EP2729790A1

EP2729790A1 - Method for measuring the scattered light of particles in a medium

Info

Publication number: EP2729790A1
Application number: EP12732643.7A
Authority: EP
Inventors: Dirk Kurowski; Christian Vesper; Gert Blankenstein
Original assignee: Boehringer Ingelheim Microparts GmbH
Current assignee: Boehringer Ingelheim Microparts GmbH
Priority date: 2011-07-05
Filing date: 2012-07-02
Publication date: 2014-05-14
Also published as: JP2014522968A; WO2013004674A1; US20150036121A1

Abstract

The invention relates to a method for measuring the scattered light (L2) of particles (P, PK) in a measuring medium (F), wherein a measuring container (1) is filled with the measuring medium (F) and incident light (L1) is shone through the measuring medium (F) at least in some regions over a certain path length (1) and in a certain direction and the light (L2) scattered from the incident light (L1) is measured within a certain angle range (a). According to the invention, the incident light (L1) is guided parallel to a longitudinal axis (S) of the measuring container (1). By means of said measures, known methods can be improved, and use is possible even for very small measuring volumes of the measuring medium (F) with accompanying small sizes of the measuring container (1).

Description

description

Method for measuring the scattered light of particles in a medium

The invention relates to a method for measuring the scattered light of particles in a measuring medium, wherein a measuring container is charged with the measuring medium and the

Measuring medium at least partially over a certain path length and in a particular direction with incident light and the light scattered by the incident light is measured light under a certain angle range.

Much known turbidity meter works according to such a method. Turbidity is the colloquial term for an optical phenomenon caused by the scattering of the light on suspended (undissolved) particles which are present in a medium (for example in a liquid).

If a light beam strikes a particle, it is reflected, scattered or absorbed, depending on the size, shape and color of the particle. Depending on particle shape and

Surface texture, the light is scattered with different intensity in all directions.

On the measurement of turbidity can thus draw conclusions about the purity of a

Be drawn measuring medium.

Turbidity measurements are therefore used in many fields of application. Thus, the turbidity measurement in the process / quality control of various industries, such. As food industry, water treatment, cosmetic and chemical industries an important role. In medical diagnostics, for example, antigen or antibody reactions (for example blood clotting) and the state of protein compounds in body fluids are determined by measuring the turbidity.

The turbidity measurement of measuring media, such as liquids, is carried out in the prior art either by means of absorption measurements (transmitted light measurements) or by means of scattered light measurements.

In transmitted light measurement, a bundled light beam is passed through the measuring medium and the light loss of the transmitted beam is determined. The thus determined Scattering coefficient corresponds to the totality of the scattered light that has been removed from the incident light beam.

In the scattered light measurement, a photosensitive detector is arranged in an axis in which scattered light is to be measured. The majority of the usual measures

Turbidity meters according to the so-called 90 ° scattering method, so that the detector for measuring the scattered light is at an angle of 90 ° to the axis of the incident light beam.

The transmitted light measurement is only suitable for stronger turbidity, while the scattered light measurement is preferably for weaker turbidity, ie low

Particle concentration is used.

As a rule, turbidimeters used in the pharmaceutical laboratory work according to the 90 ° scattering method. Typical turbidimeters typically require

Measuring volume of more than 10 ml, which is inappropriate especially for expensive sample liquids (eg, high-purity protein solutions), because this is a waste of valuable sample liquid.

Thus, measurement arrangements for the turbidity measurement are desirable, which can also be used with much smaller measurement volumes than with commercial laboratory equipment.

The basic problem with conventional measuring arrangements is that the path length of the incident light in the volume of the medium to be measured becomes too small at the measuring volumes customary in laboratory operation, in particular at low turbidity values, in order to produce sufficient "scattering potential" for a measurement. Of course, this risk increases with decreasing sample or measuring volume. Another problem is that small sample volumes also cause small measuring containers (cuvettes), which leads to disturbing scattering on the cuvette walls. Here, light signals are generated, which may be comparable to the signals of the actual turbidity measurement and therefore lead to measurement errors.

