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Method and electronic control for the analyzation of serum chemistries |
| RE28803 |
Method and electronic control for the analyzation of serum chemistries
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| Patent Drawings: | |
| Inventor: |
Durkos, et al. |
| Date Issued: |
May 4, 1976 |
| Application: |
05/541,377 |
| Filed: |
January 16, 1975 |
| Inventors: |
Cole; Robert Wayne (Zionsville, IN)
Denney; Jerry William (Carmel, IN)
Durkos; Larry George (Indianapolis, IN)
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| Assignee: |
American Monitor Corporation (Indianapolis, IN) |
| Primary Examiner: |
Morrison; Malcolm A. |
| Assistant Examiner: |
Smith; Jerry |
| Attorney Or Agent: |
Jenkins, Hanley & Coffey |
| U.S. Class: |
250/573; 356/306; 702/25 |
| Field Of Search: |
235/151.13; 235/151.3; 235/151.35; 250/43.5R; 250/573; 356/81; 356/204 |
| International Class: |
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| U.S Patent Documents: |
3428796; 3528749; 3531202; 3552863; 3553444; 3609047; 3633012; 3652850; 3701601 |
| Foreign Patent Documents: |
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| Other References: |
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| Abstract: |
An electronic control logic system for processing the results of a spectrophotometer analysis of a serum chemistry comprised of a serum and one or more chemical reagents. The spectrophotometer output representing air as a light path and another output representing the test chemistry as a light path are integrated and the air path integrated value allowed to exponentially decay until its value is equal to that of the integrated test chemistry path value. The decay time is converted into a train of digital pulses representative of the optical density of the test chemistry. These pulses are counted and their total stored for comparison with the corresponding optical density of a standard solution. The concentration of the element for which the particular test was designed to detect is known for the standard solution, so the percentage concentration of that element in the test chemistry may be thereby ascertained. Programable variations are provided to enable the evaluation of test results from a kinetic or an end point test. The results of the analysis, together with a test identification number and a patient identification number is selectively applied by a printer control logic section for suitable printing of the data. |
| Claim: |
We claim:
1. An apparatus for determining the concentration of .[.an element.]. .Iadd.a substance .Iaddend.in a .Iadd.test .Iaddend.solution, which comprises analyzation means for determiningthe light transmittance of .[.a.]. .Iadd.the .Iaddend.solution and for generating a first analog signal in accordance therewith; said analyzation means being .[.adaptable for determining the light transmittance of a reference substance and.]. .Iadd.also .Iaddend.for generating a .[.second.]. .Iadd.reference .Iaddend.analog signal .[.in accordance therewith.].; conversion means for generating a first digital signal from said first and .[.second.]. .Iadd.reference .Iaddend.analog signals,said first digital signal having a first numerical value associated therewith .[.as.]. representative of the optical density of said solution; and calculation means for calculating the .[.percentage.]. concentration of the .[.element.]. .Iadd.substance .Iaddend.in said solution from said first digital signal, said calculation means .[.including.]. .Iadd.having .Iaddend.generation means for generating and storing a second digital signal having a second numerical value associatedtherewith representative of .[.the concentration of the element needed in said solution for said first numerical value to equal one;.]. .Iadd.a standardizing scale factor value, .Iaddend. a digital pulse generator for generating a first digital pulsetrain having pulses occurring at a predeterminable frequency and having first and second outputs.[.;.]..Iadd., .Iaddend.frequency alteration means coupled to said conversion means and said first .Iadd.pulse .Iaddend.generator output for altering saidfrequency in accordance with said first digital signal whereby a second digital pulse train is generated.[.;.]..Iadd., .Iaddend.first counting means coupled to said second .Iadd.pulse .Iaddend.generator output for counting the pulses occurring in saidfirst pulse train.[.;.]..Iadd., .Iaddend.second counting means coupled to said frequency alteration means for counting the number of pulses occurring in said second pulse train.[.;.]..Iadd., .Iaddend.detection means for detecting when the number of saidfirst pulse train pulses counted by said first counting means equals said second numerical value and for inhibiting said digital pulse generator when the equation occurs, whereby the number of pulses counted by said second counting means prior to theinhibiting of said generator represents the numerical value of the concentration of the .[.element.]. .Iadd.substance .Iaddend.in said .[.first.]. solution.
2. An apparatus as claimed in claim 1 wherein said analyzation means .[.includes.]. .Iadd.comprises .Iaddend.a spectrophotometer having light sensitive means for generating said first and second analog signals and automatic feedback means foradjusting the supply voltage to said light sensitive means in accordance with changes in the operating characteristics of said spectrophotometer.
3. An automatic method for determining the .[.percentage.]. concentration of .[.an element.]. .Iadd.a substance .Iaddend.in a .Iadd.test .Iaddend.solution, which comprises the steps of reading the value of the light transmittance of thesolution; computing .[.the optical density.]. .Iadd.a .Iaddend.value .Iadd.representative .Iaddend.of the solution .Iadd.optical density .Iaddend.from said .Iadd.solution .Iaddend.light transmittance value; multiplying said .Iadd.representative.Iaddend.optical density value by a scale factor value, .[.said scale factor value being equal to the percentage concentration value of the element which would cause the optical density value to equal one,.]. said multiplying step .[.including.]. .Iadd.comprising .Iaddend.generating a first digital pulse train having pulses reoccurring at a predeterminable frequency.[.;.]..Iadd., .Iaddend.counting and storing the number of pulses generated in said first pulse train.[.;.]..Iadd.,.Iaddend.generating a second digital pulse train identical to said first pulse train.[.;.]..Iadd., .Iaddend.altering the frequency of said second pulse train in accordance with the .Iadd.representative .Iaddend.optical density .Iadd.value .Iaddend.ofsaid solution .[.;.]..Iadd., .Iaddend.counting and storing the number of pulses in the thereby altered second pulse train.[.;.]..Iadd., .Iaddend.comparing the stored number of pulses from said first pulse train with said scale factor value.[.;.]..Iadd.,.Iaddend.and stopping the generating of said first and second pulse trains when the stored number of .Iadd.pulses .Iaddend.from said first pulse train equals said scale factor value, whereby the stored number of pulses having occurred in said altered.Iadd.second .Iaddend.pulse train represents the percentage concentration of the .[.element.]. substance in the solution; and storing the resulting value of said multiplying step.
4. An apparatus for determining the concentration of .[.an element.]. .Iadd.a substance .Iaddend.in a .Iadd.test .Iaddend.solution, which comprises analyzation means for .[.determining the.]. .Iadd.generating a first electrical signal having a.Iaddend.value .Iadd.representative .Iaddend.of the optical density of the .Iadd.test .Iaddend.solution, said analyzation means .[.including.]. .Iadd.having .Iaddend.optical means for .[.determining.]. .Iadd.generating an analog signal representativeof .Iaddend.the light transmittance of the .Iadd.test .Iaddend.solution and .[.for generating an analog signal in accordance therewith.]., conversion means for converting said analog signal to .[.a digital.]. .Iadd.said first electrical .Iaddend.signal.[.representative of the value of the optical density of the solution.]., and first storage means for storing said .[.digital.]. .Iadd.first electrical .Iaddend.signal, said analyzation means also being for .[.determining.]. .Iadd.generating a secondelectrical signal having a value representative of .Iaddend.the optical density .[.value.]. of a standard solution having a known concentration .[.value.]. of the .[.element.]. .Iadd.substance .Iaddend.therein, and for .[.determining.]. .Iadd.generating a third electrical signal having a value representative of .Iaddend.the optical density .[.value.]. of a blank solution; calculation means for .[.determining a value for.]. .Iadd.automatically generating .Iaddend.a standardizing scalefactor .[.representing the concentration of the element in the solution needed for said optical density value to equal one.]. .Iadd.signal.Iaddend., said calculation means .[.including.]. .Iadd.having .Iaddend.subtraction means .Iadd.comparing and.Iaddend.for taking the difference between .[.the optical density value of the standard solution and the optical density value of the blank solution.]. .Iadd.said second and third electrical signals .Iaddend.and for storing the difference value therebyobtained .[.in said first storage means.]., second storage means for .Iadd.generating and .Iaddend.storing .Iadd.a fourth electrical signal having a value representing .Iaddend.said known concentration .[.value.]. of .Iadd.the substance in .Iaddend.saidstandard solution, and division means for dividing .Iadd.the value of .Iaddend.said .[.known concentration.]. .Iadd.fourth electrical signal .Iaddend.by said difference .[.stored in said first storage means.]. .Iadd.value between said second and thirdelectrical signals .Iaddend.to obtain said standardizing scale factor .Iadd.signal.Iaddend. ; .Iadd.and .Iaddend.multiplication means for multiplying said .[.determined optical density.]. .Iadd.first electrical signal .Iaddend.by said scale .[.factorvalue.]. .Iadd.factor signal .Iaddend.thereby .[.obtaining the .]. .Iadd.obtaining an output signal having a .Iaddend.value of the concentration of the .[.element.]. .Iadd.substance .Iaddend.in the .Iadd.test .Iaddend.solution.[.; and display meansfor presenting said concentration value.]..
5. An apparatus for determining the concentration of .[.an element.]. .Iadd.a substance .Iaddend.in a .Iadd.test .Iaddend.solution, which comprises analyzation means for determining .[.the.]. .Iadd.a .Iaddend.value .[.of.]. .Iadd.representing.Iaddend.the optical density of the solution; calculation means for .[.determining.]. .Iadd.generating .Iaddend.a value for a standardizing scale factor .[.representing the concentration of the element in the solution needed for said optical densityvalue to equal one.].; multiplication means for multiplying said .[.determined.]. .Iadd.representative .Iaddend.optical density value by said scale factor value thereby obtaining the value of the concentration of the .[.element.]. .Iadd.substance.Iaddend.in the solution, .[.including.]. .Iadd.said multiplication means having .Iaddend.a digital signal generator .[.having.]. .Iadd.with .Iaddend.first and second outputs for generating a first digital signal having a predetermined frequency onsaid first and second outputs, a digital rate multiplier coupled to said first generator output and to said analyzation means for altering said digital frequency on said first output in accordance with said .Iadd.representative .Iaddend.optical densityvalue to generate a second digital signal, first storage means for storing a third digital signal representative of said scale factor value, second storage means coupled to said digital rate multiplier for storing said .[.third.]. .Iadd.second.Iaddend.digital signal, said first storage means being coupled to said second generator output for receiving said first digital signal, and detection means for detecting when the value of said first digital signal equals the value of said third digitalsignal stored in said first storage means and for inhibiting said generator concurrently with such detection whereby the value of said second digital signal in said second storage means equals the concentration of the .[.element.]. .Iadd.substance.Iaddend.in the .Iadd.test .Iaddend.solution.
6. An apparatus for determining the concentration of .[.an element.]. .Iadd.a substance .Iaddend.in a .Iadd.test .Iaddend.solution, which comprises analyzation means for .[.determining the.]. .Iadd.generating a first electrical signal having a.Iaddend.value .Iadd.representative .Iaddend.of a parameter characteristic of the .Iadd.test .Iaddend.solution .[.and the value.]. .Iadd.and for generating a second electrical signal having a value representative .Iaddend.of said parameter for astandard solution having a known concentration of the .[.element.]. .Iadd.substance .Iaddend.therein; .Iadd.storage means for generating and storing a third electrical signal having a value representing the known concentration of the substance in saidtest solution; .Iaddend.calculation means .[.for determining a value for.]. .Iadd.automatically generating .Iaddend.a standardizing scale factor .[.representing the concentration of the element in the solution needed for said parameter value to equal apredetermined value.]. .Iadd.signal.Iaddend., said calculation means .[.including.]. .Iadd.having .Iaddend.arithmetic means for operating on .Iadd.the values of said second and third electrical signals .Iaddend..[.said parameter value for said standardsolution.]. in computing said standardizing scale factor .[.value.]. .Iadd.signal.Iaddend., said arithmetic means also being for operating on said .[.parameter of the solution with.]. .Iadd.first electrical signal and .Iaddend.said standardizing scalefactor .Iadd.signal .Iaddend.to .[.compute.]. .Iadd.obtain an output signal having a value of .Iaddend.the concentration of the .[.element.]. .Iadd.substance .Iaddend.in the .Iadd.test .Iaddend.solution.
