Yusuke Tsuji1 Yoshikazu Hirai1 Ken-ichiro Kamei1 Toshiyuki Tsuchiya1 Osamu Tabata1

1, Kyoto University, Kyoto, , Japan

Body-on-a-Chip (BoC) platform holds a great potential for new pre-clinical tests in drug screening as in vitro human models by mimicking in vivo physiological and pathological conditions. Recently, the authors have reported a proof of BoC concept for recapitulation of the cardio-toxic side effects of an anti-cancer drug [1]; however, there is still a technological challenge to integrate a pressure sensor for monitoring or controlling pressure in BoC, leading to create cellular microenvironments close to in vivo physiological conditions in the BoC platform. Among existing polydimethylsiloxane (PDMS)-based pressure sensors, the sensor with ionic liquid (IL pressure sensor) [2] is promising due to allowing direct integration into a PDMS-based BoC platform by multilayer soft lithography. But previously reported sensors lack proper performance with respect to sensitivity and linearity. Here we propose a novel fabrication approach of an IL pressure sensor by using simulation-based three-dimensional (3D) lithography and show its improved sensor performance.

An IL pressure sensor is composed of a flow channel to circulate cell culture medium and an electro-fluidic (EF) channel filled with IL, and they are overlapped with separation by a PDMS membrane (tens of µm). The pressure in flow channel can be measured by monitoring electrical resistance change of an EF channel induced by membrane deformation by pressure. Since the sensor performance such as sensitivity and linearity depend on cross-sectional shape of the EF channel, we focused to tune a cross-sectional shape of mold for EF channel.

To improve the sensor performance, the electrical resistance change of EF channel by deformation of PDMS membrane were simulated with FEM analysis for four sensors with different cross-sectional geometries (rectangle: 400, 600 µm width x 25 µm height, triangle: 400 x 25 µm2, and semi-ellipse: 400 x 25 µm2). The triangular channel showed 10-time higher sensitivity than the rectangular channel.

Then, designed sensors were fabricated by digital micromirror device-based grayscale lithography [3] with a numerical process optimization, and resistance changes were measured by an impedance analyzer. The results on static pressure with the range of 0 to 12 kPa exhibited good agreement with the numerical simulation results. Moreover, to validate the performance to measure heart beating, the periodic pressures with a triangular wave were applied to the sensor. As the results, the sensor with triangular channel was able to follow at least pressure change at 1 Hz. We believe that our proposed approach and developed sensor will allow measuring pressures at the physiological levels.

[1] K. Kamei et al., RSC Adv., 7 (2017), pp.36777−36786.
[2] C.-Y. Wu et al., Lab Chip, 11 (2011), pp.1740–1746.
[3] X. Ma et al., J. Microelectromech. Syst., 24 (2015), pp.1856−1867.