In order to be able to measure turbidity comparable, a turbidity standard liquid "formazine" was created, which can be easily reproduced from commercially available chemicals according to a recipe from the standard ISO 7027 at any time. This makes a calibration of turbidimeters well possible. The most common units for turbidity, which relate to dilutions of the liquid of formazine, are the following:

FNU (Formazine Nephelometrie Units, scattered light measurement with an angle of 90 ° in accordance with ISO 7027), FAU (Formazine Attenuation Units, transmitted light measurement at an angle of 0 degrees in accordance with ISO 7027), FTU (Formazine Turbidity Unit, use in the

Water treatment), NTU (Nephelometry Turbidity Unit, scattered light measurement at an angle of 90 ° according to USA regulations) and TE / F (turbidity unit / formazine, German unit used in water treatment).

In this case, light in the invisible wavelength range (for example 650 nanometers or 860 nanometers) is used as measurement light.

From DE 28 47 712 A1 discloses a turbidity meter is known which after a

Method with the features of the preamble of claim 1 operates. The

Turbidity meter has a housing in which a tubular measuring container can be received, further a light source are emitted by the light rays transverse to the longitudinal axis of the measuring container. A photosensitive detector is within the

Housing aligned at a right angle to the incident light beam and centric to a stray light axis. To reduce the sensitivity of the

Turbidity meter opposite not attributable to stray light light signals such. As internal reflections of the incident light beam and possibly reaching the detector ambient light, a plurality of optical shields (apertures) are provided around the detector and also to the measuring container in a very specific spatial arrangement.

However, the turbidimeter shown in this document is not suitable for very small volumes of measurement that may be preferred in the pharmaceutical laboratory.

The invention is therefore based on the object to improve a method according to the preamble of claim 1 and to provide a device suitable for this, which is suitable for the turbidity measurement of occurring in particular in the pharmaceutical laboratory area, very small measurement volumes. This object is achieved by the characterizing the features of patent claims 1 and 8.

Advantageous developments and refinements of the invention are the respective ones

Subclaims refer.

The invention is therefore based on a method for measuring the scattered light of

Particles in a measuring medium, wherein a measuring container with the measuring medium

acted upon and the measuring medium at least partially over a certain

Path length and illuminated in a particular direction with incident light and the light scattered by the incident light is measured under a certain angle range.

According to the invention, it is provided that the incident light is guided parallel to a longitudinal axis of the measuring container.

This makes it possible in a surprisingly simple way to achieve a satisfactory measurement of turbidity even at very small volumes, which require correspondingly small measuring container. Even with very small volumes of the measuring container, for example of approximately 100 μΙ, an adequate path length of the incident light beam for a sufficient measurement can be generated by the measuring medium. For example, a cuvette with an inside diameter of 3 mm and a volume of 100 μΙ measuring liquid allows a path length of the light in the sample of around 14 mm. Another advantage of this measuring method is that interfering interfaces, through which the incident light beam passes (in particular in the region of the walls of a measuring container), in this way have a much greater distance from each other than in known measuring arrangements.

According to a very expedient embodiment of the inventive concept is further provided that the incident light is guided in the axis of symmetry of the measuring container. As a result, a maximum distance to the boundary surfaces of the measuring container can also be achieved perpendicular to the incident light beam, which leads to a reduction of the reflection of the scattered light at the boundary surfaces to the wall of the measuring container. The scattered light can thus also be better decoupled from the measuring container. It has also proved to be advantageous if the scattered light is measured at an angle of approximately 90 ° to the incident light. This is high

Sensitivity even at low turbidity levels, so the presence of only small or small particles, possible.

The measurement sensitivity in the method can be further increased if the scattered light is focused before a measurement. This can be done for example by means of a simple optic such. B. a converging lens or a lens. The scattered light can thereby be directed in a simple manner to, for example, a photodetector, wherein even larger scattering angles of the scattered light from the photodetector can still be detected. The opening angle of the detector is thus virtually increased. Moreover, by focusing said optics on the incident light beam, interfering reflections and scattering at the interfaces of the measuring container are minimized for the detector.

