NEW YORK (GenomeWeb) – A team of researchers at the University of Michigan Comprehensive Cancer Center and Michigan Engineering have developed a new microfluidic technology designed to track cancer cell metastasis.
Current microfluidic devices do not allow most cells to last very long in their chambers, eventually degrading over time. Most devices manage cells for short experiments of several days, but the characteristics of cancer cells change over time and nullify any attempts at long-term studies using standard devices.
As cancer cells develop, individual cells eventually break away and travel through a patient's capillaries, spreading to distant areas in the body and creating other areas of growth. This detrimental process takes weeks, if not months, to occur.
"It's especially important to be able to capture those leader cells and understand their biology – why are they so successful, why are their resistant to traditional chemotherapy, and how can we target them selectively?" study author and Breast Oncology Program Director at UMCCC Sofia Merajver said in a statement.
In an attempt to address these problems, researchers at UMCCC developed a small, fluidic device that allows them to cultivate cells for longer periods of time. While the study, published in Scientific Reports earlier this month, highlights that the device is stable for up to three weeks of culture, the team has been able to maintain the culture past two months.
Within the microfluidic device, the cells are suspended in three dimensions, unlike normal fluidic devices that hold cells in two dimensions.
"At first glance, this device looks like any other microfluidic device," said lead study author and Michigan postdoctoral fellow Koh Meng Aw Yong in an interview. But, "the novelty about this device is that we have designed it such as it can maintain 3D culture for a long period of time, and this is what really distinguishes it from other technology out there right now in the market."
The microfluidic device's unique structure allows cancer cells to be fed into the device with minimal disturbance or alteration to the cell structure. It consists of three molded channels running parallel through 1 mg/ml collagen gel.
In their experiments, Aw Yong and his collaborators recreated a tumor mass by first localizing a large starting number of PC3 and DU145 cell lines, known as the classical cell lines of prostatic cancer. They seeded the prostate cancer cells into the middle fluidic channel, which eventually formed a tumor.
Fluid flowed through a parallel channel to create pressure and flow without bothering the prostatic cell culture, promoting tumor invasion into the surrounding extracellular matrix. The team structured the flow of fluid in the channel to imitate what occurs with the body's capillaries.
While the PC3 cells were overall two times more invasive than DU145 at 12 days of culture, the difference rapidly disappeared after three weeks. This suggests that the invasive potential of cancer cells may change over time and highlights the importance of using long-term tumor culture to study invasion.
Aw Yong began developing the microfluidic device four years ago at the start of his post-doctorate research in cancer biology.While not an engineer, Aw Yong realized that the cancer research field needed to develop a better cancer diagnostic research tool. Microfluidic technology proposed that opportunity for him.
Working with Michigan engineers, Yong dealt with multiple challenges while developing the microfluidic devices, especially when dealing with its size. His team had to find a "sweet spot where [we] could combine robustness with ease of use and functionality of [the] device". One major contribution they had to consider was if an added capacity is truly a necessity, or if it was something the team incorporated "just because we could."
Other issues the team dealt with included maintaining the structural integrity of the microfluidic channel. Aw Yong and his collaborators struggled to expose lower concentrations of soft collagen to a direct flow than previous studies, and keeping it intact over a longer period of time (1 mg/ml versus 2-3 mg/ml). They went about the problem by using polytetrafluorethylene (PTFE) adaptors to secure the gel in place, introducing free flow directly into the channels.
"We are talking about long-term culture, and this allows us to measure and model tumor invasiveness, and really achieve more of a temporal, realistic resolution of the invasion process," Aw Yong elaborated.
While Aw Yong and his team have not tried using the device onliquid tumors like leukemia or lymphoma, they believe their device will be able track such diseases in future studies.
Aw Yong also believes the technology will potentially help personalized medicine efforts by "detecting cancer aggressiveness, response to therapy, and maybe provide some personal therapy options for individual cancer patients."
Aw Yong has licensed the technology for UMCCCas intellectual property. Aw Yong also noted that he is looking for collaborators to develop the applications and potentially commercialize the device.