JP2007522459A - Method for measuring clinical and / or chemical parameters in a medium and apparatus for carrying out the method - Google Patents

Abstract

  The invention relates to a method for measuring a clinical and / or chemical parameter (S1) in a medium (10) comprising means (2) for transmitting a coherent light wave (6), for example a laser device, and a light wave. Means (4) for receiving (8), for example a method comprising a phototransistor unit. According to said method, at least some of the transmitted light wave (6) is transmitted to the medium (10), and the means (4) for receiving the light wave (8) is a light wave (reflected by the medium (10) ( At least some of 8) is measured, and the parameter (S1) is measured based on the characteristics of the transmitted and received light waves (6; 8). The light wave (6) is transmitted to the medium (10) by the laser device (2), and the light wave (8) reflected by the medium (10) is measured by the phototransistor (4), so that the target region of the laser beam is The parameter (S1) is advantageously measured in the processing and control device.

Description

  The invention relates to a method according to the preamble of claim 1 and to an apparatus for carrying out the method.

  In order to be able to accurately identify a substance or substance concentration in a living body, it is necessary to take a sample from the body and then process the sample by a special analytical method using an appropriate reagent. Sampling, for example collecting blood or consuming reagents, is regarded as disadvantageous in these known methods. Especially for diabetics who have to test their glucose content in the blood many times during the day, a non-invasive method of measuring glucose content would be a great advantage.

  For this reason, many methods and devices for measuring blood glucose content non-invasively have already been proposed. Reference is made to the following publications, WO 95/04 496 and WO 01/26 538 as representative. However, it is known that known methods are not suitable for obtaining accurate measurement results. Especially for diabetics, the measurement results are very inaccurate and cannot be used for monitoring and adjusting blood glucose levels. Certainly, known methods can be used for the basic display of instantaneous blood glucose content, but in order to determine the amount of drug needed to accurately adjust blood glucose levels, conventional monitoring measurements, That is, resampling must be performed.

  Accordingly, it is an object of the present invention to identify a highly accurate method and apparatus for measuring clinical and / or chemical parameters in a medium.

  This object is achieved by the measures mentioned in the characterizing part of claim 1. Advantageous developments of the invention and apparatus for carrying out this method are mentioned in the further claims.

  The present invention has the following advantages. A parameter that spreads to the target area of the laser beam is measured by the processing device or the monitoring unit by transmitting the light wave to the medium using the laser unit and measuring the light wave reflected by the medium using the phototransistor unit. be able to. For this purpose, in a further embodiment of the invention, the frequency or wavelength of the wave generated by the laser unit is adjusted according to the characteristics of the parameter to be measured, the parameter being a signal that is measured using a photodiode device. To be determined in relation. It has been found that the method according to the invention makes it possible to obtain very accurate results, especially for parameters such as cholesterol.

  Furthermore, in the case of parameters such as glucose, very accurate results can be obtained by the method of claim 6 and in fact both in the independent and dependent forms of claims 1-5.

The term “clinical and / or chemical parameters” should be understood to mean in particular:
-Metabolic degradation products or metabolites;
-Substances related to metabolism;
-White blood cells, especially white blood cells to check the degree of inflammation;
-Uric acid;
-Enzymes;
-Ions or ion concentrations;
-Vitamins;
-CRP (C-reactive protein);
-Substances related to anti-aging, well aging and lifestyle;
-Microorganisms;
-Alcohol;
-Drugs;
-Lactate salt;
-Doping substances;
-Color;
-Carcinogenic cells and structures;
-Pollutants, especially wastewater pollutants;
-Quality control of liquid media, especially water (clinical laboratory values are obtained without the use of reagents);
-Hormones;
-Bacteria;
-Crystals and their structures;
-Viruses.

Further, the term “medium” should be understood to mean a solid, liquid, or gas medium, or any mixed form of these media having any structure. In particular:
-The human or animal body;
-Blood;
-Color;
-Wastewater;
-Drinking water (in the sense of high quality water);
-Metal workpieces joined by welding.

  The invention is described in more detail in the examples shown in the following figures. These are exemplary embodiments that aid in understanding the claimed subject matter.

  A device for non-invasively measuring a substance in the body 10 according to the present invention is shown schematically in the upper half of FIG. The device according to the invention comprises a monitoring unit 1, a laser unit 2, a microwave unit 3 and a phototransistor unit 4. The monitoring unit 1 is the actual unit that guides the process and adjusts the signal and is operatively connected to the laser unit 2, the microwave unit 3 and the phototransistor unit 4 for this purpose. While the microwave unit 3 is suitable for transmitting and receiving the microwaves 7a and 7b, the laser unit 2 is only suitable for emitting the light wave 6. A phototransistor unit 4 is used to receive the light wave 8 reflected by the body 10, which in turn forms a measurement unit with the laser unit 2. According to the present invention, it is explicitly indicated that the presence of both the microwave unit 3 and the measurement unit including the laser unit 2 and the phototransistor unit 4 is not essential so that the present invention may be reduced in practice. Pointed out. Instead, the present invention can be fully implemented using only one of the measurement units, ie the laser unit 2 combined with the microwave unit 3 or the phototransistor unit 4. Of course, the combination of the two devices according to the invention, described in detail below, yields the widest possible use.

  An amplifier unit, signal processing unit, memory unit and other functional units are included in the monitoring unit 1, which can of course be attached to separate units. For the sake of clarity only, the various functional units are connected to the monitoring unit 1 of FIG.

  The reference symbol 10 in FIG. 1 identifies the body as a medium. This is, for example, a certain area of a living human body, where substances S1 to S3 or a plurality of substances S1 to S3 are measured as parameters. An arterial vessel 20 having vessel walls 20a and 20b is shown in the body 10. Since the substances S1 to S3 are found both in the blood vessel 20 and in the other tissue, the substances S1 to S3 can be transported by the blood flow in the blood vessel 20 and diffuse to the other tissue.

