A Universal Biomolecular Concentrator To Enhance Biomolecular Surface Binding Based on Acoustic NEMS Resonator

Abstract

In designing bioassay systems for low-abundance biomolecule detection, most research focuses on improving transduction mechanisms while ignoring the intrinsically fundamental limitations in solution: mass transfer and binding affinity. We demonstrate enhanced biomolecular surface binding using an acoustic nano-electromechanical system (NEMS) resonator, as an on-chip biomolecular concentrator which breaks both mass transfer and binding affinity limitations. As a result, a concentration factor of 105 has been obtained for various biomolecules. The resultantly enhanced surface binding between probes on the absorption surface and analytes in solution enables us to lower the limit of detection for representative proteins. We also integrated the biomolecular concentrator into an optoelectronic bioassay platform to demonstrate delivery of proteins from buffer/serum to the absorption surface. Since the manufacture of the resonator is CMOS-compatible, we expect it to be readily applied to further analysis of biomolecular interactions in molecular diagnostics.

Functionalized Polyelectrolytes for Bioengineered Interfaces and Biosensing Applications

“…294 In a follow-up study, the detection of IgG in serum and PSA in buffer was enhanced by using an acoustic nano-electrochemical system (NEMS) resonator as a biomolecular concentrator at the biorecognition spot (Figure 13b). 295 A 10-and 200-fold decrease of the LOD was found for IgG and PSA, respectively, demonstrating the NEMS resonator applicability with different target molecules and surfacebased biosensing techniques.…”

On‐Chip Generation of Vortical Flows for Microfluidic Centrifugation

“…SAWs, as well as thickness‐mode bulk waves, can also be generated on thin piezoelectric films (the latter being known as thin film bulk acoustic resonators, and has the advantage of overcoming challenges associated with fabricating interdigitated transducers with micron or submicron widths and thicknesses necessary to generate SAWs at higher (e.g., GHz) frequencies), on which similar azimuthal microfluidic centrifugation flows can be effected. In addition to demonstrating the microvortical flow arising from these devices for various applications, including hydrodynamic particle trapping, biomolecular concentration and the shearing of polyelectrolyte films for drug release, the piezoelectric films can be overlaid onto regular substrates so as to circumvent the need for the piezoelectric substrate as well as to facilitate microfluidic operations on flexible substrates . To however separate the actuator from the microfluidic components, so as to enable reuse of the actuator (i.e., the piezoelectric chip) while facilitating a disposable option for the microfluidic chip, it is necessary to transmit the SAW vibration through a liquid couplant into a superstrate (e.g., a low‐cost and hence disposable chip on which the microfluidic operations are to be carried out as opposed to the reusable higher‐cost piezoelectric substrate to drive the microfluidic actuation), as first shown by Hodgson et al, or even a capillary tube .…”

Acoustic Trapping of Proteins under Physiological Conditions

“… 2 However, the persistent issue of excessive sample preparation steps or complicated device structures of existing approaches might have motivated Duan and co-workers from Tianjin University to search for biocompatible tools that ensure simple and direct trapping of biomolecules under physiological conditions. 3 …”

“… 4 Therefore, biomolecules depart from the vortex and accumulate at the bottom of virtual micropockets, which was conclusively shown by digital image-plane holographic microscopy. 3 The research team has achieved the concentration factor of 10 5 by breaking the mass transfer limitation and enhancing the kinetics of molecular surface binding, which increased the in vitro limit of detection of low-abundance target (bio)molecules by a factor of up to 1000. A quick and efficient process of protein concentration could be used in virtually any concept of rapid biomarker detection and diagnosis.…”

“…The authors have demonstrated the feasibility of this approach by detecting immunoglobulins and antigens through specific antibody–antigen interactions using a resonator-enhanced immunoassay integrated into a biolayer interferometry sensor. 3 In this device, the acoustic NEMS resonator accumulates the analyte at the interface of the probe (an optical fiber) to enhance the surface absorption kinetics of analyte molecules.…”