Method and apparatus for determining a radiation dose received by an aqueous liquid from electron radiation

Abstract

A method and apparatus for determining the radiation dose received by an aqueous liquid from electron beam radiation are provided. The method is based on measuring the absorption or fluorescence of an aqueous liquid containing or consisting of an organic dye and water before and after direct irradiation with electron beam radiation of <600 keV for a predetermined period, and determining the difference between these measurements. Subsequently, the radiation dose received by the liquid from the electron beam radiation during the predetermined period is calculated from this difference. With this method and apparatus, it is possible to determine the radiation dose received by an aqueous liquid from electron beam radiation with an energy of <600 keV.

Description

[0001] A method and a device are provided for determining a radiation dose that an aqueous liquid experiences due to electron radiation. The method is based on measuring the absorption or fluorescence of an aqueous liquid containing or consisting of an organic dye and water before and after direct irradiation with electron radiation with an energy of <600 keV for a predetermined period of time, and determining a difference from this. The difference is then used to determine a radiation dose that the liquid has experienced due to the electron radiation during the predetermined period of time. The method and the device make it possible to determine a radiation dose that an aqueous liquid experiences due to electron radiation with an energy of <600 keV.

[0002] Irradiation with low-energy accelerated electrons (i.e., electrons with an energy of <600 keV) is increasingly used in medical technology and biotechnology, for example, to sterilize sensitive products, functionalize surfaces, and / or inactivate or stimulate viruses and bacteria in aqueous media. Furthermore, this method offers advantages for a variety of pharmaceutical processes.

[0003] Depending on the application, different dose ranges must be used. This means that to achieve the desired effects with low-energy electron beams, targeted dose delivery and reliable detection of the administered dose are necessary. For example, the dose range for cell stimulation and blood irradiation is only 1-300 Gy (very low dose range), for wastewater treatment it is 1 to 6 kGy (medium dose range), and for the inactivation of viruses and parasites it is >6 kGy (high dose range). Applications are also conceivable for a dose range of >300 Gy to <1 kGy (low dose range).

[0004] For reliable detection of the administered dose, suitable measuring tools (dosimeters) are required that cover the widest possible range of different dose ranges.

[0005] To date, film dosimeters (such as the GafChromic HDV2 or Risö B3 or alanine strips) have often been used as standard reference dosimeters for measuring radiation doses from low-energy electron beams. However, these film dosimeters have the disadvantage that they cannot image the flow of a target fluid during irradiation.

[0006] It is also known in the art to use liquid dosimeters to detect radiation doses from electromagnetic radiation or high-energy electron beams. Liquid dosimeters are based on an aqueous liquid containing a colored substance. Direct / indirect exposure to radiation excites, ionizes, or splits the liquid's water molecules according to a radical mechanism. This produces intermediate hydroxyl and hydrogen radicals (i.e., OH and H). These resulting radicals can, in turn, react with water or the colored substance in the liquid. The latter usually leads to rearrangements in the colored substance, which are perceived macroscopically as a weakening, deepening, or color change.

[0007] For example, a conventional liquid dosimeter based on a ceric sulfate solution can only detect very high radiation doses in the range of ≥ 5 kGy. A conventional Fricke dosimeter can only detect radiation doses in the very low to very low dose range of 1 Gy to 500 Gy.

[0008] The CU 22075 A1 discloses a novel Fricke dosimeter, which enables detection of a radiation dose in the dose range of 0.4 kGy to 1.5 kGy, i.e. also in the low to medium dose range.

[0009] US2018 / 074213 A1 discloses a liquid dosimeter based on a calcein solution, which is suitable for detecting a radiation dose in the low to medium dose range (dose range 0.25 kGy to 1 kGy).

[0010] DE 10 2017 105 159 A1 discloses a method for validating an irradiation system, comprising providing a liquid in which phosphor particles are suspended, irradiating the liquid with a radiation dose by means of high-energy gamma radiation or electron radiation with an energy of at least 10 keV, exciting the irradiated phosphor particles to photoluminescence with low-energy radiation, measuring the photoluminescence spectrally and / or temporally, and evaluating the measurement of the photoluminescence, whereby the radiation dose is determined.

[0011] DE 10 2016 110 672 A1 discloses a method for applying accelerated electrons to a liquid, comprising providing the liquid, mixing the liquid with particles which have at least one phosphor, wherein the particles are formed such that the particles are dispersed in the liquid after mixing, applying electromagnetic radiation to the liquid which excites the at least one phosphor to luminesce, detecting an actual value of a physical quantity characterizing the luminescence of the phosphor, and applying accelerated electrons to the liquid until the detected actual value corresponds to a desired value.

[0012] A disadvantage of existing liquid dosimeters is that they are often filled into glass ampoules and used in this form for detection. Low-energy accelerated electrons cannot penetrate the glass ampoules due to their low penetrability, making the use of these liquid dosimeters unsuitable for measuring a radiation dose from low-energy electron beams (energy <600 keV), especially for the precise detection of low radiation doses. For this reason, liquid dosimeters have not yet been used to detect a radiation dose caused by low-energy electron beams.

