KR20000048669A - Apparatus for and method of chemical analysis - Google Patents

Abstract

PURPOSE: An apparatus for chemical analysis is provided to establish the state of the serum after introducing a blood sample into the apparatus and centrifuging so as to separate blood cells from serum. CONSTITUTION: An apparatus and method for chemical analysis comprises a disc shaped member (1) which has a chamber (8), pathways (10a and b), reservoir (12) and analysis cells (16) formed integrally there within. A blood sample is introduced into the apparatus and is centrifuged so as to separate blood cells from serum. Serum is then subjected to a number of processes and/or tests, for example, in order to establish the state of the serum. The apparatus for chemical analysis is able to repeat certain processes, for example cyclical tests or reactions, by causing or permitting a sample to flow into a region or volume then allowing it to flow out, then allowing it to flow into the region or volume again. Thus washing or rinsing is possible. Optionally sealed pistons (32) which are housed in the disc (1) contain liquid reagents or solvents or water. A matrix of beads (26) whose surface has been coated with a reagent may be disposed in a reaction chamber.

Description

Chemical Analysis Apparatus and Methods {APPARATUS FOR AND METHOD OF CHEMICAL ANALYSIS}

In current chemical analysis, the development of assay methods and assay means intended for "one-shot" use is increasing. In such a device, the assay means are discarded with the biological sample itself after the analysis is performed. This is convenient for the operator in that there is no equipment to manage and measure and is particularly important for hygiene. Another advantage is the elimination of cross-contamination between a series of samples, an important issue in DNA testing.

A common feature of wet chemical analysis systems is that the analytes, together with one or more reagents, are provided in turn through a series of procedures, such as mixing, filtration, decantation, instrumentation, and partitioning. More advanced assay methods, such as polymerase chain reaction (PCR) amplification of DAN, require the sample to be thermally cycled many times, usually using optical means to detect the final product of the reaction or assay.

In summary, any form of fluid handling means is a common and important characteristic of most assay systems, although the assay system itself may differ from each other in use and purpose.

US Patent No. 5,160,702 to Molecular Devices Corp describes an analyzer in which analytical samples are introduced into a small cell in a synthetic plastic disc. The sample then travels through a series of adjacent cells by varying the capillary action and the centrifugal force generated by spinning the disk about the center point. Adjacent cells are configured to perform various functions such as separating solids and separating materials from analytical solutions by density differences.

However, there are some disadvantages when using capillaries formed in virtually shaped plastic devices. Some of these are:

1. Capillaries are difficult to form accurately in synthetic plastics.

2. Narrow channels are very easy to block.

3. The wettability (and thus the capillary properties) of the synthetic plastic surface may vary.

4. A very large pressure gradient is required to change the capillary flow.

5. Multi-head capillary cell assemblies are difficult to join together without side leakage by capillary action in the path.

6. Because the disk is spinning, visual observation of the reaction process is difficult.

7. There is a limit to the storage and introduction of reagent fluids because the use of centrifugal force to release the fluid is not optional. For example, two or more rupturable seals (sealing the volume of reagent) may be operated under a certain gravity deployed, after which all the seals will burst at the same time. This is because there can be virtually no arrangement of seals that are triggered under different gravity.

In addition, the use of centrifugal force to provide variable gravity has drawbacks in that it is difficult to control the electric force on the motor, which is expensive and requires a relatively large capacity electric motor.

U.S. Patent No. 5,162,237 to Miles Inc describes a rectangular cassette into which a blood sample is introduced and mixed with one or more reagents. Visual mixing or optical measurements are made after mixing. The cassette is associated with the effective mixing of the various fluids by vibrating back and forth the assembly containing the fluid interferences, whereby the fluids are mixed together.

However, it is not possible to perform multiple individual process steps in a controlled order using conventional systems.

The present invention relates to a chemical analysis device and method, and more particularly, but not limited to biochemical analysis.

1 is a plan view of a rotatable disc member.

Figure 2 shows in detail the compressible member for receiving a fluid while showing the principle of operation.

3 and 4 show, in different aspects, a method of operating a device using the embodiment shown in FIG. 1.

Fig. 5 is a cross-sectional exploded view showing the rotor installation of the disc member, the cap member and the centrifuge.

