DE102014104518A1 - Multifunction probe - Google Patents
Multifunction probe Download PDFInfo
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- DE102014104518A1 DE102014104518A1 DE102014104518.1A DE102014104518A DE102014104518A1 DE 102014104518 A1 DE102014104518 A1 DE 102014104518A1 DE 102014104518 A DE102014104518 A DE 102014104518A DE 102014104518 A1 DE102014104518 A1 DE 102014104518A1
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- 239000000523 sample Substances 0.000 title 1
- 238000005286 illumination Methods 0.000 claims abstract description 22
- 238000001514 detection method Methods 0.000 claims abstract description 20
- 230000005284 excitation Effects 0.000 claims abstract description 12
- 238000005259 measurement Methods 0.000 claims description 19
- 238000003841 Raman measurement Methods 0.000 claims description 4
- 229910052782 aluminium Inorganic materials 0.000 claims description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 230000005855 radiation Effects 0.000 claims description 3
- 229910001220 stainless steel Inorganic materials 0.000 claims description 2
- 239000010935 stainless steel Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 description 10
- 239000013307 optical fiber Substances 0.000 description 9
- 238000001069 Raman spectroscopy Methods 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 5
- 238000004611 spectroscopical analysis Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 2
- 238000005553 drilling Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000010146 3D printing Methods 0.000 description 1
- 238000004026 adhesive bonding Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000005670 electromagnetic radiation Effects 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
Images
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N21/03—Cuvette constructions
- G01N21/0303—Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N2021/1734—Sequential different kinds of measurements; Combining two or more methods
- G01N2021/1736—Sequential different kinds of measurements; Combining two or more methods with two or more light sources
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
- G01N21/359—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using near infrared light
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/65—Raman scattering
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2201/00—Features of devices classified in G01N21/00
- G01N2201/08—Optical fibres; light guides
Abstract
Multifunktionale Messvorrichtung wobei mehrere Beleuchtungsfenster (3, 4, 5, 6, 19) und mehrere Detektionsfenster (2, 3, 4, 4', 5', 20) derart angeordnet sind, dass das Anregungslicht in einem Beleuchtungsfleck auf einer zu analysierenden Probe zusammengeführt wird.Multi-functional measuring device wherein a plurality of illumination windows (3, 4, 5, 6, 19) and a plurality of detection windows (2, 3, 4, 4 ', 5', 20) are arranged such that the excitation light in an illumination spot on a sample to be analyzed merged becomes.
Description
Die Erfindung betrifft einen Messkopf zur Analyse verschiedener Substanzen.The invention relates to a measuring head for the analysis of various substances.
Im pharmazeutischen bzw. molekularbiologischen Bereich ist es oftmals notwendig, präzise und zuverlässige Analysen von Stoffen durchzuführen. Hierbei werden insbesondere mit Hilfe spektroskopischer Analysen verschiedenste Substanzen identifiziert und analysiert.In the pharmaceutical and molecular biology field, it is often necessary to carry out precise and reliable analyzes of substances. Here, in particular with the help of spectroscopic analyzes a variety of substances are identified and analyzed.
Üblicherweise werden verschiedene Analysemethoden an derselben Probe zeitlich und räumlich getrennt voneinander durchgeführt, da herkömmliche Geräte üblicherweise auf eine spektroskopische Methode spezialisiert sind und somit maximal eine Messung zeitgleich an einer Probe durchgeführt werden kann. Werden Messungen zu unterschiedlichen Zeitpunkten durchgeführt, so ist das Messergebnis oftmals ungenau. Ebenso kann durch die Messung einer Probe zu verschiedenen Zeitpunkten mit verschiedenen Methoden aufgrund der räumlichen Abweichung des Messpunktes oder Messfeldes zu Ungenauigkeiten führen.Usually, different analysis methods are carried out on the same sample, temporally and spatially separated, since conventional instruments are usually specialized in a spectroscopic method and thus a maximum of one measurement can be carried out simultaneously on a sample. If measurements are carried out at different times, the measurement result is often inaccurate. Likewise, the measurement of a sample at different times with different methods due to the spatial deviation of the measuring point or measuring field can lead to inaccuracies.
