WO2000046579A1 - Detector for micro-organisms - Google Patents
Detector for micro-organisms Download PDFInfo
- Publication number
- WO2000046579A1 WO2000046579A1 PCT/DE2000/000343 DE0000343W WO0046579A1 WO 2000046579 A1 WO2000046579 A1 WO 2000046579A1 DE 0000343 W DE0000343 W DE 0000343W WO 0046579 A1 WO0046579 A1 WO 0046579A1
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- WIPO (PCT)
- Prior art keywords
- organisms
- micro
- optical
- fluctuations
- microorganisms
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Classifications
-
- 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
- G01N21/21—Polarisation-affecting properties
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/025—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
Definitions
- the invention relates to measurement technology and in particular to optical biosensors. Microorganisms in liquids are currently recorded using optical microscopy, bioluminescence and selective coloring. The common disadvantage of all of these methods and their metrological implementation is the low degree of automation of the measuring process.
- a device (prototype) for recording mobile microorganisms (BM) which consists of a laser radiation source, a cuvette and a photo receiver (FE), which are optically coupled to one another [1].
- the spectrum of the intensity fluctuations of the scattered radiation is recorded. This spectrum is different for Brownian particles (BT) and for BM.
- the disadvantage of this method is its low selectivity in the detection of the microorganisms against the background of the scatter signal of the Brownian particles.
- UM immobile microorganisms against the background of Brownian particles in liquid is not possible with this method, since the fluctuation scatter spectra of BT and UM do not differ.
- Another shortcoming of this method is its low sensitivity, which is related to the fact that the useful signal is superimposed by the noise of the laser beam itself, which is particularly noticeable when using non-stabilized lasers.
- the photo receivers are each optically coupled to their associated cuvette and are illuminated by a common laser radiation source observed, the spectra of the scattering intensity fluctuation in the two cuvettes, and the difference is an indication of whether '.n one of the two cuvettes BM present or only if they have different activity in the cells.
- the aim of the invention is to develop an optical variant of the device which makes it possible to record mobile as well as immobile living microorganisms in liquid against the background of a large number of Brownian particles. This is achieved by recording both the movement (for BM) and the course of the metabolic processes (for UM and BM).
- the reliability of the detection of individual microorganisms and the improvement in sensitivity are achieved by increasing the examination volume and suppressing the noise of the radiation source.
- the essence of the invention is that a linearly polarized examination radiation penetrates the liquid to be examined in the cuvette, the examination volume being the same as the cuvette volume, and the fluctuations in the optical activity of the medium with BM and UM being recorded using two possible methods. In the first method, a combined polarizer and analyzer (at an extinction angle) and a photo receiver are arranged in the light beam that penetrates the examination volume.
- the signal from the photo receiver is sent to an amplifier that has a large gain factor, but only amplifies the variable part of the signal and does not record the constant part. This distinguishes it from the generally known devices used in saccharometry [3]. If there are no optically active particles in the examination volume or if their concentration does not change over time, then the output signal of the amplifier is zero. If, on the other hand, living microorganisms are present in the examination volume, they lead to stochastic changes in the optical activity of the medium through their life processes and the metabolic processes and organic chemical reactions taking place in them. The amplitude of the fluctuations recorded is proportional to the concentration of the microorganisms and the intensity of the metabolic processes taking place in them, which is e.g.
- the device requires a light source that is highly stabilized in terms of intensity, since its noise is recorded directly by the photoreceiver and amplified by the amplifier of the variable signal, which considerably reduces the signal-to-noise ratio and accordingly the sensitivity of the device.
- a differential circuit is used for the recording, in which the radiation, after penetrating the examination volume, is passed to a separating device for orthogonal polarizations, e.g.
- a glan prism arrives, and the intensity of the two light beams separated by the prism with orthogonal polarizations is recorded by two photo receivers, each of which is optically coupled with their polarization.
