Chemistry: analytical and immunological testing – Rate of reaction determination
Patent
1983-06-28
1987-02-03
Turk, Arnold
Chemistry: analytical and immunological testing
Rate of reaction determination
422 72, 422 73, 436 45, 436 69, G01N 2182, G01N 3386
Patent
active
046408967
DESCRIPTION:
BRIEF SUMMARY
CROSS-REFERENCE TO RELATED APPLICATIONS
This United States application stems from PCT International Application No. PCT/AU82/00180 filed Nov. 4, 1982.
The present invention relates to a whole blood clotting timer.
Clinically blood clotting timers are used to (a) investigate and diagnose disorders of the blood clotting system which concerns bleeding disorders such as failure to clot, or thrombosis, that is, excessive or uncontrolled clotting, or (b) monitor the efficacy of anticoagulation therapy either in treatment of potential thrombosis or in extracorporeal blood circulation such as takes place during haemodialysis or open heart surgery.
Blood clotting time estimations are conventionally carried out manually although attempts have been made to automate them. Attempts at automation have either involved mechanical or optical methods for the detection of the formation of a gel-like clot. Optical sensing must, however, be performed on blood plasma rather than whole blood. Plasma is obtained by removing red cells by mechanical means such as a filter or a centrifuge. This has required the blood sample to be treated to inhibit the clotting mechanism, to have the red blood cells removed and to then have the clotting mechanism reactivated. The clotting times of such reactivated samples differ systematically and greatly from those of whole blood mixed with activators, and the result is only available after an inconvenient delay.
The present invention relates to a device which combines the centrifugation and the optical sensing of clot formation into a single operation. This obviates the necessity to inhibit the clotting sequence thereby quickly giving activated clotting times on a par with those obtained mechanically from whole blood.
The present invention consists in a whole blood clotting timer comprising centrifuge means, means for mounting a whole blood sample within the centrifuge means, means to measure the optical density of the sample as the sample is being centrifuged, means to cause mixing of the whole blood sample with a blood clotting activator and means to measure the time between mixing of the blood with the clotting activator, or some other event which bears a reproducible time relationship with that event, and the time at which the centrifuged sample reaches a predetermined optical density or time rate of change of optical density or other optically pre-determined end-point corresponding to the time of clotting.
The present invention further consists in a method for determining the clotting time for a whole blood sample comprising mixing the blood with a blood clotting activator, centrifuging the mixture, measuring the optical density of a part of the mixture freed from blood cells as the mixture is centrifuged and measuring the time between the formation of the mixture, or some other event which bears a reproducible time relationship with that event, and the time at which optical density or time rate of change of optical density or other optical density criterion of the mixture reaches a predetermined level.
Centrifuges incorporating means for determining the optical density of a sample being centrifuged are known (see British Patent No. 1,405,694) however such centrifuges could not be used to measure the clotting time of whole blood and such centifuges do not include suitable timing means adapted to measure the time during which a predetermined change in the optical density of a sample occurs. The present invention lies in the realisation that by the incorporation of suitable timing means with a centrifuge having optical density determining means a rapid and convenient determination of blood clotting times for whole blood may be determined.
In a preferred embodiment of the present invention the blood sample is mounted within the centrifuge in a disposable cuvette. In this arrangement the cuvette preferably is so arranged that mixing of the blood sample and of an activator takes place by centrifugal action at a constant, and preferably very short time after the centrifuge is turned on. This arran
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Tiffany et al., Analytical Chemistry, vol. 45, No. 9, Aug. 1973, pp. 1716-1723.
Bertram Christopher D.
Farrell Peter C.
Milthorpe Bruce K.
Turk Arnold
Unisearch Limited
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