Weiterhin ist es, insbesondere bei der Überprüfung von beispielsweise Medikamenten wichtig, schnell und zuverlässig beispielsweise eine speziell vom Hersteller implizierte Verteilung des Wirkstoffes zu erkennen oder qualitative Aussagen treffen zu können, um so mögliche wirkstofffreie, falsche oder sonstige Nachahmpräparate von den Originalen zu unterscheiden. Um dies zu gewährleisten, ist es notwendig, verschiedene Analysemethoden schnell, zeitgleich und zuverlässig durchführen zu können.Furthermore, it is important, especially in the review of, for example, drugs, to quickly and reliably recognize, for example, a specific manufacturer implicit distribution of the drug or to make qualitative statements in order to distinguish possible drug-free, false or other imitation preparations from the originals. To ensure this, it is necessary to be able to carry out various analysis methods quickly, simultaneously and reliably.
Es ist daher eine Aufgabe der Erfindung, eine Messvorrichtung anzugeben, die es ermöglicht, parallel in einem lokal eng begrenzten Bereich verschiedene spektroskopische Analysemethoden in einem Gerät durchzuführen.It is therefore an object of the invention to provide a measuring device which makes it possible to carry out different spectroscopic analysis methods in one device in parallel in a locally narrow range.
Diese Aufgabe wird durch die Messvorrichtung mit den Merkmalen des Anspruchs 1 gelöst. Die Unteransprüche stellen vorteilhafte, mögliche Ausführungsformen der erfindungsgemäßen Messvorrichtung dar.This object is achieved by the measuring device with the features of
Eine erfindungsgemäße multifunktionale Messvorrichtung weist mehrere Beleuchtungsfenster und mehrere Detektionsfenster auf, die derart angeordnet sind, dass das Anregungslicht in einem Beleuchtungsfleck auf einer zu analysierenden Probe zusammengeführt wird. Das Anregungslicht kann dabei Licht unterschiedlicher Wellenlängen, insbesondere in Wellenlängenbereichen für NIR- oder UV/VIS-Messung, Raman-Messungen oder von Wellenlängenbereichen, die geeignet sind, Fluoreszenz-Messungen durchzuführen, aufweisen. So können mehrere verschiedene spektroskopische Analysen parallel in einem sehr begrenzten Bereich und unabhängig davon, ob die zu analysierende Substanz ein Feststoff, eine Flüssigkeit oder gasförmig ist, durchgeführt werden. Als Beleuchtungsfenster ist der Bereich im Messkopf, wo das Anregungslicht aus diesem austritt, zu verstehen. Als Detektionsfenster ist der Bereich im Messkopf zu verstehen, wo die von einem Beleuchtungsfleck ausgehende Strahlung erfasst wird.A multifunctional measuring device according to the invention has a plurality of illumination windows and a plurality of detection windows, which are arranged in such a way that the excitation light is brought together in an illumination spot on a sample to be analyzed. The excitation light can thereby have light of different wavelengths, in particular in wavelength ranges for NIR or UV / VIS measurement, Raman measurements or wavelength ranges which are suitable for carrying out fluorescence measurements. Thus, several different spectroscopic analyzes can be carried out in parallel in a very limited range and irrespective of whether the substance to be analyzed is a solid, a liquid or a gaseous one. The illumination window is the area in the measuring head where the excitation light emerges from it. The detection window is the area in the measuring head where the radiation emanating from a lighting spot is detected.
Der Beleuchtungsfleck weist bevorzugt eine maximale laterale Erstreckung von bis zu 20 mm, insbesondere von 5 mm auf. Die Geometrie des Beleuchtungsflecks kann dabei mittels einer Blende insbesondere kreisförmig gestaltet sein. Selbstverständlich sind auch andere geometrische Formen denkbar.The illumination spot preferably has a maximum lateral extent of up to 20 mm, in particular of 5 mm. The geometry of the illumination spot can be designed in particular circular by means of a diaphragm. Of course, other geometric shapes are conceivable.
In einer vorteilhaften Ausführungsform einer erfindungsgemäßen Messvorrichtung sind die Beleuchtungsfenster mit Lichtquellen verbunden, die geeignet sind Licht in einem Wellenlängenbereich für NIR-Messungen, UV/VIS-Messungen und/oder in einem für Fluoreszenz-Messungen geeigneten Wellenlängenbereich auszusenden. Als Lichtquelle ist hier nicht zwingend sichtbares Licht zu verstehen, sondern vielmehr elektromagnetische Strahlung verschiedener Wellenlängen. Durch eine geringe maximale laterale Erstreckung des Beleuchtungsflecks und die Beleuchtungsfenster, welche mit verschiedenen Lichtquellen verbunden sind, können an einer zu analysierende Substanz in kürzester Zeit, ohne einen Transfer in eine weitere Messvorrichtung, verschiedenste spektroskopische Messungen durchgeführt werden.In an advantageous embodiment of a measuring device according to the invention, the illumination windows are connected to light sources which are suitable for emitting light in a wavelength range for NIR measurements, UV / VIS measurements and / or in a wavelength range suitable for fluorescence measurements. The light source here is not necessarily visible light, but rather electromagnetic radiation of different wavelengths. By means of a small maximum lateral extent of the illumination spot and the illumination windows which are connected to different light sources, the most varied spectroscopic measurements can be carried out on a substance to be analyzed in the shortest possible time without a transfer to another measuring device.
