Whilst such collection is well established and well-regarded it is not entirely suitable for collecting samples for the purposes of blood viscosity and clotting measurement.

There is need for a simple, clinically acceptable, method to measure the viscosity of whole blood and to allow the monitoring of that viscosity during the coagulation process. A particular object of this invention is to allow the measurement of anti-coagulation therapies in patients with a high risk of blood clots.

The present invention provides a blood sampling container comprising a body, having chamber for holding a blood sample, an inlet to the chamber for sampling blood, at least a portion of the chamber comprising parallel walled tube, a bob located within the tube and extending outside the chamber, wherein in a first configuration the chamber is sealed and the bob is located so as to create a first chamber volume and in a second configuration the chamber is not sealed and the bob is located so as to create a second chamber volume, where in the first chamber volume is larger than the second change chamber volume, the bob being movable within the tube between the first and second configurations, the bob providing a flow path for blood between the bob and the parallel walled tube so as to, in use, blood to flow out of the first chamber past the bob and thence to the second chamber and vice versa.

In the present invention, in the first configuration the chamber may be at below atmospheric pressure. The presence of a partial vacuum in the chamber enables blood to readily enter the chamber from a needle in communication with the chamber, such as the needle in the vein of the patient. Specifically, the pressure in the chamber will be in the region of between 1 and 100 kPa pressure. More particularly the degree of vacuum, i.e., the pressure, in the chamber in the first configuration is preferably such that upon blood entering the chamber fills to between 80 and 98% by volume, i.e., leaving an ullage of between 20 and 2% by volume before residual gas pressure reaches equilibrium and further blood does not enter. This is advantageous since the bob may be advanced along the parallel walled tube without undue force as the ullage allow some degree of compression so is to break the seal between Bob and body when the chamber is no longer sealed and the bob may translate along the tube impeded primarily by the viscosity of the blood, hence the force of movement measured is dominated by the viscous resistance giving improved signal to noise.

In the present invention the inlet to the chamber is preferably a septum pierceable by a hollow needle for the admission of blood into the chamber. This provides a simple and convenient means to bring the chamber in communication with the circulatory system of the patient such as by means of a needle inserted into a vein of the patient. The septum may be held in place by means of a septum cap, such as a cylindrical tube 42 inserted over the outer wall of the chamber and having an end with a pre formed aperture accessing a cavity for guiding in a hollow needle for receiving a blood sample. The cap also secures the septum in place, such as without requiring adhesive, which may contaminate a sample.

In the present invention, in the first configuration (10A) the bob is sealed proximate to where it extends outside the chamber. This seal may be affected by means of an 0-ring seal between the bob and the body. The 0-ring seal may be located in the body for movably sealing with the bob. This has the advantage that in the third position (10C), see below, a further portion of the shaft of the bob may engage with the same 0-ring seal to again seal the chamber. The 0-ring seal may be located in an internal groove on the inside wall of the body. However, placing an 0-ring seal on an inside wall is not readily achieved in manufacture therefore it may be preferable to locate the 0-ring seal in a groove in the bob, and for a further 0-ring seal to be placed in extension of the bob suitable for a same sealing the chamber when the bob is fully advanced into the chamber In the present invention the bob preferably extends out of the body by means of an elongate shaft.

Specifically, the shaft of smaller lateral dimensions, such as a smaller radius, than that of a first end of the bob proximate to the inlet. The seal may be by means of an 0-ring seal between the shaft and the body. The 0-ring seal may be in is located in the shaft for movably sealing with the body.

In the present invention the bob may be located within the tube by means of one or more protrusions for enabling the bob to remain centrally located within the tube in moving between the first and second configurations, as the bob is of smaller diameter than the tube. This enables the bob to translate centrally along the tube so is to provide a more even flow of blood over the surface of the bob and therefore a more accurate measure of viscosity. Preferably the protrusions of the bob comprise three equidistant lugs on the circumference of the bob. This provides minimal resistance to blood flow whilst enabling the bob to be maintained centrally. However, protrusions are not essential as a symmetrical end cap such as conical, frusto conical or hemispherical self centres due to the blood flow and provides a more accurate reading thereby.

