Blood coagulation analyzer
First Claim
1. A method for determining the physical characteristics of a blood sample, comprising:
- producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing a relationship between initial concentrations of plural blood factors and fibrin polymerization at least in part by one non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multivariate backward correlation; and
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample.
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Accused Products
Abstract
One method and apparatus for analyzing clotting characteristics of a blood sample includes the use of a non-linear equation having coefficients capable of being related to the underlying clotting processes. The non-linear equation is curve fit to a waveform of a clotting sample to provide values for the coefficients of the non-linear function. Once the coefficients are obtained, an inference engine may be used to evaluate the non-linear relationship between the coefficients and factor concentrations within the blood sample. Advantageously, the waveform of the actual sample may be detrended to extract a residual oscillatory component to aid in the determination of initial coefficients for simplifying the curve fit operation. The non-linear equation may additionally be used for providing simulated clotting waveforms for testing clot analysis instruments. A residual oscillatory component may advantageously be extracted from the clotting signal. The oscillatory components may be used to provide a high quality clot time indicator for the sample. In addition, the oscillatory component may be used to correct for clot anomalies by correlating the frequency of the oscillatory to various physical characteristics of the blood clot. The oscillatory component may be used to provide initial estimates for values of the coefficients of the logistic. The logistic, because it represents knowledge as to the underlying chemistry of the clotting process, may also be used to provide initial estimates for coefficients of the logistic, and may also be used to enhance the accuracy of existing polynomial template clot analysis techniques. The logistic model may also be used to verify the operation of clot analysis tools.
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Citations
43 Claims
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1. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing a relationship between initial concentrations of plural blood factors and fibrin polymerization at least in part by one non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multivariate backward correlation; and
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample. - View Dependent Claims (2, 3, 6, 7, 8, 15, 17, 18, 19, 20)
estimating initial values of the plurality of coefficients of the non-linear function.
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15. The method for determining the physical characteristics of a blood sample of claim 1 wherein the physical parameters are selected from a group consisting essentially of initial concentration of blood clotting factors in the blood sample, anti-coagulants, FDP, d-dimer, selected chemistry anti-coagulants and antibodies.
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17. The method according to claim 1 wherein the first signal is produced by an optical nephelometer, and the density signal indicates a turbidity of the blood sample.
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18. The method according to claim 1 wherein the first signal is produced by a Fiberometer.
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19. The method for determining the physical characteristics of a blood sample according to claim 3, wherein the step of transforming further comprises the steps of:
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modifying the values of the plurality of coefficients to correct exception conditions; and
translating the modified values of the plurality of coefficients to the derived physical parameters of the blood sample according to a defined operative function.
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20. The method for determining the physical characteristics of a blood sample according to claim 19, wherein the means for translating the modified values comprises a multi-variate general linear hypothesis mechanism.
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4. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation; and
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample;
wherein the physical parameters include clot time; and
wherein the clot time substantially correlates with one of the plurality of coefficients representing a centroid location of the non-linear function.
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5. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation;
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample;
wherein the physical parameters include clot time; and
wherein the clot time substantially correlates to a centroid location of the second derivative of the non-linear function.
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9. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation;
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample;
wherein curve fitting further includes estimating initial values of the plurality of coefficients of the non-linear function; and
wherein estimating initial values determines the values of the plurality of coefficients responsive to characteristics of a low-level oscillatory component of the first signal.
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10. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation;
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample;
wherein curve fitting further includes estimating initial values of the plurality of coefficients of the non-linear function; and
wherein estimating initial values determines the values of the plurality of coefficients responsive to characteristics of the first derivative and second derivative of the first signal. - View Dependent Claims (11)
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12. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation;
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample;
wherein curve fitting further includes estimating initial values of the plurality of coefficients of the non-linear function; and
wherein the non-linear function is a polynomial function, and wherein estimating initial values of the coefficients derives the coefficients responsive to characteristics of a third derivative of the polynomial function. - View Dependent Claims (13, 14)
searching for vanishing points of the third derivative of the polynomial function to identify bounds of the third derivative of the polynomial function for analysis;
iteratively modifying the bounds of the polynomial to curve fit to the first signal to identify a plurality of potential centroid locations of the polynomial, wherein each of the plurality of identified centroid locations are stored in a table with an associated chi square error of the curve fit;
modifying the error values in the table by applying a penalty value to each of the error values in the table responsive to chaotic characteristics of the first signal; and
selecting one of the centroid locations of the plurality of centroid locations as an initial estimated coefficient responsive to the modified error value associated with the selected centroid location in the table.
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14. The method for determining the physical characteristics of a blood sample according to claim 13, wherein the step of searching for vanishing points of the third derivative of the polynomial is controlled responsive to information from the non-linear function.
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16. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation; and
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample;
wherein the non-linear function is where a, b c, d, e, f and g represent the plurality of coefficients and t represents time.
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21. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation;
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample;
transforming the values of the plurality of coefficients to provide derived physical parameters of the blood sample;
wherein transforming further includes;
modifying the values of the plurality of coefficients to correct exception conditions;
translating the modified values of the plurality of coefficients to the derived physical parameters of the blood sample according to a defined operative function; and
wherein translating the modified values is performed using a neural network.
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22. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation;
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample;
transforming the values of the plurality of coefficients to provide derived physical parameters of the blood sample;
wherein transforming further includes;
modifying the values of the plurality of coefficients to correct exception conditions;
translating the modified values of the plurality of coefficients to the derived physical parameters of the blood sample according to a defined operative function; and
wherein translating the modified values optimizing is performed using fuzzy logic.