- the two signals to be recorded are applied to different inputs of the differential amplifier (DV), the output of which is coupled to an evaluation unit that determines the mean signal amplitude for a fixed period of time, the dispersion and the Fourier spectrum.
- the noise of the light source is present at the same time and in phase at both photo receivers and is subtracted from the DV with high accuracy (up to 100 dB).
- the signal of the intensity fluctuations which is related to the fluctuation of the optical activity, is not only not subtracted from the DV, but even amplified.
- Figure 1 shows the block diagram of the device.
- 1 - source of the stabilized linearly polarized optical radiation e.g. a stabilized laser
- 2 - cuvette with the medium to be examined
- 3 - polarizer and analyzer
- 4 - photo receiver
- 5 - variable signal amplifier
- 6 - evaluation and display unit
- Figure 2 shows the same block diagram, but with a differential circuit for recording.
- Figure 3 shows the dependence of the mean fluctuation amplitude on the time for the rehydrant of the immobile microorganisms Saccharomyces cerevisiae, which were introduced into the test volume with initially sterile water with glucose. It can be seen that there are no fluctuations and consequently no metabolic processes in the course of about 20 minutes, which would be necessary for the activation of the spores of the microorganisms and an increase in the signal after the start of the active phase.
- Figure 4 shows the dependence of the dispersion of the fluctuation amplitude on the time before and after heating the test volume to 80 ° C. There is an abrupt decrease in the dispersion after heating, which is related to the partial death of the microorganisms and the reduction in the metabolic processes.
Abstract
The invention relates to measuring methods and especially to optical biosensors. The invention can be used for determining the effectiveness of different antibiotics in relation to different pathogenic micro-organisms or for monitoring water quality. The device allows to detect mobile as well as immobile micro-organisms in water by means of optical methods. The fluctuations of the optical activity belonging to the medium are recorded by means of optical methods. Said fluctuations are related to the mobility of the micro-organisms as well as to metabolic processes which takes place in the micro-organisms. A differential connection is used for recording the optical activity fluctuations in order to improve the measuring sensitivity. The jamming of the examination radiation can thus be suppressed.
Description
Detektor für MikroorganismenMicroorganism detector
Die Erfindung betrifft die Meßtechnik und im speziellen optische Biosensoren. Gegenwärtig werden Mikroorganismen in Flüssigkeiten mit Hilfe des optischen Mikroskops sowie durch Verfahren der Biolumineszenz und der selektiven Einfärbung aufgezeichnet. Der gemeinsame Nachteil aller dieser Verfahren und ihrer meßtechnischen Realisierung ist der niedrige Automatisierungsgrad des Meßvorgangs.The invention relates to measurement technology and in particular to optical biosensors. Microorganisms in liquids are currently recorded using optical microscopy, bioluminescence and selective coloring. The common disadvantage of all of these methods and their metrological implementation is the low degree of automation of the measuring process.
Bekannt ist eine Vorrichtung (Prototyp) für die Aufzeichnung beweglicher Mikroorganismen (BM), die aus einer Laserstrahlungsquelle, einer Küvette und einem Fotoempfänger (FE) besteht, die optisch miteinander gekoppelt sind [1]. Dabei wird das Spektrum der Intensitäts- fluM-uationen der Streustrahlung aufgezeichnet. Dieses Spektrum ist für Brownsche Teilchen (BT) und für BM verschieden. Der Nachteil dieses Verfahrens besteht in seiner geringen Selektivität des Nachweises der Mikroorganismen vor dem Hintergrund des Streusignals der Brownschen Teilchen. Darüber hinaus ist mit diesem Verfahren der Nachweis von unbeweglichen Mikroorganismen (UM) vor dem Hintergrund von Brownschen Teilchen in Flüssigkeit nicht möglich, da sich die Fluktuationsstreuspektren von BT und UM nicht unterscheiden. Ein weiterer Mangel dieses Verfahrens ist in seiner geringen Empfindlichkeit zu sehen, was damit zusammenhängt, daß das Nutzsignal vom Rauschen des Laserstrahiers selbst überlagert wird, was sich beim Einsatz nicht stabilisierter Laser besonders stark bemerkbar macht.A device (prototype) for recording mobile microorganisms (BM) is known which consists of a laser radiation source, a cuvette and a photo receiver (FE), which are optically coupled to one another [1]. The spectrum of the intensity fluctuations of the scattered radiation is recorded. This spectrum is different for Brownian particles (BT) and for BM. The disadvantage of this method is its low selectivity in the detection of the microorganisms against the background of the scatter signal of the Brownian particles. In addition, the detection of immobile microorganisms (UM) against the background of Brownian particles in liquid is not possible with this method, since the fluctuation scatter spectra of BT and UM do not differ. Another shortcoming of this method is its low sensitivity, which is related to the fact that the useful signal is superimposed by the noise of the laser beam itself, which is particularly noticeable when using non-stabilized lasers.
