METHOD AND APPARATUS FOR CHEMICAL ANALYSIS

• US 3,765,841 A
• Filed: 08/06/1971
• Issued: 10/16/1973
• Est. Priority Date: 08/06/1971
• Status: Expired due to Term

• Current Assignee: Gerald L. Paulson, Robert A. Ray
• Original Assignee: Gerald L. Paulson, Robert A. Ray
• Inventors: Paulson, Gerald L., Ray, Robert A.
• Primary Examiner(s): Reese, Robert M.
• Application Number:
  US05/169,687
• Time in Patent Office: 802 Days
• Field of Search: 23/23R,253R 195/103.5,127 324/3B,30 204/195
• US Class Current: 205/777.5
• CPC Class Codes: G01N 27/3271 Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001
• CPC Class Codes: Y10T 436/171538 Urea or blood urea nitrogen

Abstract

A method and apparatus for determining the concentration of a component in a sample, i.e. the concentration of urea in biological fluids, such as blood serum, wherein the sample, upon being introduced into solution with a reagent, reacts therewith, causing a continuing change in a characteristic of the solution, and wherein the rate of the reaction is indicative of the concentration of the component in the sample. A sensor is provided for monitoring the characteristic of the solution and for generating a first electrical output signal proportional thereto. Differentiator circuit means are provided for producing a second electrical signal proportional to the time derivative of the first signal, the time derivative signal being indicative of the concentration of the component in the sample.

Claims

2. A method according to claim 1 wherein said fixed time interval is long enough to permit thorough mixing of said sample with said reagent.

3. In a chemical analyzing system for determining the concentration of a component in a sample, wherein said sample, upon being introduced into solution with a reagent, reacts therewith, the rate of the reaction being indicative of said concentration, such system comprising sensor means for monitoring a characteristic of said solution or a component or a product of said reaction and for producing a first electrical output signal proportional thereto, and differentiator circuit means for producing a second electrical signal propOrtional to the time derivative of said first signal, said time derivative signal being indicative of said concentration of said component in said sample, the improvement comprising:

means for inhibiting operation of said differentiator circuit means for a predetermined, fixed time interval from introduction of said sample into said reagent, said time interval being sufficient to permit thorough mixing of said sample with said reagent.

4. In a chemical analyzing system for determining the concentration of a component in a sample, wherein said sample, upon being introduced into solution with a reagent, reacts therewith, the rate of the reaction being indicative of said concentration, such system comprising sensor means for monitoring a characteristic of said solution or a component or a product of said reaction and for producing a first electrical output signal proportional thereto, differentiator circuit means for producing a second electrical signal proportional to the time derivative of said first signal, said time derivative signal being indicative of said concentration of said component in said sample, and means responsive to said second signal for generating an output signal indicative of the value thereof, the improvement comprising:

means for inhibiting the generation of said output signal for a predetermined, fixed time interval initiated automatically upon introduction of said sample into said reagent, said time interval being sufficient to eliminate the effect of transients occurring upon introduction of said sample into said reagent.

5. In a chemical analyzing system according to claim 4, the improvement wherein said inhibiting means inhibits the operation of said differentiator circuit means during said fixed time interval.

6. In a chemical analyzing system according to claim 4, the improvement wherein said inhibiting means inhibits the operation of said generating means during said fixed time interval.

7. In a chemical analyzing system for determining the concentration of a component in a sample, wherein said sample, upon being introduced into solution with a reagent, reacts therewith, the rate of the reaction being indicative of said concentration, such system comprising sensor means for monitoring a characteristic of said solution or a component or a product of said reaction and for producing a first electrical output signal proportional thereto, differentiator circuit means for producing a second electrical signal proportional to the time derivative of said first signal, said time derivative signal being indicative of said concentration of said component in said sample, and means for measuring the value of said time derivative signal, the improvement comprising:

means for inhibiting the measurement of said time derivative signal for a predetermined, fixed time interval from introduction of said sample into said reagent, said time interval being sufficient to eliminate the effect of transients occurring upon introduction of said sample into said reagent.

8. In a chemical analyzing system according to claim 7, the improvement wherein said fixed time interval is long enough to permit thorough mixing of said sample with said reagent.

9. In a chemical analyzing system according to claim 7, the improvement wherein the rate of said reaction is not necessarily linear.

10. In a chemical analyzing system according to claim 7, the improvement wherein said inhibiting means inhibits the operation of said differentiator circuit means during said fixed time interval.

11. In a chemical analyzing system according to claim 7, the improvement wherein said inhibiting means inhibits the operation of said measuring means during said fixed time interval.

12. A chemical analyzer comprising:

means for receiving a sample and a reagent;

sensor means operatively associated with said receiving means for monitoring the concentration of a component or product of the reaction between said sample and said reagent and for producing a First output signal proportional to said concentration;

differentiator circuit means coupled to said sensor means and responsive to said first output signal for producing a second output signal proportional to the time derivative of said first output signal and thus proportional to the time rate of change of concentration of said component or product;

means coupled to said differentiator circuit means for measuring the value of said second signal; and

means coupled to said sensor means for inhibiting the measurement of the value of said second signal for a predetermined, fixed time interval from introduction of said sample and said reagent into said receiving means, said time interval being sufficient to eliminate the effect of transients occurring upon introduction of said sample and said reagent into said receiving means.

