WO2011152747A1 - Analyse de matériel photoacoustique - Google Patents

Analyse de matériel photoacoustique Download PDF

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Publication number
WO2011152747A1
WO2011152747A1 PCT/RU2010/000281 RU2010000281W WO2011152747A1 WO 2011152747 A1 WO2011152747 A1 WO 2011152747A1 RU 2010000281 W RU2010000281 W RU 2010000281W WO 2011152747 A1 WO2011152747 A1 WO 2011152747A1
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WIPO (PCT)
Prior art keywords
medium
phase
conjugated
probe
acoustic oscillations
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Application number
PCT/RU2010/000281
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English (en)
Inventor
Dzhomart Fazylovich Aliev
Anatoly Kravets
Alexandr Sergeevich Pristupnitskiy
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H.L Human Laser Limited
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Priority to PCT/RU2010/000281 priority Critical patent/WO2011152747A1/fr
Publication of WO2011152747A1 publication Critical patent/WO2011152747A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0093—Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy
    • A61B5/0095—Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy by applying light and detecting acoustic waves, i.e. photoacoustic measurements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/1702—Systems in which incident light is modified in accordance with the properties of the material investigated with opto-acoustic detection, e.g. for gases or analysing solids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence

Definitions

  • the present invention relates to electro-optics in general, and more particularly to
  • a laser beam is used to rapidly heat a sample generating an acoustic pressure wave that can be measured by high-sensitivity ultrasonic detectors such as piezo-electric crystals, microphones, optical fiber sensors, laser interferometers or diffraction sensors.
  • high-sensitivity ultrasonic detectors such as piezo-electric crystals, microphones, optical fiber sensors, laser interferometers or diffraction sensors.
  • the laser radiation wavelength is selected so as to be absorbed by the interest component in the medium being analyzed.
  • laser excitation of a medium is used to generate an acoustic response and a spectrum as the laser is tuned.
  • the use of photoacoustic spectroscopy for glucose testing in blood and human tissue can provide greater sensitivity than conventional spectroscopy. An excellent correlation between the photo-acoustic signal and blood glucose levels has been demonstrated on index fingers of both healthy and diabetic patients.
  • U.S. Pat. No. 5348002 of Caro discloses a method and apparatus for determining the presence and/or concentration of chemical species, which absorb electromagnetic energy, dependent to a degree upon the chemical species and the wavelength of electromagnetic energy applied to matter including said species. The absorbed electromagnetic energy generates acoustic energy, which is detected and analyzed to determine the presence and/or concentration of the chemical species in the matter.
  • U.S. Pat. No. 5941821, and U.S. Pat. No. 6049728 of Chou describe method and apparatus for noninvasive measurement of blood glucose by photoacoustic techniques in which an excitation source provides electromagnetic energy at a wavelength corresponding to the absorption characteristics of the analysis. Upon irradiation, acoustic energy is generated in a relatively thin layer of the sample to be measured, characterized by a heat-diffusing length. The acoustic emission is detected with a differential microphone, one end of which is positioned in a measuring cell and the other end of which is positioned in a reference cell. A processor determines the concentration of the substance being measured based upon the detected acoustic signal.
  • the excitation source is preferably tuned to the absorption bands of glucose in spectral ranges from about 1520-1850 nm and about 2050-2340 nm to induce a strong photo-acoustic emission.
  • water absorption is relatively weak and glucose absorption is relatively strong.
  • the electromagnetic radiation is able to penetrate through the tissue to a sufficient depth to allow for accurate measurements.
  • the acoustic signal which is generated by the absorption of electromagnetic radiation by glucose is not overwhelmed by that generated by water.
  • the glucose optically absorbs the energy inducing a temperature rise and generating an acoustic emission indirectly in the air.
  • the photoacoustic intensity is approximately linearly proportional to the glucose concentration.
  • U.S. Pat. No. 6403944, and U.S. Pat. No. 6833540 of MacKenzie et al. describe a system for measuring a biological parameter, such as blood glucose, the system comprising the steps of directing laser pulses from a light guide into a body part consisting of soft tissue, such as the tip of a finger to produce a photoacoustic interaction. The resulting acoustic signal is detected by a transducer and analyzed to provide the desired parameter.
  • a biological parameter such as blood glucose
  • U.S. Pat. No. 6484044 of Lilienfeld-Toal describes an apparatus for detecting a substance in a sample, particularly for in vivo detecting and measuring glucose in body tissue or blood contains a semiconductor laser for emitting mid-infrared laser light at least two discrete wavelengths, each at a different peak or valley in the absorption spectrum of the substance in the sample.
  • a photoacoustic detector detects acoustic signals originating from absorption of the laser light.
  • An indication unit evaluates the acoustic signals separately for each wavelength and calculates a detection result based on all acoustic signals from the different wavelengths.
  • the light penetration depth in human tissue at these wavelength ranges equals 0.5 - 3 mm of skin dermis layer, where glucose levels in the interstitial fluid (ISF) that surrounds the cells within the tissue are about 10% lower than glucose levels in blood.
  • ISF interstitial fluid
  • a peak or valley in the absorption spectrum of glucose can not be indicated really, and using the photoacoustic technique of Lilienfeld-Toal U.S. Pat. No. 6484044 is impossible.
  • U.S. Pat. No. 6921366 of Jeon et al. describes an apparatus and method for non-invasively measuring bio-fluid concentrations using photoacoustic spectroscopy, includes a light source for irradiating an incident light having a predetermined wavelength band to be absorbed into a targeted component of a living body, an acoustic signal generator for generating a first acoustic signal having a similar frequency band as a photoacoustic signal that is generated when the incident light is absorbed into the targeted component.
  • the frequency repetition of the light short pulses in the pulse-train is chosen equal to the natural acoustic oscillation frequency of the thin layer of the medium that can be considered as a thin membrane. So, the acoustic oscillation becomes resonant. Measuring of the amplitude and the frequency of the resonant oscillations determine the concentration of interest component.
  • the method and apparatus are suitable for monitoring of blood components, especially glucose. A sensitivity level and a signal-to-noise ratio are increased by a photoacoustic resonance method.
  • prior art photoacoustic material analysis techniques are disadvantageous in that they teach the application of energy to a medium without giving consideration to overlapping of absorption bands of different components, and irregularity of elastic properties of a medium, such as human skin. Consequently, such techniques provide an inadequate level of sensitivity and large errors of measuring.
  • the primary object of the present invention is to provide a novel method and apparatus of photoacoustic material analysis based on using phase-conjugated photoacoustic spectroscopy with probe and reference light beams having predetermined different wavelengths of equidistant short pulses having variable frequency, number, and power.