Bekannt ist auch eine „Vorrichtung zur Biotest-Überwachung der Verschmutzung von Flüssigkeiten" [2], bei der zwei Küvetten und zwei Fotoempfänger zum Einsatz kommen. Die Fotoempfänger sind jeweils mit ihrer zugehörigen Küvette optisch gekoppelt und werden von einer gemeinsamen Laserstrahlungsquelle beleuchtet. Dabei werden die Spektren der Streuintensitätsfluktuation in beiden Küvetten beobachtet, und die Differenz ist ein Anzeichen dafür, ob '.n einer der beiden Küvetten nur BM vorliegen oder ob sie unterschiedliche Aktivität in den Küvetten aufweisen. Als Nachteil dieses Verfahrens ist ebenfalls festzustellen, daß der Nachweis unbeweglicher lebender Mikroorganismen vor dem Hintergrund der Brownschen Teilchen nicht möglich ist. Gemeinsamer Mangel der bekannten Verfahren ist, daß das Untersuchungsvolumen, das durch den Durchmesser des Untersuchungsstrahls begrenzt wird, kleiner als das Küvettenvolumen ist. Unter diesen Bedingungen wird möglicherweise das Vorhandensein von Mikroorganismen in der Küvette allein schon deshalb nicht festgestellt, weil sie sich außerhalb des Untersuchungsvolumens befinden. Andererseits führt eine Vergrößerung des Durchmessers des Laserstrahls zu einer gravierenden Verschlechterung der Empfindlichkeit der Vorrichtung. Ein weiterer Nachteil dieser Vorrichtungen besteht in der durch das Rauschen der Laserstrahlung bedingten Beschränkung der Empfindlichkeit, da dieses Rauschen in beiden Aufzeichnungskanälen vorliegt.Also known is a "device for biotest monitoring of the contamination of liquids" [2], in which two cuvettes and two photo receivers are used. The photo receivers are each optically coupled to their associated cuvette and are illuminated by a common laser radiation source observed, the spectra of the scattering intensity fluctuation in the two cuvettes, and the difference is an indication of whether '.n one of the two cuvettes BM present or only if they have different activity in the cells. a disadvantage of this method should also be noted that the detection immovable living microorganisms against the background of Brownian particles is not possible.The common shortcoming of the known methods is that the examination volume, which is limited by the diameter of the examination beam, is smaller than the cuvette volume, under which conditions the presence may become One of the microorganisms in the cuvette is not found, if only because it is outside the examination volume. On the other hand, an increase in the diameter of the laser beam leads to a serious deterioration in the sensitivity of the device. Another disadvantage of these devices is the limitation in sensitivity due to the noise of the laser radiation, since this noise is present in both recording channels.
