BLOOD COAGULATION DETECTION METHOD AND APPARATUS

• US 3,699,437 A
• Filed: 08/21/1969
• Issued: 10/17/1972
• Est. Priority Date: 09/27/1968
• Status: Expired due to Term

• Current Assignee: Amiram Ur
• Original Assignee: Amiram Ur
• Inventors: Ur, Amiram
• Primary Examiner(s): Smith, Alfred E.
• Application Number:
  US04/863,411
• Time in Patent Office: 1,153 Days
• Field of Search: 324/65B,62,57B,30 23/230
• US Class Current: 324/722
• CPC Class Codes: G01N 27/06 of a liquid involving electrolysis G01N27/26
• CPC Class Codes: G01N 27/07 Construction of measuring vessels; Electrodes therefor
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/56

Abstract

Detecting blood clotting (coagulation) and determining clotting time by comparing the electrical resistance of two parts of a liquid blood sample, one of which is treated to delay or prevent its coagulation. Time or rate of clotting is determined by the rate of change of electrical resistance or impedance of the sample falling to a minimum or substantially zero at the commencement of coagulation whereafter the comparative impedance begins to increase with time. Coagulation is detected by the incidence of minimum comparative impedance. Apparatus includes an electrical bridge measuring circuit having a test cell containing an untreated part of the blood sample in one arm of the bridge and a similar test cell in the other arm of the bridge containing the part of the sample which is treated to delay or prevent coagulation. Electrodes in each test cell place corresponding parts of the blood sample in series circuit with their respective arms of the electrical bridge.

Claims

1. The method of detecting coagulation of a fluid sample comprising the steps of:

placing the sample in electrical circuit with a source of electrical energy;

causing said energy to pass principally through portions of said sample adjacent its periphery whereby changes in electrical impedance of said sample which are indicative of coagulation will take place over a period of time, said changes in electrical impedance being in the nature of lowering to a minimum and thereafter beginning to rise from said minimum upon coagulation of said sample;

monitoring said electrical impedance and determining from said monitoring the rate of lowering of said impedance; and

terminating said step of monitoring prior to said electrical impedance reaching said minimum whereupon the time of coagulation may be predicted from said determination of said rate of lowering of said impedance.

2. The method according to claim 1 including the step of removing said sample from said electrical circuit prior to coagulation.

3. The method of detecting coagulation of an obtained biological fluid sample comprising the steps of:

dividing said sample into two parts;

delaying coagulation of one of said parts of said sample;

placing each of said parts individually in electrical circuit with a source of electrical energy;

causing said electrical energy to pass principally through portions of said sample adjacent its periphery for a given period of time sufficient to allow for changes in electrical comparative impedance of at least one of said parts to take place, said changes in electrical comparative impedance being indicative of coagulation of said sample; and

monitoring said changes in comparative electrical impedance for detecting coagulation of said sample.

4. The method according to claim 3 wherein said changes in electrical comparative impedance will be in the nature of lowering to a minimum and thereafter beginning to rise from said minimum upon coagulation of said sample and said step of monitoring is continued at least until said electrical comparative impedance of said sample reaches said minimum whereby detection of coagulation is effected.

5. The method according to claim 3 wherein said changes in said electrical comparative impedance will be in the nature of lowering to a minimum and thereafter beginning to rise from said minimum upon coagulation of said sample, determining from said monitoring the rate of lowering of said comparative impedance and terminating said step of monitoring prior to said electrical comparative impedance reaching said minimum whereupon the time of coagulation may be predicted from said determination of said rate of lowering of said comparative impedance.

6. The method according to claim 3 including the step of removing said parts of said sample from said electrical circuit prior to said coagulation.

7. The method according to claim 3 including the additional step of timing the interval between obtaining the sample and said detection of coagulation for determining the time required for coagulation of said sample.

8. Apparatus for detecting coagulation of a fluid sample including:

a cell having a chamber for receiving said sample, said cell being formed of a number of abutted apertured blocks having apertures thereof in aligned relationship with each other to form said chamber, a second and fourth of said blocks being formed of an essentially electrically non-conductive sample coagulation retarding silicone material and the remaining blocks being formed of an essentially non-coagulation retarding electrically conductive graphite material;

a number of spaced electrodes in said cell each being in peripheral contact with said sample when said sample is in said chamber;

a source of electrical energy, said source of energy being in electrical circuit with said electrodes for passIng electrical energy principally through portions of said sample adjacent its periphery in said chamber; and

means for indicating the impedance of said sample to said passage of electrical energy therethrough for detecting said coagulation.

