Optimization of microfluidic microsphere-trap arrays

Abstract

Microarray devices are powerful for detecting and analyzing biological targets. However, the potential of these devices may not be fully realized due to the lack of optimization of their design and implementation. In this work, we consider a microsphere-trap array device by employing microfluidic techniques and a hydrodynamic trapping mechanism. We design a novel geometric structure of the trap array in the device, and develop a comprehensive and robust framework to optimize the values of the geometric parameters to maximize the microsphere arrays' packing density. We also simultaneously optimize multiple criteria, such as efficiently immobilizing a single microsphere in each trap, effectively eliminating fluidic errors such as channel clogging and multiple microspheres in a single trap, minimizing errors in subsequent imaging experiments, and easily recovering targets. We use finite element simulations to validate the trapping mechanism of the device, and to study the effects of the optimization geometric parameters. We further perform microsphere-trapping experiments using the optimized device and a device with randomly selected geometric parameters, which we denote as the un-optimized device. These experiments demonstrate easy control of the transportation and manipulation of the microspheres in the optimized device. They also show that the optimized device greatly outperforms the un-optimized device by increasing the packing density by a factor of two, improving the microsphere trapping efficiency from 58% to 99%, and reducing fluidic errors from 48% to a negligible level (less than 1%). The optimization framework lays the foundation for the future goal of developing a modular, reliable, efficient, and inexpensive lab-on-a-chip system.

A smartphone controlled handheld microfluidic liquid handling system

“…PBS + 0.1% Tween-20), capture antibody-coated polystyrene microbeads, sample, and fluorescently labelled detection antibodies. Inside the reaction chambers, arrays of hydrodynamic traps with openings of different sizes are used to immobilize individual capture antibody coated microbeads at predefined locations [18][19][20] . Sequential traps of different sizes (larger sizes upstream) can be used to trap different sized microbeads for multiplexed detection.…”

“…Briefly, the microfluidic channels are first blocked by a blocking buffer to reduce nonspecific binding. Then capture antibody-coated polystyrene microbeads are loaded and immobilized by the microfluidic hydrodynamic traps [19][20][21] . Microbeads of different sizes can be immobilized at different locations for multiplexed detections.…”

Transport of biomolecules to binding partners displayed on the surface of microbeads arrayed in traps in a microfluidic cell

“…These designs have an opening at the back end of the trap, to facilitate flow through the trap enabling easy capture and allowing target to stream over a trapped microbead (e.g., Refs. [19][20][21].…”

“…Two common methods for arraying microbeads in a microfluidic cell are by using wells patterned into the bottom surface of the cell, e.g., Duffy et al 17 and Ramsey et al 18 or traps arranged as a microfluidic obstacle course, e.g., Nehorai et al 19,20 and our prior study on arraying lipobeads. 21 Well deposition has also been enhanced by using electric and magnetic fields to assist in the capture, [22][23][24] or by using holes placed in the well and connected to a drain to provide fluid suction (see McDevitt et al 25,26 and Ketterson 27 ).…”

Streamline based design guideline for deterministic microfluidic hydrodynamic single cell traps

“…Xu et al developed a set of design criteria for a groove-shaped trap geometry which maximized trap density and single microsphere occupancy while minimizing clogging in microfluidic channels but sample use efficiency was not addressed. 13 The most widely used design guideline for hydrodynamic trapping is that of Tan and Takeuchi. 14 By modelling a trap design in terms of the flow resistances of the capturing and bypassing pathways, they were able to formulate an expression to describe the trapping efficiency.…”