EP1714137A1 - Procede de determination de parametres cliniques et/ou chimiques dans un milieu, et dispositif pour la mise en oeuvre de ce procede - Google Patents

Procede de determination de parametres cliniques et/ou chimiques dans un milieu, et dispositif pour la mise en oeuvre de ce procede

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Publication number
EP1714137A1
EP1714137A1 EP05700362A EP05700362A EP1714137A1 EP 1714137 A1 EP1714137 A1 EP 1714137A1 EP 05700362 A EP05700362 A EP 05700362A EP 05700362 A EP05700362 A EP 05700362A EP 1714137 A1 EP1714137 A1 EP 1714137A1
Authority
EP
European Patent Office
Prior art keywords
unit
light waves
determined
medium
microwaves
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP05700362A
Other languages
German (de)
English (en)
Inventor
Patrick Linder
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Technomedica AG
Original Assignee
Technomedica AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/CH2004/000080 external-priority patent/WO2005078410A1/fr
Priority claimed from PCT/CH2004/000079 external-priority patent/WO2005078879A1/fr
Application filed by Technomedica AG filed Critical Technomedica AG
Publication of EP1714137A1 publication Critical patent/EP1714137A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • 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
    • A61B5/145—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
    • A61B5/1455—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 using optical sensors, e.g. spectral photometrical oximeters
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/02—Details
    • G01J3/04—Slit arrangements slit adjustment
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/12—Generating the spectrum; Monochromators
    • G01J3/14—Generating the spectrum; Monochromators using refracting elements, e.g. prisms
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/2823—Imaging spectrometer
    • 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
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/02—Details
    • G01J3/0205—Optical elements not provided otherwise, e.g. optical manifolds, diffusers, windows
    • G01J3/0229—Optical elements not provided otherwise, e.g. optical manifolds, diffusers, windows using masks, aperture plates, spatial light modulators or spatial filters, e.g. reflective filters
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/02—Details
    • G01J3/0256—Compact construction

Definitions

  • the present invention relates to a method according to the preamble of claim 1 and an apparatus for performing the method.
  • samples In order to be able to precisely determine substances or a concentration of a substance in the living body, samples must be taken from the body, which are then further processed using special analysis methods using suitable reagents. In these known methods, on the one hand, the ' sampling, e.g. Legs
  • the present invention is therefore based on the object of specifying a method and a device for determining clinical and / or chemical parameters with high accuracy in a medium.
  • the invention has the following advantages: by emitting light waves into the medium with a laser unit and measuring the light waves reflected in the medium with a phototransistor unit, the parameters occurring in the target area of the laser beam can be determined in a processing or control unit.
  • the frequency or wavelength of the waves generated by the laser unit is set according to the characteristic properties of the parameters to be determined, and the parameters are determined using the Measured signals measured photodiode unit. It has been shown that extremely accurate results, in particular for parameters such as cholesterol, can be obtained with the method according to the invention.
  • medium is understood to mean both solid, liquid or gaseous media or any mixed form of these media with any structure, in particular:
  • FIGS. 2A and 2B shows an output window for use in the part of the laser unit shown in FIGS. 2A and 2B
  • FIG. 4 shows the exit window according to FIG. 3 in a section parallel to the longitudinal axis according to FIGS. 2A and 2B,
  • 6A and 6B each show a section transverse to the longitudinal axis of a laser unit
  • 7 shows a schematic illustration of an embodiment variant in which a mirror unit and an output window are always arranged centrally with respect to a laser diode unit
  • FIG. 8 shows a filter unit for use in the device according to FIG. 1,
  • FIG. 12 shows a further embodiment of a filter unit with a photosensitive layer in a perspective view
  • FIG. 13 shows a further embodiment of a filter unit with a photosensitive layer
  • a part of a microwave unit in a section parallel to a longitudinal axis 15 shows a cavity resonator with a further embodiment for part of a microwave unit
  • FIG. 16 shows a detailed view of the further embodiment for the part of the microwave unit according to FIG. 15,
  • FIG. 17 shows a detailed view according to FIG. 16 of a third embodiment for part of a microwave unit
  • FIG. 18 shows the microwave unit according to FIG. 14 with a device for aligning the microwave beam.
  • the device according to the invention for the non-invasive determination of a substance in a body 10 is shown in a schematic representation.
  • the device according to the invention consists of a control unit 1, a laser unit 2, a microwave unit 3 and a phototransistor unit 4.
  • the control unit 1 is the actual unit which guides the process and processes the signals and is for this purpose with the laser unit 2, the microwave unit 3 and the phototransistor unit 4 operatively connected.
  • the microwave unit 3 is suitable for both transmitting and receiving microwaves 7a, 7b
  • the laser unit 2 is only suitable for emitting light waves 6.
  • the phototransistor unit 4 is used, which consequently forms a measuring unit together with the laser unit 2.
