Advances in Microfluidic Systems and Numerical Modeling in Biomedical Applications: A Review

Abstract

The evolution in the biomedical engineering field boosts innovative technologies, with microfluidic systems standing out as transformative tools in disease diagnosis, treatment, and monitoring. Numerical simulation has emerged as a tool of increasing importance for better understanding and predicting fluid-flow behavior in microscale devices. This review explores fabrication techniques and common materials of microfluidic devices, focusing on soft lithography and additive manufacturing. Microfluidic systems applications, including nucleic acid amplification and protein synthesis, as well as point-of-care diagnostics, DNA analysis, cell cultures, and organ-on-a-chip models (e.g., lung-, brain-, liver-, and tumor-on-a-chip), are discussed. Recent studies have applied computational tools such as ANSYS Fluent 2024 software to numerically simulate the flow behavior. Outside of the study cases, this work reports fundamental aspects of microfluidic simulations, including fluid flow, mass transport, mixing, and diffusion, and highlights the emergent field of organ-on-a-chip simulations. Additionally, it takes into account the application of geometries to improve the mixing of samples, as well as surface wettability modification. In conclusion, the present review summarizes the most relevant contributions of microfluidic systems and their numerical modeling to biomedical engineering.

Keywords: microfluidics; microfluidics systems; mixing; numerical simulation; organ-on-a-chip.

Figure 1

Diagnostic applications: (a) design of a flow-through device (adapted from [55]), and (b) integrated microfluidic device fabricated by soft lithography (obtained from [62]).

Figure 4

(a) Diagram of cross-sections of T-type micromixer (obtained from [98]). (b) Proposed micromixer with baffles design to improve advection-based mixing (2D view) (obtained from [100]).

Figure 2

Organ-on-a-chip: (a) diagram of a three-dimensional brain-on-a-chip with an interstitial level of flow (obtained from [71]), and (b) lung airway-on-a-chip device design and set-up (obtained from [74]).

Figure 3

Schematic representation of a lab-on-chip (obtained from [79]).

Figure 5

(a) Velocity plots of the three investigated geometries for efficient blood–plasma separation (adapted from [103]). (b) The numerical model results for size-based separation of polystyrene microparticles (ρ water = 995.09 kg/m³ and ρ particles = 1060 kg/m³) (obtained from [104]).

Figure 6

Average drug concentration distribution in the tumor channel with five different tumor diameters (obtained from [106]).

Figure 7

(a) Schematic representation of the computational domain, modeled after the LOAC design (obtained from [124]). (b) A V-shape double-channel microfluidic device for chemotaxis. Inlet 1 was designed for media flow, and inlet 2 for chemokine perfusion (obtained from [76]).

Figure 8

Cardiotoxicity-on-a-chip to non-invasively monitor multiple biomarkers secreted by the cells with aptamers-functionalized biosensors (obtained from [128]).

Figure 9

(a) Top-view of the first ToC design consisting of twenty microwells (four microwells per channel) and the inlets and outlets for drugs and cells (obtained from [129]). (b) The convection–diffusion model for tumor-vascular communication within the device comprises three parallel tissue chambers, each connected to two square tissue-loading ports (obtained from [130]).

Figure 10

(a) A microfluidic device and a microphotograph of plugs (obtained from [136]). (b) Schematic diagram of a model for ultra-hydrophobic drag reduction. A combination of surface hydrophobicity and roughness allows water to stand away from the solid surface (obtained from [136]).

Figure 11

(a) Microscope image showing two inlet channels, in line and perpendicular to the outlet channel; and a graph representation of inlet means velocity as a function of time in the control case (dashed line) and in the biased sinusoidal pulsing case (solid line) (obtained from [140]). (b) Illustration of the concept of a linear temperature gradient microfluidic system (obtained from [141]).