7. An apparatus as claimed in claim 6, wherein said analyzation means .[.includes.]. .Iadd.also comprises .Iaddend.means for .[.determining the.]. .Iadd.generating a fourth electrical signal having a .Iaddend.value .Iadd.representative.Iaddend.of said parameter for a blank solution, and wherein said arithmetic means .[.includes.]. .Iadd.comprises .Iaddend.means for operating on .[.said parameter value for said blank solution in addition to said parameter value for said standardsolution.]. .Iadd.the values of said second, third, and fourth electrical signals .Iaddend.in computing said standardizing scale factor .[.value.]. .Iadd.signal.Iaddend..
8. An apparatus as claimed in claim 6, wherein said analyzation means also .[.being.]. .Iadd.comprises means .Iaddend.for .[.determining the.]. .Iadd.generating a fourth electrical signal having a .Iaddend.value .Iadd.representative.Iaddend.of said parameter for a blank solution, and said arithmetic means .[.includes.]. .Iadd.comprises .Iaddend.subtraction means for .Iadd.comparing and .Iaddend.taking the difference between said .[.standard solution parameter value and said blanksolution parameter value.]. .Iadd.second and fourth electrical signals .Iaddend.and for storing the difference value thereby obtained, .[.storage means for storing said known concentration value of said standard solution,.]. and division means fordividing .Iadd.the value of .Iaddend.said .[.known concentration value.]. .Iadd.third electrical signal .Iaddend.by said difference value .[.stored in said subtraction means.]. .Iadd.between said second and fourth electrical signals .Iaddend.to obtainsaid standardizing scale factor .Iadd.signal.Iaddend..
9. An automatic method for determining the .[.percentage.]. concentration of .[.an element.]. .Iadd.a substance .Iaddend.in a .Iadd.test .Iaddend.solution, which comprises the steps of .[.reading the.]. .Iadd.generating a first electricalsignal having a .Iaddend.value .Iadd.representative .Iaddend.of a parameter characteristic of the .Iadd.test .Iaddend.solution; .[.reading the.]. .Iadd.generating a second electrical signal having a .Iaddend.value .Iadd.representative .Iaddend.of saidparameter for a standard solution having a known concentration of the .[.element.]. .Iadd.substance .Iaddend.therein; .[.calculating a value for.]. .Iadd.generating and storing a third electrical signal having a value representing the knownconcentration of the substance in said standard solution; generating .Iaddend.a standardizing scale factor .[.representing the concentration of the element in the solution needed for said parameter of the solution to equal a predetermined value.]. .Iadd.signal with calculation means .Iaddend. .[.by.]. arithmetically operating .Iadd.automatically .Iaddend.on said .[.parameter value for said standard solution.]. .Iadd.second and third electrical signals.Iaddend.; multiplying .Iadd.withmultiplication means .Iaddend.the .[.calculated.]. scale factor .Iadd.signal .Iaddend.by .[.the value of said parameter for said solution.]. .Iadd.said first electrical signal to obtain an output signal.Iaddend.; and storing .[.the result of saidmultiplying step whereby said result is the.]. .Iadd.and presenting said output signal, said output signal having a .Iaddend.value of the .[.percentage.]. concentration of the .[.element.]. .Iadd.substance .Iaddend.in the .Iadd.test .Iaddend.solution.
10. A method as claimed in claim 9 including the step of .[.reading the.]. .Iadd.generating a fourth electrical signal having a .Iaddend.value .Iadd.representative .Iaddend.of said parameter for a blank solution and said .[.calculating stepincludes.]. .Iadd.step of generating said scale factor signal comprises .Iaddend.the steps of .Iadd.automatically .Iaddend.subtracting .[.the standard solution parameter value from the blank solution parameter value.]. .Iadd.with subtraction means thevalue of said second electrical signal from said fourth electrical signal and.Iaddend., storing the difference value .Iadd.thereby .Iaddend.obtained .[.in said calculating step, storing the value of the known concentration of said standard solution.]. and dividing .Iadd.the value of .Iaddend.said .[.known concentration value.]. .Iadd.third electrical signal .Iaddend.by said difference value to obtain .[.the value for.]. said standardizing scale factor .Iadd.signal.Iaddend.. .Iadd. 11. Anapparatus as claimed in claim 1 wherein said second numerical value has a value representative of the ratio of the concentration of the substance in said solution over the optical density of said solution. .Iaddend..Iadd. 12. An apparatus as claimedin claim 1 wherein said second numerical value has a value representative of the ratio of the concentration of the substance in a standard solution having a known concentration of said substance therein over the optical density of said standard solution. .Iaddend..Iadd. 13. An apparatus as claimed in claim 1 wherein said analyzation means also comprises means for determining the light transmittance of a standard solution having a known concentration of the substance therein and for generating a secondanalog signal in accordance therewith, and for determining the light transmittance of a blank solution and for generating a third analog signal in accordance therewith; said conversion means being also for generating a third digital signal from saidsecond and reference analog signals having a numerical value representative of the optical density of said standard solution and for generating a fourth digital signal from said third and reference analog signals having a numerical value representativeof the optical density of said blank solution; said generation means comprising subtraction means for taking the difference between said fourth digital signal value and said third digital signal value, first storage means for storing the differencevalue thereby obtained, second storage means for storing a value representative of the known substance concentration in said standard solution, and division means for dividing said representative known substance concentration value by said storeddifference value, and means for generating and storing said second digital signal having said second numerical value from the result of said division. .Iaddend..Iadd. 14. An apparatus as claimed in claim 1 wherein said analyzation means also comprisesmeans for determining the light transmittance of air, said reference analog signal being generated in accordance therewith. .Iaddend..Iadd. 15. An automatic method as set forth in claim 3 with the additional steps of reading the light transmittancevalue of a standard solution having a known concentration of the substance therein, computing a value representative of the standard solution optical density from said standard solution light transmittance value, and calculating the value of saidstandardizing scale factor from said standard solution representative optical density value. .Iaddend..Iadd. 16. An automatic method as set forth in claim 15 wherein said standardizing scale factor has a value representative of the ratio of theconcentration of the substance in said standard solution over the optical density of the standard solution. .Iaddend..Iadd. 17. An automatic method as set forth in claim 3 with the additional steps of reading the light transmittance values of astandard solution having a known concentration of the substance therein and of a blank solution, computing representative optical density values for said standard solution and said blank solution from their respective light transmittance values; andcalculating said scale factor value by taking the difference between the representative standard solution and blank solution optical density values, and dividing the difference value thereby obtained into a numerical value representing the knownconcentration of the substance in said standard solution to obtain said scale factor value. .Iaddend..Iadd. 18. An apparatus as claimed in claim 4 with the addition of display means for presenting the value of said output signal. .Iaddend..Iadd. 19. An apparatus as claimed in claim 5 wherein said analyzation means also comprises means for determining a value representing the optical density of a standard solution having a known concentration of the substance therein, said calculation meanscomprising arithmetic means for operating on said representative standard solution optical density value to compute the value of said scale factor. .Iaddend..Iadd. 20. An apparatus as claimed in claim 5 wherein said standardizing scale factor valuehas a value representative of the ratio of the concentration of the substance in a standard solution having a known concentration of said substance therein over the optical density of said standard solution. .Iaddend..Iadd. 21. An apparatus as claimedin claim 5 wherein said analyzation means also comprises means for determining a value representing the optical density value of a standard solution having a known concentration of the substance therein and for determining a value representing theoptical density of a blank solution; said calculation means comprising subtraction means for taking the difference between the representative standard solution and blank solution optical density values, and division means for dividing the differencevalue thereby obtained into a value representing the known substance concentration in the standard solution to obtain said scale factor value. .Iaddend. .Iadd.22. An apparatus as claimed in claim 6 wherein said parameter value for said test andstandard solutions comprises a value representative of the respective optical densities thereof, and said standardizing scale factor signal has a value representative of the ratio of the concentration of the substance in said standard solution over theoptical density of said standard solution. .Iaddend..Iadd. 23. An automatic method as claimed in claim 9 wherein said standardizing scale factor signal has a value representative of the ratio of the concentration of the substance in said standardsolution over the value of said parameter for said standard solution. .Iaddend..Iadd. 24. An apparatus for determining the concentration of a substance in each of a plurality of test solutions, comprising analyzation means for generating a firstelectrical signal having a value representative of a parameter characteristic of a blank solution and for generating a second electrical signal having a value representative of said parameter for a standard solution having a known concentration of thesubstance therein, storage means for generating and storing a third electrical signal having a value representative of the known concentration of the substance in said standard solution, and calculation means for automatically operating arithmetically onsaid first, second, and third electrical signals to generate a standardizing scale factor signal, said analyzation means being also for successively generating a fourth electrical signal having a value representative of said parameter for each of saidtest solutions, and said calculation means being also for arithmetically operating successively on each of said fourth electrical signals and said scale factor signal to obtain an output signal for each of the test solutions having a value of thesubstance concentration in each test solution. .Iaddend..Iadd. 25. An apparatus as claimed in claim 24 wherein said standardizing scale factor signal has a value representative of the ratio of the concentration of the substance in said standardsolution over the difference between the standard solution and blank solution parameter values. .Iaddend..Iadd. 26. An apparatus as claimed in claim 24 wherein said analyzation means comprises optical means for respectively determining the lighttransmittance of each of said solutions, generation means for generating an analog signal in accordance with said respectively determined light transmittances, and conversion means for generating said first, second, and fourth electrical signals fromsaid analog signals, said first, second, and fourth electrical signals each having a value representative of the optical density of their respective solution and corresponding with the value of said characteristic parameter for their respective solution. .Iaddend..Iadd. 27. An apparatus as claimed in claim 24 wherein said calculation means comprises subtraction means for comparing and taking the difference between said first and second electrical signals and for storing the difference value therebyobtained, and division means for dividing the value of said third electrical signal by said stored difference value to obtain said standardizing scale factor signal. .Iaddend..Iadd. 28. An apparatus as claimed in claim 24 wherein said calculationmeans comprises multiplication means for successively multiplying each of said fourth electrical signals by said scale factor signal. .Iaddend..Iadd. 29. An automatic method for determining the concentration of a substance in a succession of testsolutions which comprises the steps of generating a first electrical signal having a value representative of a parameter characteristic of a blank solution and generating a second electrical signal having a value representative of said parameter for astandard solution having a known concentration of the substance therein, generating and storing a third electrical signal having a value representing the known concentration of the substance in said standard solution, generating a standardizing scalefactor signal with calculation means for arithmetically operating automatically on said first, second, and third electrical signals, successively generating a fourth electrical signal for each of said test solutions, each of said fourth signals having avalue representative of said parameter of its respective test solution, and multiplying with multiplication means the scale factor signal by each of said fourth electrical signals to obtain a succession of output signals each having a value of thesubstance concentration for one of said test solutions. .Iaddend..Iadd. 30. An automatic method as claimed in claim 29 wherein said standardizing scale factor signal has a value representative of the ratio of the concentration of the substance in saidstandard solution over the difference between the standard solution and blank solution parameter values. .Iaddend..Iadd. 31. An automatic method as claimed in claim 29 wherein said step of generating said scale factor signal comprises the steps ofcomparing and taking the difference between said first and second electrical signals and dividing the difference value thereby obtained into the value of said third electrical signal to obtain said standardizing scale factor signal. .Iaddend..Iadd. 32. An apparatus for determining the concentration of a substance in each of a plurality of test solutions comprising analyzation means for generating a first electrical signal having a value representative of a parameter characteristic of a first blanksolution and for generating a second electrical signal having a value representative of said parameter for a standard solution having a known concentration of the substance therein, storage means for generating and storing a third