Referring to the drawings, FIG. 1 shows an apparatus in the form of a disc member 1. The disc member 1 comprises an inlet 2 which is connected to a centrifuge chamber 4 which is coupled to the reaction chamber 8 by a fluid path 6. The reaction chamber 8 is coupled to different reservoirs, including waste storage chambers 12, arrays of assay cells 16, and first and second liquid injection chambers 18, 20 by various fluid paths 10. Breathing tube 22 is also provided. The index mark 24 is a starting position by the fact that the rotation of the disc 1 is defined at various angular positions. This intention will be explained below.

Each assay cell 16 (fixed volumetric cell) contains a specific enzyme that reacts with the antigen present in the test sample, causing color change of the solution supporting the sample or suppressing fluorescence induced in the solution. Several colorimetric analysis methods are known for visual observation and automated detection and measurement. The path 10b to the analysis cell 16 is a large hole, while the outlet 25 to the waste reservoir 14 is a narrow hole. This reason will be explained below.

The disc 1 is subjected to an introduced sample (analyte) with one or more wet chemical treatment steps comprising a wetting agent, a desiccant or both so that the sample is treated using similar methods and materials as are present in a conventional laboratory. do. This is achieved completely in the device. Thus, the device provides several key advantages including flexibility of work, hygienic work, elimination of cross contamination between samples and long life.

In general, the device may be in the form of a disk 5 mm thick and 70 mm in diameter, but at the same time other shapes (such as square or hexagon). The fluid paths 10a, 10b are, for example, 0.2 mm in diameter, generally 0.5 mm, larger than the capillary size, allowing the fluid to flow relatively freely under natural gravity. The injection chamber for storing and dispensing liquids (described in more detail with reference to FIG. 2 below) is 3 mm in diameter and 10-20 mm in length. These dimensions can handle samples of size about 30-500 μl.

In use, the reaction chamber 8 comprises an aggregate of glass beads 26 having a diameter of about 0.6 mm. This diameter ensures that the beads are large enough to prevent them from exiting the remaining chamber, but small enough to provide a reasonably large surface area that is easily accessible by the diffusion process in the sample fluid. Ideally, all positions in the fluid are within 100 microns of the nearest bead surface. Bead 26 is a convenient vehicle for immobilizing chemicals because it can be poured at a particular location and mechanically countable. Very practical beads have a diameter of 0.1 mm to 3.0 mm. Preferably the diameter of the beads is from 0.5 to 1.5 mm.

The injection chambers 18 and 20 each contain a cylindrical reservoir 30 which acts as an injection device. Inside each chamber there is a foam material 32 having an impermeable upper and lower surface 34. The absorbent foam plastic sponge-like material is suitable for the piston body 32. Such materials are defined as having an open pore structure. This means that the material absorbs and retains fluid. The upper and lower surfaces 34 of the piston 32 may also be formed from foam plastic. The upper and lower surfaces 34 of the piston 32 are impermeable to prevent evaporation or leakage of any absorbed fluid when the piston body is filled. Alternatively, the top and bottom surfaces may comprise a silicone rubber material, or a wax / grease impregnation material. These materials also ensure good conformal fixation to the inner surface of the device defining the cylinder (s).

This type of piston 32 is coated with a sheet of absorbent foam material having an impermeable material on its upper and lower surfaces (having the same thickness as the length of the piston required) and then rotating hollow drill type system (not shown). It is manufactured by punching a cylinder. An actuator rod 36, indicated by the dashed line, is optionally provided for compressing the piston 32. Another actuator means may be provided.

Referring to FIG. 5, FIG. 5 is a cross-sectional view of the disc 1 and the rotor installation, which can be seen that the disc 1 has a transparent plate 50 coupled to the body of the disc 1. The lower surface of the disk 1 has a central hemispherical alignment guide 52 and an alignment dog 54 arranged around it. The guide 52 and the dog 54 correspond to the disc mounting adapter plate 60 suitable for being installed on the juter member 70 of the electric motor (not shown) by the bolt 72 and the bolt hole 74. Is combined with the guides (62, 64). The adapter plate 60 has two opposite flexible members 66. In use, the member 66 may be moved outward by acupressure to allow the disk to engage the position of the adapter plate 60 and then snap the disk to hold the disk in the proper position. The rotor is installed at an angle of 45 degrees, so that the disc is also located at a similar angle.