  The method according to the invention used for measuring substances S1 to S3 or measuring their blood concentration, carried out using the apparatus shown in FIG. 1, is described in more detail below.

  Initially, in the first stage, a measurement path 100 is established with the aid of the laser unit 2 and a measurement is subsequently carried out in this measurement path. The purpose here is to position the measurement path 100 in the central region of the arterial blood vessel 20. For this purpose, the laser unit 2 is a laser unit that will still be described in detail, but operates in the IR (infrared) region. It is known that the oxygen content is higher in arterial blood than in venous blood. Therefore, depending on the oxygen content at the position in question, a more or less strong reflection signal is obtained and measured by the phototransistor unit 4. Therefore, when the reflected signal is strong, it can be considered that either the arterial blood vessel or the part of the body tissue in which blood is greatly perfused is in the target region of the laser beam. The reflected signal additionally contains an information item about the velocity of the particles present in the target area of the laser beam, so that there is actually an arterial blood vessel (if the particles are faster) or the blood is heavily perfused It can be further clarified whether only the body tissue part is present (when the particles hardly move). The measurement path 100 is determined in this way. It can be proved that the measurement path 100 is at a given position, which is meaningful. Since only the laser shows the required target accuracy, the use of the laser unit 2 is essential here.

  In another embodiment of the method according to the invention, the time points for the measurements performed in the measurement path 100 are additionally measured in the first stage. If the position of the measurement path 100 is established in the arterial vessel 20 according to the above-described steps of the method, the velocity profile in the vessel 20 is essentially proportional to the heart cycle (QRS complex). It is then given to determine the time window established in relation to the heart cycle, where concentration measurements of one or more substances S1 to S3 are subsequently performed. In different embodiments of the invention, a time window of eg 100 ns is established around the QRS complex or for pulse waves in the peripheral blood vessels.

  Once the above steps of the method have determined the spatial and even temporal position of the measurement path 100 (stage I), the actual measurement of the substances of interest S1 to S3 can be started (stage II). ). Two measurement methods are used for this purpose, which can act simultaneously.

  The first measurement method is based on the measurement of the optical visible spectrum of the measurement path 100. Here, using the laser unit 2, optical pulses having a wavelength from 400 nm to a maximum of 1400 nm (for example, at 25 nm intervals) are transmitted. The echo signal is measured using a phototransistor unit 4 as a light measurement unit for generating a spectrum. Since the time relationship is tight and not interested in the whole spectrum, only certain wavelength regions are traversed depending on which of the substances S1, S2, S3 is measured. In either case, the minimum light pulse width is equal to twice the wavelength.

  When measuring the optical echo signal, the phototransistor unit 4 is adjusted in such a manner that selective measurement at a specified wavelength is possible. For example, the phototransistor unit 4 can be tuned to a wavelength of 400 nm, which is described below as frequency selective or wavelength selective tunability. The phototransistor unit 4 will be described in more detail.

  This first measurement method is very suitable for measuring, for example, the level of cholesterol, ie the level of substances that are present in blood at a relatively low concentration but have a considerable influence on the optical spectrum for structural reasons. is there.

  As described above, in the second measuring method that can operate simultaneously with the method described first, the concentration is measured by counting the substances S1, S2, S3 or their molecules. The microwave unit 3 is used for this purpose. The microwave unit sends very short (eg 83 picoseconds or 133.3 picoseconds) individual pulses to the measurement path 100 determined in stage I, scans the measurement path and in each case the microwave unit 3 The field strength of the echo signal received by provides information about the presence or absence of a substance S1, S2, S3 or an atom of that substance.

  In this way, by transmitting a predetermined microwave frequency for a sample having a material of interest, multiple images of the target region having various wavelengths are generated. Previously measured patterns, which are stored in advance in a memory unit attached to the monitoring unit 1 and can be searched for comparison within the pattern recognition device also included in the monitoring unit 1, are compared with these images. . In one embodiment, only the known pattern of the substance to be measured is stored due to the limited memory of the memory unit.

  This second measuring method is very suitable for measuring, for example, glucose in blood, i.e. substances which are present only in relatively low concentrations in the blood. Furthermore, the glucose content cannot be measured accurately from the optical spectrum, i.e. with sufficient accuracy.

  Combining the two measuring methods to measure the concentration of other substances, so that the effect of the optical spectrum can be established on them, and sufficient particles can be detected with the aid of the microwave unit 3 Is possible. That is, the results of both measurement methods are taken into account in determining the concentration.

  In order to generate a laser beam having an accurate wavelength, a laser unit 2 having a variable wavelength is used. If it is desired to generate various laser beams using the same laser unit, it is absolutely necessary to adjust the desired wavelength when using the method according to the invention.

It is known per se to produce laser beams with different wavelengths using the same laser unit. Thus, it has already been proposed to split the laser beam of a white light laser with the aid of a filter or prism in order to extract the desired color component in this way. It is further known to change the dimensions of the resonator present in the laser unit with the aid of a suitable mechanical system, so that the wavelength of the generated laser light can also be changed. For white light or colored light lasers, reference is made to a press release from the University of Bonn, Germany, dated 16 September 2003. It describes a new laser that can produce white light at a low cost by a simple method. The white light is decomposed into color components with the help of a suitable prism and then the required color can be selected. Reference is made to the publication entitled “Understanding Lasers” (IEEE Press, 1992, pp. 296-297) by Jeff Hecht for the first mentioned approach.

  The laser unit 2 (FIG. 1) described with respect to FIGS. 2 to 7 is particularly suitable for the apparatus illustrated in FIG. This is, for example, a semiconductor laser unit based on gallium arsenide. The laser unit 2 is characterized by high target accuracy. Using the laser unit 2, it is possible to generate wavelengths from 400 nm to 700 nm, for example.

