DE102005020911A1 - Polarized optical radiation`s polarization condition change measuring method, involves adjusting measured light polarization condition of light radiation based on value of polarization condition quantity - Google Patents

Abstract

The method involves radiating light rays of polarized optical light radiation with two different polarization conditions under different angle of incidence on the eye (1). Values of the polarization condition quantity is collected based on the angle of incidence of the light radiation or reflection angle of detection radiation. A measured light polarization condition of the light radiation is adjusted based on the collected values. An independent claim is also included for a device for measuring the change of polarization condition of polarized optical radiation through an optical active layer of a body.

Description

The The present invention relates to a method of measurement the change the polarization state of polarized optical radiation an optically active layer of a body, in particular the aqueous humor of the eye, and / or a concentration of an optically active substance in the optically active layer, in particular also the glucose content the aqueous humor of the eye, and a device for carrying out the Process.

method of the above kind can be general used for the investigation of optical properties of bodies become. Special meaning can be However, they have reasonable accuracy when examining them to be applied to the eye. The eye points to its front a structure with several layers on the cornea follows the with aqueous humor filled anterior chamber of the eye, which is followed by the eye lens, behind which the vitreous body sits. The aqueous humor contains optically active substances, so that an investigation the properties of the layer of aqueous humor passing through the anterior chamber may be of interest.

The regular blood glucose measurement represents for Diabetics are a significant burden, as they have always been with a painful blood sample, usually from a fingertip, connected is. In particular, Type I diabetics should at least daily five blood glucose measurements perform to to be able to adjust the insulin level exactly. Because of the painful However, the blood collection procedure will only take two to three on average Measurements carried out what creeping organic damage and results in a significantly reduced life expectancy.

Out There are big ones for that reason efforts a reliable one Non-invasive method for measuring blood sugar or glucose content in the body to find. A promising approach is based on the measurement the glucose content in the aqueous humor of the eye, as this representative for the Glucose content in the blood is. In addition to glucose, the aqueous humor contains other Fabrics, such as e.g. Lactate, albumin, ascorbic acid, amino acids, salts, and the like, which are diagnostic may be of interest.

Out DE 42 43 142 A1 a device for in vivo determination of an optical property of the aqueous humor in the anterior chamber of the eye is described with a light source for radiating light along a primary-side beam path in the anterior chamber, a detector for detecting light emerging from the anterior chamber along a secondary-side beam path and a signal processing unit for determining the optical characteristics based on the detection signal of the detector. In particular, it is proposed to determine the optical rotation of the polarization direction by glucose in the aqueous humor.

It However, it is to be expected that the there described method does not use one for the determination of blood sugar levels sufficient accuracy works as the optically complex construction of the eye is not exactly considered becomes.

Of the The invention is therefore based on the object of providing a method with the change a polarization state of polarized optical radiation, in particular a change the polarization direction of linearly polarized optical radiation, by an optically active layer of a body, in particular by the Anterior chamber or the aqueous humor of the eye, and / or a concentration an optically active substance in the layer, in particular also the Glucose concentration of the aqueous humor, measured reliably and non-invasively and to provide an apparatus for carrying out the method.

The object is achieved by a method for measuring the change of a polarization state of polarized optical radiation through an optically active layer of a body, which is arranged between the surface of the body and a reflective layer and contains an optically active substance, and / or the concentration of of optically active material in the optical active layer reproducing size, are irradiated at the illumination beams of polarized optical illumination radiation having at least two different predetermined polarization states at different predetermined angles of incidence on the body. Depending on the angles of incidence of the illumination beams or failure angles of detection beams emerging from the illumination beams after at least one pass through the optically active layer and reflection on the reflective layer as they exit the body, values of at least one polarization state quantity are detected which determine the state of polarization Detection beams, characterized at least with respect to the change of the polarization state by the optically active layer. A measurement illumination polarization state of the illumination radiation is set in dependence on the detected values of the at least one polarization state quantity and the predetermined polarization states, and a measurement of the change of the polarity tion state of the illumination radiation through the optically active layer or the concentration of the optically active substance reproducing size carried out.

The Task is still solved by a device for measuring the change of a polarization state polarized optical radiation through an optically active layer a body, the between the surface of the body and a reflective layer, and one optically contains active substance, and / or the concentration of the optically active substance in the optical active layer reproducing size, which is a lighting device to illuminate the body Illumination beams of polarized optical radiation, their state of polarization dependent on of control signals is adjustable, at different angles of incidence and a detection device, with the depending from the angles of incidence of the corresponding illumination beams or failure angles of the detection beams resulting from the illumination beams after at least easy passage through the optically active layer and Reflection on the reflective layer arise, values at least a polarization state quantity are detectable, the state of polarization of the detection beams, at least in terms of the change of the polarization state characterized by the optically active layer. The device has continue over one with the detection device and the illumination device connected control and evaluation device, which is designed to is, control signals for setting at least two different polarization states to the lighting device, for each of the set polarization states by means of the detection device, the values of the at least one polarization state variable in dependence from the entrance angles of the respective illumination beams and / or To detect the exit angles of the detection beams and in dependence from the recorded values the at least one polarization state quantity and the predetermined polarization states one Meßbeleuchtungspolarisationszustand to determine and appropriate control signals for setting the Measurement illumination polarization state to deliver the lighting device.

Of the Polarization state, for example, by specifying the ratio the polarization or field components in two predetermined, each other Orthogonal directions and their phase difference are described. Under the polarization state of the optical radiation is in particular the dependent of the phase difference The type of radiation is especially that of the phase difference dependent Type of polarization, i. e.g. linear or elliptical or circular Polarization, as well as the state with respect to the polarization components quantitative descriptive information, in the case of linear polarization for example, the polarization direction, understood. Is through the device used determines the type of polarization, suffice for the description the polarization state, the quantitative descriptive information.

The The method and the device are suitable for the investigation of a body, the at least the optically active layer and the reflective layer having. About that In addition, the body can still have further layers that have influence on the measurement. Especially it can affect the body act around the eye, the cornea as an optically active layer the filled with aqueous humor Anterior chamber and as a reflective layer covers the eye lens.

at the procedure becomes the body with optical illumination radiation of a predetermined polarization state irradiated, including in the device, the lighting device serves.

The Lighting device can this purpose a radiation source for unpolarized or arbitrary polarized optical radiation and one via control signals to set a desired Polarization state controllable device for setting a Polarization state. As a radiation source can For example, laser diodes, light emitting diodes or halogen lamps serve. The radiation source preferably emits optical radiation in the wavelength range between 300 nm and 3500 nm. To produce linearly polarized Illumination radiation of a predetermined polarization direction can the adjustment, for example, in the illumination beam path the radiation source according to the control signals, for example having a motor rotatable polarizer. This has the advantage that only an element in the beam path needs to be arranged. alternative can be a polarizer for linearly polarized radiation and this subordinate one by the control signals controllably provided polarization-rotating element be. As a controllable polarization-rotating element, for example a motorized rotatable λ / 2 plate according to the control signals, an element with liquid crystals in an adjustable by the control signals electric field for rotation of the polarization direction, or a Faraday rotator be used. The last two variants have the advantage that no motor driven elements need to be present. The Lighting device may further optics for focusing having the illumination radiation on the reflective layer.

The illumination radiation is radiated onto the body and penetrates, possibly to Pas Further layers, through the optically active layer, is reflected at the reflective layer and then exits after renewed passage of the optically active layer and optionally the other layers as detection radiation from the body. When the optical radiation passes through the optically active layer, the polarization state of the optical radiation is changed. For example, in the case of linearly polarized radiation, the polarization plane is rotated, the magnitude of the rotation being dependent on the path length of the optical radiation in the optically active layer and the concentration and type of optically active substances present in the optically active layer. Upon reflection, a further change in polarization state occurs, which generally depends on the angle of incidence of the optical radiation to the reflective layer and the reflective properties of the reflective layer or interface. This influence of the reflective layer on the polarization state of the illumination radiation can be greater than that of the optically active layer. The invention is based inter alia on the observation that inaccuracies or fluctuations in the adjustment of the angle of incidence of the illumination beams on the eye or the lens can affect the rotation of the polarization plane of linearly polarized optical radiation so strong that a determination of the rotation of the Polarization direction by the optical activity of the optically active layer and / or the concentration of the optically active substances in the layer with sufficient accuracy initially seems to be impossible if the angle of incidence is fixed.

To overcome of the problem use the method and the device among others the realization that the change the polarization state of the optical radiation by the reflection of the angle of incidence on the reflective layer depending on the polarization state different strong is. Depending on the state of polarization, this varies in dependence the change of the polarization state from the angle of incidence at the reflective Layer and thus also on the body will now be used for a the actual measurement cheap Meßbeleuchtungspolarisationszustand adjust.

To be first for at least two different polarization states under illumination beams different angles of incidence on the body or the reflective Layer blasted, from which then each corresponding detection beams arise, the angle of attack assigned under the angles of incidence out of the body escape. The angles of incidence are, as in the later measurement, greater than 0 ° and smaller as 90 °. Values of at least one polarization state quantity, the the polarization state of the detection beams at least in relation on the change the polarization state characterized by the optically active layer, dependent on from the failure angles and / or the angles of incidence for the two predetermined polarization states the illumination radiation determined.

among them, that the Polarization state quantity the polarization state the detection beams at least with respect to the change the polarization state characterized by the optically active layer, In particular, it is understood that using the polarization state quantity, the change the polarization state through the optically active layer, optionally using further, for example, the device used certain parameters, can be determined. As polarization state quantity can for example, assuming a linear polarization of the detection beams the polarization direction of the detection beams absolute or relative to that of the illumination rays or even the intensity of a Polarization component of the detection radiation in a given Direction can be used.