  • the wavelength of the probe beam is selected so as to be corresponded preferably to maximum of an absorption band of an interest component in a medium or may be in the range of the absorption band.
  • the wavelength of the reference beam is selected so as to be corresponded preferably to minimum of the absorption band of the said interest component or may be not far from the minimum.
  • the both beams are directed to the same testing area of the target.
  • acoustic oscillations are generated due to the light absorption in a relatively thin layer of the medium, characterized by a heat-diffusing length.
  • the amplitude, frequency and relaxation rate of the photoacoustic oscillations excited by probe beam depend on the concentration of interest component and also depend on concentration of the other components, which absorption bands overlapping with absorption band of said interest component in a medium.
  • the amplitude, frequency and relaxation rate of the photoacoustic oscillations excited by the reference beam only depend on the concentration of components, which absorption bands overlapping with absorption band of interest component, irrespective of concentration of interest component.
  • the frequency repetition of the short pulses of the probe beam is chosen equal to be in-phase with natural acoustic oscillations in the medium.
  • the frequency repetition of the short pulses of the reference beam is chosen equal to be anti-phase or independent to acoustic oscillations excited by the probe beam.
  • Measuring of the amplitude and the frequency of the phase-conjugated photoacoustic oscillations determine the concentration of interest component.
  • the second object of the present invention is to provide a novel method and apparatus of photoacoustic material analysis based on detecting frequency, number, and power of light pulses of probe and reference beams and generating representative electrical signals using for feedback operation of the apparatus.
  • the third object of the present invention is to provide a novel method and apparatus of photoacoustic material analysis based on laser-induced changes of light scattering due to photoacoustic oscillations in a turbid medium such as human tissue and determination of the concentration of an interest component in the medium by measuring of the amplitude and the frequency of the phase-conjugated oscillations.
  • the next object of the present invention is to provide a novel method and apparatus of photoacoustic material analysis based on using novel dual-wavelength pulsed laser source that comprises at least two discrete chips of pulsed laser diodes and at least two chips of photodiodes on ceramic sub-mounts in one package.
  • the laser source is suitable to generate acoustic oscillations and light scattering oscillations in the testing area and determinate the concentration of an interest component in the medium by measuring of the amplitude and the frequency of the phase-conjugated oscillations.
  • a method of calibrating an electronic-optical apparatus for determining a concentration of an interest component in a medium comprising the steps of obtaining a sample of a fluid containing an interest component; determining a first concentration of the interest component using a fluid-based apparatus; determining a second concentration of the interest component using the electronic- optical apparatus; and determining if the second concentration is equivalent to the first concentration, wherein if the second concentration is not equivalent to the first concentration, offsetting the electronic-optical apparatus such that the second concentration is equivalent to the first concentration.
  • the present invention allows to abate an influence of overlapping of absorption bands of different components, and the skin irregularity on determining a concentration of an interest component in a medium and, thus, to increase the signal-to-noise ratio and testing sensitivity.
  • the present invention is suitable for measuring blood components in human tissue, especially glucose.
  • FIG. 1 is a simplified, cross-sectional view of an implementation of an electronic-optical apparatus, constructed and operative in accordance with a preferred embodiment of the present invention.
  • FIG. 2 is a simplified block diagram of an electronic-optical apparatus of FIG. 1, constructed and operative in accordance with a preferred embodiment of the present invention.
  • FIG. 3 is a simplified graphical illustration of acoustic oscillations in a medium upon the probe and the reference light beams that to be phase-conjugated in accordance with a preferred embodiment of the present invention.
  • FIG. 4 is a simplified graphical illustration of resonant curves caused by pulse-train laser- excitation in accordance with a preferred embodiment of the present invention.
  • FIG. 5 is a simplified, cross-sectional view of an embodiment of the electronic-optical apparatus of FIG. 2 using a dual- wavelength pulsed laser diode.
  • FIG. 6 is a simplified, cross-sectional view of an embodiment of the electronic-optical apparatus of FIG. 2 using a bundle of optical wave-guides.
  • FIG. 7 is a simplified, other cross-sectional view of an embodiment of the electronic-optical apparatus of FIG. 2 using a bundle of optical wave-guides.
  • FIG. 8 is a simplified, cross-sectional view of an embodiment of the electronic-optical apparatus of FIG. 2 using an acoustic detector such as a microphone.
  • FIG. 9 is a flowchart illustrating a method for determining a concentration of an interest component in a medium, consistent with the present invention.
  • FIG. 10 is a flowchart illustrating a method for calibrating an optical apparatus consistent with the present invention.
  • FIG. 1 is a simplified, cross-sectional view of an
  • the apparatus preferably includes at least two chips of pulsed laser diodes as dual-wavelength pulsed laser source and three chips of photodiodes. Ceramic sub-mounts (not shown) for the said chips may be used into the interior of a optical cell 10 with glass window 12 that put on surface of target 14, like human skin testing area 16.
  • the optical cell 10 may be similar to TO- 5 package with thickness of glass window 12 equals 0.3 mm.
  • the chip 18 of the first pulsed laser diode preferably provides light pulses generation of probe beam 20 with wavelength corresponding to maximum of an absorption band of an interest component in a medium or in the range of the absorption band.
  • the chip 22 of the second pulsed laser diode preferably provides light pulses generation of reference beam 24 with wavelength corresponding to minimum of the absorption band of the interest component or not far from the minimum.
  • the both beams 20 and 24 comprise preferably light pulse-trains of equidistant short pulses having variable duration, frequency, number, and power.
  • Probe beam 20 and reference beam 24 are passed through glass window 12 and directed to the same testing area 16 of the target 14 such as human body to produce in said testing area 16 phase-conjugated acoustic oscillations that define changes of back light scattering 26.
  • One part power of the probe and/or the reference beam excites the acoustic oscillations in testing area due to absorption, and another part of the beams scatters in the testing area 16.
  • the acoustic oscillations induce changes of light scattering, according to EQ.l - EQ. 21 described further.
  • the back scattered light 26 of the probe beam 20 and the reference beam 24 are passed through glass window 12 and registered by photosensitive area 28 of the first photodiode 30 and photosensitive area 32 of the second photodiode 34.
  • Backside of the chip 18 generates beam 36 with power about 1% of probe beam 20.
  • backside of the chip 22 generates beam 38 with power about 1% of reference beam 24.
  • the beams 36 and 38 are registered by photosensitive area 40 of the third photodiode 42 to control of frequency and power light pulses generation of probe beam 20 and reference beam 24. It allows feedback operation of the electronic-optical apparatus using pinouts (not shown) for the laser diodes and photodiodes into the interior of the optical cell 10.
