Luminescence monitoring with modulation frequency multiplexing

• US 5,315,993 A
• Filed: 01/29/1992
• Issued: 05/31/1994
• Est. Priority Date: 02/16/1990
• Status: Expired due to Term

• Current Assignee: Becton Dickinson Critical Care Systems Pte Ltd. (Becton, Dickinson & Co)
• Original Assignee: BOC Group Pty Limited (Linde Plc)
• Inventors: Alcala, J. Ricardo
• Primary Examiner(s): Sykes, Angela D.
• Application Number:
  US07/827,658
• Time in Patent Office: 853 Days
• Field of Search: 128/633-635, 128/664-665, 422/82.06-82.07, 422/52, 422/86, 250/227.21, 250/458.1, 250/461.1-461.2, 385/123
• US Class Current: 600/341
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14556 by fluorescence A61B5/14555 takes precedence
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/6855 with a distal curved tip
• CPC Class Codes: G01N 2021/6432 Quenching
• CPC Class Codes: G01N 2021/8578 Gaseous flow IR analysers G01N21/8507
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence

Abstract

A luminescence based analytical probe is excited with light varying repetitively in amplitude at multiple modulation frequencies. A composite signal incorporating components at a plurality of these modulation frequencies, produced by emissions in all of the various decaying modes is analyzed to provide information, such as the fractional luminescence contribution and/or lifetime of each individual decaying mode because the various decaying mode are segregated by analysis of the composite signal, there is no need to segregate light from the various decaying mode according to the wavelength of the light. Therefore, the probe may incorporate plural luminescent materials which have different decay modes with different luminescent decay times and sensitive to different conditions to be monitored, even if the plural luminescent materials absorb and emit light at the same wavelengths.

Claims

1. A probe for monitoring a plurality of conditions comprising:

(a) a light-transmissive member for applying excitation light within a common band of excitation wavelengths;

(b) luminescent means connected to said member in optical communication therewith, said luminescent means having a plurality of emission modes with different lifetimes, said luminescent means being operative to simultaneously emit a plurality of response light signals having wavelengths within a common band of response wavelengths into said light-transmissive member in response to the excitation light within the common band of excitation wavelengths applied through said light-transmissive member, each such response light signal representing one said emission mode, said luminescent means being operative to vary each of said lifetimes in response to one of said conditions to be monitored.

2. A probe as claimed in claim 1 wherein said light-transmissive member is an elongated fiber optic having proximal and distal ends.

3. A probe as claimed in claim 2 wherein said elongated fiber optic includes only a single fiber.

4. A probe as claimed in claim 2 wherein said luminescent means includes a plurality of luminescent compositions mounted to said distal end of said single fiber optic.

5. A probe as claimed in claim 1 wherein said luminescent means includes a plurality of luminescent compositions mounted to said light-transmissive member.

6. A probe as claimed in claim 1 wherein said luminescent means is operative to emit a plurality of said response light signals at a single common wavelength in response to substantially monochromatic excitation light.

7. A probe as claimed in claim 1 wherein said ratio between the lifetime of each one of said emission modes and the lifetime of each other one of said emission modes is at least about 1.15:

1.

8. Apparatus for monitoring a plurality of conditions comprising

(a) a light-transmissive member;

(b) luminescent means for emitting response light connected to said member in optical communication therewith, said luminescent means having a plurality of emission modes with different lifetimes, said luminescent means being operative to vary each of said lifetimes in response to one of said conditions to be monitored;

(c) excitation light source means for simultaneously applying a plurality of excitation light components varying cyclically in amplitude at a plurality of modulation frequencies to said luminescent means through said light transmissive member so that said luminescent means emits response light simultaneously incorporating a plurality of response light components each varying cyclically in amplitude at one of said modulation frequencies and so that said response light components cooperatively represent all of said plurality of emission modes of said luminescent means;

(d) transducer means for deriving a multicomponent response signal incorporating components corresponding to a plurality of said modulation frequencies from said response light so that said multicomponent response signal represents a plurality of said emission modes; and

(e) interpretation means for deriving information relating to each said emission mode represented by said multicomponent response signal from said multicomponent response signal.

9. Apparatus as claimed in claim 8 wherein said luminescent means includes a plurality of luminescent substances having different emission modes.

10. Apparatus as claimed in claim 8 wherein each ratio of one said lifetime to another one of said lifetimes is at least about 1.15:

1.

11. Apparatus as claimed in claim 8 wherein said excitation light source means includes means for providing said excitation light components as a plurality of sets each including one or more of said components within a selected range of excitation modulation frequencies, the range of excitation modulation frequencies of each said set being different from the range of such frequencies of every other one of said sets.

12. Apparatus as claimed in claim 11 wherein said excitation light source means includes means for providing said excitation light components so that each said set includes a different principal excitation modulation frequency and so that each said principal excitation modulation frequency corresponds to a principal period between about 2 and about 100 times the lifetime of one of said emission modes.

13. Apparatus as claimed in claim 12 wherein said excitation light source means includes means for providing said excitation light components such that each said set includes a principal component at one of said principal excitation modulation frequencies and one or more additional components at excitation modulation frequencies about 2 to about 32 times the principal excitation modulation frequency in such set.

14. Apparatus as claimed in claim 13 wherein said interpretation means includes frequency separation means for separating said multicomponent response signal into a plurality of separated response signals, each said separated response signal including only components within one of said ranges of modulation frequencies.

15. Apparatus as claimed in claim 8 wherein said transducer means is also operative to derive an excitation signal representing said excitation light and incorporating components at said excitation modulation frequencies, said interpretation means including means for determining a phase difference for each said modulation frequency between the component of said response signal at such modulation frequency and the component of said excitation signal at the same frequency.

16. Apparatus as claimed in claim 15 wherein said interpretation means includes means for determining a modulation ratio for each said modulation frequency from said multicomponent response signal and said excitation signal.

17. Apparatus as claimed in claim 16 wherein said interpretation means includes means for deriving at least one of

18. Apparatus as claimed in claim 17 wherein said interpretation means includes means for deriving lifetimes for said emission modes by solving a plurality of simultaneous equations selected from the group consisting of equations of the form:

##EQU13## and combinations thereof, wherein;

N represents an integer number of said emissions modes;

f_i represents the contribution of response light arising from the i^th said emission mode to the luminescence of frequency w as a fraction of the total amplitude of said response light at frequency w; and

space="preserve" listing-type="equation">τ

.sub.i

represents the lifetime of the i^th emission mode.

19. Apparatus as claimed in claim 18 wherein said means for deriving lifetime for sad emission modes by solving a plurality of simultaneous equations includes means for solving said equations using known values for f_i in each said equation.

20. Apparatus as claimed in claim 19 wherein said means for deriving lifetimes for said emission modes by solving a plurality of simultaneous equations includes means for deriving values for N said lifetimes by solving at least N said equations for at least N said modulation frequencies.

21. Apparatus as claimed in claim 18 wherein said means for deriving lifetimes for said emission modes by solving a plurality of simultaneous equations includes means for determining values for f_i in said equations by solving said equations, said means for solving said equations being operative to derive values for N said lifetimes by solving at least 2N said equations for at leas N said modulation frequencies.