WO2000067547A2

WO2000067547A2 - Method for detecting serum and for determining the quality thereof, and corresponding devices

Info

Publication number: WO2000067547A2
Application number: PCT/CH2000/000431
Authority: WO
Inventors: Heinz Wagner; Martin Labhart
Original assignee: Optan Ag Mess- U. Analysegeräte
Priority date: 2000-01-31
Filing date: 2000-08-14
Publication date: 2000-11-16
Also published as: WO2000067547A3; AU2000264217A1; CH695000A5

Abstract

The aim of the invention is to provide a means of detecting serum in a container (1) whose wall is at least partially transparent within a predetermined spectral range. To this end, the container is exposed to light radiation (9) and the intensity of the radiation that is transmitted is measured for at least two determined wavelengths μ. The presence or absence of serum in the area of the container being irradiated is determined according to this intensity measurement.

Description

Methods for the detection of serum and for recording its quality and arrangements therefor

The present invention relates to a method for detecting serum according to the preamble of claim 1, a method for detecting the quality of blood serum according to that of claim 2 and arrangements therefor according to claims 7 and 8 respectively.

The large number of blood samples and the variety of analyzes per blood sample require a high degree of automation. Blood test tubes are labeled by the manufacturers with a label with information about specified ingredients etc. and provided with a patient code - usually a barcode - by the user. The labels largely obscure the view of the content, often also completely. In order to process the samples, an automatic analysis by means of an automat requires information about the available amount of the serum in the blood sample tube examined in each case, as well as information regarding the quality of the serum, i.e. Concentration values of fat, blood pigment and bilirubin in order to exclude incorrect results in certain tests in advance.

It is an object of the present invention to automatically detect serum in a container or its quality. This object is achieved when the detection method mentioned at the outset is carried out according to the characterizing part of claim 1 or when the detection method mentioned at the outset is carried out according to the characterizing part of claim 2.

Accordingly, for detection of serum in a container, the latter contains light containing at least parts of the spectrum S.

1000 nm <S <1400 nm exposed. It is based on the knowledge that, in particular, the blood test tubes mentioned with labels and inscriptions in the spectrum mentioned are at least partially transparent. The required partial transparency relates in particular to the wavelengths or bands used in the context of the invention and as will be explained below. The intensity of the transmitted or transflected light is also measured at at least two wavelengths, for which the following applies:

or 1000 nm <λ ₂ <1150 nm.

We understand transflected light as light, which transmits through the container wall, the container contents, i.e. is reflected on the opposite wall of the container, or also by transmission, and reflects back through content and wall: In any case, the light radiation is always transmitted at least once through the contents of the container and at least twice through the walls of the container.

The intensities mentioned are recorded at a predetermined or predeterminable location on the container, and it is further concluded that the presence / absence of serum at the examined location of the container is based on these intensity measurements.

It was therefore recognized that the intensity of the transmitted or transflected radiation, centered in the spectral bands mentioned with respect to λi and λ ₂ , uniquely identifies the presence or absence of serum at the examined container site, regardless of the material the container is therefore independent of whether a blood sample tube preferably used as a container is made of plastic, glass, etc., is further labeled or not or is labeled or not, provided, of course, the wall transmits light at λ _x and λ ₂ .

For the quality detection of blood serum according to the invention, light containing the above-mentioned spectrum S is again used, and the intensity of the transmitted or transflected light is measured at at least two wavelengths λ ₃ and λ ₄ , which are selected from the following wavelengths:

1350 nm ± 30 nm

1290 nm ± 30 nm

1160 nm ± 30 nm

1125 nm ± 30 nm,

preferably 1126 nm

1015 nm ± 30 nm,

preferably 101 ^" 6 nm,

and it is inferred as a function of these intensity values of the quality of the serum, in particular with regard to its fat content. The concentrations of blood pigment and bilirubin can be determined in the visible range of the light spectrum using known methods.

