Apparatus and method for noninvasive measurement of analytes from the conjunctiva using mid-infrared radiation

• US 7,403,805 B2
• Filed: 04/25/2003
• Issued: 07/22/2008
• Est. Priority Date: 02/23/2001
• Status: Expired due to Term

• Current Assignee: Geelux Holdings, Ltd.
• Original Assignee: Marcio Marc Abreu
• Inventors: Abreu, Marcio Marc
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US10/423,056
• Publication Number:
  US 20040039297A1
• Time in Patent Office: 1,915 Days
• Field of Search: 600/310, 600/316, 600/318, 600/319, 600/322
• US Class Current: 600/318
• CPC Class Codes: A61B 2560/0214 of power generation or supply
• CPC Class Codes: A61B 2560/0219 of externally powered implanted units
• CPC Class Codes: A61B 2560/0252 using ambient temperature
• CPC Class Codes: A61B 2560/0418 Pen-shaped housings
• CPC Class Codes: A61B 2562/0238 Optical sensor arrangements for performing transmission measurements on body tissue
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• CPC Class Codes: A61B 3/0025 characterised by electronic signal processing, e.g. eye models
• CPC Class Codes: A61B 3/0058 for multiple images
• CPC Class Codes: A61B 3/10 Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
• CPC Class Codes: A61B 3/1241 specially adapted for observation of ocular blood flow, e.g. by fluorescein angiography
• CPC Class Codes: A61B 3/14 Arrangements specially adapted for eye photography apparatus or arrangements for taking photographs per se G03B
• CPC Class Codes: A61B 3/16 for measuring intraocular pressure, e.g. tonometers
• CPC Class Codes: A61B 3/185 characterised by modular construction
• CPC Class Codes: A61B 5/0002 Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network A61B5/07 takes precedence; transmission systems for measured values G08C; transmission H04B; transmission of digital information H04L; wireless communication networks H04W
• CPC Class Codes: A61B 5/01 Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue clinical contact thermometers G01K13/20
• CPC Class Codes: A61B 5/031 Intracranial pressure
• CPC Class Codes: A61B 5/14507 specially adapted for measuring characteristics of body fluids other than blood devices for taking samples of body liquids A61B10/0045
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 : using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/14555 : specially adapted for the eye fundus
• CPC Class Codes: A61B 5/1486 : using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/18 : for vehicle drivers or machine operators
• CPC Class Codes: A61B 5/412 : Detecting or monitoring sepsis
• CPC Class Codes: A61B 5/416 : the spleen
• CPC Class Codes: A61B 5/445 : Evaluating skin irritation or skin trauma, e.g. rash, eczema, wound, bed sore
• CPC Class Codes: A61B 5/4839 : combined with drug delivery
• CPC Class Codes: A61B 5/6814 : Head
• CPC Class Codes: A61B 8/06 : Measuring blood flow measuring volume flow in general G01F, e.g. G01F1/66, G01F1/72; measuring speed of fluids in general G01P5/00
• CPC Class Codes: A61B 8/56 : Details of data transmission or power supply
• CPC Class Codes: A61F 9/0017 : implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61F 9/0026 : Ophthalmic product dispenser attachments to facilitate positioning near the eye
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 27/06 : Antiglaucoma agents or miotics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: G02C 11/10 : Electronic devices other than hearing aids
• CPC Class Codes: G02C 7/04 : Contact lenses for the eyes disinfection or sterilisation of contact lenses A61L12/00
• CPC Class Codes: Y02A 90/10 : Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Utilization of a contact device placed on the eye in order to detect physical and chemical parameters of the body as well as the non-invasive delivery of compounds according to these physical and chemical parameters, with signals being transmitted continuously as electromagnetic waves, radio waves, infrared and the like. One of the parameters to be detected includes non-invasive blood analysis utilizing chemical changes and chemical products that are found in the conjunctiva and in the tear film. A transensor mounted in the contact device laying on the cornea or the surface of the eye is capable of evaluating and measuring physical and chemical parameters in the eye including non-invasive blood analysis. The system utilizes eye lid motion and/or closure of the eye lid to activate a microminiature radio frequency sensitive transensor mounted in the contact device. The signal can be communicated by wires or radio telemetered to an externally placed receiver. The signal can then be processed, analyzed and stored. Several parameters can be detected including a complete non-invasive analysis of blood components, measurement of systemic and ocular blood flow, measurement of heart rate and respiratory rate, tracking operations, detection of ovulation, detection of radiation and drug effects, diagnosis of ocular and systemic disorders and the like.

Claims

1. An apparatus for noninvasive measurement of a concentration of at least one substance from the conjunctiva, said apparatus comprising:

a mid-infrared radiation detector configured to detect mid-infrared radiation emitted from the conjunctiva, said-mid-infrared radiation from said conjunctiva containing a radiation signature of said at least one substance, said mid-infrared detector producing a signal representative of said mid-infrared radiation signature,

a processor including a memory storing a plurality of predetermined reference values and a processing circuit for

receiving said signal representative of said mid-infrared radiation signature from said conjunctiva,

comparing said signal representative of said mid-infrared radiation signature from said conjunctiva with one of said plurality of reference values, and

determining the concentration of the at least one substance based upon said comparison, and

a display for reporting the concentration of said at least one substance from the conjunctiva.