  FIG. 2A shows a schematic structure of a part of the laser unit 2 with reference to a cross section parallel to the longitudinal axis 40. A light wave generated as a laser beam propagates parallel to the longitudinal axis 40 and the exit window, which is realized as a mirror unit and a translucent window, is not shown in FIG. 2A but will be described with reference to FIGS. The translucent window can also be a so-called Brewster window, for example.

  The support unit 30, which is made of a solid heat-conducting material such as brass or platinum and can be regarded as a housing part, surrounds the core characteristics of the laser unit 2, specifically the laser diode unit 34, and the laser diode unit In a semiconductor laser, a laser beam is generated at a junction region between the p-layer and the n-layer in a known manner. The layer designated as the laser diode unit 34 lies directly on the support unit 30 according to FIG. Next, starting with the laser diode unit 34, the first insulating layer 33, the piezo element 32 as a pressure generating element and the second insulating layer 31 are continued, and the insulating layer 31 is in contact with the surrounding support unit 30 on the opposite side. To do. Thus, the piezo element 32 is electrically insulated.

  According to the above-described design of the laser unit 2, it is possible to act on the laser diode unit 34 via the force generated by the piezo element 32 in order to change the wavelength in this way. This is because the distance between the valence band and the conduction band, and therefore the wavelength, also depends on the force acting on the laser diode unit 34.

  The piezo element 32 is preferably made of tourmaline crystals provided with a silver film on its surface, the film being produced by vapor deposition and used to communicate with and control the entire piezo element 32. Instead of silver film, aluminum or another metal film can also be provided by vapor deposition.

  As already explained, the generation of the laser beam by the laser unit 2 requires both a mirror unit and an exit window, which substantially traverse the longitudinal axis 40 (FIG. 2A or 2B) of the laser unit 2. Arranged. The rear mirror reflects as much of the light beam generated by the laser diode unit 34 as possible, but the exit window allows the light beam that satisfies the predetermined condition to exit the laser unit 2 directly through the translucent window. It works to make it possible. More detailed information can be found in a publication entitled “Understanding Lasers” by Jeff Hecht (published in 1992, New York, IEEE Press, 2nd edition, pages 110 and 111).

Another embodiment of the portion of the laser unit 2 is shown in FIG. 2B with respect to a cross section parallel to the longitudinal axis 40, similar to FIG. 2A. As already in the embodiment of FIG. 2A, the support unit 30 of the embodiment according to FIG. 2B also forms a cavity in which the two insulating layers 31 and 33, the piezo element 32 and the laser diode unit 34 are contained. In contrast to the different embodiment according to FIG. 2A, the laser diode unit 34 is initially connected by a first insulating layer 33, then by a piezo element 32 as a pressure generating element and then by a second insulating layer 31. Surrounded by the support unit 30. In this way, the laser diode unit 3
4 can be generated by the pressure generating element 32, acting from all radial directions, ie from a direction substantially perpendicular to the longitudinal axis 40.

  Shown in FIG. 3 is an exit window 50 disposed axially on the support element 30 shown in FIG. The exit window 50 essentially includes a frame element 70 and a laterally disposed insulating layer 61, an opening 60 provided through both the frame element 70 and the insulating layer 61. In addition, a section AA is shown in FIG. 3, which forms the basis of a cross section through the exit window 50 shown in FIG.

  FIG. 4 shows the exit window 50 shown in FIG. 3 in a cross-section along section AA (FIG. 3). Through a cross section parallel to the longitudinal axis 40, the frame element 70 becomes a U-shaped part, into which a translucent window 51 is inserted, which translucent window 51 is substantially perpendicular to the propagation direction, ie the longitudinal axis 40 direction. Located. Displacement of the translucent window 51, ie, axially translated cholesterol and tilting movement with respect to the longitudinal axis 40, is also achieved with the help of positioning elements 52 to 56 (more commonly referred to below as displacement elements), which are It is constructed as a piezo element. In order to have 3 degrees of freedom for the movement of the translucent window 51, the positioning elements 52 to 56 of the embodiment shown in FIG. 3 are arranged at the corners of the translucent window 51 with four corners. Furthermore, the positioning elements 52 to 56 communicate individually via electrical connections so that the positioning elements 52 to 56 can be driven independently of each other. The control takes place for example via a central control unit, but no further illustration is shown.

  The mirror unit for reflecting the light beam generated in the laser diode unit 34 (FIG. 2) in as complete and lossless manner as possible can be realized as a fixed mirror surface according to the prior art.

  In another embodiment of the invention, it is proposed that the mirror unit is not fixed, but is realized in the same way as the translucent window 51 described with reference to FIGS. Of course, in this different embodiment, a translucent window is not necessary. For this reason, what is required instead of the translucent window 51 shown in FIG. 4 is a reflective surface obtained by evaporating a metal film on a support portion, for example. The remaining elements, i.e. positioning elements or displacement elements, are used to control the reflective surface. In this way, a laser unit 2 is produced that has an expanded application range for embodiments with fixed mirror surfaces (mirror elements), as will become particularly apparent in light of the following description.

  In order to obtain resonance in the laser unit, it is measurable that the distance between the mirror surface (mirror element) and the translucent window is a multiple of half the wavelength of interest (λ / 2) or exactly equal to this. Is known to be important. Here, when the wavelength is changed by a change using the piezo element 32 (FIG. 2), the distance between the mirror surface and the translucent window 51 is a multiple of half of the target wavelength (λ / 2) or exactly this. When set equally, a particularly efficient laser unit (ie maximum coherent light) can be obtained.

  Through a combination of precise settings of the spacing between the mirror surface and the translucent window 51 performed simultaneously with the force exerted on the laser diode unit 34 from all sides (FIG. 2B), the laser unit 2 (see FIG. 2) becomes available, which is particularly characterized in that the wavelength can be set electrically, for example between 400 nm and 700 nm, without the need for prisms or color filters or the need for frequency doubling.

