WO2005050149A2

WO2005050149A2 - Method and device for collecting spectrometric measuring signals

Info

Publication number: WO2005050149A2
Application number: PCT/EP2004/013135
Authority: WO
Inventors: Holger Jungmann; Michael Schietzel; Martin Schmidt
Original assignee: Mbr Gmbh
Priority date: 2003-11-18
Filing date: 2004-11-18
Publication date: 2005-06-02
Also published as: WO2005050149A3; DE10353703A1

Abstract

The invention relates to a method and device for collecting spectrometric measuring signals. The aim of said invention is to deliver solutions which make it possible to exactly collect spectrometric measuring signals in a low-cost matter. Said aim is attained by a spectrometric measuring device comprising an input splitting device for passing studied radiation, a Rowland grid device which is associated therewith and reflects incident radiation by spectral spreading, a recording device for recording the narrow part of the spectrum spread by said Rowland grid device and a guiding device which guides and displaces the recording device on a detection path whose spectral clearness is substentially contrast, whereby making it possible to obtain an accurate spectral distribution of studied light in an advantage manner. Said invention also makes it possible to form a recording device or to couple said device to an evaluation system in an operational manner in such a way that possible dependencies of the recorded intensity with respect to the wavelength of the light incident to the recording device are compensated by evaluation procedures. Compensating parameters can determined by gauging procedures and recorded in the internal memory of the device.

Description

Method and device for collecting spectrometric measurement signals

The invention relates to a method and a device for collecting spectrometric measurement signals.

In order to collect such measurement signals, it is known to direct the radiation of a sample to be examined with regard to its spectrum through a slit arrangement to a diffraction gate and thereby to bend it as a function of frequency. The diffraction gate can be designed as a Rowland grating. The spectrum fanned out by the Rowland grating can be recorded by a CCD arrangement and evaluated automatically. With regard to the use of CCD arrangements, there is the problem that a sufficiently high analysis accuracy can only be achieved with particularly calibrated and relatively expensive arrangements.

The object of the invention is to provide solutions by means of which a precise acquisition of spectrometric measurement signals is made possible in a cost-effective manner. This object is achieved according to the invention by a spectrometric measuring arrangement comprising: - an entrance slit device, to allow the passage of radiation to be examined - a Rowland grating device assigned to the entry slit device, for reflection of incident radiation with spectral fanning thereof; a detection device for detecting a narrow section of the spectrum fanned out by the Rowland grating device; and a guide device for guiding the detection device; - The guide device is designed such that it moves the detection device on a detection path of substantially constant spectral sharpness.

This advantageously makes it possible to precisely specify the spectral distribution of the light to be examined. It is possible to design the detection device, or to operatively couple it to an evaluation system in such a way that any dependencies of the detected intensity on the wavelength of the light incident on the detection device are compensated for by evaluation procedures. Compensation parameters can be determined by calibration procedures and stored in an internal storage device.

According to a particularly preferred embodiment of the invention, the detection device is designed as a photodiode. The photodiode can be provided with diaphragm or focusing optics, so that this is only acted upon by the light of a narrow spectral range. It is possible to provide several diodes and to evaluate the measurement signals obtained by them.

As an alternative to the measure mentioned above, it is also possible to design the detection device as a small, only over a partial area of the to form a spread-out spectrum spanning CCD detection device.

The guide device is preferably designed such that the detection path runs essentially concentrically to the center of a Rowland circle defined by the Rowland grating device, in particular on the Rowland circle. This makes it possible to evaluate the fanned out light particularly sharply.

The guide device preferably comprises a drive device by means of which the detection device can be moved mechanically through the examination area. This drive device can comprise an actuator which contains a motor, in particular an actuator or stepper motor. The motor can in particular be designed as a piezo drive, so that the required advancing and possibly retracting movement is brought about by deformation of a piezo crystal and a suitable transmission mechanism. It is also possible to implement the drive device by means of an electromagnet, for example in the manner of a watch balance magnet.

A particularly inexpensive embodiment of the invention is given in that the drive device comprises a bimetal or SMA structure (shape memory alloy structure). The bimetal or SMA structure can be designed as a clock spiral spring and selectively apply a pivoting moment to the guide device.

The guide device is preferably designed as a turntable or rotary arm. The turntable or swivel arm can be supported by a tip bearing in the manner of a clock unrest. Web guide structures and / or film hinge structures can also be used. The guide device is preferably equipped with position indicator means for determining the position of the detection device on its path in association with the detected measurement signals. These position indicator means can be designed as incremental rotary encoders, wherein the angle coding can be provided directly on the turntable or on a flank section of the rotary arm. As an alternative to this, or in combination with this measure, it is also possible to determine the position of the detection device via the control of the drive device.

It is possible to design the guide device in such a way that, at least temporarily, it allows the detection device to travel several times.

