Sample Preparation Meets Farey Sequence: A New Design Technique for Free-Flowing Microfluidic Networks

TL;DR

This paper introduces a novel design methodology for free-flowing microfluidic biochips that uses Farey sequence arithmetic to perform precise fluid dilution, addressing challenges in cost, manufacturability, and operational defects.

Contribution

It presents a new algorithm based on Farey sequences for designing free-flowing microfluidic networks capable of accurate sample dilution, along with a detailed layout and simulation validation.

Findings

The proposed design achieves high accuracy in fluid dilution.

Simulation results show reduced convergence time and reactant cost.

The architecture is simpler and more robust than prior valve-based methods.

Abstract

Design of microfluidic biochips has led to newer challenges to the EDA community due to the availability of various flow-based architectures and the need for catering to diverse applications such as sample preparation, personalized medicine, point-of-care diagnostics, and drug design. The ongoing Covid-19 pandemic has increased the demand for low-cost diagnostic lab-on-chips manifold. Sample preparation (dilution or mixing of biochemical fluids) is an indispensable step of any biochemical experiment including sensitive detection and successful assay execution downstream. Although for valve-based microfluidic biochips various design automation tools are currently available, they are expensive, and prone to various manufacturing and operational defects. Additionally, many problems are left open in the domain of free-flowing biochips, where only a single layer of flow-channels is used for fluid-flow devoid of any kind of control layer/valves. In this work, we present a methodology for designing a free-flowing biochip that is capable of performing fluid dilution according to users requirement. The proposed algorithm for sample preparation utilizes the Farey-sequence arithmetic of fractions that are used to represent the concentration factor of the target fluid. We also present the detailed layout design of a free-flowing microfluidic architecture that emulates the dilution algorithm. The network is simulated using COMSOL multi-physics software accounting for relevant hydrodynamic parameters. Experiments on various test-cases support the efficacy of the proposed design in terms of accuracy, convergence time, reactant cost, and simplicity of the fluidic network compared to prior art.