As can be seen, the same spectral bands or frequencies are sometimes used for the quality detection of the blood serum and for the detection of blood serum itself in the respective container to investigate, so that the two methods can be ideally combined, especially with a view to the automatic detection of in-line containers or blood test tubes, the significance of the quality detection increases due to the fact that intensity values are recorded on more than two of the specified frequency bands and be evaluated.

The fact that, in a preferred embodiment of the detection method according to the invention, the intensity detection is shifted relative to the container, and if necessary the quality detection is carried out at the same time, results in an actual level measurement method or serum quantity measurement method or a method that To determine the quality of the serum.

With the measured intensity values at the specific wavelengths λ ₁ λ ₂ or λ ₃ , λ ₄ , actual state vectors result, depending on the number of measured wavelength-specific intensities, in two or more dimensions. The measured intensity values are preferably weighted in the sense of an axis scaling in the vector spaces mentioned.

With such a weighting, the spectral ranges measured at the measured areas may also differ

Intensity of the incident light is taken into account or differences in the transmission of the filters used.

The methods mentioned are preferably used on serum in blood sample tubes, which are preferably obtained in-line in a stream. Arrangements for the inventive serum detection or quality detection are characterized according to the characterizing part of claims 7 and 8, respectively, their preferred embodiments according to claims 9 to 12.

The invention is subsequently explained using figures, for example. Show it: 1: schematically, a blood sample tube with the blood phases;

2: the spectral absorption characteristics of the blood phases gel (a), blood cake (b) and blood serum (c);

3: the spectral absorption characteristics of different, conventional blood sample tubes;

4: the spectral absorption characteristics of conventional blood sample tubes, filled;

5: spectral characteristics of blood serum, normal (a) and too fatty (b);

Fig. 6: in the form of a signal flow / functional block diagram, a system according to the invention, and

FIG. 7: in the form of a signal flow / functional block diagram, a first embodiment of the system according to FIG. 6 with beam splitter;

8: in a representation analogous to FIG. 7, a preferred embodiment with controlled bandpass filtering, which is time-variable in the beam path, and

9: in a representation analogous to FIGS. 7, 8, a simple, now preferred embodiment of the principle according to FIG.

8th.

1 shows a blood sample tube 1 with the phase separation of the blood into serum 3, gel 5 and blood cake 7 which is carried out for analysis. The tube 1 usually consists of transparent material such as glass or plastic and is (not shown) provided with a label . In FIG. 2, typical absorpti curves of blood gel (a), blood cake (b) and blood serum (c) are shown.

3 shows the absorption curves of blood tube walls, adhesive labels and inscriptions of different, customary designs. In practice, ie seizures any blood sample tube with composite desired and quantitatively distributed blood phases, results, as ^"seen from Figs. 2 and 3, a large variation of spectral Überlagerungsmδglichkeiten. For such very different Blutprobenrδhrchen / blood phase combinations result 4, each of the spectral profiles shown in Fig. 4. Each of the spectral profiles of Fig. 4 corresponds to a blood sample-filled blood sample tube of different provenance.

It was recognized according to the invention that when the blood sample tubes 1 mentioned, as containers, contain at least parts of the spectral range S of

1000 nm <S <1400 nm

containing in transmission - or in transflection - be screened - for which the container wall material including accessories such as labels etc. must be transparent at least in parts of the spectral range mentioned, although not necessarily with ^" constant transmission" - the intensity values of the transmitted light at two specific wavelengths λi and λ _2, it is meaningful whether or not the transmission takes place in the serum area 3 with reference to Fig. 1. For wavelengths λ _λ and λ _{2 the} following applies:

1250 nm <λ _x <1400 nm

and 1000 nm <λ ₂ ≤ 1150 nm. 5 shows the spectral profiles of normal serum (a) and blood serum which is too fatty (b).

It should be noted that all spectral profiles are normalized in accordance with FIGS. 2 to 5, i.e. that the absolute transmission values vary by orders of magnitude more - depending on the type of sample, especially on the number of labels.

