EP1587415A1

EP1587415A1 - Method and assembly for measuring a dispersion in transparent media

Info

Publication number: EP1587415A1
Application number: EP03785827A
Authority: EP
Inventors: Adolf Friedrich Fercher
Original assignee: Carl Zeiss Meditec AG
Current assignee: Carl Zeiss Meditec AG
Priority date: 2003-01-23
Filing date: 2003-12-16
Publication date: 2005-10-26
Also published as: DE10302849A1; JP2006512979A; US20060244972A1; WO2004064628A1

Abstract

The invention relates to methods and assemblies for measuring a dispersion and content of glucose in organic transparent and semitransparent tissues and liquids by low-coherent interference optical refractometry. Low-coherent interferometry and spectral interferometry methods are modified in such a way that a tissue thickness and local dispersion are measurable. For a technology based on low-coherent interferometry, partial interferograms received from low-coherent interferograms G ( tau ) are used for a dispersion measurement. For a technology based on spectral interferometry, the partial areas of a spectrum omega of a spectral interferogram are used for a dispersion measurement. The figure 6 displays an assembly based on spectral interferometry. A time-dependent low-coherent light source (1) illuminates a modified Michelson interferometer. A beam splitter (4) splits an illuminant beam into a measuring beam (5) and a reference beam (6). Light waves (46 and 6) reflected outside the interferometer reach a spectrometer at the exit of the interferometer. The recorded spectral interferogram i ( omega ) provides with a basis for calculating the dispersions of different waves. The viewing direction of the eye of a subject who makes said calculation is fixed by means of a target beam (32).

Description

Method and arrangement for measuring the dispersion in transparent media

The present invention relates to methods and arrangements for measuring the dispersion and determining the concentration in substances, such as tissues and aqueous solutions, contained and influencing the dispersion. The arrangements described here are suitable for spatially localized measurement of the dispersion of different orders in transparent and partially transparent tissues and body fluids, especially in the aqueous humor of the human eye. From this dispersion measurement, the value contained therein, such as glucose, can be determined.

A still unexplored question in many respects is the dynamics of the glucose content in the different body tissues, especially the eye. The solutions proposed here also allow a quick quantitative determination of the glucose content in transparent and. semi-transparent fabrics. This provides a completely non-invasive method for determining blood sugar in diabetics.

In diabetes, especially in diabetes mellitus, an optimal adjustment of the blood sugar level is a prerequisite for avoiding secondary diseases. Only diabetics who regularly monitor their metabolic values can delay or even prevent late complications. Human blood sugar levels are normally between 50 mg / dl and a maximum of 140 mg / dl (after eating). The aim of diabetes therapy is to get as close as possible to these blood sugar levels.

The current standard blood glucose measurement based on glucose oxidation requires blood to be drawn from the body and is therefore an invasive procedure. Because of the fear of self-harm and pain, this method is severely restricted. This can be especially true with diabetic sick children, whose parents have to take the measurement, become a problem; Also, diabetics often fail to take measurements that might have to take place in public. In older people, blood sugar measurements can often no longer be carried out using conventional methods due to hornification of the fingertips and poor circulation.

According to the known state of the art, there are some partially invasive methods, such as iontophoresis (e.g. Gluco Watch from Cygnus), which require only minor injury (abrasion) to the epidermis. A disadvantage of these methods is the requirement for close skin contact, which is not disturbed by anything (not even sweat), and the time delay caused by the skin.

Most non-invasive procedures work optically (see: McNichols RJ & Cote GL (2000) Optical glucose sensing in bioiogical fluid: an overview. Journal of Biomedical Optics 5 (1): 5-16). These include methods based on NIR transmission and remission or light reflection, as well as using polarimetry and Raman spectroscopy. Furthermore, scattered light methods based on OCT, methods based on IR emission spectrometry and photoacoustic methods were described (Zuomin-Zhao and Myilyla, R. Photoacoustic determination of glucose concentration in whole blood by a near-infrared laser diode. Proc. SPIE 4256 , 77-83. 2001). However, none of these non-invasive procedures have been used to date. The reasons for this are: the sensitivity of the methods is too low, the scatter of the measured values is too great or the application is too cumbersome for the patient.

