DE102008011013A1 - Method and device for complex metabolic analysis - Google Patents
Method and device for complex metabolic analysis Download PDFInfo
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- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
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- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
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- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
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- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/48—Other medical applications
- A61B5/4866—Evaluating metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
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Abstract
Die Erfindung betrifft ein Verfahren und eine Einrichtung zur nichtinvasiven Untersuchung von Steuer- und Regelungsprozessen im menschlichen, im tierischen und im pflanzlichen Stoffwechsel, um aus fesrameter Rückschlüsse auf spezifische Erkrankungen ziehen zu können. Im Besonderen findet das Verfahren Anwendung bei präventiven Untersuchungen zur Krebsfrüherkennung, aber auch begleitend zur Behandlung von Krebserkrankungen bei allen entzündlichen, bei Stoffwechsel- und Immunerkrankungen, zur Bestimmung des Bedarfs an antioxidativen Schutzstoffen, zur Behandlungskontrolle der einzelnen Krankheitsbilder, zur Routineuntersuchung bei Berufsgruppen mit besonderer physischer und psychischer Belastung. Erfindungsgemäß wird die Aufgabe dadurch gelöst, daß aus dem nativen Fluoreszenzspektrum im Wellenlängenbereich von 287 nm bis 600 nm stoffwechselrelevante biologisch aktive Substanzen, die eine Autofluoreszenz besitzen, ausgewählt werden und in biochemischen bzw. biophysikalischen Modellen miteinander verknüpft werden, um Steuer- und Regelungsprozesse bei Mensch und Tier bzw. in Pflanzen zu beschreiben. Die Fluoreszenzspektren werden über eine optische Meßstrecke erfaßt, bestehend aus einer Lichtquelle (1), einem Lichtleitkabel (2) zur Zuführung des Anregungslichtes zum Meßort, einem Lichtleitkabel (2) zur Ableitung des Fluoreszenzlichtes zum Spektrometer (5) und einem Auswerterechner (8). Aussagen zum Mangel an und ...The invention relates to a method and a device for the noninvasive examination of control and regulatory processes in human, animal and plant metabolism in order to draw conclusions about specific diseases from fesrameter. In particular, the method is used in preventive screening for cancer detection, but also concomitantly for the treatment of cancer in all inflammatory, metabolic and immune diseases, to determine the need for antioxidant protective agents, to control the treatment of individual diseases, for routine examination in occupational groups with particular physical and mental stress. According to the invention the object is achieved in that from the native fluorescence spectrum in the wavelength range from 287 nm to 600 nm metabolic biologically active substances that have an autofluorescence, are selected and linked together in biochemical or biophysical models to control and regulatory processes in humans and animal or in plants. The fluorescence spectra are detected via an optical measuring path, consisting of a light source (1), a light guide cable (2) for supplying the excitation light to the measuring location, a light guide cable (2) for deriving the fluorescent light to the spectrometer (5) and an evaluation computer (8). Statements about the lack of and ...
Description
Die Erfindung betrifft ein Verfahren und eine Einrichtung zur nichtinvasiven oder invasiven Messung von Steuer- und Regelungsprozessen des pflanzlichen, des tierischen oder menschlichen Stoffwechsels zur Kontrolle von Störungen sowie zur Bestimmung von physikalischen oder chemischen Einflussfaktoren auf die Reaktionsbedingungen, um aus den Veränderungen einzelner Stoffwechselparameter Rückschlüsse auf spezifische Erkrankungen ziehen zu können.The The invention relates to a method and a device for noninvasive or invasive measurement of control and regulatory processes of the plant, of animal or human metabolism for the control of Disturbances as well as for the determination of physical or chemical factors influencing the reaction conditions to from the Changes in individual metabolic parameters conclusions to be able to draw on specific diseases.
