EP0419223A2
Expired / Lapsed
EP
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Characterizing biological matter in a dynamic condition using near infrared spectroscopy
Assignee: University of Washington
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Filing: 1990-09-18
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Granted: —
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Expires: 2010-09-18
Abstract
Abstract A method is provided for predicting a property of a matter of biological origin, such as biological fluid, containing water, in a dynamic condition where the biological fluid may be approximated to contain two compartments where one compartment has a proportionally larger or smaller amount of water than the other compartment having the property of interest. The method involves establishing a training set in the near-infrared (NIR) region with independent quantification of the property of the fluid using known techniques. The training set is mathematically analyzed according to a correlation developed by regression analysis after employment of a pre-processing technique such as a multiple derivative transformation of spectra or a ratioing of two wavelengths in the spectra. The result is a mathematical transformation equation which quantitatively relates spectral intensities at specific wavelengths to the property of interest. This transformation equation may be applied to unknown samples so as to predict their properties, thereby eliminating need for the reference method except for validation or recalibration. The method provides rapid and accurate prediction of the property of the unknown sample, which may be the property of hematocrit or hemoglobin concentration in whole animal blood. Other analyses of properties in the biological fluid such as oxygen saturation in hemoglobin in whole animal blood may be included in the mathematical analysis to further refine the prediction of the property of interest. Also, a loop from the patient is disclosed for the purpose of monitoring the property of interest nearly simultaneously with changes in that property of interest.
Inventors
- 👤 James B. C/O Board Of Regents Of The Callis
- 👤 David W. C/O Minnesota Mining And Osten
- 👤 Hatim M. C/O Minnesota Mining And Carim
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-06 07:10
CPC Classifications
A; A61; A61B; A61B5/00; A61B5/145; A61B5/14535; A61B5/1455; A61B5/14551; A61B5/14557; A61B5/72; A61B5/7235; A61B5/7239; G; G01; G01N; G01N21/00; G01N21/17; G01N21/25; G01N21/31; G01N21/35; G01N21/359; G01N2201/00; G01N2201/12; G01N2201/129
Claims Analysis
Total Claims: 35
Claim 1
Independent Claim
195 words
A method for analyzing a property of biological matter having a water content in a dynamic condition, the biological matter comprising a first compartment related to the property to be analyzed and a second compartment having a proportionally larger or smaller amount of water than the first compartment, the method comprising: (a) observing multiple samples of biological matter in a dynamic condition; (b) irradiating with near infrared light said multiple samples of the biological matter; (c) detecting the near infrared absorption spectrum of each of said multiple samples; (d) applying a ratio pre-processing technique to the absorption spectrum of each of said multiple samples; (e) independently quantifying the property to be analyzed for each of said multiple samples; (f) establishing a training set from said near infrared absorption spectra of said multiple samples; and (g) statistically identifying the nature of a mathematical correlation between the property to be analyzed in the first compartment and the water content in the biological matter; wherein said ratio pre-processing technique comprises applying a ratio of a near-infrared wavelength absorbance peak of the water content in said training set to another near-infrared wavelength absorbance measuring point in said training set.
Claim 2
Independent Claim
195 words
A method for analyzing a property of biological matter having a water content in a dynamic condition, the biological matter comprising a first compartment related to the property to be analyzed and a second compartment having a proportionally larger or smaller amount of water than the first compartment, the method comprising: (a) observing multiple samples of biological matter in a dynamic condition; (b) irradiating with near infrared light said multiple samples of the biological matter; (c) detecting the near infrared absorption spectrum of each of said multiple samples; (d) applying a ratio pre-processing technique to the absorption spectrum of each of said multiple samples; (e) independently quantifying the property to be analyzed for each of said multiple samples; (f) establishing a training set from said near infrared absorption spectra of said multiple samples; and (g) statistically identifying the nature of a mathematical correlation between the property to be analyzed in the first compartment and the water content in the biological matter; wherein said ratio pre-processing technique comprises applying a ratio of a near-infrared wavelength absorbance peak of the water content in said training set to another near-infrared wavelength absorbance measuring point in said training set.