Van Engen et al. Described a basic method for measuring the dispersion of different orders in transmission in 1998 (Van-Engen-AG,. Diddams-SA, and Clement-TS. Dispersion measurements of water with white-light interferometry. Applied-Optics 37 ( 24), 5679-5686. 1998). In a first step, the interferogram ^'G ^ generated by the measurement sample, for example in the essarm of a Michelson interferometer registered, Fourier-transformed and delivers ^J <^) = S ω ^Q xp [ik (ω) d] _{^ Ejn}

Polynomial fit to the phase values ^ω X forms the basis for determining the dispersions of different orders as members of a Taylor series. The van Engen process, among others, works in transmission and requires cuvettes of known depth. Such a method is therefore not applicable to the eye.

The present invention has for its object a technical solution for the non-invasive determination of the substance concentration in transparent or partially transparent ocular fluids or tissues, ^'ntration particular glucose Konze to develop.

According to the invention, the object is achieved by the features of the independent claims. Preferred developments and refinements are the subject of the dependent claims.

The methods and arrangements presented here provide reliable and accurate measured values and are easy and convenient to use. The solutions are based on measuring the dispersion of the aqueous humor in the eye. For the measurement, a glance into the target beam emerging from the device and a push of a button to trigger the measurement is sufficient. The application relates to 2 different arrangements for measuring the dispersions and the glucose content in ocular tissues and / or other partially transparent substances. Since the proposed solutions work with reflected light, the depth of the compartments detected by the measurement, such as the thickness of the coma and the depth of the anterior chamber, can also be measured.

The invention is described below using different exemplary embodiments. Show this

FIG. 1: the optical principle of the short-coherence interferometer for dispersion and giucose measurement, FIG. 2: a series of partial interferograms of ocular interfaces,

FIG. 3: the spectral interferogram for a light-reflecting point,

Figure 4: an empirical calibration diagram for the

Glucose concentration,

FIG. 5: the signal of a calibration interferometer,

Figure 6: the optical principle of the spectral interferometer for dispersion and glucose measurement and

Figure 7: the use of a glucometer according to the invention.

The arrangements and methods described below combine short coherence length measurement with short coherence dispersion measurement and are suitable for in vivo measurements on the eye. The underlying physical methods are

- the short coherence interfermetry and

- spectral interferometry.

These methods are known as time-domain LCI and as Fourier-domain LCI; see the essay by AF Fercher and CK Hitzenberger: Optical Coherence Tomography, in: Progress in Optics Vol. 44 (2003), Ch. 4, Editor E. Wolf. Compared to the methods and arrangements of short coherence length measurement described there, the proposed solutions enable both the measurement of the lengths of the compartments and the measurement of their dispersions. In particular, the measurement of the dispersions and the resulting glucose content in compartments such as tissues and aqueous solutions, for example the aqueous humor of the human Eye, are an integral part of the present solution. Compared to the previous methods of interference refractometry, the arrangements and methods proposed here measure not only the dispersion of the irradiated media but also their thickness. The solutions according to the invention are based on two different measurement beam paths and the associated two calculation methods.

The underlying technologies of short coherence correlation interferometry and spectral interferometry lead to two different measurement beam paths (according to FIGS. 1 and 6). In both cases, the sample is located in one arm of a two-beam interferometer, for example a Michelson interferometer. While at the. Short coherence correlation interferometry of the reference mirror 14 of the interferometer is moved to record the interferogram at the interferometer output, the reference mirror 14 remains stationary during the measurement by spectral interferometry. A triple mirror or triple prism is preferably used as the reference mirror 14. The light beam emerging at the interferometer output is analyzed with a spectrophotometer. Both ^'methods provide after some intermediate steps the frequency-dependent transfer function of the sample is calculated from the phase terms of the dispersions of the sample material. The individual steps of the two calculation methods and then the two measurement arrangements are described in detail below.

1. Calculation procedure

1: 1. Length and dispersion measurement using short coherence correlation interferometry

1.1.1. length measurement At the interferometer output, a continuously shifted reference mirror, for example, causes a continuously changing optical path difference L between the reference and measuring beam and thus an interferogram G (τ) which is dependent on the transit time difference r. The transit time difference τ = L / c is the time delay that occurs between the partial beams of the interferometer. G (τ) is a signal as shown in Figure 2. From the spacing of the partial interferograms 21, 22, etc. (in our exemplary embodiment to 24), the thicknesses of the compartments result, as is customary in short-coherence correlation interferometry.

