Modular Pressure and Flow Rate-Balanced Microfluidic Serial Dilution Networks for Miniaturised Point-of-Care Diagnostic Platforms

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.

Novel modular pressure and flow rate balanced microfluidic serial dilution networks on printed circuit boards: Designs, Simulations and Fabrication

“…After opening the inlet ports and the outlet wells (laser cutter machining) the inlet ports were threaded for interfacing with commercial connectors. A 2-stage PMMA serial diluter designed and prototyped following the same principle but with much bigger footprint generating dilutions of 1:6 ratio is described in [47]. Figure 5a shows the experimental setup with one syringe pump to drive both diluent and sample through the 2-stage PCB serial diluter, while Figure 5b shows the top view of the prototype device.…”

Revolutionizing sample preparation: a novel autonomous microfluidic platform for serial dilution

“…4,8 Kim et al proposed an alternative design based on the same diffusion principle to realize stepwise linear and logarithmic serial dilutions. [9][10][11] Although diffusion-based diluters can generate complex concentration profiles, their continuous flow operation requires a constant supply of multiple reagents with external pumping equipment, which is not ideal for operation in resource-limited settings.…”

Automated passive serial dilution microfluidic chip for calcium quantification based on the Arsenazo III method

“…In the proposed device, a pressure-driven network design approach consisting of a resistive-valveless circuit system 32,33 is used. It utilizes a resistive serial dilution network where each branch has a fixed hydraulic resistance equivalent to electrical resistance in an electrical network, which produces specific flow rate conditions in each inlet channel, assuming a uniform pressure input.…”