Claim 3
Dependent Claim
84 words
A method according to Claim 1, further comprising the steps of: (h) observing an unknown sample of the biological matter in a dynamic conditioning; (i) irradiating said unknown sample of the biological matter with near infrared light; (j) detecting the near infrared spectrum of said unknown sample; (k) applying said ratio pre-processing technique to said spectrum of said unknown sample; and (l) predicting the property to be analyzed in said unknown sample by utilizing said mathematical correlation obtained in said statistically identifying step (g).
Claim 4
Dependent Claim
29 words
A method according to Claim 1, wherein said statistically identifying step (g) uses linear regression analysis, multiple linear regression analysis, stepwise regression analysis, or partial least squares regression analysis.
Claim 5
Dependent Claim
45 words
A method according to Claim 1 or Claim 2, wherein said mathematical correlation in said statistically identifying step (g) comprises a linear function related to a near infrared absorbance peak of water in the absorbance spectra of said multiple samples subjected to said pre-processing technique.
Claim 6
Dependent Claim
35 words
A method according to Claim 1 or Claim 2, wherein the biological matter is whole blood and the property of the first compartment to be analyzed is hematocrit or hemoglobin concentration in the whole blood.
Claim 7
Dependent Claim
52 words
A method according to Claim 1 or Claim 2, wherein the biological matter is whole blood and said absorbance peak of water occurs in the near infrared spectra from about 1150 to about 1190 nanometers, and said another near infrared wavelength absorbance measuring point is the isosbestic point of oxyhemoglobin and deoxyhemoglobin.
Claim 8
Dependent Claim
47 words
A method according to Claim 2, wherein said detecting step (c) and said detecting step (j) use spectral analysis instrumentation which records said absorbance spectra of said multiple samples and said unknown sample in the dynamic condition of the biological matter flowing through the spectral analysis instrumentation.
Claim 9
Dependent Claim
66 words
A method according to Claim 2, wherein the property to be analyzed is hematocrit and said mathematical correlation solves the equation: Y = b + m * (Absorbance at an Isosbestic Point of Deoxyhemoglobin and Oxyhemoglobin/Absorbance at said Absorbance Peak of Water) where Y is the value of hematocrit, b ranges from about -70 to about -128, and m ranges from about 78 to about 126.
Claim 10
Dependent Claim
66 words
A method according to Claim 2, wherein the property to be analyzed is hemoglobin concentration and said mathematical correlation solves the equation: Y = b + m * (Absorbance at an Isosbestic Point of Deoxyhemoglobin and Oxyhemoglobin/Absorbance at said Absorbance Peak of Water) where Y is the hemoglobin concentration, b ranges from about -23 to about -45, and m ranges from about 26 to about 44.
Claim 11
Dependent Claim
94 words
A method according to Claim 1, further comprising the steps of: (1) observing additional samples of biological matter in a dynamic condition; (2) independently quantifying the property to be analyzed for each of said additional samples; (3) performing steps (b), (c), and (d) with respect to said additional samples; (4) predicting the property to be analyzed in said additional samples by utilizing said mathematical correlation obtained in said statistically identifying step (g); and (5) validating said mathematical correlation by comparing the property predicted in step (4) to the property independently quantified in step (2).
Claim 12
Independent Claim
158 words
A method for the analysis of a biological fluid having a water content, in a dynamic condition, comprising: observing multiple samples of a moving biological fluid of at least one organism, where the biological fluid may be approximated to comprise two compartments where one compartment has a proportionally different amount of water than the other compartment which has a property of interest; determining the two best absorbance detection points of the near infrared spectrum of each of said multiple samples; independently measuring the quantity of the property to be analyzed in each of said multiple samples; applying a ratio of said two best absorbance measuring points; identifying a mathematical correlation of the property to be analyzed and the water content in the biological fluid; and analyzing an unknown sample of the biological fluid to determine the property to be analyzed in said unknown sample by applying said mathematical correlation to a near infrared spectrum of said unknown sample.