Ziel der Erfindung ist die Entwicklung einer optischen Variante des Geräts, durch die eine Aufzeichnung von beweglichen wie auch von unbeweglichen lebenden Mikroorganismen in Flüssigkeit vor dem Hintergrund einer großen Zahl von Brownschen Teilchen möglich wird. Das wird dadurch realisiert, daß sowohl die Bewegung (für BM) wie auch der Verlauf der Stoffwechselprozesse (für UM und BM) aufgezeichnet wird. Die Zuverlässigkeit des Nachweises individueller Mikroorganismen sowie die Verbesserung der Empfindlichkeit werden durch eine Vergrößerung des Untersuchungsvolumens und die Unterdrückung des Rauschens der Strahlungsquelle erreicht.
Das Wesen der Erfindung besteht darin, daß eine linear polarisierte Untersuchungsstrahlung die in der Küvette befindliche zu untersuchende Flüssigkeit durchdringt, wobei das Untersuchungsvolumen mit dem Küvettenvolumen übereinstimmt, und die Fluktuationen der optischen Aktivität des Mediums mit BM und UM mit zwei möglichen Verfahren aufgezeichnet werden. Beim ersten Verfahren werden in dem Lichtstrahl, der das Untersuchungsvolumen durchdringt, ein kombinierter Polarisator und Analysator (unter Löschwinkel) und ein Fotoempfänger angeordnet.The aim of the invention is to develop an optical variant of the device which makes it possible to record mobile as well as immobile living microorganisms in liquid against the background of a large number of Brownian particles. This is achieved by recording both the movement (for BM) and the course of the metabolic processes (for UM and BM). The reliability of the detection of individual microorganisms and the improvement in sensitivity are achieved by increasing the examination volume and suppressing the noise of the radiation source. The essence of the invention is that a linearly polarized examination radiation penetrates the liquid to be examined in the cuvette, the examination volume being the same as the cuvette volume, and the fluctuations in the optical activity of the medium with BM and UM being recorded using two possible methods. In the first method, a combined polarizer and analyzer (at an extinction angle) and a photo receiver are arranged in the light beam that penetrates the examination volume.
Das Signal des Fotoempfängers gelangt an einen Verstärker, der einen großen Verstärkungsfaktor aufweist, aber nur den variablen Anteil des Signals verstärkt und den konstanten Anteil nicht aufzeichnet. Hierdurch unterscheidet er sich von den allgemein bekannten Vorrichtungen, die in der Saccharometrie zum Einsatz kommen [3]. Wenn im Untersuchungsvolumen keine optisch aktiven Teilchen vorliegen oder wenn sich ihre Konzentration über die Zeit nicht ändert, dann ist das Ausgangssignal des Verstärkers gleich Null. Wenn dagegen im Untersuchungsvolumen lebende Mikroorganismen vorliegen, führen sie durch ihre Lebensvorgänge und die in ihnen ablaufenden Stoffwechselprozesse und organische chemische Reaktionen zu stochastischen Veränderungen der optischen Aktivität des Mediums. Dabei ist die Amplitude der aufgezeichneten Fluktuationen proportional der Konzentration der Mikroorganismen und der Intensität der in ihnen ablaufenden Stoffwechselprozesse, was es z.B. ermöglicht, die Wirksamkeit verschiedener Antibiotika gegenüber verschiedenen pathogenen Mikroorganismen zu untersuchen. Bei der ersten Variante benötigt die Vorrichtung eine bezüglich der Intensität hochstabilisierte Lichtquelle, da ihr Rauschen direkt vom Fotoempfänger aufgezeichnet und vom Verstärker des variablen Signals verstärkt wird, wodurch der Rauschabstand und dementsprechend die Empfindlichkeit des Geräts beträchtlich verringert werden. Bei der hochempfindlichen zweiten Variante des Geräts wird eine Differenzschaltung für die Aufzeichnung verwendet, bei der die Strahlung nach dem Durchdringen des Untersuchungsvolumens an eine Trennvorrichtung für orthogonale Polarisationen, z.B. ein Glan- Prisma, gelangt, und die Intensität der beiden durch das Prisma aufgetrennten Lichtbündel mit orthogonalen