H. Li, D. Teal, Z. Liang, D. Fan
The University of Texas at Austin,
United States
Keywords: nanomanipulation, electrokinetic traps, single-cell analysis, nanoprobes
Summary:
Advancements in micro- and nano-fluidic systems have paved the way for transformative applications in life sciences and biotechnology. Central to these innovations is the precise manipulation of functional micro/nanoparticles, which serve as active tools for probing and interacting with biological systems at the subcellular level. Despite significant progress, Brownian motion—a fundamental challenge in nanoscale environments—has hindered precise control, especially when probing delicate structures like cell membranes or individual bacterial cells. In this work, we present an innovative anti-Brownian-motion manipulation scheme using electric fields to achieve ultrahigh precision control of anisotropic nanoparticles. These nanoprobes, designed with nanoscale tips and micrometer-scale lengths, enable simultaneous two-dimensional (2D) positioning and three-dimensional (3D) orientation with unprecedented accuracy—under 20 nm for position and 0.5° for angular alignment. This high level of control allows us to directly probe subcellular components and maintain stable interactions with biological structures, overcoming the inherent trade-off between resolution and manipulation stability. We demonstrate the versatility and impact of this technique through applications in single-cell analysis. By employing anisotropic particles as mobile nanosensors, we achieved location-specific detection of metabolites released from individual E. coli cells via surface-enhanced Raman spectroscopy (SERS). Additionally, the method enabled the dynamic assembly of nanoarrays and the use of plasmonic nanorods as precision tools for biochemical delivery and analysis. This advanced manipulation approach represents a significant leap in the fields of lab-on-chip technologies, microfluidics, and biomedical sensing. By motorizing nanoparticles into active probes and tools, our work opens new avenues for precision delivery, medical micro/nanorobots, position-deterministic nano-assembly, and real-time single-cell studies. These innovations align with emerging applications in drug delivery, nanoscale biosensing, and the development of dynamic nanodevices, offering exciting opportunities for integration into next-generation lab-on-chip systems.