  • microwave unit 3 and the measuring unit consisting of laser unit 2 and phototransistor unit 4
  • the invention can be implemented with one of the measuring units, ie microwave unit 3 or laser unit 2 combined with phototransistor unit 4.
  • the widest possible use is achieved with the combination of the two inventive devices to be explained in detail below.
  • the control unit 1 contains amplifier, signal processing, memory units and other functional units, which of course could be accommodated in separate units.
  • the various functional units are only the good ones in FIG. 1
  • control unit 1 For the sake of clarity, summarized in control unit 1.
  • FIG. 1 in FIG. 1 denotes a body as a medium. This is, for example, an area of a living human body in which one substance S1 to S3 is to be determined as a parameter or several substances S1 to S3.
  • An arterial blood vessel 20 with vessel walls 20a and 20b is indicated in the body 10.
  • the substances S1 to S3 can be found both in the blood vessel 20 and in the rest of the tissue, hence the substances S1 to S3 transported in the blood vessel 20 by the blood flow and can diffuse into the remaining tissue.
  • Laser unit 2 defines a measurement path 100 in which the measurements are to be carried out later.
  • the aim is to position the measurement path 100 in the central area of the arterial blood vessel 20.
  • the laser unit 2 which is a laser unit still to be explained in detail, is operated in the IR (infrared) range.
  • the oxygen content in arterial blood is higher than in venous blood.
  • a more or less strong reflection signal is obtained as a function of the oxygen content at the respective location and is measured with the phototransistor unit 4.
  • a strong reflection signal it can therefore be assumed that either an arterial blood vessel or a part of the body tissue with a high blood flow lies in the target area of the laser beam. Because in the reflection signal also
  • Information relating to the speed of the particles present in the target area of the laser beam can also be ascertained whether an arterial blood vessel actually exists (higher speed of the particles) or whether only one there is a lot of blood in the body tissue (particles hardly move).
  • the measurement path 100 is thus determined. A check whether the measurement path 100 is located at the intended location is possible and useful. The use of a laser unit 2 is imperative since only lasers have the required target accuracy.
  • a time for the measurements carried out in the measurement path 100 is additionally determined in the first phase. If the location of the measurement path 100 in an arterial blood vessel 20 has been determined in accordance with the method steps described above, the speed profile in the vessel 20 is essentially proportional to the cardiac cycle (QRS complex). It is then provided to determine a time window which is fixed in relation to the cardiac cycle, in which the following concentration measurement of one or more substances S1 to S3 is carried out.
  • QRS complex cardiac cycle
  • Phase II the actual determination of the substance or substances S1 to S3 of interest can be started (phase II).
  • Two measurement methods are used for this, which can be active at the same time:
  • the first measuring method is based on the determination of the optically visible spectrum in measuring path 100.
  • Two laser pulses with wavelengths of 400 nm to a maximum of 1400 nm (for example in a 25 nm grid) are emitted with the laser unit.
  • the echo signal is measured with the phototransistor unit 4 as a light measuring unit for generating the spectrum. Due to the narrow time relationships and because depending on the substance to be determined S1, S2, S3 the entire spectrum is not of interest, only a certain wavelength range is covered. In any case, the minimum light pulse width corresponds to twice the wavelength.
  • Phototransistor unit 4 set such that selective measurement is possible at predetermined wavelengths.
  • the phototransistor unit 4 can be set to a wavelength of 400 nm, which is referred to below as a frequency or wavelength-selective setting option.
  • the phototransistor unit 4 will be explained in detail later.
  • This first measurement method is, for example, particularly suitable for determining the cholesterol content, that is to say a substance that is only present in the blood in a relatively low concentration, but because of the structure has a considerable influence on the optical spectrum.
  • a second measuring method which, as mentioned, can be active at the same time as the first mentioned, consists in counting the substances of interest S1, S2, S3 or their molecules for determining the concentration.
  • the microwave unit 3 is used for this. This sends individual pulses of very short duration (for example 83 ps or 133.3 ps) into the measurement path 100 determined during phase I and scans it, the field strength of the respective echo signal, which in turn depends on the
  • Microwave unit 3 is received, provides information about the presence or absence of a certain substance S1, S2, S3 or an atom of this substance.
  • This second measurement method is particularly suitable, for example, for determining glucose in blood. So a substance that is only in a relatively small variable Concentration in the blood, is present. In addition, the glucose content cannot be determined correctly, that is to say with insufficient accuracy, from the optical spectrum.
  • the two measurement methods can be combined, i.e. the results of both measurement methods are used by
  • a laser unit 2 with a variable wavelength is used to generate a laser beam with an exact wavelength.
  • a setting 'of the desired wavelength is in the process of this invention absolute necessity, one wants to produce the various laser beams with the same laser unit.
  • Wavelengths with the same laser unit are known per se. It has already been proposed to split the laser beam of a white light laser using filters or prisms in order to extract the desired color component. Furthermore, it is known to change the dimensions of the resonator present in laser units with the aid of appropriate mechanics, with which the wavelength of the laser light generated can also be changed.
