CFD Modeling of Chamber Filling in a Micro-Biosensor for Protein Detection

Abstract

Tuberculosis (TB) remains one of the main causes of human death around the globe. The mortality rate for patients infected with active TB goes beyond 50% when not diagnosed. Rapid and accurate diagnostics coupled with further prompt treatment of the disease is the cornerstone for controlling TB outbreaks. To reduce this burden, the existing gap between detection and treatment must be addressed, and dedicated diagnostic tools such as biosensors should be developed. A biosensor is a sensing micro-device that consists of a biological sensing element and a transducer part to produce signals in proportion to quantitative information about the binding event. The micro-biosensor cell considered in this investigation is designed to operate based on aptamers as recognition elements against Mycobacterium tuberculosis secreted protein MPT64, combined in a microfluidic-chamber with inlet and outlet connections. The microfluidic cell is a miniaturized platform with valuable advantages such as low cost of analysis with low reagent consumption, reduced sample volume, and shortened processing time with enhanced analytical capability. The main purpose of this study is to assess the flooding characteristics of the encapsulated microfluidic cell of an existing micro-biosensor using Computational Fluid Dynamics (CFD) techniques. The main challenge in the design of the microfluidic cell lies in the extraction of entrained air bubbles, which may remain after the filling process is completed, dramatically affecting the performance of the sensing element. In this work, a CFD model was developed on the platform ANSYS-CFX using the finite volume method to discretize the domain and solving the Navier–Stokes equations for both air and water in a Eulerian framework. Second-order space discretization scheme and second-order Euler Backward time discretization were used in the numerical treatment of the equations. For a given inlet–outlet diameter and dimensions of an in-house built cell chamber, different inlet liquid flow rates were explored to determine an appropriate flow condition to guarantee an effective venting of the air while filling the chamber. The numerical model depicted free surface waves as promoters of air entrainment that ultimately may explain the significant amount of air content in the chamber observed in preliminary tests after the filling process is completed. Results demonstrated that for the present design, against the intuition, the chamber must be filled with liquid at a modest flow rate to minimize free surface waviness during the flooding stage of the chamber.

Development of a Hybrid Polymer-Based Microfluidic Platform for Culturing Hepatocytes towards Liver-on-a-Chip Applications

“…The free-surface flow is solved by implementing a compressive differencing scheme on the convection of volume fractions to keep the free surface sharp. The computation of the fluids’ volume fractions adds up to one in each control volume [ 34 , 35 ]. The CFD platform uses a pressure–velocity couple algorithm to solve the governing equations with greater demand in memory than a traditional segregated approach but faster convergence in parallel processing.…”

Microfluidics as a Novel Technique for Tuberculosis: From Diagnostics to Drug Discovery

“…Another biosensing device was developed to detect MPT64-an antigen secreted by M. tuberculosis. The protein is a biomarker for actively dividing mycobacteria, detected by electrochemical impedance spectroscopy and synthetic aptamers integrated with a microfluidic chamber [137].…”

Microfluidics as a Novel Technique for Tuberculosis: From Di-agnostics to Drug Discovery

“…Another biosensing device was developed to detect MPT64 -an antigen secreted by M. tuberculosis. The protein is a biomarker for actively dividing mycobacteria, detected by electrochemical impedance spectroscopy and synthetic aptamers integrated with a microfluidic chamber [140].…”