A further development of the invention also provides that an optic with an aperture is used for focusing the scattered light, which is smaller than the path length of the incident light through the measuring medium. In this case, the aperture of the optics is aligned such that it is approximately centered to said path length. This also helps to reduce disturbing reflections and scattering at occurring boundary surfaces of the measuring container (air / liquid, liquid / measuring container bottom) for the detector.

It has been found that the use of a rotationally symmetrical, in particular cylindrical measuring container provides optimum measurement results. This leads to a very good decoupling of the scattered light from the measuring container.

It is expedient to use the light of a laser as light, because thus monochromatic and in particular parallel light beams can be generated. The

Light radiation can thus be adjusted very accurately in a measuring arrangement.

Preferably, the wavelength of the laser light used in the near

Infrared range (NIR), ie at a wavelength between about 780 to 3000 nm.

As already mentioned, the invention also relates to a device for carrying out the method according to the invention.

The invention is based on a device comprising at least one receptacle for a measuring container which can be filled with a measuring medium, at least one light source for Generation of at least one incident into the measuring container light beam and at least one detector for measuring scattered light.

For carrying out the method according to the invention, it is now provided according to the invention that in the device the generated light has a beam path which runs at least in sections parallel to a longitudinal axis of a measuring container located in the receptacle.

According to a development of the device, it can be provided that at least one deflecting unit is provided in the beam path for deflecting the light beam, in particular by 90 °. Such a deflection unit can be realized for example by a prism or a mirror. The advantage can be seen in the fact that, for example, thereby the overall height of the device can be reduced.

Alternatively, however, the use of a beam splitter is conceivable in which a part of the light beam emitted for measurement is passed before introduction into the measuring container on a second detector and then the optical power of the input light beam can be monitored via a corresponding evaluation unit. By forming a ratio of input and output signal fluctuations in the power of the light source can thus be compensated or readjusted.

It is also expedient to provide that in front of the detector optics for

Bundling of the scattered light is provided. The optics can be for example a

Condensing lens or a lens. As already mentioned, the opening angle of the detector for incident stray radiation can thereby be virtually increased, which ultimately leads to an increase in the measuring sensitivity of the device.

So that the use of rotationally symmetrical measuring container in connection with the device is possible, the recording of the device should also be suitable for holding rotationally symmetrical measuring container expediently.

To attenuate scattering at occurring interfaces for the detector, a measuring container can be inserted into the receptacle such that an aperture of the optics is smaller than a path length of an incident light beam in the measuring container by the

Measuring medium and the aperture is aligned approximately centrally to said path length. Further advantages and embodiments of the invention are based on

Embodiments clear, which will be explained in more detail with the aid of the accompanying figures. Mean

1 is a schematic representation of the method according to the invention,

Fig. 2 is a schematic representation of a device according to the invention for

Implementation of the method and

Fig. 3 is a schematic representation of known methods according to the prior

Technology.

First, reference is made to FIG. 1.

Therein, a cylindrical measuring container 1 with a diameter D and a length L can be seen. The measuring container 1 is partly filled with a measuring liquid F.

In the liquid F undissolved particles P are present, which lead to a turbidity of the liquid F.

To measure the turbidity of the liquid F, the procedure is as follows:

It is generated with a suitable light source (not shown) in the measuring container 1 and in the liquid F incident light beam L1. In this case, the incident light beam L1 through the liquid F performs a path length I.

It can be seen that the incident light beam L1 is guided parallel to a longitudinal axis of symmetry S of the measuring container 1, in particular in this axis of symmetry S.

By way of example, here a collision particle PK is exposed, on which the incident

Light beam L1 is scattered. This results in scattered light beams L2, which are focused by means of a converging lens 3 to light rays L3 and so directed to a detector 4 (for example, photodiode). The detector 4 is aligned in a measuring axis M, which is at an angle α of about 90 ° to the incident light beam L1.