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23. A method for determining the physical characteristics of a blood sample, comprising the steps of:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time; and
extracting a low level oscillation signal from the optical density signal, wherein the low level oscillation signal is used to determine the characteristics of the blood sample. - View Dependent Claims (24, 34, 39)
providing a mathematical model of the measurement of fibrin polymerization of the blood sample over the given period of time, the mathematical model comprising a plurality of coefficients, wherein the mathematical model is curve fit to the first signal provided by the detector and wherein values of the coefficients may be used to identify physical characteristics of the blood sample; and
determining, responsive to the low level oscillation signal, initial estimates of the coefficients of the mathematical model for the curve fit.
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39. The method for determining the physical characteristics of a blood sample according to claim 23 further comprising the step of:
filtering the first signal to reduce a number of the first signals that are transferred to the curve fitter.
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25. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation;
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample;
extracting a low level oscillation signal from the first signal, wherein the low level oscillation signal is used to determine the characteristics of the blood sample; and
determining a clot time of the blood sample responsive to the low level oscillation signal;
wherein determining the clot time of the blood sample includes analyzing the frequency of the low level oscillation signal using an analysis method selected from the group consisting of Fourier analysis, fast Fourier transform analysis, wavelet analysis, peak and minimum search analysis and phase locked analysis.
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26. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation;
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample;
extracting a low level oscillation signal from the first signal, wherein the low level oscillation signal is used to determine the characteristics of the blood sample;
determining, responsive to the low level oscillation, characteristics of the blood sample; and
correcting characteristic estimations of the blood sample responsive to frequency of the low level oscillation. - View Dependent Claims (27, 28, 29, 30, 31, 32, 33)
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35. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation;
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample;
extracting a low level oscillation signal from the first signal, wherein the low level oscillation signal is used to determine the characteristics of the blood sample;
providing a mathematical model of the measurement of fibrin polymerization of the blood sample over the given period of time, the mathematical model comprising a plurality of coefficients, wherein the mathematical model is curve fit to the first signal provided by the detector and wherein values of the coefficients may be used to identify physical characteristics of the blood sample; and
determining, responsive to the low level oscillation signal, initial estimates of the coefficients of the mathematical model for the curve fit;
wherein determining the clot time of the initial coefficients includes analyzing the frequency of the low level oscillation signal using an analysis method selected from the group consisting of Fourier analysis, fast Fourier transform analysis, wavelet analysis, peak and minimum search analysis and phase locked loop analysis.
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36. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation;
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample;
extracting a low level oscillation signal from the first signal, wherein the low level oscillation signal is used to determine the characteristics of the blood sample;
providing a mathematical model of the measurement of fibrin polymerization of the blood sample over the given period of time, the mathematical model comprising a plurality of coefficients, wherein the mathematical model is curve fit to the first signal provided by the detector and wherein values of the coefficients may be used to identify physical characteristics of the blood sample; and
determining, responsive to the low level oscillation signal, initial estimates of the coefficients of the mathematical model for the curve fit;
wherein the mathematical model is represented by the below equation;
where a, b c, d, e, f and g represent the plurality of coefficients and t represents time.
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37. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation;
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample; and
extracting a low level oscillation signal from the first signal, wherein the low level oscillation signal is used to determine the characteristics of the blood sample;
wherein extracting the low level oscillation signal is performed using residuals analysis of the first signal.
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38. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation;
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample; and
extracting a low level oscillation signal from the first signal, wherein the low level oscillation signal is used to determine the characteristics of the blood sample;
wherein extracting the low level oscillation signal performs a repetitive polynomial detrending of the first signal to retrieve the low level oscillation signal.
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40. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation;
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample;
extracting a low level oscillation signal from the first signal, wherein the low level oscillation signal is used to determine the characteristics of the blood sample; and
identifying blood samples having weak clotting characteristics, wherein identifying includes polynomial detrending which removes external noise from the first signal by adjusting values of a portion the accumulated data signals; and
interpolating which smoothes the interface between said adjusted portion of said accumulated data signals and remaining accumulated data signals.
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41. A method for determining the physical characteristics of a blood sample, comprising:
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producing a first signal indicative of a measurement of fibrin polymerization of a blood sample over a period of time;
providing an analytical model of fibrin polymerization of the blood sample over a period of time, the model representing at least in part by a non-linear function having a plurality of coefficients which are related to the initial concentration of plural blood factors through multi-variate backward correlation;
curve fitting the model to the first signal to produce an output representing values of the plurality of coefficients causing the model to conform to the first signal, wherein the values of the plurality of coefficients are used to identify physical parameters of the blood sample;
storing, for each manipulation of the bounds of the polynomial model, a difference between the bounded waveform and the first signal, the table also for storing a centroid location of the associated model; and
selecting the bounds of the polynomial model responsive to a non-linear logistic model of the first signal. - View Dependent Claims (42, 43)
selecting one of the centroid locations of one of the plurality of models as a clot time of the blood sample responsive to the corresponding difference signal of the model.
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43. The method for determining the clotting characteristics of a blood sample according to claim 41, further comprising the steps of:
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storing, in a penalty table, a plurality of penalties, each penalty corresponding to the unit of time of one of the first signals and representing potential chaotic behavior of the first signal at the unit of time; and
applying the plurality of penalties to the differences in the table, wherein one of the plurality of penalties is selected for applying to one of the stored differences responsive to the centroid location of the model.
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Specification