[0013] Based on this, it was the object of the present invention to provide a method and a device with which it is possible to determine a radiation dose that an aqueous liquid experiences due to electron radiation with an energy of <600 keV, wherein it should be possible to image a flow of a target liquid to be irradiated during irradiation.

[0014] The object is achieved by the method having the features of claim 1 and the device having the features of claim 13. The dependent claims show advantageous developments.

[0015] According to the invention, a method for determining a radiation dose to which an aqueous liquid is exposed by electron radiation is provided, comprising the following steps or consisting of: (a) providing an aqueous liquid containing or consisting of an organic dye and water; b) measuring a first absorption or first fluorescence of the organic dye of the aqueous liquid; c) irradiating the aqueous liquid with electron radiation having an energy of <600 keV (optionally <300 keV) for a predetermined period of time, wherein the electron radiation, after exiting an electron exit window of a source of electron radiation, does not pass through any material different from the aqueous liquid on its way to the aqueous liquid; d) measuring a second absorption of the organic dye of the aqueous liquid after the predetermined period of time if a first absorption was measured, and determining a difference between the second absorption and the first absorption, or measuring a second fluorescence of the organic dye of the aqueous liquid after the predetermined period of time if a first fluorescence was measured, and determining a difference between the second fluorescence and the first fluorescence; and e) determining a radiation dose which the aqueous liquid has experienced due to the electron beam radiation during the predetermined period of time based on the determined difference;wherein the organic dye contains or consists of triphenyltetrazolium chloride, tartrazine, bromophenol blue, dimethylene blue, resazurin, xylenol orange, phenol red, or coumarin-3-carboxylic acid.

[0016] With the method according to the invention it is possible to determine a radiation dose that an aqueous liquid experiences due to electron radiation with an energy of <600 keV (optionally <300 keV).

[0017] This is because the liquid dosimeter uses an aqueous liquid containing or consisting of an organic dye and water. After exiting an electron beam window of an electron beam source, the electron beams are radiated directly onto the liquid. This means that no solid material passes through them on their way to the aqueous liquid (e.g., they do not pass through the glass wall of a glass ampoule). As a result, the low-energy electrons are not absorbed by a solid material on their way to the liquid dosimeter. This means that the low-energy electrons hit the liquid dosimeter without attenuation.

[0018] Furthermore, the method according to the invention makes it possible to image a flow of a target liquid to be irradiated during irradiation, since a liquid dosimeter is used in the method according to the invention.

[0019] In a preferred embodiment, after exiting the electron beam's electron exit window, the electron beam does not pass through any liquid material other than the aqueous liquid (of the liquid dosimeter) on its way to the aqueous liquid. This also prevents potential attenuation of the electrons by liquid materials other than the liquid being irradiated.

[0020] Possible alternative compositions of the liquid usable in the method are described below, along with the respective radiation dose range that can be detected with each liquid. The following alternative liquid compositions exhibit high detection sensitivity within the specified radiation dose range. Furthermore, the following alternative liquid compositions exhibit high resistance to external environmental influences and very good storage stability and biocompatibility.

[0021] In a first alternative, the organic dye in the liquid contains or consists of triphenyltetrazolium chloride. This makes it possible to accurately and reliably detect a radiation dose in the range of 6.5 kGy to 40 kGy. This dye is therefore suitable for determining a radiation dose in this range using the method. Detecting a radiation dose in this range using a liquid dosimeter has not been possible until now.

[0022] The concentration of triphenyltetrazolium chloride in the liquid may be 0.05 to 0.5% (w / v), particularly preferably 0.2 to 0.2% (w / v).

[0023] The water of the liquid can be deionized water.

[0024] In the method, the absorption of triphenyltetrazolium chloride can be measured at a wavelength in the range of 400 to 500 nm, preferably at 485 nm.

[0025] In a second alternative, the organic dye in the liquid contains or consists of tartrazine (abbreviated to "E102"). This makes it possible to accurately and reliably detect a radiation dose in the range of 0.1 kGy to 4 kGy (preferably 1 kGy to 4 kGy). This dye is therefore suitable for determining a radiation dose in this range using the method. Such a liquid dosimeter is not known to date. Detecting a radiation dose in this range using a liquid dosimeter has not been possible until now, as the upper detection limit for known state-of-the-art liquid dosimeters is 1.5 kGy.

[0026] The concentration of tartrazine in the liquid can be 0.3 mM to 0.5 mM, especially 0.40 to 0.45 mM.

[0027] The water of the liquid can be deionized water.

[0028] In the method, the absorption of tartrazine can be measured at a wavelength in the range of 420 to 430 nm, preferably at 426 nm.

[0029] In a third alternative, the organic dye in the liquid contains or consists of bromophenol blue. This makes it possible to accurately and reliably detect a radiation dose in the range of 1 kGy to 6 kGy. This dye is therefore suitable for determining a radiation dose in this range using the method. Detecting a radiation dose in this range using a liquid dosimeter has not been possible until now, as the upper detection limit for known state-of-the-art liquid dosimeters is 1.5 kGy.

[0030] The concentration of bromophenol blue in the liquid may be 0.1 to 0.6 mM, particularly preferably 0.3 to 0.5 mM.

