Surface Chemistry of Paramagnetic Submicron Particles

Paramagnetic submicron particles (MSP) are pivotal biomaterials for the physical separation of biochemicals from liquid mixtures. In general, favorable MSPs should exhibit good structural stability, fast response rates to external magnetic fields, reasonable suspension stability, abundant accessible reactive groups, high dispersion rates of both the reactive MSPs and their conjugates, high conjugation percentages of trace proteins, large capacity to conjugate proteins, high specific activities of the conjugated proteins and negligible nonspecific adsorption of proteins. The structural stability and magnetic response rates of MSPs are determined primarily by their interior structures, while other features are mainly determined by their surfaces.

MSPs usually have the core-shell structures. The paramagnetic properties of MSPs originate from Fe₃O₄ or g-Fe₂O₃ as the paramagnetic nanocores, which are susceptible to oxidation and acid corrosion. In favorable MSPs, the environment of such paramagnetic nanocores should be optimized for the structural stability of MSPs. Moreover, larger MSPs have faster magnetic response rates, but lower suspension stability and smaller capacity to conjugate proteins. In general, special core structures of lower density are needed in MSPs for the required suspension stability. On the other hand, the surface chemistries for favorable MSPs are rather sophisticated. When the averaged mass weights are considered, larger capacity of MSPs to conjugate proteins requires smaller sizes and more accessible reactive groups. The long-distance repulsion interactions among MSPs enhance their dispersion rates and suspension stability. The use of long linear arms between MSPs and the conjugated proteins is plausible for higher specific activities. The nonspecific adsorption of trace proteins of interest through hydrophobic interactions facilitates their conjugation to MSPs, but potentially causes higher nonspecific adsorption and faster denaturation rates of conjugated proteins. Electronic attractions between MSPs and proteins also facilitate the conjugation of trace proteins at no risk of the accelerated denaturation of the conjugated proteins, but are limited to proteins bearing opposite charges. The engineering of a large number of the same charged groups on MSPs and abundant reactive groups through long linear arms is needed to enhance their application performance. The systematical optimizations of the designs were demonstrated by the patent application (no. 201610963764.X in China and PCT/CN2017/082374), claimed by Chongqing Far-sighted-blue-dragon (FBD) Biotechnology Co. Ltd.(China).