Abstract

Fast, efficient and more importantly accurate serial dilution is a necessary requirement for most biochemical microfluidic-based quantitative diagnostic applications. Over the last two decades, a multitude of microfluidic devices has been proposed, each one demonstrating either a different type of dilution technique or complex system architecture based on various flow source and valving combinations. In this work, a novel serial dilution network architecture is demonstrated, implemented on two entirely different substrates for validation and performance characterisation. The single layer, stepwise serial diluter comprises an optimised microfluidic network, where identical dilution ratios per stage are ensured, either by applying equal pressure or equal flow rates at both inlets. The advantages of this serial diluter are twofold: Firstly, it is structured as a modular unit cell, simplifying the required fluid driving mechanism to a single source for both sample and buffer solution. Thus, this unit cell can be used as a fundamental microfluidic building block, forming multistage serial dilution cascades, once combined appropriately with itself or other similar unit cells. Secondly, the serial diluter can tolerate the inevitable flow source fluctuations, ensuring constant dilution ratios without the need to employ damping mechanisms, making it ideal for Point of Care (PoC) platforms. Proof-of-concept experiments with glucose have demonstrated good agreement between simulations and measurements, highlighting the validity of our serial diluter.

Highlights

  • Almost every quantitative chemical and biological assay relies heavily upon accurate and prompt serial dilution

  • The Two-Stage Serial Diluter In Table 1, columns 2 and 3, we summarise the results of the “first-cut” approximation numerical simulation based on the Matlab® code for the printed circuit board (PCB)-based device

  • Corporation, Waltham, MA 02451, USA ) and COMSOL Multiphysics®

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Summary

Introduction

Almost every quantitative chemical and biological assay relies heavily upon accurate and prompt serial dilution. Widely known quantitative assays, such as real time polymerase chain reaction (q-PCR). Antigen assays, e.g., Enzyme-Linked Immunosorbent Assay (ELISA), require serial dilutions of a known analyte to produce several reference calibration signals which can be later used for standard or calibration curves. The majority often requires multiple flow sources (pressure or flow rate) to be employed for driving fluids through the device. Their operation could be potentially unstable and they may be hard to handle [8] and integrate with other components in a monolithic manner

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