2A-D graphically illustrate the operation of the reservoir 30 and the piston 32. The cell is shown containing a foam piston 32 as described above, and a chamber “A” into which reagent is injected at a particular time. During manufacture, the piston 32 is partially inserted into the cylinder 30, leaving a portion of the foam piston 32 body exposed. Immediately before packaging, a predetermined and metered amount of liquid reagent is added to the exposed foam piston 32 by an automated titrator (not shown). The foam absorbs the reagent, and then the piston 32 is pushed into the cylinder 30, causing the upper impermeable face 34 to flow out (or slightly down) the cell surface, as shown in FIG. 2A. In this state there is no evaporation path for the fluid remaining in the reservoir. The piston is hermetically sealed by the cylinder wall and by the impermeable face 34 on the piston 32. If the reagent is to be transferred to chamber "A", the pushrod (actuator 36) is inserted in the direction of the arrow to compress the piston as shown in Figure 2b. Since the piston 32 is hermetically sealed, as shown in FIG. 2C, the piston 32 moves downward in the cylinder until the lower impermeable surface moves below the connecting tube 33. In this step, there is a fluid path along the tube 33 for the reagent exiting the foam piston 32 into the chamber "A", so that further compression of the piston 32 injects the reagent into the chamber "A". Let's do it. The push rod enters when the piston is fully compressed and then the piston collapses or snaps, absorbing air by the breathing tube 35 and the upper region of the chamber "A". This depends on the material and the cell structure. In either case, the correct amount of reagent is injected into the required compartment at the selected time. The infusion process can be quick or slow depending on the requirements and can also be performed stepwise (four times with 25% titration).

1, 3, and 4, these figures represent a representative series of procedures for the immunoassay using the present invention, wherein the change in position of the disc 1 is the index mark 24 adjacent the centrifuge chamber 4; By observation. A series of procedures after installing the disk in the centrifuge using the adapter shown in FIG. 5 are described below.

The process includes eight steps. Many other processes should be recognized as possible:

1. Sample Acquisition. The blood sample (about 30 µl) is inserted into the centrifuge chamber 4 through the inlet port 2 by setting the disk 1 to the 180 ° position. In this position, the axis of the centrifuge chamber 4 is vertically downward, and the liquid remains in the centrifuge chamber.

2. Isolation of red blood cells. Blood samples are "spun-down" by centrifugation to precipitate erythrocytes in the sample. Thereafter, the disk 1 is returned to the position where the marker 24 is close to 180 °, that is, the position having the centrifugal chamber 4. This location is shown in Figure 3b.

3. Serum isolation and affinity trapping. The serum in the centrifuge chamber 4 is poured along the reaction chamber 8 by stepwise rotation of the disk counterclockwise with respect to the 0 ° position, so that the serum is routed to the path 6 as shown in FIG. To flow under gravity. The red blood cells are subsequently left in the centrifuge chamber 4. For a short time, the antigen in serum binds to an antibody added (bound) in a previous operation to the surface of free (or ceramic) beads 26.

4. Serum removal. Serum is discharged from chamber 8 along path 10 to reservoir 12, referred to as first waste reservoir 12. This occurs by rotating the disk to the 270 ° position, which is shown in FIG. 3d. Waste reservoir 12 contains a porous foam or filter paper material (not shown) to trap the accompanying fluid. Serum antigen antibody complexes are present in addition to the beads 26. Thereafter, the disc 1 is returned clockwise to the 180 ° position.

5. Wash. The disc is returned to the 0 ° position (as described in step 3 above with reference to FIG. 3C) and the foam piston injector 30 is compressed using an actuator rod 36. This serves to inject the rinsing solution contained in the open cell foam piston 32 into the reaction chamber 8. The washing step is shown in Figure 4a. As shown in Figure 4, the movement of the disk to the proper angle is sufficient to move the solution for mixing purposes. However, other types of agitation can be performed at this stage. If the disk 1 rotates upwards one revolution per second, i.e., fast enough so that the solution does not remain in the reaction chamber and not fast enough to generate a large gravity, the solution in the chamber around the beads is then stirred to react Helps you get up more efficiently and quickly Alternatively, a vibrating bed (not shown) can be provided to accomplish this.