Polarisationen durch zwei Fotoempfänger aufgezeichnet wird, die jeweils mit ihrer Polarisation optisch gekoppelt sind. Die zwei aufzuzeichnenden Signale werden an verschiedene Eingänge des Differenzverstärkers (DV) angelegt, dessen Ausgang mit einer Auswerteeinheit gekoppelt ist, die die mittlere Signalamplitude für eine feste Zeitspanne, die Dispersion und das Fourier-Spektrum ermittelt. Dabei liegt das Rauschen der Lichtquelle gleichzeitig und gleichphasig an beiden Fotoempfängern an und wird vom DV mit hoher Genauigkeit (bis 100 dB) subtrahiert. Dabei wird das Signal der Intensitätsfluktuationen, das mit der Fluktuation der optischen Aktivität zusammenhängt, vom DV nicht nur nicht subtrahiert, sondern sogar verstärkt.The signal from the photo receiver is sent to an amplifier that has a large gain factor, but only amplifies the variable part of the signal and does not record the constant part. This distinguishes it from the generally known devices used in saccharometry [3]. If there are no optically active particles in the examination volume or if their concentration does not change over time, then the output signal of the amplifier is zero. If, on the other hand, living microorganisms are present in the examination volume, they lead to stochastic changes in the optical activity of the medium through their life processes and the metabolic processes and organic chemical reactions taking place in them. The amplitude of the fluctuations recorded is proportional to the concentration of the microorganisms and the intensity of the metabolic processes taking place in them, which is e.g. makes it possible to investigate the effectiveness of different antibiotics against different pathogenic microorganisms. In the first variant, the device requires a light source that is highly stabilized in terms of intensity, since its noise is recorded directly by the photoreceiver and amplified by the amplifier of the variable signal, which considerably reduces the signal-to-noise ratio and accordingly the sensitivity of the device. In the highly sensitive second variant of the device, a differential circuit is used for the recording, in which the radiation, after penetrating the examination volume, is passed to a separating device for orthogonal polarizations, e.g. a glan prism arrives, and the intensity of the two light beams separated by the prism with orthogonal polarizations is recorded by two photo receivers, each of which is optically coupled with their polarization. The two signals to be recorded are applied to different inputs of the differential amplifier (DV), the output of which is coupled to an evaluation unit that determines the mean signal amplitude for a fixed period of time, the dispersion and the Fourier spectrum. The noise of the light source is present at the same time and in phase at both photo receivers and is subtracted from the DV with high accuracy (up to 100 dB). The signal of the intensity fluctuations, which is related to the fluctuation of the optical activity, is not only not subtracted from the DV, but even amplified.
Die Erfindung wird durch vier Abbildungen erläutert. Abbildung 1 zeigt das Prinzipschaltbild der Vorrichtung. Dabei sind 1 - Quelle der stabilisierten linearpolarisierten optischen Strahlung, z.B. ein stabilisierter Laser; 2 - Küvette mit dem zu untersuchenden Medium; 3 - Polarisator und Analysator; 4 - Fotoempfänger; 5 - Verstärker des variablen Signals; 6 - Auswerte- und Anzeigeeinheit.The invention is illustrated by four figures. Figure 1 shows the block diagram of the device. Thereby 1 - source of the stabilized linearly polarized optical radiation, e.g. a stabilized laser; 2 - cuvette with the medium to be examined; 3 - polarizer and analyzer; 4 - photo receiver; 5 - variable signal amplifier; 6 - evaluation and display unit.
Abbildung 2 zeigt das gleiche Prinzipschaltbild, aber mit Differenzschaltung für die Aufzeichnung. Hierbei sind 7 - Glan-Prisma; 8 - Fotoempfänger; 9 - Differenzverstärker.
