METHOD AND DEVICE FOR QUALITY CONTROLLING A BLOOD-BASED PRODUCT

Abstract

A method and device for quality controlling a blood-based product. In order to control the quality of a blood-based product which comprises an erythrocyte concentrate, a thrombocyte concentrate, a granulocyte concentrate, a leukocyte concentrate, whole blood and/or blood plasma, a Raman spectrum is recorded. By means of evaluating the Raman spectrum, it is determined whether the blood-based product can be used for a transfusion.

Claims

1. A method for quality controlling a blood-based product, which comprises an erythrocyte concentrate, a thrombocyte concentrate, a granulocyte concentrate, a leukocyte concentrate, whole blood or blood plasma, wherein the method comprises: recording a Raman spectrum by means of Raman spectroscopy of a sample of the blood-based product, and determining whether the blood-based product is usable for a transfusion by evaluating the Raman spectrum.

2. The method according to claim 1, wherein the evaluating of the Raman spectrum includes identifying a functional modification of cells of at least one cell type of the blood-based product, wherein the cell type is selected from a group consisting of erythrocytes, thrombocytes, granulocytes and leukocytes.

3. The method according to claim 2, wherein the evaluating of the Raman spectrum further comprises quantitatively determining which proportion of the cells of at least one cell type is subject to a functional modification.

4. The method according to claim 3, wherein the quantitatively determining of which proportion of the cells of at least one cell type is subject to the functional modification further comprises respectively subjecting a plurality of recorded Raman spectra to a principal component analysis.

5. The method according to claim 1, wherein the evaluating of the Raman spectrum further comprises identifying the presence of bacteria or other impurities in the blood-based product.

6. The method according to claim 1, wherein the evaluation of the Raman spectrum comprises a spectral analysis of the Raman spectrum.

7. The method according to claim 1, further comprises: recording of the Raman spectrum; and wherein the recording of the Raman spectrum further comprises: collecting at least one cell of the sample in an optical trap.

8. The method according to claim 7, wherein the optical trap is produced by an excitation beam of a Raman spectroscopy system.

9. The method according to claim 7, comprising wherein the at least one cell is selected from a group consisting of erythrocytes, thrombocytes, granulocytes and leukocytes.

10. A device for quality controlling a blood-based product which comprises an erythrocyte concentrate, a thrombocyte concentrate, a granulocyte concentrate, a leukocyte concentrate, whole blood and/or blood plasma, wherein the device comprises: a Raman spectroscopy system that records a Raman spectrum of a sample of the blood-based product, and an evaluation device which is coupled to the Raman spectroscopy system and uses the recorded Raman spectrum to determine whether the blood-based product is usable for a transfusion.

11. The device according to claim 10, wherein the evaluation device performs a cluster analysis and identifies a functional modification of cells of at least one cell type of the blood-based product, wherein the cell type is selected from a group consisting of erythrocytes, thrombocytes, granulocytes and leukocytes.

12. The device according to claim 11, wherein the evaluation device quantitatively determines from the cluster analysis which proportion of the cells of the at least one cell type is subject to a functional modification.

13. (canceled)

14. A device for identifying a contamination, a disease or a progression of disease, wherein the device comprises: a Raman spectroscopy system that records at least one Raman spectrum of at least one blood sample, and an evaluation device which is coupled to the Raman spectroscopy system and which automatically identifies the disease or the progression of disease using the recorded at least one Raman spectrum.

15. The device according to claim 14, wherein the disease is selected from a group consisting of tumour diseases, blood coagulation disorders and thrombosis.

16. The device according to claim 11, wherein the cluster analysis performed by the evaluation device is a principal component analysis.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0063] The invention is explained further by means of preferred exemplary embodiments below with reference to the drawing.

[0064] FIG. 1 shows a schematic illustration of a device according to an exemplary embodiment.

[0065] FIG. 2 is a flow diagram of a method according to an exemplary embodiment.

[0066] FIG. 3 shows a schematic illustration of a Raman spectrum which is evaluated by devices and methods according to exemplary embodiments.

[0067] FIG. 4 shows a schematic illustration of a Raman spectrum which is evaluated by devices and methods according to exemplary embodiments.

[0068] FIG. 5 shows a schematic illustration of a static evaluation of the Raman spectrum of a sample.