1.1.2 Dispersion measurement

According to the invention, the location-dependent dispersion values are obtained from the isolated partial interferograms 21 to 24. First, by means of Fourier transformation, complex partial interferogram spectra 1 ₂ (ω), I ^ icX) are obtained _. etc..

The partial interferogram spectra I ₂ ι (a>), ι ( ^ω ) ^etc. - have the spectral phases Φ ₂ \ (ω) ■ = 2k (ω) dι, ■■ ^φ 2i ( ^ß) ) = ² ^ ( ^ö) ) ^ 2 ^etc. - from which - after a previously performed polynomial fit with, for example, Zernike polynomials - according to van Engen et al. (1998) expressions for the derivatives of the wave numbers k (ω) are obtained: the sth derivatives of the wavenumbers k ( ω) d ^s k dω ^s ' determined from the partial interferograms 21, 22, etc., are the first-order dispersions for the distances d \, d ₂ , etc.

1.2. Length and dispersion measurement using spectral interferometry

1.2.1 Length measurement First, the spectral interferogram i (ω) occurring at the interferometer output with a fixed reference mirror is registered. For individual lichtremittierende locations in the measurement object in the intensity course of this interferogram in ^'the spectrum plane 70 of the spectrometer has a period length P © -space, which is indirectly proportional (mirrored around the beam divider of the interferometer) to the distance of this point from the virtual position of the reference mirror. See Figure 3. Hilbert transform of i (ω) gives the complex interferogram I (ω). A Fourier transformation provides the interferogram G (τ) and thus also the partial interferograms as well as the thicknesses of the compartments, as previously described under point 117.

1.2.2 Dispersion measurement

The dispersion can basically be calculated using the partial interferograms as in point 7.7.2. However, because of the small number of samples per partial interferogram, this would provide poor sensitivity and accuracy. Greater sensitivity is obtained if the procedure according to the invention is as follows: Depending on the distance of the light-emitting point in the eye, the interferogram spectrum I (ω) contains light components with different lengths of period P in the © space. According to the Sampling-TheoreiTT, the sampling must be carried out with such a high spatial frequency that aliasing is omitted. This is according to the rules of spectral interferometry

the case when N = z _s samples are registered; Δ = is π c the scattering vector, Aω the frequency bandwidth of the light and z _s the maximum

Distance of a light-emitting measuring object point from the virtual position of the reference mirror (mirrored around the beam splitter surface of the interferometer).

As can be seen in FIG. 3, the smallest period lengths P im belong to the reflection points furthest away from the reference mirror Intensity spectrum and thus the largest 1 / P frequencies in the intensity curve in the spectral plane 70. In order to avoid confusion with the light frequency ω, this frequency is referred to as “1 / P frequency”. The scanning in the spectral plane 70 must therefore take place that the sampling theorem is fulfilled for the reflection points that are virtually the furthest away from the reference mirror position, since otherwise the signal components are shifted along the measurement path due to the “aliasing” phenomenon. For the measurement, the reference mirror is positioned in such a way that its virtual position comes as close as possible to the position of the measurement object (on the eye, for example, the front surface of the lens) where the dispersion is to be determined. For this purpose, then the lowest 1 / P frequencies in the intensity profile in the spectrum plane 70 and the greatest period lengths include P. After the scan, the higher 1 / P-frequencies are in the intensity _course in the spectrum plane 70 mathematically eliminated. According to the invention, the dispersions are formed from the phase Φ (ω) = k (ω) d of the remaining 1 / P low-pass spectrum in

Intensity curve in the spectral plane 70 determined. The dispersions to the interface which is virtually the closest to the reference mirror are obtained.

2. Orders

2.1 Short coherence correlation interferometry

The optical principle of the short coherence interferometer is shown in FIG. 1. A temporally short-coherent light source 1, for example a superluminescent diode or a multimode laser, an LED, a plasma light source, a halogen lamp or an incandescent lamp, emits a short-coherent light beam 2, which is collimated by the optics 3, into the modified Micheison interferometer with the beam splitter 4 Beam splitter 4 divides this beam into measuring beam 5 and reference beam 6. Measuring beam 5 strikes eye 7 and is separated from its interfaces, for example corneal front surface 8, corneal rear surface 9, lens front surface 10, lens Back surface 11 and fundus 12 reflected back. The reflected light waves 45 pass through the interferometer and hit the photodetector 13. The reference beam 6 is reflected by the triple prism 14, transmits the flat plate 15 (a second time) and is reflected by the rear surface of the beam splitter 4 onto the photodetector 13, where it is comes to interference with the times 45 reflected by the eye 7.