Auf Abbildung 3 ist die Abhängigkeit der mittleren Fluktuationsamplitude von der Zeit für den Rehydrant der unbeweglichen Mikroorganismen Saccharomyces cerevisiae, die in das Untersuchungsvolumen mit anfänglich sterilem Wasser mit Glukose eingebracht wurden, dargestellt. Es ist ersichtlich, daß keine Fluktuationen und folglich im Verlaufe von ca. 20 Minuten auch keine Stoffwechselvorgänge vorliegen, die für die Aktivierung der Sporen der Mikroorganismen und ein Anwachsen des Signals nach Beginn der aktiven Phase notwendig wären.Figure 2 shows the same block diagram, but with a differential circuit for recording. Here are 7 - Glan prism; 8 - photo receiver; 9 - differential amplifier. Figure 3 shows the dependence of the mean fluctuation amplitude on the time for the rehydrant of the immobile microorganisms Saccharomyces cerevisiae, which were introduced into the test volume with initially sterile water with glucose. It can be seen that there are no fluctuations and consequently no metabolic processes in the course of about 20 minutes, which would be necessary for the activation of the spores of the microorganisms and an increase in the signal after the start of the active phase.
Abbildung 4 zeigt die Abhängigkeit der Dispersion der Fluktuationsampiitude von der Zeit vor und nach Erwärmen des Untersuchungsvolumens auf 80 °C. Es ist eine sprunghafte Verringerung der Dispersion nach der Erwärmung zu verzeichnen, was mit dem partiellen Absterben der Mikroorganismen und der Reduzierung der Stoffwechselprozesse zusammenhängt.
Figure 4 shows the dependence of the dispersion of the fluctuation amplitude on the time before and after heating the test volume to 80 ° C. There is an abrupt decrease in the dispersion after heating, which is related to the partial death of the microorganisms and the reduction in the metabolic processes.
Literaturliterature
1. "Photon Correlation and Ligb' ßeating Spectroscopy", edited by H.Z.Cummins and E.R.Pike, Plenum Press, New York and London, 19741. "Photon Correlation and Ligb 'ßeating Spectroscopy", edited by H.Z. Cummins and E.R. Pike, Plenum Press, New York and London, 1974
2. A.c. CCCP Λ--1406153, KΛ.C 12 M 1/34, 1988.2. A.c. CCCP Λ - 1406153, KΛ.C 12 M 1/34, 1988.
3. JlaHcβepr T.C., OπτHκa, 5 HJA.,M., 1976.
3. JlaHcβepr T.C., OπτHκa, 5 HJA., M., 1976.
Claims
1. Detektor für Mikroorganismen z.B. in Wasser, der aus einer stabilisierten optischen Strahlungsquelle mit linearpolarisierter Strahlung, die mit der Küvette mit der Untersuchungsflüssigkeit optisch gekoppelt ist, einem kombinierten Polarisator und Analysator, einem Fotoempfänger und einer Auswerte- und Anzeigeeinheit besteht, gekennzeichnet dadurch, daß der kombinierte Polarisator und Analysator unter Löschwinkel angeordnet und der Ausgang des Fotoempfängers mit dem Eingang eines Verstärkers für variable Signale gekoppelt ist, dessen Ausgang mit dem Eingang der Auswerte- und Anzeigeeinheit verbunden ist.1. Detector for microorganisms e.g. in water, which consists of a stabilized optical radiation source with linearly polarized radiation, which is optically coupled to the cuvette with the examination liquid, a combined polarizer and analyzer, a photo receiver and an evaluation and display unit, characterized in that the combined polarizer and analyzer under Extinguishing angle arranged and the output of the photo receiver is coupled to the input of an amplifier for variable signals, the output of which is connected to the input of the evaluation and display unit.
