Inertial Microfluidics for
Biophysics and Biotechnology
Welcome to Hur Research Group
Our lab focuses on developing innovative microfluidic techniques for sheathless particle positioning, cellular biophysical property measurements and label-free target cell purification. Inertial Focusing is a unique microscale hydrodynamic phenomenon, which can be utilized to accomplish aforementioned purposes. By fine-tuning microchannel geometries and flow conditions, the lateral location of flowing particles with a wide range of varying sizes, mechanical stiffnesses and shapes, can be precisely controlled. We envision that Inertial Microfluidics will enable development of simple and cost effective target cell identifcation/purification techniques, which will have beneficial impact for numerous clinical and research applications.
It is a common, widely-spread berief in the microfluidic community that inertia effect of the fluid can be safely neglected since the length scale of system is small, thus, the Reynolds number of the system is small. In microfluidic systems, therefore, flowing particles are believed to faithfully follow their intial streamlines. However, recently Di Carlo et al. discovered that particles can migrate across the streamlines and be focused at distinct lateral position across the channel crossection when the system is operated at relatively high flow rate, greatly resembling the inertial effect described in centimeter-scale systems in the early 1960s. Since then, many potential applications utilizing the microscale inertial effect have been demonstrated (read Inertial Microfluidics review paper for more details). In breif, a balance of counteracting inertial lift forces (specailly wall-effect and shear-gradient lift) acting on flowing particles/cells leads to unique lateral and vertical positions in a microchannel with a rectangular cross-section when flow speeds are relatively high (a few centimeter to meter per second). Since flowing particles/cells are focused to predictable locations with a uniform downstream velocity, inertial focusing holds great promises for research, clinical and industrial applications, which require precise particle focusing and manipulation in flow.
Precise Particle Manipulation
[Sheathless Flow Cytometry]
Massively parallel inertial focusing for imaging flow cytometry.
Illustration by Marc Lim
Flow cytometry is the gold standard in cell analysis and it is regularly used for blood analysis (i.e., complete blood counts). Flow cytometry, however, lacks sufficient throughput to analyze rare cells in blood or other dilute solutions in a reasonable time period because it is an inherently serial process. We exploited inertial effects for label- and sheath-free parallel flow cytometry with extreme throughput (1 million cells/s
) for rapid and accurate differentiation of cells. As no additional external forces are required to create ordered streams of cells, this approach has the potential for future applications in cost-effective hematology or rare cell analysis platforms with extreme throughput capabilities when integrated with suitable large field-of view imaging or interrogation methods. [Read more
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[Inertial Focusing of Nonspherical Particles]
Orientation of inertially focused nonspherical disks and cylinders.
Particles were fabricated by
Despite rapid advancements in the field of molecular biology, fast and information-rich identification and quantification of minute analytes remains challenging for various applications. Increase in demand for such techniques has lead to development of innovative multiplexed particle-based biochemical assays. To meet the requirement for clinical applications, a method of particle manipulation in a high-throughput manner without sheath-flow or active guiding is needed. We have found that inertial effects can be utilized to focus nonspherical microparticles at uniform lateral and vertical locations. [Read more
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Cellular Biophysical Property Measurement
Mechanical properties of flowing particles can be reflected in lateral dynamic equilibrium positions, Xeq.
a/W: particle diameter to channel width ratio, λ: viscosity ratio between continuous and disperse phases
In addition to nonlinearity associated with the inertia of the fluid, nonlinear lateral migration can occur when the particle itself is deformable. Lateral migration of deformable particles was found to result from a nonlinearity caused by matching of velocities and stresses at the particle/droplet interface. That is, the magnitude of lateral drift velocity and lift force is closely related to the deformed shape of the object. The fact that deformable particles experience an additional lift force suggests the possibility of high throughput deformability-induced particle classification and separation. Deformation-induced lift forces will act in superposition with inertial lift forces to create modified lateral equilibrium positions that are dependent on particle deformability.
Lateral dynamic equilibrium positions vary depending on cellular biophysical properties.
The fact that deformable particles experience an additional lift force suggests the possibility of high throughput deformability-induced particle classification and separation. Deformation-induced lift forces will act in superposition with inertial lift forces to create modified lateral equilibrium positions that are dependent on particle deformability. [Phenotype Dependent Inertial Focusing]
Single-cell deformability has recently been recognized as a unique label-free biomarker for cell phenotype and lineage determinations.
As the flowing particles with different mechanial properties experience different magnitude of lift forces, the lateral equilibrium position can then be used as the measure of particle deformability when the particle size is taken into account. [Read more
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Label-free Target Cell Purification
[Target Cell Selection based on Cellular Biophysical Properties]
High-throughput purification of selected target cells using inertial microfluidics apears to be feasible.
The ability to detect and isolate rare target cells from heterogeneous samples is in high demand in cell biology research, immunology, tissue engineering and medicine. Techniques allowing label-free cell enrichment or detection are especially important to reduce the complexity and costs towards clinical applications. In inertial microfluidics, cells with varying biophysical properties (e.g., size and deformability), can be differentially focused at distinct locations corresponding to their properties. Thus, the differences in lateral equilibrium position among cell types can be utilized for biophysical property based target cell enrichments by directing entrained target cells to separate designated outlets or by isolating target cells in geometric compartments. [Read more DACS
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