[0031] The water of the liquid can be deionized water.

[0032] In the method, the absorption of bromophenol blue can be measured at a wavelength in the range of 430 to 440 nm, preferably at 435 nm.

[0033] In a fourth alternative, the organic dye in the liquid contains or consists of dimethylene blue (abbreviated to "MTB"). This makes it possible to accurately and reliably detect a radiation dose in the range of 100 Gy to 1000 Gy. This dye is therefore suitable for determining a radiation dose in this range using the method.

[0034] The concentration of dimethylene blue in the liquid may be 0.1 to 0.3 mM, particularly preferably 0.15 to 0.25 mM, in particular 0.2 mM.

[0035] The water of the liquid can be deionized water.

[0036] In the method, the absorption of dimethylene blue can be measured at a wavelength in the range of 605 to 615 nm, preferably at 610 nm, or at a wavelength in the range of 660 to 670 nm, preferably at 664 nm.

[0037] In a fifth alternative, the organic dye of the liquid contains or consists of resazurin (abbreviated to "RZ"). This makes it possible to detect a radiation dose in the range of 100 Gy to 1 kGy in an exact and reliable manner (e.g. 100 Gy to 1 kGy polynomial or 100 Gy to 400 Gy linear). This dye is therefore suitable for determining a radiation dose in the said range in the method.

[0038] The concentration of resazurin in the liquid may be 0.1 to 0.3 mM, particularly preferably 0.15 to 0.25 mM, in particular 0.2 mM.

[0039] The water of the liquid can be deionized water.

[0040] In the method, the absorption of resazurin can be measured at a wavelength in the range 580 to 630 nm, preferably at 602 nm.

[0041] In a sixth alternative, the organic dye in the liquid contains or consists of xylenol orange (XO for short). This makes it possible to accurately and reliably detect a radiation dose in the range of 10 Gy to 30 Gy. This dye is therefore suitable for determining a radiation dose in this range using the method.

[0042] The concentration of xylenol orange in the liquid may be 0.3 to 0.45 mM, particularly preferably 0.35 to 0.40 M, in particular 0.375 mM.

[0043] The water of the liquid can be deionized water.

[0044] In the method, the absorption of xylenol organic dye can be measured at a wavelength in the range of 430 to 440 nm, particularly preferably at 434 nm, or at a wavelength in the range of 550 to 560 nm, particularly preferably at 555 nm.

[0045] The liquid can also contain D-sorbitol, (NH4)2Fe(SO4)2, and ethanol. This makes it possible to broaden the measurable radiation dose range of xylenol orange to 10 Gy to 80 Gy, allowing a radiation dose in the range of 10 Gy to 80 Gy to be detected accurately and reliably. The combination with D-sorbitol is therefore suitable for determining a radiation dose in this range in the method.

[0046] In this case, the absorption of xylenol orange can be measured at a wavelength in the range of 550 to 560 nm, particularly preferably at 555 nm. In particular, the concentration of D-sorbitol is in the range of 20 to 200 mM, the concentration of (NH4)2Fe(SO4)2 is in the range of 0.1 to 0.5 mM, and / or the concentration of ethanol is in the range of 1 to 5 vol%, relative to the total volume of the liquid.

[0047] In a seventh alternative, the organic dye in the liquid contains or consists of phenol red. This makes it possible to accurately and reliably detect a radiation dose in the range of 5 Gy to 50 Gy. This dye is therefore suitable for determining a radiation dose in this range using the method.

[0048] The concentration of phenol red in the liquid may be 0.05 to 0.1% (w / v), more preferably 0.01 to 0.02% (w / v).

[0049] The water of the liquid can be deionized water.

[0050] In the method, the absorption of phenol red can be measured at a wavelength in the range of 400 to 500 nm, preferably at 440 nm.

[0051] In an eighth alternative, the organic dye in the liquid contains or consists of coumarin-3-carboxylic acid. This makes it possible to accurately and reliably detect a radiation dose in the range of 1 Gy to 50 Gy. This dye is therefore suitable for determining a radiation dose in this range in the method.

[0052] The concentration of coumarin-3-carboxylic acid in the liquid may be 1 to 6 mM, particularly preferably 2 to 3 mM.

[0053] The water of the liquid can be deionized water.

[0054] In the method, fluorescence of coumarin-3-carboxylic acid can be excited at a wavelength in the range of 300 to 400 nm, preferably at 380 nm.

[0055] Furthermore, in the method, the fluorescence of coumarin-3-carboxylic acid can be measured at a wavelength in the range of 400 to 500 nm, preferably at 448 nm.

[0056] In the method, the liquid can be provided in step a) in at least one well of a microtiter plate, and in step b) the first absorption or first fluorescence of the organic dye of the liquid in the microtiter plate can be measured. Preferably, 50 to 100 µl of the liquid are provided in the at least one well of the microtiter plate. The microtiter plate is preferably a 96-well microtiter plate.

[0057] Furthermore, in the method according to step c), the liquid can be provided in at least one well of a microtiter plate, and if a first absorption was measured, the second absorption of the organic dye in the liquid can be measured there. If a first fluorescence was measured, the second fluorescence of the organic dye in the liquid can be measured. Preferably, 50 to 100 µl of the liquid are provided in the at least one well of the microtiter plate. The microtiter plate is preferably a 96-well microtiter plate.

