Recent Developments in Inertial and Centrifugal Microfluidic Systems along with the Involved Forces for Cancer Cell Separation: A Review

Abstract

The treatment of cancers is a significant challenge in the healthcare context today. Spreading circulating tumor cells (CTCs) throughout the body will eventually lead to cancer metastasis and produce new tumors near the healthy tissues. Therefore, separating these invading cells and extracting cues from them is extremely important for determining the rate of cancer progression inside the body and for the development of individualized treatments, especially at the beginning of the metastasis process. The continuous and fast separation of CTCs has recently been achieved using numerous separation techniques, some of which involve multiple high-level operational protocols. Although a simple blood test can detect the presence of CTCs in the blood circulation system, the detection is still restricted due to the scarcity and heterogeneity of CTCs. The development of more reliable and effective techniques is thus highly desired. The technology of microfluidic devices is promising among many other bio-chemical and bio-physical technologies. This paper reviews recent developments in the two types of microfluidic devices, which are based on the size and/or density of cells, for separating cancer cells. The goal of this review is to identify knowledge or technology gaps and to suggest future works.

Integrated Microfluidics for Single‐Cell Separation and On‐Chip Analysis: Novel Applications and Recent Advances

“…• Label-free, contact-free separation • Continuous sample processing possible [98] • Simple fabrication process that only relies on channel geometry…”

“…[49,52,53] The miniaturization and patterning of soft magnetic materials such as NiFe alloys (e.g., permalloy) can be achieved via standard microfabrication techniques, as well as in a simple, low-cost manner by filling microstructured microcavities with magnetic powders or pastes and capping them with polydimethylsiloxane (PDMS). [54][55][56] A recent application that takes advantage of such soft magnetic materials and high gradient magnetic fields is demonstrated by Dumas et al who microfabricated a • Complex flow patterns need careful design [98] • Limitations in sorting cells with similar size and density…”

“…In the direction orthogonal to flow, the position of cells/ particles is primarily determined by the equilibrium between wall-and shear gradient-lift forces, which push them toward the channel centerline and the channel walls, respectively. [97,98] In curved channels as well as in straight channels with disturbance structures (e.g., structures that disrupt the homogenous channel cross-section geometry), the lateral position of cells/ particles is additionally affected by secondary-flow drag forces. [98,99] Secondary flow, also called rotational flow or Dean flow, occurs due to the velocity mismatch between fluids at different cross-sectional regions as a result of the inertia of the fluid itself.…”

“…[97,98] In curved channels as well as in straight channels with disturbance structures (e.g., structures that disrupt the homogenous channel cross-section geometry), the lateral position of cells/ particles is additionally affected by secondary-flow drag forces. [98,99] Secondary flow, also called rotational flow or Dean flow, occurs due to the velocity mismatch between fluids at different cross-sectional regions as a result of the inertia of the fluid itself. [98,[100][101][102] As Dean flow is oriented perpendicular to the main flow, it also exerts a drag force on the submerged cells/ particles.…”

“…[98,99] Secondary flow, also called rotational flow or Dean flow, occurs due to the velocity mismatch between fluids at different cross-sectional regions as a result of the inertia of the fluid itself. [98,[100][101][102] As Dean flow is oriented perpendicular to the main flow, it also exerts a drag force on the submerged cells/ particles. By manipulating these forces, cells and particles of varying properties can be steered into different lateral equilibrium positions in laminar streams, which facilitates inertial focusing and therefore sorting.…”