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Three-dimensional Nanoelectronics for Simultaneous Bioelectrical and Biomechanical Sensing
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Abstract
Bioelectrical and biomechanical responses generated by cardiomyocytes are two essential state indicators within human stem cell-derived cardiac tissues. These tissues are increasingly recognized as highly promising in vitro models, offering deep insights for cardiac development studies, detailed disease modeling, and comprehensive drug screening. Given the complex interrelation between these two activities through the excitation-contraction coupling process, the simultaneous measurement of them is highly desirable and critical for identifying physiological and pathological mechanisms. Drawing inspiration from biological organelles that integrate multiple sensory mechanisms for efficient parallel signaling, we have designed and fabricated multifunctional three-dimensional (3D) nanoelectronics. These advanced devices enable the simultaneous measurement of bioelectrical and biomechanical responses from both planar cardiac cells and 3D cardiac microtissues (CMTs). Initially, we developed a deterministic assembly method for constructing 3D suspended silicon (Si) nanowire structures. By integrating deterministic planar nanowire assembly with a microscope-assisted transfer process, we established a versatile approach for creating vertically protruding and suspended nanowire configurations. These assembled 3D nanowires possess precisely defined on-substrate terminals, enabling scalable addressing and integration, showing their capability for sensitive force detection. Furthermore, we demonstrated that the integrated 3D nanowire electronics were capable of simultaneously detecting electrical and mechanical cellular responses from planar human stem cell-derived cardiac tissues. The protruding configuration not only establishes a tight interface between the devices and cells for detecting electrical signals (action potential) via field effect but also provides close mechanical coupling for detecting mechanical signals (cellular contraction) through the piezoresistive effect. This highly integrated 3D nanowire transistor array facilitates scalable interrogation of correlated cell dynamics in a label-free manner, proving its effectiveness in tracking and differentiating cell dynamics during drug studies. Thanks to its ultrasmall size, the sensor can decode vector information in cellular motion, surpassing the typical scalar data acquired at the tissue level, thus offering an advanced tool for studying cell mechanics. Finally, we further expanded the multifunctional sensor concept to include soft mesh nanoelectronics, specifically designed for monitoring bioelectrical and biomechanical responses in 3D CMT. Our innovative approach involved developing graphene-integrated mesh electronics that exhibit tissue-like softness and cell-level features, ensuring stable integration within the tissue structure for single-cell detection. The multifunctional graphene sensors uniquely converge both electrical and mechanical sensing capabilities via field effect and piezoresistive effect, respectively. This system facilitates stable monitoring of the EC dynamics throughout the tissue and its developmental stages, offering a comprehensive evaluation of tissue maturation, pharmacological impacts, and disease modeling.
Type
Dissertation (Open Access)
Date
2024-09
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Embargo Lift Date
2025-09-01