[0058] In the method, in step e), a comparison can further be made with a calibration curve created for the organic dye in the liquid using a reference dosimeter, optionally a reference film dosimeter, to determine the radiation dose. In particular, the calibration curve reveals a dependence of the radiation dose on a difference in absorption or a difference in fluorescence.

[0059] The procedure may include the following steps after step e): (i) providing an aqueous liquid containing or consisting of water and biological cells, a biological pathogen and / or a chemical pollutant; ii) irradiating the further aqueous liquid with electron radiation having an energy of <600 keV for a further predetermined period of time which is identical to or different from the predetermined period of time, wherein the electron radiation does not pass through any material on its way to the further aqueous liquid which is different from the further aqueous liquid; and iii) determining a radiation dose which the further aqueous liquid has experienced as a result of the electron radiation during the predetermined period of time from the known further predetermined period of time and from a linear dependence of the radiation dose on an irradiation time, wherein the linear dependence of the radiation dose on the irradiation time was preferably determined by the radiation dose determined in step e) and the known predetermined period of time.

[0060] Low-energy accelerated electrons, administered in small doses, can have a biopositive effect on the division capacity and metabolic activity of bacteria and cells, which can be used to accelerate biotechnological processes, e.g. for raw material extraction.

[0061] The biological cells are preferably blood cells, with the fluid being blood in particular. Irradiation of transfused blood with low-energy electron beam radiation has the advantage of preventing an undesired immune response of donor blood T cells in the recipient's tissue (TA-GcHD). This can be achieved by targeted inactivation of the (more sensitive) T cells with low-energy electron beam radiation, while blood cells such as erythrocytes, granulocytes, and platelets are not damaged.

[0062] The biological pathogen is preferably selected from the group consisting of bacteria, viruses, protozoa, prions, and combinations thereof, wherein the liquid in particular contains or consists of a vaccine liquid. During vaccine production, pathogens (viruses, bacteria, parasites) can be inactivated or attenuated in liquids using low-energy accelerated electrons. Here, too, low-energy electron radiation can be used to specifically damage the DNA of the microorganisms or viruses without impairing the functionality of their components (e.g., surface antigens).

[0063] The chemical pollutant is preferably selected from the group consisting of hormones, antibiotics, painkillers, and combinations thereof, with the liquid being, in particular, wastewater. Low-energy electron beam technology is an economical, energy- and resource-saving method for reducing micropollutants (hormones, antibiotics, painkillers, etc.) and pathogens in the treatment of pharmaceutical wastewater that cannot be completely removed by mechanical, biological, and chemical treatment.

[0064] According to the invention, a device for determining a radiation dose which an aqueous liquid experiences due to electron radiation is further provided, containing or consisting of (a) an aqueous liquid containing or consisting of an organic dye and water; b) a measuring device configured to measure an absorption or a fluorescence of an organic dye of the aqueous liquid; c) a source of electron radiation configured to radiate electron radiation with an energy of <600 keV (optionally <300 keV) through an electron exit window of the source of electron radiation onto the aqueous liquid; and d) a control unit configured to determine a radiation dose experienced by the aqueous liquid due to the electron radiation during the predetermined period of time based on information from the measuring device about an absorption or fluorescence of the organic dye of the aqueous liquid; wherein the device is configured such that the electron radiation from the source of electron radiation, after exiting the electron exit window of the source of electron radiation, does not pass through any material on its way to the aqueous liquid that is different from the aqueous liquid, wherein the organic dye contains or consists of triphenyltetrazolium chloride, tartrazine, bromophenol blue, dimethylene blue, resazurin, xylenol orange, phenol red, or coumarin-3-carboxylic acid.

[0065] With the device according to the invention, it is possible to determine a radiation dose that an aqueous liquid experiences due to electron radiation with an energy of <600 keV (optionally <300 keV) and further to image a flow of a target liquid to be irradiated during irradiation.

[0066] The control unit of the device may be further configured to cause the measuring device to measure a first absorption or first fluorescence of the organic dye of the aqueous liquid.

[0067] In addition, the control unit of the device may be further configured to cause the source of electron radiation to irradiate electron radiation with an energy of <600 keV onto the aqueous liquid for a predetermined period of time.

[0068] Apart from that, the control unit of the device may be further configured to cause the measuring device to measure a second absorption of the organic dye of the aqueous liquid after the predetermined period of time if a first absorption has been measured, wherein the control unit is configured to determine a difference between the second absorption and the first absorption.

[0069] Alternatively, the control unit of the device may be further configured to cause the measuring device to measure a second fluorescence of the organic dye of the aqueous liquid after the predetermined period of time if a first fluorescence has been measured, wherein the control unit is configured to determine a difference between the second fluorescence and the first fluorescence.

[0070] The control unit of the device may further be configured to determine, based on the determined difference, a radiation dose which the aqueous liquid has experienced by electron radiation with an energy <600 keV during the predetermined period of time.