13. A chemical analyzer according to claim 12 wherein said inhibiting means comprises:

timing means responsive to an abrupt change in said first output signal for producing a control signal, a characteristic of which changes after said predetermined, fixed time interval; and

wherein said measuring means comprises;

means responsive to said second output signal and operative upon the occurrence of said change in said characteristic of said control signal for determining the value of said second output signal.

14. A chemical analyzer according to claim 13 wherein said control signal is applied to said differentiator circuit means for inhibiting the operation thereof during said fixed time interval and wherein said measuring means measures the maximum value of said second output signal.

15. A chemical analyzer according to claim 13 wherein said timing means produces a second control signal, a characteristic of which changes before the termination of said fixed time interval, wherein said second control signal is applied to said differentiator circuit means for inhibiting the operation thereof during a first portion of said fixed time interval, and wherein said first-mentioned control signal is applied to said measuring means for inhibiting the operation thereof during said fixed time interval.

16. A chemical analyzer according to claim 12 wherein said sensor means comprises:

first and second electrodes extending into said receiving means for monitoring the conductance of the solution therein, wherein;

said second output signal is proportional to the rate of change of conductance of said solution, and wherein;

said measuring means measures the value of said rate of change of conductance after said predetermined, fixed time interval.

17. A chemical analyzer according to claim 16 further comprising:

oscillator means operatively coupled to one of said electrodes of said sensor means, said oscillator means generating an AC output signal; and

demodulator means operatively coupled to the other of said electrodes of said sensor means, said demodulator means receiving an amplitude modulated signal and producing a DC signal which comprises said second output signal.

18. A chemical analyzer according to claim 16 wherein said sensor means includes a surface which is exposed to said solution, and wherein said electrodes comprise first and second conductive areas positioned on said surface, said conductive areas being spaced apart.

19. A chemical analyzer according to claim 16 wherein said sensor means includes a surface which is exposed to said solution, said surface conforming to a segment of a sphere, and wherein said electrodes comprise first and second conductive areas positioned on said surface.

20. A chemical analyzer according to claim 19 wherein said conductive areas have the shape of half circles and are positioned with their straight sides parallel and spaced apart.

21. In a chemical analyzing system for determing the concentration of a component in a sample, wherein said sample, upon being introduced into solution with a reagent, reacts therewith causing an instantaneOus change in a characteristic of said solution or a component or a product of said reaction, the rate of the reaction being indicative of said concentration, such system comprising sensor means for monitoring said characteristic, component or product and for producing a first electrical output signal proportional thereto, said change being sensed by said sensor means producing an abrupt change in said first output signal, and differentiator circuit means for producing a second electrical signal proportional to the time derivative of said first signal, said time derivative signal being indicative of said concentration of said component in said sample, the improvement comprising:

timing means responsive to an abrupt change in said first signal for producing a control signal, a characteristic of which changes after a predetermined, fixed time interval after said abrupt change in said first signal; and

means responsive to said second output signal and operative upon the occurrence of said change in said characteristic of said control signal for determining the value of said second signal.

22. In a chemical analyzing system according to claim 21, the improvement wherein said control signal is applied to said differentiator circuit means for inhibiting the operation thereof during said fixed time interval and wherein said determining means measures the maximum value of said second signal.

23. In a chemical analyzing system according to claim 21, the improvement wherein said determining means measures the instantaneous value of said second signal upon termination of said fixed time interval.

24. In a chemical analyzing system according to claim 21, the improvement wherein said determining means measures the peak value of said second signal after termination of said fixed time interval.

25. In a chemical analyzing system according to claim 21, the improvement further comprising:

means for displaying the determined value of said second signal.

26. In a chemical analyzing system according to claim 21, the improvement wherein said timing means produces a second control signal, a characteristic of which changes before the termination of said predetermined fixed time interval, wherein said second control signal is applied to said differentiator circuit means for inhibiting the operation thereof during a first portion of said fixed time interval, and wherein said first-mentioned control signal is applied to said determining means for inhibiting the operation thereof during said fixed time interval.

27. In a chemical analyzing system according to claim 26, the improvement wherein said determining means measures the instantaneous value of said second signal upon termination of said fixed time interval.

28. In a chemical analyzing system according to claim 26, the improvement wherein said determining means measures the value of said second signal at a known time after termination of said fixed time interval.

29. In a chemical analyzing system according to claim 21, the improvement wherein said sensor means comprises first and second conductive elements for monitoring the conductance of said solution, wherein said second electrical signal is proportional to the rate of change of conductance of said solution, and wherein said determining means measures the value of said rate of change of conductance after said predetermined, fixed time interval from introduction of said sample into said reagent.

30. In a chemical analyzing system according to claim 29, the improvement wherein said conductive elements are substantially planar and are positioned in said sample coplanar to minimize capacitance effects on the measurement of conductance.

31. In a chemical analyzing system according to claim 29, the improvement wherein said sensor means includes a surface which is exposed to said solution, said surface conforming to a segment of a sphere, and wherein said conductive elements comprise first and second conductive areas positioned on said surface.

32. In a chemical analyzing system according to claim 31, the improvement wherein said conductive areas have the shape of half circles which are positioned with their straight sides parallel and spaced apart.