Reagentless analysis of biological samples

• US 6,087,182 A
• Filed: 08/27/1998
• Issued: 07/11/2000
• Est. Priority Date: 08/27/1998
• Status: Expired due to Term

• Current Assignee: Abbott Laboratories
• Original Assignee: Abbott Laboratories
• Inventors: Shain, Eric B., Jeng, Tzyy-Wen, McDowell, Larry L., Oosta, Gary M., Pezzaniti, Joseph Larry
• Primary Examiner(s): WARDEN, JILL ALICE
• Application Number:
  US09/141,483
• Time in Patent Office: 684 Days
• Field of Search: 436/108, 436/171, 436/66, 436/86, 436/95, 436/97, 436/128, 436/163
• US Class Current: 436/66
• 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. A method for determining concentration of at least one analyte of interest in a liquid biological sample from an individual by means of spectroscopic analysis, said method comprising the steps of:

(a) identifying at least one analyte that is a major component of said liquid biological sample, said at least one analyte accounting for significant variations with respect to a plurality of spectra of liquid biological samples from a plurality of donors of said liquid biological samples;

(b) measuring a spectrum for each of said plurality of liquid biological samples from said plurality of donors of said liquid biological samples;

(c) calculating a model spectrum for each of said plurality of liquid biological samples from said plurality of donors of said liquid biological samples by mathematically fitting spectra of said analytes of said at least one identified analyte to each spectrum of each of said liquid biological samples from said plurality of donors of said liquid biological samples;

(d) calculating a residual spectrum havinq a non-zero value for each spectrum of each of said liquid biological samples from said plurality of donors of said liquid biological samples by subtracting each value of said model spectrum from each value of each spectrum of each of said liquid biological samples from said plurality of donors of said liquid biological samples that corresponds to said model spectrum;

(e) repeating steps (a), (b), (c), and (d) at least one time by introducing at least one additional analyte to said model spectrum until said calculated residual spectra are substantially constant from one liquid biological sample to another liquid biological sample of said plurality of liquid biological samples from said plurality of donors of said liquid biological samples;

(f) determining a set of calibration parameters from said model spectra, said set of calibration parameters accounting for effects of said substantially constant residual spectra; and

(g) using said calibration parameters to determine concentration of an analyte of interest in said liquid biological sample of said individual.

2. The method of claim 1, 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.

3. The method claim 1, wherein said biological sample is urine.

4. The method of claim 3, wherein said at least one analyte of interest is selected from the group consisting of urea, creatinine, protein, glucose, and ketones.

5. The method of claim 3, wherein said at least one analyte of interest is selected from the group consisting of hemoglobin and bilirubin.

6. The method of claim 1, 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.

7. The method of claim 1, wherein said spectroscopic analysis is filter photometry.

8. The method of claim 1, wherein said spectroscopic analysis is derivative spectroscopy.

9. The method of claim 1, wherein said spectroscopic analysis utilizes measurerilent of transmitted light.

10. The method of claim 1, wherein said spectroscopic analysis utilizes measurement of reflected light.

11. The method of claim 1, 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.