Enabling actuation and sensing in organs-on-chip using electroactive polymers

Abstract

Organ-on-chip (OoC) devices are in rising demand for high-throughput and low-cost development and toxicological screening of chemicals and pharmaceuticals, as they accurately mimic in vitro physiological conditions as in the human body. In particular, OoCs are urgently needed for screening cardiovascular drug toxicity. Physiological relevance of cardiovascular cell cultures requires moving substrates. To date cell culture substrates have been commonly actuated by pneumatic systems, which are bulky, expensive and nonuser-friendly, and may thus limit the adoption of OoCs by researchers and industry. In this paper we propose the first actuating and sensing smart material-based OoC device and demonstrate its functionality by culturing human vascular smooth muscle cells (vSMC). Our device utilizes a single ionic polymer metal composite (IPMC)-based transducer to provide both actuation and sensing. The soft IPMC substrate allows to intermittently apply cyclic loading to tissues and to sense their spontaneous contractions. We integrated the transducer within a compact, easy-to-operate, economically affordable and scalable OoC prototype, which achieves an actuation range of 0.2 mm and 0.72 V/mm sensing resolution. The 0.1 % strain induced by actuation on cells accurately corresponds to in vivo strains for vSMCs. We successfully grew vSMCs on the IPMC substrate, and actuated them for 150 min at 1 Hz. Fluorescent staining showed no evidence of adverse effects. These results are a major step towards versatile OoCs for a wide variety of biological modelling of human tissues.

Microelectromechanical Organs-on-Chip

“…[21]. Top right: an 8-mm long IPMC cantilever fitting in a single well of a 12-well plate by means of a custom electrode holder [30]. Bottom left: a silicon frame embedding 8 floating-gate field-effect transistors and supporting an optically transparent PDMS membrane.…”

“…Hz) [30]. C) Analyte detection from the output characteristics of a dual-gate nMOS-based electrochemical charge sensor [35].…”

“…The latter are typically bulky, expensive and nonuser-friendly, and may thus limit the adoption of OoC devices by researchers and industry. To this limitation, we proposed the first actuating and sensing smart material-based OoC device (Fig 2, top right), and demonstrated its functionality by culturing human vascular smooth muscle cells (vSMC) [30].…”

“…A) Contraction force exerted by a 3 µL-derived engineered heart tissue, estimated by software-based optical tracking of micropillar displacement [21]. B) Displacement of an 8 mm-long IPMC cantilever driven by low input voltage (5 Vpp, 1Hz)[30]. C) Analyte detection from the output characteristics of a dual-gate nMOS-based electrochemical charge sensor[35].…”

Manufacturing thin ionic polymer metal composite for sensing at the microscale

“…Hence lab-on-chip and organ-on-chip devices can benefit from the integration of IPMCs because of their actuation and sensing capabilities. Utilisation of a 180 µm-thick IPMC has been studied for actuating and sensing in bio-MEMS transducers applications [10], with a focus on sensing intrinsic tissue contraction [11,12]. However, these studies could not realize measurement of tissue contractions, indicating that the stiffness of the 180 µm-thick IPMC is too high to allow the cultured tissue to induce a displacement on the ionic electroactive polymer.…”