LED light source-based instrument for non-invasive blood analyte determination

• US 6,816,241 B2
• Filed: 09/17/2001
• Issued: 11/09/2004
• Est. Priority Date: 09/26/2000
• Status: Expired due to Fees

• Current Assignee: GLT Acquisition Corporation
• Original Assignee: Sensys Medical, Inc. (Sensys Medical Limited)
• Inventors: Grubisic, Dragan
• Primary Examiner(s): Font, Frank G.
• Assistant Examiner(s): Punnoose, Roy M.
• Application Number:
  US09/956,747
• Publication Number:
  US 20020041166A1
• Time in Patent Office: 1,149 Days
• Field of Search: 356/39, 356/40, 356/41, 362/551, 362/552, 362/554, 362/555, 362/572, 362/574, 362/800, 362/802, 362/230, 362/231, 362/241, 362/247
• US Class Current: 356/39
• CPC Class Codes: A61B 2562/0233 Special features of optical sensors or probes classified in A61B5/00
• CPC Class Codes: A61B 2562/046 in a matrix array
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• 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

Abstract

A compact, lightweight instrument for non-invasive blood analyte determination employs a light source incorporating an assembly of LED'"'"'s interconnected within a thermally stable substrate. A large diameter mixer couples the signal to a fiber optic probe for delivering the signal to a tissue measurement site. Back-diffused light is collected and dispersed across an array of photo detectors in a miniature spectrometer instrument. A high-speed DSP executes an algorithm for predicting concentration of a target analyte, which is output to a LCD display. Instrument control is by means of keypad or voice recognition.

High conversion efficiency of the light source results in extremely low power dissipation and virtually no heat generation, making incorporation of the light source and the spectrometer into a single unit practicable. High-speed pulsing of the signal allows application of high-sensitivity, synchronous detection techniques. Speed and flexibility in sequencing LED'"'"'s allows simultaneous measurement and skin temperature control.

Claims

1. A light source assembly for non-invasive optical sampling, comprising:

a plurality of LED'"'"'s, wherein at least one of said plurality of LED'"'"'s emits at a wavelength region different from and overlapping with that of at least another of said plurality of LED'"'"'s;

a LED substrate, said substrate providing mechanical support for said LED'"'"'s, so that said LED'"'"'s and said substrate form a LED/substrate subassembly;

means for electrically connecting said LED'"'"'s;

means for shaping light beams emitted from said LED'"'"'s;

means for controlling light intensity profile;

means for coupling said signal to a sample interface;

means for collecting light emitted from said sample;

wherein said means for shaping light beams emitted from said LED'"'"'s comprises a plurality of parabolic reflectors, wherein each reflector is mounted within a well on an anterior face of said substrate, and wherein each of said LED'"'"'s is fixedly attached within a corresponding reflector, so that divergence between light beams is minimized.

2. The assembly of claim 1, wherein said LED'"'"'s are any of single junction, hetero-junction and super-luminescence LED'"'"'s.

3. The assembly of claim 1, wherein combining light beams encompassing said wavelength regions produces a single wide band signal.

4. The assembly of claim 1, wherein said substrate has a posterior face and sides.

5. The assembly of claim 4, wherein said means for coupling said signal to a sample interface comprises a mixer, said mixer comprising a large diameter fiber optic having a hollow center and having a high index of refraction, so that wavelength content and intensity of light beams emanating from said LED/substrate sub-assembly are thoroughly mixed without introducing additional light loss.

6. The assembly of claim 5, wherein said mixer is fabricated from one of low OH⁻

silica, sapphire and silicon.

7. The assembly of claim 5, wherein said mixer is fixedly mounted on said anterior face of said substrate.

8. The assembly of claim 5, wherein said means for collecting light emitted from said sample comprises a collection fiber, said collection fiber comprising a second fiber optic threaded through said hollow center and passing through a conduit from said anterior face of said substrate to a well in said posterior face of said substrate, said well being dimensioned to receive a temperature regulation element.

9. The assembly of claim 8, wherein said collection fiber has a core diameter of approximately 600 microns, and wherein said collection fiber is fabricated from low OH⁻

silica.

10. The assembly of claim 8, wherein said means for electrically connecting said LED'"'"'s comprises bonding wires for interconnecting said LED'"'"'s.

11. The assembly of claim 10, where said means for electrically connecting said LED'"'"'s further comprises a metallization pattern on the anterior face and sides of said substrate, said metallization pattern forming electrical contacts for contacting said bonding wires.

12. The assembly of claim 11, wherein said means for electrically connecting said LED'"'"'s further comprises a metallization pattern on a printed circuit board (PCB), said PCB having an anterior face and a posterior face, said anterior face of said PCB defining a self-aligning indent adapted to receive said LED/substrate sub-assembly, said metallization providing electrical contacts that contact said electrical contacts on said substrate when said substrate is seated in said indent and that, in turn, contact a LED driver, so that said LED'"'"'s are electrically connected to said LED driver.