  • commercial chips 18 and 22 with wavelength radiation in the spectral range of 1550-1750 nm, and preferably 1550- 1625 nm, as the probe beam 20 may be used for noninvasive determination of glucose concentration in human tissue. Additional wavelength radiation in the spectral range of 1300- 1520 nm, and preferably 1480- 1520 nm, may be used as the reference beam 24.
  • the amplitude, frequency and relaxation rate of the photoacoustic oscillations excited by probe beam 20 depend on the concentration of interest component, such as glucose, and also depend on concentration of the other components, such as water, which absorption bands overlapping with absorption band of said interest component in a medium such as human tissue.
  • the frequency repetition of the short pulses of the probe beam 20 is chosen equal to be in- phase with natural acoustic oscillations in the medium.
  • the frequency repetition of the short pulses of the reference beam 24 is chosen equal to be anti-phase or independent to acoustic oscillations excited by the probe beam 20.
  • Measuring of the amplitude and the frequency of the laser-induced changes of light scattering 26 due to photoacoustic oscillations determine the concentration of interest component.
  • FIG. 2 is a simplified block diagram of an electronic-optical apparatus, constructed and operative in accordance with a preferred embodiment of the present invention and cross-sectional view shown FIG. 1.
  • the electronic-optical apparatus includes an electronics enclosure 44 connected to the optical components enclosure in the optical cell 10 that is shown FIG. 1.
  • Electronics enclosure 44 may be connected to optical components through conductors, wires, wirelessly, or electronics enclosure 44 and optical components may be contained in a single enclosure, with electrical connection there between.
  • Optical components enclosure in the optical cell 10 may be operable to irradiate target 14 by the probe beam 20 and the reference beam 24.
  • Probe beam 20 and reference beam 24 are passed through glass window 12 to produce in target 14 phase-conjugated acoustic oscillations and back scattered light oscillations.
  • Back scattered light 26 of the probe beam 20 and the reference beam 24 are passed through glass window 12 and registered by the first photodiode 30 and of the second photodiode 34.
  • Backside of the chip 18 generates beam 36 and backside of the chip 22 generates beam 38 that are registered by the third photodiode 42 to control of frequency and power light pulses generation of probe beam 20 and reference beam 24 and feedback operation of the electronic-optical apparatus.
  • the both beams 20 and 24 comprise preferably light pulse-trains of equidistant short pulses having at least variable frequency, number, and power.
  • the frequency repetition of the short pulses of the probe beam 20 is chosen equal to be in-phase with natural acoustic oscillations in the medium.
  • the frequency repetition of the short pulses of the reference beam 24 is chosen equal to be anti-phase or independent to acoustic oscillations excited by the probe beam 20.
  • the electronic-optical apparatus may be connected to power source 46 for providing power to both electronics enclosure 44 and optical components enclosure in the optical cell 10, and components located therein.
  • power source 46 may be included in either of electronics enclosure 44 or optical components enclosure in the optical cell 10, and may be AC or DC. Moreover, if electronics enclosure 44 and optical components enclosure in the optical cell 10 are connected wirelessly, a separate additional power source may be connected to optical components enclosure in the optical cell 10.
  • the electronic-optical apparatus may further be connected to an external processing device 48 for displaying, monitoring, tracking results, and calibrating the optical apparatus.
  • External processing device may comprise a personal computer (PC), a personal digital assistant (PDA), a smartphone, or other such device.
  • electronics enclosure 44 may house an array of electronic components suitable for facilitating the determination of a concentration of an interest component in a medium.
  • electronics enclosure 44 may include a processor or CPU 50, a first radiation driver 52, a second radiation driver 54, a first peak detector 56, a second peak detector 58, and third peak detector 60, a multiplexer (MUX) 62, and an analog-to-digital converter (ADC) 64.
  • a processor or CPU 50 may include a processor or CPU 50, a first radiation driver 52, a second radiation driver 54, a first peak detector 56, a second peak detector 58, and third peak detector 60, a multiplexer (MUX) 62, and an analog-to-digital converter (ADC) 64.
  • MUX multiplexer
  • ADC analog-to-digital converter
  • optical components enclosure in the optical cell 10 may house an array of optical components for use in determining the concentration of an interest component in a medium.
  • probe beam 20 and reference beam 24 may be emitted from a single radiation source including chips 18 and 22 of the pulsed laser diodes.
  • a single detector may be configured to receive back-scattered light 26 of the probe beam 20 and the reference beam 24.
  • two detectors for example, first detector 30 and a second detector 34 may be configured to separately receive back-scattered light 26 of the probe beam 20 and the reference beam 24.
  • Optical-electronics enclosures may further include beam splitters 66 and 68 of the probe beam 20 and the reference beam 24 for getting of the beams 36 and 38.
  • the beams 36 and 38 are registered by the third photodiode 42 to control of frequency and power light pulses generation of probe beam 20 and reference beam 24 and feedback operation of the electronic-optical apparatus.
  • the detectors 30, 34, and 42 may be optical receiving sensors, such as a photodiode, including a P-Intrinsic-N (PIN) photodiode, an avalanche photodiode, a photoelectrical multiplier, a photoresistor, a charge-coupled device (CCD) or other device capable of converting light into electricity.
  • An amplifier (not shown) may further be included in optical- electronics enclosures, for amplifying the power of the back-scattered radiation 26.
  • the detectors convert detected the back-scattered radiation 26 and controlling beams 36 and 38 into electrical signals for processing.
  • the electrical signals may represent at least one of the amplitude, frequency, or decay time of any transient processes that may be produced in target 14.
  • the electrical signals are then transmitted from first, second, and third peak detectors 56, 58, and 60 to multiplexer 62.
  • Multiplexer 62 combines the electrical signals from the peak detectors and outputs a single combined electrical signal to analog-to- digital converter 64.
  • Analog-to-digital converter (ADC) 64 converts the input analog electrical signal into a digital electrical signal and outputs the digital electrical signal to processor 50.
  • ADC Analog-to-digital converter
  • Processor 50 receives the digital electrical signals and executes instructions, which may be stored in an internal memory (not shown), for performing calculations using the digital electrical signals.
  • processor 50 may calculate laser-induced changes of light scattering intensity of radiation 26 caused by photoacoustic oscillations in target 14 and any subsequent transient processes that may occur in target 14 as a result of emitted probe beam 20 and the reference beam 24.
  • the result of emitting depends on variable duration, frequency, number, and power of the beams and variable delay time between pulses of probe beam 20 and the reference beam 24 as described below and shown in FIG. 3 and in FIG. 4.