Das Verfahren findet Anwendung bei präventiven Untersuchungen zur Krebsfrüherkennung oder Krebsnachsorge, bei allen entzündlichen Erkrankungen, bei Schädigungen der Immunregulation, bei Stoffwechselerkrankungen, bei Syndromen wie chronische Müdigkeit oder Multiple Chemische Sensitivität, bei Allergien, bei Autoimmunerkrankungen, Hautkrankheiten, bei neurologisch-psychischen Erkrankungen, Erkrankungen durch Viren, Bakterien oder Pilze u. v. a. und der Bestimmung des individuellen spezifischen quantitativen und qualitativen Antioxidantienbedarfs, der Therapiekontrolle der einzelnen Krankheitsbilder sowie der Routineuntersuchung bei Berufsgruppen mit besonderer physischer und psychischer Belastung.The Method is used in preventive examinations for cancer screening or cancer follow-up, for all inflammatory Diseases, damage to the immune regulation, metabolic diseases, in syndromes such as chronic fatigue or multiple chemical Sensitivity, allergies, autoimmune diseases, Skin diseases, neurological disorders, illnesses by viruses, bacteria or fungi u. v. a. and the provision of the individual specific quantitative and qualitative antioxidant needs, the therapy control of the individual clinical pictures as well as the routine examination with Occupational groups with special physical and mental stress.
Stand der TechnikState of the art
Fluoreszenzspektrometrische Untersuchungen sind seit einigen Jahren als hochgenaue und sehr spezifische Verfahren in der biologischen Grundlagenforschung zu Transportprozessen durch biologische Membranen und biomedizinische Untersuchungen als diagnostisches Hilfsmittel bekannt und befinden sich z. Zt. in einer stetigen progressiven Entwicklungsphase. Die Grundlage der Meßverfahren ist die Kenntnis der Eigenschaften künstlicher Fluorophore bzw. die Kenntnis der Excitations- und Emissionswellenlänge von Autofluorophoren.Fluoreszenzspektrometrische Investigations have been highly accurate for a few years now specific procedures in basic biological research Transport processes through biological membranes and biomedical Investigations known as diagnostic tool and are z. Currently in a steady progressive development phase. The The basis of the measuring methods is the knowledge of the properties artificial fluorophores or the knowledge of the excitation and emission wavelength of autofluorophores.
Eine Vielzahl von stoffwechselrelevanten Parametern wie Tryptophan, Adenosin triphosphat (ATP), Guanosin triphosphat (GTP), Nicotinamid adenin dinucleotid phosphat (NADP), Nicotinamid adenin dinucleotid reduziert (NADH), Kynurenin, Flavin adenin dinucleotid (FAD) und Thromboxan besitzen eine sogenannte Autofluoreszenz.A Variety of metabolic parameters such as tryptophan, adenosine triphosphate (ATP), guanosine triphosphate (GTP), nicotinamide adenine dinucleotide phosphate (NADP), nicotinamide adenine dinucleotide reduced (NADH), kynurenine, flavin adenine dinucleotide (FAD) and thromboxane have a so-called autofluorescence.
Die
Bestimmung dieser Autofluoreszenzen besitzt den Vorteil, daß dem
Stoffwechsel keine unphysiologischen Substanzen zugeführt
werden müssen. So wird im Patent,
Weiterführende
Arbeiten nutzen die hohe native Fluoreszenz von NADH zum Nachweis
von Melanomen,
Im
Patent,
Im
Patent,
Nach
umfangreichen Experimenten wurde in den Patenten,
Bei den Untersuchungen konnte nachteilig festgestellt werden, daß weder die Verwendung der maximalen Fluoreszenzintensität im Wellenlängenbereich von 320 nm–600 nm oder die absoluten Fluorezenzintensitäten relevanter Stoffwechselparameter wie NADH, Tryptophan, FAD und Kynurenin noch das Verhältnis von zwei Substanzen wie NADH und Kynurenin eine eindeutige Trennung zwischen „Gesund” und Krebsbelastung gestattet.at The investigations could be found disadvantageous that neither the use of the maximum fluorescence intensity in the wavelength range of 320 nm-600 nm or the absolute fluorescence intensities relevant metabolic parameters such as NADH, tryptophan, FAD and kynurenine nor the ratio of two substances such as NADH and Kynurenin a clear distinction between "healthy" and Cancer burden allowed.