Furthermore, it can be seen that the measuring method is carried out in such a way that the path length l of the incident light L 1 through the liquid F is greater than an aperture A of FIG

Conveying lens 3. In this case, the aperture A of the converging lens 3 is aligned approximately centrally to the path length I.

Referring now to Figure 2, a turbidimeter 10 is shown. The turbidity meter 10 has a receiving opening 1 1 for receiving a cylindrical measuring container 18. For holding the measuring container 18 holding elements 19 are provided, which abut at different circumferential points of the measuring container 18.

The measuring container 18 is partially filled with a liquid F to be measured.

To carry out a measurement, the user can now start an appropriate measuring program by means of an input unit 16 (for example a pressure-sensitive LCD screen, so-called "touchscreen").

The inputs of the user are via a suitable control, storage and

Evaluation unit 17 processes and cause a laser unit 12 to emit a light beam L0 over a predetermined measurement period. The light beam L0 is deflected by an optical deflection unit 13 in the form of a prism by 90 ° such that a light beam L1 is incident in the measuring container 18 and thus in the liquid F and this transilluminates.

Alternatively (shown in dashed lines), the deflection unit 13 but also in the form of a beam splitter (13 ') may be formed, which leads to a division of the light beam L0 in a

Light beam L0 'and the light beam L1 leads. The divided light beam L0 'can then be directed to a detector 25 connected to the evaluation unit 17.

As a result, the optical power of the input light beam L0 can be monitored. By forming a ratio of input and output signal fluctuations in the power of the laser unit 12 can thus be compensated or readjusted. It can be seen that the light beam L1 is guided through an axis of symmetry S of the cylindrical measuring container 18. In this case, the light beam L1 through the liquid F performs a path length I. For measuring the turbidity due to particles in the liquid F is in a measuring axis M, which is arranged at an angle α of about 90 ° to the light beam L1, a detector 15 in Formed a photodiode. This detector 15 is signal-wise connected to the control, storage and evaluation unit 17.

In this case, light rays L2 scattered in the liquid F are concentrated by a converging lens 14, which is arranged in front of the detector 15 and has an aperture A, in the direction of the light rays L3. It can be seen that the aperture A is selected smaller than the path length I of the light beam L1 through the liquid F, wherein the measuring container 18 is inserted in the receiving opening 1 1, that the aperture A is aligned approximately centrally to the said path length I. ,

In addition, it can be provided that an interference filter (not shown), whose transmission range corresponds to the wavelength of the laser light, is arranged in front of the detector 15. As a result, the sensitivity to extraneous light, which does not originate from the laser unit 12, can be reduced.

Furthermore, a protective cover 24 is provided, which exits the user from

Light radiation L1 protects. The protective cover 24 is designed to be flexible and / or displaceable (see double arrows), in order to facilitate insertion of the measuring container 18 into the receiving opening 1 1 despite the protective cover 24.

In connection with FIG. 3, finally, brief reference will now be made to the known state of the art.

Therein, a measuring container 20 can be seen in which liquid F to be measured is located. To measure the turbidity of the liquid F, a light beam L4 is initially generated by means of a light source 21, which light enters the measuring container 20 and emerges therefrom again as a transmitted light beam L6. The intensity of the transmitted light beam L6 is measured by a detector 22, from which the turbidity of the fluid F can be deduced. The detector 22 is arranged in a measuring axis M2, which coincides with the axis of the light beam L4. Hereby, in principle, a transmitted light measurement is realized.

Furthermore, the principle of operation of a scattered light measurement is shown. In this case, a detector 23 is arranged in a measuring axis M1, which is arranged at an angle of approximately 90 ° to the axis of the light beam L4. The detector 23 now measures light rays L5 generated due to scattering in the liquid F. In this case, the measuring container 20 is a cuvette with an axis of symmetry S.

In particular, at predetermined by the wall of the measuring container 20 interfaces G1 to G4 occur disturbing scattering and multiple reflections of the light beam L4, which is more pronounced with decreasing size of the measuring container 20.

