Nonlinearly enhanced photoacoustic microscopy by picosecond-laser-pumped excited state absorption of phthalocyanine nanoprobes

Efficient nanoprobes with unique optical properties are highly desirable for good-performance photoacoustic (PA) molecular imaging. The conventionally used PA nanoprobes basically take their ground-state absorption with contrast to the indelible wideband background absorption as the imaging mechanism, thus severely limiting the imaging contrast and sensitivity in practical applications. Herein, a nonlinearly enhanced PA microscopy mechanism with suppressed background interference and improved brightness has been proposed, by distinctively exploiting the picosecond-laser-pumped excited state absorption of the tin phthalocyanine (SnPc) nanoprobes that exhibit strong reverse saturable absorption below the laser damage threshold of tissues. Both theoretical simulation and experimental investigation have been performed to verify the nonlinearly enhanced optical and PA properties of the SnPc nanoprobes with comparison to conventional PA contrast agents. The enhanced PA imaging capability of the SnPc nanoprobes with improved sensitivity and contrast has been demonstrated by tissue-mimicking phantoms and in vivo mouse models. This work revolutionizes the traditional contrast mechanism of PA nanoprobes by introducing picosecond-laser-pumped nonlinear optical nanomaterials, which prefigures great potential for biosensing and bioimaging with improved contrast and sensitivity.