A METHOD AND A SYSTEM FOR DETERMINATION OF THE COMPOSITION OF A SUBSTANCE AND AN AMBULATORY REGISTRATION SYSTEM

Abstract: A method to determine the presence of one or several components in a e.g. liquid substance (2) by means of spectroscopy including an illumination of the substance by means of light with at least one definite wavelength, preferably within the almost infrared wavelength area, and detecting transmitted and/or reflected light as well as an analysis of the detected light characteristics. The method is characterized in that said detection is performed extremely fast, preferably so, that a step response corresponding to an approaching or fading light pulse might be detected, the step response including information on said light pulse passing wavelength by means of a measuring device (2, 4, 5).

Description: A method and a system for determination of the composition of a substance and an ambulatory registration system. The present invention relates to a method to determine the presence of one or several components in a e.g. liquid substance by means of spectroscopy including an illumination of the substance with light of at least one wave length and detecting transmitted and/or reflected light as well as analyzing the reflected light characteristics. The invention also relates to a system for performing the method and an ambulatory registration system. Methods and systems of essentially said type for measuring e.g. the blood sugar content are already known in the art. The known systems use in many cases optical measurements, in which a blood carrying body portion, such as a finger tip, arc illuminated with light of several different wave lengths , the transmitted or reflected light then being analyzed by means of differential spectroscopy to distinguish between various components and to define the amount of interesting such ones. In measurements of this known type the measuring accuracy will in many cases be not fully satisfactory and not comparable with analytic measurements. The present invention relates to a method and a system offering an increased accuracy during measurements basing on differential spectroscopy in general and especially for noninvasive, to blood compositions related measurements. Thus, the invention relates to a method according to the first part of the attached claim 1. The method is especially characterized in what is specified in the characterizing part of said claim. Moreover, the invention relates to a system according to the first part of the attached claim 10. The system is especially characterized in what is specified in the characterizing part of said last mentioned claim. The invention also relates to an ambulatory registration system according to the first part of the attached claim 15. The system is especially characterized by what is stated in the cha¬ racterizing part of claim 15. The invention is described here below in connection with an execution example and the attached drawing, on which Figure 1 shows a scheme in principal of a first embodiment of a system according to the invention, Figure 2 shows schematically and in more detail a system according to figure 1 during a measurement of a finger tip, Figure 3 shows schematically i.a. a step response for a system according to figure 1, Figure 4 shows schematically the light absorption for various wave lengths, Figure 5 shows schematically the rotation of a plane polarized beam of rays and a de¬ tection, and Figure 6 shows schematically an ambulatory registration system according to the in¬ vention. In figure 1 item 1 designates devices to illuminate a substance 2 arranged with a within a vessel 3 comprized liquid 4, and as an alternative a finger tip 5 with light of at least one well defined wave length, but preferably a multiple of well defined wave lengths, at least some wave lengths preferably lying within the almost infrared area. Item 6 designates devices for detecting transmitted and/or reflected light, to varying extent passing through the substance and thereby being effected by means of absorption in the substance, the absorption being re¬ lated to wave length and substance. Item 7 designates devices for analyzing detected light in relation to light approaching the substance by means of a method of spectroscopy, generally called differential spectroscopy, where several wave lengths are used. This kind of technology is already known in the art and is i.a. described in US-A-5,222,495. According to the present invention devices are provided for determing completing characteristics besides the mere absorption determination. According to a first embodiment the detecting devices are adapted to define extremely fast processes, i.e. to detect during extremely short time periods, so that a detailed step res¬ ponse corresponding to an approaching light pulse might be determined in the way as it is principally shown in figure 3, the detected intensity there being illustrated as a function of the time t. The correlation between intensity and time thereby comprizes a step response S' and a steady portion S" corresponding to a continuous illumination. The step response portion shows in its left part, the in time first part, the intensity for light having passed by the shortest way through the substance 2, whereas in time later parts of both the step response portion and the steady portion correspond to light having passed the substance by differently long ways. The portion S' corresponds to known measurements, the intensity level of this portion correspon¬ ding to a point in