  • the white light or colored light laser a Press release dated September 16, 2003 from the University of Bonn, Germany. It describes a new laser with which the generation of white light is possible in a simple and inexpensive manner. With the help of a suitable prism, the white light is broken down into the color components, and the required color can then be selected. With regard to the first-mentioned technique, reference is again made to Jeff Hecht's publication entitled “Understanding Lasers” (IEEE Press, 1992, pp. 296-297).
  • a laser unit 2 (Fig. 1) which will be explained with reference to FIGS. 2 to 7 are particularly suitable.
  • This is a semiconductor laser unit, for example, based on
  • the laser unit 2 is characterized by a high accuracy. For example, wavelengths of 400 nm to 700 nm can be generated with the laser unit 2.
  • FIG 2A shows the schematic structure of part of the laser unit 2 on the basis of a section parallel to a longitudinal axis 40.
  • the light waves generated as laser beams propagate parallel to the longitudinal axis 40, with a mirror unit and an output window, which is realized as a partially transparent window, in FIG 2A are not shown, but are explained with reference to FIGS. 3 and 4.
  • the partially transparent window can also be a so-called Brewster window, for example.
  • a carrier unit 30 which consists of a solid heat-conducting material - for example made of brass or platinum - and which can be regarded as a housing part, comprises an actual core of the laser unit 2, namely a laser diode unit 34, in which in the transition area between the p and n layers Laser beams are generated in a manner known in semiconductor lasers.
  • the layer referred to as laser diode unit 34 is located directly on the carrier unit 30 in accordance with FIG. 2.
  • a first insulation layer 33, a piezo element 32 as a pressure generating element and a second insulation layer 31 follow, which on the other side on the circumferential side Carrier unit 30 rests.
  • the piezo element 32 is thus electrically insulated.
  • the piezo element 32 is preferably made of a tourmaline crystal, which is provided on its surface with a silver layer which has been produced by vapor deposition and which is used for contacting and thus for Control of the entire piezo element 32 is used.
  • a silver layer aluminum or another metal layer can also be vapor-deposited.
  • both a mirror unit and an output window are required, which are arranged essentially transversely to the longitudinal axis 40 of the laser unit 2 (FIGS. 2A and 2B). While the rear mirror reflects the light beams generated by the laser diode unit 34 as completely as possible, the output window has the task of allowing light beams which meet the specified conditions to emerge from the laser unit 2 - precisely through the partially transparent window. Further information can be found in the publication
  • FIG. 2B shows a further embodiment of part of the laser unit 2 on the basis of a cut parallel to a longitudinal axis 40 analogous to FIG. 2A.
  • the carrier unit 30 of the embodiment according to FIG. 2B also forms a cavity in which two insulation layers 31 and 33, a piezo element 32 and a laser diode unit 34 are contained.
  • the laser diode unit 34 is first of the first insulation layer 33, then by the piezo element 32 as Pressure generating element, then encompassed by the second insulation layer 31 and finally by the carrier unit 30.
  • a force can thus be generated with the pressure generating element 32, which acts on the laser diode unit 34 from all radial directions, ie essentially perpendicular to the longitudinal axis 40.
  • the output window 50 consists of
  • FIG. 3 Essentially consisting of a frame element 70 and a laterally arranged insulation layer 61, an opening 60 being provided both by the frame element 70 and by the insulation layer 61. Furthermore, a sectional plane A-A is drawn in FIG. 3, which forms the basis for the section through the exit window 50 shown in FIG. 4.
  • FIG. 4 shows the exit window 50 shown in FIG. 3 in section along the section plane A-A (FIG. 3).
  • the frame element 70 becomes the U-shaped part, into which a partially transparent window 51 is inserted, which is essentially perpendicular to the direction of propagation, ie the longitudinal axis 40.
  • a displacement of the partially permeable window 51 both translationally in the axial direction and as a tilting movement about the longitudinal axis 40 is achieved with the aid of displacement elements 52 to 56 (hereinafter also referred to as displacement elements), which in turn as Piezo elements are formed.
  • displacement elements 52 to 56 in the embodiment shown in FIG. 3 are arranged in the corners of the square partially transparent window 51.
  • the displacement elements 52 to 56 are contacted individually via an electrical connection, so that the displacement elements 52 to 56 can be controlled independently of one another. The control takes place, for example, via a central control unit, which is not shown further.
  • the mirror unit which is intended to reflect the light beams generated in the laser diode unit 34 (FIG. 2) as completely and without loss as possible, can be implemented as a fixed mirror surface according to the known prior art.
  • a partially transparent window is not necessary. Therefore, instead of the partially transparent window 51 shown in FIG. 4, a reflective surface is required, which is obtained, for example, by vapor deposition of a metal layer on a carrier. The remaining elements, ie the position or displacement elements, are used to control the reflecting surface. So that's one Laser unit 2 created, which has an extended area of use compared to the embodiment with a fixed mirror surface (mirror element), which is particularly clear in the light of the following explanations.