2. Detektor gemäß Anspruch 1, gekennzeichnet dadurch, daß als kombinierter Polarisator und Analysator ein Polarisationsprisma eingesetzt wird, das die auftreffende Strahlung in zwei intensitätsgleiche Strahlenbündel mit orthogonaler Polarisation auftrennt und mit zwei Fotoempfängern optisch gekoppelt ist, deren Ausgänge mit verschiedenen Eingängen eines Differenzverstärkers verbunden sind, der nur den variablen Anteil des Signals verstärkt und dessen Ausgang mit dem Eingang der Auswerte- und Anzeigeeinheit verbunden ist. 2. Detector according to claim 1, characterized in that a polarization prism is used as a combined polarizer and analyzer that separates the incident radiation into two beams of the same intensity with orthogonal polarization and is optically coupled to two photo receivers, the outputs of which are connected to different inputs of a differential amplifier , which only amplifies the variable part of the signal and whose output is connected to the input of the evaluation and display unit.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00914026A EP1147386A1 (en) | 1999-02-05 | 2000-02-02 | Detector for micro-organisms |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU99101910 | 1999-02-05 | ||
| RU99101910/13A RU99101910A (en) | 1999-02-05 | DETECTOR OF MICROORGANISMS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2000046579A1 true WO2000046579A1 (en) | 2000-08-10 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/DE2000/000343 WO2000046579A1 (en) | 1999-02-05 | 2000-02-02 | Detector for micro-organisms |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP1147386A1 (en) |
| WO (1) | WO2000046579A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1454124A1 (en) * | 2001-09-26 | 2004-09-08 | Vinoron Technologies Ltd. | Apparatus and method for measuring optically active materials |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4902134A (en) * | 1988-02-03 | 1990-02-20 | Rudolph Research Corporation | Optical amplifier and method for amplifying optical polarization state change effects |
| US5012101A (en) * | 1986-10-24 | 1991-04-30 | National Research Development Corporation | Optical apparatus and method |
| US5427915A (en) * | 1989-06-15 | 1995-06-27 | Biocircuits Corporation | Multi-optical detection system |
| US5671301A (en) * | 1992-12-10 | 1997-09-23 | Sunshine Medical Instruments, Inc. | Optical phase modulator for high resolution phase measurements |
-
2000
- 2000-02-02 WO PCT/DE2000/000343 patent/WO2000046579A1/en not_active Application Discontinuation
- 2000-02-02 EP EP00914026A patent/EP1147386A1/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5012101A (en) * | 1986-10-24 | 1991-04-30 | National Research Development Corporation | Optical apparatus and method |
| US4902134A (en) * | 1988-02-03 | 1990-02-20 | Rudolph Research Corporation | Optical amplifier and method for amplifying optical polarization state change effects |
| US5427915A (en) * | 1989-06-15 | 1995-06-27 | Biocircuits Corporation | Multi-optical detection system |
| US5671301A (en) * | 1992-12-10 | 1997-09-23 | Sunshine Medical Instruments, Inc. | Optical phase modulator for high resolution phase measurements |
Non-Patent Citations (2)
| Title |
|---|
| MAE-WAN HO ET AL: "Imaging liquid crystalline mesophases in living organisms", IEE COLLOQUIUM ON 'NEW MICROSCOPIES IN MEDICINE AND BIOLOGY' (DIGEST NO.1994/149), IEE COLLOQUIUM ON 'NEW MICROSCOPIES IN MEDICINE AND BIOLOGY' (DIGEST NO.1994/149), LONDON, UK, 8 JUNE 1994, 1994, London, UK, IEE, UK, pages 1 - 2, XP000921453 * |
| ZHOU G X ET AL: "SENSITIVE DETECTION OF OPTICAL ROTATION IN LIQUID BY REFLECTION POLARIMETRY", REVIEW OF SCIENTIFIC INSTRUMENTS,US,AMERICAN INSTITUTE OF PHYSICS. NEW YORK, vol. 64, no. 10, 1 October 1993 (1993-10-01), pages 2801 - 2807, XP000400474, ISSN: 0034-6748 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1454124A1 (en) * | 2001-09-26 | 2004-09-08 | Vinoron Technologies Ltd. | Apparatus and method for measuring optically active materials |
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| Publication number | Publication date |
|---|---|
| EP1147386A1 (en) | 2001-10-24 |
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