In einer vorteilhaften Ausführungsform weist die Messvorrichtung neben den bereits genannten spektroskopischen Methoden zusätzlich ein weiteres Beleuchtungsfenster und ein weiteres Detektionsfenster auf, welche für Raman-Messungen geeignet sind. Dadurch kann neben den bereits erwähnten analytischen Methoden auch Kristallinität, Kristallorientierung, Zusammensetzung, Verspannung, Temperatur, Dotierung und Relaxation einer Substanz oder auch der Pressdruck beispielsweise einer Tablette analysiert werden.In an advantageous embodiment, in addition to the already mentioned spectroscopic methods, the measuring device additionally has a further illumination window and a further detection window, which are suitable for Raman measurements. As a result, in addition to the analytical methods already mentioned, it is also possible to analyze crystallinity, crystal orientation, composition, strain, temperature, doping and relaxation of a substance or also the pressing pressure, for example of a tablet.
In einer weiteren vorteilhaften Ausführungsform einer erfindungsgemäßen Messvorrichtung weisen die Beleuchtungsfenster und Detektionsfenster die Anordnung eines Arrays auf. Ein Array erlaubt Messungen analog zu Pushbroom-Messungen, wodurch ortsaufgelöste Analysen einer Substanz durchgeführt werden können.In a further advantageous embodiment of a measuring device according to the invention, the illumination windows and detection windows have the arrangement of an array. An array allows measurements analogous to pushbroom measurements, whereby spatially resolved analyzes of a substance can be performed.
Eine erfindungsgemäße Messvorrichtung weist bevorzugt einen zugehörigen Aufsatz zur Probenaufnahme auf, wobei dieser eine Küvettenhalterung, eine Halterung für eine Petrischale oder eine Halterung für eine Tablette aufweisen kann. Selbstverständlich sind auch weitere Halterungen, wie beispielsweise für Objektträger oder 96well-Platten denkbar.A measuring device according to the invention preferably has an associated attachment for sample receiving, wherein a cuvette holder, a holder for a Petri dish or may have a holder for a tablet. Of course, other brackets, such as for slides or 96well plates are conceivable.
Eine Küvettenhalterung ist dabei bevorzugt derart gebildet, dass die Strahlenführung durch die Küvette, welche die zu analysierende Substanz enthält, gelenkt wird.A cuvette holder is preferably formed such that the beam guidance is directed through the cuvette, which contains the substance to be analyzed.
Von Vorteil ist es, wenn der Aufsatz aus einem Kunststoff gebildet ist, dies verleiht dem Aufsatz die nötige Flexibilität und Anpassungsfähigkeit, um auf die Messvorrichtung montiert zu werden. Weiterhin kann durch die Verwendung von Kunststoff ein Aufsatz, entsprechend der zu analysierenden Substanz, mittels eines 3D-Druckverfahrens individuell gestaltet werden.It is advantageous if the attachment is made of a plastic, this gives the attachment the necessary flexibility and adaptability to be mounted on the measuring device. Furthermore, by the use of plastic an article, according to the substance to be analyzed, can be customized by means of a 3D printing process.
Die Messvorrichtung ist bevorzugt aus einem Edelstahl oder einem Leichtmetall, wie beispielsweise Aluminium gebildet, welche die Formstabilität der Messvorrichtung gewährleisten. Ebenso kann durch die Verwendung von beispielsweise schwarz eloxiertem Aluminium eine Bildung von Artefakten vermieden werden.The measuring device is preferably formed of a stainless steel or a light metal, such as aluminum, which ensure the dimensional stability of the measuring device. Likewise, by the use of, for example, black anodized aluminum formation of artifacts can be avoided.