In the present invention the bob preferably has a cross-section of radial dimensions perpendicular to elongate axis of the parallel walled tube so as to provide an equidistant gap between the bob and the tube, excluding any lugs. This provides more convenient calculation of viscosity based upon blood flow through a defined gap between the bob and the tube.

In the present invention the ends of the bob may be conical or hemispherical. This provides channelling of the blood to the gap between the tube wall on the bob to provide lower turbulence and hence more accurate measurement. The preferred geometry is conical, proving more consistent.

The ends of the bob are preferably of equivalent shape, e.g., conical or hemispherical, this reduced the dissimilarity in viscosity measurement in movement in either movement direction of the bob in the tube.

In the present invention, the end of the bob remote from the inlet may be frustoconical or substantially hemispherical, the frustum being the base of the elongate shaft. But in other terms there is preferably a shoulder between the narrowing cross-section shaft than the end of the bob and that shoulder is preferably conical or hemispherical. This enables more even blood flow when the bob is withdrawn from the chamber.

In the present invention, the parallel walled tube is preferably cylindrical. This has been found to provide consistent flow and hence more reproducible measurement.

As described earlier the chamber is preferably evacuated to below atmospheric pressure such that, in use, a blood sample is drawn under vacuum into the chamber so as to provide ullage at equilibrium in the second configuration. Similarly, the ullage is preferably of sufficient volume and pressure that on moving the bob from the first configuration to an unsealed configuration the ullage is not compressed significantly above atmospheric pressure.

In the present invention the end of the bob shaft remote from the inlet preferably terminates in a ferromagnetic material. This enables a magnetic connection with a viscometer configured to advance and retract the bob in the container, so as to provide a measure of force and thereby measure viscosity. Preferably the ferromagnetic material is a ball bearing. This is advantageous in that force conveyed, protected by compression to the bob is conveyed centrally, as is retraction when the joint is mediated by magnetism. The bob, as previously mentioned preferably comprises a shaft portion and a head portion and the termination is preferably in the shaft portion with said ball bearing.

In the present invention, the container may have a third configuration (10C) wherein the bob is located so as to provide a third chamber volume larger than the second chamber volume and wherein the chamber is sealed. This enables a disposing configuration in which the device can be disposed of without the risk of liquid spillage and resultant contamination for a safer and more effective determination.

The bob may be sealed to the body, such as a described above or by means of a further 0-ring seal located on the shaft proximate to all the end of the shaft remote from the inlet. This provides an improved seal for end of use and disposal. In particular, in combination with an enlarged elongate shaft portion this provides both a scope of movement of the bob without any frictional component, for more accurate measurement, from the seal but upon withdrawal to the third position enables the seal to seal to the enlarged elongate shaft portion proximate to the head of the bob.

In the present invention the container may be made of a plastics material. This enables precision moulding to provide a disposable part. Preferably the plastics material is transparent, this enables the progress of the test and adequate filling of the container to be determined visually.

The plastics material may be selected from one or more of Polypropylene, Polystyrene, Polyethylene, PETG (glycol-modified PET) and Polycarbonate (PC). These plastics provide a combination of credulity for precision moulding and potential clarity for observation, polycarbonate is the preferred plastic giving also low friction and hence more accurate readings.

The body and bob of the present invention is preferably made from one or more of: Polypropylene (PP): This thermoplastic polymer is a popular choice for producing evacuated blood collection tubes due to its high resistance to impact, chemicals, and heat. PP is also autoclavable, which makes it easy to sterilize and reuse should this be necessary.

Polystyrene (PS): This thermoplastic polymer is another common material used for producing evacuated blood collection tubes due to its transparency, strength, and ease of moulding. PS is also lightweight and cost-effective.

Polyethylene (PE): This thermoplastic polymer is used for producing evacuated blood collection tubes that require a soft and flexible material. PE is also resistant to chemicals and can withstand low 10 temperatures.

PETG (glycol-modified PET): This thermoplastic polymer is a type of polyester that is used for producing evacuated blood collection tubes that require high clarity and low gas permeability. PETG is also strong, lightweight, and recyclable.

Polycarbonate (PC): This thermoplastic polymer is used for producing evacuated blood collection tubes that require high impact resistance and transparency. PC is also heat-resistant and can withstand sterilization.

