Transport investigations of terbium chelate complexes in a type 1 collagen tissue model using quantitative microendoscopic imaging

摘要

The diffusive transport characteristics of a unique class of small fluorescent molecular probes in an interstitial tissue model are investigated using micro-endoscopy. The probes employed in the present work are organo-metallic complexes of polyazamacrocycles chelated to Terbium. These particular molecules have large Stoke's shifts, making them amendable to tissue analysis. The delocalized electronic structure of the organic chelate absorbs ultra-violate light (approximately 270 nm) and, after inter-molecular transfer, the lanthanide cation fluoresces in the visible region (550 nm). The diffusive transport properties of the probe molecules are related to their chemical structure, which governs their affinity toward the components of the interstitial model. The basic polyazamacrocycle is functionalized with three phosphate groups. Presently, methyl, ethyl, propyl and butyl alkyl chains are added to the phosphate groups on the polyazamacrocycle to modify the affinity of the probes toward the components of the interstitial model. Micro-endoscopy coupled with digital imaging allows remote, quantitative analysis of the transport process in near real time. Cross sectional analysis of the images yields the concentration profile of the probe as it diffuses through the gel. The concentration profile is fit to Fick's second law of diffusion to determine the diffusion coefficient, D, for each of the problem molecules. Presently the measured D values for each of the compounds are typical for small molecules in water (approximately 10$+$MIN@6$/ cm$+2$//sec), however, D is observed to increase with decreasing hydrocarbon chain length which demonstrates interstitial transport is structurally dependent.