FIG. 5 shows the laser unit 2 including the individual parts described with reference to FIGS. 2A, 2B, 3 and 4. Thus, the support element 30 according to FIG.
And 56 for electrical and thermal isolation.

  6A and 6B show a laser diode unit that is also manufactured by epitaxy or other methods, this laser unit showing pressure generating elements 73, 74 on all four sides of a square cross section, , 74 are spaced at each corner. In order to start all four parts of the pressure generating elements 73, 74 at the same time, they are either with the aid of a bonding wire (as shown in FIGS. 6A and 6B) or with a voltage source provided for this purpose or Directly coupled to the control unit 77 and electrically connected to each other.

  For further clarity, the pn junction is shown in FIG. 6A and the np junction is shown in FIG. 6B for the laser diode unit. From FIG. 6A and FIG. 6B, it is clear that the pressure generating elements 73 and 74 have a counter electrode with respect to the laser diode unit, so that the adverse effects between the pressure generating element and the laser diode unit can be prevented. .

The reference symbols used in FIGS. 6A and 6B can be identified as follows:
71 n (cathode) of the laser diode unit,
72 p (anode) of the laser diode unit,
73 n terminal of the pressure generating element,
74 p-terminal of the pressure generating element,
75 support elements,
76 Source of laser diode unit,
77 A control circuit for setting the force acting on the laser diode unit,
78 Air gaps between the individual parts of the pressure generating element,
79 Pressure generating element.

  FIG. 7 shows schematically the device according to the invention with the central part of the laser unit 2 located in the middle between the mirror unit 80 and the exit window 50, which laser unit is for example shown in FIGS. 6A and 6B. It is realized by the method described in connection with the above. This embodiment relies on the force that both the mirror unit 80 and the exit window 50 are generated by a pressure generating element (not shown in FIG. 7) and acting on the laser diode unit, and specifically the laser diode unit. Is always displaced in a centrally located manner between the mirror unit 80 and the exit window 50, or the diode laser surface is characterized by being away from the mirror unit by half a wavelength or a multiple of half a wavelength. However, this depends on whether an antireflection coating is applied to the diode laser surface. Specifically, when an antireflection coating is applied to the diode laser surface, no additional resonance is established between the diode laser surface and the mirror unit. On the other hand, if the diode laser surface is not anti-reflection coated, an additional resonance is created between the diode laser surface and the mirror unit, and if the distance is not correct, additional waves and hence losses are generated. Arise. This is caused by a deviation that depends on the distance of the mirror unit to the diode laser surface and applies to both exit ends of the laser diode unit. This is achieved, for example, with the help of a synchronous rotating device 100 mounted rotatably at point D as shown in FIG. Here, when the mirror unit 80 is displaced in the direction of W1 by the displacement element 52, 1: 1 transmission to the exit window 50 occurs via the synchronous rotation device 100, so that the direction of W2 of the same size is generated in the exit window. Displacement occurs.

  As a further advantage, alignment in the center of the laser diode unit or its surface produces an optimized power utilization.

Instead of the synchronous rotating device 100, the laser diode unit is always replaced by the mirror unit
There may of course be two or more displacement elements 52 which are arranged and arranged in a centrally located manner between the outlet window 50 and the outlet window 50.

  For the device according to the invention illustrated with respect to FIG. 1, the phototransistor unit 4 (FIG. 1) described with respect to FIGS. 8 to 13 is particularly suitable.

  The phototransistor unit 4 illustrated in FIG. 8 essentially includes a photosensitive layer 102 implemented, for example, by one or more phototransistors, and a filter unit 110 disposed in front of the photosensitive layer 102. The filter unit 110 includes a movable slit mask 103, a microprism unit 107, and a fixed slit mask 108. In particular, the movable slit mask 103 is essentially transverse to the slit mask 108 in the direction indicated by the arrow 105 with the help of displacement units 104 and 106 arranged transverse to the movable slit mask 103. Can move.

  In one particular embodiment, one displacement unit 104 is realized with the aid of a piezo unit and the other displacement unit 106 is realized as a viscous spring element. Here, the viscous spring element comprises, for example, a silicone insert, an insert made of natural rubber, or a steel spring. When silicone inserts are used, a buffer layer is required to prevent material migration.

  Further specific embodiments of the displacement elements 104 and 106 use microsteppers or microlinear motors, which allow the displacement of the movable mask 103 to be performed with very high accuracy as well.

  The prism unit 107 is disposed between the fixed slit mask 108 and the movable slit mask 103, and the masks 103 and 108 have corresponding first openings and second openings that form pairs of openings. . The prism unit 7 shows one prism for at least one opening pair.

  Although not shown in FIG. 8, in a further embodiment of the arrangement, instead of the movable slit mask 103, the position of the prism unit 107 is changed with the aid of a displacement unit, and the device is again realized in the form of eg piezo units and viscous spring elements. Is done. Thus, in contrast to the embodiment according to FIG. 8, it is also possible to selectively transmit these light waves L onto the photosensitive layer 102 through the slit mask 103 which is fixed here in position. The microprism unit 107 moves essentially laterally to the slit mask 103 or the slit mask 108.

  In yet another embodiment of the filter unit 110, both slit masks are movable. Since each of the slit masks moves half of the travel distance to be covered, the range of movement of the individual slit masks (Auslenkungen) is thus reduced. Here, the slit mask moves in the opposite direction in the lateral direction.