In the present invention the container may be substantially transparent. As mentioned, this enables ready visual inspection to corroborate instrumental data.

In the present invention the body may be substantially opaque to ultraviolet radiation, such as UV A and/or UV B. Ultraviolet radiation can stimulate blood clotting and when using an otherwise optically transparent container enables visual inspection without electromagnetic radiation substantially disturbing the measurement.

In the present invention the bob may be held in place in the first configuration (WA) by a releasable fastening such as clip or moulded breakable link. This enables the bob to maintain vacuum whilst in the first position so that vacuum sampling may take place.

The present invention includes a kit of parts comprising a container of any preceding claim and a sampling needle for, at a first end piercing the vein of a patient and at a second end suitable for opening the inlet of the chamber. This this greatly improves the efficacy of use as the components are matched up together The present invention also provides a method of using measuring the viscosity of blood sampled using a container of the present invention wherein the bob is advanced from the position in the first configuration to a position in the second configuration and the force required to advance or retract the bob is measured for correlation to a blood viscosity.

Detailed description

The present invention is illustrated by the following figures. Like features are provided with like numerals, the figures which provide: figure 1 shows schematic of the device of the present invention; figure 2 shows a vertical cross-section of the device of the present invention in conjunction with a fluid to be measured, namely blood; (Note: figures 1 and 2 show a gap around the bob but other figures do not, the other figures are also schematic and for the convenience of representation any gap is not shown) figure 3 shows a vertical cross-section of a further device of the present invention with an alternate geometry in conjunction with the fluid to be measured; figure 4 shows a specific device of the present invention in side view and to a scale (on A4 paper) representative of a device of the invention; figure 5 shows a cross-section along A-A figure 4 of a specific device of the present invention; figure 6 shows a close-up of the bob and tube of the present invention including the end of the body remote from the inlet; figures 7, 8 and 9 show the cross-section of figure 5 in the first, second and third configurations respectively.

Figure 10 shows a schematic of an apparatus for use with the present invention so is to measure viscosity; figure 11 shows a close-up of the coupling between an apparatus of the present invention and the measuring apparatus; and figure 12 shows an example of raw data from two measurements using the present invention with different blood samples.

The features of the figures illustrating the present invention are now listed, like a numbered features have the same designation across all drawings: in the present invention, as illustrated by the figures the following features are present: blood sampling container 10A container in 1s configuration 10B container in the 2nd configuration 10C container in 3d configuration 12 chamber 14 chamber filled with fluid parallel walled tube 22 tube piece, being the parallel walled tube portion of 20 24 outer wall of chamber formed by parallel walled tube 26 inner wall of chamber formed by parallel walled tube 30 bob 32 elongate shaft 34 hemispherical head of bob, aka bob end conical head of bob 36 lugs for distancing Bob from the inner wall of the parallel walled tube 38 end of bob remote from inlet end closure of container 42 septum cap 44 septum 46 cavity 48 sides of septum cap ferromagnetic ball, such as ball bearing 52 release catch for retaining seal 54 guiding shaft for elongate member of bob 56 0-ring seal for sealing elongate shaft of lug with guiding shaft prior to use 58 0-ring seal for sealing elongate shaft of lug with guiding shaft after use enlarged portion of elongate shaft between main body of lug 30 and elongate shaft 32 62 Ridge for engaging sealing member for securing Bob in position when sealing member present platform mounting torsion bar torsion bar 138 elongate shaft of torsion bar ferromagnetic ball measurement apparatus 250 management process flow diagram 210 Gather force data 220 Calculate viscosity 230 Report instantaneous viscosity 240 Monitor viscosity over time 260 Report and export viscosity vs time and clotting characteristics 300 example output of measurement test 320 example trace of viscosity versus time for a blood sample from a patient treated with anticoagulant therapy 340 example trace of viscosity versus time for a normal blood sample

Detailed description

The sample system of this disclosure is shown in Figures 4 and 5 both as an assembly and in section.