  • processor 50 will then execute instructions to perform an algorithm for calculating the concentration of an interest component present in testing area 16. Consistent with the present invention, the calculations may also be performed by an external processor, for example, a processor contained in PC 48. The calculated concentration may then be displayed on a display screen attached to electronics enclosure 44, or on computer 48. Moreover, the concentration may also be tabulated in computer 48 for trending and over-time analysis.
  • a system bluetooth (not shown) may be used for intersystem communication between PC 48 and processor 50.
  • processor 50 receives the digital electrical signals from the third photodiode 42 to control of frequency and power light pulses generation of probe beam 20 and reference beam 24 and executes instructions for feedback operation of the electronic-optical apparatus.
  • Processor 50 may be any suitable processor or microprocessor, and must implement conventional amplitude and frequency domain analysis techniques to analyze the amplitude, duration and temporal frequency response of the extracted diffuse light scattering signal in order to improve the signal-to-noise ratio.
  • Conventional chromometric spectral analysis techniques may also be utilized to deduce the observed diffuse light scattering spectrum in order to improve the detection limit and accuracy.
  • image analysis techniques may be used in conjunction with the optical apparatus described herein.
  • image analysis techniques may be used to ensure that first and second radiation beams 20 and 24 are consistently incident on testing area 16, with no variation.
  • Image analysis techniques may include video hardware and software, attached to and/or embedded on optical apparatus, which allows a user to accurately position optical apparatus such that radiation beams 20 and 24 are consistently incident on testing area.
  • a portable video camera could be installed such that a real time video feed could show user positioning optical apparatus on surface of target 14. Markers could be placed at testing area 16 so that user could reliably, using the video feed, align the optical apparatus with testing area 16 to ensure incidence thereon.
  • the efficacy of the laser for material analysis is highly dependent on the characteristics of the beam in terms of light amplitude distribution, mode of operation, width of fundamental pulse, instantaneous power within the pulse, wavelength, fine-tuning, and ability to change these and other beam parameters.
  • First 18 and second 22 radiation sources used in embodiments consistent with the present invention may be selected depending on such factors as the power or wavelength of radiation needed for accurately determining the concentration of an interest component, the periodicity of the radiation needed, size constraints or cost.
  • at least one of first 18 and second 22 radiation sources may be a pulsed tunable laser diode, a fiber-coupled diode laser array, a pulsed tunable fiber optical laser, a flash lamp, or a LED.
  • First 18 and second 22 radiation sources may further include combinations of these types of radiation sources.
  • at least one of first 18 and second 22 radiation sources may include an erbium (Er)-glass rod or slab laser pumped by additional diode lasers.
  • Er erbium
  • first 18 and second 22 radiation sources may include a tunable Co:MgF 2 laser.
  • at least one of first 18 and second 22 radiation sources may include a Q-switched neodymium containing optical medium laser.
  • An optical amplifier (not shown) may further be included in electronic-optical apparatus, for amplifying the power of the probe beam 20 and reference beam 24. Consistent with the present invention, optical amplifier may be an optical fiber amplifier. Electronic-optical apparatus may also further include an optical converter (not shown) for converting
  • FIG. 5 other embodiment of the electronic-optical apparatus of FIG. 2 using a dual- wavelength pulsed laser diode is shown in FIG. 5.
  • optical wave-guides may be used to inject probe beam 20 and reference beam 24 into target 14 and transmit back scattered light 26 to detectors 30 and 34 as shown in FIG. 6 and FIG. 7.
  • the dermal or epidermal area of the skin that generates acoustic waves can be considered as a thin membrane.
  • the amplitude and frequency of the acoustic oscillations may be measured by an acoustic detector such as microphone via air as shown in FIG. 8.
  • the membrane has natural oscillation frequencies that depend on the thickness of the membrane, its elastic constants, and the square of the membrane surface that is equal to the square of the aperture. If the repetition frequency of the light pulses causing the acoustic oscillations equals the oscillation frequency of the membrane, the oscillation becomes resonant as shown in FIG. 4. Under such circumstances the amplitude of the oscillations increases many times, increasing the signal-to-noise ratio and, thus, testing sensitivity.
  • FIG. 3 is a simplified graphical illustration of acoustic oscillations of a medium upon which short mono-pulse laser-excitation has been applied in accordance with a preferred embodiment of the present invention.
  • the duration ⁇ of the short laser pulse 70 of probe beam 20 or pulse 72 of reference beam 24 is much less than the period T 0 of the natural oscillations 74 of the target membrane, the oscillations will be damping. In this case, displacement of the membrane is
  • A amplitude of the membrane oscillation
  • a 0 is the primary amplitude
  • ⁇ is damping coefficient
  • ⁇ 0 is circular frequency of the natural oscillations 74 of the target membrane
  • ⁇ is the primary phase
  • oscillation phase is
  • T 0 is period of the natural oscillations of the membrane.
  • ⁇ is wavelength of the acoustic oscillations
  • v is phase velocity of the acoustic oscillations axial x normal to skin surface.
  • the mono-pulses of the probe beam and the reference beam excite phase- conjugated acoustic oscillations in-phase.
  • the mono-pulses of the probe beam and the reference beam excite phase- conjugated acoustic oscillations anti-phase.
  • the natural oscillations 74 of the target membrane will be damping and comprise about 10 amplitudes. So, the mono-pulses of the probe beam and the reference beam excite acoustic oscillations independently if the delay time At between the short mono-pulses 70 and 72 equals:
  • the delay time At between the laser mono-pulse 70 of probe beam 20 and laser mono-pulse 72 of reference beam 24 is chosen sufficient to excite phase-conjugated acoustic oscillations so as the short pulses of the reference beam 24 to be anti-phase to acoustic oscillations excited by the probe beam 20 (EQ.7) or independent (EQ.8).
  • the acoustic oscillations become anti-phase conjugated if
  • the acoustic oscillations become independent when delay time At between pulse-trains equidistant short pulses of the probe beam 20 and the reference beam 24
  • T 0 0.1-lms
  • the light pulse duration ⁇ 10-lOOns « T 0 .
  • T 0 1ms
  • the acoustic oscillations are independent if T> 10ms and f ⁇ 100Hz.
  • the frequency repetition of the short pulses of the probe beam 20 is chosen equal to be in-phase with natural acoustic oscillations in the medium.
  • the frequency repetition of the short pulses of the reference beam 24 is chosen equal to be antiphase with acoustic oscillations excited by the probe beam 20.
  • the frequency repetition of the pulse-trains equidistant short pulses of the reference beam 24 is chosen equal to be independent to acoustic oscillations excited by the probe beam 20.
