MULTIPHYSICS MODELING OF A GRAPHENE–SILICON NEMS RESONATOR FOR CRISPR-BASED LABEL-FREE NUCLEIC ACID DETECTION

Abstract

High-speed and sensitive detection of the nucleic acids is critical for the next generation point-of-care assays especially for early disease diagnosis, precision medicine and surveillance of infectious diseases. Ultrahigh mass sensitivity of the nanoelectromechanical systems (NEMS) has also made it a promising label-free sensing platform, while the molecular recognition with Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) ensures unprecedented sequence specificity when sensing desired nucleic acids (such as DNA or RNA). Multiphysics design and analysis of label free genetic and molecular detection via incorporation of label free molecular recognition (i.e. CRISPR-associated or "cas") with graphene enhanced silicon NEMS cantilever resonator is described in this work within the context of a multiphysics framework informed by physics. The proposed multilayer resonator consists of a silicon nanocantilever coated with a thin gold layer with a functionalized surface to improve biomolecules immobilization, capture efficiency and the sensing performance completed by placing a single layer graphene surface at the bottom. Euler-Bernoulli beam theory, modal mass perturbation, the Langmuir adsorption kinetics, thermoelastic damping and pressure dependent energy dissipative analysis are all integrated into a comprehensive analytical model. In addition, an implementation strategy for finite elements simulations in COMSOL Multiphysics is suggested for future optimization of the devices and experimental verifications. The 1st flexural resonance of the resonator can be found close to 18.1 MHz in the design conditions considered and shows a maximum resonance frequency shift of about 36.7 kHz for up to 10 pM target DNA which can be evaluated as a sub-attogram equivalent mass sensitivity in representative design conditions. Parametric analysis has revealed that the geometry of the beams, molecular capture efficiency, binding affinity and resonator quality factor are the main parameters that to a certain extent determine the performance of the sensing device. The proposed framework differs from classical computational studies as it puts together in a same computational framework the nanomechanical resonance modelling, the biomolecular adsorption kinetics, the multiphysics energy-loss mechanisms and the uncertainty quantification, along with an experiment-guided validation framework. The created framework offers a repeatable design methodology for next-generation graphene-enabled NEMS biosensors and is an effective foundation for future precision healthcare, point-of-care, label-free molecular diagnostics systems assisted by CRISPR. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), CRISPR-associated proteins (Cas), Nanoelectromechanical Systems (NEMS), Label-free biosensing, Molecular diagnostics, Thermocouples, Thermocouple modelling, Clustered regularly Interspaced Short Palindromic Repeats(CRISPR), Graphene, Silicon cantilever, Clustered regularly Interspaced Short Palindromic Repeats(CRISPR), CRISPR-associated proteins (Cas), Thermocouples, Thermoelastic damping, COMSOL Multiphysics, Multiphysics modelling.