[0069] FIG. 6 shows a schematic illustration of a static evaluation of the Raman spectrum of a further sample.

[0070] FIG. 7 shows a schematic illustration of a static evaluation of the Raman spectrum of a sample.

[0071] FIG. 8 shows a schematic illustration of a static evaluation of the Raman spectrum of a further sample.

[0072] FIG. 9 shows a schematic illustration of Raman spectra which are evaluated by devices and methods according to exemplary embodiments.

[0073] FIG. 10 shows a schematic illustration of the Raman spectroscopy in combination with an optical trap.

[0074] FIG. 11 shows a schematic illustration of a reserve which is configured for performing the method on the closed reserve.

DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0075] The features of the different described embodiments can be combined with each other, insofar as this is not expressly excluded in the description below.

[0076] Devices and methods according to exemplary embodiments can be used for quality controlling blood-based products. The term “blood-based product” here includes reserves with erythrocyte concentrate, reserves with thrombocyte concentrate, reserves with granulocyte concentrate, reserves with leukocyte concentrate, reserves with whole blood and reserves with blood plasma. Granulocyte concentrates also contain other leukocytes in addition to granulocytes which can cause a GvHD (graft versus host) reaction in the recipient. The reproductive capability of the lymphocytes is irreversibly impaired by means of irradiation. A leukocyte concentrate is obtained by means of leukapheresis from donor blood and in particular contains granulocytes. The leukocyte concentrate is maintainable only for a few hours and is administered for infection prophylaxis in the case of pronounced, but reversible leukocyte deficiency.

[0077] In the case of devices and methods according to exemplary embodiments, a Raman spectrum of a sample of the blood-based product is recorded. The Raman spectrum is evaluated in order to determine whether the blood-based product is still suitable for a transfusion. The blood-based product can be a blood reserve, wherein for example an erythrocyte concentrate, a thrombocyte concentrate, a granulocyte concentrate, a leukocyte concentrate, whole blood or blood plasma is contained in a suitable container.

[0078] FIG. 1 is a schematic illustration of a device 1 according to an exemplary embodiment. The device 1 is configured to determine whether a blood reserve 2 is suitable for a transfusion. The corresponding determination takes place by means of a Raman spectrum which the device 1 records and can automatically evaluate. A sample of a blood-based product 3, which may for example be an erythrocyte concentrate, a thrombocyte concentrate, a granulocyte concentrate, a leukocyte concentrate, whole blood or blood plasma, is used for a Raman spectroscopy in order to determine whether the blood-based product 3 may be used for a transfusion. The manufacture of the blood reserve 2, which can be carried out according to conventional techniques, is not subject matter of the methods and devices disclosed here.

[0079] The device 1 comprises a Raman spectroscopy system 10 and an evaluation device 20. The Raman spectroscopy system 10 is configured to record a Raman spectrum of a sample 9 of the blood-based product 3. A quantity of the blood-based product 3 can be removed from the blood reserve 2 and after further processing can be prepared as a sample 9 for the Raman spectroscopy system 10. The sample 9 can contain blood cells which are movable in a solution. The sample 9 can contain dried blood or a pellet which is produced from the blood-based product 3.

[0080] In the case of further designs, the Raman spectroscopy system 10 can also be designed such that the Raman spectrum is recorded directly on the blood reserve 2 without a quantity of the blood-based product 3 having to be first removed from said blood reserve. An entire blood reserve can then be inserted into the Raman spectroscopy system.

[0081] The Raman spectroscopy system 10 comprises a light source 11 which can in particular be a laser. The light source 11 is configured to output an excitation beam 17. The excitation beam 17 can for example have a wavelength in the range between 700 nm and 1064 nm, e.g. approximately 785 nm. A Raman spectrometer 14 receives light 18 scattered on the sample 9 by Stokes processes and/or Anti-Stokes processes. The Raman spectrometer 14 can comprise a diffractive element 15 and an image sensor 16 in order to record the Raman spectrum of the sample 9. The Raman spectroscopy system 10 can comprise further elements in a manner known per se, for example focussing optical elements 12, 13, which can be designed as lenses, and/or diaphragms.

