In vivo optical-resolution optoacoustic flow cytometry in the oral mucosa using a transparent silicon-photonics acoustic detector (SPADE).

Complete blood counts are central to clinical practice but require invasive sampling and centralized laboratory analysis. Optical-resolution photoacoustic microscopy provides intrinsic specificity to red blood cells (RBCs) through hemoglobin absorption. However, conventional implementations typically depend on bulky acoustic coupling schemes that hinder clinical translation. Here, we present a compact and integrable, label-free optoacoustic platform that combines optical-resolution excitation in an epi-illumination geometry with a transparent silicon-photonics acoustic detector (SPADE) featuring a wide acoustic acceptance angle that enables detection without strict optical-acoustic co-alignment. System performance was first characterized using optoacoustic point sources and subsequently evaluated in controlled RBC flow experiments within a tapered glass-capillary microfluidic phantom, as well as in vivo measurements of superficial inner-lip capillaries in human volunteers. The transparent SPADE preserved tight optical focusing (≤ 4 µm) and provided an acoustic bandwidth exceeding 100 MHz with a noise-equivalent pressure of approximately 2.3 mPa/Hz¹ ᐟ². Single-RBC transients were robustly detected in the phantom across varying flow conditions, while in vivo measurements at multiple capillary sites yielded reproducible transient signals consistent with individual RBC passages. These results establish a practical framework for stable, fixed-position optoacoustic detection of individual RBCs in superficial human capillaries, demonstrating the potential of transparent SPADE-based systems for non-invasive blood analysis.