Optical-resolution photoacoustic microscopy (OR-PAM) is a novel label-free microscopic imaging tool to provide in vivo optical absorbing contrasts. Specially, it is crucial to equip a real-time imaging capability without sacrificing high signal-to-noise ratios (SNRs) for identifying and tracking specific diseases in OR-PAM. Herein we demonstrate a 2-axis water-proofing MEMS scanner made of flexible PDMS. This flexible scanner results in a wide scanning range (9 × 4 mm² in a transverse plane) and a fast imaging speed (5 B-scan images per second). Further, the MEMS scanner is fabricated in a compact footprint with a size of 15 × 15 × 15 mm³. More importantly, the scanning ability in water makes the MEMS scanner possible to confocally and simultaneously reflect both ultrasound and laser, and consequently we can maintain high SNRs. The lateral and axial resolutions of the OR-PAM system are 3.6 and 27.7 μm, respectively. We have successfully monitored the flow of carbon particles in vitro with a volumetric display frame rate of 0.14 Hz. Finally, we have successfully obtained in vivo PA images of microvasculatures in a mouse ear. It is expected that our compact and fast OR-PAM system can be significantly useful in both preclinical and clinical applications.

Multifunctional nanoparticles have been widely investigated for biomedical applications, such as imaging, therapy, and drug delivery. Especially, photoactive nanoparticles have received great attention as theranostic agents because of their heat-generating abilities after exposure to laser irradiation. However, photostability and safety issues have been the technical hurdles for further clinical applications. Here, we designed nitrogen (N)-doped carbon nanodots (N-CNDs) that have strong absorption in the near-infrared region, high photostability, and excellent biodegradability. Optimized N-CNDs can be utilized not only as a new photoacoustic (PA) imaging agent but also as a superior photothermal therapy (PTT) agent in vivo because of their strong optical absorption at a specific wavelength. We used N-CNDs to perform in vivo/ex vivo noninvasive PA imaging of sentinel lymph nodes via local delivery and performed PTT for cancer ablation therapy. Finally, biodegradation and renal clearance were confirmed by performing whole-body PA monitoring and a degradation test.

Optical resolution photoacoustic microscopy (OR-PAM) is a non-invasive, label-free method of in vivo imaging with microscopic resolution and high optical contrast. Based on intrinsic contrasts, OR-PAM has expanded to include in vivo vessel imaging, flow cytometry, physiological parameter analysis, and single-cell characterization. However, since conventional OR-PAM systems have a fixed tabletop configuration, a large system size, and slow imaging speed, their use in preclinical and clinical studies remains limited. In this study, using microelectromechanical systems (MEMS) technology, we developed a handheld PAM probe with a high signal-to-noise ratio and image rate. To enable broader application of the OR-PAM system, we reduced its size and combined its fast scanning capabilities into a small handheld probe that uses a 2-axis waterproof MEMS scanner (2A-WP-MEMS scanner). All acoustical, optical, and mechanical components are integrated into a single probe with a diameter of 17 mm and a weight of 162 g. This study shows phantom and in vivo images of various samples acquired with the probe, including carbon fibers, electrospun microfibers, and the ear, iris, and brain of a living mouse. In particular, this study investigated the possibility of clinical applications for melanoma diagnosis by imaging the boundaries and morphology of a human mole.