LIST OF REFERENCE NUMBERS

I measuring container

3 condenser lens

4 detector

10 turbidity meter

I I receiving opening

12 laser unit

13 deflection unit

13 'beam splitter

14 condenser lens

15 detector (photodiode)

16 input unit

17 Control memory and evaluation unit

18 measuring containers

19 holding elements

20 measuring containers

21 light source

22 detector

23 detector

24 protective cover

25 detector

A aperture of the condenser lens

D Diameter of the measuring container

F liquid

G1 -G4 interfaces

I path length of the incident light through the liquid

L Length of the measuring container

L0 light beam

L0 'split light beam

L1 incident light beam

L2 scattered light beam

L3 bundled light beam L4 incident light beam

L5 scattered light beam

L6 transmitted light beam

M measuring axis for scattered light

M1 measuring axis for scattered light

M2 measuring axis for transmitted light

P particles

PK collision particles

S Symmetry axis of the measuring tank

α angle between incident light beam and measuring axis for stray light

Claims

claims

1 . Method for measuring the scattered light (L2) of particles (Ρ, ΡΚ) in one

Measuring medium (F), wherein a measuring container (1, 18) subjected to the measuring medium (F) and the measuring medium (F) at least partially through a certain path length (I) and in a particular direction (S) with incident light (L1) and the light (L2) scattered by the incident light (L1) is measured (4,15) below a certain angular range (a), thereby

in that the incident light (L1) is guided parallel to a longitudinal axis (S) of the measuring container (1, 18).

2. The method according to claim 1, characterized in that the incident light (L1) in the axis of symmetry (S) of the measuring container (1, 18) is guided.

3. The method according to claim 1 or 2, characterized in that the scattered light (L2) at an angle (a) of approximately 90 ° to the incident light (L1) is measured.

4. The method according to any one of claims 1 to 3, characterized in that the scattered light (L2) before a measurement (4) bundled (3, L3) is.

5. The method according to claim 4, characterized in that for bundling the scattered light (L2) an optic (3) with an aperture (A) is used, which is smaller than the path length (I) of the incident light (L1) through the Measuring medium (F) and the aperture (A) of the optics (3) is aligned such that this (A) is approximately in the middle of said path length (I).

6. The method according to any one of claims 1 to 5, characterized in that a rotationally symmetrical measuring container is used as a measuring container (1, 18).

7. The method according to any one of claims 1 to 6, characterized in that as light (L0, L1), the light of a laser, preferably having a wavelength in the near infrared range, is used.

8. Device (10) for carrying out the method according to one of claims 1 to 7, comprising at least one receptacle (1 1) for a measuring medium (F) can be filled with a measuring container (18), at least one light source (12) for generating at least one in the measuring container (18) incident light beam (L1) and at least one detector (15) for measuring scattered light (L2), characterized in that in the device (10) the generated light (L0) a

Beam path (L0, L1) which extends at least in sections (L1) parallel to a longitudinal axis (S) of a in the receptacle (1 1) located measuring container (18).

9. Device (10) according to claim 8, characterized in that in the beam path (L0, L1) at least one deflection unit (13) for deflecting the light beam (L0), in particular by 90 °, is provided.

10. Device (10) according to claim 8 or 9, characterized in that in front of the detector (15) has an optical system (14) for focusing (L3) of the scattered light (L2) is provided.

1 1. Device (10) according to one of claims 8 to 10, characterized in that the receptacle (1 1) is suitable for mounting rotationally symmetrical measuring container (18).

12. Device (10) according to claim 10 or 1 1, characterized in that a measuring container (18) in such a way in the receptacle (1 1) is insertable, that an aperture (A) of the optical system (14) is smaller than a path length ( I) of a light beam (L1) incident in the measuring container (18) through the measuring medium (F) and the aperture (A) is oriented approximately centrally to said path length (I).

13. Device (10) according to any one of claims 8 to 12, characterized in that in front of the detector (15) an interference filter is arranged, whose

Transmission range of the wavelength of the generated light (L0) corresponds.