Book excerpt: Single chain nanoparticles (SCNPs) have recently achieved great success because of their significant potential in applications such as separation science and drug delivery. A major aim of these studies was to establish the factors that control their size. However, the effect of the spacer length between the polymer backbone and the cross-linkable site is not well established. This study presents the preparation of two series of linear polymers and their SCNPs with two different spacer lengths (3- and 11-carbons) in order to investigate the effect of the spacer on various properties of the nanoparticles. Sol-gel chemistry was used to crosslink single chains under conditions that prefer intramolecular cross-linking. The first series was poly[methyl methacrylate-co-3-(triisopropoxysilyl)propyl methacrylate]. Nanoparticles were prepared from copolymers containing 9 mol% silane monomer and with different molecular weights. Nanoparticles were also prepared from copolymers containing 22 and 31 mol% silane monomer. The second copolymer series was poly[methyl methacrylate-co-11-(triisopropoxysilyl)undecyl methacrylate]. The corresponding hyperbranched polymers were being prepared to determine the effect of polymer architecture on the preparation and properties of SCNPs. For this comparison. The silane-containing inimer, [2-bromo-2-(3'-triisopropoxysilyl)propan-1-oxycarbonyl]ethyl methacrylate was synthesized by hydrosilation of the allyl inimer, [2-bromo-2-(allyl-1-oxycarbonyl]ethyl methacrylate. The hyperbranched precursor polymers were prepared via atom transfer radical polymerization of the silyl inimer. Nanoparticles were produced by hydrolysis and condensation of the triisopropoxysilyl groups under pseudo-high dilution conditions to guarantee intramolecular crosslinking. To investigate the nanoparticle applicability as a stationary phase in chromatography, inverse gas chromatography (IGC) was used to thermodynamically characterize the prepared polymers and nanoparticles.