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S.M. Maswadi, R.D. Glickman, N. Barsalou, W.R. Elliott; Detection of Pharmacological Agents in the Eye Using Photoacoustic Spectroscopy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3291.
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The objective of this research is to develop a non– or minimally–invasive method for detecting and measuring specific drugs and biomolecules in vivo using photoacoustic spectroscopy (PAS). This pilot study investigated the feasibility of measuring the concentration of model pharmacological agents in the vitreous or aqueous of the eye.
As a prototype for using PAS for molecular detection in vivo, the technique was applied in an ocular phantom containing excised porcine tissue to detect molecules with known optical absorption spectra, such as Trypan Blue, Rose Bengal, Indocyanine Green (ICG), and Amphotericin B (AB), at concentrations as low as 1 µg/ml. A Q–switched Nd:YAG laser emitting 10 ns pulses at 532 nm was used as a pump source to generate ultrasonic photo–acoustic signals in the ocular phantom in the presence and absence of drug solutions. The acoustic responses were detected with an ultrasonic hydrophone, as well as by photothermal deflection, a high sensitivity, non–contact optical method. Theoretical modeling of photoacoustic propagation in a simple eye model was performed with analytical and numerical solutions to predict the amplitude of the PAS signal in the presence of drug molecules.
A strong photoacoustic signal, generated from the tissue, was used as a reference to measure light transmission through solutions of drugs of different concentrations in the phantom, and was found to follow a linear dependence on drug concentration as predicted by the Beer–Lambert law.
Photoacoustic spectroscopy is feasible in an ocular phantom. The signals recorded using PAS were found to be linearly dependent on drug concentration, as predicted by theory. The photoacoustic technique was found to be sensitive to drug concentrations as low as 1 µg/ml, a clinically relevant concentration for many drugs. Future work will aim to apply this method in vivo, and will utilize an optical parametric oscillator to optimize the pump wavelength for specific analytes.
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