  • Mirror surface and the partially transmissive window 51 is set as a multiple or equal to the half wavelength of interest.
  • FIG. 5 shows the laser unit 2, consisting of the individual parts explained with reference to FIGS. 2A, 2B, 3 and 4.
  • the carrier element 30 according to FIG. 2 is arranged between the frame element 50 with the partially transparent window and a mirror unit 80, an insulation layer 61 being provided between the individual parts 80, 30, 56 for electrical and thermal insulation.
  • 6A and 6B show laser diode units produced by means of epitaxy or also by other methods, which have pressure generating elements 73, 74 on all four sides of the square cross section, the four
  • Parts of the pressure generating elements 73, 74 are spaced in the respective corners. For the simultaneous actuation of all four parts of the pressure generating elements 73, 74, these are electrically connected to one another with the aid of bonding wires (as shown in FIGS. 6A and 6B) or directly coupled to a voltage source or control unit 77 provided for this purpose.
  • FIG. 6A For further clarification, a p-n transition is shown in FIG. 6A and an n-p transition for the in FIG. 6B
  • Laser diode unit shown. 6A and 6B that the pressure generating elements 73, 74 have opposite poles with respect to the laser diode unit has, with which a mutual unfavorable influence between the pressure generating element and the laser diode unit can be prevented.
  • FIG. 7 shows a schematic representation of a device according to the invention with the central part of the laser unit 2 arranged centrally between the mirror unit 80 and the output window 50, which is implemented, for example, in the manner described in connection with FIGS. 6A and 6B.
  • This embodiment is characterized in that both the mirror unit 80 and also the output window 50 is shifted as a function of the force generated by the pressure generating element (not shown in FIG. 7) and acting on the laser diode unit, in such a way that the laser diode unit is always located centrally between the mirror unit 80 and the output window 50 or the Diode laser facet is half a wavelength or a multiple of half the wavelength from the mirror unit, this depends on whether the diode laser facet is anti-reflective or not.
  • the diode laser facet is anti-reflective, no additional resonance builds up between the diode laser facet and the mirror unit. If, on the other hand, the diode laser facet is not anti-reflective, an additional resonance builds up between the diode laser facet and the mirror unit, which leads to additional waves and thus to a loss if the distance is incorrect. This with deviations depending on the distance of the mirror units from the diode laser facet and applies to both exit sides of the laser diode unit. This is achieved, for example, with the aid of the synchronous rotating device 100 shown in FIG. 7, which is rotatably mounted at point D. If the mirror unit 80 is now displaced in a direction W1 with the displacement element 52, a 1: 1 takes place via the synchronous rotating device 100.
  • a central alignment of the laser diode unit or its facet provides an additional advantage of optimized power utilization.
  • two or more displacement elements 52 can of course also be provided, which are coordinated and arranged in such a way that the laser diode unit is always located centrally between the mirror unit 80 and the output window 50.
  • a phototransistor unit 4 (FIG. 1) explained with reference to FIGS. 8 to 13 is particularly suitable.
  • the phototransistor unit 4 shown in FIG. 8 essentially consists of a photosensitive layer 102, which is implemented, for example, with one or more phototransistors, and a filter unit 110 arranged in front of the photosensitive layer 102.
  • the filter unit 110 has a movable slit mask 103, a microprism unit 107 and a fixed slit mask 108.
  • the movable slit mask 103 can be moved essentially laterally to the slit mask 108 in the directions indicated by an arrow 105, with the aid of displacement units 104 and 106 arranged laterally with respect to the movable slit mask 103.
  • one displacement unit 104 is implemented with the aid of a piezo unit and the other displacement unit 106 is implemented as a viscous spring element.
  • the viscous spring element consists, for example, of a silicone insert, an insert made of natural rubber or a steel spring. When using a silicone insert, a buffer layer is required to prevent material migration.
  • displacement elements 104 and 106 consists in the use of microsteppers or microlinear motors, which likewise enable high precision in the displacement of the movable mask 103.
  • the prism unit 107 is arranged between the fixed and the movable slit mask 108 or 103, the masks 103, 108 having corresponding first and second openings which form an opening pair.
  • Prism unit 107 has a prism for at least one pair of openings.
  • the position of the microprism unit 107 is changed with the aid of displacement units, which in turn are realized, for example, in the form of a piezo unit and a viscous spring element.
  • This also allows selective those light waves L are directed through the slit mask 103, which in contrast to the embodiment according to FIG. 8 is now stationary, onto the photosensitive layer 102.
  • the microprism unit 107 is moved essentially laterally to the slit mask 103 or to the slit mask 108.
  • a still further embodiment of the filter unit 110 is that both slit masks are movable. This reduces deflections of the individual slit masks because each of the slit masks is moved by half the distance to be covered. The slit masks move laterally in opposite directions.
  • the filter unit 110 described thus represents a color filter in which the filtered wavelengths can be set electronically.
