Compliant 3D frameworks instrumented with strain sensors for characterization of millimeter-scale engineered muscle tissues

Abstract

Tissue-on-chip systems represent promising platforms for monitoring and controlling tissue functions in vitro for various purposes in biomedical research. The two-dimensional (2D) layouts of these constructs constrain the types of interactions that can be studied and limit their relevance to three-dimensional (3D) tissues. The development of 3D electronic scaffolds and microphysiological devices with geometries and functions tailored to realistic 3D tissues has the potential to create important possibilities in advanced sensing and control. This study presents classes of compliant 3D frameworks that incorporate microscale strain sensors for high-sensitivity measurements of contractile forces of engineered optogenetic muscle tissue rings, supported by quantitative simulations. Compared with traditional approaches based on optical microscopy, these 3D mechanical frameworks and sensing systems can measure not only motions but also contractile forces with high accuracy and high temporal resolution. Results of active tension force measurements of engineered muscle rings under different stimulation conditions in long-term monitoring settings for over 5 wk and in response to various chemical and drug doses demonstrate the utility of such platforms in sensing and modulation of muscle and other tissues. Possibilities for applications range from drug screening and disease modeling to biohybrid robotic engineering.

Bioinspired two-in-one nanotransistor sensor for the simultaneous measurements of electrical and mechanical cellular responses

“…S4), consistent with the giant piezoresistive effect observed previously (24,25). The gauge factor is much larger than typical values in other piezoresistive sensors used for biomechanical detection in tissue (table S2) (30)(31)(32)(33)(34). The enhanced piezoresistive sensitivity in the Si nanowire thus constitutes a unique advantage in improving force resolution for cellular detection.…”

“…1, E and F). With a nanowire diameter of ~30 to 50 nm, the nanotransistor occupies a projected area of <0.4 m 2 , much smaller than typical microelectrodes or strain sensors used in tissue recording (15)(16)(17)(18)(30)(31)(32)(33)(34). A device yield of ~63 to 93% was achieved (figs.…”

“…Electrical recording of mechanical properties in cardiac tissue offers additional advantages for constructing organs on chips (30)(31)(32)(33)(34). Previous piezoresistive sensors often used a thin-film form factor that was fully coupled to a supporting substrate, which can compromise the force transduction.…”

Flexible Ceramic Film Sensors for Free-Form Devices

“…On these 3D electronics/in-mold electronic devices, various sensor components are used, which are currently installed as ceramic chip forms [25]. Direct formation of sensor thin films on the 3D forms, on the other hand, is expected to maximize the functions of the highly designed shapes [40,41]. This industrial accomplishment provides additional impetus to study materials and fabrication processes in order to develop wearable devices to a higher level of comfort and accuracy in sensing [8][9][10].…”

“…On these 3D electronics/in-mold electronic devices, various sensor components are used, which are currently installed as ceramic chip forms [25]. Direct formation of sensor thin films on the 3D forms, on the other hand, is expected to maximize the functions of the highly designed shapes [40,41].…”