[0082] Then device 1 comprises an evaluation device 20. The evaluation device 20 can be a computer or can comprise a computer. The evaluation device 20 is coupled to the Raman spectroscopy system 10. The evaluation device 20 can control the recording of the Raman spectrum by the Raman spectroscopy system 10.

[0083] The evaluation device 20 comprises an interface 21 in order to receive data from the image sensor 16 of the Raman spectroscopy system 10. The evaluation device comprises an integrated semi-conductor circuit 22 which can comprise a processor or controller and which is configured to evaluate the recorded Raman spectrum in order to determine [Translator—end of sentence is missing]. The integrated semi-conductor circuit 22 is configured to determine by means of the Raman spectrum whether the blood reserve 2 can still be used for a transfusion. The integrated semi-conductor circuit 22 can be configured in particular in order to determine by means of evaluating the Raman spectrum whether and to what extent the functionality of the cells is impaired. The integrated semi-conductor circuit 22 can be configured to determine by means of evaluating the Raman spectrum whether a cell death of erythrocytes and/or thrombocytes and/or granulocytes and/or leukocytes has occurred. The integrated semi-conductor circuit 22 can be configured to determine by means of evaluating the Raman spectrum whether biological molecules of the cells are present, which impair the function of the cell.

[0084] As is described in detail with reference to FIG. 2 to FIG. 11, the integrated semi-conductor circuit 22 can be configured to identify the presence or absence of determined Raman peaks or to determine the spectral weight of Raman peaks which relate to the quality of the blood reserve 2. For example, the integrated semi-conductor circuit 22 can identify and/or further evaluate Raman peaks, which are assigned to red blood cells or which are assigned to a cell death of erythrocytes and/or thrombocytes, granulocytes, leukocytes. The integrated semi-conductor circuit 22 can be configured to evaluate for example the Raman spectrum in at least one predefined wavenumber range, e.g. the Raman spectrum in the wavenumber range between 1296 cm.sup.−1 and 1333 cm.sup.−1 in order to determine whether the blood-based product 3 can be used for a transfusion.

[0085] The integrated semi-conductor circuit 22 can be configured to automatically verify the sterility of the blood reserve 2 by analysing the Raman spectrum. The integrated semi-conductor circuit 22 can be configured to identify one or a plurality of Raman peaks, which are assigned to impurities, for example bacteria or viruses, in order to determine whether the blood reserve 2 is sterile.

[0086] The evaluation device 20 can comprise a memory 23 in which comparative data 24 is stored which the integrated semi-conductor circuit 22 can use when evaluating the Raman spectrum.

[0087] Information regarding the position and/or the spectral weight of different Raman peaks for the different cell types of one or a plurality of blood-based products can be stored in a non-volatile manner in the memory 23 of the device 1. Alternatively or additionally, the information regarding the position and/or the spectral weight of different Raman peaks for the different blood-based products can be determined by the device 1 by means of methods of supervised learning or other machine learning techniques.

[0088] The evaluation device 20 can comprise an optical and/or acoustic output unit 25, via which the information dependent on the analysis of the Raman spectrum is output, which shows whether or not the blood reserve 2 can still be used. The output unit 25 can also be structurally integrated into a housing of the evaluation device 20 or of the Raman spectroscopy system 10.

[0089] Even though the evaluation device 20 and the Raman spectroscopy system 10 in FIG. 1 are schematically illustrated as separate units, the functions of the evaluation device 20 can also be integrated into a housing of the Raman spectroscopy system 10. The Raman spectroscopy system 10 and the evaluation device 20 can be designed as mobile, in particular portable units.

[0090] FIG. 2 is a flow diagram of a method 30. The method 30 can be performed fully automatically by the device 1 without intermediate operational actions of a user or it can be performed dependent on user inputs. A sample 9 can be obtained from the blood-based product 9. For example, a quantity of the blood-based product 3 can be removed from the blood reserve 2 using a syringe. The quantity of the blood-based product 3 removed can be thinned in order to produce the sample 9. More than one sample can also be produced and analysed using Raman spectroscopy. For example, impurities can be firstly concentrated from samples of blood-based product removed from the blood reserve 2, for example by separating erythrocytes and/or thrombocytes and producing conditions which lead to a reproduction of any impurities present in the removed sample.