[0071] In a preferred embodiment, the device, optionally also the control unit of the device, is configured to carry out the method according to the invention. The device can have at least one feature that was mentioned in connection with the method according to the invention and that is necessary for carrying out the method according to the invention.

[0072] The subject matter of the invention will be explained in more detail with reference to the following figures and examples, without wishing to restrict it to the specific embodiments shown here. Fig. 1 shows schematically a device according to the invention. Fig. Figure 2 shows the absorption spectra of four liquid dosimeters usable in the method according to the invention. The abbreviation "XO" stands for an aqueous solution of the organic dye xylenol orange, the abbreviation "MTB" stands for an aqueous solution of the organic dye 1,9-dimethylene blue, the abbreviation "RZ" stands for an aqueous solution of the organic dye resazurin, and the abbreviation "E112" stands for an aqueous solution of the organic dye tartrazine. Fig. 3 shows the calibration curves of xylenol orange (XO) in Fig. 3A and 0.2 mM methylene blue (MTB) in Fig.3B, where each graph shows the measured response (i.e., absorbance) on the x-axis and the reference dose measured using two alanine films and the ESR method on the y-axis. While XO was calibrated using the absolute absorbance values, MTB was adjusted using the logarithmic change in absorbance from the original (unirradiated) absorbance value. Fig. Figure 4 shows the calibration curves of Resazurin (RZ) in Fig. 4A and Fig. 0.5 mM Tartrazine (E102) in Fig. 4B, where each graph shows the measured response (i.e., measured absorbance) on the x-axis and the reference dose measured using two alanine films and the ESR method on the y-axis. RZ and E102 were calibrated using the absolute absorbance values. Fig. 5 shows the evaluation of the Fig. 3 calibration curves for xylenol orange (XO) in Fig. 5A and for methylene blue (MTB) in Fig.5B, where the dose measured with the reference dosimeter (y-axis) corresponds to the dose resulting from the response and calibration curve of the respective liquid dosimeter (x-axis). Fig. 6 shows the evaluation of the Fig. 4 calibration curves for resazurin (RZ) in Fig. 6A and for tartrazine (E102) in Fig. 6B, where the dose measured with the reference dosimeter (y-axis) corresponds to the dose resulting from the response and calibration curve of the respective liquid dosimeter (x-axis). Example 1- Liquid dosimeters and their use

[0073] Four different liquid dosimeters were tested. The four liquid dosimeters were manufactured less than two days before the experiments and stored in the dark at 4°C. First liquid dosimeter (organic dye: xylenol orange)

[0074] Three different concentrations of xylenol orange ("XO") were tested: 1.3 mM XO, 0.5 mM XO, and 0.1 mM XO. The dye was dissolved in 50 ml of deionized water containing 0.2 mM ferrous ammonium sulfate and 10 mM d-sorbitol. 0.4 ml of sulfuric acid (5 M) was added. Second liquid dosimeter (organic dye: dimethylene blue)

[0075] A 0.4 mM stock solution of 1,9-dimethylene blue ("MTB") was prepared. 2.56 mg of MTB was dissolved in 20 ml of deionized water. This stock solution was diluted to 0.2 mM and 0.1 mM by adding deionized water. Third liquid dosimeter (organic dye: resazurin)

[0076] A stock solution of 0.1 mM resazurin ("RZ") was prepared with deionized water. A final concentration of 0.075 mM or 0.05 mM was achieved by diluting the previous solution with water. The pH was adjusted to 4 (pH4) with 0.1 M HCl or to 7 and 10 with NaOH. Fourth liquid dosimeter (organic dye: tartrazine)

[0077] Tartrazine ("E102") was dissolved in deionized water to achieve final concentrations of 1.0 mM, 0.5 mM, and 0.25 mM, respectively. The pH was adjusted to 4 (pH4) with 0.1 M HCl or to 7 and 10 with NaOH.

[0078] The various liquid dosimeters were placed in wells of 96-well plates and irradiated with electron beams at an energy of <600 keV. An alanine-based reference dosimeter was placed in one of the wells. The absorbance before and after each irradiation with electron beams was read using a plate reader for 96-well plates (Tecan, Infinite 200).

[0079] In order to test the long-term stability of the liquid dosimeters, in a separate experiment the different liquid dosimeters were placed in wells of 96-well plates and absorption spectra of the liquid dosimeters were recorded in the plate reader every second to third day.

[0080] For calibration, an individual calibration curve was created for each liquid dosimeter, with the measured dose value of the reference dose (determined by the alanine-based reference dosimeter) plotted on the y-axis and the absorbance on the x-axis. Individual adjustments were made with a maximum determination coefficient R 2selected. Finally, a calibration curve was derived from the individual curves. First, each measured absorption value was plotted in a graph with the respective reference dose on the y-axis, and a calibration line was created by curve fitting. This calibration line could then be used to determine a dose for all measured absorption values. Example 2 - Absorption spectra of liquid dosimeters

[0081] The absorption spectra of the four liquid dosimeters from Example 1 are shown in Fig. 2 shown.

[0082] The absorption maximum of XO ( Fig. 2, squares) was 434 nm, independent of the concentration.

