A Microfluidic Aspirator based Platform for Flow and Viscosity Sensing for Automated Tissue Culture Applications

J. Mcfall, T. Huang, D. Purcell, K. Haffey, S. Ghosh, A. Azad, P. Nath
Los Alamos National Lab,
United States

Keywords: flow viscosity sensor

Summary:

Perfusion based tissue cultures are dynamic processes where different system parameters such as flow rates, viscosity of media, pH, metabolite concentrations, etc. can change over time. To maintain homeostasis, it is important to integrate different types of sensors that can provide feedback for complete automation of perfusion based tissue cultures. In this work, we present a low cost flow and viscosity sensor that can be integrated with a perfusion based cell/tissue culture system. The working principle of the flow sensor is based on a microfluidic aspirator1, which takes advantage of Bernoulli’s principle. The sensor is composed of a microfluidic chamber having (1) an inlet with a cross-sectional area (Ai) that is larger than the cross-sectional area (Ao) outlet, such that Ai>>Ao; and (2) a stretchable membrane which is located on the top ceiling of the chamber (Fig 1). When fluid is withdrawn or infused through the inlet, it can cause a pressure drop or a pressure increase, respectively inside the microfluidic chamber according to Bernoulli’s principle. This pressure drop or increase causes the membrane to deform into or out of the chamber. In this work, we placed another air chamber with a single port on top of the membrane such that the actuation of the membrane causes a pressure change in the top chamber. By integrating a commercially available pressure sensor on the port of the top chamber, it is possible to measure the pressure changes in that chamber due to the actuation of the membrane. Based on Bernoulli’s principle, the actuation of the membrane depends on the fluid flowrate and viscosity inside the microfluidic chamber. Therefore, we can measure the flowrate or the viscosity of the fluid by reading the change measured by the pressure sensor. Prototypes of the sensing platforms were fabricated using a laser based micro-patterning and lamination method2 and were integrated with a commercially available Honeywell differential pressure sensor connected to a data acquisition system based on a Raspberry Pi. To demonstrate proof of principle, the prototypes were built with a membrane diameter of 4.0 mm, microfluidic channel cross-section of 1.5 by 4.0 mm2, inlet diameter of 1.0 mm, and an outlet diameter of 0.254 mm. The sensor was able to measure flow rates of water between 10 microL – 2000 microL (Fig 2), in both withdraw and infusion mode from a syringe pump. Changing the viscosity of the fluid passing through the sensor also demonstrated a linear relationship between viscosity and pressure change (Fig 3), indicating that the sensor can also be used to measure viscosity of the media when connected to automated perfusion based culture. We have demonstrated that a simple, low-cost, versatile sensing technology based on a microfluidic aspirator has the ability to detect flow rates or viscosity with a high dynamic range. We envision great potential for a new method of integrating these sensors into automated tissue culture applications.