[0091] In this manner, the quantitative determination of impurities can be improved for verifying the sterility. The sample 9 can also be present in solid form. For example, the removed quantity of the blood-based product 3 can be a droplet, which is firstly left to evaporate in order to use the material remaining after evaporation as the sample 9. The sample 9 can be a pellet.

[0092] In the case of step 31, the device 1 receives the sample 9. For example, a sample holder 19 can be automatically drawn in after the sample 9 has been placed there.

[0093] In the case of step 32, a Raman spectrum of the sample 9 is recorded. The light source 11 is controlled such that an excitation beam 17 is produced. The excitation beam 17 or a beam of electromagnetic radiation different from the excitation beam 17 can produce an optical trap in which cells of the sample 9 are collected for Raman spectroscopy, for example if the sample 9 is liquid.

[0094] A plurality of Raman spectra can also be recorded. For example, a plurality of Raman spectra can be recorded for the same sample or different samples in order to determine from a Raman spectrum whether the erythrocytes and/or thrombocytes and/or leukocytes are alive and in order to determine from a different Raman spectrum how many impurities the blood reserve contains.

[0095] In the case of step 33, the evaluation device 20 evaluates the recorded Raman spectrum. The evaluation device 20 can identify Raman peaks, which are for example assigned to guanine, deoxyribonucleic acid or to a cell death of erythrocytes or thrombocytes. The evaluation device 20 can identify Raman peaks which are assigned to red blood cells. The evaluation device 20 can carry out a static evaluation of the Raman spectrum, for example by means of a spectral analysis.

[0096] In the case of step 34, depending on the evaluation of the Raman spectrum, it is verified whether the blood reserve 2 with the blood-based product 3 may be used for a transfusion. To this end, the evaluation device 20 can for example compare a spectral weight of a Raman peak, which is assigned to the cell death of erythrocytes or thrombocytes, with a threshold value. Depending on whether the spectral weight of Raman peaks, which is associated with the cell death of erythrocytes or thrombocytes, is greater than the threshold value, it can be determined that the sample is no longer suitable for the transfusion. Alternatively or additionally, data points, which have been determined by a spectral analysis of the Raman spectrum, can be used in order to determine whether the blood reserve is already old or has been stored such that it can no longer be used for a transfusion. Alternatively or additionally, it can be determined by means of the analysis of the Raman spectrum whether the sample is still sterile. A type and a number of impurities can be estimated.

[0097] In the case of step 35 or step 36, an output unit is actuated such that information is indicated, which shows whether or not the blood reserve can still be used.

[0098] FIG. 3 schematically shows a Raman spectrum 40 which is evaluated by the evaluation device 20. The Raman spectrum 40 can comprise a plurality of Raman peaks 41, 42 which can be automatically identified by the evaluation device 20 and which provide information regarding whether the blood reserve can still be used. The Raman peaks 41, 42 can for example be associated with substances which indicate a cell death (e.g. apoptosis) of erythrocytes or thrombocytes. The Raman peaks 41, 42 can be assigned to red blood cells. For example, one or a plurality of the analysed Raman peaks can be in wavenumbers which are selected from the group consisting of 669 cm.sup.−1, 750 cm.sup.−1, 752 cm.sup.−1, 999 cm.sup.−1, 1122 cm.sup.−1, 1210 cm.sup.−1, 1444 cm.sup.−1, 1543 cm.sup.−1 and 1617 cm.sup.−1.

[0099] The evaluation device 20 can, in a targeted manner, analyse only a predefined wavenumber range or a plurality of predefined wavenumber ranges of the Raman spectrum 40 in order to determine whether the blood reserve is still suitable for a transfusion. The evaluation device 20 can for example analyse a wavenumber range of 1200 cm.sup.−1 to 1400 cm.sup.−1. The evaluation device 20 can for example analyse a wavenumber range of 1276 cm.sup.−1 to 1333 cm.sup.−1. Other wavenumber ranges can be used, for example wavenumber ranges in which there are characteristic Raman peaks of red blood cells.

