Acoustoelectronic nanotweezers enable dynamic and large-scale control of nanomaterials.

The ability to precisely manipulate nano-objects on a large scale can enable the fabrication of materials and devices with tunable optical, electromagnetic, and mechanical properties. However, the dynamic, parallel manipulation of nanoscale colloids and materials remains a significant challenge. Here, we demonstrate acoustoelectronic nanotweezers, which combine the precision and robustness afforded by electronic tweezers with versatility and large-field dynamic control granted by acoustic tweezing techniques, to enable the massively parallel manipulation of sub-100 nm objects with excellent versatility and controllability. Using this approach, we demonstrated the complex patterning of various nanoparticles (e.g., DNAs, exosomes, ~3 nm graphene flakes, ~6 nm quantum dots, ~3.5 nm proteins, and ~1.4 nm dextran), fabricated macroscopic materials with nano-textures, and performed high-resolution, single nanoparticle manipulation. Various nanomanipulation functions, including transportation, concentration, orientation, pattern-overlaying, and sorting, have also been achieved using a simple device configuration. Altogether, acoustoelectronic nanotweezers overcome existing limitations in nano-manipulation and hold great potential for a variety of applications in the fields of electronics, optics, condensed matter physics, metamaterials, and biomedicine.

Acoustohydrodynamic tweezers via spatial arrangement of streaming vortices.

Acoustics-based tweezers provide a unique toolset for contactless, label-free, and precise manipulation of bioparticles and bioanalytes. Most acoustic tweezers rely on acoustic radiation forces; however, the accompanying acoustic streaming often generates unpredictable effects due to its nonlinear nature and high sensitivity to the three-dimensional boundary conditions. Here, we demonstrate acoustohydrodynamic tweezers, which generate stable, symmetric pairs of vortices to create hydrodynamic traps for object manipulation. These stable vortices enable predictable control of a flow field, which translates into controlled motion of droplets or particles on the operating surface. We built a programmable droplet-handling platform to demonstrate the basic functions of planar-omnidirectional droplet transport, merging droplets, and in situ mixing via a sequential cascade of biochemical reactions. Our acoustohydrodynamic tweezers enables improved control of acoustic streaming and demonstrates a previously unidentified method for contact-free manipulation of bioanalytes and digitalized liquid handling based on a compact and scalable functional unit.

Hardware Design and Fault-Tolerant Synthesis for Digital Acoustofluidic Biochips.

A digital microfluidic biochip (DMB) is an attractive platform for automating laboratory procedures in microbiology. To overcome the problem of cross-contamination due to fouling of the electrode surface in traditional DMBs, a contactless liquid-handling biochip technology, referred to as acoustofluidics, has recently been proposed. A major challenge in operating this platform is the need for a control signal of frequency 24 MHz and voltage range ±10/±20 V to activate the IDT units in the biochip. In this paper, we present a hardware design that can efficiently activate/de-activated each IDT, and can fully automate an bio-protocol. We also present a fault-tolerant synthesis technique that allows us to automatically map biomolecular protocols to acoustofluidic biochips. We develop and experimentally validate a velocity model, and use it to guide co-optimization for operation scheduling, module placement, and droplet routing in the presence of IDT faults. Simulation results demonstrate the effectiveness of the proposed synthesis method. Our results are expected to open new research directions on design automation of digital acoustofluidic biochips.

Acoustic streaming vortices enable contactless, digital control of droplets.

Advances in lab-on-a-chip technologies are driven by the pursuit of programmable microscale bioreactors or fluidic processors that mimic electronic functionality, scalability, and convenience. However, few fluidic mechanisms allow for basic logic operations on rewritable fluidic paths due to cross-contamination, which leads to random interference between "fluidic bits" or droplets. Here, we introduce a mechanism that allows for contact-free gating of individual droplets based on the scalable features of acoustic streaming vortices (ASVs). By shifting the hydrodynamic equilibrium positions inside interconnected ASVs with multitonal electrical signals, different functions such as controlling the routing and gating of droplets on rewritable fluidic paths are demonstrated with minimal biochemical cross-contamination. Electrical control of this ASV-based mechanism allows for unidirectional routing and active gating behaviors, which can potentially be scaled to functional fluidic processors that can regulate the flow of droplets in a manner similar to the current in transistor arrays.

Contactless, programmable acoustofluidic manipulation of objects on water.

Contact-free manipulation of small objects (e.g., cells, tissues, and droplets) using acoustic waves eliminates physical contact with structures and undesired surface adsorption. Pioneering acoustic-based, contact-free manipulation techniques (e.g., acoustic levitation) enable programmable manipulation but are limited by evaporation, bulky transducers, and inefficient acoustic coupling in air. Herein, we report an acoustofluidic mechanism for the contactless manipulation of small objects on water. A hollow-square-shaped interdigital transducer (IDT) is fabricated on lithium niobate (LiNbO3), immersed in water and used as a sound source to generate acoustic waves and as a micropump to pump fluid in the ±x and ±y orthogonal directions. As a result, objects which float adjacent to the excited IDT can be pushed unidirectionally (horizontally) in ±x and ±y following the directed acoustic wave propagation. A fluidic processor was developed by patterning IDT units in a 6-by-6 array. We demonstrate contactless, programmable manipulation on water of oil droplets and zebrafish larvae. This acoustofluidic-based manipulation opens avenues for the contactless, programmable processing of materials and small biosamples.

Micro-Electrode-Dot-Array Digital Microfluidic Biochips: Technology, Design Automation, and Test Techniques.

Digital microfluidic biochips (DMFBs) are being increasingly used for DNA sequencing, point-of-care clinical diagnostics, and immunoassays. DMFBs based on a micro-electrode-dot-array (MEDA) architecture have recently been proposed, and fundamental droplet manipulations, e.g., droplet mixing and splitting, have also been experimentally demonstrated on MEDA biochips. There can be thousands of microelectrodes on a single MEDA biochip, and the fine-grained control of nanoliter volumes of biochemical samples and reagents is also enabled by this technology. MEDA biochips offer the benefits of real-time sensitivity, lower cost, easy system integration with CMOS modules, and full automation. This review paper first describes recent design tools for high-level synthesis and optimization of map bioassay protocols on a MEDA biochip. It then presents recent advances in scheduling of fluidic operations, placement of fluidic modules, droplet-size-aware routing, adaptive error recovery, sample preparation, and various testing techniques. With the help of these tools, biochip users can concentrate on the development of nanoscale bioassays, leaving details of chip optimization and implementation to software tools.