Design and Development of Integrated Displacement Sensors for Engineered Heart Tissue Platforms

Abstract

Cardiac cells derived from stem cells exhibit cellular contractions when cultured in vitro. They can be integrated with polymeric platforms consisting of micropillars, which act as anchors and pre-load for engineered heart tissue (EHT). The biomechanical response is often characterized using optical microscopy to track the displacement of pillar tops and assess the contractile properties of the EHT. This requires bulky instruments with sophisticated imaging algorithms, which are often prone to optical misalignment. The efficiency of the imaging algorithms is highly dependent on the structure of the top surface of the pillar.
In this thesis, an alternate approach to microscopy is presented. A novel sensor is designed, fabricated and characterized which converts the pillar response such as strain or displacement to a measurable output which can be further conditioned and read-out by an instrumentation module. As the first step, in-depth multiphysics simulations have been carried out analysing the response of the micropillar system integrated with sensors utilising piezoelectric, piezoresistive and capacitive sensing techniques. A quantitative and qualitative comparison based on the derived simulations was performed and the most optimal sensing platform was chosen.
Spiral sensors inspired from co-planar waveguides are designed and developed in such a manner so as to provide seamless integration with the process flow for the micropillars developed at ECTM and fabricated at EKL in TU Delft. The integrated sensors exhibit a change in capacitance due to warping of fringe electric field lines with the application of force to pillar boundaries. The simulated sensitivity of the sensors are 1.51-4.86 pF/N depending on the metallization ratio and average path length.
The sensors are fabricated via clean room processing and encapsulated within two layers of PDMS. On account of their low line widths (5−40 um), they have been successfully patterned with inductively coupled plasma. Simultaneously, the steps required for the fabrication of the EHT platform have been carried out.
The characterization of the sensors has been performed using on-wafer probing and equivalent lumped element circuitry also derived. The resulting capacitances are in excellent agreement with the optimised simulations in COMSOL. The sensors exhibit a stable base-line response to AC signals with frequencies up to 1 MHz and voltages up to 20 Vrms, the highest limits to the test signals of the instrumentation setup. Preliminary characterization of the sensor’s response to mechanical loading exhibits promising outcomes. The read-out circuitry of the time varying capacitors is simulated in SPICE leading to a successful first level assessment of the designed novel sensors for biomechanical characterization of tissues grown on EHT platforms.