electrical signalhaving a value representing the known concentration of the substance in said standard solution, and calculation means for automatically operating arithmetically on said first, second, and third electrical signals to generate a standardizing scale factorsignal, said analyzation means being also for successively generating a series of fourth electrical signals each having a value representative of said parameter for one of said test solutions and a series of fifth electrical signals each having a valuerepresentative of said parameter for one of a plurality of second blank solutions each corresponding with one of said test solutions, and said calculation means also comprises subtraction means for successively comparing and taking the difference betweeneach of said fourth electrical signals and the fifth electrical signal corresponding thereto and means for arithmetically operating on said successively obtained difference values with said scale factor signal to generate a series of output signals eachhaving a value of the substance concentration in one of said test solutions. .Iaddend..Iadd. 33. An apparatus as claimed in claim 32 wherein said standardizing scale factor signal has a value representative of the ratio of the concentration of thesubstance in said standard solution over the difference between said standard solution and first blank solution parameter values. .Iaddend. .Iadd. 34. An automatic method for determining the concentration of a substance in a succession of testsolutions which comprises the steps of generating a first electrical signal having a value representative of a parameter characteristic of a first blank solution and generating a second electrical signal having a value representative of said parameterfor a standard solution having a known concentration of the substance therein, generating and storing a third electrical signal having a value representing the known concentration of the substance in said standard solution, generating a standardizingscale factor signal with calculation means for arithmetically operating automatically on said first, second, and third electrical signals, successively generating a fourth electrical signal for each of said test solutions and a fifth electrical signalfor each of a plurality of second blank solutions each corresponding with one of said test solutions, said fourth and fifth signals each having a value representative of said parameter of its respective solution, successively comparing and taking thedifference between each of said fourth signals and the fifth electrical signal corresponding thereto, and arithmetically operating on said successively obtained difference values with the value of said scale factor signal to obtain a series of outputsignals each having a value of the substance concentration in one of said test solutions. .Iaddend. .Iadd. 35. An apparatus for determining the rate of reaction of a known reagent with a sample solution having a quantity of a reacting substancetherein, comprising analyzation means for generating a first electrical signal having a value representative of a parameter characteristic of a standard solution having a known concentration of the substance and said known reagent therein, and forgenerating a second electrical signal having a value representative of said parameter for said standard solution at the end of a preselected time interval after generation of said first electrical signal; storage means for generating and storing a thirdelectrical signal having a value representative of the known concentration of the substance in said standard solution; calculation means for automatically operating arithmetically on said first, second, and third electrical signals for generating astandardizing scale factor signal; said analyzation means being also for generating a fourth electrical signal having a value representative of said parameter for a test solution having the sample solution and said known reagent therein, and forgenerating a fifth electrical signal having a value representative of said parameter for said test solution at the end of a preselected time interval after generation of said fourth signal, said test solution time interval being equal to the standardsolution time interval; and said calculation means also comprising subtraction means for comparing and taking the difference between said fourth and fifth electrical signals and arithmetic means for arithmetically operating on said difference value withsaid scale factor signal to obtain an output signal having a value of the rate of reaction of the reagent with the sample solution. .Iaddend..Iadd. 36. An apparatus as set forth in claim 35 wherein said calculation means comprises subtraction meansfor comparing and taking the difference between said first and second electrical signals, and division means for dividing the resultant difference value into the value of said third electrical signal to obtain the value of said standardizing scale factorsignal. |
| Description: |
BACKGROUND OF THE INVENTION
This invention relates to an electronic system and method for processing a signal obtained from the electro-optical analyzation of a precisely prepared serum chemistry.
The chemical analyzation of a serum, e.g., for the presence of sugar or albumin content, or any of many other assays vital to medical diagnosis, is generally performed by adding specific amounts of various reactive chemicals or reagents to asample of serum in a specific sequence and under specified conditions of temperature and time thereby causing a change in color or light absorbance to occur which is related to the amount of the substance being measured in serum. Various manual andautomated procedures have been used.
Manual procedures are usually performed in a laboratory by a trained technician. The technician prepares a test sample, commonly referred to as a test chemistry, comprised of a portion of a serum specimen to be tested and the proper amounts ofthe chemical reagents specified for that particular test. The resulting test chemistry, after formulation, must be analyzed with specific care taken to note the extent to which a desired reaction has taken place.
The reaction evaluation is done using a spectrophotometer. The output of the spectrophotometer represents the amount of a certain band width of light which the chemistry under test passes with respect to the amount of the same band width oflight passed by a sample containing all other constituents in the test except the serum. The level of this comparative transmittance must be then transformed into units which represent the element concentrations or optical density of the test chemistryto present meaningful data to the technician so that he might evaluate the test.
Disadvantages of manual procedures include not only an undue amount of time and labor, but this type of laboratory testing is at most, even under the most optimum conditions only proportioned to the skill of the technician.
Several systems have also been proposed and used which present the optical density of test chemistries by means of a strip recorder. This technique results in a cumbersome amount of data paper, along with the inherent reading problems which arehighly susceptible to error.
SUMMARY OF THE INVENTION
In accordance with the invention, a serum chemistry may be loaded into the flow cell of a spectrophotometer for optical analysis. The difference in light transmittance between an air path and a path through the test chemistry is detected by aphotomultiplier tube, the output of which is connected to an amplifier and associated control circuits. Feeback means may be provided to automatically adjust the voltage across the photomultiplier tube to provide changes in its sensitivity due tooperating temperature or to the wave length of the observed light.
The position of the flow cell may be used to set up logic conditions to institute the selective integration at the amplified photomultiplier tube output for both the test and reference air paths. The integrated value of the reference path signalis always greater than that of the integrated value of the test path signal since the reference path consists of air while the test path consists of test solution. The integrated value of the reference signal may be permitted to logarithmically decayuntil it equals that of the integrated value of the test signal. The time required for the integrated reference signal to decay to the value of the integrated test value is proportional to the optical density at the test solution. This relies in parton the relationship that optical density is equal to the logarithm of the incident light minus the logarithm of the transmitted light. The required decay time is transformed into a proportional digital pulse train and selectively placed in an opticaldensity memory.
The processing of the digital representation of the optical density of a test chemistry is done under the control of a logic programmer section. This programmer section receives information from a programmed card which is interpreted by a cardreader in a manner explained and described in a co-pending application, U.S. Ser. No. 179,133.
Several different types of tests may be programmed each of which require the processing of the optical density signal in a different manner. For the most part, the end point light absorbance of the reaction between a serum sample and testreagents is observed. The optical density of the reacted test chemistry may be compared within a calculation portion of the electronic system to that of a serum blank or a reagent blank. In the performance of the former, two serum samples are mixedwith two different combinations of reagents to effect two different test reactions. The optical density of the first test chemistry must then be compared with the optical density of the second test chemistry to obtain the desired comparative opticaldensity.
An end point reagent blank test requires that a chemistry consisting of reagents alone must be first spectrally analyzed and the resulting optical density reading stored for comparison with subsequent test chemistry readings. The testchemistries in this case are comprised of different serum samples all having the same reagents added to them.
A test may also be performed which requires that the optical density of the same test chemistry be ascertained at two precisely controlled points in time. Furthermore, it may be required that this be done for two or three such intervals toensure that the reaction is taking place properly and is linear.
The arithmetic portion of the electronic system is preferably calibrated before the performance of any of the above tests to effect a standardization of the results with respect to a known base value and to simultaneously convert the opticaldensity of the chemistries into concentration units. This calibration is completely automatic and may be done by the use of a solution with a known .Iadd.substance .Iaddend.concentration.Iadd., herein referred to as a standard solution. .Iaddend.Asolution, herein referred to as the blank and comprised of a full complement of reagents for a given test, is first placed in the flow cell for ascertainment of its optical density. The difference in optical densities of the blank and the specimen testchemistry may be stored in an optical density memory. The contents of this memory are used to alter the frequency of a known clock frequency. Unaltered clock frequency may be used to clock a counter at the same time that the altered clock frequency isused to clock a second counter. This has the effect of creating a ratio representative of the difference between the optical density of the blank reagent solution and the optical density of the standard solution. This standard value is stored so thatall subsequent test results may be derived from it. The optical density of each of the solutions is proportional to its percentage concentrations so that by using a standard solution of a known percentage concentration to develop a proportionalityconstant based on optical density, the percentage concentrations of each of the test chemistries may be ascertained.
Printer logic may be provided which is able to sequentially and selectively present the test results, a patient identification number and the test identification number to a drum printer.
BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawings illustrate the invention and, by way of example, show a preferred embodiment of the invention. In such drawings:
FIG. 1 is a perspective view of a machine compatible for use with the invention;
FIG. 2 is a vertical section view showing the reciprocating apparatus for the flow cell;
FIG. 3 is a block diagram showing the interrelationship of the various portions of the invention;
FIG. 4 is a schematic diagram showing the pre-amp and voltage comparator;
FIG. 5 is a schematic diagram showing the high voltage supply and its control;
FIG. 6 is a schematic diagram showing the integrator and its controlling switches;
FIG. 7 is a schematic diagram showing the track/store control logic and the cross-over comparator control logic;
FIG. 8 is a schematic diagram of the spectrophotometer control logic;
FIG. 9 is a schematic diagram showing part of the spectrophotometer logic control;
FIG. 10 is a schematic diagram showing the one megahertz clock source and its related gate and controls;
FIGS. 11 A and B are schematic diagrams showing the optical density counter, the digital rate multiplier and the master counter;
FIG. 12 is a schematic diagram showing the blank storage register and a nines complementor;
FIGS. 13 A and B are schematic diagrams showing the calculation counter and nines complementor, the multiplication accumulator, the percentage concentration counter and the standard unit switches;
FIG. 14 is a schematic diagram showing the multiply and divide selection logic;
FIGS. 15 A and B are schematic diagrams showing portions of the programmer control logic;
FIG. 16 is a schematic diagram showing another portion of the programmer control logic;
FIG. 17 is a schematic diagram showing a portion of the programmer control logic;
FIG. 18 is a schematic diagram showing a portion of the programmer control logic;
FIG. 19 is a schematic diagram showing part of the printer control logic;
FIG. 20 is a schematic diagram showing a portion of the printer control logic;
FIG. 21 is a schematic diagram showing part of the printer control logic;
FIG. 22 is a schematic diagram showing a portion of the printer control logic;
FIG. 23 is a schematic diagram showing a portion of the printer control logic;
FIG. 24 is a schematic diagram showing a portion of the printer control logic; and
FIG. 25 is a schematic diagram showing a portion of the printer control logic.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The chemical analyzation machine shown in FIG. 1 is for the serial analyzation of serum samples which have been obtained from respective patients by conventional means. The term "serum" is used to designate any animal fluid. This analyzationmachine and the electronic control logic which controls its operation are shown and described in copending applications, U.S. Ser. No. 179,013 and U.S. Ser. No. 179,133 respectively.