  • FIG. 4 is a simplified graphical illustration of resonant curves 76 caused by equidistant pulses of laser-excitation.
  • the frequency ⁇ of the equidistant short pulses equals the natural oscillation frequency ⁇ 0 of a medium for different damping coefficients ⁇ . It may thus be seen from FIG. 4 that a desirable resonant condition may be expressed by the equation:
  • the resonant oscillation frequency of human skin equals 1 - 3 kHz and number of the natural oscillation of the membrane more than 10.
  • a laser light pulse upon absorption induces an adiabatic temperature rise resulting in a pressure build-up, followed by an acoustic shock wave propagating to the surface.
  • the product of the absorption coefficient and local fluence rate, as well as thermophysical properties of the medium determines the amplitude of the generated photoacoustic signal.
  • the light path of the photon as it is scattered before being absorbed is therefore not relevant.
  • Ultrasonic transduction is preferably used for detection of acoustic oscillations of the surface.
  • resonant acoustic oscillations is the simplest case of in-phase conjugated acoustic oscillations in a medium.
  • a natural acoustic oscillations equals 2 kHz
  • pulsed probe light beam having pulse power equals 10 W and pulse duration equals 100 ns.
  • pulse energy equals 1 uJ
  • FIG. 5 illustrates a simplified, cross-sectional view of an embodiment of the electronic-optical apparatus of FIG. 2 using a dual-wavelength pulsed laser diode 10 for determining a concentration of interest component, consistent with the present invention.
  • the dual-wavelength pulsed laser diode 10 may comprise at least two discrete chips 18 and 22 of pulsed laser diodes. At least one chip of photodiode 42 for feedback operation of the electronic-optical apparatus 44 using pinouts (not shown). All the chips are arranged on ceramic sub-mounts (not shown) in one package.
  • the chip 18 preferably provides light pulses generation of probe beam 20 and giving equidistant short laser pulses having variable frequency and power with wavelength corresponding to maximum of an absorption band of an interest component in a medium or in the range of the absorption band.
  • the chip 22 preferably provides light pulses generation of reference beam 24 and giving equidistant short laser pulses having variable frequency and power with wavelength corresponding to minimum of the absorption band of the interest component or not far from the minimum.
  • the both beams 20 and 24 are passed through glass window 12 and directed to the same testing area 16 of the target 14 such as human finger that defines the laser-induced changes of light scattering 26, which is registered by a remote photodetector 30.
  • One part power of the probe and/or the reference beam excites the acoustic oscillations in testing area due to absorption, and another part of the beams scatters in the testing area 16.
  • the acoustic oscillations induce changes of light scattering, according to EQ.13 - EQ. 21 described below.
  • a distance "d" between the dual- wavelength pulsed laser diode and remote photodetector 30 may be tuned in the range 1- 10 mm, and preferably 2- 3 mm that is sufficient to detect phase- conjugated acoustic oscillations in a medium such as human finger.
  • An angle "a" between directions of the probe beam 20 and surface normal of remote photodetector 30 may be tuned in the range 0 - 180 degrees, and preferably 20 - 90 degrees that is sufficient to detect phase-conjugated acoustic oscillations in a medium such as human finger.
  • Backside of the chip 18 generates beam 36 with power about 1% of probe beam 20.
  • backside of the chip 22 generates beam 38 with power about 1% of reference beam 24.
  • the beams 36 and 38 are registered by photodiode 42 to control of frequency and power light pulses generation of probe beam 20 and reference beam 24 and feedback operation of the electronic-optical apparatus using pinouts (not shown).
  • commercial chips 18 and 22 with wavelength radiation in the spectral range of 1550-1750 nm, and preferably 1550- 1625 nm, as the probe beam 20 may be used for noninvasive determination of glucose concentration in human tissue. Additional wavelength radiation in the spectral range of 1300- 1520 nm, and preferably 1480-1520 nm, may be used as the reference beam 24.
  • the amplitude and relaxation rate of the photoacoustic oscillations excited by probe beam 20 depend on the concentration of interest component, such as glucose, and also depend on concentration of the other components, such as water, which absorption bands overlapping with absorption band of said interest component in a medium such as human tissue.
  • the amplitude and relaxation rate of the photoacoustic oscillations excited by the reference beam 24, only depend on the concentration of components, which absorption bands overlapping with absorption band of interest component, irrespective of concentration of interest component.
  • the frequency repetition of the short pulses of the probe beam 20 is chosen equal to be in- phase with natural acoustic oscillations in the medium.
  • the frequency repetition of the short pulses of the reference beam 24 is chosen equal to be anti-phase or independent to acoustic oscillations excited by the probe beam 20.
  • Measuring of the amplitude and the frequency of the laser-induced changes of light scattering 26 due to photoacoustic oscillations determine the concentration of interest component.
  • the photoacoustic signal expressed as a pressure, is determined by the thermo-elastic expansion coefficient ⁇ , optical absorption coefficient, ⁇ ⁇ , and distribution of the absorbed photons H (z) as follows:
  • ⁇ ( ⁇ ) ⁇ 2 ⁇ ( ⁇ ) ⁇ ⁇ /0 / , (EQ. 13)
  • EQ. 13 is strictly valid only when the heating process is instantaneous compared to the medium expansion resulting in instant stress generation.
  • Temporal stress confinement requires laser pulse durations that are much shorter than the time propagation across the light penetration depth in the medium. Laser pulses with duration of 10-100 nanoseconds are an ideal light source for excitation of acoustic oscillations in human tissue.
  • the pulse of the light applied to the medium causes heating of the local area under absorbed light energy, which is converted into heat.
  • the thermal shock pulse applied to the molecule of a medium causes a rapid change of the molecule's amplitude oscillation, and generation of the damped back scattered light oscillations.
  • the amplitude of oscillation is proportional to rate of the temperature change or to density of absorption power: ⁇ ( ⁇ ) ⁇ dT/dt.
  • the attenuation of the light back-scattered amplitude is proportional to the density of the light power and absorption coefficient of the medium ⁇ ( ⁇ ) ⁇ ⁇ ⁇ ( ⁇ ) ⁇ ⁇ (EQ. 14)
  • the light penetration depth represents the rate of decay of intensity of light in scattering media with respect to the path traveled by the light in the same direction as the incident light.
  • the Beer- Lambert Law describes the absorption of light intensity in a non-scattering medium:
  • I 0 is the light intensity incident on medium, / is the light intensity transmitted through the medium, x is optical path that usually equals thickness of sample; and the absorption coefficient:
  • the absorption coefficient is the probability of light absorption per unit path length.
  • the Lambert and the Beer laws are applicable only for transparent not turbid medium.
