Technical Field of the Invention

The present invention relates to assay apparatus, for example, assay apparatus for testing low volumes of fluids of interest. Background to the Invention

Assay strips are widely used in the medical field to determine different characteristics of a sample of interest. Assay strips can be used to measure the coagulation characteristics of a sample of blood by determining, for example, the promothrombin time (PT) of blood or plasma, activated partial thromboplastin time (APPT), activated clotting time (ACT), protein C activation time (PCAT). Assays can also be used to determine non-clotting properties of a sample of interest such as the blood or plasma viscosity and blood haematocrit.

A known system for determining properties of a sample of interest such as blood is disclosed in PCT/GB2011/051292 which describes apparatus having a chamber for receiving at least one sample. The chamber is arranged to receive a quantity of the sample of interest and typically contains a reagent that is intended to react with the sample. The type of reagent used is specific to the test intended to be conducted on the sample of interest. The chamber also contains a rotor which is arranged to rotate under the influence of an external magnetic field. The rotation speed of the rotor within the chamber is measured by an external detector so that as a sample of blood within the chamber begins to clot, the reduction in speed of rotation due to friction between the sample and the rotor can be determined. By measuring the reduction in rotation speed of the rotor, the apparatus can be used to determine, for example, the PT properties of a sample of blood.

A problem with such apparatus is that it is not capable of determining the properties of a sample when the test on the sample requires the use of more than one reagent used in sequence. For example, the APTT, which measure the activity of the intrinsic and common pathways of coagulation, is determined by mixing the sample of interest with more than one reagent. Another test that involves more than one reagent involves the use of an in- vitro diagnostic device intended to be used for the quantitative measurement of direct thrombin inhibitors (DTI), such as hirudin, Argatroban ® and dabigatran in human citrate plasmas.

It is an object of the present invention to provide an improved assay apparatus that is capable of carrying out tests on a substance of interest that involves the use of more than one reagent.

Summary of the Invention According to a first aspect of the present invention, there is provided an assay apparatus for determining properties of a sample comprising first and second chambers for receiving a sample, wherein the first chamber has an inlet and an outlet and the second chamber has an inlet, and wherein the outlet of the first chamber is connected to the inlet of the second chamber by a conduit along which at least part of the sample may travel so that the sample can move downstream from the first chamber to the second chamber in series; characterised by an openable vent arranged such that opening the vent allows flow from the first chamber to the second chamber. Advantageously, apparatus according to the present invention can be used to conduct tests on samples that require the use of more than one reagent. An assay apparatus according to the present invention therefore allows immunoassay tests requiring two or more different reagents used in sequence, which would normally only be possible in laboratories where technical operator intervention is necessary, to be performed automatically in hand held instruments using small volumes of a sample.

Indeed, the apparatus may comprise a hand held instrument or may be a sample strip.

The provision of an openable vent which, when opened to the surrounding atmosphere, allows flow from the first chamber to the second chamber provides a simple means by which the sample can be kept within the first chamber (by keeping the vent closed) and then, by opening the vent, the sample can be allowed to pass from the first chamber to the second chamber, e.g. after a predetermined time has elapsed.

The openable vent may be openable and closeable, or may be initially closed and openable, but not closeable, e.g. puncturable.

The apparatus may comprise an actuator for opening the openable vent and optionally for closing the openable vent. The actuator may comprise an electromechanical solenoid.

The openable vent may be situated in, or downstream of, the second chamber. Alternatively, the openable vent may be upstream of the second chamber and an open vent may be provided in, or downstream of, the second chamber.

The apparatus may comprise a reservoir and the reservoir may have an opening therein, open to the surrounding atmosphere. Alternatively the reservoir may be closed or closable and comprise an openable vent, whereby opening the vent in the reservoir allows gas from the surrounding atmosphere to enter the reservoir whilst gas within the apparatus escapes through the open vent in, or downstream of, the second chamber.

The apparatus may comprise a reservoir having an opening therein, an open vent in or downstream of the first chamber and the openable vent in or downstream of the second chamber. In this particular embodiment, control of flow is simple - because of the opening in the reservoir and the open vent in, or downstream of, the first chamber, a sample placed in the reservoir will naturally flow from the reservoir to the first chamber, with gas from the surrounding atmosphere entering through the opening in the reservoir and gas from within the first chamber exiting through the open vent as it is replaced by the sample. With the openable vent closed, the sample will flow no further than the open vent, which is either in the first chamber or downstream of it, but upstream of the second chamber, because gas between the open vent and the openable vent cannot be displaced. Only once the openable vent is opened, will gas that is situated between the open vent and the openable vent (including gas in the second chamber) be able to exit the apparatus through the openable vent and be replaced by the sample. Thus, the openable vent can be a closed, openable vent that cannot be reclosed, since only one opening operation, e.g. puncturing, is required.

