Glioblastoma (GBM) is the most common and aggressive adult primary brain tumor. The average age- adjusted incidence rate is 3.2 per 100,000 population. GBM is known for its poor survival rate. Surgical resection, radiation, and chemotherapy is only palliative. GBM cells are especially motile, compared to other cancers. This enables a novel strategy, to eradicate glioblastoma by introducing high motility conditions in the extracellular matrix, and directing glioblastoma cells by means of cytokine/chemokine gradients to a site from where they can be permanently removed from the brain. We have designed, tested, and validated a microfluidic device capable of quantitatively measuring the velocity of cell (cluster) migration following cytokine gradients. The principal outcome of this EAGER grant is that a novel glioblastoma treatment strategy based on mechanobiology is possible. 

The following research & development has been successfully performed during this EAGER grant: 

A 3D printing method was developed for molds to shape PDMS gradient devices. This method for fabricating PDMS devices will cost approximately 100 times less than traditional photolithography for mold production when considering the equipment and materials needed. 3D printing molds is also considerably easier and requires less time. A PDMS baking procedure was developed using the printed resin molds. Contact angle analysis was used to investigate if volatile species from the resin were transferring into the PDMS during baking. This work confirmed that the resin was not impacting the PDMS surface properties. In fact, after both single and replicate use of the resin molds, the mold surface became more like the native PDMS surface.

It was confirmed that the 3M? 9795R microfluidic tape could be used to seal PDMS devices. A method was developed to eliminate bubbles during device filling through periods of increasing and relatively constant applied pressure using the filling apparatus syringe and monitoring using the in-line pressure sensor.

A post-print treatment process was adopted to aid in removal of toxins from the cured resin material that could leach into PDMS during baking. Once the 3D-printed molds have been rinsed in isopropyl alcohol, dried, and exposed to the final post-print cure, the molds are sterilized with 70% ethanol and placed into a biosafety cabinet to dry under UV light. The prints are then soaked in sterile 1x phosphate buffered saline for 24 hours at 37 ?C. After soaking, the molds are rinsed in ultrapure water, dried, and stored in petri dishes before PDMS molding.

Last Modified: 08/29/2023
Modified by: Stefan H Bossmann