  • the filter unit 110 is a temperature-independent color filter that can be set, for example, to wavelengths from 1400 to 430 nm.
  • the filter unit 110 and therefore the entire phototransistor unit 1 are distinguished by one or more of the following advantages:
  • the design of the filter unit 110 or the phototransistor unit 1 can be selected to be extremely small; electronic and precise adjustability of the desired wavelength of those light beams which are to strike the photosensitive layer 102; - minimal mechanical effort; - extremely short reaction times; - Increasing the sensitivity of the phototransistor unit 1 if all pairs of openings are set to a wavelength or the same wavelength range in which measurements are to be carried out. Then the signals measured on the photosensitive layer can then be added, which leads to larger signal components.
  • a calibration must be carried out in advance.
  • Such a calibration can be carried out as follows, for example:
  • the phototransistor unit 1 is exposed to a light source with a known wavelength.
  • the movable slit mask 103 or 108 - or possibly the microprism unit 107, if it is movable - is then moved with the aid of the displacement units 104, 106 until a signal maximum is obtained on the photosensitive layer 102.
  • the corresponding degree of displacement can be recorded depending on the displacement mechanism used for the calibration.
  • Piezo elements used, so the electrical signal applied to the piezo elements can be related to the wavelength of the light source, thus completing the calibration for this wavelength. Further calibrations with different wavelengths of the light sources are advantageous made in order to be able to record any non-linearities.
  • microprism unit 107 can be produced in crystalline form from a substance with the chemical formula NaCl.
  • FIG. 9 shows a perspective view of a further embodiment of the filter unit.
  • this embodiment has only one slot in the slot masks 103 and 108.
  • the micro prism unit 107 has a single prism.
  • An incident light beam is parallelized by the slit mask 108.
  • the parallelized light beam is subsequently broken down into light components of different wavelengths by the microprism unit 107.
  • the movable slit mask 103 the light component of interest is selected by positioning the movable slit mask 103 accordingly. It is thereby achieved that only the light with the desired wavelength hits the photosensitive layer 102 and is measured.
  • FIG. 10 shows a micro prism unit 107, as is used for example in the embodiment according to FIG. 8.
  • the microprism unit 107 is made, for example, of glass, into which the individual prisms have been ground. It should be noted when manufacturing the micro prism unit that the individual prisms with the corresponding dimensions of the slot or Hole mask are in line, that is, the arrangement of a slot or a hole matches the corresponding prism, so that the desired wavelengths or wavelength ranges can be measured.
  • the corresponding slots or holes are generally referred to as pairs of openings, which accordingly consist of first and second openings.
  • the microprism unit 107 consists of a polymer instead of glass. This simplifies production and the costs are lower than when using glass. A combination of individual prisms to form the
  • Microprism layer The individual prisms are then glued together with an adhesive.
  • one application of the filter unit is to combine it with a photosensitive layer 102.
  • a phototransistor unit is thus obtained with which extremely precise measurements can be made in a specific wavelength range can be, whereby an electronic adjustment of the wavelength to be measured is possible.
  • Another embodiment of the filter unit consists in that the wavelengths transmitted by the slit or shadow mask can be set.
  • two masks lying one above the other, which can be laterally displaced relative to one another are provided as a mask, as indicated in FIG.
  • Such an embodiment is shown in FIG. 11, with two masks 108a and 108b lying directly one above the other, which can be laterally displaced relative to one another, for example again with piezo elements in combination with viscous spring elements.
  • the slot or Hole size changed, therefore a slit or hole mask has been obtained in which the opening is adjustable.
  • the slit or shadow mask with adjustable opening above the micro prism unit i.e. be provided on the side of the light source L, or below the micro prism unit. It is also conceivable that both the opening of the slit or perforated masks above and below the microprism unit can be adjusted in the sense of the above statements.
  • FIG. 12 shows a further embodiment of a filter unit 1 with a movable slit mask 108, a prism unit 107, a fixed slit mask 103 and a photosensitive layer 102 corresponding to FIG Embodiment, which is shown in Fig. 9.
  • the embodiment according to FIG. 12 on the one hand has a movable slit mask 108, the side walls of which form the slit have a conical shape, namely the slit is narrower on the light exit side than on the light entry side.
  • the fixed slit mask 103 also has conical side walls, but in the opposite direction, so that the slit width on the light entry side is smaller than on the light exit side. In other words, the slit width on the side of the prism unit 107 is smaller than on the side of the photosensitive layer 102.
  • the slit of the movable slit mask 108 is equipped with a collecting lens 13 and / or the slit of the fixed slit mask 103 is equipped with a diffuser 14. While a higher quantity of light or quantity of light quantum is obtained by the collecting optics 13, which impinges on the prism unit 107, the light exiting through the prism unit 107 in monochrome is distributed essentially uniformly and over a large area on the photosensitive layer 102 by the diffuser 14. Overall, this results in a higher sensitivity of the phototransistor unit.
