Fluorescent detector systems for the detection of chemical perturbations in sterile storage devices

• US 20070251337A1
• Filed: 04/23/2007
• Published: 11/01/2007
• Est. Priority Date: 08/19/2004
• Status: Active Grant

• Current Assignee: Blood Cell Storage, Inc.
• Original Assignee: Blood Cell Storage, Inc.
• Inventors: Harris, Paul, Reed, Michael, Nanassy, Oliver, Hargrave, Perry, Geelhood, Steven, Barker, Lynn
• Granted Patent: US 8,497,134 B2
• Time in Patent Office: Days
• US Class Current: 73/866
• CPC Class Codes: C12Q 1/04 Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor C12Q1/6897 takes precedence
• CPC Class Codes: C12Q 1/22 Testing for sterility conditions
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: G01N 2021/6421 Measuring at two or more wavelengths
• CPC Class Codes: G01N 2021/6434 Optrodes
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/77 by observing the effect on a chemical indicator
• CPC Class Codes: G01N 21/80 Indicating pH value
• CPC Class Codes: G01N 2201/062 LED's
• CPC Class Codes: G01N 2201/068 Optics, miscellaneous
• CPC Class Codes: G01N 2201/0826 Fibre array at source, distributing
• CPC Class Codes: G01N 2201/084 Fibres for remote transmission
• CPC Class Codes: G01N 2400/00 Assays, e.g. immunoassays or enzyme assays, involving carbohydrates
• CPC Class Codes: G01N 33/492 Determining multiple analytes
• CPC Class Codes: G01N 33/542 with steric inhibition or signal modification, e.g. fluorescent quenching
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose
• CPC Class Codes: G01N 33/84 involving inorganic compounds or pH

Abstract

System and method for detecting and measuring chemical perturbations in a sample. The system and method are useful for non-invasive pH monitoring of blood or blood products sealed in storage bags.

Claims

1. A method for monitoring a parameter of a sample, comprising:

(a) irradiating a fluorescent species having an emission that is dependent on a parameter with excitation light emanating from a probe physically isolated from the fluorescent species to provide a fluorescent emission, wherein the fluorescent species is in liquid communication with a sample contained in a vessel;

(b) measuring the emission to determine a first parameter reading of the sample; and

(c) repeating step (a) after a pre-determined time and measuring the emission to determine a second parameter reading of the sample.

2. The method of claim 1, wherein step (c) is repeated to provide multiple parameter readings to monitor the parameter of the sample over time.

3. The method of claim 1, wherein the parameter is pH.

4. The method of claim 1, wherein the parameter is CO₂.

5. The method of claim 1 further comprising writing parameter readings to the vessel containing the sample.

9. The method of claim 1, wherein the pre-determined time is from about 1 minute to about 1 day.

10. The method of claim 1, wherein the pre-determined time is from about 1 hour to about 12 hours.

11. The method of claim 2, wherein the multiple readings over time provide a profile of the sample.

12. The method of claim 11, wherein the profile of the sample is used to determine a quality of a sample.

14. The method of claim 1, wherein the fluorescent species is selected from the group consisting of a naphthofluorescein compound, a seminaphthofluorescein compound, a seminaphthorhodamine compound, and a 8-hydroxy-1,3,6-pyrenetrisulfonic acid compound.

15. The method of claim 14, wherein the compound is a seminaphthofluorescein compound.

16. The method of claim 1, wherein the fluorescent species is a seminaphthofluorescein compound selected from the group consisting of 5′

(and 6′

)-carboxy-3,10-dihydroxy-spiro[7H-benzo[c]xanthene-7,1′

(3′

H)-isobenzofuran]-3′

-one and 2-(2-chloro-3-hydroxy-9-carboxyethyl-10-oxo-10H-benzo[c]xanthen-7-yl)benzoic acid.