So ist z. B. ein geringes Verhältnis zwischen den Intensitäten von NADH und Kynurenin nicht nur charakteristisch für eine Krebsbelastung, sondern alle entzündlichen Erkrankungen weisen ein ähnliches Verhältnis auf. Dies ist nicht absonderlich, da viele Krebserkrankungen mit entzündlichen Erscheinungen einhergehen.So is z. B. a low ratio between the intensities from NADH and Kynurenin not only characteristic for one Cancer burden, but all inflammatory diseases have a similar relationship. This is Not peculiar, as many cancers with inflammatory Phenomena go along.
Ein weiterer Nachteil der oben beschriebenen invasiven Methoden ist es, daß durch die Stressbelastung des Messvorganges eine verfälschte Momentaufnahme des Stoffwechsels entsteht und keine Aussagen über Stoffwechselregelungsprozesse möglich sind. Eine solche Aussage kann nur durch eine in kurzen Abständen wiederholbare streßfreie Meßung oder durch zeitlich definierte Messungen vor und nach einer Streßbelastung erfolgen.One Another disadvantage of the above-described invasive methods it, that by the stress load of the measuring process a falsified snapshot of the metabolism arises and no statements about metabolic control processes possible are. Such a statement can only be made by one at short intervals repeatable stress-free measurement or by time defined measurements before and after a stress load respectively.
Aufgabenstellungtask
Der Erfindung liegt die Aufgabe zu Grunde, ein Verfahren und eine Einrichtung vorzuschlagen, die es ermöglichen, Steuer- und Regelungsprozesse des menschlichen und tierischen bzw. auch pflanzlichen Stoffwechsels zu messen, um bei Veränderungen dieser Prozesse Rückschlüsse auf spezifische Krankheitsbilder ziehen zu können. Das Verfahren soll den eigentlichen Messvorgang nichtinvasiv, oder invasiv und schnell wiederholbar machen, um keine Streßbelastung durch den Meßprozeß hervorzurufen.Of the The invention is based on the object, a method and a device to propose that the tax and regulatory processes of the human and animal or vegetable metabolism to measure changes in these processes to be able to draw on specific clinical pictures. The Procedures should be noninvasive, or invasive and quickly repeatable to avoid stress caused by the measuring process.
Erfindungsgemäß wird diese Aufgabe durch die in den Patentansprüchen offenbarten Merkmale gelöst.According to the invention this object by the disclosed in the patent claims Characteristics solved.
Das Kennzeichnende besteht darin, dass aus dem nativen Fluoreszenzspektrum im Wellenlängenbereich von 287 nm bis 600 nm stoffwechselrelevante biologisch aktive Substanzen, die eine Autofluoreszenz besitzen, ausgewählt werden und in biochemischen bzw. biophysikalischen Modellen miteinander verknüpft werden, um Steuer- und Regelungsprozesse bei Mensch und Tier bzw. in Pflanzen zu beschreiben.The Characteristic is that from the native fluorescence spectrum in the wavelength range from 287 nm to 600 nm metabolically relevant biologically active substances that have autofluorescence, be selected and in biochemical or biophysical Models are linked together to control processes in humans and animals or in plants to describe.
Die Fluoreszenzspektren werden über eine optische Messstrecke erfasst, die aus einer Lichtquelle, einem Lichtleitkabel zur Zuführung des Anregungslichtes zum Messort, einem Lichtleitkabel zur Ableitung des Fluoreszenzlichtes zum Spektrometer und einem Auswerterechner besteht.The Fluorescence spectra are transmitted over an optical measuring path detected, consisting of a light source, a light guide cable for feeding of the excitation light to the measuring location, a light guide cable for the derivation of the fluorescent light to the spectrometer and an evaluation computer consists.
