A first approach toward understanding the targeted design of molecular photoacoustic contrast agents (MPACs) is presented. Optical and photoacoustic Z-scan spectroscopy was used to identify how nonlinear (excited-state) absorption contributes to enhancing the photoacoustic emission of the curcuminBF2 and bis-styryl (MeOPh)2BODIPY dyes relative to Cy3.

Saturable and reverse saturable absorptions are well-known phenomena, originating from the imaginary component of the third order nonlinear optical susceptibility. We note that structures with an axially asymmetric nonlinear absorption can be easily realized from saturable and reverse saturable absorption materials arranged in tandem. In this paper, the basic transmission behavior of such a structure is worked out. Detailed numerical simulations demonstrate passive all-optical diode behavior, and the results are verified experimentally. The principle will work for all light polarizations, has no phase-matching restrictions, and can be extended to a large number of available nonlinear media for possible applications.

An archetypal study is presented to correlate both the optical and the photoacoustic (PA) properties for a diverse selection of dyes whose structural properties range across organic and inorganic, symmetric and asymmetric, and neutral and cationic systems. Three distinct classes of molecular PA contrast agents have been identified and classified according to their optical-PA response as either (i) linear absorbers linear PA emitter, (ii) saturable absorbers weak PA emitter, or (iii) reverse saturable absorbers nonlinear PA emitter. The molecular characteristics instrumental in determining the nature of the dyes optical absorption properties, i.e., ground state molar extinction coefficient (εg), excited state molar extinction coefficient (εe), and excited state lifetime (τ), are discussed to aid in the interpretation of a molecule’s optical vs PA response. An excellent linear PA emitter is established in crystal violet, which exhibits the strongest possible PA signal under low laser fluence conditions in both PA Z-scan and tomography experiments. Ultimately, however, nonlinear reverse saturable absorber (RSA) materials are anticipated to be the most promising dye category for generation of an enhanced nonlinear PA response. Effective RSA behavior is expected for materials showing a high ratio of their excited state vs ground state absorption (εe/εg) while also possessing a long-lived excited state lifetime (τ) permitting sequential two-photon absorption. ZnTPP, C60, and methylene blue each show a nonlinear PA response which correlates well with their RSA optical behavior. Relative to the linear PA emission profile of crystal violet, a 3.8-fold enhancement is observed for the PA emission of ZnTPP at the highest laser fluence of 366 mJ cm–2. Similarly, C60 and methylene blue exhibit nonlinear enhancements of 2.15-fold and 1.38-fold, respectively. Finally, to investigate the practical pros and cons with respect to application of these dyes in PA imaging applications, a concentration dependence of their PA emission is presented at both low and high laser fluences, in addition to a complementary photoacoustic tomography study.

We report a novel photoacoustic Z-scan (PAZ-scan) technique that combines the advantages offered by the conventional Z-scan method and the sensitivity of the photoacoustic detection. The sample is scanned through the focused laser beam and the generated photoacoustic signal is recorded using a 10 MHz focused ultrasound transducer. Since the signal strength is directly proportional to the optical absorption, PAZ-scan displays nonlinear behavior depicting the nonlinear optical absorption of the material. Among many advantages, our experiments on mouse blood show that PAZ-scan can potentially be used as a standard technique to calibrate contrast agents used in theranostics in general and photoacoustics in particular.

The synthesis and characterization of a series of donor-π-acceptor-π-donor (D-A-D) curcuminoid molecules is presented herein that incorporates π-extended aryl and electron-donating amino terminal functionalization. Computational evaluation shows these molecules possess quadrupolar character with the lowest energy transitions displaying high molar extinction coefficients with broad tunability through manipulation of terminal donating groups. Consistent with their quadrupolar nature, these molecules show varying degrees of solvatochromic behavior in both their absorption and emission spectra, which has been analyzed by Lippert-Mataga and Kamlet-Taft analysis. Photophysical and photoacoustic (PA) properties of these molecules have been investigated by the optical photoacoustic z-scan (OPAZ) method. Selected curcuminoid molecules display nonlinear behavior at a high laser fluence through excited state absorption that translates to the production of an enhanced photoacoustic emission. A relative comparison of "molar PA emission" is also presented with the crystal violet linear optical absorbing/linear PA emitting system being utilized as a standard reference material for OPAZ experiments. Furthermore, PA tomography experiments are presented to illustrate the enhanced PA contrast obtainable via an excited state absorption.