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Currently silicon nanoparticles (SiNPs) has high potential for biophotonics applications due to combination of specific optical properties with fast biodegradation, biocompability and low toxic level [1, 2]. For efficient penetration of such structures into living tissue they should preferably be less than 100 nm in size. Traditional nanoparticle fabrication techniques of mechanical milling and ultrasound grinding do not allow to ensure the required size. As an alternative, chemically pure SiNPs with the desirable size can be synthesized via pulsed laser ablation of crystalline silicon targets in liquids [3]. However, relatively low product yield is a significant disadvantage of this technique. In our work we present a hybrid approach based on sequential electrochemical etching and pulsed laser ablation in liquids. As a result, the porous silicon layers serving as targets possess reduced ablation threshold and larger ablation yield in comparison with unprocessed crystalline silicon. Laser ablation of the porous silicon layers produced by electrochemical etching was performed in ethanol and liquid nitrogen using a picosecond Nd:YAG laser ESKPLA PL2143A (1064 nm, 35 ps, 10 mJ, 10 Hz). Atomic force and scanning electron microscopy revealed that the applied technology allows to form SiNPs with sizes from 5 to 100 nm depending on the employed buffer medium. In accordance with Raman spectroscopy data,the volume fraction of the crystalline phase in SiNPs is higher than 87% for all considered liquids. The SiNPs fabricated in ethanol and liquid nitrogen demonstrate efficient photoluminescence with emission maxima in the range of 700 – 800 nm, which suits the requirements for biomedical in vivo applications. Therefore, such nanoparticles are promising as fluorescent markers. Spectrophotometry measurements of suspensions of ablated SiNPs in ethanol revealed effective light scattering. Optical coherence tomography (OCT) imaging of the suspensions drops administered on agar gel surfaces indicated high efficiency of the SiNPs as contrast agents providing the contrast up to 30 dB. Thus, the perspectives of the SiNPs formed via pulsed laser ablation of porous silicon in optical bioimaging are demonstrated. This work was supported by the Russian Science Foundation (project № 19-12-00192). 1. Stojanoviс V., Cunin F., Durand J.O., et al. J. Mater. Chem. B 4, 7050–7059 (2016). 2. Tolstik E., Osminkina L.A., Matthäus C., et al., Nanomedicine: NBM 12(7), 1931–1940 (2016). 3. Perminov P.A., Dzhun I.O., A.A. Ezhov, et al. Las. Phys. 21(4), 801–804 (2011).