[0083] In the absorption spectrum of MTB, a double peak appeared at 610 nm and 664 nm ( Fig.2, black circles). The second peak at 664 nm was higher than the first and most significant at the concentration of 0.2 mM. Therefore, the second peak was selected for further investigation.

[0084] Since RZ undergoes a color shift from acidic (blue) to neutral pH (pink), the absorption maximum was at pH 4 ( Fig. 2, inverted triangle) at 528 nm. Conversely, the absorption maximum was at pH 7 and 10 ( Fig. 1, triangle) at 602 nm. At neutral and alkaline values, the color of RZ appeared deep purple. The 602 nm peaks at pH 7 became broader and smaller with increasing RZ concentration (the absorbance of the other concentrations is not shown).

[0085] E102 had a single absorption maximum at 426 nm, which was not affected by the adjusted pH value (data not shown). For further experiments, pH 4 was chosen ( Fig. 2, squares). Example 3 - Long-term stability of liquid dosimeters

[0086] The absorption variation over time determined the storage stability of the liquid radiochromic dosimeters and is crucial for their use in process monitoring.

[0087] After three days, the absorption of XO decreased by 1.8% and remained stable until day 14, when absorption increased to 1.6% of the previous value. Within 80 days, the difference in absorption was a maximum of 2.2% of the original value.

[0088] The storage stability of unirradiated MTB was investigated for 70 days. The absorption peak at 664 nm decreased slightly within one week due to bleaching, but after 63 days, it decreased by no more than 2.1%.

[0089] The absorbance of RZ was investigated over a period of 35 days for each pH value (4, 7, and 10). The RZ solution with a pH value of 4 was considered unstable because the absorbance decreased after three days. At neutral and alkaline pH values, however, the values ​​were more constant. Within 30 days, the maximum percentage deviation at pH was 108.2%.

[0090] The storage stability of Tartrazine E102 was tested for pH 4, 7, and 10. At pH 4 and 7, good storage stability was observed over a period of 14 days. During this period, the absorption values ​​increased to a maximum of 107.7% (pH 4) and 107.4% (pH 7), respectively. Storage stability at pH 10 was insufficient for use as a liquid dosimeter.

[0091] The long-term stability results are summarized in Table 1 below. Table 1: Summary of the long-term stability of the individual liquid dosimeters. dye Concentration [mM] pH Absorption maximum [nm] Time [days] Percentage deviation [%] XO 0.4 1 434 (555 nm) 70 2.1 MTB 0.2 5 610 / 664 nm 63 2.1 RZ 0.2 10 602 < 4 6.4 E102 0.5 4 426 < 2 5.7 Example 4 - Creating the calibration curves for the liquid dosimeters

[0092] The calibration curves for the four liquid dosimeters from Example 1 are shown in the Fig. 3 and Fig. 4. Each of the Fig. 3 and Fig. The diagrams shown in Figure 4 show the measured response (e.g. absorption) on the x-axis and the reference dose measured with two alanine films and the ESR method on the y-axis.

[0093] The dose-response relationship of XO was already saturated at a dose below 50 Gy. The absorption values ​​were adjusted for the linear decrease in a dose range between 15 and 35 Gy ( Fig. 3A).

[0094] A linear calibration line was fitted based on the logarithmic decrease of the absorbance of MTB measured at 664 nm ( Fig. 3B). This adjustment covers a dose range from 25 Gy to 1800 Gy with 20 dose points.

[0095] The calibration function of RZ was also fitted by a second-order polynomial function only in a low dose range from 63 Gy to 1040 Gy ( Fig. 4A).

[0096] The absorption measurements of E102 were fitted by a fourth-order polynomial ( Fig. 4B). E102 covers a dose range from 24 Gy to 4180 Gy. In contrast, all previous dosimeters were bleached in the mid-dose range above 1000 Gy. Example 5 - Evaluation of the calibration curves of the liquid dosimeters

[0097] The verification of the calibration adjustment and the evaluation of the calibration curves of the four liquid dosimeters from Example 1 are described in the Fig. 5 and Fig. 6. The dose value calculated with the calibration function (y-axis in Fig. 5 and Fig. 6) was plotted against the measured reference dose (x-axis in Fig. 5 and Fig. 6). Each of the Fig.5 and Fig. The diagrams shown in Figure 6 show the dose measured with the reference dosimeter (y-axis) as a function of the response (e.g., absorption) of the respective organic dye to a specific dose. The dose measured with the reference dosimeter corresponds to the dose resulting from the response and calibration curve of the respective liquid dosimeter (x-axis).

[0098] For XO, the linear regression coefficient R was 2 0.96958 ( Fig. 6A), for MTB the linear regression coefficient R was 2 0.97433 ( Fig. 6B), for RZ the linear regression coefficient R was 2 of 0.98823 ( Fig. 7A) and at E102 the linear regression coefficient R 2 0.9957 ( Fig. 7B).