The measuring arrangement comprising the Rowland grating and the detection device is preferably designed to be gas-tight, the gap area is preferably covered with a window element which has an absorption spectrum which is permissible with regard to the examination-relevant light spectrum. It is possible to take the absorption spectrum of the upstream, translucent or light-guiding system into account in the evaluation, it is possible to fill the light-permeated space with a gas, with regard to its composition, in particular to flush it.

The device according to the invention preferably comprises a memory device for recording the acquired measurement signals. The storage device can be designed as a modularly connectable storage device, in particular as a flash stick. It is possible to provide a programmable evaluation circuit in the area of the measurement arrangement, so that the measurement data is recorded in a manner which is already internal to the device and carries a desired data format and a certain measurement deviation compensation. The measurement signals are preferably recorded as intensity specifications with assignment to their wavelength. The wavelength to be assigned to the currently measured intensity can be determined on the basis of the position of the detection device.

It is also possible to determine the wavelength to be assigned by pulsed irradiation of one or more reference spectra and evaluation of the intensity signal.

The object specified at the outset is also achieved by a method for collecting spectrometric measurement signals, in which the radiation to be examined is spectrally fanned via an entry slit device, in particular directed to a Rowland grating device and reflected by the latter with spectral fanning, with respect to the spectral distribution indicative spectrometric measurement signals are detected by guiding a detection device using a guide device through the fanned-out spectrum on a detection path of essentially constant spectral sharpness.

Preferably, the intensity signals are recorded while the detection device is being guided through the fanned-out spectrum and recorded with assignment to the respective wavelength.

The light to be examined is preferably generated by illuminating a sample through a light source device in order to emit the light to be examined as remission radiation.

The light source device can be designed as a diode device. The diode device can be operated in a pulsed manner. External light suppression can be carried out using the pulse pattern. The light source device is preferably designed such that its light has selected spectral properties. The method according to the invention can be used in particular for the detection of substances in vital tissue, in that light with a predetermined wavelength is directed onto the tissue in such a way that the light penetrates into the tissue, at least part of the light emerging from the tissue is detected, and the Intensity of the remitted light, or the optical density of the illuminated medium is determined in association with its wavelength and the intensity distribution of the remitted light or optical density determined in this way is compared with at least one reference system, with the presence and / or concentration being based on the comparison result a substance is closed.

This advantageously makes it possible to record various substances in vivo, non-invasively, and to tailor any medical auxiliary or therapeutic measures precisely to the physiological state of this person. In a particularly advantageous manner, it is also possible to detect substances in the person's circulation due to illness and to adjust medication based thereon. In a further advantageous manner, it becomes possible to record psychoactive substances, their breakdown products, illegal drugs and pharmaceuticals and also their metabolites.

According to a particularly preferred embodiment of the method, the references are selected, for example in the form of reference spectra specified in the manner of data sets, such that these - or correlations therewith, for example in the form of matches / deviations therefrom - are in each case indicative of a specific substance - or a group of substances.

As an alternative to this - or in a particularly advantageous manner also in combination with the measure mentioned above - it is also possible to use several reference systems, in particular a large number of data sets to provide stored reference spectra, depending on the fulfillment of predefined relationships with the reference systems, in particular reference spectra and the recorded spectral distribution, concluding on the presence and / or concentration of a substance.

A substance is advantageously identified on the basis of the intensity of selected wavelength ranges and the concentration of the recognized substance is inferred. According to a particularly preferred embodiment of the method according to the invention, these wavelength ranges are selected with a view to an expected classification result.

The spectrum of the light radiated onto the tissue preferably extends over a wavelength range from 200 to 800 nm. A wavelength window between 220 and 400 nm is particularly suitable for the detection of psychoactive substances.

It is possible to set the spectral width of the light emitted onto the tissue to a value that is smaller than the bandwidth of the analysis area, for example 60 nm. In particular, it is possible to use essentially monochrome, in particular coherent, light and to successively modulate its frequency over the analysis range, for example from 220 to 400 nm. When using monochrome light, it becomes possible to use band-shift effects, which are caused by the substance sought, in the detection of the same. It is possible to use white light with this procedure.

According to a particularly preferred embodiment of the invention, the comparison of the detected wavelength / intensity distribution takes place on the basis of a correlation analysis. Depending on the fulfillment of a correlation relationship, the presence and / or concentration of a substance or groups of substances can be concluded. Several reference bases are preferably provided for the identification of amphetamines, benzodiazepines, cannabinoids, methadone and ecgonines.

Furthermore, the reference bases preferably also include data sets for identifying heroin derivatives, cocaine, LSD, Nor-LSD, opiates, buprenorphine, gabapentin, carbamazepine, oxcarbazepine, antidepressants, neuroleptics, barbiturates and antibiotics.

