Surgery – Diagnostic testing – Measuring or detecting nonradioactive constituent of body...
Reexamination Certificate
1999-09-09
2002-05-21
Winakur, Eric F. (Department: 3736)
Surgery
Diagnostic testing
Measuring or detecting nonradioactive constituent of body...
C600S310000, C600S328000
Reexamination Certificate
active
06393310
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to noninvasive clinical analyte determination by visible and infrared spectrsocopy, and more particularly, to methods and systems for measuring relative individual percentages of a plurality of hemoglobin species including oxy-, deoxy-, carboxy- and met- hemoglobin (HbO
2
, Hb, HbCO and Hi, respectively) and for measuring hemoglobin species concentrations including, oxyhemoglobin, deoxyhemoglobin, carboxyhemoglobin, methemoglobin and sulfhemoglobin (HbS). These methods and systems may also be applied invasively or to whole blood samples.
BACKGROUND
The measurement of the levels of blood borne analytes, such as hemoglobin species and total hemoglobin concentration in a patient, is an often utilized clinical procedure. Typically, a needle or some other device is used to deeply penetrate a patient's skin and draw a sample, such as blood, which is then analyzed by chemical techniques to determine the concentration of the analyte(s) of interest. The drawbacks of these procedures include the pain and apprehension experienced by the patient, the risk of infection to both the patient and any health care worker handling the sample or the sample-taking device, and the delay in feedback associated with sending the sample to a laboratory for analysis.
The use of absorbance data at multiple wavelengths combined in ratio form and the use of derivative absorbance ratios for noninvasive measurements of hemoglobin was first described in my U.S. Pat. No. 5,377,674, the disclosures of which is hereby incorporated by reference. As set forth in U.S. Pat. No. 5,377,674, hemoglobin concentration may be accurately measured noninvasively (in-vivo), as well as invasively or in whole blood (in-vitro), using many regions of the visible and near-infrared spectrum and many different data treatments. The data treatments which were presented included derivative data treatments which do not require a path-length or scattering measurement and therefore could be readily used with a device modeled on the pulse oximeter to obtain measurements at the peak and trough of blood pulsation. The use of absorbance data at multiple wavelengths combined in ratio form and the use of derivative absorbance ratios for noninvasive measurements of hemoglobin was first described in U.S. Pat. No. 5,377,674.
Spectroscopy deals with the measurement and interpretation of light waves resulting from exposing a substance to a known light wave. The measurements can be based on the reflectance, transmission or emission of the light wave. When exposing a mixture of substances to a known light wave, each of the substances absorbs, to varying degrees, parts of the light wave. As a result of this absorption, a unique light wave is created. Thus, the unique resultant light wave can be measured and interpreted to determine the presence and concentration of substances that comprise the mixture. I have shown in prior work that spectral regions may be normalized prior to PLS analysis by dividing by the area of the absolute value of the derivative spectrum to yield analyte concentration information. (Kuenstner et. al., “Rapid Measurement of Analytes in Whole Blood with NfR Transmittance,”
Leaping Ahead With Near Infrared Spectroscopy
, edited by G. Batten et. al., Proceedings of the 6th International Conference on Near Infrared Spectroscopy at Lorne, Australia in April 1994).
Transmittance, reflectance and emission techniques have been developed for measuring analytes in samples. In general, however, these methods have been found to be accurate for some, but not all, patients. To improve the accuracy, the prior art typically requires the use of complex analysis, complex equipment, or both. Thus, these methods are not well-suited for convenient, quick and simple use.
Additionally, to overcome the delay in feedback associated with sending the sample to a laboratory for analysis, the use of point of care testing has increased. Generally, this type of testing means that patient samples are tested at the bedside or within the intensive care unit of the hospital ward rather than in a centralized laboratory. Many of the present point of care methods, however, are more expensive than the conventional methods. For example, one widely-used point of care device, made by the I-Stat Corporation of Princeton, N.J., analyzes whole blood for sodium, potassium, chloride, CO
2
, urea, glucose and hematocrit. The cost of reagents for this panel of tests is about twelve dollars. In contrast, the reagent cost per analyte for a typical large central laboratory analyzer is approximately a few cents. Thus, the benefit and practicality of current devices providing immediate feedback may be outweighed by the cost, especially given the fiscal constraints of today's hospital environment.
Another point of care device is the pulse oximeter. Current pulse oximeters, however, measure HbO
2
and Hb, and are subject to inaccuracy when there are significant quantities of HbCO and Hi.
Further details and background relating to hemoglobin species concentration measurement may be found in my U.S. Pat. No. 5,692,503, the disclosure of which is also incorporated herein by reference.
SUMMARY OF THE INVENTION
The present invention provides methods and systems for evaluating hemoglobin in a patient. The methods and systems of the present invention may be utilized to measure relative individual percentages of a plurality of hemoglobin species in tissue including oxy-, deoxy-, carboxy- and met- hemoglobin (HbO
2
, Hb, HbCO and Hi, respectively) and to measure total hemoglobin concentration in tissue and/or the concentration of individual hemoglobin species including, oxyhemoglobin, deoxyhemoglobin, carboxyhemoglobin, methemoglobin and sulfhemoglobin (HbS).
According to the methods and systems of the present invention, the relative percentages of a plurality of hemoglobin species and the concentration measurements of hemoglobin species are obtained through the use of spectrophotometric measurements in the visible and/or the short-wavelength near infrared regions. The advantages of using this part of the electromagnetic spectrum include: that light sources, such as LED's, suitable for use in hand-held instruments for the spectrophotometric measurements are currently available; and the possibility of measuring the various species of hemoglobin in addition to the total hemoglobin concentration. The spectrophotometric measurements are described with reference to absorbance, however the methods and systems of the present invention may also utilize other spectrophotometric measurements such as transmission, reflectance or emission.
In a first aspect, methods and systems of the present invention utilize spectrophotometric measurements in the visible region from 510 nanometers (nm) to 620 nm. The resulting spectrophotometric data is normalized by dividing by a difference of spectrophotometric data at two other wavelengths and is entered in a series of four simultaneous equations with four unknowns (the concentrations of HbO
2
, Hb, HbCO and Hi) which can then be solved for each unknown by applying matrix algebra. Insight into the nature of the absorbance spectra of the hemoglobin species shows that one favorable difference term is the absorbance at 510 nm minus the absorbance at 620 nm. At 510 nm and at 620 nm, the absorptivity of all four species is similar but not equal and the difference in absorptivity for each type of hemoglobin between these two points is similar. A difference of absorbance at 510 nm and at 620 nm should not vary greatly regardless of the concentration of the various hemoglobin species in any mixture.
In a second aspect, the methods and systems of the present invention may utilize spectrophotometric measurements in the near-infrared region. Detailed spectroscopic measurements of whole arterial blood in the region from 650 nm to 1000 nm would be obtained. This information is analyzed in order to find the best region or regions for measuring the various hemoglobin species. The spectra would be normalized by divi
Kilpatrick & Stockton LLP
Kremer Matthew
Winakur Eric F.
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