Nanomechanical transduction of molecular interactions on microcantilevers for biochemical detection and diagnostics.

摘要

There is a strong demand for a reliable detection platform that can provide the benefits of enhanced sensitivity and selectivity with greater simplicity and cost-effectiveness. The new generations of biosensors also require microfabricated platforms with integrated biologically sensitive components for specific and quantitative detection of analytes in a miniaturized format as well as capabilities for label-free detection and massive parallelization.;It has been unambiguously demonstrated that the molecular binding-induced surface stress can be used to monitor specific biochemical binding events and kinetics in real-time with high sensitivity, representing the promising potential for nanomechanical sensors. The fundamental validation of the receptor immobilization and target binding as well as the transduction and quantitative detection of such molecular recognition events taking place on microcantilevers are demonstrated utilizing the optical approach for monitoring the cantilever deflection. The label-free detection of cholera toxin using microcantilevers functionalized with ganglioside-Nanodiscs is demonstrated as a new strategy for immobilizing receptors on microcantilevers.;The microcantilever-based sensors, however, require a new paradigm for signal transduction and detection beyond the optical method that supports the unique multiplexing capability by operating a large array of cantilevers with means for simple and accurate readout. Hence, a new electrical readout mechanism comprising a microcantilever array with MOSFETs embedded in the high stress region of the microcantilevers is developed, which provides label- and optics-free signal transduction mechanism.;In this work, significant strides have been made towards the MOSFET-microcantilever detection approach. The process and device simulations for embedded-MOSFETs are performed to optimize process parameters and establish guidelines for device design and fabrication. Various designs of MOSFET-embedded microcantilevers are evaluated to validate their performance and the bending-induced change in drain current is experimentally verified and analyzed. Furthermore, model systems are employed to assess and confirm the capability for detecting biomolecules.;The MOSFET-embedded microcantilever platform meets the necessary criteria for creating a widely deployable multiplexed detection system that can be integrated into a miniaturized device, representing the realistic prospects for various applications spanning through many fields including biological and chemical sensing, inexpensive diagnostics systems for healthcare, point-of-use environmental monitoring, and detection systems for biodefense.