  • thermo energy In general conversion of the light into thermal energy (heat) depends not only on absorption phenomena but also on light scattering.
  • the scattering coefficient of the medium is expressed:
  • the scattering coefficient is the probability of equivalently isotropic (uniform in all directions) scattering per unit path length.
  • the elastic scattering of light of human tissue may be approximated by an equation that expresses the scattering coefficient for a tissue or a turbid medium as:
  • ⁇ 3.28 ⁇ 2 ⁇ (2 ⁇ intend,/ ⁇ )°' 4 (m- 1 ) 2 , (EQ. 19)
  • a the average cell diameter
  • p the density of the scattering particles (number concentration of cells)
  • n m the refractive index of interstitial fluid
  • ⁇ the wavelength.
  • the refractive index mismatch m n n m , where 3 ⁇ 4 represents the refractive index of the cells, and n m is the refractive index of the interstitial fluid.
  • the scattering coefficient changes as cell size a, density of the scattering particles p or refractive index n m change.
  • the scattering coefficient variation of tissue is dependent on the refractive index mismatch between the interstitial fluid (ISF) and the cellular membranes. So, it depends on the concentration of glucose in the ISF fluid. Glucose levels in ISF are about 10% lower than glucose levels in blood. An increase the glucose concentration, the absorption coefficient and refractive index of the ISF will increase, and refractive index mismatch will decrease. So, elastic scattering of light will decrease too if other parameters will be constant.
  • the wavelength of the light source corresponds to the absorption bands of glucose in two spectral ranges: 1520-1850 nm and 2050-2340 nm.
  • absorption by glucose is relatively stronger then absorption by water.
  • the absorption spectrum of glucose shows the two peaks at about 1600 and 2120 nm.
  • commercial pulsed or QCW laser diodes with wavelength radiation in the spectral range of 1550-1750 nm may be used as the probe beam 20, and commercial pulsed or QCW laser diodes with wavelength radiation in the spectral range of 1480-1520 nm may be used as the reference beam 24.
  • the scattering coefficients of human tissues are generally within the range 10-100 mm "1 , roughly (10 - 100) times greater than those for absorption.
  • the most highly scattering tissues include skin dermis, cerebral white matter, and bone.
  • Beer-Lambert (EQ. 17) law When a highly scattering medium is considered, the Beer-Lambert (EQ. 17) law must be modified to include an additive term due to scattering losses and a multiplier, to account for the increased optical pathlength due to scattering. Therefore this law cannot be solved to provide a measure of the absolute concentration of an interest component in a medium.
  • concentration of the interest constituent in the medium may be determined by measuring of difference between light scattering intensity of the probe 20 and reference 24 beams in accordance with the present invention.
  • the photoacoustic pressure induces change in the density of the scattering particles p, and therefore changes in scattering coefficient according to EQ.13 and EQ.19.
  • laser- induced changes of light scattering coefficient ⁇ 5 due to photoacoustic oscillations are proportional to the optical absorption coefficient ⁇ ⁇ , as the photoacoustic pressure, because the density of the scattering particles p change is proportional to the photoacoustic pressure P.
  • probe beam 20 and reference beam 24 produce in target 14 phase-conjugated acoustic oscillations and light scattering oscillations 26.
  • the acoustic oscillations may be registered by measuring the light scattering oscillations 26 using the first photodiode 30 and of the second photodiode 34.
  • An external pressure effects on light scattering oscillations 26 as well as internal photoacoustic pressure. So, the external pressure must be constant and controlled by a pressure sensor.
  • the scattering of light by human tissue depends on the refractive index mismatch. Thereby, decreasing refractive index mismatch between the background and the scattering particles and led consequently to decreased scattering. So, the glucose concentration in the interstitial fluid may be measured if other parameters in EQ.19 are constant. It is possible at low density of incident light power (static/elastic spectroscopy). The photoacoustic pressure induces change in the density of the scattering particles p, and therefore changes of scattering coefficient and the light scattering signal that is proportional to glucose
  • concentration in the interstitial fluid (dynamic/inelastic spectroscopy). It allows to abate an influence of other different components, and the skin irregularity, to increase the signal-to- noise ratio and, thus, testing sensitivity.
  • the optical absorption coefficient of the probe beam 20 at the wavelength corresponding to maximum of an absorption band of an interest component equals:
  • ⁇ ⁇ ⁇ is optical absorption coefficient causing only by the interest component
  • ⁇ ⁇ 2 is optical absorption coefficient causing only by another components, which absorption bands overlapping with absorption band of said interest component in a medium.
  • the optical absorption coefficient, and consequently the photoacoustic signal, excited by pulses of the probe beam 20, depends on concentration of the interest component, and also other components, which absorption bands overlapping with absorption band of said interest component in a medium.
  • the photoacoustic signal, excited by pulses of the reference beam 24, is related to optical absorption coefficient ⁇ ⁇ 2. So, it is proportionate only to the concentration of the other components, which absorption bands overlapping with absorption band of interest component in a medium, irrespective of said interest component.
  • the probe beam 20 may be used only to excite resonant acoustic oscillations according to prior art photoacoustic material analysis that described in U.S. Pat. No. 6466806 of Geva et al., in which the concentration of an interest component in a medium is determined by measuring of the amplitude and the frequency of the resonant oscillations.
  • the frequency repetition of the short pulses of the reference beam 24 is chosen equal to be anti-phase with acoustic oscillations excited by the probe beam 20 according to EQ.10, or independent to them according to EQ.l 1.
  • the frequency repetition of the short pulses of the both beams may be chosen equal to be in-phase with natural acoustic oscillations in the medium at i > 1. Measuring of the amplitude and the frequency of the phase-conjugated photoacoustic oscillations determine the concentration of interest component.
  • FIG. 6 illustrates a simplified, cross-sectional view of an embodiment of the electronic-optical apparatus of FIG. 2 using a bundle of optical waveguides.
  • the apparatus of FIG. 2 is designed as a sensor head inside a housing 78 comprising the optical wave-guides 80, 82, 84 and 86, typically a bundle of optical fibers.
  • the fiber 80 transmits the probe beam 20 to the testing area 16 of the target 14 such as human skin.
  • the fiber 82 transmits the reference beam 24 to the same testing area 16 of the target 14.
  • the fibers 84 and 86 transmit the back-scattered light 26 from the same testing area 16 of the target 14 to photodetector 30 and 34.
  • FIG. 7 illustrates a simplified, other cross-sectional view of an implementation the embodiment showed in FIG. 6.
  • the apparatus may be designed as a sensor head inside a housing 78 comprising the optical wave-guides 80, 82, 84 and 86, typically a bundle of optical fibers.