the absorption/wave length-diagram, figure 4, of a known type. The step response portion S' is during its course in many cases both depending of the substance and the wave length and is according to the invention adapted to be used as a completing information BAD ORIGINAL * for distinguishing various components of the substance and for a quantity determination of the presence of a certain component, the analysis of detected light being achieved in relation to previous step responses being fixd under well defined conditions. For various points of corre¬ lation as depicted in figure 4 also a characterizing step response might be defined and used to analyze detected light. According to a second embodiment the plan-polarized light 8, figure 5, is used to il¬ luminate the substance, devices 1 being adapted to generate plan-polarized light and the fact being used, that certain components, such as glucose in the blood, are turning the plan- polarized light as scheamtically illustrated in figure 5. Detecting devices 9 are provided for detecting the light thus turned, the amount of said turning being related to both substance and wave length, which are used for an analysis for distinguishing various components in the substance and a quantity definition of the presence of a certain component with the described turning capacity. Also embodiments might be envisaged as combinations of said first and said second embodiment. According to emboidments preferred in certain cases embodiments (not shown) are provided to supply a varying and/or steady electrical and/or magnetic field across the sub¬ stance, the dipole moment of certain component molecules being influenced, the detected light characteristics thus being influenced and said influence being used to distinguish various components and for quantity analysis of the presence of certain components. As for embodiments for plan-polarized light devices 1 are provided for generating plan- polarized light with at least one wave length and to combine this with a light with at least one reference wave length and with a light with at least one measuring wave length. During said analysis the angle distortion of the plan-polarized light is adapted to be related to the charac¬ teristics of a transmitted and/or reflected light by means of a reference and a measuring wave length. The invention can be applied to determine and measure all kind of solid, liquid and gaseous substances. According to a preferred application the invention is adapted to be used for mainly a noninvasive determination of the blood glucose contents in human beings, such as individuals with diabetes. The invention combined with an ambulatory registration of the blood sugar contents, figure 6, is here a new and extraordinarily suitable method and system compared with already known ones. Item 10 designates a digital registration unit adapted for an ambu- BAD ORIGINAL latory use connected to a blood-sugar-sensor adapted to be placed onto an individual. The connection 11 can be electrical and/or fibreoptical or be wireless, e.g. telemetric or infrared based. Said sensors are also preferably optical as above mentioned and preferably noninvasive. The unit 10 is thus further combined with illumination elements 12 and detecting ele¬ ments 13, at least one of these elements possibly being included in the unit. Both kind of elements might also be external. According to an embodiment the unit has an alarm function 14 to be triggered of the defined glucose content, an alarm then being triggered, when the content passes over a previously defined level and/or when the content passes below a pre¬ viously defined level. It is preferred that the unit comprises a rcgistrating capacity of at least 8 hours and is equipped with symptom and event controls 15 so that the registration might be supplemented with data on events, such as intake of food and medicin, and symptoms. Moreover, the unit is preferably and simultaneously adapted for a registration of one or several parameters out of the group consisting of EGG, pulse, conductivity, EEG, eye movement, respiration, leg move¬ ment, refluz, percentage SaO 2 , urea, albumin, cholesterol, etc. Preferably, the unit is also adapted to communicate with a computer or printer to sub¬ stantiate the registered information in form of a report (not shown). It is also preferred that the unit is adapted so that information can be transmitted directly to a patients records, e.g. Sy- nectics Polygram for Windows or similar (not shown). An ambulatory unit of the type previously described might also be used in connection with an invasive recording (not shown) of the blood-sugar-content. Sensors might then be based on deoxyhydrogenase. According to an embodiment the sensor is situated outside of the measuring place,e.g. in a microdialysc system. The method as well as the function of the system according to the invention should be essentially evident from what is stated above. The basis are known principles for spectroscopic detection of transmitted and/or reflected light of at least one defined wave length and of the analysis of the absorption characteristics. In using extremely fast detection over extremely short periods the characteristic step response is determined and by using plan-polarized light the characteristic angle distorsions arc evaluated. Thus, the obtained information supplements already known absorption determinations and the analysis basing on such determinations as to the quality and quantity presence and enables more exact determinations and even