– Humphrey Obuobi ’18

What do you get when you put cancerous cells in a cramped well? Tiny cancer balls, of course.

This may seem like the introduction for a dangerous biological weapon or simply a disaster, but researchers through the Singapore-MIT Alliance for Research and Technology (SMART) have dedicated much time and effort towards the efficient generation of these multicellular cancer aggregates, or MCAs for short. Instead of being used for some diabolical purpose, these cancer balls can be used to further understand metastasis of tumors in vivo — that is, the process by which malignant tumors spread through the circulatory system and bind to other surfaces in the body.

So how does one make a MCA? The secret is in the tendency of these cells to bind to a surface, thereby rooting themselves into position. By placing the cells in a conical indentation in a biocompatible gel and “passivating” the surface to prevent the cells from binding to the gel, the cancer cells can only stick to themselves. In the process, these cells form “spheroids,” a type of organized MCA that can then be used in metastasis studies.

The researchers at SMART focused on developing a protocol that would rapidly produce hundreds of these wells in a controlled, replicated manner. Given the speed and versatility of ultrashort laser pulses in bioengineering applications, Tu and associates used a far-infrared CO2 laser on a femtosecond (10-15 seconds) timescale to vaporize or melt small, distinct wells into various materials, including polystyrene, polymethylmethacrylate (PMMA), and poly-dimethysiloxane (PDMS). The wells themselves were characterized according to their aspect ratios (diameter divided by well depth), as well as the surface quality and end curvature. As a result of their experiments, Tu et al. concluded that polystyrene produced the most favorable characteristics for the microwells and future seeding of cancerous cells.

Still, researchers believe that they can further optimize the production of these wells by changing parameters of the laser used to create them. By modifying the distance between the laser head and the gel, the laser’s power, and the amount of time that the laser fires, one can alter the diameter and depth of the resulting well. Research conducted in the lab of Jordan Miller, PhD at Rice University has optimized the production of microwells in PDMS by altering these parameters and more, thus creating cleaner, more compact microwells for future metastasis studies.

With further studies, the involved researchers might be able to use these rapidly manufactured wells to study the metastasis of tumors more accurately and efficiently — a huge step in understanding the nature of cancer progression.

Source:

Tu, T., Wang, Z., Bai, J., Sun, W., Peng, W. K., Huang, R. Y., et al. (2013). Rapid Prototyping of Concave Microwells for the Formation of 3D Multicellular Cancer Aggregates for Drug Screening. Advanced Healthcare Materials, 3(4), 609-616.

Image credit: http://www.fluofarma.com

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