  • the distance between the movable slit mask 108 and the prism unit 107 is a
  • the distance between the prism unit 107 and the fixed slit mask is b
  • the distance between the fixed slit mask 103 and the photosensitive layer 102 is c designated. It has been shown that the distances a and c are preferably chosen to be as small as possible.
  • the distance b is preferably variable and serves to limit or adjust the bandwidth - or the wavelength range - of the light beams that pass through the slit of the fixed slit mask 103.
  • the conical course - i.e. the steepness of the side walls delimiting the slit - of the fixed slit mask 103 is selected such that the relevant measurement area on the photosensitive layer is illuminated over the entire area. This ensures that there are no errors in the measurement results, because a non-full-area illumination of a photo transistor usually leads to measurement errors.
  • FIG 13 shows a further embodiment of the filter unit according to the invention with a photosensitive
  • Layer 102 with a plurality of slits or holes in the slit or perforated mask 108 is shown analogously to the embodiment according to FIG. 8.
  • Mixed light is identified by 12 and monochromatic light is identified by 15, the latter hitting the photosensitive layer 102 alone.
  • the side walls forming the slits are tapered, the slit opening on the side of the light entry being selected to be maximum, so that as much light as possible can enter each slit. Corresponding the side walls forming the slits converge into a point which coincides with the top of the movable slit mask 108.
  • the fixed slit mask 103 is arranged upside down in the sense that the wide opening comes to lie on the side of the photosensitive layer 102.
  • the diffuser 14 contained in the slot ensures that the photosensitive layer is illuminated to the maximum and evenly, with the result that a higher sensitivity and more accurate measurement results are achieved.
  • the conical side walls of the slot are mirrored in a further embodiment of the invention.
  • holes are provided in the masks 108 and 103 instead of slots.
  • the holes in the masks 108 and 103 are therefore frusto-conical, as are the inserts embedded in the masks 108 and 103 as converging lenses 13, in the case of the movable shadow mask 108, or as a diffuser 14, in the case of the fixed shadow mask 103.
  • the movable mask 108 can also be fixed in the embodiments according to FIGS. 12 and 13 and the fixed mask 108 can be made movable.
  • Constellations according to FIG. 11 are also conceivable in the embodiments according to FIGS. 12 and 13.
  • microprism units consist of crystalline NaCl, glass or a polymer. Crystals, gemstones such as diamonds for high color purity, quartz or neodymium are also conceivable.
  • multiple prisms can be used in all of the above-mentioned embodiments in the microprism or prism units.
  • Such multiple prisms also called straight prisms, are composed of several prisms with different materials, for example different types of glass, so that despite a spectral deflection, the center beam passes essentially undeflected. Further information on the multiple prisms can be found, for example, in DE-37 37 775 AI.
  • FIG. 14 shows an embodiment for the microwave unit 3 mentioned in connection with FIG. 1. This is a possible schematic structure of part of the microwave unit 3 based on a section parallel to one
  • the microwave unit 3 (FIG. 1) comprises a carrier unit 200 a resilient material, such as brass or platinum. This means that high forces can be absorbed if necessary.
  • a carrier unit 200 a resilient material, such as brass or platinum. This means that high forces can be absorbed if necessary.
  • the following layers, starting from an upper carrier wall, are contained in a compact design: a first insulation layer 201, a Gunn diode 202, a second insulation layer 203 and a piezo element 204.
  • Various control lines with corresponding contact points for controlling the individual ones Layers from the control unit 1 (FIG. 1) are not shown in FIG. 14.
  • the Gunn diode 202 is a diode based on the Gunn effect (John Gunn, 1963) and is used in a known manner to generate microwaves.
  • Gunn effect or Gunn diodes please refer to Donald Christiansen's standard work entitled “Electronics Engineers' Handbook” (McGraw-Hill, fourth edition, 1997, pages 12.71, 12.79 and 12.80). This publication also contains other standard works on this topic.
  • the Gunn diode 202 is clamped between the first and second insulation layers 201 and 203.
  • the frequency of the microwaves generated by the Gunn diode 202 can now be set, for example, between 8.7 and 12 GHz.
  • the frequency shift takes place on the one hand through the pressure on the Gunn diode 202 (ie the so-called "die") itself, as a result of which a change in the material inside the Gunn diode 202 results the molecular vibration change - similar to a strong temperature change - arises, on the other hand, by a change in the capacitance by a
  • Capacitor in which the capacitor plates are shifted against each other.
  • Piezo element 204 thus provides the possibility of precisely setting the frequency of the microwaves generated by Gunn diodes 202.
  • the microwave unit 3 described thus differs from known devices in particular in that the frequency of the microwaves generated can be precisely set electronically, without mechanical adjustment devices.
  • the piezo element 204 is, in a further embodiment of the microwave unit 3, with a PLL (phase-locked loop) or FLL (frequency-locked loop) known per se ) Circuit.
