Nanoscale Experimental Methods Applied to Atomically-Thin Resonators and Single-Cell Analysis

Nathamgari, Samba Shiva Prasad

doi:https://doi.org/10.21985/n2-tmtw-4n98

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Nanoscale Experimental Methods Applied to Atomically-Thin Resonators and Single-Cell Analysis

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Nanoelectromechanical (NEMS) systems fabricated using atomically-thin materials have low mass and high stiffness and are thus ideal candidates for force and mass sensing applications. Transition metal dichalcogenides (TMDCs) offer certain unique properties in their few-layered form – such as piezoelectricity and a direct band gap in some cases – and are an interesting alternative to graphene based NEMS. Among the demonstrated methods for displacement transduction in NEMS, cavity-interferometry provides exquisite displacement sensitivity. Typically, interferometric measurements are complemented with Raman spectroscopy to characterize the number of layers in 2D materials, and the measurements necessitate high vacuum conditions to eliminate viscous damping. In this thesis, we report an experimental setup that facilitates both Raman spectroscopy and interferometric measurements on atomically-thin materials. Specifically, we report measurements on few-layered Tungsten Disulfide (WS2) resonators in high vacuum (less than 10^-5 Torr) conditions. The lowest resolvable force in NEMS is limited by ambient thermal noise, and as a result, the resonators (which form the sensing element) are either operated at cryogenic temperatures or coupled to a high-finesse optical or microwave cavity to reach sub aN Hz^-1/2 sensitivity. In the present thesis, we show that operating a monolayer WS2 nanoresonator in the strongly nonlinear regime can lead to comparable force sensitivities at room temperature. Cavity-interferometry was used to transduce the nonlinear response of the nanoresonator, which was characterized by multiple pairs of 1:1 internal resonance. Some of the modes exhibited exotic line-shapes due to the appearance of Hopf bifurcations, where the bifurcation frequency varied linearly with the driving force and forms the basis of the advanced sensing modality. The modality is less sensitive to the measurement bandwidth, limited only by the intrinsic frequency fluctuations, and therefore, advantageous in the detection of weak incoherent forces. Localized electroporation has evolved as an effective technology for the delivery of foreign molecules into cells while preserving their viability. Consequently, this technique has potential applications in sampling the contents of live cells and the temporal assessment of cellular states at the single-cell level. Although there have been numerous experimental reports on localized electroporation-based delivery, a lack of a mechanistic understanding of the process hinders its implementation in sampling. In the present thesis, we develop a multiphysics model that predicts the transport of molecules into and out of the cell during localized electroporation. Based on the model predictions, we optimize experimental parameters such as buffer conditions, electric field strength, cell confluency, and density of nanochannels in the substrate for successful delivery and sampling via localized electroporation. We also identify that cell membrane tension plays a crucial role in enhancing both the amount and the uniformity of molecular transport, particularly for macromolecules. We qualitatively validate the model predictions on a localized electroporation platform by delivering large molecules (bovine serum albumin and mCherry-encoding plasmid) and by sampling an exogeneous protein (tdTomato) in an engineered cell line. The insights from the model developed here form an important advancement towards the goal of single-cell sampling using localized electroporation.

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