It is all the more surprising that the transmitted light intensities at at least two of the following wavelengths

1290 nm ± 30 nm

1160 nm ± 30 nm

1125 nm ± 30 nm,

preferably 1126 nm

1015 nm ± 30 nm,

preferably 1016 nm

in the sense of a vector space, two-dimensional or multidimensional areas can be defined, which identify the serum quality, and the quality of a serum sample can be identified by measuring these intensities, by comparing the measured vector with the vector space areas mentioned. By measuring the intensity at more than two of the wavelengths mentioned, the serum qualities can be analyzed more precisely.

6 shows a system according to the invention in the form of a function block / signal flow diagram, in a minimal configuration, which is equally suitable for the design of tection of serum or the detection of the serum level in a blood sample tube or the quality of the serum.

According to FIG. 6, a blood sample tube 1 to be examined, as a container, is irradiated with light in the near infrared range, namely containing at least parts of the spectral range from 1000 nm to 1400 nm, from a schematically represented source 9. The radiation emitted by tubes with labels, lettering etc. and the blood phases is collected in at least two measuring channels 10a and 10b. There it is filtered by filters, preferably interference filters 12a and 12b, for serum detection at least approximated with the center wavelengths λi and λ ₂ , for serum quality detection with the above-defined center wavelengths λ ₃ , λ ₄ . Filters with a bandwidth of at most 200 nm, preferably even at most 100 nm, are preferably used. The intensity of the light transmitted on the output side of the filters 12a or 12b is converted into electrical signals by means of optoelectric converters 14a or 14b and fed to each weighting or amplification unit 16a or 16b, the weighting being achieved in that either the amplifications are compared or the intensity measurement values are each divided by reference intensity measurement values, which are measured when the optical beam path is empty, for example between the tubes. The electrical signals corresponding to the weighted intensity values are then fed to an evaluation unit with arithmetic unit 18, which feeds the input signals together offset.

If I denotes the weighted radiation intensity at λ and I ₂ that at λ ₂ , possibly I ₃ at λ ₃ etc., the computing unit 18 determines the vector I _ιm / l ₂ / l _3m currently measured on the sample - by comparison with an or several pre- _{Mean TARGET} areas B _S0LL are the output of the calculation or. Evaluation unit 18 outputs signals which indicate the presence of serum or which are representative of the quality of the serum present. For the level or serum quantity measurement in the blood sample tube 1, the latter is shifted in the direction y shown in FIG. 6 relative to the light beam transmission and from the output signal of the computing unit 18, which is meaningful for the presence / absence of serum, the level or the level difference and so that the amount of serum in the

Blood sample tube 1 determined.

The arrangement shown schematically is excellently suited for an automatic in-line examination of filled blood sample tubes which occur in rapid succession. For this purpose, the blood sample tubes 1, as shown schematically at 20, are moved in rapid succession through the detection light barrier on a conveyor, such as a belt conveyor or carousel. The cycle length of individual measuring cycles is very short, so that, of course, clocked, but also continuously, the blood sample tubes can be moved through the measuring light barrier. With a correspondingly fast computing capacity, the cycle length is approx. 1 - 5 seconds.

FIG. 7 shows the arrangement analogous to that of FIG. 6, working with a beam splitter 20. The channels on the output side of the beam splitter 20 are provided according to FIGS. 10a and 10b. Of course, the filtering functions according to the filter elements 12a and 12b and beam splitting on the beam splitter 20 can at least partially be combined at least in part by appropriate design of thin-film systems.

8, in a preferred embodiment, the transmitted light beam T is controlled by a controllable filter Order 12 _{c sent} before it strikes the optoelectric transducer arrangement 14 _c . The schematically entered control S sequentially activates one or the other filtering according to the filters 12 _a and 1-2 _b of FIG. 6 in the illustrated single beam path to the optoelectric converter 14 _c . In a preferred embodiment according to FIG. 9, this is achieved by mechanically inserting one or the other of the filter elements 12 _a or 12 into the beam path mechanically, as represented by the double arrow F. In the manner shown in Figs. 8 and 9, the

Design expenditure for the arrangement according to the invention is reduced by practically half compared to an embodiment with channels operated in parallel.