Aussagen zum Mangel an und Bestimmungen des spezifischen Vitalstoffbedarfs, für eine regulierende Einflussnahme werden aus den nichtinvasiven Messwerten über die Feststellung der Abweichungen von Statusaussagen zum optimalen Gesundheits-Status ermittelt. Dabei werden die Abweichungswerte entsprechend der Bedeutung der Vitalstoffe für diese Abweichungen gewichtet. Die gewichteten Mittelwerte erlauben schließlich durch Einsetzen in Ausgleichspolynome dritter Ordnung die Berechnung der Dosiereinheiten für die fehlenden Vitalstoffe.statement to the lack of and determinations of the specific vital substance requirement, for a regulating influence are from the non-invasive Measurements about the determination of deviations from status statements determined to optimal health status. Thereby the deviation values become according to the importance of the vital substances for these deviations weighted. The weighted averages finally allow by substituting in third order equalization polynomials the calculation the dosing units for the missing vital substances.
Die zur Durchführung des Verfahrens vorgeschlagene Einrichtung besteht aus einer Lichtquelle, vorzugsweise einem Laser oder Xenon-Blitzlampe, einem optischem Filter, Miniaturspektrometer und verbindende Lichtleitkabeln zwischen der Lichtquelle mit Messsonde am Messort und einer Auswerteeinheit.The proposed device for carrying out the method consists of a light source, preferably a laser or xenon flash lamp, a optical filter, miniature spectrometer and connecting optical cables between the light source with measuring probe at the measuring location and an evaluation unit.
Die Vorteile der Erfindung liegen in der nichtinvasiven Messung der Fluoreszenzspektren und der dadurch garantierten Stressfreiheit. Infolge dieses Messvorganges können in sehr kurzen zeitlichen Abständen Wiederholungsmessungen erfolgen und somit Regulationsvorgänge im Stoffwechsel erkannt werden. Durch Veränderungen dieser Regulationsprozesse unter definierten Stressbedingungen können Rückschlüsse auf krankhafte Veränderungen des Organismus gezogen werden.The Advantages of the invention lie in the non-invasive measurement of Fluorescence spectra and guaranteed freedom from stress. As a result of this measurement process can be in very short temporal Repeated measurements take place and thus regulatory processes be recognized in the metabolism. By changing this Regulation processes under defined stress conditions can Conclusions about pathological changes of the Be pulled organism.
Ausführungsbeispielembodiment
Die Erfindung wird nachfolgend an einem Ausführungsbeispiel näher erläutert. Es zeigen:The Invention will become apparent from an embodiment explained in more detail. Show it:
Gemäß dem
Blockschaltbild der Messstrecke nach
Ein
Miniaturspektrometer
Eine kombinierte Mess- und Auswertesoftware, die auf einen an sich bekannten Computer installiert ist, dient der Erfassung, Auswertung, Interpretation und Visualisierung der Messergebnisse. Im Ergebnis des Screenings entsteht ein Befund mit prozentual aufgeschlüsselten Aussagen zum aktuellen Gesundheitszustand des Probanden.A Combined measurement and evaluation software based on a known Computer is installed, serves the capture, evaluation, interpretation and visualization of the measurement results. As a result of the screening A finding is produced with percentage-based statements to the current state of health of the subject.
Die
Bauelemente
Die im Rechner gespeicherten Fluoreszenzspektren, die aus den erfassten Wellenlängen im Bereich von 287 nm bis 600 nm und den dazugehörigen Fluoreszenzintensitäten bestehen, werden in einem geeigneten Tabellenformat zur Auswertung vorbereitet.The stored in the computer fluorescence spectra, from the detected Wavelengths in the range of 287 nm to 600 nm and the associated fluorescence intensities exist, are evaluated in a suitable table format prepared.