[0099] The results are summarized in Table 2 below. Table 2: Summary of the calibration functions of the individual liquid dosimeters. dye Response Fit Dose range R 2 XO Absorption (A i ) Linear 14 - 33 Gy 0.96958 MTB Log(A0 / A i ) Linear 25 - 1800 Gy 0.97433 RZ Absorption (A i ) 2. polynomial 63 - 1040 Gy 0.98823 E102 Absorption (A i ) 4. polynomial 24 - 4180 Gy 0.99576 List of reference symbols 1 aqueous liquid containing or consisting of an organic dye and water; 2 alanine reference dosimeters; 3 Source of electron radiation; 4 Electron radiation with an energy of <600 keV; 5 Electron exit window of the device; 6 Vessel for the aqueous liquid (e.g. microtiter plate); 7 Direction of movement; 8 Measuring device configured to measure an absorption or a fluorescence of an organic dye of the aqueous liquid (e.g. microtiter plate reader).

Claims

[1] A method for determining a radiation dose to which an aqueous liquid is exposed by electron beams, comprising the following steps or consisting of: (a) providing an aqueous liquid containing or consisting of an organic dye and water; b) measuring a first absorption or first fluorescence of the organic dye of the aqueous liquid; c) irradiating the aqueous liquid with electron radiation having an energy of <600 keV for a predetermined period of time, wherein the electron radiation does not pass through any solid material on its way to the aqueous liquid after exiting an electron exit window of a source of electron radiation; d) measuring a second absorption of the organic dye of the aqueous liquid after the predetermined period of time if a first absorption was measured, and determining a difference between the second absorption and the first absorption, or measuring a second fluorescence of the organic dye of the aqueous liquid after the predetermined period of time if a first fluorescence was measured, and determining a difference between the second fluorescence and the first fluorescence; and e) determining a radiation dose which the aqueous liquid has experienced due to the electron beam radiation during the predetermined period of time based on the determined difference; wherein the organic dye contains or consists of triphenyltetrazolium chloride, tartrazine, bromophenol blue, dimethylene blue, resazurin, xylenol orange, phenol red, or coumarin-3-carboxylic acid. [2] Method according to claim 1, characterized bythat the organic dye contains or consists of triphenyltetrazolium chloride, where i) the concentration of triphenyltetrazolium chloride in the liquid is 0.05 to 0.5% (w / v), particularly preferably 0.2 to 0.2% (w / v); and / or ii) the water is deionized water; and / or iii) the absorption of triphenyltetrazolium chloride is measured at a wavelength in the range of 400 to 500 nm, preferably at 485 nm. [3] Method according to claim 1, characterized by that the organic dye contains or consists of tartrazine, where (i) the concentration of tartrazine in the liquid is 0.3 mM to 0.5 mM, in particular 0.40 to 0.45 mM; and / or ii) the water is deionized water; and / or iii) the absorption of tartrazine is measured at a wavelength in the range of 420 to 430 nm, preferably at 426 nm. [4] Method according to claim 1, characterized bythat the organic dye contains or consists of bromophenol blue, where i) the concentration of bromophenol blue in the liquid is 0.1 to 0.6 mM, particularly preferably 0.3 to 0.5 mM; and / or ii) the water is deionized water; and / or iii) the absorption of bromophenol blue is measured at a wavelength in the range of 430 to 440 nm, preferably at 435 nm. [5] Method according to claim 1, characterized by that the organic dye contains or consists of dimethylene blue, where i) the concentration of dimethylene blue in the liquid is 0.1 to 0.3 mM, particularly preferably 0.15 to 0.25 mM, in particular 0.2 mM; and / or ii) the water is deionized water; and / or iii) the absorption of dimethylene blue is measured at a wavelength in the range of 605 to 615 nm, preferably at 610 nm, or at a wavelength in the range of 660 to 670 nm, preferably at 664 nm. [6] Method according to claim 1, characterized by that the organic dye contains or consists of resazurin, where i) the concentration of resazurin in the liquid is 0.1 to 0.4 mM, particularly preferably 0.15 to 0.25 mM, in particular 0.2 mM; and / or ii) the water is deionized water; and / or iii) the absorption of resazurin is measured at a wavelength in the range of 580 to 630 nm, preferably at 602 nm. [7] Method according to claim 1, characterized by that the organic dye contains or consists of xylenol orange, where i) the concentration of xylenol orange in the liquid is 0.3 to 0.45 mM, particularly preferably 0.35 to 0.40 M, in particular 0.375 mM; and / or ii) the water is deionized water; and / or iii) the absorption of xylene orange is measured at a wavelength in the range of 430 to 440 nm, particularly preferably at 434 nm, or at a wavelength in the range of 550 to 560 nm, particularly preferably at 555 nm; and / or iv) the liquid further contains D-sorbitol, (NH4)2Fe(SO4)2 and ethanol for broader linear measurements of 10-80 Gy and the absorption of xylenol orange is measured at a wavelength in the range of 550 to 560 nm, particularly preferably at 555 nm, wherein in particular the concentration of D-sorbitol is in the range of 20 to 200 mM, the concentration of (NH4)2Fe(SO4)2 is in the range of 0.1 to 0.5 mM and / or the concentration of ethanol is in the range of 1 to 5 vol%, with respect to the total volume of the liquid. [8] Method according to claim 1, characterized by that the organic dye contains or consists of phenol red, where i) the concentration of phenol red in the liquid is 0.05 to 0.1% (w / v), particularly preferably 0.01 to 0.02% (w / v); and / or ii) the water is deionized water; and / or iii) the absorption of phenol red is measured at a wavelength in the range of 400 to 500 nm, preferably at 440 nm. [9] Method according to claim 1, characterized by that the organic dye contains or consists of coumarin-3-carboxylic acid, where i) the concentration of coumarin-3-carboxylic