Claims

Claims:

1. Method for the detection of serum in a container, the wall of which in spectrum S applies to which

1000 nm <S <1400 nm,

is at least partially transparent, characterized in that one.

The container is exposed to light containing at least parts of the spectrum S,

• measures the intensity of the transmitted or transflected light at at least two wavelengths λi and λ ₂ , to which applies

1250 nm <λx <1400 nm

1000 nm <λ ₂ ≤ 1150 nm,

at a predetermined or predeterminable location of the container,

• as a function of these intensity measurements, suggests the presence / absence of serum at the said location in the container.

2. Method for determining the quality of blood serum in a container, the wall of which applies to light of the spectrum S to which

1000 nm <S <1400 nm,

is at least partially transparent, characterized in that - exposing the container to light containing at least parts of the spectrum S;

- one measures the intensity of the transmitted or transflected light at at least two wavelengths λ ₃ and λ ₄ , o- when these wavelengths λ ₃ and λ _{4 are} selected from the following wavelengths λ ₀ :

1350 nm ± 30 n

1290 nm ± 30 nm

1160 nm ± 30 nm

1125 nm ± 30 nm,

preferably 1126 nm,

1015 nm ± 30 nm,

preferably 1016 nm

and inferring the quality of the serum in relation to its fat content as a function of these intensity values.

3. The method according to any one of claims 1 or 2, characterized in that one shifts the intensity detection with respect to the container for the detection of the serum fill level and / or the quality.

4. The method according to any one of claims 1 to 3, characterized in that the measured intensity values are each weighted and the weighted intensity values are used to infer the presence / absence of serum or its quality.

5. Use of the method according to one of claims 1 to 4 of serum in blood test tubes, which are preferably obtained in a stream.

6. Use according to claim 5 for the in-line series test on blood sample tubes.

7. Arrangement for the detection of serum in filled containers, the wall of which in spectrum S is at least partially transparent with

l ^' ÖOO nm <S <1400 n,

characterized in that it includes:

a holder for at least one container,

an illumination source for a container in the holder containing at least parts of the spectrum S,

- At least two optical measuring channels, each with an optical bandpass filter, centered around the corresponding wavelengths λi and λ ₂ , for which the following applies:

1250 nm <λ _x <1400 nm

1000 nm <λ ₂ <1150 nm,

with an optoelectric converter arrangement connected downstream of the filter, the output of which is led to an evaluation unit.

8. Arrangement for recording the quality of blood serum in a container, the wall of which is at least partially transparent to light in the spectrum S, to which applies 1000 nm <S <1400 nm,

characterized in that the following are provided:

A holder for at least one container,

An illumination source for a container in the holder with at least parts of the spectrum S,

• At least two optical channels, each with an optical bandpass filter, centered around the corresponding wavelengths λ ₃ , λ ₄ , which are selected from the following wavelengths

1350 nm ± 30 nm

1290 nm ± 30 nm

1160 nm ± 30 nm

1125 nm ± 30 nm

preferably 1126 nm

1015 nm ± 3 nm

preferably 1016 nm,

9. Arrangement according to one of claims 7 or 8, characterized in that the bandpass filters have a bandwidth of at most 200 nm, preferably of at most 100 nm.

10. Arrangement according to one of claims 7 to 9, characterized in that the holder is part of a transport device for several of the containers.

11. Arrangement according to one of claims 7 to 10, characterized in that the outputs of the optoelectric converter arrangement are operatively connected to the adjustable weighting units assigned to the filter.

12. Arrangement according to one of claims 7-11, characterized in that the at least two optical measuring channels act on a common opto-electrical converter of the arrangement and the filters are operated sequentially.

13. Use of the arrangement according to one of claims 7 to 12 for the in-line examination of blood samples in blood sample tubes.