According to a particularly preferred embodiment of the invention, the remission light is measured at body parts with different degrees of blood oxygenation. This makes it possible to determine the oxygen content of the blood and the hemoglobin content of the blood and to take influences of the degree of blood oxygenation into account when evaluating the signal.

In terms of device technology, the object specified at the outset is also achieved by a further embodiment of the above-mentioned measuring arrangement for a device for detecting substances in vital tissue, with a light source for generating light with a predetermined spectrum and irradiating the light onto the vital tissue in such a way that that the light penetrates into the tissue, a light detection device for detecting at least a portion of the light remitted from the tissue, a detection device for detecting the intensity of the remitted light with assignment to the wavelength and a comparison device for comparing the determined intensity distribution of the reflectance spectrum with at least one Reference data record, based on the comparison result on the presence and / or concentration of a substance or group of substances.

In a particularly advantageous manner, the device comprises an evaluation system which is designed such that it incorporates the algorithm, the evaluation procedure and / or the reference system measured data adaptively changed. The device is advantageously designed such that self-calibration takes place on the basis of the acquired measurement data. The device is advantageously designed such that a function check is carried out on the basis of the acquired measurement data. The device is advantageously designed in such a way that probability statements are made about the presence of possibly interchangeable substances. In a further advantageous manner, the device is designed in such a way that an automatic error analysis takes place with each measurement process. The device is advantageously designed such that an automatic error analysis takes place, which, for example, minimizes the probability of future possible measurement errors or incorrect substance identification.

Further details of the invention emerge from the following description in conjunction with the drawing. Show it:

1 shows a perspective sketch for explaining a variant of a measuring arrangement according to the invention for remission light spectroscopy realized as a pocket device;

Figure 2 is a schematic diagram to illustrate the concept of the movement of the detection device on the Rowlandkreis.

3 shows a schematic diagram for further explanation of a construction variant of the measuring arrangement according to the invention;

4 shows a spectrum which is characteristic of the intensity distribution of the light remitted from vital tissue in a wavelength range from 240 to 390 nm for amphetamines; 5 shows a spectrum characteristic of the intensity distribution of the light remitted from vital tissue in a wavelength range from 240 to 410 nm for benzodiazepines;

The measuring arrangement shown in FIG. 1 comprises a housing device 1 which is approximately the size of a highlighter. A sensor head 2 is attached to the housing device. In the center of the sensor head 2 there is a light guide 3 whose end face is flush with the end face of the sensor head 2. The light guide 3 is provided in the area of the sensor head 2 with an opaque sheathing. In the area of the sensor head 2, a light source device (not shown in more detail) is provided, through which light with a predetermined wavelength distribution according to a predetermined pulse pattern can be coupled into the translucent sensor head 2, and via this the upper skin layer of a living being to be examined.

The light guide leads to an entrance slit device 4, through which the remission light coupled into the light guide 3 can be dispersed. Downstream of that entrance slit device 4 there is a concavely curved Rowland grating 5. This Rowland grating 5 spectrally breaks down and deflects the incident light.

A bearing device 7 is provided concentrically with a Rowland circle 6 defined by the Rowland grid, on which a guide device 8 is pivotably mounted.

A photodiode 9 is provided on the guide device 8, which has a narrow slit window which is essentially perpendicular to the plane of the Rowland circle and faces the Rowland grating 5. The device is preferably designed such that the radius of the Rowland circle is in the range of 4.2 to 18 mm, preferably 6.4 mm. The photodiode 9 is coupled to a control device 10 via a flexible conductor track (not shown in any more detail) such that the intensity of the light entering the slit window can be detected via the control device 10 on the basis of the voltage generated via the photodiode 9.

The photodiode 9 is mounted on the guide device 8 in such a way that it is moved by the guide device on the Rowland circle, and as a result can detect the incident, spectrally decomposed light largely without overlap and with high selectivity.

For the movement of the guide device 8, a drive device 11, which is implemented here merely as an example of a spindle drive, is provided. The drive device 11 comprises a spindle 12 which is in engagement with a toothed circle segment 13 which is formed integrally with the guide device 8. The spindle 12 is driven by a stepper motor 14. The stepper motor 14 is controlled via the control device 10. The movement of the photodiode 9 or a light tapping structure is preferably carried out using a piezo motor, which causes the required drive movement by means of deformations which are brought about in a defined high frequency. These deformations can be transmitted, in particular, via a pushing and retracting finger to a structure carrying the tapping device. It is also possible to integrate the piezo drive directly into the tapping device, in particular a diode body.

The drive device 11 makes it possible to guide the photodiode over the entire area of the light broken down by the Rowland grating 5. Each angular position corresponds to a certain wavelength.