  • PLL phase-locked loop
  • FLL frequency-locked loop
  • a window for the exit of the microwaves 205 is identified at the side of the Gunn diode 202.
  • the window 206 is preferably obtained by suitable doping with foreign atoms. This enables a controlled escape of microwaves from the Gunn diode 202. Suitable for the doping especially GaAs (gallium arsenide).
  • the diameter of the window 206 is, for example, approximately 10 ⁇ m and the depth of the doping is, for example, 320 A (angstroms).
  • the +/- connections are shown in FIG. 14, electrical contacting of the former being made in window 206 and electrical contacting of the latter being outside window 206.
  • FIG. 1 An embodiment for a microwave unit 3 (FIG. 1) is shown schematically in FIG.
  • a cavity resonator is designated by 250, in which the part of the microwave unit 3 explained with reference to FIG. 14 can also be contained.
  • FIG. 15 shows an alternative embodiment to FIG. 14, which is described in detail with reference to FIG. 16.
  • the cavity resonator 250 is made of metal and has an outlet opening 251 through which the microwaves emerge from the cavity resonator 250 in the direction of propagation 205.
  • the cavity resonator 250 contains, on the one hand, a ceramic body 234, which projects into the interior of the cavity resonator 250 from above, and on the other hand, a body 235, which projects into the interior of the cavity resonator 250 from below, the upper ceramic body 234 and the body 235 being aligned with one another , ie have a common axis, but do not touch.
  • a further ceramic body 236 is arranged, which is explained with reference to the detailed view according to FIG. 16.
  • the body 235 is made of a metal, such as brass or copper, and serves as Cathode. At the same time, 235 excess heat can be dissipated through the body.
  • the lower ceramic body 235 is a carrier element for the following units or layers (sequence starting from the ceramic body 235): a piezo element 204; a contact layer 203 made of a metal, for example of silver or copper; - a Gunn diode 202.
  • a control line 231 is provided, which is connected to a contact point 232 on the further body 236.
  • the contact point 232 is led out of the cavity resonator 250 via an electrical conductor contained in the further body 236, which gives the possibility of activating the piezo element 204 from outside the cavity resonator 250.
  • the Gunn diode 202 arranged above the contact layer 203 is also connected via a contact loop 230 to the ceramic body 234, which at the same time serves as a feedthrough capacitor and enables the Gunn diode 202 to be contacted from outside the cavity resonator 250.
  • the Gunn diode 202 is on the contact layer 203 and the piezo element 204 applied.
  • the frequency of the microwaves generated by the Gunn diode 202 can now be set, for example, between 8.7 and 12 GHz.
  • the frequency shift takes place on the one hand through the capacitive change as a result of a change in the distance between the Gunn diode 202 and the body 235 acting as a cathode, and on the other hand through the change in position relative to the ceramic body 234 acting as a feed-through capacitor using the Gunn diode 202 to precisely set and change microwaves.
  • This embodiment also differs from known microwave units in that the frequency of the microwaves generated can be set electronically.
  • Another advantage of this variant is the very small design of, for example, 2 x 1 x 1 mm for the outer dimensions of the cavity resonator 250, which only has three connections, namely V Gn d ⁇ V Gunn and Vpie z o / where V Gnd the common earth - or mass potential, GU ⁇ the supply voltage or the signal tap of the Gunn diode and V P ⁇ e zo the supply voltage of the piezo element and the associated tuning of the resonant circuit.
  • the self-contained cavity resonator has a low susceptibility to external influences, since all RF-containing components are contained in the cavity resonator. This fact makes it ideal for use in microsensor technology.
  • the set frequency of the microwaves to be emitted can be called PLL (phase locked loop) or FLL (frequency locked loop). - Circuits are kept constant, which is of course also conceivable in this embodiment.
  • FIG. 17 shows a variant supplemented with the embodiment according to FIG. 16 with an additional inductance and an additional capacitance. This prevents high-frequency signal components or microwaves from escaping from the cavity at undesired points.
  • the carrier unit 200 can be displaced or tilted as a whole, in other words the direction of the microwave steel 205 can be set. So that the largest possible area can be covered with the microwave beam, the displacement element 207 and its counterpart (cannot be seen in FIG. 8 due to the covering by the displacement element 207) are attached in the region of the outlet opening of the microwave beam. With these displacement elements 208, the carrier unit 200 can be moved according to the arrows marked 210, which are perpendicular to the drawing plane are moved perpendicular to the drawing plane.
  • the two further displacement elements 208 and 209 are arranged at the opposite end of the carrier unit 200, in such a way that the carrier unit 200 can be moved in the plane of the drawing in FIG. 18 in accordance with the arrows labeled 211.
  • the displacement elements 208 and 209 act on two of the parallel surfaces of the carrier unit 200, while the displacement element 207 and its counterpart act on the other two of the parallel surfaces of the cuboid carrier unit 200.
