A direct-laser-written heart-on-a-chip platform for generation and stimulation of engineered heart tissues

In this dissertation, we first develop a versatile microfluidic heart-on-a-chip model to generate 3D-engineered human cardiac microtissues in highly-controlled microenvironments. The platform, which is enabled by direct laser writing (DLW), has tailor-made attachment sites for cardiac microtissues and comes with integrated strain actuators and force sensors. Application of external pressure waves to the platform results in controllable time-dependent forces on the microtissues. Conversely, oscillatory forces generated by the microtissues are transduced into measurable electrical outputs. After characterization of the responsivity of the transducers, we demonstrate the capabilities of this platform by studying the response of cardiac microtissues to prescribed mechanical loading and pacing. Next, we tune the geometry and mechanical properties of the platform to enable parametric studies on engineered heart tissues. We explore two geometries: a rectangular seeding well with two attachment sites, and a stadium-like seeding well with six attachment sites. The attachment sites are placed symmetrically in the longitudinal direction. The former geometry promotes uniaxial contraction of the tissues; the latter additionally induces diagonal fiber alignment. We systematically increase the length for both configurations and observe a positive correlation between fiber alignment at the center of the microtissues and tissue length. However, progressive thinning and “necking” is also observed, leading to the failure of longer tissues over time. We use the DLW technique to improve the platform, softening the mechanical environment and optimizing the attachment sites for generation of stable microtissues at each length and geometry. Furthermore, electrical pacing is incorporated into the platform to evaluate the functional dynamics of stable microtissues over the entire range of physiological heart rates. Here, we typically observe a decrease in active force and contraction duration as a function of frequency. Lastly, we use a more traditional ?TUG platform to demonstrate the effects of subthreshold electrical pacing on the rhythm of the spontaneously contracting cardiac microtissues. Here, we observe periodic M:N patterns, in which there are ? cycles of stimulation for every ? tissue contractions. Using electric field amplitude, pacing frequency, and homeostatic beating frequencies of the tissues, we provide an empirical map for predicting the emergence of these rhythms

Intermodal coupling as a probe for detecting nanomechanical modes

Nanoelectromechanical systems provide ultrahigh performance in sensing applications. The sensing performance and functionality can be enhanced by utilizing more than one resonance mode of a nanoelectromechanical-systems device. However, it is often challenging to measure mechanical modes at high frequencies or modes that couple weakly to output transducers. In this paper, we propose the use of intermodal coupling as a mechanism to enable the detection of such modes. To implement this method, a probe mode is continuously driven and monitored using a phase-locked loop, while an auxiliary drive signal scans for other modes. Each time the auxiliary drive signal excites the corresponding mode by matching the mechanical frequency, the effective tension within the structure increases, which in turn causes a frequency shift in the probe mode. The location and width of these frequency shifts can be used to determine the frequency and quality factor of mechanical modes indirectly. Intermodal coupling can be used as a tool to obtain the spectrum of a mechanical structure even if some of these modes cannot be detected conventionally