[0100] FIG. 4 schematically shows the Raman spectrum 40 which is evaluated by the evaluation device 20. A wavenumber range of 1276 cm.sup.−1 to 1333 cm.sup.−1 is illustrated only as an example, in which there are one or a plurality of Raman peaks 41, 42, which are identified by the evaluation device 20. A further evaluation by a spectral analysis can take place. For example, the evaluation device 20 can determine an integral 44, 45 of the signal 40 for the respective Raman peaks 41, 42, e.g. by numeric integration or totalling the signal amounts in a plurality of discrete wavenumber bands in order to obtain a measure for the spectral weight of the Raman peaks 41, 42. Further evaluations can be carried out, for example by a principal component analysis of the Raman spectrum 40, by evaluating the mean value spectrum or by a SVM, without being limited thereto.

[0101] FIG. 5 and FIG. 6 illustrate exemplary results of a principal component analysis or a different cluster analysis which is performed by the evaluation device 20 in order to determine whether the blood reserve is still suitable for a transfusion. In this connection, the principal component analysis is performed for a Raman spectrum or a plurality of Raman spectra which have been recorded from the sample 9. The data points are illustrated according to a pair of different principal components PC-1 and PC-2. FIG. 5 shows the data points 51 which have been obtained by processing the Raman spectrum of a relatively fresh blood reserve. FIG. 6 shows data points 52 which have been obtained by processing the Raman spectrum of a blood reserve which has been stored for longer and/or not at the correct temperature.

[0102] As can be discerned from a comparison of FIG. 5 and FIG. 6, the data points obtained by the principal component analysis are shifted depending on whether or not the blood reserve is still suitable for the transfusion. Accordingly, the evaluation device 20 can automatically determine by means of the principal component analysis of a Raman spectrum whether the respectively tested blood reserve 2 is still suitable for a transfusion.

[0103] Different regions 53, 54 can be defined in an N-dimensional space in which the points of the cluster analysis are arranged depending on whether cellular components of the blood-based product are intact cells or functionally impaired cells.

[0104] The data points, assigned to fresh and thus intact cellular components, can be arranged in a region 53. The data points, assigned to old and functionally modified cellular components, can be arranged in a region 54 of the N-dimensional space different therefrom. The dimension N of the space in which the cluster analysis is performed can be greater than two, in particular many times greater than two.

[0105] In order to identify which proportion of cells of a cell type, e.g. which proportion of erythrocytes, thrombocytes, granulocytes or leukocytes is subject to a functional modification, which makes the blood-based product unsuitable for a transfusion, the evaluation device 20 can thus be configured to perform a cluster analysis of a plurality of Raman spectra of cells of this cell type. The cluster analysis can be a principal component analysis. The evaluation device 20 can be configured to quantitatively identify by means of the cluster analysis whether cells have to be assigned to a cluster 51 of intact cells or to a different cluster 52 of functionally impaired cells. The number of cells in the different clusters 51, 52 can be determined by the evaluation device 20 in order to determine which proportion of cells of the cell type is subject to the functional modification.

[0106] For blood-based products, which comprise a plurality of different cellular components of the blood, the evaluation device 20, by means of a cluster analysis, can distinguish not only between intact cells and functionally modified cells, but also between different cell types. For each of the plurality of different cells types, it can then be determined which proportion of cells of this cell type is subject to a functional modification.

[0107] FIG. 7 and FIG. 8 show the results of a cluster analysis, e.g. of a principal component analysis for a further cell type which is different from the further cell types examined in FIG. 5 and FIG. 6. FIG. 7 and FIG. 8 show, by way of example, results for erythrocytes in comparison with exemplary results for thrombocytes like those illustrated in FIG. 5 and FIG. 6. FIG. 7 and FIG. 8 show arrangements of data points, of which each is assigned to a Raman spectrum in an N-dimensional data space in the case of a principal component analysis. Other techniques of the cluster analysis can be used. FIG. 7 shows, by way of example, data points for Raman spectra of fresh intact cells. FIG. 8 shows, by way of example, data points for Raman spectra of old, functionally modified cells. As explained with reference to FIG. 5 and FIG. 6, by means of the cluster analysis, a distinction can be made between data 56, which can be assigned to intact cells, and data 57, which can be assigned to functionally modified cells.

[0108] Data points, which belong to cells of different cell types, are also in different regions of the data space in the case of the cluster analysis. Different cells can thus be distinguished. An assignment of data points to cellular components such as erythrocytes, thrombocytes, granulocytes or leukocytes can take place by a comparison with the position of data points assigned to intact cells. Such reference data can be stored in a non-volatile manner in the device 1.