Claim 13
Independent Claim
158 words
A method for the analysis of a biological fluid having a water content, in a dynamic condition, comprising: observing multiple samples of a moving biological fluid of at least one organism, where the biological fluid may be approximated to comprise two compartments where one compartment has a proportionally different amount of water than the other compartment which has a property of interest; determining the two best absorbance detection points of the near infrared spectrum of each of said multiple samples; independently measuring the quantity of the property to be analyzed in each of said multiple samples; applying a ratio of said two best absorbance measuring points; identifying a mathematical correlation of the property to be analyzed and the water content in the biological fluid; and analyzing an unknown sample of the biological fluid to determine the property to be analyzed in said unknown sample by applying said mathematical correlation to a near infrared spectrum of said unknown sample.
Claim 14
Independent Claim
167 words
A method for analyzing a property of whole animal blood having a water content, the whole animal blood comprising a first compartment related to the property to be analyzed and a second compartment having a proportionally larger or smaller amount of water than the first compartment, the method comprising: (a) irradiating with near infrared light multiple samples of the whole animal blood; (b) detecting the near infrared spectrum of each of said multiple samples; (c) applying a pre-processing technique to the spectrum of each of said multiple samples; (d) independently quantifying the property to be analyzed for each of said multiple samples; (e) independently quantifying a value proportional to the percentage oxygen saturation in the whole animal blood for each of said multiple samples; (f) establishing a training set from said near infrared spectra of said multiple samples; and (g) statistically identifying the nature of a mathematical correlation between the property to be analyzed in the first compartment and the water content in the whole animal blood.
Claim 15
Independent Claim
167 words
A method for analyzing a property of whole animal blood having a water content, the whole animal blood comprising a first compartment related to the property to be analyzed and a second compartment having a proportionally larger or smaller amount of water than the first compartment, the method comprising: (a) irradiating with near infrared light multiple samples of the whole animal blood; (b) detecting the near infrared spectrum of each of said multiple samples; (c) applying a pre-processing technique to the spectrum of each of said multiple samples; (d) independently quantifying the property to be analyzed for each of said multiple samples; (e) independently quantifying a value proportional to the percentage oxygen saturation in the whole animal blood for each of said multiple samples; (f) establishing a training set from said near infrared spectra of said multiple samples; and (g) statistically identifying the nature of a mathematical correlation between the property to be analyzed in the first compartment and the water content in the whole animal blood.
Claim 16
Dependent Claim
84 words
A method according to Claim 12, further comprising the steps of: (h) irradiating an unknown sample of whole animal blood with near infrared light; (i) detecting the near infrared spectrum of said unknown sample; (j) applying said pre-processing technique to said spectrum of said unknown sample; (k) determining a value proportional to the percent oxygen saturation of the unknown sample; and (l) predicting the property to be analyzed in said unknown sample by utilizing said mathematical correlation obtained in said statistically identifying step (g).
Claim 17
Dependent Claim
56 words
A method according to Claim 12, wherein said statistically identifying step (g) uses multiple linear regression analysis, multiple stepwise regression analysis, partial least squares regression analysis and wherein said statistically identifying step (g) uses the independently quantified percent oxygen saturation in said multiple samples as a regression variable in said analysis to determine said mathematical correlation.
Claim 18
Dependent Claim
53 words
A method according to Claim 12 or 13, wherein said mathematical correlation in said statistically identifying step (g) comprises a linear function related to a near infrared absorbance peak of water in the absorbance spectra of said multiple samples subjected to said pre-processing technique and the percent oxygen saturation in said multiple samples.
Claim 19
Dependent Claim
33 words
A method according to Claim 12 or 13, wherein said pre-processing technique comprises transforming said spectra of said multiple samples of said training set by computing a multiple derivative of said multiple samples.
Claim 20
Dependent Claim
44 words
A method according to Claim 12 or 13, wherein said pre-processing technique comprises applying a ratio of a near infrared wavelength absorbance peak of the water content in said training set to another near infrared wavelength absorbance measuring point in said source spectra set.
Claim 21
Dependent Claim
27 words
A method according to Claim 12 or 13, wherein the property of the first compartment to be analyzed is hematocrit or hemoglobin concentration in the whole blood.