Aus diesen Tabellen werden die Wertepaarungen (Wellenlänge und Fluoreszenzintensität) für stoffwechselrelevante, biologisch aktive Substanzen wie ATP, GTP, Tryptophan, Orotsäure, NADP, NADH, FAD usw. ausgewählt. Die Anregungswellenlängen und Emissionswellenlängen dieser Substanzen wurden in umfangreichen Vorversuchen bestimmt. Da unterschiedliche Hautstrukturen und Hautbestandteile die Verwendung der Absolutwerte nicht zulassen, kann nur mit Relativwerten eine weitere Auswertung erfolgen. Es ist also notwendig, Wertepaarungen der relevanten, biologisch aktiven Substanzen zu bestimmen, und in biophysikalischen und biochemischen Modellen zu verknüpfen. Diese Modelle beinhalten Substanzen, die während der Stoffwechselvorgänge miteinander reagieren, ineinander umwandeln und/oder sich gegenseitig in ihrer Konzentration und Reaktionsfähigkeit beeinflussen.Out These tables are the value pairings (wavelength and fluorescence intensity) for metabolically relevant, biologically active substances such as ATP, GTP, tryptophan, orotic acid, NADP, NADH, FAD etc. selected. The excitation wavelengths and Emission wavelengths of these substances were in extensive Preliminary tests determined. Because different skin structures and skin constituents Do not allow the use of absolute values, can only with relative values another evaluation done. It is therefore necessary to make value pairings determine the relevant biologically active substances, and in biophysical and biochemical models. These models include substances that interact with each other during metabolic processes react, interconvert and / or interact with each other Influence concentration and responsiveness.
Im Anschluss werden weitere Selektionsstufen durchlaufen, um entzündliche Erkrankungen von Krebserkrankungen zu differenzieren bzw. auch unter den entzündlichen Erkrankungen eine Differenzierung zu erkennen.in the Connection will undergo further selection stages to become inflammatory Differentiate diseases of cancers or under the inflammatory diseases differentiation detect.
Parallel zur Auswertung der Spektren durch Selektion der Erkrankungen mittels biophysikalischer und biochemischer Modelle auf der Basis bekannter biologisch aktiver Substanzen, erfolgt eine Auswertung durch selbstlernende Systeme, die nach Unterschieden in den Spektren von gesunden Probanden und Patienten suchen, ohne eine bekannte Wertepaarung (Wellenlänge und Intensität) biologisch aktiver Substanzen zu verwenden.Parallel to evaluate the spectra by selecting the diseases by means of biophysical and biochemical models based on known biological active substances, an evaluation is carried out by self-learning Systems that look for differences in the spectra of healthy volunteers and Search patients without a known value pairing (wavelength and intensity) of biologically active substances.
Im ersten Schritt werden die Aussagen zum Gesundheitsstatus durch die nichtinvasive Messung als Prozentwerte ermittelt. Davon abgeleitet erfolgt die Berechnung der Abweichungen der aktuellen Prozentwerte zum Optimalwert des Gesundheitsstatus.in the The first step is the statements on health status by the Non-invasive measurement determined as percentages. Derived from it the calculation of the deviations of the current percentages takes place to the optimal value of the health status.
Durch das Verfahren der multivariaten Regression ist unter Bezugnahme auf Aussagen zum Korrekturbedarf der Ergebnisse aus zwei Meßverfahren die bestmögliche mathematische Übereinstimmung herzustellen.By The method of multivariate regression is by reference on statements on the need for correction of the results of two measuring methods the best possible mathematical match manufacture.
Die Regressionsrechnung erlaubt somit eine Korrekturempfehlung als Ableitung aus den Meßergebnissen des Verfahrens der Komplexen Serum-Redoxdifferenz-Provokationsanalyse und den Meßwerten der spezifischen Fluoreszenzintensitäten der nichtinvasiven Methode.The regression calculation thus allows a correction recommendation as a derivation from the measurement results of the method of the complex serum redox difference provocation analysis and the measured values of the specific fluorescence intensities the non-invasive method.