[0109] As is illustrated by way of example in FIG. 7 in comparison to FIG. 5, the region 58, in which there are data points for cells of a second cell type in the case of the cluster analysis, differs from the region 53, in which there are data points for cells of a second cell type in the case of the cluster analysis.

[0110] Functional modifications of the cells, e.g. due to age or storage conditions of the blood-based product, lead to a shifting of the data points in the case of the cluster analysis from the region 58 into a region 59 different therefrom.

[0111] The evaluation device 20 can carry out an assignment to different cell types for example by means of different wavenumber ranges in the case of a cluster analysis or in the case of a different analysis of the recorded Raman spectra, in which wavenumber ranges the Raman spectra for cells of different cell types respectively comprise a characteristic behaviour. In order to identify thrombocytes and/or in order to identify functional modifications of thrombocytes, at least one wavenumber in the wavenumber range of 1296 cm.sup.−1 to 1333 cm.sup.−1 can for example be evaluated by means of the evaluation device 20 in order to determine whether the blood-based product can be used for a transfusion.

[0112] In order to identify erythrocytes and/or in order to identify functional modifications of erythrocytes by means of the evaluating device 20, at least one wavenumber from one or a plurality of wavenumber regions from 1650 to 1600 cm.sup.−1, from 1350 to 1250 cm.sup.−1, from 1180 cm.sup.−1 to 1120 cm.sup.−1, from 1100 cm.sup.−1 to 1050 cm.sup.−1, from 930 cm.sup.−1 to 890 cm.sup.−1 or from 700 cm.sup.−1 to 650 cm.sup.−1 can for example be evaluated in order to determine whether the blood-based product can be used for a transfusion.

[0113] Depending on the proportion of cells of one or a plurality of cell types, which are subject to a functional modification, the evaluation device 20 can automatically determine whether the blood-based product is suitable for a transfusion.

[0114] A threshold value for a cell type of the blood-based product can be stored in a non-volatile manner in the device 1. If the proportion of cells of the cell type, which are functionally impaired after the result of the principal component analysis or a different cluster analysis, exceeds the threshold value, the evaluation device 20 automatically identifies that the blood-based product is not suitable for the transfusion.

[0115] A further threshold value for a further cell type of the blood-based product can be stored in a non-volatile manner in the device 1. If the proportion of cells of the further cell type, which are functionally impaired after the result of the principal component analysis or a different cluster analysis, exceeds the further threshold value, the evaluation device 20 automatically identifies that the blood-based product is not suitable for the transfusion.

[0116] The cell type and the further cell type can both be selected from a group consisting of erythrocytes, thrombocytes, granulocytes and leukocytes.

[0117] FIG. 9 shows a Raman spectrum 71 of thrombocytes and a Raman spectrum 72 of erythrocytes. Mean value spectra are respectively illustrated according to storage of the blood-based product.

[0118] The position of Raman peaks enables a distinction of different cell types. For example, the Raman spectrum 71 of thrombocytes comprises Raman peaks in the case of a wavenumber or a plurality of wavenumbers 74, which enable a distinction of thrombocytes and other cell types. In a wavenumber range 84 or in a plurality of wavenumber ranges, which can reach for example from 1550 cm.sup.−1 to 1590 cm.sup.−1, a cell of the cell type thrombocytes can be identified from the presence of a Raman peak.

[0119] The Raman spectrum 72 of erythrocytes comprises Raman peaks in the case of wavenumbers 75, 76, 77, which allow a distinction between thrombocytes and other cell types. In a wavenumber range or in a plurality of wavenumber ranges 85, 76, 87, a cell of the cell type erythrocytes can be identified from the presence of a Raman peak. The one or plurality of wavenumber ranges 85, 86, 87 can be selected from the group consisting of a wavenumber range from 1480 cm.sup.−1 to 1550 cm.sup.−1, a wavenumber range from 1050 cm.sup.−1 to 1120 cm.sup.−1 and a wavenumber range from 600 cm.sup.−1 to 700 cm.sup.−1.

[0120] In order to distinguish different cell types and the functional modifications, to which the cells are respectively subjected, a cluster analysis can be performed, as has already been described above.

[0121] In addition to a determination of the proportions of cellular components of the blood-based products, which are subjected to functional modifications, impurities such as contaminations, bacteria or viruses can also be identified by the Raman spectroscopy.