Claim 22
Dependent Claim
59 words
A method according to Claim 12 or 13, wherein said water content has an absorbance peak in the near infrared spectra from about 1150 to about 1190 nanometers and the biological fluid has an isosbestic point of oxyhemoglobin and deoxyhemoglobin and wherein said pre-processing technique comprises applying a ratio of said water content absorbance peak to said isosbestic point.
Claim 23
Dependent Claim
48 words
A method according to Claim 13, wherein said detecting step (b) and said detecting step (i) use spectral analysis instrumentation which records said absorbance spectra of said multiple samples and said unknown sample in the dynamic condition of the whole animal blood flowing through the spectral analysis instrumentation.
Claim 24
Dependent Claim
120 words
A method according to Claim 13, wherein the property to be analyzed is hematocrit and said mathematical correlation solves the equation: C = B₀ + B₁ (A₁) + B₂ (A₂) where C is the Hematocrit; B₀ ranges from about -31 to about 32; where A₁ is a value proportional to the percent oxygen saturation and B₁ is a regression coefficient for the percent oxygen saturation and ranges from about -0.4 to about 36; where A₂ is a second derivative transformation of an absorbance peak of water and ranges from about 1160 to about 1175 nm and B₂ is a regression coefficient of a second derivative transformation of said absorbance peak of water and ranges from about 439 to about 496.
Claim 25
Dependent Claim
124 words
A method according to Claim 13, wherein the property to be analyzed is concentration of hemoglobin and said mathematical correlation solves the equation: C = B₀ + B₁ (A₁) + B₂ (A₂) where C is the concentration of hemoglobin; B₀ ranges from about -11 to about 11; where A₁ is a value proportional to the percent oxygen saturation and B₁ is the regression coefficient for the percent oxygen saturation and ranges from about -0.08 to about 13; where A₂ is a second derivative transformation of an absorbance peak of water and ranges from about 1160 to about 1175 nm and B₂ is a regression coefficient of a second derivative transformation of an absorbance peak of water and ranges from about 147 to about 169.
Claim 26
Dependent Claim
118 words
A method according to Claim 13, wherein the property to be analyzed is hematocrit and said mathematical correlation solves the equation: C = B₀ + B₁ (A₁) + B₂ (A₂) where C is the Hematocrit; B₀ ranges from about -106 to about -134; where A₁ is a value proportional to the percent oxygen saturation and B₁ is a regression coefficient for the percent oxygen saturation and ranges from about -15 to about 0.1; where A₂ is a ratio of the Absorbance at an Isosbestic Point of Dexoyhemoglobin and Oxyhemoglobin to an Absorbance at an Absorbance Peak of Water and B₂ is a regression coefficient of an absorbance peak of water and ranges from about 116 to about 121.
Claim 27
Dependent Claim
121 words
A method according to Claim 13, wherein the property to be analyzed is hemoglobin concentration and said mathematical correlation solves the equation: C = B₀ + B₁ (A₁) + B₂ (A₂) where C is the concentration of hemoglobin; B₀ ranges from about -46 to about -36; where A₁ is a value proportional to the percent oxygen saturation and B₁ is a regression coefficient for the percent oxygen saturation and ranges from about -5 to about 0.02; where A₂ is a ratio of an Absorbance at an Isosbestic Point of Deoxyhemoglobin and Oxyhemoglobin to an Absorbance at an Absorbance Peak of Water and B₂ is a regression coefficient of an absorbance peak of water and ranges from about 40 to about 42.
Claim 28
Dependent Claim
24 words
A method according to Claim 12 or 13, wherein said multiple samples are of at least one known organism of a given biological species.
Claim 29
Dependent Claim
58 words
A method according to Claim 13, wherein, to measure the percent oxygen saturation of the unknown sample, said determining step (k) comprises using a pulse oximeter, a co-oximeter, or the ratio of absorbances of two wavelengths where the ratio of extinction coefficients for oxyhemoglobin and deoxyhemoglobin at one wavelength is different than that ratio at the second wavelength.