The described filter unit 110 thus represents a color filter whose filtered wavelength can be adjusted electronically. Furthermore, the filter unit 110 is a temperature-independent color filter that can be adjusted to a wavelength of, for example, 1400 nm to 430 nm. The filter unit 110 and therefore the phototransistor unit 1 as a whole is characterized by one or more of the following advantages:
The structure of the filter unit 110 or the structure of each of the phototransistor units 1 can be selected very small;
The desired wavelength of the light beam impinging on the photosensitive layer 102 can be adjusted electronically accurately;
-Minimal mechanical force;
-Extremely short reaction times;
The sensitivity of the phototransistor unit 1 increases if all aperture pairs are tuned to a certain wavelength or the same wavelength region where the measurements are made. In particular, then, the signal measured on the photosensitive layer can be applied, which leads to a higher signal content.

  In order to obtain an accurate measurement result using the phototransistor unit 1, calibration must be performed in advance. Such calibration can be performed as follows, for example.

  The phototransistor unit 1 is exposed to a light source having a known wavelength. Thereafter, the movable slit mask 103 or 108 or, if necessary, the microprism unit 107 is displaced with the aid of the displacement units 104, 106 until a signal maximum is obtained on the photosensitive layer 102 as long as it is movable. The The corresponding degree of displacement according to the displacement mechanism used can be kept constant for calibration. When a piezo element is used as an effective displacement unit, the electrical signal applied to the piezo element can be related to the wavelength of the light source, thus completing the calibration for this wavelength. In order to account for any non-linearities, it is advantageous if further calibration of other wavelengths of the light source is performed.

  It is known that the microprism unit 107 can be manufactured with a substance having a chemical formula NaCl in a crystalline form.

  FIG. 9 is a perspective view showing a further embodiment of the filter unit. In contrast to the embodiment according to FIG. 8, this embodiment shows only one slit in the slit masks 103 and 108. The microprism unit 107 correspondingly shows a single prism. The incident light beam is collimated by the slit mask 108. Thereafter, the collimated light beam is divided into light components of various wavelengths by the microprism unit 107. The light component of interest is selected with the help of the movable slit mask 103 by appropriately locating the movable slit mask 103. Thus, only light having a desired wavelength hits the photosensitive layer 102 and is measured.

  A further embodiment uses a hole mask instead of a slit mask. In this case, the corresponding image on the photosensitive layer is not a band shape but a point shape.

  FIG. 10 shows a microprism unit 107 used, for example, in the embodiment according to FIG. The microprism unit 107 is made of, for example, glass, and individual prisms are cut there. It should be noted that in the manufacture of the microprism unit, the individual prisms match the corresponding dimensions of the slit mask or hole mask. That is, the arrangement of the slits or holes coincides with the corresponding prism, and as a result, a desired wavelength or wavelength region can be measured. Corresponding slits or holes are generally designated as pairs of openings and correspondingly include a first opening and a second opening.

  In a further embodiment, the microprism unit 107 is made of polymer instead of glass. Manufacturing is thus simplified and less expensive than when glass is used. It is also conceivable to combine individual prisms to form a microprism layer. The individual prisms are then joined with an adhesive.

As is apparent from the foregoing description, an example application of the filter unit is to combine the photosensitive layer 102 and the filter unit, particularly in connection with the different embodiments according to FIGS. Thus, a phototransistor unit capable of performing extremely accurate measurement in a certain wavelength region is obtained, and electronic adjustment of the wavelength to be measured is possible.

  In a further embodiment of the filter unit, the wavelength passed through the slit mask or hole mask can be adjusted. For this purpose, two masks, one overlying the other, are given as masks, identified in FIG. 8 as reference numerals 103 and 108, which one is displaced laterally with respect to the other. can do. Such an embodiment is shown in FIG. 11, in which two masks 108a and 108b are placed one directly on top of the other, the mask being used laterally, for example, again using piezo elements in combination with viscous spring elements. Can be displaced. In this way, the slit size or hole size is changed, and as a result, a slit mask or hole mask with an adjustable opening can be obtained. A slit mask or hole mask with adjustable openings can be above the microprism unit, ie on the side of the light source L, or below the microprism unit, depending on the application. Furthermore, it is also conceivable that the opening of the slit mask or hole mask can be adjusted both above and below the microprism unit in the sense of the previous description.

  FIG. 12 shows a further embodiment of the filter unit 1 having a movable slit mask 108, a prism unit 107, a fixed slit mask 103, and a photosensitive layer 102 corresponding to the embodiment shown in FIG. In contrast to FIG. 9, the embodiment of FIG. 12 shows a movable slit mask 108 on the one hand, the side walls forming the slit have a conical shape, and the actual slit is narrower on the light exit side than on the light entrance side. On the other hand, the fixed slit mask 103 also shows a conical side wall, but the slit width is smaller on the light entrance side than on the light exit side because of the reverse direction. In other words, the slit width is smaller on the prism unit 107 side than on the photosensitive layer 102 side.

  In a different embodiment, the slit of the movable slit mask 108 comprises the converging optical system 13 and / or the slit of the fixed slit mask 103 comprises the diffuser 14. The converging optical system 13 obtains a larger amount of light or a slightly larger number of photons and strikes the prism unit 107 while the light exiting monochromaticly through the prism unit 107 is essentially uniform by the diffuser 14. Thus, the photosensitive layer 102 is dispersed over a larger area. The net result is an increased sensitivity of the phototransistor unit.

  In FIG. 12, the distance between the movable slit mask 108 and the prism unit 107 is indicated by a, the distance between the prism unit 107 and the fixed slit mask is indicated by b, and the fixed slit mask 103 and the photosensitive layer 102 are The distance between is indicated by c. It has been found that the distances a and c are preferably chosen as small as possible. The distance b is preferably variable, and thus functions to limit or adjust the bandwidth or wavelength region of the light beam that passes through the slits of the fixed slit mask 103.

  It is pointed out that the conical shape of the fixed slit mask 103, i.e. the steepness of the side walls that bound the slit, is selected in such a way that the relevant measurement area on the photosensitive layer is totally illuminated. In this way it is ensured that there will be no errors in the measurement results. This is because non-global illumination of the phototransistor generally leads to measurement errors.