Via the control unit 10, the intensities measured continuously by the diode are stored while the spectrum is being scanned, with assignment to the wavelength or the angular position. Compensation procedures can be implemented in the control device 10, by means of which certain system properties of the measuring system can be compensated, possibly corrected.

The measured signals determined can be stored in a storage device which, for example in the manner of a flash stick, forms a sub-module of the device. The stored data can then be used as the basis for a more in-depth evaluation. It is also possible to carry out a signal evaluation in the device in the area of the device, in particular by corresponding configuration of the control device 10, and to determine certain evaluation results, e.g. display the detection of certain substances.

The light guide shown here, which terminates flat with the sensor head 2, can also be designed as a protruding light guide needle, which is preferably sheathed by steel tubes and protrudes beyond the sensor head. This makes it possible to absorb radiation invasively from deeper tissue layers. It is possible to design the needle device in such a way that a series of spectra can be obtained with different penetration depths. The different spectra obtained in this way make it possible, as in patent application DE 101 22 109, which relates to the applicant, to determine the concentration of certain substances. The evaluation can be carried out directly by an internal, appropriately configured computer device (10).

FIG. 2 shows a schematic diagram to illustrate the functional principle on which the measurement arrangement according to the invention is based. The incident light is directed onto the Rowland grating 5 via the entry slit 4 and is spectrally broken down by the latter. The intensity of the individual spectral components of the split light is measured by using only a partial area of the spectrum width, in particular only a slit section of the Spectrum-detecting detection device on a path of high measuring sharpness through which light is moved.

The preceding statements apply analogously to the sketch according to FIG. 3, in particular for the components provided with reference numerals therein. The measuring arrangement can be implemented in such a way that the diameter of the Rowland circle is approximately 18 mm. The mechanics provided for realizing the guide device can be implemented on a circuit board. The actuating movement can also be realized by a magnetic coil (e.g. rotating armature device) or a bimetal structure. The guide device is preferably balanced in such a way that external accelerations do not cause impermissible torques on the guide device. The guide device 8 is preferably mounted directly on a support structure supporting the Rowland grating, so that no inadmissible displacements can take place between these components apart from the relative movement required for guiding the photodiode 9 through the spectrum.

4 shows a light for different amphetamines with respect to the intensity distribution of the light remitted from vital tissue and detectable by the measuring device according to the invention.

Graph a shows the reflectance light spectrum for DL-MDA D5. The graph a has a characteristic local minimum at a wavelength of 256 nm. At wavelengths of 275nm, 250nm and 296nm, there are striking local maxima of the optical density of the detected remission light. The optical density of the reflected light is 0.6 for the wavelength of 256nm, 1.25 for the wavelength 274nm, 1.5 for the wavelength of 286nm and 1.7 for the wavelength of 298nm.

Graph b describes the reflectance light spectrum for D-amphetamine in a concentration of 500 ng / ml. The characteristic of the D-amphetamine Graph b has a local maximum at a wavelength of 260 nm. In comparison to the other amphetamines described, the D-amphetamine is reliably detectable even at the concentration of 500 ng / ml shown here in the wavelength window of 250 to 400 nm, to the extent that the spectrum characteristic of D-amphetamine differs significantly from that otherwise Typical spectra of amphetamines differs and has a maximum in particular at 260 nm.

Graph c shows a characteristic reflectance light spectrum for DL-MDMA in a concentration of 500 ng / ml. The graph c has a characteristic absolute maximum at a wavelength of 286nm. The graph c has no further local extreme values in the range from 260 to 310 nm. The graph c is characterized by a bell-like course which is essentially symmetrical to the absolute maximum at 286 nm. The absolute maximum of the DL-MDMA is in the range of a central nervous relevant concentration approximately in the range of the local maximum of the DL-MDA (graph a).

The graph d shows a characteristic curve of the optical density over the wavelength for DL-metamphetamine. A characteristic local minimum results at a wavelength of 257 nm and a characteristic absolute maximum at a wavelength of 261 nm. In the wavelength range of 265nm and at 269nm, there are characteristic maxima for the second derivative of the optical density after the wavelength.

The graph e shows a reflection light spectrum characteristic of DL-3.4-MDEA at a concentration of 500 ng / ml. The graph e is characterized by a local minimum at a wavelength in the range of 255 nm. At a wavelength in the range of 286nm, a local maximum results similar to DL-MDMA (500 ng / ml). Beyond a wavelength of 310 nm, the optical density of the remission light for DL-3,4-MDEA (500 ng / ml) is almost 0. Graph f describes the course of the reflectance light spectrum for D-metamphetamine (500ng / ml). At a wavelength of 254nm there is a local maximum. At a wavelength of 257nm there is a local minimum. At a wavelength of 260nm there is an absolute maximum. At wavelengths of 265nm and 269nm there are maxima with regard to the derivation of the optical density over the wavelength.