Die erfindungsgemäße Messvorrichtung kann vorteilhaft in einem Lichtmikroskop angeordnet sein, wobei die Objektive des Lichtmikroskops bevorzugt reflektierende Elemente, wie beispielsweise Spiegel aufweisen. Dadurch sind die Abbildungseigenschaften unabhängig von den verwendeten Wellenlängen.The measuring device according to the invention can advantageously be arranged in a light microscope, wherein the lenses of the light microscope preferably have reflective elements, such as mirrors. As a result, the imaging properties are independent of the wavelengths used.
Nachfolgend werden anhand der Zeichnungen, exemplarisch verschiedene Ausführungsformen der Erfindungen erläutert.Hereinafter, various embodiments of the inventions will be explained by way of example with reference to the drawings.
Es zeigt:It shows:
In
In
Die Austrittsöffnungen der Bohrungen
Die Anordnung der Lichtleiter in verschiedenen Bohrungen, welche im Folgenden als Kanal bezeichnet werden, soll anhand der Schnitte A-A, B-B und C-C ausgehend von
Der Schnitt A-A durch einen Multifunktionsmesskopf zeigt schematisch eine Anordnung einzelner Elemente für die Fluoreszenz-Anregung. Der Kanal
Der Schnitt B-B durch einen Multifunktionsmesskopf zeigt schematisch eine Anordnung einzelner Elemente für die Raman-Detektion. Auch hier ist der Lichtleiter in einem Kanal
Der Schnitt C-C durch einen Multifunktionsmesskopf zeigt schematisch eine Anordnung einzelner Elemente für die Raman-Anregung. Wie bereits aus den Schnitten A-A und B-B bekannt tritt auch hier Licht mit einer bestimmten Wellenlänge aus einem Lichtleiter, welcher in einem Kanal
Eine weitere Variante eines erfindungsgemäßen Multifunktionsmesskopfes ist in
In
Claims (17)
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DE102014104518.1A DE102014104518B4 (en) | 2014-03-31 | 2014-03-31 | multifunction measuring head |
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2322206A (en) * | 1997-02-13 | 1998-08-19 | Spectra Tech Inc | Confocal microspectrometer system |
US20090310213A1 (en) * | 2005-06-13 | 2009-12-17 | Paul Hing | Microscope |
EP2157415A1 (en) * | 2008-08-22 | 2010-02-24 | President And Fellows Of Harvard College | Microscopy imaging system and method employing stimulated Raman spectroscopy as a contrast mechanism |
DE102010032600A1 (en) * | 2010-07-28 | 2012-02-02 | Byk-Gardner Gmbh | Apparatus and method for the determination of surface properties with multiple measurement |
EP2463616A1 (en) * | 2009-08-07 | 2012-06-13 | Kabushiki Kaisha TOPCON | Interference microscope and measuring apparatus |
JP2012150107A (en) * | 2010-12-27 | 2012-08-09 | Nippon Zeon Co Ltd | Evaluation method of optical anisotropic film, measuring apparatus for optical characteristics of optical anisotropic film and manufacturing method of optical anisotropic film |
JP2013076607A (en) * | 2011-09-30 | 2013-04-25 | Fujifilm Corp | Scattered light detector and scattered light detection method |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9015793D0 (en) | 1990-07-18 | 1990-09-05 | Medical Res Council | Confocal scanning optical microscope |
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- 2014-03-31 DE DE102014104518.1A patent/DE102014104518B4/en active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2322206A (en) * | 1997-02-13 | 1998-08-19 | Spectra Tech Inc | Confocal microspectrometer system |
US20090310213A1 (en) * | 2005-06-13 | 2009-12-17 | Paul Hing | Microscope |
EP2157415A1 (en) * | 2008-08-22 | 2010-02-24 | President And Fellows Of Harvard College | Microscopy imaging system and method employing stimulated Raman spectroscopy as a contrast mechanism |
EP2463616A1 (en) * | 2009-08-07 | 2012-06-13 | Kabushiki Kaisha TOPCON | Interference microscope and measuring apparatus |
DE102010032600A1 (en) * | 2010-07-28 | 2012-02-02 | Byk-Gardner Gmbh | Apparatus and method for the determination of surface properties with multiple measurement |
JP2012150107A (en) * | 2010-12-27 | 2012-08-09 | Nippon Zeon Co Ltd | Evaluation method of optical anisotropic film, measuring apparatus for optical characteristics of optical anisotropic film and manufacturing method of optical anisotropic film |
JP2013076607A (en) * | 2011-09-30 | 2013-04-25 | Fujifilm Corp | Scattered light detector and scattered light detection method |
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