By contrast, when the openable vent is upstream of the second chamber, and an open vent is provided in, or downstream of, the second chamber, opening and closing the openable vent must be carefully controlled. This is because, since gas can constantly escape through the open vent, an air-lock must be provided, preventing air from entering the apparatus upstream of the sample, in order to prevent it from flowing downstream. Accordingly, the openable vent must first be opened, to allow flow to the first chamber, then closed to keep the sample in the first chamber for a predetermined time, then opened once again to allow it to flow to the second chamber.

The apparatus may comprise more than two chambers and each chamber may be connected in series by a corresponding conduit. The apparatus may comprise more than one openable vent.

The apparatus may further comprise a controller which opens and optionally closes the or each openable vent so that the or each openable vent can be set to either a closed or an open position. The controller may comprise a timer that determines when the controller sets the or each vent to either a closed or an open position. The apparatus may further comprise a substantially cylindrical magnet within each chamber which may be urged to rotate within the chamber by an external magnetic field. Each chamber may comprise a support to separate the corresponding chamber magnet from walls of the chamber. The support may comprise pillars upon which the chamber magnet rests. The apparatus may comprise two separate sets of chambers and conduits. Each set may comprise the same number of chambers and conduits. One set may be used for conducting a control test on a sample of interest and the other set may be used to test the sample of interest.

At least part of the vent may be sized to allow the passage of gas, but not liquid. This can prevent the sample from accidentally exiting the apparatus through the vent.

The apparatus may comprise a sample strip body and a sample strip lid wherein the body comprises shaped recesses defining the chambers and the conduit (and optionally the reservoir and any further conduits) and the openable vent is formed by a further recess in the body extending from the second chamber to an openable region of the lid, e.g. a fracturable region or holes in the lid, such that when the openable vent is opened (e.g. by puncturing the fracturable region, or removing a closure from the holes), gas within the chamber is able to escape through the vent

According to a second aspect of the invention, there is provided a method of controlling flow of a sample through an apparatus as set out above, the method comprising opening an openable vent to allow the sample to pass from the first chamber to the second chamber. The method may comprise placing a sample in a reservoir and allowing the sample to flow to the first chamber, allowing a predetermined time to elapse and then opening the openable vent to allow the sample to pass from the first chamber to the second chamber.

The method may comprise placing a sample in a reservoir, opening the openable vent to allow the sample to flow to the first chamber, closing the openable vent to keep the sample in the first chamber, allowing a predetermined time to elapse and then opening the openable vent to allow the sample to pass from the first chamber to the second chamber.

The method may comprise rotating a cylindrical magnet in the first chamber during the predetermined time that the first sample is kept in the first chamber and the method may comprise rotating a cylindrical magnet in the second chamber once the sample has passed from the first chamber to the second chamber. According to a third aspect of the invention, there is provided an assay apparatus for determining properties of a sample comprising first and second chambers for receiving a sample, wherein the first chamber has an inlet and an outlet and the second chamber has an inlet, and wherein the outlet of the first chamber is connected to the inlet of the second chamber by a conduit along which at least part of the sample may travel so that the sample can move downstream from the first chamber to the second chamber in series, wherein the conduit comprises a valve seat through which an aperture is formed to permit a sample to flow through the conduit via the valve seat from the first chamber to the second chamber, wherein the conduit further comprises a valve body which is movable between a first position and a second position, and wherein the valve body comprises a surface which is arranged to contact the valve seat in the first position to block the aperture and restrict a sample from passing through the valve seat, characterised in that the shape of the valve body surface and the shape of the valve seat are such that the valve body surface contacts the valve seat along a plane and in that the valve body surface extends away from or beyond the region of contact between the valve body surface and the valve seat.

