Radio frequency spectral analysis for in-vitro or in-vivo environments

• US 5,792,668 A
• Filed: 04/15/1996
• Issued: 08/11/1998
• Est. Priority Date: 08/06/1993
• Status: Expired due to Fees

• Current Assignee: Solid State Farms Incorporated
• Original Assignee: Solid State Farms Incorporated
• Inventors: Iverson, Mark N., Koshy, deceased, Ajit J., Deamer, David W., Fuller, Milton E.
• Primary Examiner(s): Soderquist, Arlen
• Application Number:
  US08/631,916
• Time in Patent Office: 848 Days
• Field of Search: 128/633, 128/664, 128/665, 128/666, 128/635, 73/53.01, 324/642-646, 422/82.01, 436/63, 436/79, 436/95, 436/149, 436/150, 436/151, 436/108, 600/322, 600/347
• US Class Current: 436/149
• CPC Class Codes: A61B 5/053 Measuring electrical impedance or conductance of a portion of the body
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: Y10T 436/144444 Glucose
• CPC Class Codes: Y10T 436/171538 Urea or blood urea nitrogen

Abstract

Concentration of a target chemical in the presence of other substances in a specimen is determined by subjecting the specimen to radio frequency electromagnetic components, sequentially or otherwise, ranging to about 5 GHz. The reflected and/or transmitted signal real and imaginary components at the specimen are spectrally examined as a function of frequency to identify the presence and/or concentration of the chemical of interest. Such examination includes analysis of the effective complex impedance presented by the specimen, and/or effective phase shift between the transmitted and reflected signal at the specimen. The effects upon glucose concentration measurements of varying electrolytes, primarily NaCl, can be nulled-out by examining impedance magnitude at a cross-over frequency, for example about 2.5 GHz. NaCl concentration exhibits a very linear relationship with phase shift change at frequencies in the 2 GHz-3 GHz range. In a specimen that is blood, such phase shift measurements provide data proportional to NaCl concentration. Impedance magnitude measurements using 1 MHz to 400 MHz frequencies provides a measure of combined concentration of glucose and NaCl. The phase shift data may then be used to substrate out the NaCl concentration from the combined concentration, to yield a good measure of glucose concentration. Such tests may be conducted in-vitro or in-vivo and lend themselves to blood level glucose analyses by diabetics.

Claims

1. A method, capable of in vivo operation, for determining concentration of glucose in the presence of a second substance that includes NaCl in a specimen that includes blood, the method including the following steps:

(a) subjecting said specimen to radio frequency signals having a frequency regime ranging from about 0.1 Mhz to about 5 Ghz;

(b) at a first frequency regime, using at least some of said radio frequency signals to obtain data proportional to magnitude of concentration of said second substance in said specimen;

(c) at a second frequency regime, using at least some of said radio frequency signals to obtain data proportional to combined concentration in said specimen of said glucose and said second substance; and

(d) using data from said first frequency regime and data from said second frequency regime to obtain a measure of concentration of said glucose in said specimen.

2. The method of claim 1, wherein at step (a), at least some of said frequencies are presented sequentially.

3. The method of claim 1, wherein at step (a), at least some of said frequencies are presented simultaneously.

4. The method of claim 1, wherein at step (b), said first frequency regime ranges from about 1 GHz to about 3 GHz.

5. The method of claim 1, wherein at step (b), said data proportional to magnitude is obtained by measuring phase shift between radio frequency signals input to said specimen and radio frequency signals returned from said specimen.

6. The method of claim 1, wherein at step (c), said second frequency regime ranges from about 0.11 MHz to about 3 GHz.

7. The method of claim 1, wherein at step (c), said second frequency regime ranges from about 800 MHz to about 900 MHz, in which regime temperature effects upon data are minimized.

8. The method of claim 1, wherein at step (c), said data proportional to combined concentration is obtained by measuring magnitude of impedance at said specimen.

9. The method of claim 1, wherein at step (d) a concentration value determined in step (b) is subtracted from a combined concentration determined in step (c) to provide said measure of concentration of said glucose.

10. The method of claim 1, in which said method is carried out non-invasively on a human subject, and wherein step (a) includes coupling said radio frequency signals via at least one probe that contacts a distal portion of said subject'"'"'s body.

11. A method, capable of in vivo operation, for determining concentration of glucose in the presence of a second substance that includes NaCl in a specimen that includes blood, the method including the following steps:

(a) subjecting said specimen to radio frequency signals at a cross-over frequency at which frequency concentration effects of said second substance are essentially nulled-out; and

(b) determining from data taken at said cross-over frequency concentration of said glucose.

12. The method of claim 11, wherein said cross-over frequency is about 2.5 GHz.

13. The method of claim 11, wherein at step (b), said data is impedance data.

14. The method of claim 11, wherein step (a) is carried out non-invasively on a human subject by coupling said cross-over frequency via at least one probe that contacts a distal portion of said subject'"'"'s body.

15. A system, capable of in vivo operation, for determining concentration of a first chemical in the presence of a second substance in a specimen, including:

a transmitter outputting radio frequency signals having a frequency regime ranging from about 0.1 MHz to about 5 GHz;

at least one probe, coupling to said transmitter, contacting a portion of said specimen; and

a receiver-signal processor system, coupled to said at least one probe, that analyzes at least some of said radio frequency signals present at said probe;

said receiver-signal processor system providing data including at least impedance and/or phase shift present at an interface between said specimen and said at least one probe;

wherein data provided by said receiver-signal processor system is used to determine said concentration of said first chemical in said specimen.

16. The system of claim 15, wherein said transmitter transmits signals appropriate for a specimen that is human blood, for a said first chemical that is glucose, and for a said second chemical that includes NaCl, and wherein said transmitter includes a network analyzer.

17. The system of claim 15, wherein:

said specimen is a human subject including said subject'"'"'s blood;

said first chemical is glucose;

said second chemical includes NaCl;

said transmitter transmits signals appropriate for discerning concentration of glucose present in NaCl within human blood; and

said at least one probe contacts an exterior portion of a finger of said subject such that non-invasive data is provided by said system.