What exactly is the “Cancer Cell Migration Pack”?

It is a microfluidic system designed to allow real-time monitoring of cancer cell movement on a microscope over a long period of time. The point is easy enough, keep the cells in controlled conditions (temperature in particular) and you image them over hours, even a day, without the typical tradeoffs that accompany the long-term presence of cells on the microscope stage.

Why cell migration in cancer cells is such a big issue to researchers working on metastasis?

Since migration is a characteristic stage of metastasis, cells dissociate from a primary tumor and migrate to a different location. Clinically, it is generally accepted that metastasis is the primary motive of cancer deaths; this page refers to the numbers commonly used in the context (approximately 90% of cancer deaths are metastatic and 5-year survival in this scenario is less than 30%). Migration is difficult to overlook, whether your discipline is the basic mechanisms or the translational screening.

What is the added value in microfluidics to the “classic” migration assays (scratch assay, Transwell, etc.)?

Classic assays are convenient, but distort reality: they are in more realistic statistics, and they have less gradient control and average out heterogeneous behaviors. Microfluidic migration models provide this ability to tune flow, nutrient delivery and microenvironmental constraints with much further precision, and are compatible with continuous imaging. It is of particular importance when you want to measure specific or subpopulation-specific behaviors instead of a bulk readout.

What is in the standard configuration?

A typical installation that is customizable can be described in the page, although the minimum setup includes:

-A flow sensor (Galileo, MIC)

-A stage-top incubator (referred to as in development).

-User interface control software (Galileo user interface)

-A flow controller

-Two 15 mL Falcon reservoirs

-An example microfluidic ChipShop (currently called Fluidic 834) microfluidic chip proposal.

-Accessories like tubing, connectors, filters, etc. with consideration of compatibility between various tubing sizes.

Is it possible to migrate assays in flow without destroying my image?

That is one of the points of the pack. It is placed as adapted to cultures under flow with better quality of image data collection, namely due to the fact that the platform is expected to maintain cells in long term viability and stability on the microscope even as the fluid is perfused. Practically this is where attention to thermal control and the measurement of steady flow begin to become valuable than supposed.

Does it assist in tumor microenvironment such as hypoxia or nutrient deprivation?

Yes, indirectly, as it provides the ability to control microenvironment and observe it over a long period. It emphasizes that the tumor microenvironmental limitations (depleting nutrients and oxygen) can alter the pattern of secretion, motility and drug resistance and that microfluidic manipulation and live imaging is a viable path forward to investigate such effects wherein fewer black box variables exist in the presence of microfluidic control compared to mono-culture. In case your work particularly requires oxygen tension gradients, you would normally add that as an overlay control layer to the expanded platform design.

Can you give an example of a concrete experiment this pack is intended for?

An on-chip migration experiment of the ethanol impact on breast cancer cells (MCF-7). In that case, cells were cultured in a flowing condition; a simulation of a wound was done through laminar flow to localize the exposure of trypsin; and migration was followed at various concentrations of ethanol. The most tested condition of ethanol (65 mmol/L) yielded the greatest migration of the conditions tested over 24 hours indicating a dose-linked effect in that arrangement.

Clinical question: Is it possible to sterilize the stage-top incubator, and how painful is cleaning?

Yes, it is, according to the page: there is a straightforward sterilization and cleaning procedure that is supplied with the user manual. This counts in real laboratory life, since sterilizable is a relative term, the other half is whether it gets done consistently.

Should I place the stage-top incubator in a CO2 incubator to ensure that the cells are happy?

Not by default. The stage-top incubator is programmed to be positioned outside of the CO2 incubator (to maintain your microscope work process simple), but can be customized on the fly. Also important to note: it is said to be not gas-tight i.e. allow gas exchange with the ambient atmosphere.

Are media reservoirs to be maintained at 37 °C temperatures in the course of perfusion?

No. The page even states that reservoirs may be kept at room temperature, since the stage-top incubator is designed such that the medium would be at the desired temperature at the cells despite the temperature of the reservoir. Quite a convenient detail–considering that long-run operation with hot reservoirs may be active and has additional failure modes.

We are creating a Horizon Europe consortium: why do we need a microfluidics SME partner (such as MIC) in this case?

Should you require microfluidic platform engineering, microfluidic platform prototyping, microfluidic platform integration with imaging, or with powerful experimental setups that work on Day One, an SME that already designs and manufactures such systems can de-risk the technical work packages. And, in reality, when implementation, prototyping, and exploitation plans are in the hands of an expert SME, they tend to increase the plausibility of the science, which is what evaluators examine when the science is high but the path to validation remains vague.