By way of background, the machine shown in FIG. 1 comprises an upper housing 10 supported on a lower housing 12 by a post 14. A serum specimen wheel 16 and a test wheel 18 are supported in and by the top of the lower housing 12. The drive motorfor these wheels 16 and 18 is located within the lower housing 12. The bottom portion of the lower housing 12 encloses an array of pressurized bottles 20, some of which are enclosed in a refrigerated compartment 22. These bottles 20 contain the variouschemical reagents used in the performance of a serum analysis by the machine. They may be pressurized with inert nitrogen gas to prevent degradation of the reagents. Dark transparent doors on the front of the lower housing 12 permit the bottlecompartment to be observed.
A serum transfer apparatus 24, a plurality of reagent dispensing heads 26, 27 and 28, and a test chemistry extraction head 29 are located in close proximity to the serum specimen wheel 16 and the test wheel 18.
Serum specimens may be placed in a plurality of specimen cups 30 which are carried in equally-spaced cavities in the top of the sample conveyor wheel 16. Each of the cavities is numbered and has a patient identification selection switch (notshown) associated with it. In a similar manner, test tubes 34 are carried in equally-spaced peripheral holes (not shown) in the test conveyor wheel 18. A serum specimen is appropriately taken from the specimen cups 30 in the specimen wheel 16 andtransferred to a waiting test tube 34 in the test wheel 18 by the serum transfer apparatus 24. Properly selected reagents are added via the dispensing head 26, 27 and 28 to each of the serum samples which have been transferred to test tubes as the testtubes 34 are indexed through the dispensing stations. The resulting test chemistries are then serially extracted for subsequent optical analyzation as in a spectrophotometer or a fluorometer by the test chemistry extraction head 29. Thespectrophotometer or fluorometer may be housed within the supporting post 14.
The electronic control circuitry for controlling each of these operations may be contained in the upper housing 10. This circuitry may be programmed by a specially prepared card which is inserted in a slot 36 leading to a card reader (not shown)also supported in and by the upper housing 10. An array of push buttons 38 may be located adjacent the card reader slot 36 for manually controlling part or all of the machine operations. An electronic measurement and reporting system consisting of thespectrophotometer, calculator, programmer and printer electronics in addition to a printer mechanism may also be housed in the upper housing 10 to convert the output signal from the spectrophotometer or like device into more usable forms of data such asmilligram percentage concentrations.
The spectral analysis of fully complemented specimen test chemistries is conducted in a conventional spectrophotometer which has been modified to provide means by which the flow cell is moved in and out of a light path instead of disturbing thatpath with rotating mirrors or chopper and beam splitter techniques. The directing of the light beam is required so that its transmittance through air may be compared with its transmittance through the test chemistry in the flow cell.
A flow cell 40 is shown in FIG. 2 with its associated reciprocating apparatus. This cell 40 is supported by bearings 42 on a rail 44 which permits and guides linear movement of the flow cell 40. The base of the flow cell is connected, as by apin 46, to a slotted member 48. A finger member 50 is mounted and is eccentrically driven on a wheel 52 and moves within the slot 54 in the slotted member 48. A shaft 56 is eccentrically mounted by a ball bearing 58 to its finger supporting wheel 52. The shaft 56 is connected to a second circular and rotating wheel 60 at a location offset from the center of rotation of that wheel 60. The latter wheel 60 is rotated at approximately 30 rpm by an electric motor 62. The finger supporting member 52 iseccentrically driven as the motor rotates this wheel 60 to reciprocate the flow cell 40 on its supporting rod 44. As can be seen from FIG. 2, this reciprocation serves to move the flow cell and the test chemistry contained therein in and out of thelight path. The light source intensity .[. 64.]. is highly regulated and prefocused. The reciprocation of the flow cell and test chemistry provides a continuous source of calibrating signals for the spectrophotometer. The electronic measurement andreporting system used to convert the spectrophotometer output into a more usable and meaningful form of data will be hereinafter described.
The above described machine is capable of performing what are known as end point serum blank tests, end point reagent blank tests and kinetic tests. In the end point serum blank test, an amount of each serum sample to be tested is placed in twoconsecutive test tubes 34 in the test wheel 18. One group of reagents is dispensed into and combined with the serum samples in one of the thereby associated pairs of test tubes, while a different set of reagents is added to and combined with theremaining serum sample. These two sets of reagents may have one or more reagents in common. The former being referred to as the blank and the latter being referred to as the test. It is required to measure the optical density (O.D.) of both the blankand test and subtract the O.D. of the blank from the O.D. of the test to obtain the desired results. The resulting difference of optical densities is proportional to the concentration of the material for which the test is designed to measure.
An end point reagent blank consists of adding the same combination of reagents to a number of test tubes and then adding a sample of water to the first tube, which is referred to as the reagent blank, and a different serum sample to each of thefollowing tubes. In order to arrive at the desired test results, it is required to measure the optical density of the contents of each test tube and subtract from the optical density thereby measured the optical density of the reagent blank. Thedifference is proportional to the concentration of the material in the sample for which the test was designed to measure.
The kinetic test analyzes the rate of reaction of a specific combination of reagents and a serum sample. The test consists of measuring the rate of reaction of a specific combination of reagents and a serum sample. It is possible to do this bymeasuring the optical density of the test solution at a certain time, +1, and again at a subsequent time, +2, and subtract the difference between these readings. This may be repeated any number of times for the same test; and each time the resultsshould be the same as long as the reaction rate is linear. It is important to determine if the rate is constant and to record results during that portion of the reaction. The optical density difference as a function of time may be calibrated byperforming an identical test on a .[.sample.]. .Iadd.standard solution .Iaddend.with a known concentration of the material for which the test is designed. The above described procedure may be performed in several ways. The first being that of placingthe test solution in the flow cell and measuring its optical density at precisely controlled timed intervals. A second procedure, which provides for a higher overall rate of sample analysis involves placing an amount of serum sample into threeconsecutive test tubes. Reagents are appropriately and selectively added to each of the three samples at a different point in time. Each group of three test chemistries are identical in composition when extracted and placed in the flow cell except thatthey are serially extracted at the end of precisely controlled time intervals. This latter method has been found to yield better and faster results, since the necessary time intervals have elapsed prior to placing the test chemistries in the flow cell.
A block diagram is shown in FIG. 3 which illustrates in block form the electronic processing of the spectrophotometer output to transform the output into a more meaningful form of data to enable comparison with a standard solution whosecharacteristics are known. The light emitted by the light source .[., shown in FIG. 2 in conjunction with the flow cell 40,.]. falls upon a photomultiplier tube 66. The output of the photomultiplier tube 66 is connected directly to a preamplifier 68for converting the output current at the photomultiplier tube to a proportional DC level.
Assuming that the test chemistries are still being formulated in the test wheel 18, and that none have reached the flow cell for analysis as yet, the spectro module control logic 70 maintains a solid state switch 72 leading from the preamp 68 toan integrator 74 .[.opens .]. .Iadd.open .Iaddend.so that the preamp output is applied through a closed switch 76 to one input of a voltage comparator 78. A reference voltage is also applied to this comparator 78. The comparator 78 compares the preampoutput with the reference voltage and uses the difference between the two to control a high voltage supply 80 for application across the photomultiplier tube 66.
The loop comprising the photomultiplier tube 66, the preamp 68, the voltage comparator 78 and the high voltage supply 80 is used as an automatic gain control and calibration adjustment for the photomultiplier tube 66. This adjustment is neededbecause the photomulitipler tube characteristics change a great deal with time and temperature, and because the photomultiplier tube does not have the same sensitivity over the entire light spectrum. This closed loop feedback condition permits thephotomultiplier tube output to be stabilized with respect to the particular wave length of light which it will be concerned with in the upcoming test.
The presence of a first test chemistry to be analyzed in the flow cell is sensed by the spectro control logic 70 which then opens the switch 76 in the feedback path leading from the preamp to the high voltage supply 80 and closes the integratorswitch 72 leading from the preamp 68 to the integrator 74. Preferably, this switch is also opened each time the empty flow cell interrupts the light path by the spectro control logic 70 acting on a signal from a flow cell position detection switch 82.
The flow cell position detection switch 82 signals the spectro control logic 70 when the flow cell is between the light source and the photomultiplier tube 66 and, conversely, when the flow cell is out of this path so that the light uninterruptedfrom the light source is incident on the photomultiplier tube 66. The photomultiplier tube 66, and thereby the preamp 68, have a higher DC level output when the light path comprises only air than when the light passes through a test chemistry and theflow cell. Both signals are important for later comparison.
The first signal to be applied by the preamp 68 to the integrator 74, after the integrator switch 72 has been closed, represents the amount .Iadd.of .Iaddend.a given wave length of light striking the photomultiplier tube after passing through atest chemistry. This DC signal is integrated by the integrator 74 for a specific length of time, as controlled by the spectro control logic 70. The integrator output is initially zero, but as it integrates the preamp output its output then become aramp function.
The ramp function, as it is generated, is applied through a closed tracking switch 84 to a track and store network block 86. The tracking switch 84 is also controlled by the spectro control logic 70. The track and store network 86 tracks theintegrator output until the integration interval is terminated by the spectro control logic 70. The termination signal is also used to open the tracking switch 84 which then causes the DC level to which the preamp output has been integrated to be storedin the track and store network 86.
The flow cell is then moved out of the light path from the light source to the photomultiplier tube 66. This movement is detected by the flow cell position detector switch 82 which signals the spectro control logic 70. The preamp 68 output nowrepresents the photomultiplier tube output with only an air path between the light source and that tube 66.
The control logic 70 initiates a reference signal integration interval and causes the integrator 74 to integrate the preamp output for an amount of time precisely identical to the integration time for the test chemistry. The integrator 74 nowintegrates the DC signal representing the photomultiplier tube 66 output for an air path for an interval of time precisely equal to that of the integration interval for the test chemistry. At the conclusion of this interval, a decay switch 88 in afeedback path around the integrator 74 is closed by the control logic 70 which causes the voltage at the output of the integrator to decay exponentially.
It should be noted that if, at the end of both integration intervals, the integrator 74 output representing the air path, and the track and store circuit 86 output representing the test chemistry path were equal, it would mean that the opticaldensity of the test chemistry is zero and that it has a light transmittance equal to that of air. This, however, is never the case even for an empty flow cell, so the light transmittance of a flow cell containing a test chemistry is always less thanthat of free air. The exponential decay of the air path reference integrator output is conducted as the first part of an analog to digital conversion of the light transmittance of the test chemistry with a simultaneous conversion to optical densityunit.
The exponential decay of the reference air path integrated output is continued until the decreasing signal is equal in amplitude to the signal level held by the track and store network 86. The comparison of the decaying signal and the track andstore held signal is effected in a crossover comparator 90. The signal which closed the decay switch 88 also enabled a latch 91 coupled to the output of the crossover comparator 90 to allow the comparator output to be applied to one input of a countergate 92. The output of a one megahertz clock 94 is divided by 10 by a division section 96 and the resulting 100 kilohertz clock applied to the other input of the counter gate 92. The output of the counter gate 92 is a train of pulses occurring at a 100kilohertz rate when there is an enabling signal from the output of the comparator .[.74.]. .Iadd.90.Iaddend.. This output is enabling only as long as coincidence has not been detected by the crossover comparator 90 between the track and store network86 contents and the decaying integrating output. When such coincidence is detected by the comparator 90, the input from that comparator to the counter gate 92 is turned off, thereby stopping the pulse train.