6. Removal of wash solution. The rinse solution is poured along the first waste reservoir 12 by rotating the disk to the 270 ° position (shown in FIG. 4B) and returning it counterclockwise to the 0 ° position. In this step, the chemicals present in the reaction chamber 8 are washed antibody-antigen complexes.

7. Elution is performed at position 0 ° as shown in FIG. 4C. The eluent contained in the piston 32 of the chamber 20 is released to the reaction chamber 8 by compressing the piston 32 to change the pH of the solution. This disrupts antigen-antibody binding, whereby the trapped antigen is released back into solution.

8. Instrumentation and optical measurements. Finally, the contents of the reaction chamber are poured into a plurality of fixed volume assay cells 16 for optical irradiation by rotating the disk 1 to a 90 ° position. This is shown in Figure 4c. Fixed volume assay cell 16 includes a relatively large orifice inlet 10b leading to each fixed volume cell. A relatively small hole outlet pipe leads from each cell to a common waste reservoir 14. This structure has a fluid impedance that depends on the level of charge. The fluid can flow relatively easily into each cell 16 until it reaches a small hole, and at this stage the force required to continuously guide the fluid into the cell rises significantly. At this time, the fluid flowing very easily along the path of lowest resistance is effectively converted to conduits leading to adjacent cells and the like. Thus, each cell 16 is effectively charged in turn. This ensures sequential charging of the cell. Once the cells are filled, there is little additional fluid flowing into each cell, so the effective volume in the cell is properly defined. This may be important in terms of quantitative measurements.

By carefully selecting the diameter of the fluid path, the deformation of the cross-sectional area of the fluid path, and the loop or bend formed by the fluid path, the number of delays set for the fluid flow from one reservoir to another or from one reservoir to the assay cell Can be introduced. These pathways are effectively formed to define a fluid logic circuit such that, for example, the sample can be separated into two or more volumes, and one subsample can be led directly to the reaction chamber along the pathway, while another subsample is Can be transferred to different chambers via delay lines and treated with different reactions at different set time points.

The breathing tube 22 ensures that the fluid can move freely by releasing air over it. The breathing tube 22 is configured to connect the non-critical volume while ensuring that excess fluid does not interfere with chemical analysis.

Disc shaped embodiments of the present invention can be made in the form of two synthetic plastic moldings, which, for convenience, represent the upper half and lower half of the final assembly. The lower half moulding includes indentations and recesses defining the lower half of the chamber, reservoir, cell, conduit path and injection cylinder. The upper half moulding only includes an indentation defining the upper half of the injection cylinder. The additional member may be located in a suitable cavity in the lower half. The upper half of the disk is combined with the lower half. Additional members include, but are not limited to:

1. Foam piston injector (preloaded with reagent or dried for subsequent loading before dispensing).

2. Absorbents (for waste reservoirs or reservoirs such as porous paper pads).

3. Float or antibody added glass / ceramic microbeads.

4. Heparin-loaded gel or paper to prevent clotting.

5. Enzyme Loaded Paper Discs (in Detox Cells)

Bonding of the top and bottom halves can be accomplished using the porous gasket technique described in US Pat. No. 4,865,716 or variations thereof. For example, a gasket of tissue paper or polymer is impregnated with wax or low temperature heated glue and punched into a shape such that holes are created in the area without glue. The gasket is then sandwiched between the upper and lower half of the disk 1 by snapping the two halves together. The assembly is then thermally cycled at a temperature above the melting point (typically 55 ° C.) or glue (typically 110 ° C.) of the wax, thereby sealing the batch. The mechanical mating properties of the two halves of the disk assembly ensure a very accurate arrangement and "snap-fit".

Thus, it can be seen that the present invention has the following advantages in at least preferred embodiments:

Modifications of the aforementioned methods can be made to reflect embodiments.