For this purpose, the detection device is used in the device, which may in particular have a one- or two-dimensional arrangement of detection elements for detecting the intensity of the detection radiation falling on them. In particular, CCD or CMOS cameras can be used. The arrangement is chosen so that the polarization state quantity can be detected as an angle. The detection device can furthermore have an optical system for focusing the detection beams onto the detection elements. Depending on the choice of the state of polarization state, the detection device can also have at least one analyzer which can be set in dependence on control signals in the polarization direction or at least one analyzer fixed in its polarization direction and optionally a controllably polarization-rotating element, for example a Faraday rotator, a λ / 2 plate which can be rotated by a motor or an element with liquid crystals in an electric field adjustable by the control signals, by means of which the detection radiation can be changed or filtered in a predetermined manner with respect to the polarization state. To detect the state of polarization, it is also possible to provide two detection elements or detection element arrangements, each of which is arranged downstream of one of two crossed analyzers, one of which is the aforementioned arrangement. In particular, the detection device can also be designed to carry out a zero measurement, in which at least one element which can be adjusted in an adjustable way to polarization state is set such that a predetermined polarization state is achieved, so that the radiation with the polarization state predetermines NEN analyzer does not happen and no intensity is determined. The adjustment of the element may then correspond to the determination of a value of the state of polarization state.

at another preferred embodiment forms the polarization direction of the analyzer with the plane of incidence in terms of the reflection at the reflective layer is an angle between about 40 ° and 50 °, preferably an angle of 45 °. This has the advantage that In This angle range reaches a particularly high sensitivity can be.

On the base of the detected Values or measured data can now be a for the measurement cheaper Meßbeleuchtungspolarisationszustand for the Illuminating radiation in front of the body be determined and set. By irradiation with illumination radiation this measurement illumination polarization state and analysis of the irradiation detected values of the state of polarization the detection radiation reproducing size, for example, under Using a model for the influence of Reflection on the reflective layer on the polarization state, the change the polarization state of the illumination radiation through the optical active layer or the concentration of the optically active substance determined reproducing size become.

Under Another purpose of this is in the device, the control and evaluation, for receiving signals, the values of the polarization state variable depending on of failure angles of the detection beams or angles of incidence of Illuminating rays on the body correspond, with the detection device and for transmission of control signals for setting a polarization state of Illumination radiation connected to the illumination device is. The control and evaluation device controls the illumination device also for setting the predetermined polarization states and Irradiation of the body with the illumination beams and the detection device for Acquire the values of the polarization state quantity.

The inventive method has the advantage that through Analysis of the angle dependence of the change of the polarization state, the polarization state or the polarization direction the incident on the reflective layer illumination radiation determined and starting from this or this using the knowledge of the predetermined polarization states of the desired Meßbeleuchtungspolarisationszustand can be adjusted. This can be non-invasive easy and with high accuracy the change of the state of polarization measured by the optically active layer become. The measurement illumination polarization state can be chosen in particular be that a high Accuracy is achieved.

The corresponding device is simply constructed in an advantageous manner and allowed by using only a few mechanically adjustable elements or even giving up mechanically adjustable elements a quick Measurement, especially in the examination of the eye in vivo, at the eye can move relative to the illumination radiation, a significant advantage.

in principle can for each the angle of incidence is successively irradiated with light rays on the body and corresponding values of the polarization state of the corresponding Detection beams in dependence be detected from the angle of incidence or angle reproducing size. However, it is preferable in the method that for each of the predetermined polarization states Illumination beam on the body is blasted, which includes the illumination beams, the hit the body under the various predetermined angles of incidence. In the device, it is preferable that the illumination device for Illumination of the body with a lighting beam for each the predetermined polarization states is formed, which is the Includes illumination beams, under the various predetermined angles of incidence on the body incident. This embodiment has the advantage that the Acquisition of polarization state magnitude values for different angles of incidence parallel, which significantly speeds up the process. For another in the lighting device corresponding illumination beam anyway result, for example, when using a focusing optics which is the illumination beam on the reflective layer focused.

In principle, the Meßbeleuchtungspolarisationszustand in any way, preferably to achieve a high accuracy can be selected. However, in the method, it is preferable that an excellent polarization state for the illumination radiation is determined for setting the measurement illumination polarization state based on the values of the polarization state quantity depending on the angles of incidence of the respective illumination beams and / or failure modes of the detection beams and the respective predetermined polarization states a dependence of the change of the polarization state of the illumination radiation by interaction with the body of the incident and / or exit angle is at least approximately minimal, and in which the Meßbeleuchtungspolarisationszustand is set in dependence on the excellent polarization state. At the Vorrich The control and evaluation device is designed to determine an excellent polarization state for the illumination radiation for determining the measurement illumination polarization state on the basis of the values of the polarization state variable as a function of the angles of incidence of the corresponding illumination beams and / or the failure angles of the detection beams and the respective predetermined polarization state for which a dependence of the change of the polarization state of the illumination radiation by interaction with the body on the incident and / or exit angle is at least approximately minimal, and by issuing corresponding control signals to set the Meßpolarisationszustand depending on the excellent polarization state. This approach makes it possible in particular, based on the excellent polarization state for the illumination radiation in front of the body, which is determined for a given angle of incidence, and the corresponding polarization state of the illumination radiation at the reflective layer, by appropriate choice of Meßbeleuchtungspolarisationszustands the polarization state at the reflective layer in the desired Set way.

Then it is particularly preferred in the method that as Messbeleuchtungspolarisationszustand the excellent polarization state is set. In the Device is the control and evaluation preferably for this purpose Control signals to the illumination device, so that as Meßbeleuchtungspolarisationszustand the excellent polarization state is set. These embodiment has the advantage that a exact adherence to the chosen Incidence angle of the illumination radiation on the body is not essential for the accuracy of determining the optical activity or the Concentration of the optically active substance is because the dependence is minimal. It was found, especially for the eye, that two such excellent polarization states, each serving as a measurement illumination polarization state can, can exist. In the case of illumination radiation, which results in the optically active layer at least approximately linearly polarized is, at the reflective layer at least approximately s-polarization. This polarization results in a particularly high signal-to-noise ratio. at the other excellent polarization state results Illumination radiation in the optically active layer at least approximately is linearly polarized, at the reflective layer at least approximately p-polarization.

alternative it is preferable in the method that the Meßbeleuchtungspolarisationszustand so is set that one expected influence of optically active layer on the rotation of the polarization direction linearly polarized radiation in the optically active layer at least approximately maximum is. In the device is preferably the control and Evaluation device for setting the Meßbeleuchtungs polarization state control signals to the lighting device, so that an expected influence of the optical active layer on the rotation of the polarization direction linear polarized radiation is at least approximately maximum. This In other words, a measurement illumination polarization state chosen in which the sensitivity of the measurement for the optical activity of the optical active layer is particularly high. This is of particular advantage if, as in the case of the eye, the influence of optical activity of the optical active layer is very small. The measurement illumination polarization state can be experimental or starting from a model for the influence of the body the polarization state of the illumination radiation assuming a typical area for the strenght the optical activity of the be determined optically active layer.

Should with high sensitivity only a small dependence on variations of the Incidence angles are reached, the Meßbeleuchtungspolarisationszustand preferably in the range between the Meßbeleuchtungspolarisationszustand for high sensitivity and the measurement illumination polarization state for minimal Angle of incidence dependence, the the measurement illumination polarization state for high Sensitivity next is, set.

The body may contain, in addition to the optically active substance in the optically active layer, at least one further substance or another layer penetrated by the radiation which influences the polarization state of the radiation. It is therefore preferable in the method that illuminating radiation of different predetermined wavelengths is used as illumination radiation, the values of the at least one polarization state quantity are detected as a function of the wavelength, and the change of the polarization state or the concentration of the optically active substance caused by the optically active layer is determined using the detected wavelength dependence of the values of the at least one polarization state quantity. In the apparatus, the illumination device for this purpose preferably a radiation source or multiple radiation sources for emitting illumination radiation at different predetermined wavelengths and the control and evaluation is adapted to detect the values of at least one polarization state variable depending on the wavelength and the optical active layer caused change of the polarization state or the Determine the concentration of the optically active substance using the detected wavelength dependence of the values of the at least one polarization state quantity. For this purpose, in particular data stored in the control and evaluation device can be used, which determines the wavelength dependence of optical properties of the optically active substance used in the determination and / or at least one other substance or another layer, which in the method a change of Polarization state causes be used. This embodiment has the advantage that the sensitivity of the measurement for the optically active substance can be increased since other influences can be separated by calculation. Preferably, wavelengths are used in areas where the optical activity or refractive index of the optically active material is strongly dependent on the wavelength.