Advantageously, as with the first aspect, apparatus according to the second aspect of the invention can be used to conduct tests on samples that require the use of more than one reagent. An assay apparatus according to the present invention therefore allows immunoassay tests requiring two or more different reagents used in sequence, which would normally only be possible in laboratories where technical operator intervention is necessary, to be performed automatically in hand held instruments using small volumes of a sample

Again, the apparatus may be a hand held instrument or a sample strip. By making the respective shapes of the valve body surface and valve seat so that the valve body surface contacts the valve seat along a single plane, and having the valve body surface extend beyond, or away from the plane of contact, rather than conforming with the surrounding area, it is possible to minimise the surface area of contact between the valve body and valve seat whilst still closing the aperture. Any defect in the valve body surface or valve seat in the contact region could compromise the valve body's ability to close the aperture, so minimising the area of the contact region between the valve body and valve seat reduces the likelihood of a defect being present in the contact region. Apparatus according to the present invention is therefore more reliable and easier to manufacture than conventional apparatus as precise shaping is only necessary in the plane of contact.

The valve body surface may be substantially continuous.

The valve seat may comprise a substantially tapered surface. The valve seat may comprise a substantially convex surface. The valve seat may comprise a substantially straight surface. At least part of the valve seat may be substantially frustoconical.

The valve body surface may be substantially curved. The valve body may comprise a substantially circular cross section. The valve body may be substantially spherical. The conduit may define a space within which the valve body is restricted to move between the first and second positions; the space may not conform to the shape of the valve body and the length of the valve body surface may be greater than the distance between the first and second positions. The valve body may be magnetised across a cross section. The apparatus may further comprise a magnetic field generator arranged in use to apply a magnetic field to the valve body to move the valve body between the first and second positions.

Detailed Description of the Invention

In order that the invention may be more clearly understood, embodiments thereof will now be described, by way of example only, with reference to the accompanying drawings, of which:

Fig. 1 shows a perspective view of a sample strip and an actuator used as part of a first embodiment of the present invention.

Fig. 2 shows a cross section through part of the sample strip and actuator shown in Fig. 1;

Fig. 3 shows apparatus according to the present invention but without the actuator;

Fig. 4 shows a cross section through part of the sample strip and actuator of a second embodiment of the present invention;

Fig. 5 shows a perspective view of an alternative sample strip used as part of a third embodiment of the present invention;

Fig. 6 shows a section view of a part of the sample strip shown in Figure. 5 when the valve is in a closed position;

Fig. 7 shows an enlarged section view of the part of the sample strip shown in

Figure 6 highlighted with a circle; Fig. 8 shows a section view of a part of the sample strip shown in Figure. 5 when the valve is in an open position;

Fig 9 shows an enlarged section view of the part of the sample strip shown in

Figure 8 highlighted with a circle; Fig. 10 shows a section view of apparatus according to the present invention comprising the sample strip shown in Figures 5 to 9;

Fig. 11 shows an alternative section view of the apparatus shown in Fig

With reference to figures 1-4, there is shown an assay strip 1 having a body 2 made from plastics material comprising a first chamber 3 having an inlet and an outlet and a second chamber 5 having an inlet. The two chambers 3, 5 are connected by a conduit or capillary 7 which runs along the strip between the outlet of the first chamber 3 and the inlet of the second chamber 5. The strip further comprises a reservoir 9 at one end which is connected to the first chamber by a further conduit 11. The reservoir 9 forms a deposition area where a sample fluid may be presented to the strip 1 so that the sample can flow along the first conduit 11 to the first chamber 3 and along the linking conduit 7 to the second chamber 5. The volume of the reservoir 9 is substantially equivalent to the combined volume of the chambers 3, 5 and conduits 7, 11 to ensure that a sufficient volume of sample is presented to the strip 1 for testing purposes. The strip 1 further comprises a lid 13 to cover the chambers 3, 5, conduits 7, 11 and reservoir 9 so that the sample is restricted to flow along those elements of the strip 1. An opening 4 is provided in the reservoir, allowing surrounding gas (e.g. air) from the atmosphere to enter the reservoir and displace the sample as it moves along the conduits 7, 11 to the chambers 3, 5. The diameter of each conduit 7, 11 is chosen so that a sample of interest such as blood will flow along the conduits 7, 11 without assistance. To encourage this capillary motion, the internal surface of each conduit 7, 11 is treated with corona discharge plasma to form a hydrophilic coating. The first chamber 3 is provided with an open vent 6, which is made up of a recessed portion in the top surface of the body 2 of the assay strip 1, extending from the top of the first chamber 3 in the form of an air-release passage, having a small diameter to allow gas, but not liquid to pass along the passage, which broadens to form a bowl. To complete the open air vent 6, directly above the bowl, the lid 13 is provided with open air holes 15, that are arranged to sit over the recessed bowl, when the lid is positioned on the strip 1 to provide an open passage through which air can escape from the first chamber and thereby encourage capillary motion of the sample along the flow path from the reservoir to the first chamber 3.

