|Abstract||There is a growing need for efficient, biocompatible delivery methods to transport therapeutic genetic material and drugs to specific sites in the body. For the former goal, the successful delivery of genetic material (e.g., DNA, RNA, and oligonucleotides) to cells is a critical step for gene therapy. Nano-scale porous silicon (pSi) materials offer advantages over traditional viral transfection vectors as a consequence of their broadly tunable range of porosities, established surface modification protocols, and high surface area-to-volume ratio. While anodization of silicon wafers remains the most common preparative method for pSi formation, low cost/high throughput production makes stain-etching of metallurgical-grade silicon powder a practical alternative. Surface oxidation of stain-etch derived pSi provides ample sites for further functionalization and electrostatic coupling, as well as high bioavailability as demonstrated by in vitro and in vivo studies of similar materials. In this work we modified nanostructured porous silicon microparticles (SiMPs) using an aminosilanization route and developed an efficient protocol for fluorescent labeling with a fluorescein derivative. This material was then subjected to a novel dispersion method yielding the optimum concentration for in vitro studies. Upon addition to human embryonic kidney (HEK293) cells, we observed no cytotoxicity and a high affinity interaction between the modified SiMPs and the cell surface. Immunofluorescence staining of the cytoskeleton of HEK293 cells and confocal imaging revealed adsorption of fluorescently labeled SiMPs onto the cell membrane. By demonstrating the biocompatibility and high-affinity membrane interaction of surface oxidized, metal-assisted stain-etched mesoporous silicon microparticles with HEK293 cells, we present the possibility of using such material for transfection and gene delivery.