The sample system comprises a parallel walled tube, i.e., a tube of uniform bore 20, such as formed by a moulding process. The tube is sealed at one end by 40, such as by a septum seal 44 retained in place by means of a cap (48). The tube is sealed at the other end by the shaft (1) by a bob 30, located within the tube, and sealed via a rubber o-ring 56. The o-ring is installed on an enlarged section of the shaft 32, such that when the bob is pushed into the tube the remaining shaft can pass freely within the opening. The bob is held in place by a clip 52, or moulded breakable joining, which engages with the shaft to prevent the bob moving into the sample tube until the test is ready to start. The tube is evacuated to a pressure of approximately 10kPa (0.1 Bar) absolute. The bob is manufactured, such that it is a precise diameter dimension relative to the tube, so that the annular gap between the bob and the tube is constant along the entire length of the tube. The annular gap is typically 0.2mm, but could be a small as 0.05mm, or as large as 1mm. The bob has an easement 30, 38 at each end to aid the flow of fluid into the annular gap.

In use, the tube is first filled with blood direct from the patient using a blood sampling needle assembly. The vacuum in the tube is such that the tube will fill to a 90% full level. The tube is placed in the measurement unit and the clip 52 removed to release the bob, where a breakable link is used the engagement of the drive system is sufficient to break the link. The measurement machine drive head engages magnetically with the steel ball (50) on the end of the shaft and drives down to push the bob into the tube such that the narrow part of the shaft is now within the neck area and the bob can move freely. The drive mechanism now drives the bob in a reciprocating up and down motion at low speed, typically 1mm/sec but this value may be as low as 0.1mm/sec or as high as 10mm/s. The speed at which the bob is driven effectively sets the shear rate in the annular gap.

Whilst the bob is being driven in this way, the force required to drive the bob or the tube pressure is monitored, to give a measure of the blood viscosity.

The magnetic coupling of the bob to the drive system via the ball linkage is important, as it allows the bob to self-centre in the measurement tube. If a fixed linkage were used it would be necessary to closely control the alignment of the tube with the drive system.

The blood viscosity begins at 3-7mPa.s but will increase over time as the blood clots. This clotting process can thereby be monitored and measured. After some time has passed the blood viscosity will increase abruptly and a clot will form. The viscosity of the clot will increase to by an order of magnitude and the test will end. The clot strength, a value of some physiological importance, can be estimated from the ultimate viscosity reached.

At the end of the test, the measurement machine drives the bob down beyond the range of reciprocation, until the enlarged area 38 at the drive end of the shaft 32 plugs the tube and seals it with the o-ring (58). The sample is now ejected from the machine, ready for the next measurement.

Method of Measurement The measurement system used is shown schematically in Figure 10. The mechanism comprises a drive system capable of driving the bob (30) in a reciprocating fashion within the tube (10) at a closely controlled velocity, preferably linear velocity between the reciprocating changes in direction. The sample under test (14) is forced, by the bob motion, to flow through the annular gap between the bob and the tube and shearing of the sample occurs. The viscosity is measured either in terms of the force applied to the bob (30), or the pressure exerted by the sample at (14) in container (10). Both pressure and force are proportional to viscosity.

Utility of the Disclosed Method Figure 3 shows a comparison of the blood viscosity of two patients. Patient 1 is in good general health and is included as a control sample. Patient 2 suffers from atrial fibrillation and is treated with a daily dose of an anti-coagulant medication.

The test was carried out with a bob speed of 1mm/s with the bob reciprocating over a distance of 10mm. The internal diameter of the measurement tube was 14mm and the outside diameter of the bob was 13.6mm to give an annular gap of 0.2mm.

It is apparent that patient 1 showed clotting after a time of 400 seconds and that the clot formed with high strength exceeding a viscosity of 1000 mPa.s. For patient 2 the clotting time is extended to 900 seconds and the clot strength is significantly lower.

It is clear that the disclosed method has utility in the study of the effects of anticoagulant medication and in the optimisation of anticoagulation.