It should be seen that the number of pulses in this train corresponds to the amount of time that the integrator output was permitted to decay before it reached the signal level of the signal held in the track and store network 86. It should alsobe seen that the pulse train represents or is proportional to the logarithm of the transmittance of light in an air path minus the logarithm of the transmittance of light through a test chemistry. This makes the pulse train proportional to the opticaldensity of the test chemistry.
As previously mentioned, the entire analog to digital conversion as well as the light transmittance readings are taken under the control of the spectrophotometer control logic 70. This logic is appropriately controlled through a programmer 98whose output signals to the control logic 70 reflect the particular test which has been selected on the program card, i.e., end point serum blank test, end point reagent blank or kinetic test. The remaining blocks of the calculator section will beexplained with reference to the specific tests under way.
At the beginning of each of the tests mentioned a blank calibration is performed. The first test chemistry which would be put into a flow cell is either a reagent blank or a serum blank. In the end point reagent blank test the reagent blank iscomprised of the reagents which the rest of the chemistries will receive but without any serum. The optical density of this blank is used, as will hereinafter be explained, to calibrate the calculator section 100 of the spectrophotometer processinglogic. In the case of the serum blank test, the first test chemistry to reach the flow cell is a .Iadd.standard .Iaddend.serum blank comprised of .[.a serum specimen.]. .Iadd.a standard solution .Iaddend.and reagents. .[.The next chemistry to reachthe flow cell subsequent to this one will be one comprised of the same serum with different reagents..].
A blank storage register 102 for later storing the optical density of the reagent or serum blank is first reset to zero by the programmer 98. A master counter 104 which is clocked through a master counter control gate 106, the operation of whichwill be described later, from the 1 megahertz clock 94 is then reset to zero. An optical density counter 108 for storing the digital counterpart of the optical density of the solution in the flow cell is also reset to zero. A calculation counter 110and the percentage concentration counter 112 used in the calculation of percentage concentrations are also reset to zero.
After the resetting phase is completed, the optical density counter 108 is preset with the nines complement of the contents of the blank storage register 102. The nines complement of the blank storage 102 is taken by a nines complementconversion block 114. Since the blank storage register 102 had been reset to zero, the nines complement preset into the optical density counter 108 would be equal to 1999. The percentage concentration counter 112 is then preset with the number whichhas been dialed in on a set of switches 116. This value represents the .Iadd.known .Iaddend.percentage concentration of .[.a.]. .Iadd.the substance for which the test is designed to measure in the .Iaddend.standard solution which will be placed in theflow cell at a subsequent point in time. A multiplier accumulator 118 is then preset with the percentage concentration in the percentage concentration counter 112. The nines complement is then taken of this value, which has been preset into themultiplier accumulator 118, by a nines complement converter 120. The nines complement of the known standard concentration is then preset into the calculation counter 110. The percentage concentration counter 112 is then reset to zero.
After completion of the above, the integration and analog to digital conversion is permitted to take place to determine the optical density of the blank solution in the flow cell. Up until this time, the feedback switch 76 in the preamp 68feedback circuit has been closed when the flow cell was out of the light path which permitted the photomultiplier tube to be calibrated. The string of pulses representing the optical density of the flow cell and its contained blank solution is appliedto the optical density counter 108 through the counter gate 92. The counter gate 92, as before explained, is opened when the correct number of pulses has been applied to the optical density counter 108. The value in the optical density counter is thenpreset into the blank storage register 102 and the nines complement of this value taken by the nines complementor 114 and the result preset back into the optical density counter 108.
The blank solution is then removed from the flow cell. The next chemistry to be put into the flow cell is the standard .[.chemistry.]. .Iadd.solution.Iaddend., the .[.element.]. .Iadd.substance .Iaddend.concentration for which was dialed in onthe standard switch input 116. The light transmittance of this chemistry is then determined and the analog to digital conversions repeated, with the optical density pulse train of the standard chemistry being put into the optical density counter 108together with the nines complement of the optical density of the blank chemistry. The resulting number in the optical density counter represents the difference in optical density between the blank and the standard solutions.
The scale factor for use in all further percentage element concentration calculations must be determined using this difference between the blank optical density and the standard optical density. To do this, a 100 kilohertz clock is applied bythe master counter 104 to a digital rate multiplier 124 and through a multiply and divide selector block 126 to the percentage concentration counter 112. The 100 kilohertz pulse train is multiplied in the digital rate multiplier 124 by the value in theoptical density counter 108 to proportionately alter the frequency of the 100 kilohertz pulse train. The altered pulse train is applied through the multiply and divide block 126 to the calculation counter 110 which already contains the nines complementof the known percentage concentration of the standard solution. The calculation counter 110 and the percentage concentration counter 112 continue to be clocked by their respective clock lines until a fill detector 128 senses that a number of pulses havebeen received by the calculation counter 110 from the digital rate multiplier 124 equal to the known standard percentage concentration. This fill detector 128 is used to inhibit the master counter gate 106 which has heretofore been supplying the mastercounter 104 with clock pulses from the 1 megahertz clock 94. The number of pulses which have reached the percentage concentration counter 112 in this interval represent the scale factor which will be used as the basis for all subsequent tests. Ineffect, this procedure divides the dialed in standard .Iadd.solution substance .Iaddend.concentration by the difference in optical density between the standard chemistry and the blank chemistry and stores the resulting value in the percentageconcentration counter 112. As will be seen, the optical densities of the test chemistries will be multiplied by this normalized value to calculate their percentage concentrations. It should be seen that such calculated values will be in the same unitsas the standard .Iadd.solution substance .Iaddend.concentration that was dialed in. By way of example of the above process, assume an optical density difference between the blank solution and the standard chemistry of 0.5. The optical density counter108 will then contain the binary equivalent of 0500. The multiply and divide section 126 enables the master counter 104 to apply 100 kilohertz clocking pulses to the percentage concentration counter 112. The 100 kilohertz clock is also applied to thedigital rate multiplier 124 which multiplies this frequency by the number in the optical density counter 108, i.e., 0.500. the calculation counter 110 thereby receives 500 pulses each time the percentage concentration counter 112 receives 1,000 pulses. Assume further that the known standard concentration dialed in on the input switches 116 was represented by 1,000. The nines complement of 1,000 would now be in the calculation counter 110. By the time the calculation counter 110 has received the 1,000pulses necessary to initiate the inhibiting action of the fill detector 128 the percentage concentration counter 112 will have received 2,000 pulses which represents the normalized value by which all subsequent O.D. values will be multiplied toascertain the corresponding percentage concentrations. As a last step, the multiplication accumulator 118 is preset with this number, i.e., 2,000, and the programmer 98 is reset.
The actual test procedure is now ready for initiation. The blank storage register 102 contains the value of the optical density of the blank solution. The master counter 104, the calculation counter 110 and the percentage concentration counter112 are all reset to zero. The optical density counter 108 is then preset with the nines complement of the blank storage register 102 which, in effect, is the negative of that number. The calculation counter 110 is then preset with the ninescomplement, from the nines complementor 120, of the scale factor contained in the multiplication accumulator 118.
By this time, .Iadd.in the end point reagent blank test, .Iaddend.a test chemistry has entered the flow cell and the photomultiplier tube 66 has an output which is applied to the preamp 68. Under control of the spectrophotometer control logic70, this output is integrated and converted from an analog signal to the digital pulse train representative of the optical density of the test chemistry in the flow cell. This pulse train is then applied to the optical density counter 108 on top of thenines complement of the optical density of the blank solution which in effect subtracts the blank optical density from the test optical density. The value now in the optical density counter 108 represents the true optical density of the test chemistry.
The calculation of the concentration of the test chemistry with respect to that of the standard chemistry is now performed. The first step in this procedure is that the programmer logic 98 selects the multiplication portion of the multiplier anddivide circuit 126. This selection serves to route the digital rate multiplier 124 output to the input of the percentage concentration counter 112. A 100 kilohertz master counter 104 output is concurrently routed to the calculation counter 110. Themaster counter 104 begins on signal from the programmer clocking the percentage concentration counter 110 with its 100 kilohertz output.
The digital rate multiplier 124 multiplies the frequency of another 100 kilohertz output frequency clock of the master counter 104 by the optical density value in the optical density counter 108 and applies the resulting pulse train to thepercentage concentration counter 112. This clocking continues until the fill detector 128 detects that the calculation counter 110 has received a number of pulses from the master counter 104 equal to the scale factor which originated in the multiplieraccumulator 118.
At this time, the master counter gate 106 is inhibited, thereby prohibiting further pulsing of the master counter 104 by the 1 megahertz clock 94. The opening of the gate 106 also stops the pulsing of the percentage concentration counter 112. The contents of this counter 112 at this time represents the concentration of the test chemistry in the flow cell with respect to the known standard value. This value is applied through printer logic 132 to the printer 134 along with identificationinformation.
At the beginning of an end point blank serum test the blank storage register 102, the master counter 104, the optical density counter 108, the percentage concentration counter 112 and the calculation counter 110 are all reset to zero. Thisresetting is performed at the conclusion of the blank and standard calibration explained above. The programmer 98 then presets the optical density counter 108 with the nines complement of the contents in the blank storage register 102. This register102 was reset to zero, so the value of the nines complement is equal to 1,999. The calculation counter 110 is the preset with the nines complement; through the nines complementor 120, of the scale factor contained in the multiplication accumulator 118.
The programmer logic initiates, at this time, the analog to digital conversion of the light transmittance of the patient blank test chemistry in the flow cell at that time which is comprised of a serum specimen plus one or more reagents. Therepresentative pulse train of the optical density of this patient blank is applied to the optical density counter 108. This value is then preset into the blank storage register 102, is nines complemented by the nines complementor 114 and is preset intothe optical density counter 108.
The patient test chemistry is then examined by the photomultiplier tube 66 and the pulse train representing its optical density is applied to the optical density counter 108 which already contains the nines complement of the optical density ofthe patient blank. This results in the difference in optical density between the two residing in the optical density counter 108. The master counter 104 is then allowed to apply, through the multiplication and divide circuit 126, its 100 kilohertzpulses to the calculation counter 110 which already contains the nines complement of the standard scale value. The digital rate multiplier 124 multiplies another 100 kilohertz output of the master counter 104 by the contents of the optical densitycounter 108 and accordingly clocks the standard units value counter 112.
Again, when the fill detector 128 notes that the number of master counter pulses applied to the calculation counter 110 equals the standard scale factor, the detector 128 opens the master counter gate 106 from the one megahertz clock 94 to themaster counter 104. The value in the percentage concentration counter 112 then represents the percentage concentration of the patient test with respect to the patient blank. This value is applied by the printer logic to the printer 134 along withidentification information. The programmer 98 is reset at the conclusion of the test series.
The performance of a kinetic test requires a special calibration. This calibration includes resetting the blank storage register 102, the master counter 104, the optical density counter 108, the calculation counter 110 and the percentageconcentration counter 112. The only other thing that occurs in the kinetic calibration mode is the presetting of the percentage concentration counter 112 with the standard .Iadd.solution .Iaddend.percentage concentration value dialed in on the switches116. The contents of the percentage concentration counter 112 is then preset into the multiplication accumulator 118 to complete the calibration for the kinetic test.
The kinetic test may be conducted in one of two different ways due to the difference in reactions possible in the various test chemistries. The first way involves the inspection of a test chemistry upon the elapse of two or more preciselycontrolled intervals of time. A rate of increase in optical density is looked for, thereby permitting the first test chemistry reading to be used as the base for all subsequent readings. The other type of kinetic tests involves a rate of decrease inoptical density. To standardize this mode of operation, the standard element concentration is used and all subsequent readings taken in relation to that value.