1. All sample and reagent fluids are in a sealed environment and as a result the invention is hygienic in use.

2. The present invention can be manipulated in a wide variety of different assays and is nonspecific to a single form.

3. All the members are inexpensive, and the manufacturing and assembly is simple.

4. Automation of the system using a simple control system is practical.

5. Visual check of ongoing analysis is possible.

6. The pocketable (not machine bound) form of the present invention is possible (field work and third world use), and credit card size forms in the form of squares, pentagons or hexagons may be dependent on the edge. Manual rotation should be enabled and positioned in the appropriate period and / or in the proper order.

7. Internal fluid dispensing means is optional. Thus, several different reagents can be administered at different times, at different rates.

8. The internal fluid distribution means is correct.

9. The internal fluid distribution means is welded to provide a long life.

10. The corners of the path are rounded or curved to prevent accumulation of material at or near sharp corners. It also improves the removal of moldings from the mold during manufacture.

11. The wettability of the pathway surface can be improved by coating it with a microlayer of sugar or similar material.

The invention has been described by way of example only, and variations thereof may be made without departing from the scope of the invention. For example, the device of the present invention may be formed from a material transparent to a given radiation band. An optical reader can be positioned adjacent the assay cell 16 to monitor or detect color changes within the cell. The signal indication of the color change can be absorbed or reflected by the sample in the cell. Optical readers, such as optical fibers, are placed on the sample to detect color changes, convert them into electronic signals, and display, analyze, or transmit them to a remote laboratory for analysis. In the latter case, the transmission may for example be by telephone line link or GSM connection. The system comprising means for converting the signal obtained by the reader into the electronic signal, the reader and the disk member can be connected to a high speed electronic data link such as a modem. Thus, the configured system can be used to send signals to remote laboratories for analysis by experts. Alternatively, telemetry can be performed using a computer programmed to receive signals from the assay cell. Thus, a programmed computer can perform hundreds of analyzes or diagnostics.

It is an object of the present invention to provide a simplified apparatus and method for performing a wet chemical assay with multiple process steps that can be configured for a wide variety of assay types. In addition, the device of the present invention is inexpensive, easy to operate, and suitable for use away from the laboratory.

In accordance with the present invention, a member is positioned in a first orientation in use, including a member having at least one assay cell, at least one reservoir, and a reaction chamber in fluid communication with at least one centrifuge chamber suitable for receiving a sample via an inlet. Sample is provided from the centrifuge chamber to the reaction chamber, if the member is located at the second position, flows from the reaction chamber to the first reservoir, and if the member is located at the third position, the sample flows from the reservoir to the reaction chamber. And a chemical analysis device characterized by flow from the reaction cell to one or more assay cells when the member is positioned at the fourth position.

Preferably the first and third positions are substantially identical, thus allowing or allowing the sample to be returned to the previous chamber.

In a particularly preferred embodiment, the member can rotate inversely at an angular velocity less than the centrifugal angular velocity supporting the member. Thus, for example, washing or rinsing of a sample can be achieved by repeated cycling of the member from one location to another. Advantageously, the displacement of the member from one position to another is achieved by moving the member through a predetermined path, for example an arc.

The aforementioned devices can be used for chemical analysis and / or diagnosis of disease.

The reservoir, chamber and path may be defined as being located at different heights from the reference level of the member. The interconnecting fluid path or conduit may be inclined and may be formed by having all features at one level.

According to another aspect of the present invention, a chemical analysis including a rotary chamber in which a sample inlet connected to a centrifuge chamber is formed, a reaction chamber connected to a centrifuge chamber by a fluid path, and one or more assay cells connected to a reaction chamber by a fluid path In the apparatus, the rotating chamber is spun in use for centrifuging the sample to be analyzed in the centrifuge chamber, which is then stepped for at least partially rotation into a vertical plane through a fixed and established arc such that the sample for analysis is one or more reagents. It is possible to allow the reaction to flow into the reaction chamber under the influence of gravity, and then the product of the reaction chamber flows into one or more assay cells.

According to another aspect of the present invention, the reaction chamber is installed by a rotating member having a centrifugal chamber formed therein, the reaction chamber connected to the centrifugal chamber by a fluid path, and the fluid path installed for rotation with one or more members in a vertical plane. Providing one or more connected analysis cells,

Introducing an analytical sample into the centrifuge chamber and spinning the rotating member to centrifuge the sample,

Stopping spinning of the rotating member and rotating the rotating member through the first set arc so that the centrifugal product flows through the fluid path into the reaction chamber under the influence of gravity,

Treating the centrifugation product in the reaction chamber with one or more reagents, and

Rotating the rotating member through the set second arc to provide a chemical analysis method comprising flowing the contents of the reaction chamber to one or more analysis cells under the influence of gravity.

