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Biology subjects

Dahl, J. B.

Publications and source records attributed to Dahl, J. B..

2 recordsLinked to original sources

Microfluidic creep experiment for measuring linear viscoelastic mechanical properties of microparticles in a cross-slot extensional flow device

The micromechanical measurement field has struggled to establish repeatable techniques, likely because the deforming stresses can be complicated and difficult to model. Here we demonstrate experimentally the ability of cross-slot microfluidic device to create a quasi-steady deformation state in agarose hydrogel microparticles to replicate a traditional uniaxial creep test at the microscale and at relatively high throughput. A recent numerical study by Lu et al. [Lu, Guo, Yu, Sui. J. Fluid Mech., 2023, 962, A26] showed that viscoelastic capsules flowing through a cross-slot can achieve a quasi-steady strain near the extensional flow stagnation point that is equal to the equilibrium static strain, thereby implying that continuous operation of a cross-slot can accurately capture capsule elastic mechanical behavior in addition to transient behavior. However, no microfluidic cross-slot studies have reported quasi-steady strains for suspended cells or particles, to our knowledge. By using large dimension cross-slots relative to the microparticle diameter, our cross-slot implementation created an extensional flow region that was large enough for agarose hydrogel microparticles to achieve a strain plateau while dwelling near the stagnation point. This strain plateau will be key for accurately and precisely measuring linear viscoelastic properties of small microscale biological objects. The mechanical test was performed in the linear regime, so an analytical mechanical model derived using the elastic-viscoelastic correspondence principle was proposed to extract linear viscoelastic mechanical properties from observed particle strain histories. Particle image velocimetry measurements of the unperturbed velocity field were used to determine where in the device particles experienced extensional flow and the mechanical model should be applied. The measurement throughput in this work was 1 - 2 particles achieving a quasi-steady strain plateau per second, though measurement yield and throughput can be increased with particle-centering upstream device design features. Finally, we provide recommendations for applying the cross-slot microscale creep experiment to other biomaterials and criteria to identify particles that likely achieved a quasi-steady strain state.

bioengineering↗

Non-contact microfluidic analysis of the stiffness of single large extracellular vesicles from IDH1-mutated glioblastoma cells

In preparation for leveraging extracellular vesicles (EVs) for disease diagnostics and therapeutics, fundamental research is being done to understand EV biological, chemical, and physical properties. Most published studies investigate nanoscale EVs and focus on EV biochemical content. There is much less understanding of large microscale EV characteristics and EV mechanical properties. We recently introduced a non-contact microfluidic technique that measures the stiffness of large EVs (>1 m diameter). This study probes the sensitivity of the microfluidic technique to distinguish between EV populations by comparing stiffness distributions of large EVs derived from glioblastoma cell lines. EVs derived from cells expressing the IDH1 mutation, a common glioblastoma mutation known to disrupt lipid metabolism, were significantly stiffer than those expressed from wild-type cells. A supporting lipidomics analysis shows that the IDH1 mutation increases the amount of saturated lipids in EVs. Taken together, these data suggest that high-throughput microfluidics is capable of distinguishing between large EV populations that differ in biomolecular composition and therefore structure. These findings advance the understanding of EV biomechanics, in particular for the less studied microscale EVs, and demonstrate microfluidics to be a promising technique to perform clinical EV mechanophenotyping.

bioengineering↗