With reference to figure 2, the second chamber 5 is provided with an openable vent 8, which again comprises a recessed portion in the top surface of the body 2 of the assay strip 1, extending from the top of the second chamber 5 in the form of an air- release passage which broadens to form a shallow straight-sided flat-bottomed bowl 10. The openable air vent 8 further comprises, openable and closable air holes 17 in the lid 13, that are arranged to sit over the recessed bowl 10, when the lid is positioned on the strip 1. Above the air holes 17, an actuator 12, in the form of an electromechanical solenoid, having a valve member 14 is provided. The actuator 12 is operable to move between a closed position (shown in figure 2), in which the holes are covered by the valve member 14, such that the vent is closed and air cannot escape through the vent, and an open position, in which the valve member 14 is raised to provide an open passage through which air can escape from the second chamber 5 and thereby encourage capillary motion of the sample along the flow path from the first chamber 3 to the second chamber 5. In this first embodiment, the valve member 14 has a flat lower surface which seats on the flat upper surface of the lid 13 covering and surrounding the hole to close it.

As shown in figure 3, contained within each chamber 3, 5 is a substantially cylindrical rotor 23 made from sintered neodymium magnetic material. Optionally, the material is encased in another material such as plastic to minimise the effect of the neodymium on the blood sample. Each rotor 23 is magnetised such that its poles are on opposite sides respectively of the rotor 23 across its diameter. This is to enable rotation of the rotors 23 when subjected to an alternating magnetic field. The shape and dimensions of each rotor 23 is chosen such that it can freely rotate within its chamber 3, 5 but such that its lateral movement along the length ofthe chamber 3, 5 is limited. The shape and dimensions of each rotor are also chosen so that a space is formed between the rotor 23 and its corresponding chamber 3, 5. A quantity of dried clotting reagent which is intended to be mixed with the sample is deposited within the space formed between the rotor 23 and the chamber 3, 5. Different reagents may be deposited in each respective chamber 3, 5 depending on the type of test to be conducted on the sample. At the base of each chamber 3, 5 four small pillars may be arranged at each corner of the chamber to support the rotors 23 and separate the rotors 23 from the base wall. Separating the rotors 23 from the base wall ofthe corresponding chambers 3, 5 facilitates reagent disposition within the chambers 3, 5,

A sample strip reader 27 is also provided comprising a slot into which the sample strip 1 may be inserted for measurements to be taken. The slot is shaped and configured to receive the sample strip in a relatively tight fit. The sample strip reader 27 also comprises electrical coils (solenoids) or electromagnetic field generators 31 which are positioned such that, when the sample strip 1 is inserted into the reader 27, the chambers 3, 5 are adjacent and in close proximity to the coils 31. Each of the coils 3 is arranged in one of a pair of ring-arrays one ring around each chamber and oriented to extend substantially perpendicularly away from its corresponding chamber 3, 5 such that one end lies adjacent its chamber 3, 5. Each coil 31 of each array is paired with its diametrically opposed coil and arranged to be energised and de-energised in pairs in sequence. Thus, when a current is passed through one pair of diametrically opposed coils 31, a magnetic pole is created adjacent the chamber 3, 5, Each pair of coils 31 are powered by a small battery unit 32 contained within the reader 27 and are configured to generate a DC magnetic field between the pairs along their respective axes.

The electromechanical solenoid 12 shown in figure 2 forms part of the reader 27 and comprises a dedicated DC coil which is positioned within the reader 27 such that when the assay strip 1 is inserted into the reader 27, the coil is adjacent the hole 17. The coil is arranged to generate a static unidirectional field that is capable of repelling an arm 16 carrying the valve member 14 out from the housing to block the flow gas from within the assay strip 1 and hence block the flow of the sample between the first and the second chamber. By reversing the current through the coil, the arm 16 can be attracted back into the housing thus lifting the valve member 14 from its seat covering the hole 17, thereby opening the hole permitting the sample to flow from the first chamber 3 to the second chamber 5 and displace air within the conduit 7 and second chamber 5 out through the hole 17. Thus, the DC coil opens and closes the openable vent 8. The DC coil is controlled by an electronic control device 34 which comprises a timer to control the operation of the DC coil and thus control when the valve member 14 is moved between positions. This timing depends on the time required by the particular assay being conducted to mix the first reagent with the sample (blood, plasma or other fluids) and then mix the sample with the second reagent.