Graph g shows a reflectance light spectrum that is significant for a DL-amphetamine at a concentration of 500 ng / ml. Significant is a local minimum at a wavelength of 270nm, a minimum at a wavelength of 262nm and a maximum at a wavelength of 312nm.

5 shows the reflectance light spectrum for several psychoactive substances belonging to the group of benzodiazepines. Graph h describes the reflectance light spectrum for desmethyldiazepam in a concentration of 500 ng / ml. The spectrum in the range from 240 to 300 nm is particularly characteristic of this substance. This results in a local minimum at a wavelength of 254nm and an absolute maximum at a wavelength of 282nm. Beyond a wavelength of 294nm, this substance shows no spectral component.

The graph i describes the course of a course of the remission light spectrum which is characteristic of flunitrazepam (500ng / ml).

Graph j shows the course of the reflectance light spectrum for α-hydroxy-alprazolam.

The graph k shows the reflectance light spectrum for lorazepam in a concentration of 500 ng / ml. Graph I shows the course for oxazepam in a concentration of (500 ng / ml).

The graph m shows the course of the reflectance light spectrum for nitrazepam (500 ng / ml).

The graph n shows the course of the reflectance light spectrum in a wavelength range from 240 to 400 nm for nor-diazepam also in a concentration of 500 ng / ml.

With regard to the characteristics characteristic of the individual reflectance light spectra, reference is expressly made to FIG. 2. The psychoactive substances in vital tissue are preferably identified by the combined use of several correlation criteria.

The detectability and clear assignments of a spectrum to a substance or a group of substances result in particular when paired gradients of the weighted, non-linear derivatives, e.g. for the group of cocaine and ecgonine, the group of amphetamines and the group of cannabinoids. If this gradient formation shows that absorption maxima at specific wavelengths that are characteristic of this substance or group of substances can be detected for each substance or a chemically related group of substances, then these maxima are the result of identical substances or groups of substances.

The generation of a reflectance light spectrum according to the invention makes it possible to reliably detect psychoactive substances in extremely low substance concentrations. It is possible to clearly separate the individual spectra that overlap to form a total emission light spectrum. The evaluation results are available after the shortest evaluation time. The reflection light spectrum can advantageously be recorded in a non-invasive manner. This results in a inexpensive and particularly informative screening process for psychotropic drugs (neuroleptics, antidepressants, sedatives and hypnotics), antiepileptics and antibiotics and their metabolites.

The selection method according to the invention creates the possibility of proving the presence of illegal drugs and medicaments of the named pharmaceutical groups in the human organism without taking blood, hair analysis or urine tests. The investigations carried out in connection with the testing of the solution according to the invention show that the method according to the invention is suitable for routine detection of illegal substances in the blood. The analysis method, which can be carried out by means of a comparatively inexpensive hardware, is therefore suitable for routine checks in road traffic, for the detection of illegal drugs and other drugs and psychoactive substances that restrict the ability to drive.

Since both the substances themselves and their concentration can be determined in a reliable manner by the method according to the invention, a qualitative differentiation is also possible within substance groups. In particular, it is also possible to reliably detect metabolites of the psychoactive substances. In this regard, the method according to the invention is particularly suitable for the detection of cannabinoids, amphetamines and cocaine. In particular in a concentration relevant to a person's suitability for road traffic, the psychoactive substances can be routinely detected by illuminating the skin of the person to be examined. Other areas of application are the level control of antiepileptics, which are used in humans in a level-controlled manner. Drug monitoring-supported pharmacotherapeutic intervention options are supported in the field of antibiotic therapy and drug monitoring

Psychopharmacotherapy with neuroleptics and antidepressants. The resulting individual dosage options form as such Basis for an individually tailored drug therapy. Such a therapy can also be essential to the invention in itself. This eliminates the risks of overdosing and underdosing.

A particularly reliable evaluation of the reflection spectra recorded in vivo is preferably carried out by a central evaluation unit. With regard to the recorded

Reflective light spectrum indicative data records can be forwarded to a central computer, possibly via the Internet, via a mobile communication device. Using the central computer, extensive correlational algorithms can be processed in order to calculate the type and concentration of any impermissible substances in the human organism from the reflected light spectrum. It is also possible to take known matrix effects into account.

On the basis of the detection and quantification of the substance groups made possible by the method according to the invention, it becomes possible to assess the current physiological state of the person to be examined. It has been shown that the method according to the invention also makes it possible to reliably detect metabolites of the psychoactive substances transdermally in the capillary bed. The method according to the invention is based on the principle that light of different wavelengths penetrates the living tissue to different depths. In particular, longer-wave (low-energy) light penetrates deeper into the tissue than shorter-wave (higher-energy) light. This means that short-wave light reaches less substance at the same measuring point than long-wave light. A concentration gradient is obtained within the spectrum from short-wave to long-wave light. The measurement method according to the invention for determining the concentration of psychoactive substances, in particular chromophores in the tissue, advantageously uses this effect. If the same measuring point is now illuminated with light of different intensities, spectra are obtained which come from different depths. If these spectra are weighted accordingly and subtracted from one another, the concentration of certain substances is obtained as a function of the depth difference.

