Ultraviolet irradiation of blood and blood components is receiving new attention as a therapy for certain leukemias, as a component of immunosuppression therapies, as a method of combatting refractoriness of patients to repeated platelet transfusions, and as a method of sterilizing blood components intended for therapeutic use. While the physical principles that underline the delivery of UV are known, they have not been carefully applied to analysis and design of such systems. A large body of potentially useful information exists within the literature of chemical engineering that deals with the design of industrial photoreactors, including those processing suspensions. This proposal envisions adaptation and application of this knowledge as a means: (i) of better interpreting biological research into the effects of UV on blood constituents, (ii) of attacking the problem of concentrating UV energy on the particular constituents or organelles of blood where photoreaction is desired, and (iii) of improving the uniformity with which UV energy is delivered to individual members (e.g. cells) of a desired target population. Effort will be directed to understanding the fraction of incident energy absorbed in different microscopic """"""""regions"""""""": suspending fluid between cells, at cell surfaces, and intracellulary, using chemical actinometers based on fluorescence bleaching which have been concentrated in the regions of interest. The quantitative role of """"""""sensitizers"""""""" (including the dose response to them) in modifying where energy is deposited will be examined. A one-source-multiple-sink model for these processes is proposed to summarize possibly complex results usefully. A """"""""microscopic"""""""" analysis of the whole reactor is also proposed including ascertaining -- and assessing the importance of -- residence time distributions, spatial segregation of components (particularly cells), and the distribution of radiant energy. The assessment of uniformity of UV dosage to cells will be determined by cytofluorography of may single cells after they have been photobleached in prototype reactors.
|Mandrusov, E; Houng, A; Klein, E et al. (1995) Membrane-based cell affinity chromatography to retrieve viable cells. Biotechnol Prog 11:208-13|