9. Apparatus for detecting coagulation of a fluid sample including:

a cell having a chamber for receiving said sample, said cell comprising a tube of electrical insulating material having a bore constituting said chamber;

a number of spaced electrodes in said cell each being in peripheral contact with said sample when said sample is placed in said chamber, said electrodes being in the form of spaced electrically conductive linings against the wall of said bore;

a sample coagulation retarding medium extending between at least two of said electrically conductive linings peripherally about the length of said chamber between said two linings;

a source of electrical energy, said source of energy being in electrical circuit with said electrodes for passing electrical energy principally through said portions of said sample adjacent its periphery in said chamber;

electrical leads extending laterally through said tube to said electrically conductive linings and connected in electrical circuit with said source of electrical energy; and

means for indicating the impedance of said sample to said passage of electrical energy therethrough for detecting said coagulation of said sample.

10. Apparatus for detecting differences in instantaneous electrical comparative impedances of two parts of a liquid sample medium comprising:

a pair of cells each having a liquid holding chamber and spaced electrodes within said chamber between which a part of said sample medium is positioned, one of said cells comprising three blocks of structural material, said blocks being apertured and positioned in abutting relationship with each other with respective apertures therein all aligned to form said liquid-holding chamber, the intermediate one of said blocks being formed of silicone and remaining blocks being formed of graphite;

a source of electrical energy having electrical output terminals;

a pair of electrical circuits connected in parallel to said output terminals, said circuits each including at least one electrical impedance bridge arm, with electrodes in one of said cell chambers being serially connected in circuit with one of said arms and the electrodes in the other of said cell chambers being serially connected in circuit with the other of said arms; and

means responsive to current in said pair of circuits for indicating differences in instantaneous comparative impedances of said parts of said sample medium.

11. A cell for use in determining coagulation of liquid samples comprising:

a tube of electrical insulating material;

a first block of electrically insulating sample coagulation retarding silicone material within said tube intermediately of its length;

second and third blocks of electrically conductive essentially non-coagulation-retarding graphite material one abutting each of opposite ends of said first block within said tube;

said blocks each having a centrally disposed bore therein, said bores being in coaxial communication with one another; and

electrical conductors extending through said tube one into electrically connected relationship with each of said second and third blocks.

12. Apparatus for monitoring one or more selected activities of a chemical, bio-chemical or biological process in a medium, characterized by receptacles (2, 3) for one or more test samples and one or more control samples of the medium, means to inhibit or activate the selected activity or activities in the one or more test samples, but not the one or more control samples, or vice versa, and means (1) to monitor changes in a relationship between the electrical impedance(s) of the test sample(s) on the one hand and the electrical impedance(s) of the control sample(s) on the other hand over a period of time to provide an indication of progress of the one or more selected activities.

13. Apparatus for monitoring at least one selected activity of a process, in the class of chemical, bio-chemical and biological processes in a medium, characterized by receptacles for at least one test sample and at least one control sample of the medium, means for at least permitting occurrence of the selected activity in the at least one test sample, means for at least inhibiting occurrence of the selected activity in the at least one control sample, and means to monitor changes in a relationship between the electrical impedances of the at least one test sample on the one hand and of the at least one control sample on the other hand over a period of time to provide an indication of progress of the selected activity.

14. The method of detecting coagulation of a fluid sample comprising the steps of:

dividing said sample into two parts;

delaying coagulation of one of said parts of said sample;

placing each of said parts individually in electrical circuit with a source of electrical energy;

causing said electrical energy to pass principally through portions of said sample adjacent its periphery for a given period of time sufficient to allow for changes in electrical comparative impedance of at least one of said parts to take place, said changes in electrical comparative impedance being indicative of coagulation of said sample; and

monitoring said changes in comparative electrical impedance for detecting coagulation of said sample.

15. Apparatus for detecting differences in instantaneous electrical comparative impedances of two parts of a liquid sample medium comprising:

a pair of cells each having a liquid holding chamber and spaced electrodes within said chamber between which first and second parts of said sample medium are respectively positioned, one of said cells having liquid sample coagulation retarding means within its liquid holding chamber intermediately of said spaced electrodes thereof and said other of said cells being essentially non-retarding to liquid sample coagulation between corresponding spaced electrodes thereof within its chamber;

a source of electrical energy having electrical output terminals;

a pair of electrical circuits connected in parallel to said output terminals, said circuits each including one electrical impedance bridge arm, the electrodes in one of said cell chambers being serially connected in circuit with one of said arms and the electrodes in the other of said cell chambers being serially connected in circuit with the other of said arms; and

means responsive to current in said pair of circuits for indicating differences in instantaneous comparative impedances of said first and second parts of said sample medium.