A heating element 33 is provided toward the upper surface of the reader 27 and is positioned to be substantially parallel with the upper face of the sample strip 1 and adjacent the two chambers 3, 5. The heating element 33 is also powered by the battery unit and serves to maintain the temperature of the sample at 37°C (human body temperature) so as to replicate the conditions in the body. To maintain the sample at the desired temperature, a temperature sensor is provided toward the lower portion of the reader 27 adjacent the lower section of the sample strip 1 so that the temperature of the sample in the chambers 3, 5 can be monitored and the operation of the heating element 33 adjusted accordingly. The operation of the heating element 33 and the coils 31 is also controlled by the electronic control means 34.

To determine the time at which the sample enters the chambers 3, 5, an optical detector 37 is provided which monitors the light levels within the chambers 3, 5. When the sample enters the chambers 3, 5 and fills the respective spaces between the rotors 23 and chamber walls, the light level drops to a predetermined level which signifies the starting time for the test (T zero). Measurement of the properties of the sample is facilitated by two magnetic field detectors e.g. Hall Effect sensors (not shown) which are positioned within the reader 27 such that they are substantial ly parallel with and adjacent to respective chambers 3, 5 when the sample strip 1 is inserted into the reader 27.

In use, the sample strip 1 is inserted into the reader 27 and a blood sample is deposited on the reservoir 9. When the sample strip 1 is in place, diametrically opposed pairs of coils 31 are energised and then de-energised in sequence around the array. Thus, one pair of diametrically opposed coils is energised to generate a DC field between the pair, then de-energised to turn off the DC field and the next pair of coils in the sequence is energised and de-energised and so on around each pair (e.g. four pairs) to generate a rotating magnetic field across the two rotors 23.

When the pole of a rotor 23 and the pole of an adjacent coil 31 are alike at their closest proximity, the two poles repel one another and cause the rotor 23 to rotate. As the rotor 23 rotates within its chamber 3, 5, the opposite pole of the rotor 23 moves closer to and is attracted by the opposite pole of the coil 31. At the point at which the two opposite poles are at their closest proximity, the magnetic field generated by the coil 31 is reversed and the aforementioned process repeats itself around the array to maintain the rotating action of the rotors 23.

Through capillar' action, the sample proceeds from the reservoir 9 to the first chamber 3 via the conduit 11 and gradually fills the first chamber 3. At this stage, the DC coil is set to repel the arm 16 and urge the valve member 14 into the closed position so that the sample is restricted from flowing along the linking conduit 7 into the second chamber 5 (because air between the chambers cannot be displaced through the openable vent). Rotation of the rotors 23 helps to dissolve and mix (re-suspend) the reagent in the first chamber 3 with the sample. When the reagent has mixed with the sample in the first chamber 3, the DC coil is set to attract the arm 16 and thus withdraw it into the housing, lifting the valve member, and opening a passage through the openable vent 8, from the second chamber to the surrounding so that the sample can displace gas within the linking conduit 7 and the second chamber 5 and flow into the second chamber 5. Activation of the DC coil to move the openable air vent 8 to an open position may be set to occur at a predetermined time (dependent upon the type of test being conducted) as controlled by the el ectronic control means 34. When the sample flows into the second chamber 5, it mixes with the reagent contained therein so that measurements can be taken.

The rotating magnetic field of each rotor 23 gives rise to peak outputs detected by the adjacent Hall Effect sensor. The peak output corresponds to the point at which a pole of the rotor 23 passes in closest proximity to an adjacent sensor. By measuring the time between the peak outputs of the sensor it is possible to determine the rotational velocity of the rotors 23. When the chambers 3, 5 contain a predetermined quantity of the sample, which is indicated by a specific drop in light intensity as measured by the optical detector 37, the test start time is triggered. As the blood sample within the first chamber 3 and second chamber 5 coagulates and the viscosity of the sample changes, the resistance of the sample to the rotation of the rotors 23 increases, thereby reducing the rotational velocity of the rotors 23 as detected by the respective Hall Effect sensors. When a predetermined rotational velocity is measured which corresponds to coagulation of the sample, the tinier is stopped and the property of the sample is determined. Whilst two chambers in sequence are disclosed in this embodiment, it is envisaged that further chambers could be linked in series to enable tests requiring multiple reagents. The number of chambers would correspond to the number of separate reagents required for a particular test.