  • the many optical fibers may be arranged as shown in FIG. 7.
  • FIG. 7 illustrates an optical fiber arrangement, which includes two fibers 80 and 82 for transmitting the probe beam 20 and the reference beam 24 to target 14, and a plurality of pickup fibers 84 and 86 for transmitting scattered radiation 26 from the target 14 to a
  • FIG. 7 illustrates example of optical fiber arrangements consistent with the present invention, which include four fibers 84 for transmitting scattered radiation 26 from the target 14 to a photodetector 30 and 86 for transmitting scattered radiation 26 from the target 14 to a photodetector 34.
  • the use of the bundle of optical fibers allows for providing housing 78 for head of the bundle, which is small, lightweight, and easily able to be placed in contact with surface of the target 14.
  • One part power of the probe and/or the reference beam excites the acoustic oscillations in testing area due to absorption, and another part of the beams scatters in the testing area 16.
  • the acoustic oscillations induce changes of light scattering, according to EQ.l - EQ. 21.
  • the probe beam 20 may be used only to excite resonant acoustic oscillations according to prior art photoacoustic material analysis that described in U.S. Pat. No. 6466806 of Geva et al., in which the concentration of an interest component in a medium is determined by measuring of the amplitude and the frequency of the resonant oscillations. Consistent with the present invention, using in-phase conjugated acoustic oscillations at / > 1 allows excite resonant oscillations by probe beam having lower average power than it needs in prior art.
  • the frequency repetition of the short pulses of the probe beam is chosen equal to be in-phase with natural acoustic oscillations in the medium.
  • the frequency repetition of the short pulses of the reference beam is chosen equal to be anti-phase or independent to acoustic oscillations excited by the probe beam. Measuring of the amplitude and the frequency of the phase-conjugated photoacoustic oscillations determine the concentration of interest component.
  • Human skin includes an outer epidermis layer and an inner dermis layer. Microscopic roughness of the human skin surface causes the diffraction diffuse reflectance of light in edition to specular reflectance.
  • the specular reflected light is significantly wavelength dependent. It contains information about the complex refractive index of the material and an imaginary term that relates to the absorption coefficient.
  • the epidermis layer contains very little blood, and thus reflected rays contain little information about glucose. Specular reflectance is only useful when the bulk material is adequately represented by surface composition. When this is not the case, such as when performing noninvasive blood analyte measurements, this methodology can give a spurious result.
  • the bundle of optical fibers allows for providing very sensitive acoustic detector using the specular reflected light for measuring skin displacements.
  • FIG. 8 is a simplified, cross-sectional view of an
  • the apparatus of FIG. 2 is preferably arranged such that probe beam 20 is injected by wave-guide 88 at incidence angle and reference beam 24 is injected by wave-guide 90 at incidence angle a 2 into the interior of an acoustic cell 92.
  • Acoustic cell 92 may be constructed from any suitable material, preferably ABS plastic material. Acoustic cell 92 transmits the acoustic oscillations 94 from testing area 16 of the target 14 to acoustic detector 96 such as microphone via air.
  • Acoustic cell 92 preferably acts as a housing for acoustic detector 96 and a convex lenses 98, 100.
  • Acoustic cell 92 is designed to be positioned on the surface of a testing area 16 of target 14, such as human skin, and has an aperture 102 to permit laser light to be applied to the testing area.
  • Convex lens 98 serves to focus probe beam 20 and convex lens 100 serves to focus reference beam 24 in the same point 15 of the testing area 16 at certain distance " ⁇ " under target surface 14 that defines the natural acoustic oscillation of the surface.
  • Acoustic detector 96 detects the acoustic oscillations 94 from target testing area 16 within acoustic cell 92. Tuning an angle between directions of the probe and reference beams provide means sufficient to detect phase-conjugated acoustic oscillations in a medium.
  • the dermal or epidermal area of the skin that generates acoustic waves can be considered as a thin membrane.
  • the membrane has natural oscillation frequencies that depend on the thickness of the membrane, its elastic constants, and the square of the membrane surface that is equal to the square of the aperture 102. If the repetition frequency of the light pulses causing the acoustic oscillations equals to the oscillation frequency of the membrane, the oscillation becomes resonant. Under such circumstances the amplitude of the oscillations increases many times, increasing the signal-to-noise ratio and, thus, testing sensitivity.
  • the amplitude and frequency of the acoustic oscillations, excited by the probe beam 20 depend on the concentration of interest component in the human tissue due to absorption of light with a predetermined wavelength. Usually the photo-acoustic signal excited by probe beam 20 also depends on concentration of the other components, which absorption bands overlapping with absorption band of said interest component in a medium. The amplitude and frequency of the acoustic oscillations, excited by the reference beam 24, only depend on the concentration of components, which absorption bands overlapping with absorption band of interest component in a medium, irrespective of said interest component.
  • the glucose optically absorbs the light energy of probe beam 20, thereby inducing a temperature rise in target testing area 16 and generating acoustic oscillations 94 indirectly in air.
  • the acoustic wave spectrum depends on the glucose concentration in the interstitial fluid (ISF) that surrounds the cells within the tissue. Glucose levels in ISF are about 10% lower than glucose levels in blood.
  • the probe beam 20 may be used only to excite resonant acoustic oscillations according to prior art photoacoustic material analysis that described in U.S. Pat. No. 6466806 of Geva et al., in which the concentration of an interest component in a medium is determined by measuring of the amplitude and the frequency of the resonant oscillations. Consistent with the present invention, using in-phase conjugated acoustic oscillations at i > 1 allows to excite resonant oscillations by probe beam having lower average power than it needs in prior art.
  • the frequency repetition of the short pulses of the probe beam is chosen equal to be in-phase with natural acoustic oscillations in the medium.
  • the frequency repetition of the short pulses of the reference beam is chosen equal to be anti-phase or independent to acoustic oscillations excited by the probe beam. Measuring of the amplitude and the frequency of the phase-conjugated photoacoustic oscillations determine the concentration of interest component.
  • FIG. 9 is a flowchart illustrating a method for determining a concentration of an interest component in a medium, consistent with the present invention.
  • the method illustrated in FIG. 2 may be performed using the optical apparatus illustrated in FIG. 1.
  • the steps of FIG. 9 will be described in conjunction with the operation of FIG. 2.
  • a head of sensor which may be the optical cell 10 or an acoustic cell 92, is initially placed in contact with surface of the target 14 (104). Consistent with the present invention, testing area 16 may be at a surface of the target 14, or may be below surface of the target 14. Next testing area 16 is irradiated with a probe beam 20 (106). Testing area 16 is subsequently irradiated with a reference beam 24 (108).