  FIG. 13 shows a further embodiment of a filter unit according to the invention with a photosensitive layer 102 having a plurality of slits or holes in a slit mask or hole mask 108, similar to the embodiment according to FIG. Reference numeral 12 indicates mixed light, 15 indicates monochromatic light, and only the latter is incident on the photosensitive layer 102.

In the embodiment with the movable slit mask 108, the side walls forming the slit have a conical shape, and the slit opening is selected at the maximum on the light entrance side, so that as much light as possible enters each slit. Can do. In contrast, the side walls that form the slits come together at some point and in each case coincide with the top side of the movable slit mask 108. On the other hand, the fixed slit mask 103 is arranged in the opposite direction in the sense that the wide opening comes to the photosensitive layer 102 side. The diffuser 14 included in the slit ensures that the photosensitive layer is illuminated maximally and uniformly, so that higher sensitivity and more accurate measurement results can be obtained.

  In a further embodiment of the invention, the conical side walls of the slit are verspiegelted to further increase the illumination efficiency (Lichtausbeutung).

  In a further embodiment, the cross-sectional representation according to FIG. 13 is equally effective, and the masks 108 and 103 have holes instead of slits. Accordingly, the holes of the masks 108 and 103 have a truncated cone shape and are fitted into the masks 108 and 103 as the converging lens 13 in the case of the movable hole mask 108 or as the diffuser 14 in the case of the fixed hole mask 103. The insert (Einsaetze) also has a frustoconical shape.

  As already explained in connection with the embodiment according to FIGS. 8 and 9, in the embodiment according to FIGS. 12 and 13, the movable mask 108 can also be made fixed and the fixed mask 108 is also movable. It is explicitly pointed out that it can be made. Furthermore, the position according to FIG. 11 can be considered in the same way also in the embodiment according to FIGS.

  It has already been pointed out that the microprism unit is made of NaCl crystal, glass or polymer. Further conceivable are crystals, for example gemstones such as diamond with high color purity, quartz or neodymium.

  It is further pointed out that in all the embodiments described above, so-called multiprisms can be used for the microprism unit or the prism unit. Such multi-prisms, more commonly referred to as direct-view prisms (Geradsichtprismen), are assembled from a plurality of prisms with different materials, for example different grades of glass, so that the central ray is in spite of spectral deviations. Passes essentially without deflection. More detailed information about the multiprism can be found, for example, in DE-3737775A1.

  Finally, FIG. 14 shows an embodiment of the microwave unit 3 referred to in connection with FIG. This is a possible schematic structure of a part of the microwave unit 3 with respect to a cross section parallel to the microwave propagation direction 205. Like the laser unit 2 described with reference to FIG. 2, the microwave unit 3 (FIG. 1) includes a support unit 200 made of a material that can withstand loads, such as brass or platinum. Therefore, it is possible to cope with a large force as necessary. The following layers are included in the support unit 200 in a small structure. Starting from the upper support wall, there are a first insulator layer 201, a Gunn-Diode 202, a second insulator layer 203 and a piezo element 204. The various control lines with corresponding contacts for controlling the individual layers from the monitoring unit 1 (FIG. 1) are not shown in FIG.

  The Gunn diode 202 is a diode based on the Gun effect (John Gunn, 1963) and is used in a known manner to generate microwaves. For more detailed information about the Gun effect or Gunn diode, typically, the “Electronics Engineer's Handbook” (McGraw-Hill 4th Edition, 1997, 12.71, 12 Reference is made to a standard study by Donald Christiansen, entitled “.79 and 12.80”). This publication refers to further standard work on this subject.

  According to the above description, the Gunn diode 202 is clamped between the first insulator layer 201 and the second insulator layer 203. The frequency of the microwave generated by the Gunn diode 202 can now be adjusted, for example from 8.7 GHz to 12 GHz, with the aid of the piezo element 204. Here, the frequency shift is achieved, on the one hand, by the pressure on the Gunn diode 202 (ie, the so-called “die”) itself, which causes material alteration within the Gunn diode 202 as a result of molecular vibrational changes. This occurs in the same manner as when the temperature changes greatly. On the other hand, this is due to a change in capacitance caused by a change in the distance from the Gunn diode 202 to the support unit 200, and is similar to a change in capacitance in the capacitor in which the power storage plates are displaced relative to each other. In this way, the frequency generated by the Gunn diode 202 can be accurately adjusted via the piezo element 204. In this way, the described microwave unit 3 is particularly distinguished from known devices in that the frequency of the generated microwave can be accurately adjusted in an electronic manner without a mechanical adjustment device. .

  The piezo element 204 in a further embodiment of the microwave unit 3 has a known so-called PLL (phase-locked loop) or FLL (frequency) so that the frequency of the transmitted microwave 205 is kept constant once adjusted. A lock loop) circuit is provided. One of these circuits regulates the voltage applied to the piezo element 204 in such a way that the desired frequency of the microwave 205 is kept constant.

  Reference numeral 206 denotes an exit window of the microwave 205 on the Gunn diode 202 side. The window 206 is preferably obtained by appropriate doping with foreign atoms. In this way, controlled emission from the microwave Gunn diode 202 is possible. Particularly suitable for doping is GaAs (gallium arsenide). The diameter of the window 206 is, for example, about 10 μm, and the doping depth is, for example, 320 A (angstrom). Further, a +/− terminal is shown in FIG. 14, with the former electrical contact occurring within the window 206 and the latter electrical contact occurring outside the window 206.

  An embodiment of the microwave unit 3 (FIG. 1) is schematically shown in FIG. Reference numeral 250 indicates a cavity resonator and may also include a portion of the microwave unit 3 described with respect to FIG. FIG. 15 shows an alternative embodiment of FIG. 14, which will be described in detail with reference to FIG.