To register the interferogram G (τ), the reference mirror 14 is also used

Moved with the aid of a scanning device consisting of slide 16, guide 17, drive spindle 18 and motor 19. This is associated with a double shift of the reflected reference wave. The interferogram G (τ) is obtained from the photoelectric signal of the detector 13 by frequency band filtering at the Doppler frequency. If the optical paths in the measuring beam 5 and reference beam 6 are of equal size within the coherence length, as indicated, for example, in FIG. 1 by the distance D for the lens front surface 10, a photoelectric alternating signal with this Doppler frequency occurs at the photodetector 13, as is the case with the Doppler frequency indicated in FIG. 2 with the partial interferogram 23. The z coordinate of FIG. 2 is linked to the τ coordinate via the speed v of the reference mirror 14: τ = 2zlc and z = vt, where l _{c is} the coherence length

G (z) contains a series of partial interferograms, according to FIG. 2: 21 is the interferogram of the wave reflected by the corneal front surface 8 with the reference wave 6; 22 that of the wave reflected by the corneal rear surface 9 with the reference wave 6; 23 that wave reflected by the lens front surface 10 with the reference wave 6 and 24 that wave reflected by the lens rear surface 11 with the reference wave 6. The interferogram of the wave reflected by the fundus 12 with the reference wave 6 is not shown. In physics, these interferograms are also described as the interference of wave groups reflected at the interfaces with that of the reference arm. Figure 2 indicates the dispersion-related Increase in the coherence length l _c along the abscissa and a change in the waveform of these wave groups.

The dispersion-related change in the partial interferograms G (z) outlined in FIG. 2 is the basis for the dispersion and glucose measurement presented here. The locations at which the partial interferograms are created in the measurement object are therefore possible positions for the dk dispersion measurement. The 1st order dispersion, that is -, causes a dω different from the phase velocity c of light

Group speed: v _G is the

Wavenumber, ω _Q = 2πv ₀ with the mean frequency v _{0 of} the light wave. dn n _G = 77-1 - is the group index, n is the refractive index. The dispersion d λ ^■ d ² k 1 cdn 2nd order is - - = - -; this changes the coherence length and the dω ² 2π v ³ dλ ² shape of the partial interferograms. Since the spectral course of the refractive index n is determined by the polarizability of the molecules of the medium, d ^s n, as well as its s th differential quotient, are characteristic of the dλ ^s light-transmitting molecule types. Both the spectral profile of n (λ) and the spectral profile can be used for such a characterization

of the s th differential quotient - - are used. dλ ^s

It has been shown that the use of the second-order dispersion d ² n (oc - -) allows the giucose content in aqueous solutions to be determined with a sensitivity dλ that is dependent on the size of the physiologically relevant values [Liu et al., Proc , SPIE 2003]. A corresponding preliminary calibration graphic is shown in Figure 4. The method can be made even more sensitive and precise by using particularly broadband light sources and taking into account the spectral values of the 1st order dispersion, the spectral values of the 3rd order dispersion and the spectral refractive index.

In order not to interfere with data registration and processing with device-related dispersion, it makes sense to compensate for the dispersion in the measuring arm up to the position of the dispersion measurement with the same amount of dispersion in the reference arm. In order to compensate for the influence of water on the dispersion of the aqueous humor in the dispersion measurement on the eye, a water-filled cuvette can be arranged in the reference jet, the water distance of which corresponds to that of the chamber depth plus the corneal thickness. Because of the high water content of the cornea, it can be included in the dispersion compensation for water. Instead of the water-filled cuvette, you can also, according to Figure 1, a flat plate 15 made of glass in. Arrange the reference beam. This must produce the same dispersion as the 3.6 mm long section from the comea apex to the front lens apex (Gullstrand eye). For BK 7 and dispersion 2 _; This is the case for λ = -, 5μm to λ - = 0.8μm, for example with a thickness of around 2.3mm. Then, in the ideal case, only the effect of the dispersion produced by the dissolved substance, such as glucose, remains in the interferogram.

