Acoustic Wave-Driven Functionalized Particles for Aptamer-Based Target Biomolecule Separation

Abstract

We developed a hybrid microfluidic device that utilized acoustic waves to drive functionalized microparticles inside a continuous flow microchannel and to separate particle-conjugated target proteins from a complex fluid. The acoustofluidic device is composed of an interdigitated transducer that produces high-frequency surface acoustic waves (SAW) and a polydimethylsiloxane (PDMS) microfluidic channel. The SAW interacted with the sample fluid inside the microchannel and deflected particles from their original streamlines to achieve separation. Streptavidin-functionalized polystyrene (PS) microparticles were used to capture aptamer (single-stranded DNA) labeled at one end with a biotin molecule. The free end of the customized aptamer15 (apt15), which was attached to the microparticles via streptavidin-biotin linkage to form the PS-apt15 conjugate, was used to capture the model target protein, thrombin (th), by binding at exosite I to form the PS-apt15-th complex. We demonstrated that the PS-apt15 conjugate selectively captured thrombin molecules in a complex fluid. After the PS-apt15-th complex was formed, the sample fluid was pumped through a PDMS microchannel along with two buffer sheath flows that hydrodynamically focused the sample flow prior to SAW exposure for PS-apt15-th separation from the non-target proteins. We successfully separated thrombin from mCardinal2 and human serum using the proposed acoustofluidic device.

Recent Microdevice-Based Aptamer Sensors

“…The acoustic wave induced by an IDT is propagated in a thin layer at a piezoelectric surface. Ahmad et al [ 100 ] proposed a microfluidic device that applies acoustic waves to drive functionalized microparticles into a continuous flow microchannel to separate particle-conjugated target proteins from the sample. This platform utilized an IDT transducer (with an Au-Cr layer) that was patterned on top of the piezoelectric lithium niobate (LiNbO 3 ) substrate to generate high-frequency surface acoustic waves (SAWs).…”

“… ( a ) Specific aptamer to form a microparticle−aptamer−target complex; the unbound particles remained in a free condition; ( b ) Separation process of the mixture solution through an acoustofluidic device. Reproduced with permission from reference [ 100 ]. Copyright 2017 American Chemical Society.…”

Lab-on-a-Chip Systems for Aptamer-Based Biosensing

“…SAW biosensors have been applied in clinical diagnosis due to their inherent advantages of high sensitivity, low cost, low power requirement and real-time monitoring capability. The integration of SAW technologies with microfluidics has created a new field called acoustofluidics that offers continuous, rapid and real-time monitoring of biomolecules as well as separation of microparticles based on size [126,127]. As an example, Ahmad et al [127] have proposed a microfluidic device for size-based acoustofluidic separation of target proteins conjugated to microparticles.…”

“…The integration of SAW technologies with microfluidics has created a new field called acoustofluidics that offers continuous, rapid and real-time monitoring of biomolecules as well as separation of microparticles based on size [126,127]. As an example, Ahmad et al [127] have proposed a microfluidic device for size-based acoustofluidic separation of target proteins conjugated to microparticles. This platform contained a PDMS microchannel with an interdigitated transducer which was patterned on top of the piezoelectric lithium niobite (LiNbO 3 ) substrate as a source of high-frequency SAWs.…”

“…(B) Microfluidic separation of target biomolecules from the non-target ones (red) using surface acoustic waves (SAWs) originating from the interdigital transducers (IDTs). Reprinted with permission from[127]. Copyright 2017 American Chemical Society.…”