For a kinetic optical density increase test, the blank storage register 102 and all of the counters 104, 108, 110 and 112 are reset to zero. The optical density counter 108 is then preset with the nines complement of the contents of the blankstorage register 102, which is 1999. The calculation counter 110 is then preset with the nines complement, through the nines complementor 120, of the scale factor contained in the multiplication accumulator 118. The sequence is then inhibited and thefirst digital pulse train representing the optical density of the test chemistry in the flow cell is put into the optical density counter 108.
The optical density counter contents is then preset into the blank storage register 102 and the sequence inhibited again until a second reading is taken of the test chemistry in the flow cell. The application of the digital pulse trainrepresenting the optical density obtained at the latter reading 1999. put into the optical density counter 108 with the nines complement of the blank storage register contents, which serves to subtract the former from the latter.
The multiply and divide circuit 126 is then enabled to apply the 100 kilohertz output of the master counter 104 to the calculation counter 110 at the same time that the 100 kilohertz rate is multiplied by the contents of the optical densitycounter 108 in the digital rate multiplier 124 and applied to the percentage concentration counter 112. As before, when the number of pulses from the master counter 104 reaching the calculation counter 110 equals the standard value which originated inthe multiplier accumulator 118, the fill detector 128 opens the master counter gate 106 and stops its enabling pulses.
The value in the percentage concentration counter at this time represents the change in optical density in the time interval between test chemistry readings. Several such pairs of readings may be obtained to ensure that the desired linearreaction is taking place. This value is then applied to the printer logic 132 which controls the printer 134 accordingly.
An optical density loss kinetic test, as previously mentioned, is used to determine the rate at which the optical density of a test chemistry decreases from that of a known standard starting point.[.,.]..Iadd.. .Iaddend.Initially, the blankstorage register 102 as well as all of the counters 104, 108, 110 and 112 are reset to zero. The calculation counter 110 is then preset with the nines complement of the scale factor from the multiplication accumulator 118. Further sequencing isinhibited until a first light transmittance reading is obtained from the test chemistry and the value obtained converted to an optical density pulse train and clocked into the optical density counter 108. The contents of this counter 108 is then presetinto the blank storage register 102, nines complemented by the nines complementor .[.104.]. .Iadd.114 .Iaddend.and preset into the optical density counter 108.
A second reading is then taken of the light transmittance of the test chemistry, and the resulting optical density pulse train applied to the optical density counter 108 on top of the nines complemented value of the first reading. The resultingcontents of the optical density counter 108 is then equal to the net change in optical density of the test chemistry in the time interval between the two readings.
This value is then preset into the blank storage register 102 and nines complemented before reinsertion in the optical density counter 108. The multiplier line in the multiply and divide circuits 126 is selected by the programmer 98 and the 100kilohertz output from the master counter 104 is thereby applied to the calculation counter 110. Concurrently, the nines complement of the change in optical density during the time interval is multiplied by the rate of the 100 kilohertz pulses receivedby the digital multiplier 124 from the master counter 104.
The fill detector 128 detects when the number of pulses from the master counter 104 has reached the standard value already in the calculation counter 110 and terminates the one megahertz clock 94 input to the master counter 104 by inhibiting theclock gate 106. The value in the percentage concentration counter 112 represents the amount the optical density of the test chemistry decreased from that of the standard value during the reaction time interval. This value is applied by the printerlogic 132 to the printer 134 for appropriate print out.
It should be understood that the type of kinetic test, i.e., an increasing or decreasing optical density analysis, may be controlled two different ways. One way has just been described in that the programmer 98 changes the electronic processingof the signals in accordance with the type of test under way. Instead of changing or reversing the electronic calculation of the test analysis, the order in which the test chemistries are placed in the flow cell may be reversed to effect the samereversal as that done by the programmer 98.
The actual circuit configuration for the photomultiplier tube output preamp 68 and the combination high voltage supply and comparator 80 and 78 in the automatic gain control path from the output of the preamp 68 to the photomultiplier tube 66, isshown in FIG. 4 and FIG. 5. The comparator 78 and high voltage supply 80 maintain and adjust the sensitivity and gain of the photomultiplier tube resulting from temperature and light frequency variances. The pre-amp 68 includes an operational amplifier140 with a dual field effect transistor (FET) 143 connected across its input leads. A resistive balancing network 144 may be used to adjust the operational amplifier input offset voltage.
The photomultiplier tube 66 is connected to the operational amplifier input FET 142 in a current mode. The photomultiplier tube receives light from the light source and creates a current, due to photoelectric emission, proportional to theintensity of the light reaching it. The output of the operational amplifier (op-amp) 140 is a DC voltage whose level is proportional to the amount of current received by it from the photomultiplier tube. Feedback is provided for the op-amp 140 by aresistor 146 connected from the output of the amplifier 140 to its input. A capacitor 148 is connected in parallel to this resistor 146 to provide high frequency gain suppression.
The pre-amp output is applied to a current summing point 150 in the comparator 78 through a resistor 152. The reference voltage is applied to the comparator 78 from a reference operational amplifier 154 whose input is supplied from a B+ voltagesupply. A Zener diode 156 is used as feedback for the operational amplifier 154 to establish the reference voltage at the output of the op-amp 154. The current resulting from the voltage drop across an adjustable resistor 158 of the reference amplifier154 output is summed at the current summing point 150 with the current originating at the pre-amp output 68.
An FET 160 and its biasing transistor 162 comprise the feedback path switch 76 in the pre-amp to comparator path of FIG. 3. The path from the drain to the source of the FET 160 is closed by the spectro control logic 70 which places a true signalon the base 164 of the biasing transistor 162. Current either flows into or out of the drain 166 of the FET 160 according to the difference between the pre-amp output and the reference amplifier output .[.156.]. .Iadd.154.Iaddend.. The resultingvoltage applied to the dual input FET 168 of a first stage comparator op-amp 170 is the difference between the pre-amp output and the B.sup.+ reference voltage.
The feedback path switch 76 is opened by the flow cell position detection switch .[.84.]. .Iadd.82 .Iaddend.as the empty spectro flow cell is moved into the light path to interrupt the light reaching the photomultiplier tube 66. The output ofthe operational amplifier 170 which is the negation of the voltage on its input 150 is retained when the feedback switch 76 is opened by a feedback capacitor 172 which has charged to this value.
The retained voltage on the output of the first stage comparator op-amp 170 is applied across an input resistor 174 to the summing junction 176 of a second stage comparator op-amp 178. The output terminal 180 of this op-amp 178 is connected tothe variable high voltage supply source 80. More specifically, the output terminal of the second comparator op-amp 178 is inverted by an inverting amp 182 before passing through a pair of current amplifiers 184 and 186. The output of the second currentamplifier 186 is connected to the base of a power amplifier transistor 188. The collector 190 of this transistor 188 is connected to a highly regulated voltage supply C.sup.+. The output of the power gain transistor 188 is applied to the center tap 192of the primary winding 194 of a step-up transformer 196. The two ends 204 and 206 of the primary winding 194 are alternately connected to ground by a chopping multivibrator 198 whose two outputs are connected to power switches 200 and 202. The twoleads 204 and 206 of the primary winding 194 of the transformer 196 are also respectively connected to these power switches 200 and 202. The secondary 208 of the step-up transformer 196 is connected to a voltage doubling and rectifier circuit 210. Thisvoltage doubling circuit 210 has two outputs, one through resistors 212 to the summing junction 176 of the second comparator operational amp 178; and the other output is connected through a resistor-capacitor filter circuit 214 to power thephotomultiplier tube 66.
The output of the voltage doubling circuit 210 which is applied through resistors 212 to the summing junction 176 of the second comparator op-amp 178 is summed at that point with the output voltage of the first comparator 170 which is thedifference between the output of the pre-amp 68 and the output of the reference voltage op-amp 154. The summing junction 176, due to the characteristics of the operational amp 178, must be maintained at zero voltage, or a virtual ground. The outputvoltage moves up and down to effect this zero voltage maintenance. In terms of the photomultiplier tube 66, the moving around of the voltage on the output 180 of the second comparator amp 178 serves as an automatic gain control and sensitivityadjustment.
The placing of a test chemistry in the flow cell and the flow cell being positioned in the light path, as signalled by the flow cell position detection switch 82, signals the spectro control logic 70 to open the pre-amp feedback switch 76 and toselectively close the integrator switch 72 leading from the pre-amp 68 to the integrator 74.
The switch 72 and integrator 74 are shown in detail in FIG. 6. The integrator switch 72 is comprised of an FET 220 which is controlled from a biasing network 222. The biasing network 222 receives a true or positive voltage input from thespectro control logic 70 for the period of time during which the integrator 74 is to integrate the output of the pre-amp 68. The precisely controlled integration interval is preferably 160 milliseconds in duration. During this interval, the positivevoltage applied to the base of the first transistor 224 is inverted and applied to the base of the first transistor 224 is inverted and applied to the base of a second transistor 226 which again inverts the voltage to apply a positive voltage to the gateof the FET 220 to turn the FET on. During its ON period, the FET 220 permits the output of the op-amp 140 in the pre-amp 68 to be applied through a potentiometer 228 and resistor 230 to the gate of a dual FET 232.
This dual FET 232 serves as the input device for the op-amp 234 providing a very low input bias current for the op-amp. The input offset voltage for this op-amp 234, as well as the gate to source FET resistance, is balanced by an adjustableresistance balancing network 236 connected to the other input of the integrator amp 234. Three feedback paths are selectively provided for the amp 234. The first contains the integrating capacitor 238. The second feedback path contains an FETintegrator resetting switch 240 and a serially connected resistor 242. The FET switch 240 is turned on by a biasing network 244 identical to the one hereinbefore described when a positive or true voltage is applied to this network 244.
The third feedback path is provided through an FET swtich 246, a serially connected precise resistance 248 and a potentiometer 250. The FET 246 is controlled by a positive signal applied to its biasing network 252.
The output conductor 254 from the integrator amp 234 is connected to one side of an input resistor 256 of the track and store network 86 shown with the comparator 90 in FIG. 7. It is also connected to one side of a resistor 258 serving as aninput for an inverting amplifier 260 in the crossover comparator 90. The other side of the former resistor 256 is connected to the gate terminal of a dual FET 262 serving as the input device for an op-amp 264. The op-amp 264 inverts the incoming signalfrom the integrator op-amp 234 and applies it through a resistor 266 to the emitter of a transistor 268 used as a Zener diode. The base of this transistor 268 is unconnected. The transistor 268 maintains a voltage on the base of a linear modetransistor 270 of approximately 9 volts to 15 volts DC. The output signal from the second transistor 270, taken from its .[.base.]. .Iadd.collector .Iaddend.electrode, is applied to the drain of an FET 272 which, with its biasing network 274, comprisesthe track and store switch 84. This switch 84 is closed by a positive signal on its input conductor .[.276.]. .Iadd.275 .Iaddend.from the spectro control logic 70 during the integration interval occurring when a test chemistry is being examined. Whenthis switch 84 is closed, the output from the linear mode transistor 270 is connected by the FET 272 to the input resistor 276 leading to the gate of a dual FET 278.
The dual FET 278 is the input device for an integrating amp 280. Feedback for the op-amp 280 is obtained through a feedback capacitor 282. A resistive network 284 is connected to one input of the op-amp 280 to balance the input offset voltageof the operational amp 280. The op-amp 280 integrates the input from the linear mode transistor 270 to negatively duplicate the main integrator 74 output. This integrating op-amp 280 continues to integrate and follow the output of the integrator 74until the expiration of the test chemistry integration interval which causes the spectro control logic 70 to open the track and store input switch 84.
