Method of analyzing clinically relevant liquids and suspensions

• US 5,734,587 A
• Filed: 09/19/1994
• Issued: 03/31/1998
• Est. Priority Date: 09/17/1993
• Status: Expired due to Fees

• Current Assignee: Boehringer Mannheim GmbH (Roche Holding AG)
• Original Assignee: Boehringer Mannheim GmbH (Roche Holding AG)
• Inventors: Mischler, Reinhard, Boecker, Dirk, Backhaus, Juergen
• Primary Examiner(s): Voeltz, Emanuel T.
• Assistant Examiner(s): CHOI, KYLE JAEHUN
• Application Number:
  US08/307,416
• Time in Patent Office: 1,289 Days
• Field of Search: 364/496-499, 364/413.07-413.11, 436/46, 436/50, 436/63, 382/133, 382/134, 382/155-161, 356/36-42, 356/51
• US Class Current: 702/25
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: G01N 2001/4027 evaporation leaving a concentrated sample
• CPC Class Codes: G01N 21/3577 for analysing liquids, e.g. polluted water
• CPC Class Codes: G01N 21/47 Scattering, i.e. diffuse reflection G01N21/25, G01N21/41 take precedence G01N21/55 takes precedence
• CPC Class Codes: G01N 2201/129 Using chemometrical methods
• CPC Class Codes: Y10T 436/112499 with sample on test slide
• CPC Class Codes: Y10T 436/115831 Condition or time responsive

Abstract

A method of analyzing clinically relevant sample liquids and suspensions is such that where infrared spectra of dried samples are generated and evaluated using a multivariate evaluation procedure. In the evaluation procedure, the samples to be analyzed are assigned to classes. The evaluation procedure is trained with samples of known classes to adjust the parameters of the evaluation procedures such that samples of unknown classification can be assigned to known classes. In an advantageous manner, the infrared spectra can be generated by a transmittance measurement on a dried film of the sample.

Claims

1. A method of analyzing clinically relevant liquids and/or suspensions, comprising

a) measuring the infrared spectra of a plurality of samples belonging to known classes,

b) implementing a multivariate evaluation procedure and training the multivariate evaluation procedure by selecting parameters ensuring a reliable assignment of the samples to the known classes,

c) storing the parameters of the multivariate evaluation procedures obtained,

d) providing a sample of the liquid and/or suspension to be analyzed,

e) applying the sample to a carrier,

f) drying the sample,

g) exposing the sample to infrared radiation,

h) generating an infrared spectrum of the sample,

i) analyzing the infrared spectrum by means of a multivariate evaluation procedure, and

j) assigning the sample to a class of the multivariate evaluation procedure.

2. Method of claim 1, wherein the carrier reflects infrared radiation to generate a reflection spectrum of the sample.

3. Method of claim 2 wherein the reflection spectrum is a diffuse reflection spectrum.

4. Method of claim 1, wherein the liquids and/or suspensions which are analyzed are body fluids which are whole blood, hemolysate, serum and/or plasma.

5. Method of claim 1, wherein a suspension of cell and/or bacteria is analyzed.

6. Method of claim 2, wherein in step (g), the entire sample is irradiated with the infrared radiation.

7. Method of claim 1, wherein steps (a), (b), and (c) are carried out one or more times while steps (d) to (j) are carried out in multiples and cyclically using different samples.

8. Method of claim 1, wherein the multivariate evaluation procedure is a discriminant analysis, a neuronal net, or a cluster analysis.

9. Method of claim 8, wherein the discriminant analysis is a regularized discriminant analysis.

10. Method of claim 1, wherein infrared spectrum ranging from 400 to 15000 cm^-1 are generated.

11. Method of claim 10, wherein infrared spectrum ranging from 400 to 4000 cm^-1 are generated.

12. Method of claim 1, wherein the samples of known classification are samples from which it is known that an internal disease is present.

13. Method of claim 1, wherein the samples of known classification are samples from which it is known that a liver or renal disease is present.

14. Method of claim 1, wherein the samples of known classification are samples of patients with type I or type II diabetes.

15. Method of claim 1, wherein additionally at least one sample is used which is a sample of a healthy patient.

16. Method of analyzing clinically relevant liquids and/or suspensions, comprising

a) providing a sample of the liquid and/or suspension,

b) placing the sample onto a carrier having at least one opening in which the sample forms a hanging film,

c) drying the sample,

d) allowing radiation to traverse the dried sample contained in the opening,

e) detecting radiation transmitted across the dried sample to generate an infrared spectrum,

f) evaluating the infrared spectrum to determine the concentration of at least one analyte contained in the sample, and/or to classify the sample.

17. Method of claim 16, wherein the at least one opening has a diameter of 200 to 1000 μ

m.

18. Method of claim 16, wherein the carrier is an eye, a net or a perforated foil.

19. Method of claim 16, wherein a defined quantity of a reference substance is added to the sample, and the amount of the sample material detected by the infrared beam is determined from the absorption of the reference substance.

20. Method of claim 16, wherein the thickness of the suspended film is interferometrically determined, and the thickness of the film is used to determine the amount of sample detected by the infrared beam.

21. Method of claim 16, wherein film-forming substances are added to the sample liquid to increase the stability of the hanging film.

22. Method of claim 16, wherein the infrared spectrum obtained in step (e) is analyzed by means of a multivariate evaluation procedure.

23. Method of claim 22, wherein the multivariate evaluation procedure is a discriminant analysis, a neuronal net, or a cluster analysis.

24. Method of claim 23, wherein the discriminant analysis is a regularized discriminant analysis.

25. Method of claim 16, wherein infrared spectrum ranging from 400 to 15000 cm^-1 are generated.

26. Method of claim 25, wherein infrared spectrum ranging from 400 to 4000 cm^-1 are generated.

27. Method of claim 16, wherein cell/bacteria suspensions are used as the samples.