Ionic polymer metal composite-based microfluidic flow sensor for bio-MEMS applications

Sensing flow rates in structured microenvironments like lab-on-chip (LOC) and organ-on-chip (OoC) is crucial to assess important parameters such as transport of media and molecules of interest. So far, these micro-electromechanical systems for biology (bio-MEMS) mostly rely on flow sensing systems based on thermal sensors. However, thermal flow sensing has limitations, since the measurement principle, which is based on generation of heat, can negatively affect the biological system by increasing the fluid temperature above physiological conditions. To overcome this issue, we propose a novel electro-mechanical flow sensor centered around the deformation of a cantilever made of a thin and biocompatible ionic electroactive polymer. The polymer, called ionic polymer metal composite (IPMC), is doped with ions naturally present in most cell media for LOC and OoC devices. Unlike already existing cantilever-based systems which rely on piezo sensitive materials, our IPMC-based flow sensor shows durability in wet environment. We were able to successfully measure pulsatile flow induced by pipetting with flowrate gradually increasing from $10\mu\mathrm{L}/\mathrm{s}$ to $40\ \mu\mathrm{L}/\mathrm{s}$. The proposed flow sensor shows good sensing capabilities (4.78 $\text{mV}/(\mu\mathrm{L}/\mathrm{s}))$ with a linear behavior in the studied range. This work sets a milestone for using flexible, electroactive materials for sensing applications in delicate biological microenvironments.

I. Introduction

An organ-on-chip (OoC) is an engineered microphysiological system that aims to recapitulate the smallest functional unit of an organ in order to perform in-vitro realistic drug analysis or disease modeling. A lab-on-chip (LOC) is a MEMS device that aims at analyzing chemical components in order to study disease and biomolecular species e.g. DNA, RNA, proteins, drugs. OoC and LOC can be both defined as biological micro-electromechanical systems (bio-MEMS). Since the very beginning of bio-MEMS, microfluidics has been a cornerstone to control precisely the microenvironment and mechanical clues in OoC or delivery of molecules of interest in LOC [1]. Therefore, monitoring flow inside microfluidic devices is a crucial need. To date, widely used systems for flow sensing rely on thermal flow sensors [2]. In these sensors the difference in fluid temperature between a heating element and a temperature probe provides a measure of flow rate. This measurement technique presents certain drawbacks. For instance, the heat transfer might deteriorate the biological molecules of interest and disturb cell phenotype. Other sensing techniques exist, such as Coriolis flow measurement [3] or acoustic flow measurement [4]. However both techniques cannot record backflow easily which is essential for vasculature modeling in OoC [5]. In addition acoustic flow measurement and Coriolis flow measurement are complex, costly, bulky, and might be hampered by the presence of circulating cells in an OoC. Alternatively, cantilever-based approaches have been proposed in order to precisely measure flow rate. The displacement of beams can either be recorded optically or through a piezoresistive system [6], [7]. However, the optical approach is not integrated in the microfluidics device, while the piezo material characteristics get altered overtime by temperature and liquid exposure [2].