With reference to Fig. 4, in a second embodiment, the actuator 12 has an arm 16 which rather than culminating in a valve member 14 has a pointed tip 18. The pointed tip of the arm of the actuator 12 is located in the same position described in relation to the first embodiment. However, in the second embodiment, the lid 13 of the assay strip J is not initially provided with a hole above the bowl 10 of the openable vent 8, Instead, a fracturable region 20 is provided in the lid 13, arranged so as to sit above the bowl 10 and beneath the pointed tip 18 of the arm 16 of the actuator 12. Accordingly, the vent is initially closed, and the DC coil is set to attract the arm such that the pointed tip is retracted away from the fracturable region 20 of the lid 13, The process of moving the sample from the reservoir 9 to the first chamber 3 proceeds as before, and because the vent 8 is closed, the sample will not flow down the conduit 7. After a predetermined time has lapsed, the DC coil is set to extend the arm, to the position shown in figure 4, whereby the pointed tip 18 fractures the fracturable region of the lid 13 and thereby opening the openable vent 8. The tip 20 is then retracted to avoid restricting the size of the hole in the fracturable region and the sample flows from the first chamber 5 to the second chamber 7

Thus it can be seen that in the second embodiment the openable air vent 8 is closed and openable, but not closable. In all other respects, the second embodiment shares the same features as the first embodiment and operates in the same way.

A reference to figures 5-9, there is shown an assay strip 101 according to a third embodiment of the invention, having a body 102 made from plastics material comprising a first chamber 103 having an inlet and an outlet and a second chamber 105 having an inlet. The two chambers 103, 105 are connected by a conduit or capillary 107 which runs along the strip between the outlet of the first chamber 103 and the inlet of the second chamber 105. The strip further comprises a reservoir 109 at one end which is connected to the first chamber by a further conduit 111. The reservoir 109 forms a deposition area where a sample fluid may be presented to the strip 101 so that the sample can flow along the first conduit 111 to the first chamber 103 and along the linking conduit 107 to the second chamber 105. The volume of the reservoir 109 is substantially equivalent to the combined volume of the chambers 103, 105 and conduits 107, 111 to ensure that a sufficient volume of sample is presented to the strip 101 for testing purposes. The strip 101 further comprises a lid 113 to cover the chambers 103, 105, conduits 107, 111 and reservoir 109 so that the sample is restricted to flow along those elements of the strip 101. An opening 104 is provided at one end of the sample strip 101 between the reservoir 109 and the lid 113, allowing surrounding gas (e.g. air) from the atmosphere to enter the reservoir 109 and displace the sample as it moves along the conduits 107, 111 to the chambers 3,

The diameter of each conduit 107, 111 is chosen so that a sample of interest such as blood will flow along the conduits 107, 111 without assistance. To encourage this capillary motion, the internal surface of each conduit 107, 111 is treated with corona discharge plasma to form a hydrophilic coating. The first and second chambers 103, 105 are each provided with an open vent 106, 108, which are made up of a recessed portion in the top surface of the body 102 of the assay strip 101, extending from the top of the first and second chambers 103, 105 respectively in the form of an air-release passage, having a small diameter to allow gas, but not liquid to pass along the passage, which broadens to form a bowl. To complete the open air vents 106, 108, directly above the bowls, the lid 113 is provided with open air holes 115, that are arranged to sit over the recessed bowls, when the lid is positioned on the strip 1 to provide an open passage through which air can escape from the first and second chambers and thereby encourage capillary motion ofthe sample along the flow path from the reservoir to the first and second chambers 103, 105. The conduit 107 between the first chamber 3 and the second chamber 105 comprises a substantially circular recess or depression which houses a valve 112. The valve 112 comprises a valve seat 114 and a valve body 116 which is housed within the depression and restricted to move within the space defined by the depression and the lid 113. The valve body comprises a spherical micro bead made from magnetic material and the valve seat 114 comprises a frustoconical structure formed along the conduit 107.

The frustoconical structure comprises a substantially circular opening into which the conduit 107 extends from the first chamber 103. The valve seat wall tapers toward a smaller opening near the base of the sample strip 101 which links to a further section of the conduit that extends along the sample strip into the second chamber 105. Thus, the frustoconical structure comprises a substantially flat, continuous lateral surface or wall extending between the two openings and serves to funnel a sample from a first upper section of the conduit 107 to a lower section of the conduit at or near the base of the strip 101. The neck of the smaller opening comprises a substantially convex portion 160 to create a larger opening and facilitate the flow of a sample through the conduit 107 and help minimise any retention of a sample within the frustoconically shaped valve seat 114.

