A piezoelectric electrospun platform for in situ cardiomyocyte contraction analysis

Laura Toth Beringer

doi:10.17918/etd-6323

Flexible, self-powered materials are in demand for a multitude of applications such as energy harvesting, robotic devices, and lab-on-a chip medical diagnostics. Lab-on-a-chip materials or cell-based biosensors can provide new diagnostic or therapeutic tools for numerous diseases. This dissertation explores the fabrication and characterization of a cell-based sensor termed a nanogenerator with three major aims. The first aim of this research was to fabricate a piezoelectric material that could act as both a cell scaffold and sensor and characterize the response to cell-scale deformation. Electrospinning piezoelectric fluoropolymers into nanofibers can provide both of these functionalities in a facile method. PVDF-TrFe was electrospun in an aligned format and interfaced with a flexible plastic substrate in order to create a platform for voltage response characterization after small force cantilever deformations. Voltage peak signals were an average of ± 0.4 V, and this response did not change after platform sterilization. However, when placed in cell culture media, piezoelectric response was dampened, which was taken into consideration for the next two aims. An aligned electrospun coaxial fiber system of PVDF-TrFe and collagen was created and interfaced with with the nanogenerator for the second aim in order to provide a more biologically favorable surface for cells to adhere to. These nanogenerators were successfully characterized for their piezoelectric response, which was an average of ± 0.1 V. Additionally, the aligned coaxial collagen/PVDF-TrFe fibers supported both neuron and HeLa cell attachment and growth, demonstrating that they were not cytotoxic. To assess the potential for the nanogenerators to be used as a contractile analysis lab-on-a-chip based device, HeLa cell contraction was induced with potassium chloride and signal response was analyzed. The nanogenerator system was able to detect both the resting state of HeLa cells, a contraction state, and a hyperpolarized state, proving their potential use as contractile analysis microdevices. The third and final aim of this dissertation was to be able to measure contraction events from both cultured cardiomyocytes and whole tissues in situ. Rat neonatal cardiomyocytes grew on the prepared collagen/PVDF-TrFe nanogenerators and yielded a distinct signal after 8 days of growth. These contractions were verified with live cell imaging and video recording. In addition, cardiomyocyte exposure to the drug isoproterenol increased contraction strength and frequency, which was reflected in the nanogenerator recordings. Frog whole heart and heart tissue slices also were interfaced with the fabricated nanogenerators and signals were recorded. The same held true for heart slices from male Sprague-Dawley rats. These signals were determined to be statistically different compared to the control baseline nanogenerator recordings in media in the absence of cell culture. Overall the fabricated nanogenerators have demonstrated their potential to be used as in situ analysis tools for contractile events and have potential in the field of personalized medicine and drug diagnostic assays. The facile fabrication and ease of setup to obtain the electrical voltage signal corresponding to the contractile events are what sets the nanogenerator apart from any polymer based sensor available today.

A piezoelectric electrospun platform for in situ cardiomyocyte contraction analysis

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A piezoelectric electrospun platform for in situ cardiomyocyte contraction analysis

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