This means that every change in concentration includes a defined change in intensity over a defined wavelength, which is only within a certain wavelength range that is characteristic of the substance. Assuming that the optical properties of the tissue surrounding the material are constant, the associated light path can be determined directly from the intensity and distribution differences. A distribution difference thus advantageously corresponds to a specific concentration difference. The path can be determined according to the Lambert-Beer law from the difference in light intensity belonging to the concentration difference.

The assumption of constant optical properties of the tissue in the measurement volume was mainly assumed for the sake of simplicity. Appropriately differentiated algorithms can also take into account changes in the optical properties of the tissue surrounding the fabric, as is often the case in practice.

The method according to the invention makes it possible, in the stratum corneum, in the epidermis and down to the dermis, to determine substances qualitatively even with an inhomogeneous distribution in a measuring volume of about 10 μm thickness. This method is therefore suitable for making quantitative statements about the concentration of a substance in a defined depth of penetration. The depth resolution is preferably approximately 8 μm. This makes it possible to examine the skin in layers of 8 μm from the outside in, quantitatively and non-invasively by spectroscopy. According to the invention, the method according to the invention is carried out by a spectral photometer whose spectral resolution is 0.33 nm. This makes it possible to carry out 3 measurements per nm, so that each spectrum can be resolved and calculated at very small intervals. This makes it possible to distinguish substances with similar spectra from one another. This high resolution can advantageously be achieved by a CCD array with 2048 cells.

The generation of the light emitted onto the person to be examined is preferably carried out using a deuterium lamp and a halogen lamp, which provide sufficient light in the range from 200 to 800 nm. It has been shown that the in-vivo drug quantities in the tissue amount to approximately 0.05% of the total absorption. The intensity fluctuations of the emitted light from the lamp should therefore be considerably smaller than the absorption changes due to the drugs. The voltage and current stability of the lamp is preferably less than 6 x 10 ^"6 (pp) and the current and voltage drift is preferably less than 0.01% per hour.

In order to change the light intensity, an attenuation element can be used in an advantageous manner, which can continuously change the intensity of the incident light with the aid of a mechanically adjustable diaphragm. The light source is connected to the attenuator via an optical fiber cable using an SMA connector. An optical system can be used to project parallel light onto the output of the attenuator, which is also formed by an SMA connector. From here, the light reaches the object via a light guide. There is preferably an aperture between the two SMA plugs, which can be adjusted with a stepper motor. The aperture opening is preferably calculated in such a way that the light characteristic is not significantly influenced during the dimming. The stepper motor is preferably controlled by a computer, which also the optical recording unit is located. The motor is preferably designed such that it can carry out 10,000 steps per revolution. This enables a sufficiently fine-step change in the light intensity in order to achieve sufficient spatial resolution at different depths.

As an alternative to the measure described above, it is also possible to use LED spotlights to achieve defined changes in the light intensity without changing the emission properties of the emitted light. The above-described control of the diaphragm, achieved for example by means of a stepper motor, can be omitted here.

A sensor head was developed for carrying out the method according to the invention by measuring the incident light on human skin. This preferably has 19 light guides that bring the light onto the skin. 4 light guides collect the reflected light and guide it to the entrance slit area of the exhibition arrangement. The cone of light hits the Rowland grating and is spectrally broken down by it. A guide device guides a photodiode on the Rowland circle through the emitted, spectrally split light. While the photodiode is being guided, the measured light intensity is continuously stored, with assignment to the detection position of the diode or the wavelength calculated from it. By taking the characteristic diagram of the diode into account, it is possible to determine the spectral distribution on the Rowland circle with high sharpness using this measuring arrangement.

A further increase in the quality of the measured values can be achieved by using a light guide upstream of the entrance slit, which comprises an even larger number of light guides, for example 70 light guide wires, which enables an even more homogeneous illumination of the tissue. Illegal drugs, psychotropic drugs (neuroleptics, antidepressants, sedatives and hypnotics). Antiepileptics and antibiotics can be detected by the method according to the invention, since it has been shown that a large number of these substances, in particular in a wavelength range from 200 to 800 nm, clearly change the in vivo obtained Remission light spectrum caused. On the basis of pure spectra preferably generated with regard to the substances to be detected and taking into account their solution behavior, by taking into account the influence of the solvents on any shifts in the reflectance light spectra, by taking into account photo effects, spectroscopically relevant interactions between the respective substances, their absorption properties in different physiological media and their transcutaneous Measurement properties make it possible to further increase the meaningfulness of the analysis result.