The diameter of the micro bead 116 is chosen to be greater than that of the smaller opening of the valve seat 1 14 so that the surface of the bead 1 16 abuts the tapered sidewall of the valve seat 1 14 to close the valve 112. Since the bead's surface is curved and since the valve seat' s sidewall is substantially straight, the bead contacts the sidewall of the valve seat 114 along a plane defined by a single circular contact portion in the region where the sidewall is tangential to the bead. Thus, the contact area between the bead 116 and the valve seat 114 is minimised. By reducing the contact area between the valve body 116 and the valve seat 1 14, the likelihood of a defect in either interfacing surface affecting the seal formed between the valve body 1 16 and valve seat 114 is reduced.

The micro bead 116 can move from a closed position in which it is seated against and interfaces with the valve seat 114 along a plane, thereby closing the aperture extending through the valve seat, and an open position in which the micro bead is spaced from the valve seat 114 so that the aperture is open and a sample can flow along the conduit 107 from the first chamber 103 to the second chamber 105.

Referring to figures 10 and 11, contained within each chamber 103, 105 is a substantially cylindrical rotor 123 made from sintered neodymium magnetic material. Optionally, the material is encased in another material such as plastic to minimise the effect of the neodymium on the blood sample. Each rotor 123 is magnetised such that its poles are on opposite sides respectively of the rotor 123 across its diameter. This is to enable rotation of the rotors 123 when subjected to an alternating magnetic field.

The shape and dimensions of each rotor 123 is chosen such that it can freely rotate within its chamber 103, 105 but such that its lateral movement along the length of the chamber 103, 105 is limited. The shape and dimensions of each rotor are also chosen so that a space is formed between the rotor 123 and its corresponding chamber 103, 105. A quantity of dried clotting reagent which is intended to be mixed with the sample is deposited within the space formed between the rotor 123 and the chamber 103, 105. Different reagents may be deposited in each respective chamber 103, 105 depending on the type of test to be conducted on the sample.

A sample strip reader 127 is also provided comprising a slot into which the sample strip 101 may be inserted for measurements to be taken. The slot is shaped and configured to receive the sample strip in a relatively tight fit. The sample strip reader 127 also comprises electrical coils (solenoids) or electromagnetic field generators 13 which are positioned such that, when the sample strip 101 is inserted into the reader 27, the chambers 103, 105 are adjacent and in close proximity to the coils 131. Each of the coils 131 is arranged in one of a pair of ring-arrays, one ring around each chamber and oriented to extend substantially perpendicularly away from its corresponding chamber 103, 105 such that one end lies adjacent its chamber 103, 105. Each coil 131 of each array is paired with its diametrically opposed coil and arranged to be energised and de- energised in pairs in sequence. Thus, when a current is passed through one pair of diametrically opposed coils 131 , a magnetic pole is created adjacent the chamber 103, 105. Each pair of coils 131 are powered by a small battery unit 132 contained within the reader 127 and are configured to generate a DC magnetic field between the pairs along their respective axes. Two dedicated DC coils 140a, 140b are positioned within the reader 127 such that when the assay strip 101 is inserted into the reader 127, the coils 140a, 140b are above and below the valve 1 2. The coils 140a, 140b are arranged to generate a static unidirectional field that so that opposing magnetic poles are created above and below the micro bead 116. Thus, the coil 140a above the micro bead 116 may be arranged to attract the micro bead and the coil below the micro bead may be arranged to repel the micro bead. In this way, both coils 140a, 140b work to urge the bead 116 away from the smaller aperture of the valve seat 114 to an open position. This permits the sample to flow from the first chamber 103 to the second chamber 105 via the conduit 107. By reversing the current through the coils 140a, 140b, the bead 116 can be attracted back and urged toward the smaller aperture until it sits within the valve seat 114 and abuts its sidewali, thereby closing the valve 1 12 and hence blocking the conduit and restricting the flow of a sample along the conduit 107 from the first chamber 103 to the second chamber 105. The DC coils 140a, 140b are controlled by an electronic control device 134 which comprises a timer to control the operation of the DC coil and thus control when the bead 116 is moved between positions. This timing depends on the time required by the particular assay being conducted to mix the first reagent with the sample (blood, plasma or other fluids) and then mix the sample with the second reagent.

