Yunseok Heo

Micro- and Nanofluidics for Cell Biology, Cell Therapy, and Cell-Based Drug Testing

Many biological studies, drug screening methods, and cellular therapies require culture and manipulation of living cells outside of their natural environment in the body. The gap between the cellular microenvironment in vivo and in vitro, however, poses challenges for obtaining physiologically relevant responses from cells used in basic biological studies or drug screens and for drawing out the maximum functional potential from cells used therapeutically. One of the reasons for this gap is because the fluidic environment of mammalian cells in vivo is microscale and dynamic whereas typical in vitro cultures are macroscopic and static. This presentation will give an overview of efforts in our laboratory to develop microfluidic systems that enable spatio-temporal control of both the chemical and fluid mechanical environment of cells. The technologies and methods close the physiology gap to provide biological information otherwise unobtainable and to enhance cellular performance in therapeutic applications. Specific biomedical topics that will be discussed include, in vitro fertilization on a chip, microfluidic tissue engineering of small airway injuries, breast cancer metastasis on a chip, electrochemical biosensors, and development of tuneable nanofluidic systems towards applications in single molecule DNA analysis.Copyright

Bubble lodging in bifurcating microvessel networks: a microfluidic model

Lodging of cardiovascular gas bubbles is investigated in a microfluidic model of small arteriole bifurcations. These experiments address the dynamics of the lodging mechanism of gas bubbles in bifurcations. This work is motivated by a novel gas embolotherapy technique for the potential treatment of cancer by tumor infarction. The experimental model arteriole bifurcations were constructed from a transparent elastomer (polydimethylsiloxane). A single air bubble was suspended in water within the parent tube of the bifurcation and a specified driving pressure was imposed via constant elevation reservoirs that were open to atmospheric pressure. The driving pressure and bubble size were varied, and their effects on the bubble lodging were assessed. The results show that the pressure to lodge a bubble in a bifurcation is less than to dislodge it. It was also possible to occlude an entire bifurcation and multiple bifurcation devices with bubbles. Splitting ratios were assessed in the range of lodging to dislodging pressure where we observed an instability in bubble splitting. From the results we estimate that gas bubbles from embolotherapy can lodge in vessels 21 mum or smaller in diameter. These findings may be useful in developing strategies for microbubble delivery in gas embolotherapy

A microfluidic model of microbubble lodging in small arteriole bifurcations

Lodging of cardiovascular gas bubbles is investigated in a microfluidic model of small arteriole bifurcations. This work is motivated by a novel gas embolotherapy technique for the potential treatment of cancer by tumor infarction and by air embolism. The experimental model arteriole bifurcations were constructed from a transparent elastomer, poly(dimethylsiloxane), using soft lithography. A single air bubble was suspended in water within the parent tube of the bifurcation and a specified driving pressure was imposed via constant elevation reservoirs that were open to atmospheric pressure. The driving pressure and bubble size were varied, and their effects on the bubble lodging were assessed. These findings may be useful in developing strategies for microbubble delivery in gas embolotherapy.