The present invention is concerned with an analytical method and apparatus, useful, inter alia, for inducing and monitoring coagulation and other reactions.

The apparatus according to the present invention is particularly applicable for studying the coagulation of human blood (although it can be used for any other reaction involving viscosity change or where thorough circulation and mixing is required in an open- topped receptacle) . It is often necessary to detect the precise time at which coagulation occurs following the addition of certain substances to blood. The analysis generally comprises agitation of the sample whilst simultaneously monitoring its viscosity. It is known to shake reaction vessels (such as microplates) during an analytical procedure and subsequently monitor the extent of the reaction. However, with such apparatus it is difficult, or impossible, to carry out reproducible sample agitation.

There is now provided by the present invention an analytical method and apparatus capable of simultaneously agitating and monitoring one or more samples, such that the agitation is carried out in a controlled and reproducible manner. According to the present invention, therefore, there is provided analytical apparatus comprising: a) a reagent package comprising at least one open-topped receptacle arranged for the reaction therein of a sample and a reagent; b) support means for said package comprising a platform having, around a peripheral region thereof, a plurality of magnetisable elements;

c) a plurality of electromagnets, each being spaced from and adjacent to a corresponding magnetisable element, and being arranged to produce controlled oscillatory movement of said support means and thereby inducing circulation in a liquid present in the or each said receptacle about a respective vertical axis in the or each said receptacle; and d) means for monitoring the extent of reaction between said sample and said reagent during induction of said circulation.

It is preferred that the magnetisable elements are located at substantially equi-distant positions around the peripheral regio of the platform. Typically the magnetisable elements are of mil steel or other ferromagnetic material.

In use of apparatus according to the invention each electromagne is preferably switched sequentially (using known stepper motor technology) so as to cause attraction between a respective electromagnet and its corresponding adjacent magnetisable element. The frequency, amplitude and direction of this sequential "attraction process" can be varied and thus a vortex can be induced in the liquid in each receptacle, rotating around a vertical axis.

Typically, the monitoring means can be arranged to follow separately the reaction within a single receptacle or simultaneously the reactions within a plurality of receptacles.

SUBSTITUTESHEET

A floating object is often included in each receptacle and the monitoring means follows the movement characteristics of this object. This gives a measure of the sample viscosity and hence an indication of the extent of the reaction. Suitable monitori means include any one of the following:- a) a video camera arranged to view a plurality of receptacles simultaneous1y; b) an optical device such as a photodiode arranged to view ea receptacle individually; c) a scanning device arranged to view receptacles in turn (e. using optical fibres or a beam splitter); or d) electromagnetic means to detect a change in flux linkage with said object.

There is further provided a method comprising:- a) locating within at least one open topped receptacle, disposed on a platform; a reaction mixture comprising a sample and reagent capable of undergoing a coagulation reaction with said sample; b) electromagnetically inducing circulation of said reaction mixture in the or each said receptacle about a respective vertical axis by controlled oscillatory movement of said platform; and c) monitoring the extent of reaction between said sample and said reagent during induction of said circulation.

The invention will now be further illustrated, by way of exampl only, with reference to the accompanying drawings wherein:-

SUBSTITUTE SHEET

Figure 1 is a plan view of apparatus according to the invention; Figure 2 is a vertical section along plane A-A of Figure 1; and Figure 3 is an enlarged plan view of a single receptacle used in the apparatus of Figure 1.

Referring to Figures 1 and 2 there is shown apparatus generally designated 1 comprising a base portion 2, a movable support 3 an an uppermost platform 4. Central axis 5 attaches the upper face of base portion 2 to support 3, whereas support legs 6 attach th upper face of support 3 to the lower face of platform 4. Fixed to platform 4, at substantially equi-distant positions, are four magnetisable elements 7. In the illustrated embodiment, these extend outwards beyond the outer circumference of support 3. Support legs 6 and magnetisable elements 7 occupy alternating positions around the periphery of support 3. Remote from suppor 3 and adjacent to each element 7 are separate electromagnets 8. Each electromagnet 8 sequentially attracts the corresponding adjacent magnetisable element 7 to produce oscillatory vibrational movement of platform 4. Microplate 9 lies on the surface of platform 4 and comprises an array (such as an 8 x 12 array) of open-topped microwells 10.

Referring to Figure 3 there is shown the circulation of the reagents within each microwell 10 as a result of the oscillatory movement of platform 4; this is anticlockwise in the illustrated embodiment, but it is of course possible to arrange for the circulation to be clockwise.