Claims

Claims 1) A blood sampling container comprising a body having chamber for holding a blood sample, an inlet to the chamber for sampling blood, at least a portion of the chamber comprising parallel walled tube, a bob located within the tube and extending outside the chamber, wherein in a first configuration the chamber is sealed and the bob is located so as to create a first chamber volume and in a second configuration the chamber is not sealed and the bob is located so as to create a second chamber volume, were in the first chamber volume is larger than the second change chamber volume, the bob being movable within the tube between the first and second configurations, the bob providing a flow path for blood between the bob and the parallel walled tube so as to, in use, blood to flow out of the chamber past the bob.
2) The container of claim 1 wherein in the first configuration the chamber is below atmospheric pressure.
3) The container of claim 1 or claim 2 were in the inlet to the chamber is a septum pierceable by a hollow needle for the admission of blood into the chamber.
4) The container of any preceding claim wherein in the first configuration the bob is sealed proximate to where it extends outside the chamber.
5) The container of claim 4 wherein in the seal is by means of an 0-ring seal between the bob and the body.
6) The container of claim 5 wherein the 0-ring seal is located in the body for movabaly sealing with the bob.
7) The container of any preceding claim wherein the bob extends out of the body by means of an elongate shaft.
8) The container of claim 7 wherein the seal is by means of an 0-ring seal between the shaft and the body.
9) The container of claim 8 were in is seal located in the shaft for movably sealing with the body.
10) The container of any preceding claim wherein the bob is located within the tube by means of one or more protrusions for enabling the bob to remain centrally located within the tube in moving between the first and second configurations.
11) The container of claim 7 were in the protrusions of the bob comprise three equidistant lugs on the circumference of the bob.
12) The container of any preceding claim wherein the bob has a cross-section of radial dimensions perpendicular to elongate axis of the parallel walled tube so as to provide an equidistant gap between the bob and the tube, excluding any lugs.
13) The container of any preceding claim wherein the end of the bob ends are conical.
14) The container of any of claims 1 to 9 were in the end of the bob ends are hemispherical.
15) The container of any of claims 6 to 11 wherein the end of the bob remote from the inlet is frustoconical, the frustum being the base of the elongate shaft.
16) The container of any preceding claim wherein the parallel walled tube is cylindrical.
17) The container of any of claims 2 to 8 wherein the chamber is evacuated below atmospheric pressure such that, in use, a blood sample is drawn under vacuum into the chamber so as to provide ullage at equilibrium in the second configuration.
18) The container of claim 13 wherein the ullage is of sufficient pressure so start on moving the bob from the first configuration to an unsealed configuration the ullage is not compressed significantly above atmospheric pressure.
19) The container of any of any preceding claim wherein the end of the bob remote from the inlet terminates in a ferromagnetic material.
20) The container of claim 19 were in the ferromagnetic material is a ball bearing.
21) The container of claim 20 wherein the shaft of claim 7 terminates in said ball bearing.
22) The container of any preceding claim wherein the container has a third configuration wherein the bob is located so as to provide a third chamber volume larger than the second chamber volume and the chamber is sealed.
23) The container of claim 22 were in the bob is sealed to the body as defined in any of claims 4 to 6 or by means of a further 0-ring seal located on the shaft proximate to the end of the shaft remote from the inlet.
24) The container of any preceding claim wherein the container is made of a plastics material.
25) The container of claim 24 were in the plastics material is selected from one or more of Polypropylene, Polystyrene, Polyethylene, PETG (glycol-modified PET) and Polycarbonate (PC).
26) Container of any preceding claim wherein the container is substantially transparent.
27) The container of claim 26 were in the body is substantially opaque to ultraviolet radiation.
28) The container of any preceding claim wherein the wherein the bob is held in place in the first configuration by a releasable fastening such as clip or moulded breakable link.
29) The container of any preceding claim wherein the bob is held in place in the third configuration by means of a fastening, such as the or a clip or moulded breakable link.
30) A kit of parts comprising a container of any preceding claim and a sampling needle for, at a first end piercing the vein of a patient and at a second end suitable for opening the inlet of the chamber.
31) A method of using measuring the viscosity of blood sampled using a container of any of claims 1 to 28, wherein the bob is advanced from the position in the first configuration to a position in the second or third configuration and the force required to advance the bob is measured for correlation to a blood viscosity.
32) A method of using measuring the viscosity of blood sampled using a container of any of claims 1 to 28, wherein the bob reciprocated between the position in the first configuration to a position in the second configuration and the force required to advance or withdraw the bob is measured for correlation to a blood viscosity.