The Lighting can be simultaneous with several of the different ones predetermined wavelengths carried out, including either corresponding wavelength-sensitive detection elements or one between the body and the detection elements arranged adjustable to predetermined wavelength ranges Filtering devices can be used. This allows a fast measurement. However, the device can be particularly simple be constructed when the illumination radiation in succession with different wavelengths he follows. In this case, the detection device needs the detection radiation not spectrally resolved to be able to detect. The lighting device can for this purpose several individually controllable Radiation sources for the have different predetermined wavelengths activated in succession become. However, it is also possible to use a broadband radiating radiation source and in the illumination beam path, for example motor, in succession to bring appropriate filters, which only the respectively desired wavelength let through. In particular, you can in the case of glucose as the optically active substance, different predetermined wavelengths in the Range from 300 nm to 3500 nm, preferably when measuring the glucose content for utilizing the dispersion or rotational dispersion of glucose in the ranges of 400 nm to 1100 nm or 2000 to 2500 nm become.

The change of the state of polarization by the body may depend on its temperature, for example about a corresponding change the density, depend. It is therefore preferred in the method that the temperature of the body detected and at the determination of the concentration of the optically active material used becomes. Preferably, the device has an associated with the control and evaluation device connected to temperature sensor, so is arranged that means the temperature sensor, the temperature of the body reproducing data are detected can. The control and evaluation can then in particular be trained, the detected Polarization state size values using the temperature data evaluate. You can do this in particular data is stored in the control and evaluation device be the influence of the Temperature on at least one parameter, which at the Evaluation of the values of the polarization state quantity is used. this has the advantage that a higher Accuracy in particular in determining the concentration of the optically active substance can be achieved. As a temperature sensor can preferably a non-contact working, in particular optical temperature sensor can be used. Particularly preferably, this has a temperature resolution better as 0.1 ° C.

Upon adjustment of the measurement illumination polarization state, measurement polarization state quantity values are detected that indicate the polarization state of detection rays resulting from the illumination rays after at least one pass through the optically active layer and reflection at the reflective layer in the body, at least with respect to the change in the state of polarization characterized optically active layer. It may be the same size used to determine the excellent state of polarization, or a different size, but satisfying the same criteria above. The values can be used in different ways. In the method, it is preferable that for measurement after adjustment of the measurement illumination polarization state by irradiating the body with at least one illumination beam, a value of at least one measurement polarization state quantity indicating the polarization state of detection rays emerging from the illumination rays after at least one pass through the optically active layer and reflection the reflective layer formed in the body, characterized at least in relation to the change in the polarization state by the optically active layer, detected and determined in dependence on the detected value data indicating the rotation of the polarization direction linearly polarized radiation through the optically active layer and / or a concentration of an optically active material in the optically active layer. In the apparatus, preferably, the control and evaluation means for measuring after setting the Meßbeleuchtungspolarisationszustands upon irradiation of the body with at least one illumination beam by means of the detection means a value of at least one Meßpolarisationszustandsgröße indicating the polarization state of detection beams from the illumination beams after at least one pass through the optical active layer and reflection at the reflecting layer in the body, at least with respect to the change of the state of polarization characterized by the optically active layer, and determined in dependence on the detected value data indicating the rotation of the direction of polarization of linearly polarized radiation through the optically active layer and or a concentration of an optically active substance in the optically active layer. In this way, the concentration of the optically active substance can be determined by its optical activity. If the optical path length in the optically active layer is not known, a calibration relationship stored, for example, in the form of a table in the control and evaluation device, which determines the concentration of the optically active substance as a function of the values of the measured polarization state variable or of the determined change in polarization state by the optically active layer, in particular a rotation of the polarization direction, can be used to determine the concentration. In the case of the eye, the calibration relationship is preferably determined person-specific and stored.

Additionally or alternatively, in the method, the values of a measurement polarization state quantity other than the the concentration of the optically active substance reflecting the size of the refractive index the optically active layer can be determined. For this purpose, the tax and evaluation device of the device preferably designed to from values of a measurement polarization state quantity containing the Polarization state of detection beams resulting from the illumination beams after at least easy passage through the optically active layer and Reflection on the reflective layer in the body arise at least in terms of the change the polarization state characterized by the optically active layer, as the concentration of the optically active substance Size the refractive index to determine the optically active layer. Again, by means of a known relationship between refractive index and concentration of the optically active substance and, where appropriate, other substances of the refractive index on the concentration of the substance closed become.

As already mentioned can the body in the beam path of the illumination beam another, in particular changing the polarization state of the illumination radiation, Have layer. In the case of the eye, such a layer is going through formed the cornea, which has birefringent properties. To accurately determine the change of the Polarization state through the optically active layer or the Concentration of the optically active material is preferred considered the birefringence of the birefringent layer. This can be done in different ways.

at a first preferred variant of the method is the influence of a penetrated by the illumination radiation birefringent layer of the body by a change the polarization state of the illumination radiation in front of the body and / or by a change the polarization state of the detection radiation compensated. Preferably the compensation is such that the illumination radiation in the optically active layer and / or the detection radiation at least approximately is linearly polarized. Before the compensation, the illumination radiation then be linearly polarized. For this purpose, in particular a Splitting linearly polarized illumination radiation in two the position of the birefringent layer and thus the optical axis or axes of the layer certain polarization components and a Phase shift between the components done. In the device includes the Lighting device for this purpose preferably a section to Generation of linearly polarized optical illumination radiation with desired Polarization direction and means for adjusting a desired Phase shift between two through a birefringent layer of the body predetermined polarization components of the linearly polarized illumination radiation. This has the advantage that a increased Accuracy in determining the optical activity of the optical active layer or the concentration of the optically active substance can be achieved in the layer. In particular, uncertainties, that can occur when using a model can be reduced. The predetermined polarization components through the birefringent layer or directions in particular parallel to the optical axes of the birefringent Layer and the phase shift determined by the birefringent layer through the phase difference between orderly and extraordinary Be given beam. The corresponding values can, preferably at the eye Person-specific, determined for example with the device when used as an ellipsometer, and in the control and evaluation are stored. As a facility for Setting a desired Phase shift, for example, a holder for a Phase shifter be provided in the one-person adapted phase shifter, For example, a birefringent phase shifter in the illumination beam path can be used. It can, however also controllable by control signals of the control and evaluation device phase-shifting devices, for example Kerr or Pockels cells, be used.

It is further preferred that the detection means comprise means for setting a desired phase shift between two through a birefringent layer of the body predetermined polarization components of the detection beams and a downstream in the detection beam means for detecting the polarization direction of the detection beams after the means for setting a desired phase shift. In this way, a disturbing influence of the birefringent layer on the illumination beam after the reflection at the reflecting layer can be compensated.

at The procedure can basically an arbitrary average angle of incidence for the illumination radiation be used, with larger mean Angle of incidence to stronger Lead and effects thus a higher one measurement accuracy can be achieved. Set all other settings of the procedure depending on the mean angle of incidence. Below the mean angle of incidence is in particular an angle between the largest and the smallest angle of incidence used in determining angle dependence, or when using a light beam, the angle of incidence of the center of gravity beam of the bundle, Understood. As a further, alternative or additional possibility for consideration The birefringence in the method may preferably be the angle of incidence the illumination radiation and / or the illumination on the body the measurement is chosen be that Influence of a irradiated by the illumination radiation birefringent layer of the body is at least approximately minimized to the detection beams. In the apparatus for this purpose, the illumination device is arranged so that the angle of incidence the illumination radiation and / or the illumination on the body the measurement is set so that the influence of a irradiated by the illumination radiation birefringent layer of the body is at least approximately minimized to the detection beams. This has the advantage that compensation or corrective action either are not necessary or only to a small extent carried out need to be. In particular, in the case of the eye as a body of the Illuminating beam path selected be that the Illumination radiation and / or the detection radiation through the Center or the center of the cornea runs. This has the advantage that in the middle of the cornea usually the birefringence the least spatial dependence having. Particularly preferably, the illumination radiation is relative aligned to the cornea so that a centroid of the along the beam formed by the illumination radiation one of the optical axis of the cornea is aligned or on the optical axis that lies along the optical axes, which is the Significantly influence the birefringence properties of the cornea, the birefringence is minimal.

Furthermore can take into account the Influence of a radiated by the illumination radiation birefringent Layer of the body to the detection beams in an evaluation of the detected values the polarization state quantity a the Birefringence descriptive model for the interaction of the illumination and detection radiation can be used with the layers of the body. Under The use of the model is also understood to mean that a provision for Determination of the change the polarization state through the optically active layer of the Values of the state of polarization of the detection radiation Size the birefringence descriptive parameters, for example corresponding refractive indices, contains. The control and evaluation device of the device is preferred for this purpose designed to be considered the influence of a radiated by the illumination radiation birefringent layer of the body to the detection beams in an evaluation of the detected values the polarization state quantity a the Birefringence descriptive model for the interaction of the illumination and to use detection radiation with the layers of the body. this has the advantage that a extensive correction for the birefringent effects are made and so the accuracy of the procedure increases can be. Corresponding parameters describing birefringence can in the control and evaluation device, in the case of the investigation of the eye to be person-specific, saved.

The Data used in the model can vary in different ways and in every measurement or, for example, for the eye a person, once in the sense of a calibration measurement are determined.

According to one first alternative is the change the polarization state at least two, preferably more measured at different predetermined wavelengths. Due to the different dispersion of optical activity and birefringence let yourself the birefringence and possibly also the path length of Outline illumination radiation in the layers.

at In a second alternative, measurements are made with measurement illumination polarization states that result in s- or p-polarization at the reflective layer. There in these cases the influence of Incident angle is minimal and that of the optically active layer constant is, can the birefringence descriptive parameters are determined.

In a third alternative, two orthogonally polarized beams are formed from the detection beams and after rotation into a common spatially superimposed on the same direction of polarization in order to measure, based on the interference which occurs, its phase relationship, which gives information about the birefringence.

