Magnetically powered microbots for thrombolysis

(a,b) With application of the rotating magnetic field Bx+By in the surface plane, colloids assemble via isotropic interactions and ‘sit and spin’ (scale bar, 20 μm). (c) With addition of a normal variable-phase component (Bz), the field rotation axis is oriented towards the surface plane, wheels ‘stand up’ at a camber angle, θc, and roll along the surface.

Propulsion at the microscale requires unique strategies such as the undulating or rotating filaments that microorganisms have evolved to swim. These features however can be difficult to artificially replicate and control, limiting the ability to actuate and direct engineered microdevices to targeted locations within practical timeframes. An alternative propulsion strategy to swimming is rolling. In this project we show that low-strength magnetic fields can reversibly assemble wheel-shaped devices in situ from individual colloidal building blocks and also drive, rotate and direct them along surfaces at velocities faster than most other microscale propulsion schemes. By varying spin frequency and angle relative to the surface, we have shown that microwheels can be directed rapidly and precisely along user-defined paths. Such in situ assembly of readily-modified colloidal devices capable of targeted movements provides a practical transport and delivery tool for microscale applications, especially those in complex or tortuous geometries.

One application of microwheels is for dissolution of blood clots that occlude blood vessels such as in thrombosis and stroke.  Immobilizing tissue plasminogen activator (tPA), the only FDA approved fibrinolytic, to superparamagnetic creates a drug delivery platform in which tPA-coated particles are injected into the bloodstream at a sub-therapeutic concentration, assembled and targeted to an occlusion using external magnetic fields, and accumulate and lyse a thrombus at higher rates that soluble tPA. IWe found that tPA-coated microwheels lyse clots at rate five-fold faster than 1 µg/mL soluble tPA (therapeutic concentration). The mechanism for the enhanced lysis relies on the penetration of wheels into the fibrin gel, dissolving it from the inside out, via bulk degradation-like kinetics combined with a high concentration at the interface that promotes surface degradation. We have also demonstrated that these fibrinolytic microwheels can dissolve platelet-rich clots formed in our microfluidic models.

This project is in collaboration with Dave Marr in Chemical and Biological Engineering at the Colorado School of Mines and Paco Herson in Anesthesiology and Neuroscience at the University of Colorado, Denver.

Related Publications

T.O. Tasci, P.S. Herson, K.B. Neeves, D.W.M. Marr. Surface-enabled propulsion and control of colloidal microwheels. Nature Communications, 7 (2016): 10225. doi:10.1038/ncomms10225

T.O. Tasci, D. Disharoon, R.M. Schoeman, K. Rana, P.S. Herson, D.W.M. Marr, K.B. Neeves. Enhanced fibrinolysis with magnetically powered colloidal microwheels. Small, 13 (2017): 1700954. PMID:28719063

T. Yang, T.O. Tasci, K.B. Neeves, N. Wu, D.W.M. Marr. Magnetic microlassos for reversible cargo capture, transport, and release. Langmuir, 33 (2017): 5932-5937. PMID:28318267

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