Method and device for the noninvasive determination of hemoglobin and hematocrit

• US 6,662,031 B1
• Filed: 05/08/2000
• Issued: 12/09/2003
• Est. Priority Date: 05/18/1998
• Status: Expired due to Term

• Current Assignee: Abbott Laboratories Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Khalil, Omar S., Jeng, Tzyy-Wen, Hanna, Charles F., Kantor, Stanislaw, Yeh, Shu-jen, Wu, Xiaomao
• Primary Examiner(s): Winakur, Eric F.
• Assistant Examiner(s): KREMER, MATTHEW J
• Application Number:
  US09/566,415
• Time in Patent Office: 1,310 Days
• Field of Search: 600/309-310, 600/322-324, 600/316, 600/326, 356/39-42
• US Class Current: 600/322
• CPC Class Codes: A61B 2562/0233 Special features of optical sensors or probes classified in A61B5/00
• CPC Class Codes: A61B 2562/0242 for varying or adjusting the optical path length in the tissue
• CPC Class Codes: A61B 2562/043 in a linear array
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/14535 for measuring haematocrit
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1491 Heated applicators
• CPC Class Codes: A61B 5/6824 Arm or wrist
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B

Abstract

A method for the determination of hemoglobin and hematocrit by means of an apparatus that is capable of controlling the temperature of a defined subcutaneous volume of human skin. The method involves a calculation of hemoglobin concentration and hematocrit value that takes into consideration the values of optical parameters of the sample at various pre-set temperatures. The apparatus and method employ steady state optical measurements of samples, such as, for example, human tissue, by means of a reflectance tissue photometer and localized control of the temperature of the sample. According to the method of this invention, an optical signal from a defined subcutaneous volume of human skin is measured as the temperature of this volume is controlled. The method and apparatus of this invention allow determination of hemoglobin concentration and hematocrit value non-invasively in a population of subjects having different skin colors by means of steady state reflectance measurements. The method of this invention for determination of hemoglobin concentration and hematocrit value is useful for monitoring patients, testing at the point of care, and screening for anemia. In contrast to other attempts in the prior art that rely on signals of cardiac pulses, the method of this invention has the advantage for the determination of analytes in weak cardiac pulse situations, such as, for example, in elderly patients.

Claims

1. A method for the non-invasive determination of hemoglobin concentration and hematocrit value in human tissue, said method comprising the steps of:

(a) setting the temperature of an area of skin of a body part to a first temperature, said first temperature being below the core temperature of the body,

(b) performing an optical measurement in which at least one light introduction site on the surface of said skin is illuminated by a light beam at a plurality of wavelengths and the light re-emitted from the underlying dermal layers is collected at at least one light collection site, the at least one light introduction site and the at least one light collection site being separated by at least one sampling distance, the at least one sampling distance between said at least one light introduction site and said at least one collection site being selected to restrict the sampling depth of said body part to within the epidermis layer and dermis layer only, whereby contributions from light re-emitted from adipose tissue and muscle tissue are minimized and contributions from light re-emitted from the epidermis and dermis layers are collected, said temperature being maintained at a constant value during said optical measurement,

(c) setting the temperature of said area of said skin of said body part to at least a second temperature that is within the physiological temperature range,

(d) repeating step (b) at said at least second temperature,

(e) determining a plurality of optical parameters at each temperature and determining the dependence of at least one of said aforementioned optical parameters on temperature,

(f) establishing a calibration relationship that relates (1) at least one of said plurality of optical parameters at a given temperature and (2) the dependence of at least one of said plurality of optical parameters on temperature with the concentration of hemoglobin or the hematocrit value measured independently, and

(g) determining the concentration of hemoglobin or the hematocrit value by means of a subsequent determination of the plurality of optical parameters at a given temperature and the dependence of the at least one of said aforementioned optical parameters on temperature and the calibration relationship established in step (f), wherein said biological sample comprises intake human tissue.

2. The method of claim 1, wherein said temperatures at which said area of said skin is maintained ranges from about 15°

C. to about 42°

C.