When fourth alternative is the polarization ellipse of the detection beams be rotated in at least two different layers and in these layers are each measured to obtain information about the birefringence. The rotation can be done for example with a Faraday rotator.

When fifth Alternative may be a means of tracking when taking measurements on the eye eye movement, a so-called eye tracker, used to determine the birefringence. Because the corneal birefringence depending on location or angle of incidence is, this dependence becomes Measured with the eye tracker and for the mathematical correction of Birefringence or elimination of the effects of birefringence used.

Provided the birefringence is a characteristic angle dependence This can also be used as a recognition or normalization signal for the Detection device can be used.

Becomes the device used to examine the aqueous humor of the eye, the device preferably has a positioning aid for positioning of the eye relative to the device. In particular, as a positioning aid a device with a contact surface for the head or parts thereof serve, which is shaped so that the Head relative to the device one in at least two dimensions occupies a fixed position in which the eye in the illumination beam path lies. Preferably then the lighting device and the Detection device according to a predetermined angle of incidence the illumination radiation and the resulting exit angle the detection radiation aligned with their beam paths to each other. The beam paths can include an angle which is twice the angle of incidence.

The Eye or more accurately the cornea, however, can also with a fixed head posture to be moved. For more precise alignment between the illumination beam path and cornea features the device preferably over a fixing light source arranged so that when viewed from the Fixing light emitted fixing light with the eye the cornea one for the implementation the procedure favorable Situation takes.

By Although the fixation light can be viewed conscious Movements of the eye are largely suppressed, but not unconscious movements or micromovements (saccades). Preferably, therefore the device over a connected to the control and evaluation camera with a two-dimensional array of detection elements, by means of those pictures of the body, especially of the pupil and iris of the eye, are detectable, and the control and evaluation device is to be considered the motion of the body detected by images of the camera relative to the device in the determination by the optically active Shift caused change the polarization state or the concentration of the optical formed active substance reproducing size.

Preferably has the device over a optical coherence tomographs connected to the control and evaluation device and the control and evaluation device is adapted to the Adjust the distance of the device to the eye and / or the refractive index to determine the aqueous humor. This can be done in an advantageous manner increases the accuracy of the measurement become.

The Method and apparatus are particularly suitable for examination of the human or animal eye, being as an optically active substance the glucose content in the aqueous humor or, after conversion, that in the blood the person can be determined. In the same way can also the Content of lactate, proteins, amino acids or ascorbic acid in aqueous humor be determined. In the method it is particularly preferred that concentration of glucose, lactate, proteins, ascorbic acid and / or amino acids in the Aqueous humor of the eye of a human or an animal measured become.

The The invention will be explained in more detail below with reference to the drawings. It demonstrate:

1 a schematic representation of an apparatus according to a first preferred embodiment of the invention,

2 a simplified flow diagram of a method according to a first preferred embodiment of the invention,

3 a flowchart for a first method portion of the method in 2 .

4 a flowchart for a third method portion of the method in 2 .

5 a flowchart for a fifth method portion of the method in 2 .

6 a schematic partial representation of a device according to a third preferred embodiment of the invention,

7 a schematic partial representation of an apparatus according to a fourth preferred embodiment of the invention,

8th a schematic partial representation of an apparatus according to a fifth preferred embodiment of the invention,

9 a schematic partial representation of an apparatus according to a sixth preferred embodiment of the invention, and

10 a schematic partial representation of an apparatus according to a seventh preferred embodiment of the invention.

A schematic in 1 shown device for determining the glucose content in the aqueous humor of an eye 1 discloses an apparatus for measuring the change in a polarization state of polarized optical radiation through an optically active layer of a body containing an optically active agent and / or a variable representing the concentration of optically active agent in the optically active layer according to a preferred embodiment of the invention where the body is through the eye 1 is given, at which the eye lens 2 a reflective layer, the cornea 3 a birefringent layer and the filled with aqueous humor, between the eye lens 2 and the cornea 3 located anterior chamber 4 of the eye, an optically active layer which contains, among other things, glucose as the optically active substance.

The device comprises a lighting device illustrated by dashed lines 5 to illuminate the body or eye 1 with a lighting beam 6 , a detection device 7 for detecting one of the eye 1 reflected detection beam 8th that from the illumination beam 6 after passing through the cornea 3 and the anterior chamber or aqueous humor layer 4 , Reflection on the front of the eye lens 2 as well as renewed passage through the aqueous humor layer 4 and the cornea 3 arises, and a control and evaluation 9 that with the lighting device 5 and the detection device 7 connected via signal connections. The position of the eye 1 relative to the device is characterized by an in 1 not shown Positioning aid stabilized in the form of a chin rest and a curved contact surface for the forehead.

The lighting device 5 serves to generate the illumination beam 6 optical radiation with a by control signals of the control and evaluation 9 adjustable polarization state. It includes for this purpose a radiation source 10 for emitting a collimated, unpolarized illumination beam, in the example a halogen lamp with collimator, and a linear polarizer along the illumination beam path of the illumination beam 11 , a first and a second controllably polarization-rotating element 12 respectively. 13 each in the form of a Faraday rotator, a controllable phase shifting device 14 in the form of a Pockels cell and an optic 15 for focusing the illumination beam 6 on the front of the eye lens 2 ,

The one from the radiation source 10 emitted collimated illumination beam is linearly polarized with the linear polarizer, in the example a Glan-Thompson prism, in the example perpendicular to the plane of incidence. However, another direction is possible, preferably parallel to the plane of incidence of the illumination beam 6 , The first and second controllable polarization rotating elements 12 respectively. 13 rotate in dependence on the control and evaluation 9 supplied control signals, the polarization direction of the linearly polarized illumination radiation about an encoded by the control signals angle. The controllable polarization-rotating elements 12 and 13 are designed so that the rotation angle is quickly controlled. The first controllable polarization-rotating element 12 is the coarse adjustment of the polarization direction, the second controllable polarization-rotating element 13 designed for fine adjustment. More precise is the Faraday rotator 13 is designed for an angular range of a few degrees, eg ± 5 °, in which it can reproducibly rotate the polarization vector to 10 ^-4 °. The essential for the basic function of the device Faraday rotator 12 is designed for large angles of rotation of up to ± 180 °, so that the device can also be used as a complete ellipsometer. If the device is not operated as an ellipsometer, it does not change the polarization direction.

The controllable phase shifting device or pocket cell 14 allowed on corresponding control signals of the control and evaluation 9 towards a division of the illumination beam 6 into two orthogonal polarized components along directions given by the signals and a phase shift between these components.

By using the linear polarizer 11 , the polarization rotating elements 12 and 13 and the controllable phase shifting device 14 can the polarization state of the illumination beam 6 So be set arbitrarily.

The optics 15 focuses the illumination beam 6 on the front of the eye lens 2 , To illuminate beams at different predetermined angles of incidence on the eye 1 Being able to radiate is the optic 15 designed so that illumination rays over an incident angle spectrum θ ₁ to θ ₂ of a few degrees, in the example about ± 3 °, to the eye 1 where θ is the mean predetermined angle of incidence of the illumination beam 6 or the center of gravity beam. The width of the incident angle spectrum is chosen so that the angular dependence of the polarization rotation upon reflection at the eye lens 2 is detectable.

That under a failure angle θ '= θ out of the eye 1 emerging detection beam 8th First, an aperture happens 16 , which ensures that only the reflex from the front of the eye lens 2 enters the detection beam path, and then enters the detection device 7 ,

The detection device 7 comprises collimation optics along its detection beam path 17 that the detection beam after leaving the eye 1 again collimated, another controllable phase-shifting device 18 that is like controllable phase-shifting device 14 is formed, a third controllable polarization-rotating element 19 that acts like the controllable polarization-rotating element 13 is formed, an analyzer 20 , an imaging optics 21 and one for the UV-VIS-NIR range, in the example of 300 nm to 1100 nm, sensitive, connected to the control and evaluation line scan camera 22 comprising a one-dimensional array of detection elements for the detection radiation and by means of which the detection beam 8th angular resolution can be detected. The line scan camera 22 is realized in this example by a 2D CMOS camera whose pixels are electrically interconnected in one dimension, ie, binned.

The analyzer 20 in the detection beam path is set to be in the case that the Faraday rotators 12 . 13 and 19 do not turn the polarization direction, minimum intensity of the eye lens 10 reflected detection beam 8th passes.

The control and evaluation device 9 has - not shown in the figures - a memory device in which temporary and permanent data and instructions of a computer program are stored, and a processor, the illumination device on the instructions 5 , ie more precisely at least the controllable polarization-rotating elements 12 and 13 and the controllable phase shifting device 14 , and the detection device 7 , ie more precisely the controllable phase-shifting device 18 and the third controllable polarization rotating element 19 , as well as signals or data of the detection device 7 or the line camera 22 detects and controls the device so that the method described below is performed.

Around the eye 1 Keep in a quiet position and reproducible in the same place of the eye lens 2 To be able to measure, by means of a Fixierlichteinrichtung a usual for eye diagnostic devices Fixierlicht is irradiated. This is a Fixierlichtquelle 23 provided, the fixing light via a first beam splitter 24 , an optic 25 , which collimates the light, and a second beam splitter 26 is directed in the area in which the detection beam path and the illumination beam path intersect, ie, in the use of the device, the center of the cornea 3 , In an examination, the person to be examined directs the eye 1 on the fixation light and thus makes the eye essentially calm.