Claim 30
Dependent Claim
120 words
A method according to Claim 12, further comprising the steps of: (1) observing additional samples of biological matter in a dynamic condition; (2) independently quantifying the property to be analyzed for each of said additional samples; (3) independently quantifying a value proportional to the percentage oxygen saturation in the whole animal blood for each of said additional samples; (4) performing steps (a), (b), and (c) with respect to said additional samples; (5) predicting the property to be analyzed in said additional samples by utilizing said mathematical correlation obtained in said statistically identifying step (g); and (6) validating by a statistical method said mathematical correlation by comparing the property predicted in step (5) to the property independently quantified in step (2).
Claim 31
Independent Claim
129 words
A method for the analysis of a whole blood having a water content comprising: observing multiple samples of whole blood of at least one organism, where the whole blood may be approximated to comprise two compartments where one compartment has a proportionally different amount of water than the other compartment which has a property of interest; determining the best absorbance detection point comprising the absorbance peak of the water content in the near infrared spectrum of each of said multiple samples; independently measuring the quantity of the property to be analyzed in each of said multiple samples and a value proportional to percent oxygen saturation of each of said multiple samples; identifying a mathematical correlation of the property to be analyzed and the water content in the whole blood.
Claim 32
Independent Claim
129 words
A method for the analysis of a whole blood having a water content comprising: observing multiple samples of whole blood of at least one organism, where the whole blood may be approximated to comprise two compartments where one compartment has a proportionally different amount of water than the other compartment which has a property of interest; determining the best absorbance detection point comprising the absorbance peak of the water content in the near infrared spectrum of each of said multiple samples; independently measuring the quantity of the property to be analyzed in each of said multiple samples and a value proportional to percent oxygen saturation of each of said multiple samples; identifying a mathematical correlation of the property to be analyzed and the water content in the whole blood.
Claim 33
Dependent Claim
41 words
A method according to Claim 28, further comprising: analyzing an unknown sample of the whole blood to determine the property to be analyzed in said unknown sample by applying said mathematical correlation to a near infrared spectrum of said unknown sample.
Claim 34
Independent Claim
231 words
A method for monitoring a property of interest in whole blood of a live patient, nearly simultaneously with flow of the whole blood in the patient, comprising: (a) establishing a blood flow loop having a diversion section departing from the patient terminating at a flow cell, a return section returning to the patient beginning at a flow cell, and a bypass section between the diversion section and the return section; (b) flowing the whole blood through the blood loop; (c) using near infrared detecting means to monitor the property of interest in the whole blood flowing through the blood loop; and (d) identifying the value of the property of interest using a method of correlation of a linear functional relationship; wherein said linear functional relationship comprises (1) observing multiple samples of whole blood of at least one organism, where the whole blood may be approximated to comprise two compartments where one compartment has a proportionally different amount of water than the other compartment which has the property of interest; (2) determining the best absorbance detection point comprising the absorbance peak of the water content in the near infrared spectrum of each of said multiple samples; (3) independently measuring the quantity of the property to be analyzed in each of said multiple samples; (4) identifying a mathematical correlation of the property to be analyzed and the water content in the whole blood.
Claim 35
Independent Claim
231 words
A method for monitoring a property of interest in whole blood of a live patient, nearly simultaneously with flow of the whole blood in the patient, comprising: (a) establishing a blood flow loop having a diversion section departing from the patient terminating at a flow cell, a return section returning to the patient beginning at a flow cell, and a bypass section between the diversion section and the return section; (b) flowing the whole blood through the blood loop; (c) using near infrared detecting means to monitor the property of interest in the whole blood flowing through the blood loop; and (d) identifying the value of the property of interest using a method of correlation of a linear functional relationship; wherein said linear functional relationship comprises (1) observing multiple samples of whole blood of at least one organism, where the whole blood may be approximated to comprise two compartments where one compartment has a proportionally different amount of water than the other compartment which has the property of interest; (2) determining the best absorbance detection point comprising the absorbance peak of the water content in the near infrared spectrum of each of said multiple samples; (3) independently measuring the quantity of the property to be analyzed in each of said multiple samples; (4) identifying a mathematical correlation of the property to be analyzed and the water content in the whole blood.
References Cited (Backward Citations)
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