Pinch-off droplet generator using microscale gigahertz acoustics.

The generation and dispensing of microdroplets is a vital process in various fields such as biomedicine, medical diagnosis and chemistry. However, most methods still require the structures of nozzles or microchannels to assist droplet generation, which leads to limitations on system flexibility and restrictions on the size range of the generated droplets. In this paper, we propose a nozzle-free acoustic-based method for generating droplets using a gigahertz (GHz) bulk acoustic wave (BAW). Unlike most of the acoustofluidic approaches, the proposed method produces the droplet by pinching-off the liquid column generated by the acoustic body force at the oil-water interface. Benefitting from the focused acoustic energy and small footprint of the device, four orders of magnitude (ranging from 2 µm to 1800 µm) of droplet size could be produced by controlling the working time and power of the device. We also demonstrated cell encapsulation in the droplet and a high cell viability was achieved. The proposed acoustic-based droplet generation method exhibits capacity for generating droplets with a wide size range, versatility toward different viscosities, as well as biocompatibility for handling viable samples, which shows potential in miniaturization and scalability.

Self-adaptive virtual microchannel for continuous enrichment and separation of nanoparticles.

The transport, enrichment, and purification of nanoparticles are fundamental activities in the fields of biology, chemistry, material science, and medicine. Here, we demonstrate an approach for manipulating nanospecimens in which a virtual channel with a diameter that can be spontaneously self-adjusted from dozens to a few micrometers based on the concentration of samples is formed by acoustic waves and streams that are triggered and stabilized by a gigahertz bulk acoustic resonator and microfluidics, respectively. By combining a specially designed arc-shaped resonator and lateral flow, the in situ enrichment, focusing, displacement, and continuous size-based separation of nanoparticles were achieved, with the ability to capture 30-nm polystyrene nanoparticles and continuously focus 150-nm polystyrene nanoparticles. Furthermore, exosome separation was also demonstrated. This technology overcomes the limitation of continuously manipulating particles under 200 nm and has the potential to be useful for a wide range of applications in chemistry, life sciences, and medicine.

100% Single Cell Encapsulation via Acoustofluidic Printing Based on a Gigahertz Acoustic Resonator.

In this study, an acoustofluidic printing system for generation of single-cell droplets based on a gigahertz acoustic resonator was proposed and verified. The working area of the resonator has a typical dimension of 10×10 micrometer which is very suitable for single cell printing. Single cells were encapsulated in picoliter droplets and printed directly to a flat substrate without any significant influence on their viability. By combining an optic feed-back loop, a 100% single-cell encapsulation rate is achieved.Clinical Relevance- This acoustic-based system has good biocompatibility and high encapsulation rate, which expands the mechanism of medical and biology studies.

Continuous Enrichment and Separation of Nanoparticles via Acoustic Streaming.

Enrichment and separation of Micro/Nano-scale specimens are fundamental requirements in biomedical researches. In this paper, we demonstrated a simple and efficient microfluidic chip for the continuous enrichment and separation of nanoscale polystyrene particles using the acoustic streaming induced by gigahertz(GHz) bulk acoustic waves(BAW). The bulk acoustic resonator released ultrahigh frequency (2GHz) acoustic waves into the fluid and triggered the acoustic streaming. The nanoparticles were continuous concentrated and segregated by the combination action of the viscosity force and the acoustic radiation force. The separation of 300 and 100 nm particles was achieved with the high purity (92.4%). These data contribute proof-in-principle that acoustic streaming is a label-free strategy that can be used to enrich and separate nanoscale specimens with high efficiency.

An on-demand femtoliter droplet dispensing system based on a gigahertz acoustic resonator.

On-demand droplet dispensing systems are indispensable tools in bioanalytical fields, such as microarray fabrication. Biomaterial solutions can be very limited and expensive, so minimizing the use of solution per spot produced is highly desirable. Here, we proposed a novel droplet dispensing method which utilizes a gigahertz (GHz) acoustic resonator to deposit well-defined droplets on-demand. This ultra-high frequency acoustic resonator induces a highly localized and strong body force at the solid-liquid interface, which pushes the liquid to generate a stable and sharp "liquid needle" and further delivers droplets to the target substrate surface by transient contact. This approach is between contact and non-contact methods, thus avoiding some issues of traditional methods (such as nozzle clogging or satellite spots). We demonstrated the feasibility of this approach by fabricating high quality DNA and protein microarrays on glass and flexible substrates. Notably, the spot size can be delicately controlled down to a few microns (femtoliter in volume). Because of the CMOS compatibility, we expect this technique to be readily applied to advanced biofabrication processes.

Cellphone-Enabled Microwell-Based Microbead Aggregation Assay for Portable Biomarker Detection.

Quantitative biomarker detection methods featured with rapidity, high accuracy, and label-free are demonstrated for the development of point-of-care (POC) technologies or "beside" diagnostics. Microbead aggregation via protein-specific linkage provides an effective approach for selective capture of biomarkers from the samples, and can directly readout the presence and amount of the targets. However, sensors or microfluidic analyzers that can accurately quantify the microbead aggregation are scared. In this work, we demonstrate a microwell-based microbeads analyzing system, by which online manipulations of microbeads including trapping, arraying, and rotations can be realized, providing a series of microfluidic approaches to layout the aggregated microbeads for further convenient characterizations. Prostate specific antigen is detected using the proposed system, demonstrating the limit of detection as low as 0.125 ng/mL (3.67 pM). A two-step reaction kinetics model is proposed for the first time to explain the dynamic process of microbeads aggregation. The developed microbeads aggregation analysis system has the advantages of label-free detection, high throughput, and low cost, showing great potential for portable biomarker detection.