determi¬ nations of a new kind. BAD ORIGINAL * As also is evident from what was stated above, the invention provides essential advan¬ tages compared with what is known in the art. Such an advantage, being of course very im¬ portant in a medical respect, is the increased accuracy, when further information is obtained by means of the invention. In connection with the extremely fast detection the measuring result is reflecting a momentary state and not an average state prevailing during a longer period. The invention provides a noninvasive determination with thereto related advantages and new and important possible applications. The invention has previously been described in connection with execution examples. Further embodiments might of course be envisaged as well as minor changes and amplifica¬ tions without leaving the scope of the invention. Thus, the determination might be provided at various wave lengths passing the substance in question for establishing further important information, as the step responses can be studied by means of the invention. Moreover, embodiments might be envisaged, where a constant and/or changing electrical and/or magnetic field is applied as a supplementing measurement without the use of an ex¬ tremely fast detection and the detection of the plan-polarized light angle distortion. Various combinations of two or three of these process steps might also be envisaged. Embodiments might also be envisaged with a detecting of approaching light not neces¬ sarily being provided extremely fast, but sufficiently fast, so that the measurement object, the substance, might be regarded being steady, i.e. that molecules, in adaptable cases the red blood cells, etc., are stationary during an actual measurement. For this purpose such a fast measu¬ rement is not necessarily required for obtaining a step response, but only so fast, that nothing might be changed in the measurement area. For an extremely fast measurement time periods of the magnitude of picoseconds are applicable. Embodiments might also be envisaged with a step response provided, in that the light pulse is terminated, the step response then being an illustration of the progress, how the pulse is fading from a stationary level S" down to an intensity, e.g. zero, corresponding to that no light pulse is prevailing, possibly being illustrated by a progress from the right to the left along the time axis in figure 3. Thus the invention is considered not to be limited to the embodiments specified above and can be modified within the scope provided by the attached claims. AD ORIGINAL

Claims: C L A I M S 1. A method to determine the presence of one or several components in a e.g. liquid substance by means of spectroscopy including an illumination of the substance by means of light with at least one definite wave length, preferably within the almost infrared wave length area, and detecting transmitted and/or reflected light well as the analysis of detected light characteristics, characterized in that said detection is performed extremely fast, preferably so, that a step response corresponding to an approaching or fading light pulse might be detected, the step response comprising information of said light pulse passing wave length through a measuring device (2, 4, 5). 2. A method to determine the presence of one or several components in a e.g. liquid substance by means of spectroscopy including an illumination of the substance by means of light with at least one definite wave length, preferably within the almost infrared wave length area, and detecting transmitted and/or reflected light well as the analysis of detected light characteristics, characterized in that the plan-polarized light (8) angle distorsion is detected. 3. A method to determine the presence of one or several components in a e.g. liquid substance by means of spectroscopy including an illumination of the substance by means of light with at least one definite wave length, preferably within the almost infrared wave length area, and detecting transmitted and/or reflected light well as the analysis of detected light characteristics, characterized in that a varying and/or steady electrical and/or magnetic field is applied over the substance during said determination. 4. A method according to claim 1, 2 or 3. characterized in combinations of two or three of the steps - the detection is extremely fast, - plan-polarized light angle distorsion is detected, - a varying and/or steady electrical and/or magnetic field is applied over the substance during said determination. 5. A method according to claim 1 or 4, characterized in that said determination takes place during such a short period that the measuring subject, the substance, might be regarded as steady. 6. A method according to one of the claims 1 to 5, characterized in that said substance is blood, the blood-glucose-contents then being determined. BAD ORIGINAL 7. A method according to one of the claims 1 to 6, characterized in that said determi¬ nation relates to a substance in the human body and is noninvasive. 8. A method according to one of the claims 1 to 7, characterized in that said determi¬ nation takes place with various passing wave lengths through said substance. 