Preferably, the member is subjected to a number of steps and counter-rotation such that the sample in the reaction chamber is subjected to a repeated series of reactions and / or processes. An example of this may be when the sample is chemically bonded to a substrate supported on the surface of the beads, for example, such that the washing or rinsing step of the beads is repeated.

Thus, when using the present invention, the processing steps can be performed in a controlled order. The sample can be moved under the influence of gravity through the fluid path, which fluid diameter is large enough so that capillary forces do not interfere with the fluid flow. Typically the path is about 1 mm in diameter. More specifically, the path is larger than 0.5 mm in diameter.

The rotating member is preferably formed of a synthetic disk material in the form of a flat disk and having at least one surface substantially transparent to the irradiation of the visible band. The transparent surface allows visual observation and facilitates monitoring of the progress of the reaction. Very preferably, the rotating member may be discarded after one analysis to avoid contamination.

In a preferred embodiment of the invention, the reaction chamber contains a collection of small glass or ceramic beads, for example coated with a reagent such as an antibody, or onto which the reagent can be applied during operation. The use of these glass or ceramic beads (hereinafter referred to as microbeads) induces natural turbulence when fluid is supplied to the reaction chamber and permeates through the matrix defined by the beads. In addition, the beads expose a large surface area of the reagent to the sample fluid. As the beads are used, the diffusion path to the nearest bead surface at any point in the fluid becomes relatively short. In fact, the mutual bead distance is on the order of tens of microns.

According to another aspect, the present invention relates to a chemical analysis device including a rotating chamber in which a reaction chamber including a collection of beads for receiving a reagent on a surface thereof and one or more analysis cells connected to the reaction chamber by a fluid path are provided. In this case, the rotating member is fixed and is stepped for rotation through a set arc, thereby providing a device that allows the product of the reaction chamber to flow into one or more assay cells.

In a preferred embodiment, the liquid reagent is introduced into the reaction chamber by providing the rotating member with at least one compressible open cell structure such as a sponge in which the liquid reagent is stored. Pistons or other means for receiving and storing the liquid may be provided to compress the open cell member to compress the liquid (which may be a reagent or a rinse medium) into the fluid path associated with the reaction chamber. Several such pistons may be provided. In a particularly preferred embodiment, the first and second open cell members are each provided in separate cylinders containing different liquid reagents, both of which can be operated independently by the first and second pistons.

According to yet another aspect of the present invention, the present invention provides a rotary member in which a reaction chamber is formed, at least one analysis cell connected to the reaction chamber by a fluid path, and storage means for introducing at least one liquid acting on the sample into the reaction chamber. A chemical analysis apparatus comprising: a storage means comprising a compressible open cell member suitable for installation in a chamber, wherein the storage means contains liquid in use such that upon compression the liquid is discharged into a fluid flow path connected to the reaction chamber. Provide the device.

The present invention includes an adapter for connecting the member with the centrifuge and is also suitable for receiving the above-described disc member and can be controlled to be selectively operated in a high speed centrifugation mode and a relatively low stepping mode. Inclusion of a centrifugal system in which the member can be rotated in a relatively slow clockwise and slow counterclockwise direction.

Preferably the centrifugal system has a stepper motor that can be directly connected to the main centrifugal rotor or can be connected to the rotor by a gear system.

The control of the system can be manual or by computer.

Preferred embodiments of the invention will now be described by way of examples with reference to the drawings.

