1. Field of the Invention
The present invention relates to devices and methods for determining the amount of energy absorbed during irradiation. The present invention particularly relates to devices comprising a material that absorbs radiation in a quantifiable manner and a cooling agent to maintain the temperature of that material within a predetermined range, and the use of these devices for determining the amount of energy absorbed during irradiation, for example during sterilization of a biological material.
2. Background of the Related Art
Many biological materials that are prepared for human, veterinary, diagnostic and/or experimental use may contain unwanted and potentially dangerous biological contaminants or pathogens, such as viruses, bacteria, in both vegetative and spore states, yeasts, molds, fungi, prions or similar agents responsible, alone or in combination, for TSEs and/or single-cell or multicellular parasites. Consequently, it is of utmost importance that any biological contaminant or pathogen in the biological material be inactivated before the product is used. This is especially critical when the material is to be administered directly to a patient, for example in blood transfusions, blood factor replacement therapy, tissue implants, including organ transplants, and other forms of human and/or other animal therapy corrected or treated by surgical implantation, intravenous, intramuscular or other forms of injection or introduction. This is also critical for the various biological materials that are prepared in media or via the culture of cells, or recombinant cells which contain various types of plasma and/or plasma derivatives or other biologic materials and which may be subject to mycoplasmal, prion, ureaplasmal, bacterial, viral and/or other biological contaminants or pathogens.
In order to inactivate such biological contaminants or pathogens, it is often desirable to expose the biological material to radiation. For instance, viruses and bacteria are readily inactivated by gamma radiation at high total doses.
In order to determine the amount of radiation received by a biological material during treatment with radiation, dosimetry is employed. Dosimetry is the part of a radiation process where the amount of energy absorbed during irradiation is quantified. Dosimetry is employed, for instance, to correctly monitor radiation processes during the development, validation and routine process control stages.
For instance, when irradiating biological materials to inactivate biological contaminants and pathogens, dosimetry may be used to determine whether the amount of radiation received by the biological product during irradiation is within a predetermined range. If the amount of radiation received is below a predetermined amount, the contaminants or pathogens in the biological material may not be inactivated. Conversely, if the amount of radiation received is above a predetermined amount, the biological material may lose biological activity. In either case, the biological material would be unsuitable for use.
Dosimeters are devices that, when irradiated, exhibit a quantifiable and reproducible change in some property of the device that may be related to absorbed dose in a given material. Physical and/or chemical changes take place in the device than can be measured using appropriate analytical instrumentation and techniques.
Examples of solid state dosimeters include thermoluminescent dosimeters, lyoluminescent dosimeters, polymethyl methacrylate dosimeters, radiochromicatic film dosimeters, cobalt glass dosimeters and alanine dosimeters. Dosimeters may have various geometries, such as pellets, films and cylinders.
In practice, the dosimeter is irradiated and the amount of radiation received is determined by measuring a characteristic of the dosimeter sensitive to the radiation. For instance, depending on the type of dosimeter employed, luminescence, absorption, or free radical generation may be measured.
When the crystalline form of alanine is irradiated, stable, characteristic free radicals are produced. The number of free radicals is proportional to the radiation dose absorbed by the crystal. By determining the amount of free radicals produced during irradiation, the dose of radiation received may be determined. For alanine dosimeters, the amount of free radicals produced is typically determined by electron spin resonance spectroscopy (ESR). The free radicals generated during irradiation of alanine remain stable; their concentration is subject to only a minor amount of time-dependent change. Additionally, the free radicals generated in crystalline alanine are relatively stable with respect to heat. Examples of alanine dosimeters are disclosed in U.S. Pat. Nos. 4,668,714 and 5,066,863.
Dosimeters may also be used for dose mapping. The process of dose mapping typically includes simulating radiation conditions to be employed for a sample of interest. A dosimeter is fixed in, on or near a simulated sample, the simulated sample is irradiated and the amount of radiation received by the dosimeter during irradiation is determined. The amount of radiation received by the dosimeter corresponds to the amount received by the simulated sample.
U.S. Pat. No. 6,157,028 to Purtle discloses a method of dose mapping. According to Purtle, a dosimeter is packed inside a container under conditions that simulate the conditions under which a material of interest is to be irradiated, e.g., the density of the material within the container approximates the density of the material to be irradiated, the relationship between the container and the radiation source approximates that to be used during irradiation of the material of interest, etc. A mixture of dry animal food and salt pellets approximating the density of dry ice is packed around the container and the container is irradiated. Following irradiation, the dosimeter is analyzed.
Purtle teaches that biological materials are typically irradiated at temperatures below ambient, but states that a dry ice substitute is employed during dose mapping because “[d]osimeters . . . do not give accurate data in cold conditions . . . ” In addition to the dry ice substitute, a material other than the material of interest is employed, such as agar.
The above references are incorporated by reference herein where appropriate for teachings of additional or alternative details, features and/or technical background.
USPTO Backgrounds
USPTO Backgrounds