The dispersion effect of glucose is proportional to its concentration in the aqueous humor as well as to the depth of the anterior chamber. To determine the aqueous humor glucose, you therefore need to know the anterior chamber depth and the corneal thickness. These thicknesses correspond to the distances of the interferograms 21 and 22 as well as 22 and 23. The corneal thickness is τ _c - VGC _> the anterior chamber depth is K ' ^V GVK _> where v _GC ^■ and VQ _{VK are} the group velocities in the cornea and in the anterior chamber. The information about the anterior chamber glucose is contained in the interferogram 23 of the front surface 10 of the lens. A very short movement of the reference mirror 14 is sufficient to detect the interferogram 23 of the front surface 10 of the lens; in principle, a distance of a few coherence lengths is sufficient. Depending on the bandwidth of the light source 1, this is a few micrometers to a few tens of micrometers. In addition to the short coherence depth scan carried out by the slide 16 (also known in the literature as an A scan), a short scan mode for the reference mirror is provided for this dispersion measurement; in which it is only moved a short distance, for example Vz mm virtually centered around the position of the dispersion measurement, for example around the position of the lens front surface 10. This can be done by a corresponding electrical short scan mode of the control unit 25 controlling the drive motor 19. Such a short scan mode can also be realized in that the reference mirror 14 by means of a piezoelectric. Adjustment unit 20 is fastened on the carriage 16, with the aid of which a precise movement of a few tens of micrometers to a few hundred micrometers is carried out when the carriage 16 is stationary. Instead of the piezoelectric adjustment, the short scan mode can also be implemented by an electrodynamic adjustment by means of a so-called "voice coil" or another fine adjustment. It should be pointed out that the short coherence depth scan itself can also be carried out using one of the last-mentioned devices. In this case too, the short scan mode can be implemented by means of the electrical control unit 25. Finally, the A-scan can also be carried out using the method described by Kwong et al 1993 [Kwong-KF, Yankelevich-D, Chu-KC, Heritage-JP-, and Dienes-A: 400-Hz mechanical scanning optical delay line. Opt. Lett. 18 (7), 558-560, 1993]. Here ^■ can a tilting mirror realized the short scan mode by appropriate electrical control.

However, in the short scan mode, care must be taken to ensure that this is actually centered around the position of the dispersion measurement, for example the front surface of the lens 10. That is with free Movement of the head (especially the subject's eye) relative to the interferometer cannot be guaranteed. For this reason, a forehead support 63 is provided, with the help of which one is supported up to approximately by supporting the head on the measuring device! mm can ensure exact device distance (see Figure 7). Since the anatomical position of the eye 7 with respect to the forehead varies from subject to subject, this forehead support must allow a variable device distance to be set. The correct position of the lens front surface 10 of the eye 7 and, accordingly, the position of the iris and the entrance pupil are decisive.

A device is therefore provided which allows the entrance pupil of the eye 7 to be reproducibly brought to the same position with respect to the interferometer. This consists of a (pierced) spherical concave mirror 30. The test person must bring his eye 7 into such a position that the concave mirror 30 images the entrance pupil 31 of the eye 7 on it itself on a 1: 1 scale. This is the case if the subject, eye 7 approaching the device, has no light sensation for the first time - or if the subject, eye 7 removed from the device, has no light sensation for the last time. This process is facilitated by a forehead support 63 with a continuously adjustable distance.

Furthermore, the viewing direction of the eye 7 must be fixed. It should be noted that the visual axis is approx. 5 ° to 10 ° nasal (towards the nose) to the imaginary axis of symmetry of the optical system, the optical axis. In order to get the reflections from the interfaces of the eye 7 into the interferometer beam path, the eye 7 must be oriented accordingly. This is achieved by means of a target beam 32, which is generated by the punctiform light source 33 and the collimation optics 34 and is directed onto the eye 7 via the pierced deflection mirror 35. The collimation optics 34 can be moved in their holder 36 in the x and y directions, so that different inclinations of the target beam 32 relative to the axis of the measuring beam-5 can be set. To compensate for non-linearities in the displacement of the reference mirror 14, a further quay calibration interferometer is shown: This consists of the light source 40, which, in contrast to the light source 1, is highly coherent in time, such as a monomode semiconductor laser or a Heiium neon -Laser. Furthermore, this calibration interferometer consists of collimation optics 41, a deflecting mirror 42, an end mirror 43 and the photodetector 44. The beam splitter 4 and the reference mirror 14 of the short-coherence-iriterferometer act as a beam splitter and reference mirror. The beam path of the calibration interferometer is shown in dashed lines in FIG. 1 offset to the side of the beam course of the short-coherence interferometer. However, it is actually slightly above or below the beam path of the short coherence interferometer.