Claims (23)

A sample may be formed when the member is in the first orientation, in use, including a member having at least one assay cell, at least one reservoir, and a reaction chamber in fluid communication with at least one centrifuge chamber suitable for receiving the sample via an inlet. From the centrifuge chamber to the reaction chamber, if the member is located at the second position, flows from the reaction chamber to the first reservoir; if the member is located at the third position, the sample flows from the reservoir to the reaction chamber, and the member is 4 If located at a position, a chemical analysis device characterized by the flow from the reaction cell to one or more analysis cells 2. The apparatus of claim 1, wherein the first and third positions are nearly identical to convey or allow the sample to the chamber or to a reservoir already introduced. The device according to claim 1 or 2, wherein the member can rotate inversely at an angular velocity less than the centrifugal angular velocity supporting the member. In a chemical analysis device comprising a rotary chamber having a sample inlet connected to the centrifuge chamber, a reaction chamber connected to the centrifuge chamber by a fluid path, and one or more analysis cells connected to the reaction chamber by a fluid path, wherein the rotary chamber is Spinning, in use, to centrifuge the sample to be analyzed in the centrifuge chamber, the rotary chamber is then stepped for at least partially rotation into a vertical plane through a fixed and established arc so that the sample for analysis is gravity for reaction with one or more reagents. And the product of the reaction chamber flows into one or more assay cells. Apparatus according to claim 2 or 3, characterized in that the rotating member is in the form of a flat disk. 6. The device of claim 1, wherein the member comprises a synthetic plastic material having at least one surface that is substantially transparent to radiation in the visible line band. 7. The device according to claim 1, wherein a plurality of beads or particles are provided to the reaction chamber in use, the beads or particles having a reagent present on their surface. A chemical analysis device comprising a rotating chamber in which a reaction chamber including a collection of beads for receiving a reagent on a surface thereof and one or more analysis cells connected to the reaction chamber by a fluid path, wherein the rotating member is fixed and set And stepped for rotation through the arc to allow the product of the reaction chamber to flow into one or more assay cells. 9. An apparatus according to any one of the preceding claims, wherein a fluid storage means is provided such that the fluid is released into one or more chambers upon compression of the fluid storage means. A chemical analysis device comprising a rotating member in which a reaction chamber is formed, at least one analysis cell connected to the reaction chamber by a fluid path, and storage means for introducing at least one liquid acting on the sample into the reaction chamber. And a compressible open cell member suitable for installation in the chamber, wherein the storage means contains liquid in use such that upon compression the liquid is discharged into a fluid flow path connected to the reaction chamber. 10. The apparatus of claim 7 or 9, wherein the beads are spherical and have an average diameter of 0.1 mm to 3 mm. 12. The apparatus of claim 11, wherein the average diameter of the beads is between 0.5 mm and 0.7. 10. A device according to claim 9, wherein the fluid storage means is elongate and has two closed opposite ends. 2. The apparatus of claim 1, wherein the member is in the form of a polygon having an almost flat edge. The apparatus of claim 1, 4, 8 or 10 comprising a plate cap member coupled to the top surface of the member in the vicinity of the chamber and the path. 16. The device of any one of claims 1 to 15, comprising an array of assay cells having a relatively large inlet passage connected to the reaction chamber and a relatively small aperture outlet passage connected to the waste reservoir. Adapter plate for installing the device according to claim 1 in the rotor of the centrifuge. A centrifuge comprising an adapter according to claim 17 and a device according to claims 1 to 16, wherein the centrifuge can be controlled to be selectively operated in a high speed centrifugal mode and vice versa in a relatively low stepping mode, A centrifuge characterized in that the member can be rotated in a relatively slow clockwise and a slow counterclockwise direction. Provided with a rotating member having a centrifuge chamber formed therein, a reaction chamber connected to the winshim separation chamber by a fluid path, and one or more analysis cells connected to the reaction chamber by a fluid path, for rotation with one or more members in a vertical plane Steps, Introducing an analytical sample into the centrifuge chamber and spinning the rotating member to centrifuge the sample, Stopping spinning of the rotating member and rotating the rotating member through the first set arc so that the centrifugal product flows through the fluid path into the reaction chamber under the influence of gravity, Treating the centrifugation product in the reaction chamber with one or more reagents, and Rotating the rotating member through the set second arc to flow the contents of the reaction chamber into one or more analysis cells under the influence of gravity. 20. The method of claim 19 including obtaining a signal from at least one analysis cell and transmitting the signal to a remote location using a telecommunications link. A diagnostic method according to claim 19 or 20. Substantially the same as described with reference to the drawings. Substantially the same as described with reference to the drawings.