Synthesis, Characterization, and Directional Binding of Anisotropic Biohybrid Microparticles for Multiplexed Biosensing

Abstract

Anisotropic microarchitectures with different physicochemical properties have been developed as advanced materials for challenging industrial and biomedical applications including switchable displays, multiplexed biosensors and bioassays, spatially-controlled drug delivery systems, and tissue engineering scaffolds. In this study, anisotropic biohybrid microparticles (MPs) spatio-selectively conjugated with two different antibodies (Abs) are first developed for fluorescence-based, multiplexed sensing of biological molecules. Poly(acrylamide-co-acrylic acid) is chemically modified with maleimide- or acetylene groups to introduce different targeting biological moieties into each compartment of anisotropic MPs. Modified polymer solutions containing two different fluorescent dyes are separately used for electrohydrodynamic co-jetting with side-by-side needle geometry. The anisotropic MPs are chemically stabilized by thermal imidization, followed by bioconjugation of two different sets of polyclonal Abs with two individual compartments via maleimide-thiol coupling reaction and Huisgen 1,3-dipolar cycloaddition. Finally, two compartments of the anisotropic biohybrid MPs are spatio-selectively associated with the respective monoclonal Ab-immobilized substrate in the presence of the antigen by sandwich-type immunocomplex formation, resulting in their ordered orientation due to the spatio-specific molecular interaction, as confirmed by confocal laser scanning microscopy. In conclusion, anisotropic biohybrid MPs capable of directional binding have great potential as a new fluorescence-based multiplexing biosensing system.

Janus particles for (bio)sensing

“…As Fig. 9 shows, sandwich-type immunoassays were performed by biofunctionalization of specific antibodies onto poly(dimethylsiloxane) (PDMS) glass substrates after immunocomplexation with the respective antigen [50]. Janus particles have also been designed to combine sensing and barcoding functions for multiplexed bioanalysis.…”

Magnetic Janus Particles for Static and Dynamic (Bio)Sensing

“…The surface anisotropy of these particles spatially decouples analytical functions (e.g., targeting and sensing) and allows spatial-selective bioconjugation that would otherwise be difficult to combine within the uniform composition or heterogeneous nanoparticles. Therefore, Janus nanoparticles have properties and functions, such as dual-targeting [5] and molecular sensing, which are incompatible when combined in a single structural unit or in heterogeneous "not Janus" nanoparticles, thus, opening opportunities for the construction of truly multifunctional entities [6,7]. Moreover, the asymmetry of the Janus particles surface (ratio of surface area devoted to different surface types on the two sides of the particle) can be varied at will depending on the particular applications without altering, interfering or losing the intrinsic properties of both faces, which makes them a unique category of materials in contrast to other particles.…”

Thermally-Induced Actuations of Stimuli-Responsive, Bicompartmental Nanofibers for Decoupled Drug Release

“…Development of stimuli-responsive, multi-compartmentalized microstructures or nanostructures in the form of particles, cylinders, and fibers has increased interest in a variety of industrial and biomedical applications because they have different physicochemical, optical, and electromagnetic properties and environmental sensitivity in each compartment (Bhaskar et al, 2009; Rahmani and Lahann, 2014). These structures have been widely applied to electronic paper devices, switchable displays, colloidal stabilizers at an interface, self-propelled motors, spontaneous formation of complex structures, multiplexed optical biosensors, multi-modal drug delivery systems, tissue engineering scaffolds, and filamentous actuators for soft robotics (Kaewsaneha et al, 2013; Jung et al, 2014; Pang et al, 2014; Stoychev and Ionov, 2016; Zhou et al, 2016). Specifically, multi-compartmental polymer microcylinders and nanofibers with compositional anisotropy showed controlled shape reconfigurations and reversible anisotropic actuations, depending on environmental stimuli including ultrasound, solvent exchange, temperature, pH, and ionic strength (Lendlein et al, 2001; Chen et al, 2010; Lee et al, 2012; Liu et al, 2012; Qi et al, 2016).…”

“…A number of original platform technologies for synthesis of multi-compartmentalized structures at micro- or nanoscale have been devised based on composition and surface anisotropy: electrohydrodynamic (EHD) co-jetting, microfluidics, flow-focusing lithography, template-assisted polymerization, differential solvent evaporation, spinning disks, selective crystallization, and deposition, partial masking, Pickering emulsion, and self-assembly (Paunov, 2003; Bong et al, 2009; Pardhy and Budhlall, 2010; Du and O'reilly, 2011; Jung et al, 2014; Guignard and Lattuada, 2015; Nisisako, 2016). In particular, EHD co-jetting enables different polymer solutions in miscible aqueous or organic solvent with side-by-side needle geometry to have equilibrated laminar flow and ejection from the vertex of the multi-phasic Taylor cone in a thin-jet stream, induced by charge-charge repulsion under high electrical potential (Barrero et al, 1998; Hogan Jr et al, 2007).…”