13. The assembly of claim 12, wherein said LED'"'"'s are connected to a LED driver individually.

14. The assembly of claim 12, wherein said LED'"'"'s are connected to a LED driver in groups.

15. The assembly of claim 12, wherein said PCB defines an aperture, so that said substrate conduit and said PCB aperture align when said LED/substrate sub-assembly is seated in said PCB.

16. The assembly of claim 15, wherein said means for regulating temperature comprises a thermo-electric cooler, having a cold side and a hot side, that fits through said aperture to be received by said posterior well so that said cold side is in contact with said posterior face of said substrate;

and

a heat sink, said heat sink in contact with said hot side of said cooler;

wherein said thermoelectric cooler and said heat sink together comprise a sub-assembly.

17. The assembly of claim 16, further comprising a support ferrule, wherein said collection fiber passes through said PCB aperture and said thermoelectric cooler-heat sink sub-assembly to be received by said ferrule at the posterior face of said PCB.

18. The assembly of claim 1, wherein said LED/substrate sub-assembly is coated with one of optical epoxy and a polymeric resin to provide mechanical protection and minimize Fresnel'"'"'s losses, said coating having favorable transmission characteristics in the wavelength range of the light source assembly.

19. The assembly of claim 18, wherein said substrate is fabricated from one of a ceramic resin and a plastic resin.

20. The assembly of claim 19, wherein said coating has a refractive index of:

21. The assembly of claim 1, further comprises at least one sensor for monitoring and controlling any of skin temperature and surface hydration at said measurement site.

22. The assembly of claim 1, wherein said assembly is incorporated into an instrument for noninvasive glucose determination.

50. The instrument of claim 22, wherein said sample interface comprises a fiber optic probe.

53. The instrument of claim 22, further comprising at least one sensor for monitoring and controlling any of skin temperature and surface hydration at said measurement site.

23. An instrument for non-invasive blood analyte determination comprising:

a light source assembly for non-invasive optical sampling comprising;

a plurality of LED'"'"'s, wherein at least one of said plurality of LED'"'"'s emits at a wavelength region different from and overlapping with that of at least another of said plurality of LED'"'"'s;

a LED substrate;

said substrate providing mechanical support for said LED'"'"'s, so that said LED'"'"'s and said substrate form a LED/substrate subassembly;

means for controlling light intensity profile;

means for electrically connecting said LED'"'"'s;

means for shaping light beams emitted from said LED'"'"'s;

means for coupling said signal to a sample interface;

means for collecting light emitted from said sample;

wherein said LED'"'"'s are combined to provide a wide band signal coupled to a tissue measurement site and wherein light emitted from a sample is collected; and

wherein said means for shaping light beams emitted from said LED'"'"'s comprises a plurality of parabolic reflectors, wherein each reflector is mounted within a well on an anterior face of said substrate, and wherein each of said LED'"'"'s is fixedly attached within a corresponding reflector, so that divergence between light beams is minimized;

an optical module, for any of dispersing, focusing and detecting said emitted light;

a LED driver for powering said LED'"'"'s;

processor means for executing a prediction algorithm; and

display means for outputting said analyte determination.

24. The instrument of claim 23, wherein said substrate has a posterior face and sides.

25. The instrument of claim 23, wherein said LED/substrate sub-assembly is coated with one of optical epoxy and a polymeric resin to provide mechanical protection and minimize Fresnel'"'"'s losses, said coating having favorable transmission characteristics in the wavelength range of the light source assembly.

26. The instrument of claim 25, wherein said means for electrically connecting said LED'"'"'s comprises bonding wires for interconnecting said LED'"'"'s.

27. The instrument of claim 26, where said means for electrically connecting said LED'"'"'s further comprises a metallization pattern on the anterior face and sides of said substrate, said metallization pattern forming electrical contacts for contacting said bonding wires.

28. The instrument of claim 27, wherein said means for electrically connecting said LED'"'"'s further comprises a metallization pattern on a printed circuit board (PCB), said PCB having an anterior face and a posterior face, said anterior face of said PCB defining a self-aligning indent adapted to receive said LED/substrate sub-assembly, said metallization providing electrical contacts that contact said electrical contacts on said substrate when said substrate is seated in said indent;

wherein said PBC that in turn contacts said LED driver, so that said LED'"'"'s are electrically connected to said LED driver;

wherein said LED'"'"'s are connected to said LED driver either individually or in groups.

29. The instruments of claim 28, wherein said PCB defines an aperture, so that said substrate conduit and said PCB aperture align when said LED/substrate sub-assembly is seated in said PCB.