17. The method of claim 1, wherein the fluorescent species is a conjugate of a fluorescent species and a macromolecule.

18. The method of claim 17, wherein the macromolecule is an albumin.

19. The method of claim 1, wherein the fluorescent species is a seminaphthofluorescein/human serum albumin conjugate.

20. The method of claim 1, wherein the sample comprises blood or a blood product.

21. The method of claim 1, wherein the vessel is a sealed vessel.

6. A method for monitoring the pH of a sample, comprising:

(a) irradiating a fluorescent species in liquid communication with a sample contained in a vessel with excitation light emanating from a probe physically isolated from the fluorescent species, wherein the excitation light has a wavelength sufficient to effect fluorescent emission from the fluorescent species, wherein the fluorescent species exhibits a first emission intensity at a first emission wavelength and a second emission intensity at a second emission wavelength, the ratio of the first and second emission intensities being dependent on pH;

(b) measuring the first and second emission intensities to determine the first pH of the sample; and

(c) repeating step (a) after a pre-determined time and measuring the first and second emission intensities to determine the second pH of the sample.

7. The method of claim 6, wherein step (c) is repeated to provide multiple pH readings to monitor the pH of the sample over time.

8. The method of claim 6 further comprising writing pH readings to the vessel containing the sample.

13. The method of claim 6, wherein the probe is physically isolated from the fluorescent species by a window transparent to the excitation light and the fluorescent emission.

22. A system for monitoring a parameter, comprising:

(a) a light source for exciting a fluorescent species having an emission that is dependent on the parameter, wherein the fluorescent species is in liquid communication with a sample contained in a vessel;

(b) an emission detector for measuring emission from the fluorescent species and creating emission data;

(c) an excitation lightguide for transmitting excitation light from the light source to the fluorescent species, wherein the lightguide comprises a first terminus proximate to the light source and a second terminus distal to the light source;

(d) an emission lightguide for transmitting emission from the fluorescent species to the emission detector, wherein the lightguide comprises a first terminus proximate to the detector and a second terminus distal to the detector;

(e) a probe housing the distal termini of the excitation lightguide and the emission light guide;

(f) a housing for receiving the probe, wherein the housing is adapted for receiving the probe at a first end and terminating with a window at the second end, the window being transparent to the excitation and the emission light, and wherein the window physically isolates the probe from the fluorescent species;

(g) a memory device for storing the emission data; and

(h) a processor device for converting the emission data to a profile of the parameter over time.

24. The system of claim 22 further comprising a means for writing data to the vessel containing the sample.

25. The system of claim 22, wherein the light source is a light-emitting diode.

32. The system of claim 22, wherein the fluorescent species is immobilized on a substrate.

33. The system of claim 22, wherein the fluorescent species is a seminaphthofluorescein/human serum albumin conjugate.

23. A system for monitoring pH, comprising:

(a) a light source for exciting a fluorescent species, wherein the fluorescent species has a first emission intensity at a first emission wavelength and a second emission intensity at a second emission wavelength;

(b) a first emission detector for measuring the first emission intensity;

(c) a second emission detector for measuring the second emission intensity;

(d) an excitation lightguide for transmitting excitation light from the light source to the fluorescent species, wherein the lightguide comprises a first terminus proximate to the light source and a second terminus distal to the light source;

(e) a first emission lightguide for transmitting emission from the fluorescent species to the first emission detector, wherein the lightguide comprises a first terminus proximate to the detector and a second terminus distal to the detector;

(f) a second emission lightguide for transmitting emission from the fluorescent species to the second emission detector, wherein the lightguide comprises a first terminus proximate to the detector and a second terminus distal to the detector;

(g) a probe housing the distal termini of the excitation lightguide, first emission lightguide, and second emission light guide; and

(h) a housing for receiving the probe, wherein the housing is adapted for receiving the probe at a first end and terminating with a window at the second end, the window being transparent to the excitation and the emission light, and wherein the window physically isolates the probe from the fluorescent species;

(i) a memory device for storing the data, and

(j) a processor device for converting the data to a pH profile of a sample.

26. The system of claim 23, wherein the first and second detectors are the same.

27. The system of claim 23, wherein the first and second detectors are different.

28. The system of claim 23, wherein the first and second detectors are photodiodes.

29. The system of claim 23, wherein the first emission lightguide and the second emission lightguide are the same.

30. The system of claim 23, wherein the first emission lightguide and the second emission lightguide are different.

31. The system of claim 23, wherein the first emission lightguide and the second emission lightguide are optical fibers.