9. A method according to one of the claims 1 to 8, characterized in that said determi¬ nation takes place with at least two wave lengths (λ) by means of so-called differential spectroscopy, said wave lengths corresponding to the almost infrared wave length area. 10. A system to determine the presence of one or several components in a preferably liquid substance by means of spectroscopy including devices for an illumination of the sub¬ stance by means of light with at least one wave length, preferably within the almost infrared wave length area, an for detecting transmitted and/or reflected light as well as analyzing the detected light characteristics, characterized in that devices (6, 7, 12, 13) are provided to perform said detection extremely fast, preferably so that a step response corrsponding to an approaching light pulse might be detected and/or that devices (8, 9, 12, 13) are provided for the illumination by means of plan-polarized light (8) to detect the plan-polarized light angle distortion. 11. A system according to claim 10, characterized in that devices are provided to apply a varying and/or steady electrical and/or magnetic field over the substance during said de¬ termination. 12. A system according to claim 10 or 11, characterized in that devices (1, 6, 7, 12, 13) are provided to perform said determination in a noninvasive way. 13. A system according to claim 10, 11 or 12, characterized in that said substance is blood, the presence of glucose being possibly be determined. 14. A system according to any one of claims 7 to 10, characterized in that devices (1, 6, 7, 12, 13) are provided to perform said determination with at least two different wave lengths (λ) by means of so-called differential spectroscopy, said wave lengths corresponding to the almost infrared wave length area. 15. An ambulatory registration system to register an individuals blood-sugar-content, characterized in a digital registration unit (10) connected to a sensor (12, 13) for blood-sugar. 16. A system according to claim 15, characterized in that the sensor is connected to the unit by means of electrical and/or fibre-optical cables. 17. A system according to claim 15, characterized in that the sensor is an optical one and is connected to the unit by means of fibre-optical cables. S 18. A system according to claim 15, characterized in that the sensor is connected to the unit without any wires. 19. A system according to claim 15, 16, 17 or 18, characterized in that the sensor is noninvasive. 20. A system according to claim 17, 18 or 19. characterized in that the sensor is adapted for a spectroscopical determination, a light source being provided for generating light with at least one definite wave length. 21. A system according to any of the claims 17 to 20, characterized in that plan- polarized light (8) of at least one wave length is adapted to be used, preferably in combination with a light of at least one reference wave length and a light with a measuring wave length. 22. A system according to claim 21, characterized in that the plan-polarized light angle distortion is intended to be detected and be related to a reflected and/or transmitted light with reference and measuring wave lengths. 23. A system according to any of the claims 17 to 22, characterized in that devices (6, 7) are provided for an extremely fast light detection, by means of which a step response might be detected. 24. A system according to any of the claims 17 to 23, characterized in that devices are provided for applying an electrical and/or magnetic field over a by means of the sensor scanned portion to influence the dipole moment of any existing molecules, including blood- sugar. 25. A system according to any of the claims 17 to 24, characterized in that the sensor is noninvasive. 26. A system according to claim 25, characterized in that the sensor is based on a glucosedeoxy hy drogenase . 27. A system according to claim 25 or 26, characterized in that said sensor is situated outside of the measuring area, e.g. in a microdialysis system. 28. A system according to claim 17, characterized in that at least one of the illumina¬ ting and detecting devices is incorporated in said unit. 29. A system according to claim 17, characterized in that said unit is connected to ex¬ ternal illumination and detecting devices (12, 13). 30. A system according to any of the claims 15 to 29, characterized in that an alarm function (14) is provided to be triggered automatically, when the blood-sugar-content is be- BAD ORIGINAL A low a predetermined level and/or when the blood-sugar-content lies over a predetermined level. 31. A system according to any of the claims 15 to 30, characterized in that the unit has a registration capacity of at least 8 hours. 32. A system according to any of the claims 15 to 31, characterized in that the unit has event controls (15) to indicate symptoms and events. 33. A system according to any of the claims 15 to 32, characterized in that the unit is adapted to register besides the blood-sugar-content also at least one of the parameters out of the group consisting of ECG, pulse, conductivity, EEG, eye mouvement, respiration, leg mouvement, reflux, percentage SaO 2 , urea, albumin, cholesterole, etc. 34. A system according to any of the claims 15 to 33, characterized in that the unit is adapted to communicate with a computer or a printer to substantiate registered information in form of a report. 35. A system according to any of the claims 15 to 34, characterized in that the unit is adapted to transmit registered information directly to a patients records, e.g. a Synectics Po¬ lygram for Windows or similar. B& rκ / ■ *•-*« —

Inventors: ESSEN-MOELLER ANDERS, ESSEN-MOELLER, ANDERS
Applicants: ESSEN MOELLER ANDERS, SYNECTICS BIOTECHNOLOGY AB, ESSEN-MOELLER, ANDERS
Application year: 1996
Main classification: G01N21
IPC codes: A61B5, G01N21