  • the both beams 20 and 24 define the laser-induced oscillations of light scattering 26, which are registered (110) by photodetectors 30 and 34.
  • the acoustic oscillations 94 from testing area 16 of the target 14 may be registered also using acoustic detector 96 such as microphone via air.
  • the frequency repetition of the short pulses of the probe beam is chosen equal to be in-phase with natural acoustic oscillations in the medium.
  • the frequency repetition of the short pulses of the reference beam is chosen equal to be anti-phase or independent to acoustic oscillations excited by the probe beam. Measuring of the amplitude and the frequency of the phase-conjugated photoacoustic oscillations determine the concentration of interest component.
  • the probe beam 20 and the reference beam 24 may further cause periodic or non-periodic transient processes in the target 14, which may at least partially modulate scatterings of radiation 26.
  • the detector 96 (or photodetectors 30 and 34) converts detected acoustic oscillations 94 or scattered light oscillations 26 into electrical signals for processing.
  • the electrical signals may represent at least one of the amplitude, frequency, or decay time of any transient processes that may be produced in the target 14.
  • the electrical signals are then transmitted from first and second peak detectors 56 and 58 to multiplexer 62.
  • Multiplexer 62 combines the electrical signals from first and second peak detectors 56 and 58, and outputs a single combined electrical signal to analog-to-digital converter 64.
  • Analog- to-digital converter 64 converts the input analog electrical signal into a digital electrical signal and outputs the digital electrical signal to processor 50.
  • Processor 50 receives the digital electrical signals and executes instructions, which may be stored in an internal memory (not shown), for performing calculations using the digital electrical signals. For example, processor 50 may calculate changes in the intensity of scatterings of radiation 26 (112) caused by repeated emission of the probe beam 20 and the reference beam 24. From the calculated changes in intensity, processor 50 will then execute instructions to perform an algorithm for calculating the concentration of an interest component present at testing area 16 (114). Consistent with the present invention, the calculations may also be performed by an external processor, for example, a processor contained in PC 48. The calculated concentration may then be displayed for a user to view (116). Consistent with the present invention, the concentration may be displayed on a display screen attached to electronics enclosure 44, or on computer 48. Moreover, the concentration may also be tabulated in computer 48 for trending and over-time analysis.
  • processor 50 may calculate changes in the intensity of scatterings of radiation 26 (112) caused by repeated emission of the probe beam 20 and the reference beam 24. From the calculated changes in intensity, processor 50 will then execute instructions to perform an
  • image analysis techniques may be used in conjunction with the optical apparatus described herein.
  • image analysis techniques may be used to ensure that the probe beam 20 and the reference beam 24 are consistently incident on testing area 16, with no variation.
  • Image analysis techniques may include video hardware and software, attached to and/or embedded on optical apparatus, which allows a user to accurately position optical apparatus such that the probe beam 20 and the reference beam 24 are consistently incident on testing area.
  • a portable video camera could be installed such that a real time video feed could show user positioning optical apparatus on surface of the target 14. Markers could be placed at testing area 16 so that user could reliably, using the video feed, align the optical apparatus with testing area 16 to ensure incidence thereon.
  • FIG. 10 is a flowchart illustrating a method for calibrating an optical apparatus consistent with the present invention.
  • the interest component being tested is glucose, as described above, it is important for the health of the user that the concentrations obtained are accurate, and in conformance with other accepted means of testing glucose concentration. Accordingly, in performing a calibration process, the results of a standard in vitro blood test is compared to the results in vivo of the optical apparatus, and the optical apparatus is offset to match the blood test.
  • this calibration process has been summarized with respect to glucose testing, the calibration process described in detail below may also be used when using the optical apparatus consistent with the present invention to determine the concentration of interest component other than glucose.
  • Y is the glucose concentration
  • X is measuring value, for example amplitude of acoustic oscillations 94 from testing area 16 of the target 14 measured by acoustic detector 96 such as microphone;
  • At least two independent invasive measuring of different glucose concentration should be used for determining "a" and "b” parameters.
  • a calibrating needs to match in vivo with in vitro measuring within a predetermined degree of accuracy.
  • FIG. 10 flowchart illustrating, first, a fluid sample is obtained in vitro (118), and using a fluid concentration determining in vitro means, a first concentration of an interest component is determined (120). This first concentration is recorded, and then the optical apparatus consistent with the present invention is used to take a concentration measurement in vivo (122).
  • the optical apparatus performs a method, such as illustrated in FIG. 2, and determines a second concentration of the interest component in vivo (124).
  • the first concentration and the second concentration are compared to one another to determine if they match within a predetermined degree of accuracy (126). If the first concentration and the second concentration match, no further calibration is needed (128).
  • the optical apparatus is offset by a predetermined amount such that the second concentration will match the first concentration (130). After this step, the calibration is complete (132). Consistent with embodiments of the present invention, a computer, external to the optical apparatus or on-board the optical apparatus, may perform the recordation of the concentrations, the match determination, and the offset.

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Abstract

La présente invention concerne un procédé et un appareil destinés à déterminer la concentration d'un composant d'intérêt dans un milieu par spectroscopie photoacoustique à conjugaison de phases avec des faisceaux lumineux de sonde et de référence ayant des longueurs d'ondes différentes prédéterminées de courtes impulsions équidistantes ayant une fréquence, un nombre et une puissance variables. La longueur d'onde du faisceau de sonde est choisie pour être absorbée par le composant d'intérêt. La longueur d'onde du faisceau de référence est choisie pour être absorbée par les autres composants, les bandes s'absorption chevauchant la bande d'absorption du composant d'intérêt. Lors de l'irradiation, des oscillations acoustiques sont générées par la lumière absorbée dans une couche relativement fine du milieu, caractérisée par une longueur diffusant la chaleur. La répétition de fréquence des impulsions courtes du faisceau de sonde est choisie égale pour être en phase avec une oscillation acoustique naturelle dans le milieu. La répétition de fréquence des impulsions courtes du faisceau de référence est choisie égale pour être en opposition de phase avec les oscillations acoustiques excitées par le faisceau de sonde, ou indépendante de celles-ci. La mesure de l'amplitude et de la fréquence des oscillations photoacoustiques à conjugaison de phases détermine la concentration du composant d'intérêt. Le procédé et l'appareil constituent une surveillance adaptée des composants sanguins, notamment du glucose.
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CN106983494B (zh) * 2017-04-21 2021-02-09 中国科学院深圳先进技术研究院 多模态成像系统及其成像方法
CN109589106A (zh) * 2018-10-19 2019-04-09 天津大学 一种等差距的动态光谱差值提取方法

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