Furthermore, to align the device relative to the center of the cornea 3 or in the iris 28 formed pupil a pupil monitor provided, which is a light source 27 for the illumination of the iris 28 of the eye 1 , an imaging optics 29 , a spectral filter 30 as well as a camera 31 having a two-dimensional array of detection elements. Light of the light source 27 is through the first beam splitter 24 , the optics 25 and the second beam splitter 26 on the iris 28 directed. Light thrown back by the iris passes through the second beam splitter 26 and is through the imaging optics 29 after filtering through the spectral filter 30 to the camera 31 focused.

The pupil and the iris 28 are used to align the device with the camera 31 observed. The camera image is used to determine how the device is currently aligned relative to the center of the pupil. The user is informed if the alignment is within a suitable tolerance range. If not, the orientation of the device should be corrected by manual or motorized devices known to those skilled in the art.

In those described below and shown in the other figures Devices are for clarity half the Fixierlichteinrichtung and the pupil monitor not again described or shown, but available.

Since both the optical activity and the refractive index of the aqueous humor are sensitive to the temperature, in the device is a non-contact optical temperature sensor 32 with a resolution of better than 0.1 ° C provided with the control and evaluation 9 connected is. Temperature changes of the eye 1 can be considered mathematically become.

In the control and evaluation device 9 are stored data that reflect how the controllable phase shifting devices 14 and 18 adjust so that the effect of birefringence through the cornea 3 is compensated. By outputting appropriate control signals to the control and evaluation 9 become the controllable phase-shifting devices 14 and 18 adjusted so that illumination radiation upon passage of the device 14 and the cornea 3 or the cornea 3 and subsequently as detection radiation of the device 18 does not change its polarization state. The data required for this purpose can be determined, for example, in a person-specific calibration by using the device as an ellipsometer and then measuring the birefringence at constant optical activity.

The behind the controllable polarization rotating element 13 occurring linearly polarized illumination radiation is therefore also in the optically active layer 4 linearly polarized. Likewise, the detection beam 8th after the controllable phase shifting device 18 linearly polarized when the reflection on the eye lens 2 at most one rotation of the polarization direction of the illumination beam 6 causes.

For measuring the change in the polarization state of the illumination beam through the aqueous humor or the optically active layer 4 and for measuring the concentration of glucose in the aqueous humor or the optically active layer, the following procedure is performed, which is divided into five main sections (see FIG. 2 ) can be broken down. At the beginning of the process, the Faraday rotators are set to cause no rotation of the direction of polarization. The Faraday rotator 12 remains functionless even when the process is executed.

Because except for the Faraday rotator 13 all others the polarization state of the illumination beam 6 determining parameters and devices are fixed, the polarization state of the illumination beam 6 only by adjusting the polarization direction after the Faraday rotator 13 to be changed. The polarization state of the detection beam 8th is at least partially, but sufficient for the measurement, by the angle of rotation of the Faraday rotator 19 characterized in that the intensity of the detection beam 8th after the analyzer 19 is minimal.

First, will in section S10, an excellent polarization state of the illumination radiation or a corresponding setting determined for the Einfallswinkelabhängigkeit the change the polarization state through the eye or the polarization state the detection radiation is minimized.

Thereafter, a first Meßbeleuchtungspolarisationszustand the illumination radiation by driving the illumination device in section S12 5 and in particular the controllable polarization rotating device 13 set, which is very favorable for the performed in the following step measurement.

In the following section S14, the rotation of the polarization direction by the optically active layer 4 and the concentration of glucose in the aqueous humor is determined or measured.

Thereafter, in section S16, a second Meßbeleuchtungs polarization state of the illumination radiation by driving the illumination device 5 and in particular the controllable polarization rotating device 13 set which is very favorable for the measurement performed in the following step S18.

Finally done in section S18, a measurement of the refractive index of the aqueous humor and another refractive index based determination of Concentration of glucose in the aqueous humor.

In section S10, the following, in 3 illustrated steps performed.

The linear polarizer 11 is aligned so that the illumination beam is at least approximately orthogonal to the plane defined by the illumination and the detection beam.

In step S20, the control and evaluation device 9 if necessary, the Faraday rotator 13 first to an initial angle and thus the initial polarization state, in the example s-polarization with respect to the eye, a. It then controls the control and evaluation device 9 the Faraday rotator 13 so that the polarization direction is rotated by a small predetermined angle δ ₁ , so that a first predetermined polarization state of the illumination beam 6 is obtained. In the example, δ ₁ can be about 1 °. An entrance polarization direction of about 90 ° + δ ₁ is then present at the eye lens.

In step S22, a lighting beam having the set predetermined polarization state is applied to the eye 1 blasted and the intensity of the analyzer 19 transmitted portion of the detection beam 8th winkelab pending by means of the line scan camera 22 detected. The values are expressed as values of the polarization state variable in the control and evaluation device 9 stored angle-dependent.

In step S24, the control and evaluation device rotates 9 by appropriate control signals to the Faraday rotator 13 the polarization direction by an angle δ ₂ <-6 relative to the last set angle, in the example -2 °, so that a second predetermined polarization state of the illumination beam 6 is obtained. At the eye lens there is then an entrance polarization of about 89 °.

In step S26, as in step S22, an illumination beam having the second set predetermined polarization state is applied to the eye 1 blasted and the intensity of the analyzer 19 transmitted portion of the detection beam 8th angle dependent by means of the line scan camera 22 recorded and in the control and evaluation 9 stored angle-dependent.

In step S28, from the values detected in steps S22 and S26, the control and evaluation means becomes dependent on the angles and the corresponding predetermined polarization states 9 determined by interpolation, in which excellent polarization state of the illumination beam 6 ie at which angle of rotation of the Faraday rotator 13 , the lowest angle dependence of the intensity of the detection beam 8th after the analyzer 19 is achieved. The angle of rotation can then be saved.

The section S12 comprises in this embodiment, only the setting of the determined rotation angle on the Faraday rotator 13 since the excellent polarization state is used as the measurement illumination polarization state. At the front of the eye lens 2 the illumination radiation now has a maximum proportion of s-polarization, ie it is approximately s-polarized there.

If p-polarization is to be set instead of the s-polarization, only the initial polarization state needs to be changed accordingly. For this purpose, the linear polarizer 11 be rotated at the beginning of the process by 90 ° relative to the described embodiment. Alternatively, could also be the Faraday rotator 12 be used.

The steps of section S14 are in 4 shown in more detail.

In step S30 is from the control and evaluation 9 the polarization direction of the detection beam 8th after the birefringence through the cornea 3 compensating device 18 by driving the Faraday rotator 19 rotated by a small angle δ ₃ , which is chosen equal to the angle δ ₁ in this embodiment.

Thereafter, in step S32, by means of the line camera 22 the intensity of the detection beam 8th behind the analyzer 19 integrated and stored integrating over the angle.

In step S34, the control and evaluation device is analogous to step S24 9 the polarization direction of the detection beam 8th after the birefringence through the cornea 3 compensating device 18 by driving the Faraday rotator 19 rotated by a small angle δ ₄ in opposite direction to the rotation in step S28. The angle δ ₄ is chosen equal to the angle δ ₂ in this embodiment.

Thereafter, in step S36, by means of the line scan camera 22 the intensity of the detection beam 8th behind the analyzer 19 integrated and stored integrating over the angle.

From the detected intensity values, it is determined in step S38 by interpolation, at which angle of rotation of the Faraday rotator 19 the value of the measurement polarization state quantity is the intensity behind the analyzer 19 is minimal. This angle of rotation is then proportional to the optical activity of the aqueous humor, the proportionality factor being substantially different from the path length in the layer 4 depends.

In step S40, the temperature of the eye is detected by means of the temperature sensor 32 detected and finally determined in step S42, the glucose content. For this purpose, it can be assumed, for example, that other optically active substances in the aqueous humor have a constant concentration over the measurements, so that there is a correlation between the optical activity of the aqueous humor and the concentration of glucose from a calibration measurement.

The section S16 is first set to a second Meßbeleuchtungspolarisationszustand in which a particularly high sensitivity for the range of typically occurring refractive indices or glucose levels is expected. This Meßbeleuchtungspolarisationszustand, except for the polarization direction after the Faraday rotator 13 As given in the previous section of the method, either due to orientation measurement or to a model for the polarization-dependent propagation of the illumination beam lenbündels in the eye 1 be determined. The Meßpolarisationszustand depends in general on the selected angle of incidence. At an angle of incidence of 55 ° on the cornea 3 results in a rotation angle of about 15 ° with respect to the s-polarization at the front of the eye lens 2 , To adjust the angle, use is made of the fact that in the case that once known, such as the s or p polarization at the front of the eye lens 2 with the help of the Faraday rotators can be adjusted to 10 ^-4 °, with the help of the same rotators and any other setting of the polarization direction with the same accuracy is possible. This is provided by the control and evaluation device 9 by delivering appropriate control signals to the second Faraday rotator 13 the Meßbeleuchtungspolarisationszustand starting from the last existing Meßbeleuchtungspolarisationszustand.

The steps of the refractive index measurement section S18 in the layer 4 or the aqueous humor are schematically in 5 shown.

It be for the second Meßbeleuchtungspolarisationszustand executed again steps S28 to S36, wherein the rotations of the Polarization direction relative to the current second Meßbeleuchtungspolarisationszustand be executed.

