A novel stretchable micro-electrode array (SMEA) design for directional stretching of cells

Abstract

Stretchable micro-electrode arrays (SMEAs) are useful tools to study the electrophysiology of living cells seeded on the devices under mechanical stimulation. For such applications, the SMEAs are used as cell culture substrates; therefore, the surface topography and mechanical properties of the devices should be minimally affected by the embedded stretchable electrical interconnects. In this paper, a novel design and micro-fabrication technology for a pneumatically actuated SMEA are presented to achieve stretchability with minimal surface area dedicated to the electrical interconnects and a well-defined surface strain distribution combined with integrated diverse micro-patterns to enable alignment and directional stretching of cells. The special mechanical design also enables the SMEA to have a prolonged electro-mechanical fatigue life time required for long-term cyclic stretching of the cell cultures (stable resistance of electrical interconnects for more than 160 thousand cycles of 20% stretching and relaxing). The proposed fabrication method is based on the state of the art micro-fabrication techniques and materials and circumvents the processing problems associated with using unconventional methods and materials to fabricate stretchable electrode arrays. The electrochemical impedance spectroscopy characterization of the SMEA shows 4.5 M impedance magnitude at 1 kHz for a TiN electrode 12 um in diameter. Cell culture experiments demonstrate the robustness of the SMEAs for long-term culturing experiments and compatibility with inverted fluorescent microscopy.

Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing

“…The implementation of miniaturized relevant actuators and sensors into the devices enables necessary features for in vivo -like tissue-specific electro-mechano-biochemical signaling. They support expansion and compression forces, especially relevant for lung, bone and cartilage, and microelectrodes for the electrical stimulation and readout of muscle tissue (Ahadian et al, 2012; Dvir et al, 2012) or stimulation of cardiac cells or neurons (Bussek et al, 2009; Gramowski et al, 2011; Himmel et al, 2012; Johnstone et al, 2010, Koshferat Pakazad 2014). Moreover, such devices could be able to apply other technical means of measurement and control, such as noninvasive optical imaging.…”

Biosensors Based on Mechanical and Electrical Detection Techniques

“…This can be used to track cell processes, monitor analyte concentrations or to follow monolayer growth and migration [ 141 , 142 ]. These systems have the advantage of a real-time response and can be used with an array of electrodes to achieve spatial resolution [ 143 , 144 ]. Furthermore this technique may be used in combination with microfluidics to achieve high throughput flow cytometry without the need for labelling [ 145 ].…”

Building gyms for cells : development of combinatorial screening platforms for mechanical stimulation

“…For cells cultured on hydrogels, ECM coated polyacrylamide hydrogels have been commonly used 14,30,31 , while for culture within hydrogels, ECM hydrogels such as collagen [32][33][34] or fibrin 35 gels have been generally used. When cultured within hydrogels, cells see a significantly different attachment milieu compared to a substrate surface and this has been suggested to be responsible for the observed significant differences in cell behavior 36 . The nutrient transport to the cells from the culture media is also modified 36 .…”

“…When cultured within hydrogels, cells see a significantly different attachment milieu compared to a substrate surface and this has been suggested to be responsible for the observed significant differences in cell behavior 36 . The nutrient transport to the cells from the culture media is also modified 36 .…”

“…Addition of electrodes to get electrical readouts from cells can make the developed devices more suitable for this application 36 .…”