Innovative 3D Microfluidic Tools for On-Chip Fluids and Particles Manipulation: From Design to Experimental Validation

Abstract

Micromixers are essential components in lab-on-a-chip devices, of which the low efficiency can limit many bio-application studies. Effective mixing with automation capabilities is still a crucial requirement. In this paper, we present a method to fabricate a three-dimensional (3D) poly(methyl methacrylate) (PMMA) fluidic mixer by combining computer-aided design (CAD), micromilling technology, and experimental application via manipulating fluids and nanoparticles. The entire platform consists of three microfabricated layers with a bottom reservoir-shaped microchannel, a central serpentine channel, and a through-hole for interconnection and an upper layer containing inlets and outlet. The sealing process of the three layers and the high-precision and customizable methods used for fabrication ensure the realization of the monolithic 3D architecture. This provides buried running channels able to perform passive chaotic mixing and dilution functions, thanks to a portion of the pathway in common between the reservoir and serpentine layers. The possibility to plug-and-play micropumping systems allows us to easily demonstrate the feasibility and working features of our device for tracking the mixing and dilution performances of the micromixer by using colored fluids and fluorescent nanoparticles as the proof of concept. Exploiting the good transparency of the PMMA, spatial liquid composition and better control over reaction variables are possible, and the real-time monitoring of experiments under a fluorescence microscope is also allowed. The tools shown in this paper are easily integrable in more complex lab-on-chip platforms.

Fabrication Methods for Microfluidic Devices: An Overview

“…Micro-milling can, however, be a very effective and low-cost way of prototyping microfluidic devices. Chiriaco et al have described a convenient fabrication approach for multilevel/3D PMMA fluidic mixer device comprising three layers structured using micro-milling and with a through hole to connect the different layers which were joined by spin-coating hot isopropyl alcohol on the surface of the substrate [42]. The hydrophilicity of the PMMA channels was improved by O 2 plasma treatment.…”

Beyond liquid biopsy: Toward non-invasive assays for distanced cancer diagnostics in pandemics

“…For commercial applications, the “ chip in a lab ” bottleneck must be sadly overlooked in favour of a more simplistic yet crucial technology that prioritizes usability and smooth component integration. Moreover, the choice of materials, user-friendly design and plug-n-play connections ( Zoupanou et al, 2021a ) are basic components that are necessary for ensuring market penetration and exploiting the added value that the technology offers. In many cases, indeed, the proof-of-concept devices use methods and materials which allow a high customization of architectures but are not suitable for the rapid shift to industrial context.…”

Microfluidic Point-of-Care (POC) Devices in Early Diagnosis: A Review of Opportunities and Challenges

“…In general, 3D printing technologies have influenced the development of microfluidics [63]; these technologies are automated, eliminating the human resources required for manufacturing conventional PDMS microfluidics [64], and have not only reduced costs but also achieved a good resolution and throughput, increasing their recognition by the scientific community [65,66]. High latitude means that the real flow of fluid can be simulated more accurately; thus, microfluidic devices with more dimensions are currently being developed [67]. Furthermore, 3D printing methods have substantial commercial potential and can rapidly produce prototype products, increasing the frequency and efficiency of experiments, and enabling the rapid commercialization of experimental technologies [68,69].…”