From a characteristic curve for the dependence of the change in the polarization state, in particular the rotation of the polarization state, by the optically active layer 4 from the refractive index of this layer can this in step S44, preferably taking into account the temperature of the eye 1 be determined.

The steps mentioned are carried out as quickly as possible, preferably within 20 ms, in order to determine the influence of relative movements between the device and the eye 1 or eye lens 10 to keep minimal.

to Improvement of the measurement result can the measurements are repeated and the individual results are averaged.

With the device, the following variant of the method with appropriate programming of the control and evaluation 9 be carried out at the phase-shifting devices 14 and 18 automatically set to compensating values. So that the phase-shifting device 14 a compensation of corneal birefringence when entering the eye and the phase shifting device and 18 a compensation of the same corneal birefringence on exit from the eye 1 cause so that in the layer 4 and after the phase-shifting device 18 If only linearly polarized radiation is present, both phase-shifting devices are set in the same way. The rotation of the controllable polarization-rotating element 13 , the position of the axis of the phase shifting devices and the phase of the phase shifting devices are then determined so that the angular dependence of the intensity on the camera is minimal.

It is assumed that both the phase and the position of the slow axis of the phase-shifting devices 14 and 18 from the control and evaluation device 9 are separately adjustable.

To In the above-described method, before step S18, the Phase to an average value of corneal birefringence for humans set. Then, the steps of the section S10 are performed.

In successive iteration loops, the axes of the phase-shifting devices are now each rotated in small increments in each iteration loop, until the angular dependence of the intensity on the line scan camera 22 is minimal, and then the phase changed by a small amount.

The iteration is aborted when, according to a predetermined criterion, for example the relative accuracy of the values for the position of the axes and the phases, the absolute minimum for the angular dependence of the intensity on the line scan camera 22 is found. The found settings can then be saved as compensation data.

to Improvement can the section S10 and the determination of the compensation data alternately carried out iteratively be until a minimum for the angle dependence is reached.

Due to the measured compensation data, an individually adapted compensation plate can also be produced and instead of the controllable phase-shifting devices 14 and 18 be installed in a person-specific device. It is also possible to provide instead of a fixed mounting brackets that allow easy insertion of a person-specific compensation plate.

With the (optional) detection-side phase-shifting device 18 If necessary, the shape and position of the polarization ellipse can also be manipulated in order to increase the detection sensitivity.

A device according to a second preferred embodiment of the invention differs from that of the first embodiment in that it has no phase-shifting means, and the control and evaluation means the polarization-rotating influence of the cornea 3 after the step S26, so that the optimum rotation angle is changed from that determined in step S26. The data used to describe the birefringence can be obtained as described in the first embodiment.

A device according to a third preferred embodiment of the invention in 6 differs from the device of the first embodiment in that it provides a determination of the birefringence properties of the cornea 3 by the use of illumination radiation with different predetermined wavelengths and for this purpose a modified lighting, detection and control and evaluation 5 ' . 7 ' and 9 ' includes. Unchanged components are identified with the same reference numerals and the corresponding explanations to the first embodiment also apply here.

The radiation source 10 ' the lighting device 5 ' now includes four light emitting diodes, each of which control signals of the control and evaluation 9 ' towards emitting illumination radiation at a different predetermined wavelengths. In addition, the Faraday rotator is missing here 12 , All other components of the lighting device 5 ' are unchanged from the first embodiment.

The detection device 7 ' is opposite to the detection device 7 modified to replace the Faraday rotator 19 and the analyzer 20 one preferably at 45 ° with respect to the plane of incidence of the illumination beam 6 with its polarization direction tilted polarizing beam splitter 33 and one with the control and evaluation 9 ' connected detector 34 , for example, a photodiode or camera, to which the polarizing beam splitter 33 a proportion of the Detektionsstrah lenbündels corresponding to its polarization direction 8th directs. The other portion of the detection beam reaches the line scan camera 22 ,

The control and evaluation device 9 ' is designed to carry out the following method.

For each of the four wavelengths, a measurement is performed in which the phase-shifting devices are initially without function. In this case, similar to the above-described method of the first embodiment, a determination of an excellent polarization state and the adjustment of a Meßbeleuchtungspolarisationszustands with the same steps as in the first embodiment. However, now the polarization state after the second phase-shifting device 19 characterized by a direction of polarization, which differs from that with the line scan camera 22 and the detector 34 detected intensities of the orthogonal polarized portions of the detection radiation results. The other steps of the procedure remain unchanged.

Due to the different wavelength of the optical activity and the birefringence, the birefringence and possibly also the path length in the optically active layer can be determined 4 calculate using a suitable model. The wavelengths are chosen so that the determination of the birefringence and the path length can be done as safely as possible. The birefringence data can be person-specific in the control and evaluation device 9 ' be saved for later use. However, it is also possible to carry out the determination of the birefringence in each measurement of the glucose content.

If a camera is used instead of the photodiode, it can be determined from intensity profiles whether the entire detection device is relative to the birefringent cornea 3 has moved.

A device according to a fourth preferred embodiment of the invention in 7 differs from the device of the preceding embodiment in that it provides a determination of the birefringence properties of the cornea 3 by the use of illumination radiation with two different predetermined polarization directions and for this purpose a modified illumination device 5 '' and control and evaluation 9 '' includes. Unchanged components are identified by the same reference numerals and the corresponding explanations to the preceding embodiment apply here as well.

The illumination device now comprises instead of the radiation source 10 ' and the polarizer 11 two same with the control and evaluation 9 '' connected radiation sources 35 and 36 whose radiation is via a polarizing beam splitter 37 be coupled into the illumination beam path. It can thus optional illumination radiation with s and p polarization in front of the Faraday rotator 13 be generated.

The control and evaluation device 9 '' differs from the tax and evaluation direction 9 ' in that they now the two radiation source 35 and 36 can switch on and off in succession, wherein in each case the method described in the preceding embodiment, but only for one wavelength, is performed. The polarization is thus for two different polarization direction of the eye lens 2 , s- or p-polarization, measured. The measurements would be redundant if the cornea 3 would not exist. Therefore, information about the birefringence can be obtained from the measurements, which is a mathematical consideration of the birefringence in determining the through the layer 4 caused change in the polarization state, ie the rotation of the polarization state allows.

A device according to a fifth preferred embodiment of the invention in 8th differs from the device of the first embodiment by the design of the illumination device 5 ''' , the detection device 7 ''' and the control and evaluation device 9 ''' , Unchanged components are identified by the same reference numerals and the corresponding explanations to the preceding embodiment apply here as well.

The Device allows to obtain information about birefringence by measuring the polarization ellipse in two different layers becomes. The rotation takes place with a controllable polarization-rotating Element in the example a Faraday rotator.

The lighting device 5 ''' differs from the lighting device 5 only in that the Faraday rotator 12 is missing.

The detection device 7 ''' is similar to the detection device 7 built up. Instead of the analyzer 20 it has a preferably with its polarization direction by 45 ° with respect to the plane of incidence of the illumination beam 6 tilted polarizing beam splitter 33 ''' and one with the control and evaluation 9 ''' connected detector 34 ''' , for example, a photodiode or camera, to which the polarizing beam splitter 33 ''' one of its polarization direction corresponding proportion of the detection beam 8th directs. The other portion of the detection beam reaches the line scan camera 22 ,

The control and evaluation device 9 ''' differs from the control and evaluation device 9 through the interface for the detector 34 ''' and by their programming, which allows at least partially automatic implementation of the following procedure.

First, the eye lens 2 s polarization set in the same manner as in the first embodiment. The controllable polarization rotating device 19 , ie in the example of the Faraday rotator is placed in a state in which it does not rotate the polarization plane. Then, the intensity ratio of the orthogonal polarized detection radiation components to the line scan camera becomes 22 and the detector 33 ''' determined and saved.

Then the Faraday rotator 19 adjusted so that the transmitted intensity is maximum.

Then, the intensity ratio of the orthogonal polarized detection radiation components to the line scan camera becomes 22 and the detector 33 ''' determined and saved.

From the two intensity ratios can then be deduced how the polarization ellipse between the first and the second setting of the Faraday rotator 19 has changed.

A device according to a sixth preferred embodiment of the invention in 9 differs from the device of the previous embodiment by the formation of the detection device 7 '''' and the control and evaluation device 9 '''' , Unchanged components are identified by the same reference numerals and the corresponding explanations to the preceding embodiment apply here as well.

The device allows information about the birefringence to be obtained by reading from the detection beam 8th formed two orthogonal polarized portions, spatially superimposed and partially brought using a polarizing beam splitter to interfere. This gives information about the phase relationships of the two orthogonally polarized beams and thus the birefringence.

The detection device 7 '''' is similar to the detection device 7 ''' built up. Between the polarizing beam splitter 33 ''' and the optics 21 is another beam splitter 38 arranged, the polarized in a first direction portion of the detection beam 8th divided into approximately equal proportions, from one to the line scan camera 33 passes and the other via a beam splitter 39 to one with its polarization direction with respect to the Einfallsebe ne of the illumination beam 6 preferably by 45 ° tilted polarizing beam splitter 40 is steered.

Between the polarizing beam splitter 33 ''' and the detector 34 ''' shares a beam splitter 41 in the orthogonally polarized to the first direction portion of the detection beam 8th in two approximately equal parts, one of which is on the detector 34 ''' passes and the other on the beam splitter 41 deflected and spatially superimposed by this spatially with the polarized in the first direction portion. The polarizing beam splitter 42 filters out from both parts equally polarized components that interfere and one with the control and evaluation 9 '''' connected detector 44 be detected.

