(J-365) Precise Electrokinetic Position and 3D Orientation Control of a Nanowire Bioprobe in Solution

Introduction:: Motorizing micro/nanoparticles into active nanotools and probes with ultrahigh precision will open unmatched opportunities in single-cell biology, drug delivery, and cell-cell communication. However, the temperature-inherited Brownian motion force on a particle in solution has greatly hindered this potential. Therefore, most nanoprobes used in biomedical and electronic studies are attached to a cantilever. In this work, we report an innovative anti-Brownian-motion scheme that, for the first time, simultaneously controls both the two-dimensional (2D) positioning and three-dimensional (3D) orientation of an anisotropic particle, which makes it possible to probe biosamples with the particle’s nanotips while offering ultrahigh manipulation precision owing to its microlong body with suppressed Brownian motion. With this technique, both simple and sophisticated longitudinal nanoparticles can be manipulated; the precision reaches 17 nm in positioning and 0.5° in angle, the highest performance achieved among those of various manipulation techniques. A nanowire as small as 300 nm in length and 125 nm in diameter can be fully controlled. This technique is applied to detect the metabolite release from single E. coli cells with a mobile nanosensor for extended periods via surface-enhanced Raman spectroscopy (SERS). The reported concept, scheme, and device could underpin myriad opportunities in precision medicine, single-cell biology.


Materials and Methods:: The device consists of in-plane Au quadruple microelectrodes on the XY plane and two Indium Tin Oxide (ITO) glasses in the Z direction. Nanoparticles in suspension are confined in the PDMS microwell and subjected to electric signals applied along three directions, X, Y, and Z. Here, the transportation of particles is realized by applying DC voltages on microelectrode pairs through electroosmosis/electrophoresis. Alignment of the particle is realized by applying AC E-field through electroalignment. Rotation of the particles is achieved by applying four AC voltages with a 90° sequential phase shift through electrorotation. By superimposing the DC and AC voltages, both the transportation and orientation can be controlled simultaneously. A vision-based feedback loop is implemented to actively counter the translational and rotational Brownian motion and realize high-precision control.

Fabrication of SERS-active nanoprobe: Au nanowires are electrodeposited into nanoporous templates followed by dispersion in water. Then, a SiO₂ layer is coated on the Au nanowires via hydrolysis of Tetraethyl orthosilicate. Finally, high-density Ag nanoparticles are grown on the silica-coated surface via polyvinylpyrrolidone-assisted Ag ions reduction. The high-density Ag nanoparticles provide large arrays of hot spots for SERS detection.


Results, Conclusions, and Discussions:: In summary, we report an electric nanomanipulation system that can simultaneously control both the 3D orientation and 2D position of an anisotropic nanoparticle with unprecedented spatial and temporal control, and versatile motion gaits and tracing capability. Furthermore, the system can easily operate via (i) passive trapping a particle, which operates like optical tweezers, and (ii) active transporting a particle without a mechanical moving part. We obtain a manipulation precision as high as 21 ± 3 nm and 0.51 ± 0.04°, corresponding to a trapping stiffness of 4.3×10^-6 N/m and 5.2×10^-17 N·m/rad. The demonstrated capability is the best among various untethered nanoparticle manipulation techniques. For demonstration, we operate a vertically aligned nanoprobe and precisely position its tip on an E. coli cell to sense the released metabolites. This work could break new ground for research in micro/nanorobotics, subcellular bio-probing, nanosurgery, and single-cell signal release and detection.

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