The electrical signals supplied by the photodetectors are processed in the computing unit 60. A strictly linear abscissa with τ is important. Due to speed fluctuations of the reference mirror 14, however, serious non-linearities in τ arise here. These are eliminated with the help of the photodetector signal of the calibration interferometer. The calibration interferometer delivers a periodic signal with a period length of half the wavelength of its light during the entire displacement of the reference mirror 14, as outlined in FIG. 5. This divides the abscissa into constant sections, which can serve as a time base for the synchronously recorded measurement signal and thus linearize the time scale of the measurement signal.

2.2 Spectral interferometry

This optical principle is shown in FIG. 6. A temporally short-coherent light source 1, such as a superluminescent diode, a multimode laser, an LED, a piasmal lamp, an incandescent lamp or a halogen lamp, emits a short-coherent light beam 2, which is collimated by the optics 3 into the modified Michelson interferometer with the beam splitter 4. The beam splitter 4 divides this beam into the measuring beam 5 and the reference beam 6. The measuring beam 5 strikes the eye 7 and is separated from its interfaces, for example the front surface of the cornea 8, the rear surface of the cornea 9, the front surface of the lens 10, the rear surface of the lens 11 and the fundus 12 reflected back. These reflected light waves 45 pass through the interferometer and strike the spectrometer consisting of entrance aperture 51, collimation optics 52, diffraction grating 53, focusing optics 55 and detector array 56. The reference beam 6 transmits the plane plate 15, is reflected by the reference mirror 14, transmits the plane plate 15 a second time and is directed from the rear surface of the beam splitter 4 into the entrance aperture 51 of the spectrometer, where it interferes with the waves 45 reflected by the eye 7 ,

Here, the spectral interferogram i (ω) registered in the spectral plane 70 by the detector array 56 forms the basis for the calculation of the first-order dispersions, as described under item 7.2.2. The measurement of the intraocular sections such as corneal thickness, anterior chamber depth and lens thickness is carried out according to the rules of short coherence interferometry ("Fourier-domain LCI", see the above-cited review AF Fercher and CK Hitzenberger: Optical Coherence Tomography, in: Progress in Optics _. Vol. 44 (2003), Ch. 4, editor E. Wolf) For this purpose, the virtual position of the reference mirror (mirrored around the beam splitter surface of the interferometer) must be approximately twice the distance of the sum of these sections in front of the cornea be that it allows you to set this distance.

Here, too, it makes sense not to burden the data registration and processing with device-related dispersion and to compensate for the dispersion in the measuring arm with an equally large dispersion in the reference arm. For example by means of a water-filled cuvette or a suitable flat plate 15 made of glass or another transparent material with a suitable dispersion.

Since the information about the anterior chamber glucose is contained in the light reflected by the position of the dispersion measurement, for example the front surface of the lens 10, this position should be detected with maximum resolution. In order to register the Fourier components of the light reflected from the position of the dispersion measurement with the maximum sampling rate, the virtual position of the reference mirror (mirrored around the beam splitter surface of the interferometer) - unlike the already known Fourier-domain LCI length measurement technology - must be as close as possible to that Position of the dispersion measurement lie. For this purpose, a forehead support 63 is provided, by means of which one can ensure an accurate device distance of up to approximately 1 mm by supporting the head on the measuring device. Since the anatomical position of the eye 7 with respect to the forehead varies from subject to subject, the device distance must be variably adjustable.