Detection of methadone / polamidone

Methadone occurs in two stereo-enantiomeric forms. One molecular form - hereinafter referred to as D-methadone - turns polarized light to the right, the other - hereinafter referred to as L-polamidone - to the left. The analgesic and withdrawal compensatory form is predominantly the L form. Since in medical / therapeutic practice both a mixture of both and the L-polamidone occur as a pure form, it is important to be able to distinguish between the two methadones.

The method according to the invention can be carried out as follows:

To examine a person, a sensor head is placed on their skin surface, for example in the inner arm area, through which light in a

Wavelength range of 240 to 800nm is radiated into the skin.

This from a certain section of skin depth from the skin reflected light is detected by an optical fiber device and fed to a spectrometer according to the invention. The spectrum of the remission light collected via the light guide is recorded. The recorded spectrum is subjected to a mathematical evaluation procedure by a computer device. This mathematical evaluation procedure preferably takes into account certain ones

Correlation properties between spectra that are indicative of a large number of potentially relevant drugs and medications. Since the reflectance light spectrum recorded by the spectrometer device is both for the type of substance that has interacted with the light and for its concentration, it is possible to use the reference spectra for a large number of substances, the type and concentration of the substances to be detected from the remission - Calculate light spectrum.

Both the light source for generating the examination light and the sensor head for receiving the remission light, including the spectrometer, are preferably constructed as mobile handheld devices. For the evaluation of the recorded reflection light spectrum, it is possible to forward this to a central evaluation unit, for example via a mobile communication system. The evaluation of the reflected light spectrum transmitted in this way can then be evaluated on the basis of a comprehensive data set and by means of powerful hardware. The evaluation result obtained in this way can then be transmitted back, for example, as an SMS data record to the area of the detection device.

It is also possible to carry out detection and evaluation online on the examination device itself, for example in traffic, in medical practices or in inpatient treatment facilities in hospitals. In this case, the examiner receives the measurement results printed out directly via a connected printer device. Furthermore, oxygen determinations can be carried out intraoperatively online without the need for invasive blood gas analytical oxygen measurements.

In pediatrics, oxygen, hemoglobin and drug levels can be determined without the need for traumatic and technically cumbersome blood tests.

In emergency medicine, acute intoxication of drugs and medication can be diagnosed in a very short time and treated earlier than before.

Claims

Pate n ta nsp rue

1. Spectrometric measuring arrangement comprising: an entry slit device for permitting the passage of radiation to be examined; a Rowland grating device assigned to the entrance slit device, for reflection of incident radiation while spectrally fanning it out; a detection device for detecting a narrow section of the spectrum fanned out by the Rowland grating device; and a guide device for guiding the detection device through the fanned spectrum; - The guide device is designed such that it moves the detection device on a detection path of substantially constant spectral sharpness.

2. Measuring arrangement according to claim 1, characterized in that the detection device is designed as a photodiode.

3. Measuring arrangement according to claim 2, characterized in that the photodiode is provided with an aperture or focusing optics.

4. Measuring arrangement according to claim 1, characterized in that the detection device is designed as a CCD detection device.

5. Measuring arrangement according to at least one of claims 1 to 4, characterized in that the detection path is substantially concentric with

The center of a Rowland circle defined by the Rowland grating device runs.

6. Measuring arrangement according to claim 5, characterized in that the detection path runs on the Rowland circle.

7. Measuring arrangement according to at least one of claims 1 to 6, characterized in that the guide device comprises a drive device.

8. Measuring arrangement according to at least one of claims 1 to 7, characterized in that the drive device comprises an actuator.

9. Measuring arrangement according to at least one of claims 1 to 8, characterized in that the drive device comprises a motor, in particular a servo or stepper motor.

10. Measuring arrangement according to at least one of claims 1 to 9, characterized in that the drive device comprises an electromagnet.

11. Measuring arrangement according to at least one of claims 1 to 8, characterized in that the drive device is a bimetal or SMA structure

(shape memory alloy structure).

12. Measuring arrangement according to at least one of claims 1 to 11, characterized in that the guide device is designed as a turntable or rotating arm.

13. Measuring arrangement according to at least one of claims 1 to 12, characterized in that position indication means are provided for determining the position of the detection device on its path in association with the detected measurement signals.

14. Measuring arrangement according to at least one of claims 1 to 13, characterized in that the position indicator means are designed as incremental rotary encoders.

15. Measuring arrangement according to at least one of claims 1 to 14, characterized in that the guiding device is designed in such a way that it temporarily causes subsequent orbits.

