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Inertial Microfluidics for
Biophysics and Biotechnology

Welcome to Hur Research Group

Our lab focuses on developing microfluidic platforms to understand complex fluid dynamics principles and to translate acquired knowledge into practical applications. Such platforms can facilitate simple cellular assays elucidating underlying veiled relationships between cellular functions and their physical phenotypes. We utilize a unique microscale hydrodynamic phenomenon called Inertial Focusing to accomplish high-throughput target cell detection, cost-effective cell separation, and sequential multimolecular delivery. By fine-tuning microchannel geometries and flow conditions, positions of flowing microscale particles and cells can be manipulated solely by fluid forces based on their size, shape, and softness. We envision that Inertial Microfluidics will enable simple and cost effective biological assays with potential for clinical adoption to improve diagnosis and disease management quality.

Inertial Microfluidics

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.   Top ↑

Precise Particle Manipulation

MpiM
Massively parallel inertial focusing for imaging flow cytometry.
Illustration by Marc Lim .
[Sheathless Flow Cytometry] 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]  Top ↑

NonSphear
Orientation of inertially focused nonspherical disks and cylinders.
Particles were fabricated by BiNEL.
[Inertial Focusing of Nonspherical Particles] 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]  Top ↑

 

Cellular Biophysical Property Measurement

MechDependent
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.
CellXeq
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]   Top ↑

 

Label-free Target Cell Purification

CCTV
High-throughput purification of selected target cells using inertial microfluidics apears to be feasible.
[Target Cell Selection based on Cellular Biophysical Properties] 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 & CCTV]  Top ↑

 

Vortex Assisted Electroporation

VortexElectropoation
Sequential multimolecular delivery via gentle vortex-assisted electroporation.
Illustration by Marc Lim .
[Exogeneous Molecular Delivery on Purified Target Cells] There is an increasing demand for techniques allowing intracellular delivery of exogenous substances with minimal toxicity for the purposes of cellular reprogramming studies, development of multigenic disorder therapies, as well as production of industrial and pharmaceutical compounds. The vortex-assisted electroporator uniquely provides the ability to sequentially deliver multiple molecules with different electroporation conditions into identical cell populations by trapping cells in microfluidic vortices as exogenous substances are serially flown over them. The developed electroporation system has practical potential as a versatile tool for cellular reprogramming studies, drug delivery applications, and studies optimizing complex molecular delivery processes. [Read more Single-chamber, JOVE , Drug cocktail analyses & Symmetric Array Electrodes]   Top ↑

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