The control and evaluation device 9 '''' differs from the control and evaluation device 9 ''' through the interface for the detector 44 and by their programming, the determination of the phase between the interfering portions of the detection beam and thus the orthogonal polarized portions of the detection beam 6 allowed. A phase difference is because in determining the phase shifting devices 14 and 18 have no effect, due to birefringence and therefore allows a determination of birefringence descriptive data by means of a suitable model.

The birefringence of the cornea may depend more on the angle of incidence than the other polarization state changing influences of the optically active layer 4 with aqueous humor and the eye lens 2 , In order to largely avoid this, the following changes are proposed in a seventh embodiment compared to the first embodiment.

To minimize birefringence, it is therefore proposed to set the mean angle of incidence on the eye lens 10 to be chosen so that an optimized with respect to the birefringence angle of incidence is selected.

To Current knowledge provides a biaxial, birefringent Crystal the best model for corneal birefringence The two optical axes of the corneal birefringence are characterized from that the Phase shift for all input polarizations is zero when the propagation vector the wavefront of the illumination beam exactly on one of the optical Axes lies. According to G. J. van Blokland and 5. C. Verhelst, "Corneal polarization in the living human eye explained with a biaxial model ", 3rd Opt. Soc. Am. A, Vol. 4, No, 1, January 1987, p. 82-90 the angle between the corneal surface normals and the two optical axes ± 17.5 °.

To minimize birefringence, it is therefore proposed to set the mean angle of incidence on the eye lens 10 to be chosen so that the wavefront vector of the illumination beam within the cornea 3 lies on one of the optical axes. It should be noted that the wavefront vector within the cornea 3 does not exactly match the pointing vector. A particularly favorable angle of incidence on the eye lens 2 is in the vicinity of the Brewster angle, but not exactly at the Brewster angle of about 46.7 °.

Another condition is the illumination beam 6 in the middle of the eye lens 10 impinge, since the location dependence of the birefringence of the cornea 3 is lowest in the middle. Next, the plane of incidence should be horizontal, so that the entry and exit points of the illumination beam 6 at the cornea / air interface.

Regardless of the described choice of the incidence condition, a correction for the influence of incidence angle fluctuations on the birefringence of the cornea 3 performed, since even with the use of a fixing light fluctuations of the point of impact and angle of incidence on the cornea 3 can occur when the user repeatedly looks into the device. These fluctuations can lead to fluctuations of the birefringence and thus to measurement errors.

Therefore, the said fluctuations are measured simultaneously for the measurement of and used for correction. The measurement is done with a control and evaluation 9 ''''' a two-dimensionally resolving detector connected via a signal connection 43 on how in 10 shown by means of another imaging optics 44 that from the front of the cornea 3 reflected illumination beams 6 ' is focused. The Fixierlichteinrichtung, the means for monitoring the position of the pupil or iris and the temperature sensor are not shown in this figure for clarity again. For components that are unchanged compared to the first exemplary embodiment, the same reference numbers are used and the explanations regarding these apply correspondingly.

The detector 43 is mechanically rigidly connected to the other components of the device. Particularly suitable as a detector is a two-dimensional position-sensitive detector (PSD), since this is evaluated analogously and therefore allows an almost arbitrarily fine angular resolution. The angular resolution is limited only by the precision of the electronic circuitry. The PSD measures the center of gravity of the illumination beam reflected from the front of the cornea 6 ' which makes the measurement very robust. Alternatively, however, a digital camera, for example a CCD or CMOS camera, can also be used. The intensity center of gravity is then to be determined by computation, with the possibility of computationally eliminating disturbance light.

In the detection device 7 ''''' will be behind the analyzer 19 the detection beam 8th via a non-polarizing beam splitter 45 , preferably a dichroic, on the optics 21 and the line scan camera 22 for the UV-VIS-NIR range from 300 to 1100 nm and also one with the control and evaluation device 9 '''' connected another line camera 46 directed with imaging optics, not shown, which works in the IR range. With the help of these line scan cameras, the reflected radiation can be detected with angular resolution.

The control and evaluation device 9 ''''' differs from the control and evaluation device 9 through the interfaces for the detector 43 and the line scan camera 46 and by their programming allowing for at least a partial automatic performance of the subsequent calibration and use of the data obtained during the calibration.

With the help of the detector 43 For example, in a one-time calibration, a correction matrix for the optical activity measurements is generated as follows.

at known blood sugar content, for example, by blood analysis with the "gold standard" meter of the company Hemacue can be measured, the optical activity in the aqueous humor measured several times under the influence of Einfallswinkelfluktuationen. The incident angle fluctuations are z.T. involuntarily through the saccades, i. Micro motions caused by the eye. In addition, should For this one-time calibration process, the eye also repeatedly compared to the Device be realigned.

Since a single measurement should take about 10 ms, several hundred measured values can be generated within a short time. For each individual measurement, a value for the optical activity falsified by the non-ideal position or the movement of the eye relative to the device as well as an associated position on the detector now lie 43 in front. Since the glucose content in the aqueous humor is constant and known in all individual measurements, one obtains for each layer of the light reflected from the cornea front illumination beam 6 ' on the detector 43 ie, for each angle of incidence with respect to the cornea, a correction factor. In a correction matrix are now in the control and evaluation 9 ''''' the positions on the detector and the corresponding optical activities stored.

The Correction matrix created thereby is stored for each user, whereby the device without mechanical changes for several User is usable.

To The calibration can be done at any glucose concentration in the blood the optical activity in the Aqueous humor and thus also the blood sugar content with the help of the correction matrix be determined. This can happen when not occurring in the correction matrix listed Intermediate values one on the entries in the correction matrix based interpolation are performed.

Around different substances with spectrally different optical activity quantitatively in the aqueous humor (glucose, lactate, proteins, Amino acids, Ascorbic acid), becomes at several wavelengths be measured so that the Calibration for each of the wavelengths perform is.

Alternatively to the above-described layers of the plane of incidence of the illumination beam 6 the plane of incidence can be placed in the direction of the fast or slow axis of birefringence.

In another embodiment, a characteristic angular dependence of the birefringence of the cornea 3 as a recognition or normalization signal for the line detector 31 used to at least approximately eliminate their influence.

Basically, can take place said radiation sources in the embodiments also light-emitting diodes or laser diodes are used.

Further can all Faraday rotators also by other components with the same functionality e.g. rotating λ / 2 plates, rotating liquid crystals in an electric field, or the combination of polarizer or analyzer and Faraday rotator by a rotating linear polarizer be replaced.

Instead of the Pockels cells can as phase-shifting elements, for example also Babinet compensators, Soleil compensators or Kerr cells are used.

The slidable methods and apparatus can also be used for other bodies not parts of the human body are, in particular coating systems.

in the Trap of use for the eye is the device preferably as a tabletop device or especially preferably as a hand-held device educated. The handset in particular, a battery or a compartment for receiving at least a battery or a battery so that they have batteries or rechargeable batteries Electricity can be supplied.

Especially The device may also be in the form of another ophthalmic device a tabletop device be integrated.

Claims (24)