Mittels
Regressionsrechnung werden zur Korrektur die Koeffizienten für
ein Ausgleichspolynom
Diese
Koeffizienten werden für die eingesetzten Wirkstoffe (Vitalstoffe)
in
Durch
Einsetzen dieser Polynomkoeffizienten als Werte von X in das Ausgleichspolynom 0,00014 × 14 × x3 – 0,00337 × x2 + 0,03259 × X – 0,10534
= y (y = Dosiereinheiten: z. B. 1,565) ergeben sich die Dosiereinheiten
(y) für die verschiedenen Vitalstoffe. Das Berechnungsbeispiel
gilt für den Bedarf an Mangan bei Einsatz des gewichteten
Mittelwertes von 17,23. (
Bei
der nach
- 11
- Lichtquelle PX-2 Xenonlampelight source PX-2 xenon lamp
- 22
- Lichtleitkabel zur Ableitung für Anregungslicht und Fluoreszenzsignaloptical cable for the derivation of excitation light and fluorescence signal
- 33
- Messsonde/MesskopfProbe / probe
- 44
- Optisches Filteroptical filter
- 55
- Miniaturspektrometer USB 2000 mit OFVL-Filterminiature spectrometer USB 2000 with OFVL filter
- 66
- Hautoberfläche (Messort)skin surface (Measurement location)
- 77
- Gehäusecasing
- 88th
- Computer ACER Aspire 1310, Windows XP, Office Paket (Excel/Access)computer ACER Aspire 1310, Windows XP, Office suite (Excel / Access)
- 99
- Netzteilpower adapter
ZITATE ENTHALTEN IN DER BESCHREIBUNGQUOTES INCLUDE IN THE DESCRIPTION
Diese Liste der vom Anmelder aufgeführten Dokumente wurde automatisiert erzeugt und ist ausschließlich zur besseren Information des Lesers aufgenommen. Die Liste ist nicht Bestandteil der deutschen Patent- bzw. Gebrauchsmusteranmeldung. Das DPMA übernimmt keinerlei Haftung für etwaige Fehler oder Auslassungen.This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.
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Claims (17)
Priority Applications (3)
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DE200810011013 DE102008011013B4 (en) | 2008-02-25 | 2008-02-25 | Method and device for complex metabolic analysis |
EP09715141A EP2252197A2 (en) | 2008-02-25 | 2009-02-24 | Method and device for complex metabolic analysis |
PCT/EP2009/052171 WO2009106524A2 (en) | 2008-02-25 | 2009-02-24 | Method and device for complex metabolic analysis |
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DE200810011013 DE102008011013B4 (en) | 2008-02-25 | 2008-02-25 | Method and device for complex metabolic analysis |
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DE102008011013A1 true DE102008011013A1 (en) | 2009-09-03 |
DE102008011013B4 DE102008011013B4 (en) | 2014-11-13 |
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EP2295953A1 (en) | 2009-09-12 | 2011-03-16 | SITA Messtechnik GmbH | Device for measuring substance concentrations in solutions on the basis of a fluorescence measurement |
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DE102010023486A1 (en) * | 2010-06-11 | 2011-12-15 | B. Braun Avitum Ag | Detection device and method |
DE102012002086A1 (en) * | 2012-02-06 | 2013-08-08 | Carl Zeiss Meditec Ag | A method of examining biological tissue and devices for examining and treating the tissue |
DE102013108189A1 (en) * | 2013-07-31 | 2015-02-05 | Endress + Hauser Conducta Gesellschaft für Mess- und Regeltechnik mbH + Co. KG | Arrangement for the optical measurement of a process variable and measuring device comprising such |
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DE102016001080A1 (en) | 2015-02-09 | 2016-08-11 | Stefan Liebelt | Method and diagnostic device for the determination of cancer in the human body due to the higher iron concentration of malignant cells |
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Also Published As
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WO2009106524A2 (en) | 2009-09-03 |
WO2009106524A3 (en) | 2009-12-17 |
DE102008011013B4 (en) | 2014-11-13 |
EP2252197A2 (en) | 2010-11-24 |
WO2009106524A4 (en) | 2010-02-11 |
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