  The cavity resonator 250 is made of metal and has an exit hole 251 through which the microwave exits the cavity resonator 250 in the propagation direction 205. Included in the cavity resonator 250 is a ceramic body 234 on the one hand that extends from above into the cavity resonator 250, and on the other hand, a body 235 extends from below into the cavity resonator 250, The ceramic body 234 and the body 235 are oriented towards each other, i.e. they show a common axis but are not in contact. In addition to the body 235, an additional ceramic body 236 is further arranged, which will be described with reference to the detailed view of FIG. The main body 235 is made of a metal such as brass or copper and functions as a cathode. At the same time, excess heat can be removed through the body 235.

From FIG. 16, which is a detailed view of A according to FIG. 15, it is clear that there is a lower ceramic body 235 as a respective support element for the following devices or layers. (In order starting from ceramic body 235):
A piezo element 204;
A contact layer 203 made of a metal, for example silver or copper;
A Gunn diode 202;

  A control line 231 is provided to control the piezo element 204 and is connected to a contact 232 on the additional body 236. The contact 232 is led out from the cavity resonator 250 via a conductor included in the additional body 236, so that the piezo element 204 can be driven from the outside of the cavity resonator 250. The Gunn diode 202 arranged on the contact layer 203 is further connected to the ceramic body 234 via the contact loop 230, which simultaneously functions as a feed-through capacitor (Durchfuehrungskondensator) to the Gunn diode 202 from the outside of the cavity resonator 250. Makes it possible to touch.

  According to the above description, the Gunn diode 202 is attached to the contact layer 203 and the piezo element 204. The frequency of the microwave generated by the Gunn diode 202 can now be adjusted, for example from 8.7 GHz to 12 GHz, with the aid of the piezo element 204. Here, the frequency shift is achieved on the one hand due to a change in capacitance due to a change in the spacing between the Gunn diode 202 and the body 235 acting as the cathode, and on the other hand acting as a feedthrough capacitor. This is due to a change in position relative to the ceramic body 234. Therefore, it is possible to adjust the frequency of the microwave generated by the Gunn diode 202 through the piezo element 234 in an accurate manner. This embodiment is also distinguished from the known microwave unit in that the frequency of the generated microwave can be adjusted electronically.

A further advantage of this different embodiment is the shape of a very small structure, for example the outer dimension of the cavity resonator 250 is 2 × 1 × 1 mm, and only 3 terminals, namely V _Gnd , V _Gunn , and V _{With Piezo} , V _Gnd is equal to a common ground or coupling potential (Erd-bzw. Massenpotential), V _Gunn is equal to the supply voltage or Gunn diode signal pick-off, and V _Piezo is connected to the supply voltage of the piezo element and to it It is equal to the adjustment of the oscillator circuit (Schwingkreis). The built-in cavity resonator has almost no sensitivity to external influences because all components exhibiting high frequencies are contained in the cavity resonator. This situation makes the application to microsensor technology almost ideal.

  As already mentioned in connection with the description of the different embodiments according to FIG. 14, the tuned frequency of the transmitted microwave is constant with the help of a so-called PLL (phase-locked loop) or FLL (frequency-locked loop) circuit. This is naturally conceivable in the case of this embodiment.

  FIG. 17 shows an enlarged variant on the embodiment according to FIG. 16 with additional inductance and additional capacitance. In this way, high frequency signal components or microwaves are prevented from escaping from the cavity resonator in undesirable locations.

  FIG. 18 shows the support unit 200 in a side view, and reference numeral 205 again identifies the microwave beam generated by the Gunn diode 202 (FIG. 14). By embedding the support unit 200 using displacement elements 207 to 209, each of which is formed from a piezo element, the entire support unit 200 can be displaced or tilted, in other words, the direction of the microwave beam 205 is set. can do. The displacement element 207 and its counterpart (not visible in FIG. 8 because it is covered by the displacement element 207) are attached to the exit opening area of the microwave beam so that the largest area can be covered with the microwave beam. . These displacement elements 208 allow the support unit 200 to move perpendicular to the drawing, corresponding to the arrow 210 that is perpendicular to the drawing.

Two further displacement elements 208 and 209 are actually arranged at the opposite ends of the support unit 200 in such a way that the support unit 200 can move on the drawing of FIG. Accordingly, the displacement elements 208 and 209 act on two of the parallel surfaces of the support unit 200, while the displacement element 207 and its mating portion are the other of the parallel surfaces of the parallelepiped support unit 200. Acts on two.

  In order for the displacement elements 207 to 209 to contact without problems, a silver layer is preferably provided on the outside thereof. This allows simple contact with the control lines 220 through 222 through known joining techniques. In order to establish a reference potential (Referenzpotential), a reference connection (Referenzanschluss) 223 is associated therewith. For this purpose, the reference connection 223 is again preferably connected to the support unit 200 by means of a joining technique.

  The microwave beam can be tilted with respect to the two axes using the described positioning device, so that a cone of about 2.5 ° can be traversed. If a further displacement element acting on the third pair of surfaces of the support unit 200 is used, a translational movement in the third axis can occur.

  It is known that a Gunn diode can be used as both a transmitter and a receiver. Correspondingly, the microwave unit 3 is used not only for microwave transmission but also for reception in a similar manner.

It is explicitly pointed out again that the present invention shows possible applications from a broad perspective. Although non-invasive measurements of substances in the body, i.e. glucose and cholesterol, have been cited as exemplary examples, the present invention is not limited to any clinical and / or chemical as initially enumerated but enumerated. It is also suitable for non-contact measurement of parameters. Based on the list of possible clinical and / or chemical parameters that can be measured using the method according to the invention or the corresponding device, the following application results directly.
-An automated analyzer for determining clinical parameters up to DNA determination;
− Doping tests for sporting events. Rapid non-invasive testing is possible with the method according to the invention;
− Alcohol test car. Again, non-invasive measurements prove to be particularly advantageous;
-In the colorant industry, the exact formulation of the colored pigments in question is particularly important;
-Non-contact measurement of pollutants in wastewater. The method according to the invention can be used to determine the composition of a substance without having to take a sample. In this way, highly toxic substances can be investigated without danger.
The invention is excellently suitable for all microbiological applications relating to the detection of viruses or bacteria. It does not matter whether the virus or bacteria to be measured is contained in a solid, liquid or gas medium.
-Weld inspection. The method according to the present invention can detect microcracks with high reliability.