30. The instrument of claim 29, wherein said temperature regulating elements comprises a thermo-electric cooler, having a cold side and hot side, that fits through said aperture to be recieved by said posterior well so that said cold side is in contact with said posterior face of said substrate;

and

a heat sink, said heat sink in contact with said hot side of said cooler, wherein said thermo-electric cooler and said heat sink together comprise a thermoelectric cooler-heat sink subassembly.

31. The instrument of claim 30, further comprising a support ferrule, wherein said collection fiber passes through said PCB aperture and said thermoelectric cooler-heat sink subassembly to be recieved by said ferrule at the posterior face of said PCB.

32. The instrument of claim 26, wherein said LED driver comprises:

a module for powering said LED'"'"'s, so that said individual LED'"'"'s and said groups of LED'"'"'s are;

serially addressable, one LED or group of LED'"'"'s at a time;

simultaneously addressable, all LED'"'"'s or groups of LED'"'"'s at a time; and

wherein selected groups or selected LED'"'"'s are flexibly sequenceable according to one or more stored, pre-programmed sequences.

33. The instrument of claim 32, wherein said module produces pulses of approximately 100-400 nanoseconds, with programmable high peak current of up to 10 amps, and wherein said module drives LED'"'"'s or groups of LED'"'"'s in continous wave mode at current levels of approximately 100-500 mA, and wherein said LED module drives said LED'"'"'s or groups of LED'"'"'s under either of AC or DC conditions.

34. The instrument of claim 23, wherein said means for coupling said signal to a sample interface comprises a mixer, said mixer comprising a large diameter fiber optic having a hollow center and having a high index of refraction, so that wavelength content and intensity of light beams emanating from said LED/substrate sub-assembly are throughly mixed without introducing additional light loss.

35. The instrument of claim 34, wherein said mixer is fixedly mounted on said anterior face of said substrate.

36. The instrument of claim 35, wherein said means for collecting light emitted from said sample comprises a collection fiber, said collection fiber comprising a second fiber optic threaded through said hollow center and passing through a conduit from said anterior face of said substrate to a well in said posterior face of said substrate, said well being dimensioned to receive a temperature regulation element.

37. The instrument of claim 36, wherein said optical module comprises:

a miniature spectrum analyzer having entry and output slits;

a linear detector array module, said spectrometer and said dector array module fixedly attached to each other such that said output slit and a face of said detector array module are facing.

38. The instrument of claim 37, wherein width of said entry slit equals width of an individual pixel in a linear detector array within said linear detector array assembly.

39. The instrument of claim 38, wherein said spectrum analyzer comprises:

a mirror, wherein a light beam emmitted from said collection fiber and projected through said entry slit is folded by said mirror;

a concave holographic grating, wherein said folded light beam is projected from said mirror and dispersed and focused by said grating;

wherein a flat field section of said spectrum is projected toward said array through said output slit.

40. The instrument of claim 37, wherein said linear detector array comprises a linear photodiode array, each photodiode comprising a detection element and an associated multiplexer element, each photodiode representing a pixel, wherein said photodiodes each simultaneously record a one pixel portion of said projected spectrum, so that the entire spectrum is recorded, and wherein said portions of said recorded spectrum are converted into a voltage by said detection elements.

41. The instrument of claim 40, wherein said multiplexing elements read signals output from each of said detection elements in a serial fashion.

42. the instrument of claim 41, wherein said linear detector array module further comprises a signal conditioning circuit, wherein said multiplexing elements transfer said signals to said conditioning circuit of conditioning though any of:

buffering;

impedance matching;

frequency smoothing; and

level-shifting.

43. The instrument of claim 42, wherein said linear detector array assembly further comprises an analog-to-digital conversion circuit (ADC), wherein said signal conditioning circuit transfers said conditioned signal to said ADC;

wherein said ADC converts said conditoned signal to digital values and transfers said digital values to said processor means.

44. The instrument of claim 43, wherin said processor means comprises a high speed digital electronics module, said module including:

a digital signal processor; and

at least one memory;

wherein said module receives said digital values form said optical module and processes said digital values according to said prediction algorithm to arrive at an estimate of target analyte concentration.

45. The instrument of claim 44, wherein said memory comprises non-volatile memory, and wherein said algorithm is stored in said non-volatile memory.

46. The instrument of claim 44, wherein said memory comprises volatile memory, and wherein said digital values are stored in said volatile memory.

47. The instrument of claim 23, wherein said display means comprises a high-resolution LCD.

48. The instrument of claim 23, further comprising a power supply, said power supply comprising a nickel-metal-hydride battery.

49. The instrument of claim 23, further comprising a control means, said control means comprising one of keypad and a speech recognition module.

51. The instrument of claim 23, wherein said prediction algorithm estimates concentration of a target analyte based on spectroscopic analysis of light emitted from a sampling site.

52. The instrument of claim 23, wherein said analyte comprises glucose.