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.

Highlights

  • Mycobacterium tuberculosis (Mtb) is a dangerous pathogenic bacterium that causes Tuberculosis (TB), which is one of the leading causes of death from infectious diseases in the world

  • Following cleaning and washing steps at higher flow rates (>1000 μL/min), the protein buffer was allowed to flow across the working area at

  • The impedance signal was recorded after injecting MPT64 protein and pausing the flow

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Summary

Introduction

Mycobacterium tuberculosis (Mtb) is a dangerous pathogenic bacterium that causes Tuberculosis (TB), which is one of the leading causes of death from infectious diseases in the world. The rapid and early diagnosis, as well as its treatment, is crucial for the effective control of TB. Kazakhstan is one of the 24 countries in the European region that has a high number of multiple drug resistant strains [1]. This resistance to one or several forms of treatment occurs when the bacterium develops the ability to withstand antibiotics and relays that ability to its offspring. Drug-resistant TB is difficult and costly to treat, extending the time a person needs to be treated, which sometimes is fatal [2]. Detection of the disease provides fast recovery and mild course of the disease, reducing the number of fatal cases

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