[0122] With devices and methods according to exemplary embodiments, objective statements can be made regarding whether the blood reserve 2 may be used for a transfusion. The quantitative evaluation of the Raman spectrum provides objective information on the cells present and/or regarding whether the function of a significant proportion of erythrocytes or thrombocytes is impaired, for example by cell death or other processes. The quantitative evaluation of the Raman spectrum can, alternatively or additionally, be used in order to identify impurities and thus to verify the sterility of the blood reserve.

[0123] For the best possible evaluation even in the case of smaller sample quantities, the device 1 can be configured such that cells for example erythrocytes or thrombocytes are held in an optical trap in the case of the Raman spectroscopy. The optical trap can be produced by the excitation beam 17 of the Raman spectroscopy system 1 or a beam of electromagnetic radiation different therefrom.

[0124] FIG. 10 shows, by way of example, a configuration 60 in the case of a device 1 according to an exemplary embodiment, in which biological objects are held in an optical trap in order to perform the Raman spectroscopy. A focal point 61 of a beam produces an optical trap potential, in which biological objects 62-64 are collected for the Raman spectroscopy. The focal point 61 can be produced by the excitation beam 17, which is output by the light source 11. The excitation beam 17 can thus be used both as excitation for the Raman scattering and for producing the optical trap. Alternatively, the optical trap can also be produced by a separate beam.

[0125] The Raman spectroscopy system 10 can also comprise a light conductor, for example an optical fibre, by means of which the excitation beam 17 and/or the Raman scattered light is guided. The light conductor can be positioned such that the excitation beam leaving said light conductor produces the optical trap with the focal point 61.

[0126] While exemplary embodiments have been described with reference to the figures, variations can be implemented in the case of further exemplary embodiments. For example, the Raman spectrum can be evaluated in a number of different wavenumber ranges or with a number of different methods of the spectral analysis in order to determine whether the blood-based product may be used for a transfusion. While exemplary embodiments have been described, in the case of which the sample is produced by removing it from a blood-based product, in the case of further exemplary embodiments the Raman spectroscopy can be performed on the blood reserve itself.

[0127] FIG. 11 shows a blood reserve 2 with a bag 5 made from plastic material. For use in the case of methods or devices according to exemplary embodiments, the bag 5 can consist of a material which has high transmissivity for the excitation beam and the Raman scattered light of the relevant biological objects.

[0128] The bag 5 can comprise a window 6 made of a material which has high transmissivity for the excitation beam and the Raman scattered light of the relevant biological objects (for example erythrocytes, thrombocytes, bacteria and/or germs). The device 1 can comprise an object slide which is configured to receive the bag 5 such that the window 6 is positioned so as to allow the excitation beam from the light source 11 to pass through and the Raman scattered light to exit to the Raman spectrometer 14.

[0129] While devices and methods have been described in the context of quality controlling blood-based products with reference to FIG. 1 to FIG. 11, Raman spectroscopy can also be used in order to identify diseases or progressions of disease.

[0130] Accordingly, the device 1 from FIG. 1 can also be configured to process a blood sample 9 of a patient. The device 1 can evaluate the recorded Raman spectrum in order to identify a disease or a progression of disease. The device 1 can record and evaluate Raman spectra of a plurality of blood samples 9, which have been obtained in a time-sequential manner, in order to identify a progression of disease.

[0131] The device 1 can be configured to identify and evaluate, for example Raman peaks which are assigned to erythrocytes or thrombocytes. The device 1 can be configured to identify and evaluate, for example Raman peaks which are assigned to leukocytes.

[0132] By means of evaluating the recorded Raman spectrum or the recorded Raman spectra, an illness in the patient, from whom the blood sample 9 has been taken, can be identified. The evaluation can take place automatically by means of the device 1.

[0133] The device 1 can for example be configured to identify a disease or a progression of a disease which is selected from a group consisting of tumour diseases, blood coagulation disorders (e.g. PMH) or thrombosis. The device 1 can be configured to perform a spectral analysis of the recorded Raman spectrum or the recorded Raman spectra in order to identify the disease or the progression of disease.

[0134] Devices and methods according to exemplary embodiments can generally be used for quantitatively examining blood, for example for quality controlling blood reserves in blood banks.