The correct position of the lens front surface 10 of the eye 7 is decisive for the measurement of the aqueous humor dispersion; this corresponds to the position of the iris and thus the entrance pupil 31 of the eye 7. A device is therefore also provided here, by means of which the test person can bring the entrance pupil 31 of his eye 7 reproducibly to the same position with respect to the interferometer. For this purpose, a (pierced) spherical concave mirror 30 is attached to the measuring window of the interferometer. The test subject must move his eye 7 into such a position that the concave mirror 30 images the entrance pupil 31 of the eye 7 on it itself on a 1: 1 scale. This is the case when the subject, who approaches his eye 7 to the device, no longer has any light sensation for the first time - or, when the subject, who removes his eye 7 from the device, has no light sensation for the last time. This process is facilitated by a forehead support 63 with a continuously variable distance. Here too, the gaze direction of the subject's eye 7 must be fixed. This. is also achieved here by means of a target beam 32, which is generated by the punctiform light source 33 and the collimation optics 34 and is directed onto the subject's eye 7 via the (pierced) deflecting mirror 35. The optics 34 can be displaced in their holder 36 in the x and y directions, so that different inclinations of the target beam 32 relative to the axis of the measuring beam 5 can thereby be set.

3. Glucometer

The calculation methods described under point 7 are carried out in a computing unit 60 or 61. The glucose content is determined from the calculated dispersions on the basis of stored empirical tables, such as that shown in FIG. 4. Figure 7 shows the use of such a device. For individual glucose control, the entire arrangement including the computing unit (60 or 61) can easily be accommodated in a housing 62 which can be held in front of the eye 7 with one hand and supported on the forehead by means of the forehead support 63. On the surface there is also a display unit 64 for the glucose content determined from the measured dispersions by means of internally stored tables and rotary knobs 65 for setting the target beam 32.

It should also be pointed out that the distance adjustment by means of the forehead support 63 and the adjustment of the aiming beam 32 only occur for a test subject at the beginning of the use of the device. These settings can be omitted for further glucose measurements.

The described methods measure the cumulative dispersion up to the position of the dispersion measurement. These methods can therefore be used to measure the dispersions in tissues other than cornea and aqueous humor be used. For example, to measure the cumulative dispersion in the cornea, aqueous humor and lens; or to measure the cumulative dispersion in cornea, aqueous humor, lens, and vitreous. These methods can be also used for measurement of the dispersions in other tissues and ^• liquids.

The decisive factor here is the position of the reference mirror: In spectral interferometry, this must be virtually as close as possible to the position of the dispersion measurement so that the low-pass spectrum contains the signal from the position of the dispersion measurement. With short-coherence correlation interferometry, the scan path of the short-scan mode must contain the position of the dispersion measurement. By forming the difference, the dispersion of individual tissues alone, for example the dispersion of the eye lens, can also be determined from these measured values.

Bezuαszeichenϊistβ

1 light source

2 short-coherent light beam

3 optics

4 beam splitters

5 measuring beam

6 reference beam

7 eye

8 front surface of the cornea

9 comea back surface

10 front lenses

11 lens rear surface

12 fundus

13 photodetector

14 reference mirror

15 flat plate

16 sledges

17 leadership

18 drive spindle

19 engine

20 piezoelectric adjustment unit

21 partial interferogram (for 8)

22 partial interferogram (for 9)

23 partial interferogram (for 10)

24 partial interferogram (for 11)

25 control unit

30 spherical concave mirror

31 entrance pupil

32 target straight

33 point light source

34 Collimation optics deflecting

bracket

light source

collimating optics

Umlenkspiegei

end mirror

Photodetector reflected light waves

entrance diaphragm

collimating optics

diffraction grating

focusing optics

detector array

computer unit

casing

forehead support

display unit

knobs

Spectral plane

Claims

claims

1. Method ^' for measuring the thickness and dispersion of transparent or partially transparent tissues or body fluids, by applying ^' short-coherence interferometry, in which the content of substances influencing the optical properties is determined from the results of the dispersion measurement.

2. The method according to claim 1, wherein the content of the substances contained is determined using stored tables.

3. The method according to at least one of claims 1 to 2, in which the glucose content is determined with the aid of stored tables from the results of the dispersion measurement.

4. The method according to at least one of claims 1 to 3, in which only partial interferograms from the short coherence interferogram G (τ) are used for the dispersion measurement.

5. The method according to at least one of claims 1 to 4, in which the dispersion measurement is carried out by a short scan around a preselected location, in particular the virtual position of the dispersion measurement.

6. The method according to at least one of claims 1 to 5, in which the dispersion measurement is carried out by applying the short coherence interferometry to the eye.

7. The method according to claim 6, wherein the relative position of a reference mirror (14) to the eye (7) with the help of a forehead support (63) is fixed and by means of a concave mirror (30) is set.

