Programmable multi-DNA release from multilayered polyelectrolytes using gigahertz nano-electromechanical resonator

Abstract

Background Controllable and multiple DNA release is critical in modern gene-based therapies. Current approaches require complex assistant molecules for combined release. To overcome the restrictions on the materials and environment, a novel and versatile DNA release method using a nano-electromechanical (NEMS) hypersonic resonator of gigahertz (GHz) frequency is developed. Results The micro-vortexes excited by ultra-high frequency acoustic wave can generate tunable shear stress at solid–liquid interface, thereby disrupting molecular interactions in immobilized multilayered polyelectrolyte thin films and releasing embedded DNA strands in a controlled fashion. Both finite element model analysis and experiment results verify the feasibility of this method. The release rate and released amount are confirmed to be well tuned. Owing to the different forces generated at different depth of the films, release of two types of DNA molecules with different velocities is achieved, which further explores its application in combined gene therapy. Conclusions Our research confirmed that this novel platform based on a nano-electromechanical hypersonic resonator works well for controllable single and multi-DNA release. In addition, the unique features of this resonator such as miniaturization and batch manufacturing open its possibility to be developed into a high-throughput, implantable and site targeting DNA release and delivery system. Electronic supplementary material The online version of this article (10.1186/s12951-019-0518-7) contains supplementary material, which is available to authorized users.

Acoustofluidic Tweezers for the 3D Manipulation of Microparticles

“…4(a). Previous publication has confirmed that at the gigahertz frequency, the power of the acoustic wave attenuates to almost zero within hundreds of micrometers in water [33]. In this study, the distance between the manipulated particle and the transducer over one centimeter, the particle is only affected by the hydrodynamic force but without the influence of the acoustic radiation force.…”

Controllable Cell Deformation Using Acoustic Streaming for Membrane Permeability Modulation

“…Gigahertz acoustic resonator was fabricated as described in previous publication. [ 35 ] Briefly, Bragg mirror structure consisting of alternating layers of silicon dioxide (SiO 2 ) and aluminum nitride (AlN) was deposited on Si wafer for acoustic wave reflection. 600 nm molybdenum (Mo), 1000 nm AlN, 60 nm chromium (Cr), and 300 nm gold (Au) were then deposited and patterned to form a sandwich structure for acoustic vibration.…”

“…Here, we present a noncontact platform for the controllable and tunable cell deformation based on the hydrodynamic force generated from acoustic streaming under gigahertz (GHz) resonator excitation. Previous studies from our group have revealed the ability of such microfabricated resonator to generate localized and high‐speed fluid motion due to the rapid attenuation of acoustic energy in liquid environment, and its biomedical applications for microscale fluidic mixing, [ 34 ] tuning biomolecule–surface interactions [ 35,36 ] and particle manipulations. [ 37 ] We have reported a drug delivery method based on gigahertz resonator, [ 38 ] in which the delivery mechanism and the acoustic streaming generation were not fully explored.…”

DNA Interaction with a Polyelectrolyte Monolayer at Solution—Air Interface

“…A similar behavior was also reported in our recent work on solutions of the mixture of DNA and synthetic polyelectrolytes [ 38 ]. Indeed, while previous works have addressed the conformation of DNA with synthetic polyelectrolytes at the solution–solid interface [ 39 , 40 ], far fewer studies have addressed such interactions at the solution—air interface. Our recent work on the interactions of DNA with synthetic polyelectrolytes revealed that fibrous aggregates formed at the solution surface depend both on the hydrophobicity of the synthetic polyelectrolyte and the bulk molar mixing ratio [ 38 ].…”