acid in the liquid is 1 to 6 mM, particularly preferably 2 to 3 mM; and / or ii) the water is deionized water; and / or iii) a fluorescence of coumarin-3-carboxylic acid is excited at a wavelength in the range of 300 to 400 nm, preferably at 380 nm; and / or iv) the fluorescence of coumarin-3-carboxylic acid is measured at a wavelength in the range of 400 to 500 nm, preferably at 448 nm. [10] Method according to one of the preceding claims, characterized by that the liquid i) in step a) is provided in at least one well of a microtiter plate and in step b) the first absorption or first fluorescence of the organic dye of the liquid in the microtiter plate is measured, wherein preferably 50 to 100 µl of the liquid is provided in the at least one well of the microtiter plate and / or the microtiter plate is a 96-well microtiter plate; and / or ii) after step c) is provided in at least one well of a microtiter plate and there, if a first absorption was measured, the second absorption of the organic dye of the liquid is measured, or, if a first fluorescence was measured, the second fluorescence of the organic dye of the liquid is measured, wherein preferably 50 to 100 µl of the liquid is provided in the at least one well of the microtiter plate and / or the microtiter plate is a 96-well microtiter plate. [11] Method according to one of the preceding claims, characterized by that in step e) to determine the radiation dose, a comparison is made with a calibration curve which was created for the organic dye in the liquid using a reference dosimeter, optionally a reference film dosimeter, wherein in particular a dependence of the radiation dose on an absorption difference or a fluorescence difference can be derived from the calibration curve. [12] Method according to one of the preceding claims, characterized by that the method according to step e) comprises the following steps: (i) providing an aqueous liquid containing or consisting of water and biological cells, a biological pathogen and / or a chemical pollutant; ii) irradiating the further aqueous liquid with electron radiation having an energy of <600 keV for a further predetermined period of time which is identical to or different from the predetermined period of time, wherein the electron radiation does not pass through any material on its way to the further aqueous liquid which is different from the further aqueous liquid; iii) determining a radiation dose which the further aqueous liquid has experienced due to the electron radiation during the predetermined period of time, from the known further predetermined period of time and from a linear dependence of the radiation dose on an irradiation time, wherein the linear dependence of the radiation dose on the irradiation time was preferably determined by the radiation dose determined in step e) and the known predetermined period of time; wherein particularly preferably - the biological cells are blood cells, the fluid being in particular blood; and / or - the biological pathogen is selected from the group consisting of bacteria, viruses, single-cell organisms, prions and combinations thereof, wherein the liquid in particular contains or consists of a vaccine liquid; and / or - the chemical pollutant is selected from the group consisting of hormones, antibiotics, painkillers and combinations thereof, wherein the liquid is in particular wastewater. [13] Device for determining a radiation dose to which an aqueous liquid is exposed by electron radiation, containing or consisting of (a) an aqueous liquid containing or consisting of an organic dye and water; b) a measuring device configured to measure an absorption or a fluorescence of an organic dye of the aqueous liquid; c) a source of electron radiation configured to radiate electron radiation with an energy of <600 keV through an electron exit window of the source of electron radiation onto the aqueous liquid; and d) a control unit configured to determine a radiation dose that the aqueous liquid has experienced due to the electron beam radiation during the predetermined period of time based on information from the measuring device about an absorption or fluorescence of the organic dye of the aqueous liquid; wherein the device is configured such that the electron radiation from the source of electron radiation does not pass through any solid material on its way to the aqueous liquid after exiting the electron exit window of the source of electron radiation, wherein the organic dye contains or consists of triphenyltetrazolium chloride, tartrazine, bromophenol blue, dimethylene blue, resazurin, xylenol orange, phenol red, or coumarin-3-carboxylic acid. [14] Device according to claim 13, characterized by that the control unit is further configured (i) causing the measuring device to measure a first absorption or first fluorescence of the organic dye of the aqueous liquid; (ii) causing the source of electron radiation to radiate electron radiation with an energy of <600 keV onto the aqueous liquid for a predetermined period of time; f) to cause the measuring device to measure a second absorption of the organic dye of the aqueous liquid after the predetermined period of time if a first absorption was measured, wherein the control unit is configured to determine a difference between the second absorption and the first absorption, or to cause the measuring device to measure a second fluorescence of the organic dye of the aqueous liquid after the predetermined period of time if a first fluorescence was measured, wherein the control unit is configured to determine a difference between the second fluorescence and the first fluorescence; and iii) Based on the difference determined, determine a radiation dose received by the aqueous liquid from electron beam radiation with an energy <600 keV during the predetermined period. [15] Device according to one of claims 13 or 14, characterized bythat the device, optionally also the control unit of the device, is configured to carry out the method according to one of claims 1 to 12.

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