The removal of the input to the integrator 281 stops the integration, but the DC level to which the output has risen is maintained by the feedback capacitor 282. The output of the integrator 281, it should be noted, is also applied to the input286 of an op-amp 288 serving as the basis for the crossover comparator 90.
The inverting amplifier 260 to which the output of the integrator 74 is also connected provides a negation of the integrator output and applies such inverted signal to the other input of the crossover comparator op-amp 288.
In operation, two identical length integration intervals are associated with the analysis of each test chemistry. The first of these is used to integrate the pre-amp 68 output when the test chemistry and flow cell are in the light path fallingon the photomultiplier tube 66. The second interval is used to integrate the pre-amp 68 output when the flow cell is retracted and the light falling on the photomultiplier tube 66 passes through only an air path. Each of these integration intervals is160 milliseconds long. At the beginning of the first of these intervals, the integration switch 72 is turned on to permit the output of the op-amp 140 in the pre-amp 68 to be applied to the input of the integrating operational amp 234. This DC signalis integrated causing the output of the integrator amp 234 to rise in a ramp function. The ramp function is applied to the first operational amp 264 in the track and store section and is limited to a certain voltage range by the transistor 268 used as aZener diode. The resulting DC voltage level is applied through the track and store switch 84 to the input of a second integrator op-amp 280 which integrates the signal for application to one input 286 of the crossover comparator .Iadd.op-amp.Iaddend.288.
The conclusion of the test integration interval signals the control logic 70 to open the track and store FET switch 272 thereby removing the input from the integrating amp 280 so that the DC level to which the output has risen is maintainedacross the feedback capacitor 282. The expiration of the test integrating interval is also used, at a delayed point in time to close the FET 240 in the second feedback path for the integrating amp 234 to provide a rapid discharge of the integratorcapacitor 238. This discharge returns the integrator output to zero.
The flow cell, at the conclusion of its two second inspection cycle, is removed from the light path to the photomultiplier tube 66. This movement is sensed by the flow cell position detection device 82 which signals the spectro control logic 70to begin the second integration interval. This second interval is used to integrate the output of the preamp 68 corresponding to the photomultiplier tube output when the path from the light source is comprised of air only. During the air integration,the integrating amp 234 output is again applied to an amp 264 in the track and store tracking integrator by the closed track and store switch 84. The integrating amp 234 output is also applied through an inverting amplifier 260 to the crossovercomparator .[.288.]. .Iadd.90.Iaddend.. The output of this comparator, as will be seen hereinafter, is inhibited until the termination of the air integration interval.
At the conclusion of the second, or air integration interval, the integrator 74 has integrated to a DC level which is greater than that to which it integrated for the test integration interval. This occurs because the light transmittance of airis always greater than any other material. The FET 246 in the top or third feedback path around the integrating operational amp 234 is turned on by a true pulse from the spectro control logic 70 which also removes the inhibit on the comparator outputlatch 91. The closed feedback switch provides a discharge path through the resistor 248 and adjustable potentiometer 250 for the integrator capacitor 238. The output voltage on the integrating amp 234 is thereby caused to exponentially decay. Theexponential decay continues until the crossover comparing op-amp 288 senses that the output of the integrator 74 has decayed to a DC level equal to that of the DC voltage stored in a track and store integrator 281. When such coincidence is obtained, theoutput of the comparator amp 288 goes false. The amount of time which the output of the comparator op-amp 288 was true after the initiation of the integrator output decay is proportional to the optical density of the test chemistry which was examined.
The output of the comparator op-amp 288 is connected to a latching circuit 91 which applies the crossover comparator output to the optical density counter gate 92 only on command from the control logic 70. The latching of this signal by thelatch 91, will hereinafter be explained in connection with the spectro control logic 70. In general, the latch 91 applies the output of the crossover comparator 90 to the optical density counter gate 92 at the beginning of the decay period on signalfrom the spectro control logic 70.
The spectro control logic 70 is shown in detail in FIGS. 8 and 9. It should be recalled that the flow cell is moved into the light path of the spectro for two seconds and out for two seconds. A signal from the flow cell position detectionswitch 82 applies a signal to a one-shot 290 in the spectro control logic 70 when the flow cell leaves the light path. The output of this one-shot, preferably having a duration of approximately 1.2 seconds, allows the flow cell to get out of the lightpath. The output is applied to a NOR gate 292. At the conclusion of the 1.2 second time period, the negative going edge of the output of the one-shot 290 allows the NOR gate 292 to place a positive pulse at the input of another NOR gate 294. Thesignal from the flow cell position detection switch 82 also initiates the timing cycle of a second one-shot 296 whose output lasts approximately 10 milliseconds. The trailing edge of the output of this one-shot 296 causes the output of a NOR 298 towhich the one-shot 296 is applied to go positive for a short time. The output of this NOR 298 is also applied to the input of the NOR gate 294 so that whenever either of the NOR gate inputs go false the output .Iadd.of the gate 294 .Iaddend.will go truefor the same amount of time.
The output of the one-shot controlled NOR gate 294 is connected to the preset input of a J-K flip-flop 302. One of the outputs 300 of this J-K flip-flop 302 is normally true while the other output 304 is normally false. The normally falseoutput 304 maintains a resetting signal on the reset terminal 305 of an integration interval counter 306 as well as holding a reset signal on the reset input 309 on a 100 hertz oscillator 310, shown in FIG. 10 as part of the programmer 98. This 100hertz clock 310 is controlled by the 1 megahertz clock 94.
The 100 hertz oscillator 310 output is applied to the clocking input of the integration interval counter 306. The expiration of the output signal of the 10 millisecond one-shot 296 results in a preset signal being applied to the J-K flip-flop302. This reverses the signals on the two outputs of the J-K flip-flop 302 such that the formerly false output 304 now becomes true and the formerly true output 300 becomes false. This reversal removes the reset from 100 hertz oscillator 310 and theintegration interval counter 306 so that the integration interval counter 306 begins to be clocked at 100 hertz.
On the 15th clock pulse, a conductor 312 connected to the 2.sup.3 output line of the integration interval counter 306 has a true signal applied to it. On the 16th count this line 312 goes false so that the flip-flop 302, which has its clockingimpulse connected to this conductor 312, is clocked which again reverses the flip-flop outputs. This resets the 100 hertz counter 310 and the integration interval counter 306. This reversal also applies a true signal to the input of two NAND gates 314and 316 which have their inputs connected to the now true terminal 300 of the J-K flip-flop 302.
The output of the first of these NAND gates 314 is connected to the integrator switch 72 between the pre-amp 68 and the integrator 74. The output of this NAND gate 314 was true during the time in which the integration interval counter 306 wasable to count. The resetting of the integration interval counter 306 also removed the true output from this NAND gate 314 which opened the integrator switch 72 to stop the integration.
The output of the other NAND gate 316 is connected to initiate the action of three one-shots 318, 319 and 320 shown in FIG. 8. The second 319 of these one-shots has an output pulse twice as long as the first 318 and the third of these one-shots320 has an output pulse width twice as large as the pulse width of the second one-shot 319. The output of the first one-shot 318 will hereafter be called .[.I.sub.1 .]. .Iadd.T.sub.1.Iaddend., the output of the second one-shot 319 will hereafter becalled .[.I.sub.2 .]. .Iadd.T.sub.2 .Iaddend. and the output of the third one-shot 320 will hereafter be called T.sub.3. T.sub.1 is inverted by an inverting amplifier 322 and applied to a NAND gate 324 to which T.sub.2 is also applied. The output ofthis NAND gate 324 is inverted in another inverting amplifier 326 so that the pulse width of the output of the second inverting amplifier 326 is equal to T.sub.2 minus T.sub.1. In a similar manner, T.sub.2 is inverted in an inverting amplifier 328 andapplied .[.I.sub.2 .]. a NAND gate 330 whose other input is T.sub.3. The output of this NAND gate 330 is negated by an inverting amplifier 332 so that the output of the second inverting amplifier 332 has a pulse width represented by T.sub.3 minusT.sub.2. These two signals T.sub.2 - T.sub.1 and T.sub.3 - T.sub.2 are used with the signals 334 and 335 from the .Badd.1.2 second one-shot 290 leading from the flow cell position detector switch 82. The first of these signals 334 goes true when theflow cell position detector switch 82 applies an input to the one-shot 290. The other one-shot output 335 only goes true at the end of the 1.2 second time interval of the one-shot.
The remaining portion of the spectrophotometer control logic 70 is comprised of the controls for the various functions hereinbefore expalined. These functions are controlled by the use of the various time intervals, i.e., T.sub.1, T.sub.2 -T.sub.1, T.sub.3 - T.sub.2, and the signals from the flow cell position one-shot 290 which are always opposite in sign.
More specifically, the high voltage feedback loop switch 76 (FIG. 3) is controlled through two NAND gates 336 and 337. The output signal from the latter NAND gate 337 is true only when the output of a read command flip-flop 338 controlled by theprogrammer and set when a test reading is sought by the programmer section 98 from the spectro logic section .[.90.]. .Iadd.70 .Iaddend.is false. The other requirement for the high voltage gain adjust switch 76 to be closed is that the 1.2 secondone-shot 290 has timed out, putting a true signal on its second output 335 which signifies that the flow cell is well out of the light path.
The control for the track and store enabling switch 84 comprises two NAND gates 340 and 342 and a flip-flop 344. The flip-flop 344 is normally set so that a true signal is present on its output .[.346.]. 345 which keeps the track and storeswitch 84 closed, enabling the track and store circuit 86 to track the output of the integrator 74. The normally set condition of the flip-flop 344 is the result of the inputs from its controlling NAND gates 340 and 342. The inputs to the first ofthese NAND gates 340 are the time intervals T.sub.1 and the output from the 1.2 second one-shot 290 which goes true for 1.2 seconds when the one-shot 290 is pulsed. This output will be called the "Q" output of the one-shot 290. Its other output will becalled the "not Q" output. The inputs to the other NAND gate 342 are the T.sub.3 - T.sub.2 time interval and the "not Q" output of the 1.2 second one-shot 290. It should be recalled that the Q output of the one-shot 290 is true for 1.2 seconds afterthe flow cell position detection switch 82 initiates its operation. The "not Q" output of the one-shot 290 is always the opposite of the Q output. The T.sub.1, T.sub.2, and T.sub.3 time intervals begin, as mentioned above, after the 160 millisecondintegration interval has been completed. The Q input is always true during the first such integration interval, but since its trailing edge triggers the second integration interval it is always false during that second interval. During the firstintegration interval, the flip-flop 344 is in a set condition and has a true output. At the conclusion of that interval T.sub.1 goes true to reset the output of the flip-flop to zero. This opens the FET 272 in the track and store switch 84 to store theoutput of the integrator 74 in the track and store circuit 86.
The output of the flip-flop 344 remains false until the trailing edge or conclusion of the second integration interval which is used to integrate the air path or reference pre-amp output. At this time, the "not Q" output of the one-shot 290 istrue and, when the time interval T.sub.3 - T.sub.2 occurs, the output of the NAND gate 342 goes true to once again set the flip-flop 344 in preparation for the next test chemistry integration interval.
The expiration of the second integration interval begins the analog to digital conversion of the value to which the test chemistry photomultiplier tube output was integrated. The exponential decay control 346 is comprised of a control NAND 348and an inverting NAND 350. The output of the inverting NAND 350 is connected to operate the FET 246 in the exponential decay switch 88 in the third path of the integrating op-amp 234. This FET 246 is rendered operational by a true output from theinverting NAND 350 in the exponential decay control 346. The conditions needed for this NAND 350 to have a true output are that the control NAND 348 have two true inputs. This condition occurs when the "not Q" signal of the one-shot 290 is true at thesame time that the time interval T.sub.2 - T.sub.1 time interval at the conclusion of the second integration interval.
