Method of measuring blood clotting time

• US 4,217,107 A
• Filed: 09/22/1978
• Issued: 08/12/1980
• Est. Priority Date: 09/30/1977
• Status: Expired due to Term

• Current Assignee: Sankyo Company Limited (Daiichi Sankyo Company Limited)
• Original Assignee: Sankyo Company Limited (Daiichi Sankyo Company Limited)
• Inventors: Takahashi, Masaaki, Saito, Yukio, Sekiya, Koichi
• Primary Examiner(s): Marcus, Michael S.
• Application Number:
  US05/944,783
• Time in Patent Office: 690 Days
• Field of Search: 23/230 B, 23/918, 23/926, 422/73, 364/414, 364/415, 364/425, 364/426, 364/733, 356/39, 250/565, 73/61.4
• US Class Current: 436/69
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/54

Abstract

A blood clotting end point detector which includes means for monitoring an electrical signal representing the value A of one or more optical properties of a blood plasma sample to which a coagulating agent has been added, means for deriving the first and the second differentials with respect to time of the value A, means for detecting the moment Ta when the second differential changes from negative to positive or becomes positive, means for detecting the moment Tb when the second differential next changes from positive to negative, means for deriving the difference (R) between the tangent to the curve A at the moment Ta and the curve A, means for determining whether the difference (R) or the integral, with respect to time from moment Ta to moment Tb, of the difference (R) exceeds a predetermined threshold value, in which case moment Tb is taken as the true clotting end point.

Claims

1. A method of detecting the blood clotting end point of a blood plasma sample to which a coagulating agent has been added, which includes:

monitoring an electrical signal representing the value A of one or more optical properties of the sample,

substantially continuously deriving the first and second differentials with respect to time of the electrical signals representing the value A,

detecting the moment Ta when the second differential changes from negative to positive or becomes positive,

detecting the moment Tb when the second differential next changes from positive to negative, and

identifying the moment Tb as the true clotting end point only if at least one of the following two conditions are satisfied;

(i) the difference (R) between the tangent to the electrical signals representing the value A at moment Ta and the value of said value A signals exceeds a first predetermined threshold value; and

(ii) the integral, with respect to time from the moment Ta to the moment Tb, of said difference (R) exceeds a second predetermined threshold value.

2. A blood clotting end point detector which includes:

means for monitoring an electrical signal A representing the values of one or more optical properties of a blood plasma sample to which a coagulating agent has been added,

means coupled to said monitoring means for substantially continuously deriving the first and the second differentials with respect to time of the electrical signal A, and for generating respective signals representing the derived first and second differentials,

means responsive to the signal representing the second differential for detecting the moment Ta when the second differential of the electrical signal A changes from negative to positive or becomes positive,

means responsive to the signal representing the second differential for detecting the moment Tb when the second differential of the electrical signal A next changes from positive to negative,

means responsive to at least one of the respective signals representing the first and second differentials for deriving the difference (R) between the tangent to the electrical signal A at the time Ta and the electrical signal A,

means for determining whether the difference (R) or the integral, with respect to time from time Ta to time Tb, of the difference (R) exceeds a predetermined threshold value, in which case time Tb is taken as the true clotting end point.

3. A detector as claimed in claim 2, which includes means for twice integrating the second differential.

4. A detector as claimed in claim 2, which includes means for detecting whether the value of the second differential at moment Tb exceeds a predetermined threshold value, the time Tb being taken as the true end point only if said value is exceeded.

5. A detector as claimed in claim 2, wherein the means for deriving the difference (R) includes means for deriving the difference between the first differential and the value of the first differential at the time Ta.

6. A detector as claimed in claim 5, which includes means for twice integrating the difference (R) with respect to time from the time Ta to the moment Tb, the time Tb being taken as the true end point provided the twice integrated value exceeds a predetermined threshold value.

7. In a device where the blood clotting time is measured, displayed and recorded which includes an electronic timer which is started at the point when a coagulating agent is added to a plasma solution in a coagulation measuring sample cell, an amplifier for amplifying the electric signals generated as the light from a light source is applied to a photo-electric transducer via said sample cell, said amplified signals being designated as measured value A signals, and means for generating clotting and point detection signals for stopping said electronic timer, said clotting end point detection signals being obtained by applying a signal corresponding to said amplified signals to a clotting end point detector,

the improvement wherein said blood clotting end point detector comprises:

a first differentiator coupled to said amplifier for substantially continuously differentiating said measured value A signals with respect to time,

a second differentiator coupled to said first differentiator for substantially continuously differentiating the differentiated signals from said first differentiator,

means coupled to said second differentiator for detecting a first point where the second differential changes from negative to positive, said first point being set as the first standard point Ta, and for detecting a second point where the second differential changes from positive to negative, said second point being set as the second standard point Tb,

means for deriving the difference (R) between the tangent of the measured value A signals with time at the said first standard point Ta and the measured value A, and

means coupled to said deriving means for detecting when the said difference (R) exceeds a predetermined threshold value, or when the integrated value of the difference (R) with respect to time from the first standard point Ta to the second standard point Tb exceeds a predetermined threshold value, in which case the second standard point Tb is taken as the true clotting end point.