8. The method according to at least one of claims 6 to 7, wherein the orientation of the eye (7) relative to the measuring beam (5) of an interferometer is carried out with the aid of a target beam (32).

9. The method according to at least one of claims 6 to 8, in which a modified Michelson interferometer is used as the interferometer.

10. The method according to at least one of claims 6 to 9, in which the movement of the reference mirror (14) is registered with the aid of a calibration interferometer.

11. Arrangement for measuring the thickness and dispersion of transparent and partially transparent tissues and body fluids, consisting of a short-coherence interferometer and one as an evaluation unit. serving. Computing unit for determining the content of substances that influence the optical properties.

12. The arrangement according to claim 11, in which tables for determining the content, in particular of glucose, are stored in the computing unit.

13. The arrangement according to at least one of claims 11 to 12, in which the short-coherence interferometer and the computing unit (60) serving as an evaluation unit are used for determination on the eye (7).

14. Arrangement according to claim 13, which has an additional control unit (25) and a photodetector (44) for performing short scans around a preselected location, in particular the virtual position of the dispersion measurement.

15. The arrangement according to at least one of claims 13 to 14, which has a forehead support (63) and a concave mirror (30) for the relative positioning and fixing of a reference mirror (14) to the eye (7).

16, Arrangement according to at least one of Claims 13 to 15, which is used to orient the eye (7) relative to the measuring beam (5) of an interferometer via a target device, consisting of a light source (33), collimation optics (34) and a deflecting mirror (35) , has.

17. The arrangement according to at least one of claims 13 to 16, in which a modified Michelson interferometer is used as the interferometer.

18. Arrangement according to at least one of claims 13 to 17, which has a calibration interferometer for registering the movement of the reference mirror (14).

19. Method for measuring the thickness and dispersion of transparent and partially transparent tissues and body fluids, by using spectral interferometry, in which the content of substances influencing the optical properties is determined from the results of the dispersion measurement.

20. The method according to claim 19, in which the content of the substances contained is determined using ^• stored tables.

21. The method according to at least one of claims 19 to 20, in which the glucose content is determined with the aid of stored tables from the results of the dispersion measurement.

22. The method according to at least one of claims 19 to 21, in which only a portion of the 1 / P-frequency spectrum of the spectral interferogram ms is used for the dispersion measurement.

23. The method according to at least one of claims W to 22, in which only a low-pass filtered part of the 1 / P spectrum of the spectral interferogram is used for the dispersion measurement.

24. The method according to at least one of claims 19 to 23, in which the dispersion measurement is carried out by applying spectral interferometry to the eye.

25. The method according to claim 24, wherein the relative position of the eye (7) with respect to a reference mirror (14) is fixed with the help of a forehead support (63) and adjusted by means of a concave mirror (30).

26. The method according to at least one of claims 24 to 25, wherein the orientation of the eye (7) relative to the measuring beam (5) of an interferometer is carried out with the aid of a target beam (32).

27. The method according to at least one of claims 24 to 26, in which a modified Michelson interferometer is used as the interferometer.

28. Arrangement for measuring the thickness and dispersion of transparent and partially transparent tissues and body fluids, consisting of a spectral interferometer, and a computing unit serving as an evaluation unit for determining the content of substances therein which influence the optical properties.

29. The arrangement as claimed in claim 28, in which tables for determining the content, in particular glucose, are stored in the computing unit.

30. Arrangement according to at least one of claims 28 to 29, in which only a low-pass filtered part of the 1 / P spectrum of the spectral interferogram ms is used for the dispersion measurement.

31. Arrangement according to at least one of claims 28 to 30, in which the spectral interferometer and the computing unit (61) serving as an evaluation unit are used for determination on the eye (7).

32. Arrangement according to claim 31, which has a forehead support (63) and a concave mirror (30) for the relative positioning and fixing of the eye (7) with respect to a reference mirror (14).

33. Arrangement according to at least one of claims 32 to 33, which for orienting the eye "(7) relative to the measuring beam (5) of an interferometer via a target device, consisting of a light source (33), collimation optics (34) and a deflection mirror (35 ).

34. Arrangement according to at least one of claims 32 to 34, in which a modified Michelson interferometer is used as the interferometer.

35. Arrangement according to at least one of ^' claims 32 to 35, which has a calibration interferometer for registering the movement of the reference mirror (14).