  • Displacement elements 207 to 209 are preferably provided with a silver layer on the outside thereof. This enables simple contacting with control lines 220 to 222 by means of known bonding technology. Associated with this is a reference connection 223 for establishing a reference potential. For this purpose, the reference connection 223 is connected to the carrier unit 200, preferably again by means of the bonding technology.
  • the microwave beam can be tilted about two axes, so that a cone of approximately 2.5 ° can be traversed. If further displacement elements are used which act on the third surface pair of the carrier unit 200, then a translatory movement in a third axis can also be achieved.
  • microwave unit 3 is used not only for transmitting but also for receiving microwaves in an analogous manner.
  • the present invention has a broad spectrum of possible uses. Although the non-invasive determination of substances, i.e. of glucose and cholesterol, has been specified in the human body, the present invention is particularly suitable for the non-contact determination of any clinical and / or chemical parameters, such as those which were initially introduced in a non-exhaustive manner. Based on the enumeration as possible clinical and / or chemical
  • Non-contact determination of contaminants in wastewater Using the method according to the invention, substance compositions can be determined without having to take samples. This means that even highly toxic substances can be examined safely.
  • the invention is excellently suited for any microbiological application with the detection of viruses or bacteria. It is irrelevant whether the viruses or bacteria to be determined are contained in a solid, liquid or gaseous medium.
  • Inspection of weld seams With the method according to the invention, micro cracks can be detected with high reliability.

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Abstract

L'invention concerne un procédé de détermination de paramètres cliniques et/ou chimiques (S1) dans un milieu (10), des moyens étant prévus (2), par exemple une unité laser, pour l'émission d'ondes lumineuses cohérentes (6), ainsi que des moyens (4), par exemple, une unité à phototransistor, pour la réception d'ondes lumineuses (8). Au moins une partie des ondes lumineuses émises (6) parvient dans le milieu (10) et les moyens (4) de réception des ondes lumineuses (8) mesurent au moins une partie des ondes lumineuses (8) réfléchies dans le milieu (10), les paramètres (S1) étant déterminés en se basant sur les propriétés des ondes lumineuses émises et reçues. Du fait qu'au moyen d'une unité laser (2), les ondes lumineuses (6) sont cédées au milieu (10) et, qu'au moyen d'une unité à phototransistor (4), les ondes lumineuses (8) réfléchies dans le milieu (10) sont mesurées, il est possible de déterminer avantageusement, dans une unité de traitement ou de contrôle, les paramètres (S1) se présentant dans une zone cible du faisceau laser.
EP05700362A 2004-02-11 2005-02-09 Procede de determination de parametres cliniques et/ou chimiques dans un milieu, et dispositif pour la mise en oeuvre de ce procede Withdrawn EP1714137A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
PCT/CH2004/000080 WO2005078410A1 (fr) 2004-02-11 2004-02-11 Procede de determination de parametres cliniques et/ou chimiques dans un fluide et dispositif destine a la mise en oeuvre du procede
PCT/CH2004/000079 WO2005078879A1 (fr) 2004-02-11 2004-02-11 Diode laser a resonateur externe et longueur d'onde pouvant etre reglee sur la diode laser par pression
EP04020810A EP1564535A1 (fr) 2004-02-11 2004-09-02 Filtre optique à longueur d'onde réglable et dispositif utilisant ce filtre
PCT/CH2005/000071 WO2005078411A1 (fr) 2004-02-11 2005-02-09 Procede de determination de parametres cliniques et/ou chimiques dans un milieu, et dispositif pour la mise en oeuvre de ce procede

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EP1714137A1 true EP1714137A1 (fr) 2006-10-25

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GB2445758A (en) * 2007-01-17 2008-07-23 Univ Hospital Of North Staffor Intraoperative electromagnetic apparatus and related technology
DE102021004609A1 (de) 2021-09-11 2023-03-16 Eques Consulting GmbH Vorrichtung und damit durchführbares Verfahren zur non-invasiven Konzentrationsbestimmung von Komponenten im menschlichen Blutkreislauf und Verwendung des Verfahrens.

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US4655225A (en) * 1985-04-18 1987-04-07 Kurabo Industries Ltd. Spectrophotometric method and apparatus for the non-invasive
US6070093A (en) * 1997-12-02 2000-05-30 Abbott Laboratories Multiplex sensor and method of use
US6526298B1 (en) * 1998-05-18 2003-02-25 Abbott Laboratories Method for the non-invasive determination of analytes in a selected volume of tissue
US6662030B2 (en) * 1998-05-18 2003-12-09 Abbott Laboratories Non-invasive sensor having controllable temperature feature
DE10000324A1 (de) * 2000-01-07 2001-07-19 Roesler Hans Joachim Analysegerät
GB2360842B (en) * 2000-03-31 2002-06-26 Toshiba Res Europ Ltd An apparatus and method for investigating a sample
US6477393B1 (en) * 2000-07-19 2002-11-05 Trw Inc. Non-invasive blood glucose measurement techniques

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