A heating element 133 is provided toward the upper surface of the reader 127 and is positioned to be substantially parallel with the upper face of the sample strip 101 and adjacent the two chambers 103, 105. The heating element 133 is also powered by the battery unit and serves to maintain the temperature of the sample at 37°C (human body temperature) so as to replicate the conditions in the body. To maintain the sample at the desired temperature, a temperature sensor is provided toward the lower portion of the reader 127 adjacent the lower section of the sample strip 101 so that the temperature of the sample in the chambers 103, 105 can be monitored and the operation of the heating element 133 adjusted accordingly. The operation of the heating element 133 and the coils 131 is also controlled by the electronic control means 134.

To determine the time at which the sample enters the chambers 103, 105, an optical detector 137 is provided which monitors the light levels within the chambers 3, 5. When the sample enters the chambers 103, 105 and fills the respective spaces between the rotors 123 and chamber walls, the light level drops to a predetermined level which signifies the starting time for the test (T zero). Measurement of the properties of the sample is facilitated by two magnetic field detectors e.g. Hall Effect sensors which are positioned within the reader 127 such that they are substantially parallel with and adjacent to respective chambers 103, 105 when the sample strip 101 is inserted into the reader 127.

In use, the sample strip 101 is inserted into the reader 127 and a blood sample is deposited on the reservoir 109. When the sample strip 101 is in place, diametrically opposed pairs of coils 131 are energised and then de-energised in sequence around the array. Thus, one pair of diametrically opposed coils is energised to generate a DC field between the pair, then de-energised to turn off the DC field and the next pair of coils in the sequence is energised and de-energised and so on ( e.g. 4 pairs) to generate a rotating magnetic field across the two rotors 123. When the pole of a rotor 123 and the pole of an adj acent coil 131 are alike at their closest proximity, the two poles repel one another and cause the rotor 123 to rotate. As the rotor 123 rotates within its chamber 103, 105, the opposite pole of the rotor 123 moves closer to and is attracted by the opposite pole of the coil 131. At the point at which the two opposite poles are at their closest proximity, the magnetic field generated by the coil 131 is reversed and the aforementioned process repeats itself around the array to maintain the rotating action of the rotors 123 ,

Through capillary action, the sample proceeds from the reservoir 109 to the first chamber 103 via the conduit 111 and gradually fills the first chamber 103. At this stage, the DC coils 140a, 140b are set to repel and attract the valve body respectively to urge the valve body 1 16 toward the closed position so that the sample is restricted from flowing along the linking conduit 107 into the second chamber 105, Rotation of the rotors 123 helps to dissolve and mix (re-suspend) the reagent in the first chamber 103 with the sample. When the reagent has mixed with the sample in the first chamber 103, the DC coils 140a, 140b are set to attract and repel the micro bead 116 respectively and thus urge the micro bead 1 6 away from the valve seat 1 14 so that the sample can flow into the second chamber 105. Activation of the DC coils to move the micro bead 116 to an open position may be set to occur at a predetermined time (dependent upon the type of test being conducted) as controlled by the electronic control means 134. When the sample flows into the second chamber 105, it mixes with the reagent contained therein so that measurements can be taken.

The rotating magnetic field of each rotor 123 gives rise to peak outputs detected by the adjacent Hall Effect sensor. The peak output corresponds to the point at which a pole of the rotor 123 passes in closest proximity to an adjacent sensor. By measuring the time between the peak outputs of the sensor it is possible to determine the rotational velocity of the rotors 123. When the chambers 103, 105 contain a predetermined quantity of the sample, which is indicated by a specific drop in light intensity as measured by the optical detector 137, the test start time is triggered. As the blood sample within the first chamber 103 and second chamber 105 coagulates and the viscosity of the sample changes, the resistance of the sample to the rotation of the rotors 123 increases, thereby reducing the rotational velocity of the rotors 123 as detected by the respective sensors. When a predetermined rotational velocity is measured which corresponds to coagulation of the sample, the timer is stopped and the property of the sample is determined. Whilst two chambers in sequence are disclosed in this embodiment, it is envisaged that further chambers could be linked in series to enable tests requiring multiple reagents. The number of chambers would correspond to the number of separate reagents required for a particular test. The above embodiments are described by way of example only. Many variations are possible without departing from the scope of the invention as defined in the appended claims.