Method for measuring the change of a polarization state of polarized optical radiation through an optically active layer ( 4 ) of a body ( 1 ) between the surface of the body ( 1 ) and a reflective layer ( 2 ) and contains an optically active substance, and / or the concentration of the optically active substance in the optically active layer ( 4 ) in which - illumination beams of polarized optical illumination radiation having at least two different predetermined polarization states at different predetermined angles of incidence on the body ( 1 ) as a function of the angles of incidence of the illumination beams or angles of reflection of detection beams emerging from the illumination beams after at least one pass through the optically active layer ( 4 ) and reflection on the reflective layer ( 2 ) when exiting the body ( 1 ), values of at least one polarization state quantity are detected, which determine the polarization state of the detection beams, at least with respect to the change of the polarization state by the optically active layer (FIG. 4 ), and a measurement illumination polarization state of the illumination radiation is set as a function of the detected values of the at least one polarization state variable and the predetermined polarization states and a measurement of the change in the polarization state of the illumination radiation by the optically active layer ( 4 ) or the size representing the concentration of the optically active substance is carried out. Method according to Claim 1, in which, for each of the predetermined states of polarization, a beam of illumination is irradiated onto the body ( 1 ) which comprises the illuminating beams which, at the different predetermined angles of incidence, are applied to the body ( 1 ). A method according to claim 1 or 2, wherein an excellent polarization state for the illumination radiation is determined for setting the measurement illumination polarization state on the basis of the values of the polarization state quantity depending on the angles of incidence of the respective illumination beams and / or failure angles of the detection beams and the respective predetermined polarization states a dependence of the change of the polarization state of the illumination radiation by interaction with the body ( 1 ) is at least approximately minimized from the incident and / or exit angles, and wherein the measurement illumination polarization state is adjusted in accordance with the excellent polarization state. A method according to claim 3, wherein as the Meßbeleuchtungspolarisationszustand the excellent polarization state is set. A method according to claim 3, wherein the measurement illumination polarization state is adjusted so that an expected influence of the optically active layer ( 4 ) on the rotation of the polarization direction of linearly polarized radiation in the optically active layer ( 4 ) is at least approximately maximum. Method according to one of the preceding claims, in which illumination radiation of different predetermined wavelengths is used as illuminating radiation, the values of the at least one polarization state variable are detected as a function of the wavelength, and those transmitted through the optically active layer ( 4 ), or the quantity representing the concentration of the optically active substance is determined using the detected wavelength dependence of the values of the at least one polarization state variable. Method according to one of the preceding claims, in which the temperature of the body ( 1 ) and used in determining the size reflecting the concentration of the optically active material. Method according to one of the preceding claims, in which, after measurement of the measurement illumination polarization state by irradiation of the body ( 1 ) with at least one illumination beam a value of a Meßpolarisationszustandsgröße indicating the polarization state of detection beams emerging from the illumination beams after at least one pass through the optically active layer ( 4 ) and reflection at the reflecting layer ( 2 ) in the body ( 1 ) arise, at least in relation to the change of the polarization state by the optically active layer ( 4 ) are detected, and in dependence on the detected value, data are determined which the rotation of the polarization direction of linearly polarized radiation through the optically active layer (FIG. 4 ) and / or a concentration of an optically active substance in the optically active layer ( 4 ) play. A method according to any one of the preceding claims, wherein from the values of a measurement polarization state quantity representing the polarization state of detection beams emerging from the illumination beams after at least one pass through the optically active layer, 4 ) and reflection the reflective layer ( 2 ) in the body ( 1 ) arise, at least in relation to the change of the polarization state by the optically active layer ( 4 ) is characterized as the size of the refractive index of the optically active layer which reflects the concentration of the optically active substance ( 4 ) is determined. Method according to one of the preceding claims, in which the influence of a birefringent layer penetrated by the illumination radiation ( 3 ) of the body ( 1 ) by a change in the polarization state of the illumination radiation in front of the body ( 1 ) is compensated. Method according to one of the preceding claims, in which the angle of incidence of the illumination radiation and / or the illumination location on the body ( 1 ) is selected during the measurement such that the influence of a birefringent layer irradiated by the illumination radiation ( 3 ) of the body ( 1 ) is at least approximately minimized to the detection beams. Method according to one of the preceding claims, in which, in order to take account of the influence of a birefringent layer irradiated by the illumination radiation ( 3 ) of the body ( 1 ) on the detection beams in an evaluation of the detected values of the polarization state quantity a birefringence describing model for the interaction of the illumination and detection beams with the layers ( 2 . 3 . 4 ) of the body ( 1 ) is used. Device for measuring the change in polarization state of polarized optical radiation through an optically active layer ( 4 ) of a body ( 1 ) between the surface of the body ( 1 ) and a reflective layer ( 2 ) and contains an optically active substance, and / or the concentration of the optically active substance in the optically active layer ( 4 ) reproducing size with - a lighting device ( 5 ; 5 '; 5 ''; 5 ''' ) for illuminating the body ( 1 ) with illumination beams of polarized optical radiation whose polarization state is adjustable as a function of control signals, at different angles of incidence, - a detection device ( 7 ; 7 '; 7 '''; 7 ''''; 7 ''''' ), which depends on the angles of incidence of the corresponding illumination beams or failure angles of the detection beams emerging from the illumination beams after at least one pass through the optically active layer (FIG. 4 ) and reflection on the reflective layer ( 2 ), values of at least one polarization state quantity can be detected, which determine the polarization state of the detection beams, at least with respect to the change of the polarization state by the optically active layer (FIG. 4 ), and - one with the detection device ( 7 ; 7 '; 7 '''; 7 ''''; 7 ''''' ) and the illumination device ( 5 ; 5 '; 5 ''; 5 ''' ) control and evaluation device ( 9 ; 9 '; 9 ''; 9 ''' . 9 ''''; 9 ''''' ), which is adapted to control signals for setting at least two different polarization states to the illumination device ( 5 ; 5 '; 5 ''; 5 ''' ) for each of the set polarization states by means of the detection device ( 7 ; 7 '; 7 '''; 7 ''''; 7 ''''' ) to detect the values of the at least one polarization state quantity as a function of the entrance angles of the respective illumination beams and / or exit angles of the detection beams and to determine a measurement illumination polarization state and corresponding control signals for adjustment of the measurement illumination polarization state depending on the detected values of the at least one polarization state quantity and the predetermined polarization states to the lighting device ( 5 ; 5 '; 5 ''; 5 ''' ). Device according to Claim 13, in which the illumination device ( 5 ; 5 '; 5 ''; 5 ''' ) for illuminating the body ( 1 ) is formed with an illumination beam for each of the predetermined states of polarization comprising the illumination beams incident on the body at the various predetermined angles of incidence ( 1 ). Apparatus according to claim 13 or 14, wherein the control and evaluation device ( 9 ; 9 '; 9 ''; 9 ''' . 9 ''''; 9 ''''' ) is adapted to determine an excellent polarization state for the illumination radiation for determining the measurement illumination polarization state on the basis of the values of the polarization state variable as a function of the angles of incidence of the corresponding illumination beams and / or the angles of failure of the detection beams and the respective predetermined polarization state Change of the polarization state of the illumination radiation by interaction with the body ( 1 ) is at least approximately minimized from the angle of incidence and / or exit, and by issuing corresponding control signals to set the measuring polarization state as a function of the excellent polarization state. Device according to Claim 15, in which the control and evaluation device ( 9 ; 9 '; 9 ''; 9 ''' 9 ''''; 9 ''''' ) Control signals to the illumination device ( 5 ; 5 '; 5 ''; 5 ''' ), so that the excellent polarization state is set as the measurement illumination polarization state. Device according to Claim 15, in which the control and evaluation device ( 9 ; 9 '; 9 ''; 9 ''' . 9 ''''; 9 ''''' ) for setting the measurement illumination polarization state, control signals to the illumination direction ( 5 ; 5 '; 5 ''; 5 ''' ), so that an expected influence of the optically active layer ( 4 ) is at least approximately maximum on the rotation of the polarization direction of linearly polarized radiation. Device according to one of Claims 13 to 17, in which the illumination device ( 5 ; 5 '; 5 ''; 5 ''' ) one radiation source or several radiation sources ( 35 . 36 ) for emitting illumination radiation at different predetermined wavelengths and the control and evaluation device ( 9 ; 9 '; 9 ''; 9 ''' . 9 ''''; 9 ''''' ) is adapted to detect the values of the at least one polarization state variable as a function of the wavelength, and those through the optically active layer ( 4 ), or the magnitude representing the concentration of the optically active substance, using the detected wavelength dependence of the values of the at least one polarization state quantity. Device according to one of claims 13 to 18, one with the control and evaluation device ( 9 ; 9 '; 9 ''; 9 ''' . 9 ''''; 9 ''''' ) connected temperature sensor ( 32 ), which is arranged so that by means of the temperature sensor, the temperature of the body ( 1 ) reproducing data can be detected. Device according to one of claims 13 to 19, in which the control and evaluation device ( 9 ; 9 '; 9 ''; 9 ''' . 9 ''''; 9 ''''' ) for measurement after adjustment of Meßpolarisationszustand in irradiation of the body ( 1 ) with at least one illumination beam by means of the detection device ( 7 ; 7 '; 7 '''; 7 ''''; 7 ''''' ) a value of a Meßpolarisationszustandsgröße indicating the polarization state of detection beams, which from the illumination beams after at least one pass through the optically active layer ( 4 ) and reflection on the reflective layer ( 2 ) in the body ( 1 ) arise, at least in relation to the change of the polarization state by the optically active layer ( 4 ), and, depending on the detected value, obtains data indicating the rotation of the direction of polarization of linearly polarized radiation through the optically active layer (12). 4 ) and / or a concentration of an optically active substance in the optically active layer ( 4 ) play. Device according to one of Claims 13 to 20, in which the control and evaluation device ( 9 ; 9 '; 9 ''; 9 ''' . 9 ''''; 9 ''''' ) is adapted, from the throwing of a Meßpolarisationszustandsgröße, the polarization state of detection beams emerging from the illumination beams after at least one pass through the optically active layer ( 4 ) and reflection on the reflective layer ( 2 ) in the body ( 1 ) arise, at least in relation to the change of the polarization state by the optically active layer ( 4 ), as the quantity representing the concentration of the optically active substance, the refractive index of the optically active layer ( 4 ) to investigate. Device according to one of Claims 13 to 21, in which the illumination device ( 5 ; 5 '; 5 ''; 5 ''' ) a section ( 10 . 11 . 12 . 13 ) for producing linearly polarized optical illumination radiation with the desired polarization direction and a device ( 14 ) for setting a desired phase shift between two through a birefringent layer ( 3 ) of the body ( 1 ) predetermined polarization components of the linearly polarized illumination radiation. Device according to one of Claims 13 to 22, in which the detection device ( 7 ; 7 '; 7 '''; 7 ''''; 7 ''''' ) An institution ( 18 ) for setting a desired phase shift between two through a birefringent layer ( 3 ) of the body ( 1 ) predetermined polarization components of the detection beams and a downstream in the detection beam means for detecting the polarization direction of the detection beams after the means for setting a desired phase shift. Device according to one of Claims 13 to 23, in which the control and evaluation device ( 9 ; 9 '; 9 ''; 9 ''' . 9 ''''; 9 ''''' ) is designed to take account of the influence of a birefringent layer irradiated by the illumination radiation ( 3 ) of the body ( 1 in the case of an evaluation of the detected values of the polarization state variable, a birefringence-describing model for the interaction of the illumination and detection radiation with the layers (FIG. 2 . 3 . 4 ) of the body ( 1 ) to use.