16. Measuring arrangement according to at least one of claims 1 to 15, characterized in that the measuring arrangement comprising the Rowland grating and the detection device is encapsulated.

17. Measuring arrangement according to at least one of claims 1 to 16, characterized in that the device comprises a storage device for recording the detected measurement signals.

18. Measuring arrangement according to at least one of claims 1 to 17, characterized in that the measuring signals are recorded with assignment to their wavelength.

19. Measuring arrangement according to at least one of claims 1 to 18, characterized in that the wavelength to be assigned is determined via the position of the detection device.

20. Measuring arrangement according to at least one of claims 1 to 19, characterized in that the wavelength to be assigned is determined by pulsed irradiation of a reference spectrum and evaluation of the intensity signal.

21. Measuring arrangement according to at least one of claims 1 to 20, for detecting substances in vital tissue, with a light source for generating light of a defined wavelength and irradiating the light on the vital Tissue in such a way that the light penetrates the tissue, a light detection device for detecting at least a part of the light remitted / reflected from the tissue, one

Light intensity detection device for detecting the intensity of the remitted / reflected light in association with the wavelength, and a correlation determination device for determining

Correlation features of the determined intensity distribution of the remission spectrum with at least one reference system, the presence and / or concentration of a substance being inferred on the basis of the determined correlation features.

22. Measuring arrangement according to claim 21, characterized in that a light guide device is provided for guiding the light emitted by the light source onto the tissue.

23. Measuring arrangement according to claim 21 or 22, characterized in that a light guide device is provided for deriving the remitted light.

24. Measuring arrangement according to at least one of claims 21 to 23, characterized in that a device is provided for detecting the

Light from a given measuring depth.

25. Measuring arrangement according to at least one of claims 21 to 24, characterized in that a plurality of reflectance spectra are recorded for different, defined measuring depths.

26. Measuring arrangement according to at least one of claims 21 to claim 25, characterized in that a memory device is provided and that a reference system is stored in this memory device in the form of a reference data record.

27. Measuring arrangement according to claim 26, characterized in that the reference data set contains characteristic data with respect to the substance-specific spectra.

28. Measuring arrangement according to at least one of claims 21 to 27, characterized in that the correlation determination device provides several correlation criteria for analyzing the spectra.

29. A method for collecting spectrometric measurement signals, in which the radiation to be examined is directed via an entrance slit device and is radiated by the latter with spectral fanning, the spectrometric measurement signals, which are indicative of the spectral distribution, being recorded by using a detection device Guide device is guided on a detection path of essentially constant spectral sharpness through the fanned spectrum.

30. The method according to claim 29, characterized in that during the guidance of the detection device, intensity signals are detected by the fanned spectrum and recorded with assignment to a wavelength.

31. The method according to claim 30, characterized in that the measurement data are recorded by the detection device and assigned to a specific wavelength.

32. The method according to at least one of claims 29 to 31, characterized in that a light source device is provided for illuminating a sample for emitting the light to be examined as remission radiation.

33. The method according to at least one of claims 29 to 32, characterized in that the light source device is designed as a diode device.

34. The method according to at least one of claims 29 to 33, characterized in that the diode device is operated in a pulsed manner.

35. The method according to at least one of claims 29 to 34, characterized in that extraneous light suppression takes place on the basis of the pulse pattern.

36. A method for detecting substances in vital tissue, according to at least one of claims 29 to 35, in which light is directed onto the tissue with a predetermined wavelength such that the light penetrates into the tissue,

- At least part of the light emerging from the tissue is detected and the remitted light is determined by assigning its wavelength to the intensity, and

the properties of the remitted light determined in this way are compared with at least one reference system, the presence and / or concentration of a substance being inferred on the basis of a correlation with the reference system.

37. The method according to claim 36, characterized in that the reference system provides reference values, each of which is significant for a specific substance or group of substances, and compares an intensity distribution of the light over its wavelength with these reference values.

38. The method according to claim 36 or 37, characterized in that a plurality of reference spectra is predetermined, and that depending on the fulfillment of predetermined relationships between the plurality Reference spectra and the recorded intensity distribution to the presence and / or concentration of a substance or a group of substances.

39. The method according to at least one of claims 36 to 38, characterized in that selected based on the intensity

Wavelength ranges are concluded on the concentration of a recognized substance.

40. The method according to at least one of claims 36 to 39, characterized in that the excitation spectrum is in the range from 200 to 800 nm.

41. The method according to at least one of claims 36 to 40, characterized in that the frequency of the excitation light used for excitation lies outside the detected reflectance spectrum.

42. The method according to at least one of claims 36 to 41, characterized in that the comparison of the detected wavelength / intensity distribution is carried out on the basis of a correlation analysis.

43. The method according to at least one of claims 36 to 42, characterized in that the reference system provides reference data provided for the identification of psychoactive substances.