An integrator reset control 352 is also controlled by the various time intervals created in the spectro control logic 70. The setting of an enabling flip-flop 354 in this resetting control 352 is controlled through an OR gate 356, an invertingNAND gate 358 and a control NAND gate 360. The control NAND 360 has as its inputs the time interval .[.T.sub.2 -T.sub.1 .]. .Iadd.T.sub.3 -T.sub.2 .Iaddend. as well as the "Q" output of the 1.2 second one-shot 290. This combination of inputs to thecontrol NAND 360 enables the inverting NAND 358 to have a true output at the conclusion of the first integration interval. The true output of the inverting NAND 358 is applied through an OR gate 356 to the setting input of the flip-flop 354. Anotherinput to this OR gate 356 is from the flow cell position detection switch 82 which also applies a true signal to the flip-flop 354 when it is actuated. The combination of these signals to the input of the OR gate 356 set the flip-flop 354 when the flowcell moves out of the light path and again at the conclusion of the first integration interval. The output of the flip-flop 354 is used to close the FET 240 in the integrator 74 feedback path to rapidly reset the integrator output to zero.
The enabling flip-flop 354 has a resetting input 366 which is supplied to it through an inverting NAND gate 368 and three control NAND gates 370, 371 and 372. The outputs of the two latter NAND gates 371 and 372 are used to control the formergate 370. This configuration of NAND gates is such that only when both inputs of either of the latter two NAND gates 371 and 372 go true will the flip-flop 354 be reset. The first of these NAND gates 371 has its inputs the "Q" output of the 1.2 secondone-shot 290 and the time interval .Iadd.T.sub.2 -T.sub.1.Iaddend.. This NAND gate 371 thereby causes the resetting of the flip-flop 354 only at the completion of the first integration interval. The second NAND gate 372 has as its inputs the "not Q"output of the 1.2 second one-shot 290 and the signal T.sub.3 - T.sub.2 so that this NAND gate 372 causes the resetting of the flip-flop 354 at the expiration of the T.sub.2 signal subsequent to the second integration interval.
The output of the crossover comparator amplifier 288, as previously mentioned, is applied to the latching circuit 91. The latching circuit comprises a flip-flop 374 and an inverting amplifier 376 leading to the reset line of that flip-flop 374. The input to this inverting amplifier 376 is supplied from the op-amp output 288 in the crossover comparator 90. The setting input 378 of the flip-flop 374 is connected to the output of the inverting NAND gate 350 which, when it goes true, initiates theexponential discharge of the output of the integrating op-amp 234. The initiation of this discharge also sets the flip-flop 374 in the latching circuit 91. The flip-flop 374 continues in this condition until the output of the comparator op-amp 288 goestrue signifying that the integrator 74 has been discharged until its output equals the value of the integrated test chemistry level. The comparator op-amp 288 output is inverted in the inverting amplifier 376 and the resulting false signal on the resetline of the flip-flop 374 resets the output of the flip-flop to zero. The amount of time for which this flip-flop 374 had a true output is thereby representative of the optical density of the particular test chemistry being analyzed.
The output of the latching flip-flop 374 is connected as one input of the optical density counter gate 92 (FIG. 10). This gate is comprised of a NAND gate which has one other input from the one megahertz clock 94 and a third input from theoutput NAND gate 350 in the exponential discharge control 346. The 1 megahertz clock 94 is comprised of a one megahertz crystal oscillator 380 whose output is shaped by a transistor amplifier 382 and inverted by a NAND gate 384 before application to thegating NAND 92. A true signal at the input of the optical density control gate 92 from the latching circuit 91 and from the exponential discharge control 346 enables a 1 megahertz clocking pulse to be applied to a counter 386. This counter 386 is abinary coded decimal counter. Its output is taken from the 2.sup.3 weighted output line so that the line has a negative going signal on it every time the counter 386 has been clocked nine times by the 1 megahertz clock 94. This divides the clockfrequency by 10. The resulting 100 kilohertz output clock pulses are applied to the optical density counter 108.
Each block element in the calculating section 100, as shown in FIG. 3, will be first explained individually with reference to the other blocks. The interaction of the blocks will be explained with more specificity when the details of theprogrammer 98 are explained.
The optical density counter 108, the blank storage register 102 and the nines complementor 114 are shown in FIGS. 11a, 11b, and 12. The optical density counter .[.102.]. .Iadd.108 .Iaddend.is comprised of four stages 390, 391, 392 and 393 whichare combined in a binarily coded decimal counter. The first stage in this counter 390 represents the 100 digit in the decimal equivalent of the optical density. The contents of the remaining three stages 391 - 393 represent the 0.1 place, the 0.01place, and the 0.001 place in the decimal representation of an optical density. For all practical purposes, the optical density never exceeds 1.999 so that the units digit stage 390 is only capable of being set to zero or one.
The output of the optical density counter gate 92 is inverted in a NAND gate 394 before being applied to clock the 0.001 digit 393 of the optical density counter 108. The 2.sup.3 output of this fourth stage 393 is connected by a conductor 396 toclock the third stage 392 each time the fourth stage 393 receives 10 clock pulses from the counter gate 92. In a similar manner, .[.this.]. .Iadd.the .Iaddend.second stage 391 has its 2.sup.3 weighted output line 398 connected to clock the second stage391 when the third stage has received 10 pulses. The first stage 390 is also clocked by the second stage 391 in this same way.
Each of the last three stages 391, 392 and 393 of the optical density counter 108 have four parallel output lines weighted in binary sequence from 2.sup.0 to 2.sup.3. The most significant stage 390 has only one output which has a weight of2.sup.0. The four output lines of each of the last three stages 391 through 393 are applied in parallel to the respective preset lines of a like number of stages in the blank storage register 102. As will be seen below, it is necessary to apply onlythe one output line of the first stage 390 to the corresponding stage 403 in the blank storage register 102.
Each of the first three stages 400 through 402 in the blank storage register 102 pass through a separate but identical stage 404 of the nines complementor 114. Each of the nines complementor stages 404 comprises an inverting amplifier 406, anexclusive OR gate 408 and a NOR gate 410. The 2.sup.0 output line of the blank storage stage is applied to the input of the inverting amplifier 406. The exclusive OR gate 408 has the 2.sup.1 and the 2.sup.2 output lines as its inputs. The NOR gate 410has inputs from the 2.sup.1, 2.sup.2 and 2.sup.3 output lines of the register stage. The 2.sup.2 output line is shorted by a jumper 405 to the 2.sup.2 nines complementor output line.
To use an example for the explanation of the functioning of the nines complementor 404, if the particular stage of the blank storage register has a zero stored in it, the nines complement of that zero would be nine. Each of the four output linesof the particular storage register stage would be false. The false signal applied to the inverting amplifier 406 would yield a true output. The false input to the jumper 405 would thereby have a false output from the nines complementor 404. The twofalse inputs to the exclusive NOR gate would yield a false output. The three false inputs to the NOR gate 410 would yield a true output. The binarily weighted output lines of the nines complementor stage 404 would then be true, false, false and true,respectively which is the binary equivalent of the number nine.
The presetting of the contents of the 1.0 digit stage 390 into its corresponding blank storage stage 403 is different from the presetting of the contents of the remaining stages .[.390-392.]. .Iadd. 391-393 .Iaddend.because this stage .[.393.]. 390 can only have a 1 or 0 content. This stage .[.393.]. .Iadd.390 .Iaddend.is comprised of a clockable J-K flip-flop. When the preset signal is initiated by the programmer 98 to preset the contents of the optical density counter 108 into the blankstorage register 102, the output of the 1.0 digit 390 in the counter 108 is applied to an inverting NAND gate 412 and a setting NAND gate 414 for the 1.0 digit 403 of the blank storage register which also comprises a clockable J-K flip-flop. The outputof the inverting NAND 412 is applied to a resetting NAND 416 along with the output of a second inverting NAND 418 which inverts the preset signal from the programmer 98 applied to its input. The inverted preset signal also serves as the other input tothe setting NAND 414. This combination of NAND gates 412, 414, 416 and 418, upon a preset signal from the programmer 98 sets the J-K flip-flop 403 if the output of the 1.0 stage 390 in the optical density counter was false, and reset it if the outputwere true. This has the effect of storing in the first blank storage register stage 403 the inversion of what was stored in the first stage of the optical density counter and effects a pseudo nines complement of that stage 390.
A preset signal from the programmer 98 may subsequently be applied to the blank storage register stages 400 through 403 to preset the nines complemented form of the number in the storage register stages back into the optical density counterstages 390-393. In many instances, the 100 kilohertz pulse train representing the optical density output from the crossover comparator latch 91 is clocked into the optical density counter 108 after it contains this nines complemented number. Thisprocess has the effect of subtracting the number whose nines complement is in the optical density counter 108 from the incoming value.
Information is also applied to the calculator section 100 from the known standard switch inputs 116 to the percentage concentration counter 112 as shown in FIGS. 13a and 13b. The percentage concentration counter 112 is comprised of four binarycoded decimal output stages 420 through 423. These stages have a weighted value of 10.sup.3, 10.sup.2, 10.sup.1 and 10.sup.0 respectively. Each of these stages 420 through 423 is connected to a common preset line 424. The programmer 98 applies a truesignal to this line 424 to preset each of the values dialed in the known standard switch input 116 into the respective stages in the percentage concentration counter 112.
The clocking input to the units stage 423 of the percentage concentration counter 112 is an output line 426 of the multiply and divide decision circuitry 126. Each of the remaining stages 422, 421 and 420 are clocked by a carry condition in theprevious stage. The binarily weighted outputs of each of the stages 420 through 423 are applied in parallel to corresponding stages 428, 429, 430 and 431 in the multiplication accumulator 118. The parallel outputs of the percentage concentrationcounter 112 are also applied to the printer logic 132.
The contents of the percentage concentration counter 112 is preset into the corresponding stages 428 through 431 in the multiplier accumulator 118 when a preset line 432 connected to each of the stages from the programmer 98 has a true signal onit. The four stages 428 through 431 of the multiplier accumulator are not clocked, but are used as a form of buffer storage for the contents of the percentage concentration counter 112 which are preset into it.
The parallel outputs of the four stages 428 through 431 of the multiplier accumulator are complemented in the nines complementor 120 and the resultant values preset into the corresponding four stages 436 through 439 of the calculator counter 110upon those stages receiving a preset signal on a preset line 440 from the programmer 98. The calculator counter stages 436-439 may also be reset by a signal on a reset line 441 also from the programmer 98.
The nine complementor 120 has individual stages 432 through 435 which are identical in composition to the nines complementor stage 404 described with respect to the nines complementor 114 between the blank storage register 102 and the opticaldensity counter 108.
It should be recalled that in the normal operation or analysis of the test, the calculation counter 110 is normally preset with the nines complement of some scale factor value stored in the multiplier accumulator 118. The counter 110 is thenclocked through the multiply and divide circuitry 126 by either the digital rate multiplier 124 or the master counter 104. This clocking continues until a fill detector 128 detects that the counter 110 has received a number of clock pulses equal to thenumber whose nines complement is stored in that counter 110. More specifically, the filling of the calculator counter 110 with the nines complement of the desired value serves to subtract that value from the total number of incoming pulses. The desirednumber of pulses have been received when the outputs of each of the sta | | | |
