Reagentless analysis of biological samples

• US 20040197927A1
• Filed: 04/22/2004
• Published: 10/07/2004
• Est. Priority Date: 08/27/1998
• Status: Active Grant

• Current Assignee: Eric B. Shain, Gary M. Oosta, Joseph Larry Pezzaniti, Larry L. Mcdowell, Tzyy-Wen Jeng
• Original Assignee: Eric B. Shain, Gary M. Oosta, Joseph Larry Pezzaniti, Larry L. Mcdowell, Tzyy-Wen Jeng
• Inventors: Shain, Eric B., Jeng, Tzyy-Wen, McDowell, Larry L., Oosta, Gary M., Pezzaniti, Joseph Larry
• Granted Patent: US 7,303,922 B2
• Time in Patent Office: Days
• US Class Current: 436/171
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/274 Calibration, base line adjustment, drift correction
• CPC Class Codes: G01N 21/4133 Refractometers, e.g. differential
• CPC Class Codes: Y10T 436/144444 Glucose
• CPC Class Codes: Y10T 436/146666 Bile pigment
• CPC Class Codes: Y10T 436/147777 Plural nitrogen in the same ring [e.g., barbituates, creatinine, etc.]
• CPC Class Codes: Y10T 436/171538 Urea or blood urea nitrogen
• CPC Class Codes: Y10T 436/200833 Carbonyl, ether, aldehyde or ketone containing

Abstract

Apparatus and method for determining at least one parameter, e. g., concentration, of at least one analyte, e. g., urea, of a biological sample, e. g., urine. A biological sample particularly suitable for the apparatus and method of this invention is urine. In general, spectroscopic measurements can be used to quantify the concentrations of one or more analytes in a biological sample. In order to obtain concentration values of certain analytes, such as hemoglobin and bilirubin, visible light absorption spectroscopy can be used. In order to obtain concentration values of other analytes, such as urea, creatinine, glucose, ketones, and protein, infrared light absorption spectroscopy can be used. The apparatus and method of this invention utilize one or more mathematical techniques to improve the accuracy of measurement of parameters of analytes in a biological sample. The invention also provides an apparatus and method for measuring the refractive index of a sample of biological fluid while making spectroscopic measurements substantially simultaneously.

Claims

1-46. -46. (canceled)

47. A method for reducing noise in a determination of concentration of at least one analyte of interest in a biological sample by means of spectroscopic analysis, said method comprising the steps of:

(a) identifying a mathematical function that is substantially similar to a region of a non-smoothed spectrum of said sample over a selected range of the non-smoothed spectrum;

(b) selecting a portion of said region of said non-smoothed spectrum such that noise in said selected portion is substantially random;

(c) determining coefficients of said mathematical function that result in a close fit of the function to said selected portion of said non-smoothed spectrum;

(d) calculating at least one value of said non-smoothed spectrum at at least one wavelength of said non-smoothed spectrum by means of said coefficients and said mathematical function of step (c), wherein said at least one wavelength includes the center of said region of said non-smoothed spectrum;

(e) assigning said at least one calculated value of said non-smoothed spectrum to a wavelength including the center of said selected portion of said region of said non-smoothed spectrum to form at least one point of a smoothed spectrum;

(f) shifting a selected distance in said non-smoothed spectrum and repeating steps (c), (d), and (e) until a desired amount of said smoothed spectrum is formed;

(g) forming a residual spectrum by subtracting each point of said desired amount of said smoothed spectrum at a given wavelength from each point of said non-smoothed spectrum at said given wavelength;

(h) inspecting said residual spectrum to determine if it is random; and

(i) if said residual spectrum is not random, repeating steps (b), (c), (d), (e), (f), (g), and (h) to achieve a smoothing, wherein said residual spectrum is random.

48. The method claim 47, wherein said biological sample is a fluid.

49. The method of claim 47, wherein said biological sample is selected from the group consisting of urine, whole blood, plasma, serum, sputum, saliva, sweat, interstitial fluid, cerebral spinal fluid, and dialysate obtained in kidney dialysis.

50. The method claim 47, wherein said biological sample is urine.

51. The method of claim 50, wherein said at least one analyte of interest is selected from the group consisting of urea, creatinine, protein, glucose, and ketones.

52. The method of claim 50, wherein said at least one analyte of interest is selected from the group consisting of hemoglobin and bilirubin.

53. The method of claim 47, wherein said spectroscopic analysis is selected from the group consisting of ultraviolet absorption spectroscopy, visible absorption spectroscopy, infrared absorption spectroscopy, ultraviolet scattering spectroscopy, visible scattering spectroscopy, infrared scattering spectroscopy, fluorescence spectroscopy, and Raman spectroscopy.

54. The method of claim 47, wherein said spectroscopic analysis is filter photometry.

55. The method of claim 47, wherein said spectroscopic analysis is derivative spectroscopy.

56. The method of claim 47, wherein said spectroscopic analysis utilizes measurement of transmitted light.

57. The method of claim 47, wherein said spectroscopic analysis utilizes measurement of reflected light.

58. The method of claim 47, wherein said mathematical function is a polynomial function.

59. The method of claim 47, wherein said spectral range selected has a width of from about 190 nm to about 40,000 nm.

60. The method of claim 47, wherein said portion has a width of from 1 nm to about 100 nm.

61. The method of claim 47, wherein said mathematical function is selected from the group consisting of polynomial functions, Taylor series functions, Fourier series functions, and Gaussian functions.

62. The method of claim 47, wherein randomness is inspected by means of an auto-correlation function.

63. The method of claim 47, wherein said mathematical function is fitted by a least squares technique.

64. The method of claim 47, wherein said mathematical function is fitted by a sum and difference method.

65. The method of claim 47, wherein the width of the spectral portions can be varied from spectral region to spectral region across the spectrum.

66. The method of claim 47, wherein the order of the polynomial function can be varied from spectral region to spectral region across the spectrum.

67. The method of claim 47, further including the step of employing at least one measurement selected from the following additional measurements:

light scattering, impedance, pH, ion, temperature, and refractive index.

68-71. -71 (canceled)