2. The apparatus of claim 1, wherein said at least one substance includes at least one of glucose, ethanol and cholesterol.

3. The apparatus of claim 1, further comprising at least one filter for selecting a radiation wavelength.

4. The apparatus of claim 3, wherein said at least one filter has a mid-infrared bandwidth centered on about 9,400 nm corresponding to the radiation signature of glucose.

5. The apparatus of claim 3, wherein said at least one filter has a mid-infrared bandwidth centered on about 9,900 nm corresponding to the radiation signature of ethanol.

6. The apparatus of claim 3, wherein said at least one filter has a mid-infrared bandwidth centered on about 8,300 nm corresponding to the radiation signature of cholesterol.

7. The apparatus of claim 3, wherein said at least one filter passes mid-infrared radiation having wavelengths between about 9,000 nanometers and about 11,000 nanometers.

8. The apparatus of claim 1, wherein a cooling device is used to increase a temperature gradient between a cold junction and a hot junction of an infrared sensor of said mid-infrared detector.

9. The apparatus of claim 1, wherein said plurality of reference values includes a radiation wavelength corresponding to the concentration of said at least one substance.

10. The apparatus of claim 1, further comprising an infrared spectrometer.

11. The apparatus of claim 1, wherein said display includes at least one of a numerical display of a value of said concentration and an audio device for audibly communicating a value of said concentration.

12. The apparatus of claim 1, further comprising a housing for the detector and the processor, said housing is one of a pen device and a wired handle to be held by a hand of a subject so that the housing is spaced away from the conjunctiva and measurements are performed without contacting the conjunctiva.

13. The apparatus of claim 1, further comprising a housing for the detector and the processor, said housing is a contact device for contacting the conjunctiva during measurement.

14. Amethod for noninvasive of at least one substance from the conjunctiva, said method comprising the steps of:

detecting mid-infrared radiation emitted from said conjunctiva, said mid-infrared radiation containing a radiation a radiation signature of said at least one substance from the conjunctiva,

determining the radiation signature of at least one substance from said mid-infrared radiation from said conjunctiva, and

determining a concentration of said at least one substance present in the conjunctiva from the mid-infrared radiation signature from the conjunctiva.

15. The method of claim 14, further comprising a step of selecting a desired wavelength of said mid-infrared radiation.

16. The method of claim 14, wherein said mid-infrared radiation comprises mid-infrared radiation having wavelengths between about 9,000 nanometers and about 11,000 nanometers.

17. The method of claim 14, wherein said step for determining the concentration of said at least one substance includes the step of comparing the detected radiation signature from said mid-infrared radiation with a plurality of predetermined reference values.

18. The method of claim 17, wherein said plurality of predetermined reference values includes a radiation wavelength corresponding to the concentration of said at least one substance.

19. The method of claim 14, wherein said at least one substance includes at least one of glucose, ethanol and cholesterol.

20. The method of claim 14, wherein said mid-infrared radiation comprises mid-infrared radiation having wavelengths between about 4,000 nanometers and about 14,000 nanometers.

21. The method of claim 14, wherein said detecting step includes detecting mid-infrared radiation from said conjunctiva without contact with the surface of said conjunctiva.

22. A method of determining an analyte concentration in a tissue of a subject, the subject including an eye with an ocular surface and a conjunctiva surface, comprising the steps:

a. detecting naturally occurring mid-infrared radiation emitted from the conjunctiva without contact with the ocular surface using a non-invasive instrument comprising a mid-infrared detector;

b. comparing a radiation signature of said mid-infrared radiation to a radiation signature of mid-infrared radiation corresponding to an analyte concentration; and

c. analyzing said radiation signature of said mid-infrared radiation from said subject to determine said analyte concentration in a tissue of said subject.

23. The method of claim 22, wherein said analyte is selected from the group consisting of metabolic compounds or substances, carbohydrates, sugars, glucose, proteins, peptides, amino acids, fats, fatty acids, triglycerides, polysaccharides, alcohols, ethanol, toxins, hormones, vitamins, bacteria-related substances, fungus-related substances, parasite-related substances, pharmaceutical compounds, non-pharmaceutical compounds, pro-drugs, drugs, and any precursor, metabolite, degradation product or surrogate marker.

24. The method of claim 23, wherein said analyte is glucose.

25. The method of claim 22, wherein said naturally occurring mid-infrared radiation comprises infrared radiation having wavelengths between about 2.5 microns and about 25.0 microns.

26. The method of claim 22, wherein said detecting step further comprises selecting and detecting desired wavelengths of said naturally occurring mid-infrared radiation.

27. The method of claim 22, wherein said comparing step and said analyzing step further comprise using a microprocessor.

28. A method of downloading and storing a subject'"'"'s measured analyte concentration, comprising the steps of:

a. measuring said analyte concentration according to the method of claim 22, using a non-invasive mid-infrared detecting instrument having a communications interface;

b. connecting said instrument through said communications interface to a computer system having a computer processor, a computer program which executes in said computer processor, and an analogous communications interface; and

c. downloading from said instrument to said computer system said measured analyte concentrations.