Lab on a Chip Blog

Researchers at the University of California, Los Angeles have developed a method to rapidly quantify the mechanical properties of single cells at high resolution using hydrodynamic and inertial fluid focusing. 

Cells undergo structural changes during disease states, particularly in certain cancer cell lines. For example, tumor cells with increased invasive potential exhibit increased deformability, which aids them during their migration into surrounding tissues¹. Measuring the mechanical properties of single cells as a biomarker of cell health using conventional Atomic Force Microscopy (AFM) or micropipette aspiration is time-consuming and requires extensive sample prep, limiting the analysis to a few cells. Dino Di Carlo’s group and collaborators developed a way to apply fluids to stretch single cells along two axes using hydrodynamic flow and perpendicular cross-flows without waiting for cells to stop within the channel. This method, termed ‘hydropipetting’, is compatible with inline microfluidic rinsing, capable of processing 65000 cells/sec, and utilizes automatic image processing to rapidly derive the mechanical phenotype of cell populations. 

Hydropipetting starts with inertial fluid focusing of cells to position them precisely in a flow channel by balancing lift forces and secondary flows by fine control over the Reynolds number of the fluid. Cell-free liquid is then excluded and cells are deformed both parallel and perpendicular to the main channel flow. Automated image data analysis then extracts metrics of cell strain, viscosity, diameter and deformability from high speed observation during cell deformation. 

Di Carlo and his group demonstrated the hydropipetting technique on two cancer cell lines (HeLa and Jurkat cells) and observed increases in cell deformability upon drug treatment to increase invasiveness, metastatic potential, and when disrupting structural cellular filaments. 

References:
[1] S. E. Cross, Y. Jin, J. Rao and J. K. Gimzewski, Nature Nanotechnology, 2007, 2, 780-783. 

Pinched-flow hydrodynamic stretching of single-cells
Jaideep S. Dudani, Daniel R. Gossett, Henry T. K. Tse and Dino Di Carlo. Lab Chip, 2013, 13, 3728-3734.
DOI: 10.1039/C3LC50649E

New research shows that it is possible to carry out flow switching in microfluidic devices via a single active hardware element: a tunable frequency periodic pressure source.

A common hindrance to the design of microfluidic systems is the large amount of unwieldy and expensive hardware (valves, actuators, etc.) required to control fluid flow rates in different parts of the chip. A team of engineers and chemists from UC Santa Barbara, the University of Virginia, and the University of Southampton has devised a method to address this problem. In the new method, a single variable-frequency pressure source communicates with the microfluidic chip via tubes connected to deformable films (“capacitors”) on the chip. The length of each tube is chosen such that the tubes will have well-separated resonance frequencies. Then, the frequency of the actuator is tuned to drive fluid flow in the desired channel only.

As demonstrated in their recent paper, the authors produced three separate devices with clearly differentiated excitation frequencies (see figure below). In addition, they demonstrated a single device with two separate flow channels that could be switched between by modulation of the driving frequency.

Fluid flow in the chip (left, from Figure 1E) is controlled by a periodic pressure source connected to a deformable film by a tube. By using tubes of different lengths, one can selectively drive fluid flow in a channel by tuning the pressure source to that channel’s resonant frequency (right, from Figure 2A).

The authors state that by utilizing a large range of excitation frequencies it should be possible to independently control up to 10 flow channels on a single chip using their technique. They also project that it should be possible to control multiple channels simultaneously by employing an excitation signal incorporating multiple frequencies. Thus, this new flow control technique has the potential to be an elegant and low-cost solution for many types of diagnostic applications.

Read this article in Lab on a Chip today:

Flow switching in microfluidic networks using passive features and frequency tuning
Rachel R. Collino, Neil Reilly-Shapiro, Bryant Foresman, Kerui Xu, Marcel Utz, James P. Landers, and Matthew R. Begley
DOI: 10.1039/c3lc50481f