FIG. 2 schematically represents a device according to the invention for measuring a substance or a concentration of a substance as a parameter or parameter concentration in the body, respectively. FIG. 2 is a schematic perspective view showing a part of a laser unit, one cutting plane extending parallel to the longitudinal axis, and a further cutting plane extending across the longitudinal axis. FIG. 1B is a schematic perspective view showing a part of a further embodiment of the laser unit according to FIG. 1A. It is a figure which shows the exit window used in the case of a part of laser unit shown by FIG. 2A or 2B. 4 shows the exit window according to FIG. 3 in a section parallel to the longitudinal axis according to FIG. 2A or FIG. 2B. FIG. 5 shows a fully assembled laser unit according to FIGS. 2A, 2B, 3 and 4. It is a figure which shows the cross section which crosses the longitudinal axis of a laser unit. It is a figure which shows the cross section which crosses the longitudinal axis of a laser unit. FIG. 5 is a schematic view of a different embodiment in which the mirror unit and the exit window are always centered with respect to the laser diode unit. FIG. 2 shows a filter unit for use with the device according to FIG. 1. It is a perspective view which shows the further Example of a filter unit. It is a figure which shows the microprism unit for using with a filter unit. It is a figure which shows two masks in which one overlaps the other in order to adjust the wavelength to pass. It is a perspective view which shows the further Example of the filter unit which has a photosensitive layer. It is a figure which shows the further Example of the filter unit which has a photosensitive layer. It is the schematic which shows a part of microwave unit in the cross section parallel to a longitudinal axis. FIG. 5 shows a cavity resonator with a further embodiment for a part of the microwave unit. FIG. 16 is a detailed view of a further embodiment of a part of the microwave unit according to FIG. 15. FIG. 17 is a detailed view according to FIG. 16 of a third embodiment of a part of the microwave unit. FIG. 15 shows the microwave unit according to FIG. 14 with a device for aligning the microwave beam.

Claims (18)

A method for measuring clinical and / or chemical parameters (S1) in a medium (10) comprising:
There are means (2) for transmitting coherent light waves (6) and means (4) for receiving light waves (8);
-At least part of the transmitted light wave (6) is transmitted to the medium (10);
The means (4) for receiving a light wave (8) measures at least part of the light wave (8) reflected by the medium (10),
The method wherein the parameter (S1) is measured based on the characteristics of the transmitted and received light waves (6; 8).   The method according to claim 1, characterized in that the frequency or wavelength of the coherent light wave (6) is adjusted according to the characteristics of the parameter (S1) to be measured.   Method according to claim 1 or 2, characterized in that the means (4) for receiving light waves (8) are adjusted in a frequency selective or wavelength selective manner.   Method according to any of the preceding claims, characterized in that said means (2) for transmitting coherent light waves (6) are operated to generate wavelengths between 400 nm and 1400 nm.   5. A method according to any one of claims 1 to 4, characterized in that cholesterol is determined as parameter (S1) and / or its blood concentration is measured. A method for measuring clinical and / or chemical parameters (S2) in a medium (10) comprising:
-Means (3) for transmitting the microwave (7a) and means (3) for receiving the microwave (7b);
-At least part of the transmitted microwave (7a) is transmitted to the medium (10);
The means (3) for receiving the microwave (7b) measure at least part of the microwave (7b) reflected by the medium (10),
6. The method according to claim 1, wherein the parameter (S2) is measured on the basis of transmitted and received microwaves.   Method according to claim 6, characterized in that the frequency or wavelength of the transmitted microwave (7a) is adjusted according to the characteristics of the parameter (S2) to be measured.   Method according to claim 6 or 7, characterized in that said means (3) for transmission and reception of microwaves (7a, 7b) generate pulses with a duration of 83 picoseconds to 133.3 picoseconds. .   9. A method according to any of claims 5 to 8, characterized in that glucose is determined as parameter (S2) and its blood concentration is measured.   The position of the measurement path (100) in the medium (10) is established with the aid of means (2) for transmitting coherent light waves (6) and means (4) for receiving light waves (8); 10. The method according to claim 1, wherein the measurement of the parameters (S1, S2) is limited to the measurement path (199).   Method according to claim 10, characterized in that the means (2) for transmitting coherent light waves (6) are operated to generate light waves in the infrared region. 12. Method according to claim 10 or 11, characterized in that the time points of the measurements made in the measurement path (100) are established on the basis of an identifiable time signal, in particular a cardiac cycle.   A laser unit (2), a phototransistor unit (4), and a monitoring unit (1) are provided. The monitoring unit (1) includes each of the laser unit (2) and the phototransistor unit (4). An apparatus for performing the method of any of claims 1 to 12, wherein the apparatus is operatively connected.   14. Device according to claim 13, characterized in that there is a microwave unit (3) in operative connection with the monitoring unit (1).   15. The device according to claim 14, characterized in that the microwave unit (3) or its transmitter is movably supported in at least one plane, preferably in two planes.   Device according to any of claims 13 to 15, characterized in that the phototransistor unit (4) exhibits a frequency-responsive or wavelength-responsive adjustment mode.   17. A device according to claim 16, characterized in that the frequency or wavelength of the detected wave (8) is adjustable.   Device according to any of claims 13 to 17, characterized in that the time points of the measurements made in the measurement path (100) can be established on the basis of an identifiable time signal, in particular a cardiac cycle. .

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