3. The method of claim 1, wherein said temperatures at which said area of said skin is maintained ranges from about 20°

C. to 40°

C.

4. The method of claim 1, wherein said at least one wavelength of light used ranges from 400 nm to 2500 nm.

5. The method of claim 1, wherein said at least one optical parameter is selected from the group consisting of absorption coefficient, scattering coefficient, effective attenuation coefficient, and light penetration depth in tissue.

6. The method of claim 1, wherein said dependence of optical parameters on temperature includes change in the light penetration depth in tissue as a function of temperature.

7. The method of claim 1, wherein said optical measurement is a spatially resolved diffuse reflectance measurement.

8. The method of claim 1, wherein said distance between said at least one light introduction site and said at least one light collection site ranges from about 0.1 mm to about 10 mm.

9. The method of claim 1, wherein said area of skin of said body part under temperature control and being optically examined covers a volume of tissue ranging from about 0.1 to about 10 cubic millimeters.

10. The method of claim 1, wherein said volume of tissue under temperature control and being optically examined ranges from about 0.2 to about 5 cubic millimeters.

11. The method of claim 1, wherein said volume of tissue under temperature control and being optically examined ranges from about 0.2 to about 2 cubic millimeters.

12. The method of claim 1, wherein said method for establishing said calibration relationship is selected from the group consisting of linear least squares, partial least squares, and principal component analysis.

13. A method for the determination of hemoglobin and hematocrit in human body, said method comprising the steps of:

(a) setting the temperature of an area of skin of a body part to a given temperature, the given temperature being below the core temperature of the body,

(b) performing an optical measurement in which at least one light introduction site on the surface of the skin is illuminated by a light beam at a plurality of wavelengths and the light re-emitted from the underlying dermal layers is collected at at least one light collection site, the at least one light introduction site and the at least one collection site being separated by at least one sampling distance, the at least one sampling distance between the at least one light introduction site and the at least one light collection site being selected to restrict the sampling depth of the body part to within the epidermis layer and dermis layer only, whereby contributions from light re-emitted from adipose tissue and muscle tissue are minimized and contributions from light re-emitted from the epidermis and dermis avers are collected, the given temperature being maintained at a constant value during the optical measurement, whereby the optical measurement generates a measurable signal corresponding to at least one optical parameter,

(c) correlating the measurable signal of step (b) with hemoglobin concentration or hematocrit value determined by an independent method to establish a calibration relationship, and

(d) determining the concentration of hemoglobin or the hematocrit value from a signal from a subsequent optical measurement and the calibration relationship of step (c), wherein said biological sample comprises intact human tissue.

14. The method of claim 13, wherein said temperatures at which said area of said skin is maintained ranges from about 15°

C. to about 42°

C.

15. The method of claim 13, wherein said temperatures at which said area of said skin is maintained ranges from about 20°

C. to 40°

C.

16. The method of claim 13, wherein said at least one wavelength of light used ranges from 400 nm to 2500 nm.

17. The method of claim 13, wherein said at least one optical parameter is selected from the group consisting of absorption coefficient, scattering coefficient, effective attenuation coefficient, and light penetration depth in tissue.

18. The method of claim 13, wherein said optical measurement is a spatially resolved diffuse reflectance measurement.

19. The method of claim 13, wherein said distance between said at least one light introduction site and said at least one light collection site ranges from about 0.1 mm to about 10 mm.

20. The method of claim 13, wherein said area of skin of said body part under temperature control and being optically examined covers a volume of tissue ranging from about 0.1 to about 10 cubic millimeters.

21. The method of claim 13, wherein said area of skin of said body part under temperature control and being optically examined covers a volume of tissue ranging from about 0.2 to about 5 cubic millimeters.

22. The method of claim 13, wherein said area of skin of said body part under temperature control and being optically examined covers a volume of tissue ranging from about 0.2 to about 2 cubic millimeters.

23. The method of claim 13, wherein said method for establishing said calibration relationship is selected from the group consisting of linear least squares, partial least squares, and principal component analysis.