MIT engineers remedy the sticky-cell drawback in bioreactors and different industries | MIT Information

To assist mitigate local weather change, corporations are utilizing bioreactors to develop algae and different microorganisms which might be lots of of instances extra environment friendly at absorbing CO2 than timber. Meanwhile, within the pharmaceutical trade, cell tradition is used to fabricate biologic medication and different superior remedies, together with lifesaving gene and cell therapies.

Both processes are hampered by cells’ tendency to stay to surfaces, which ends up in an enormous quantity of waste and downtime for cleansing. An analogous drawback slows down biofuel manufacturing, interferes with biosensors and implants, and makes the meals and beverage trade much less environment friendly.

Now, MIT researchers have developed an method for detaching cells from surfaces on demand, utilizing electrochemically generated bubbles. In an open-access paper published in Science Advances, the researchers demonstrated their method in a lab prototype and confirmed it might work throughout a spread of cells and surfaces with out harming the cells.

“We wanted to develop a technology that could be high-throughput and plug-and-play, and that would allow cells to attach and detach on demand to improve the workflow in these industrial processes,” says Professor Kripa Varanasi, senior creator of the research. “This is a fundamental issue with cells, and we’ve solved it with a process that can scale. It lends itself to many different applications.”

Joining Varanasi on the research are co-first authors Bert Vandereydt, a PhD pupil in mechanical engineering, and former postdoc Baptiste Blanc.

Solving a sticky drawback

The researchers started with a mission.

“We’ve been working on figuring out how we can efficiently capture CO2 across different sources and convert it into valuable products for various end markets,” Varanasi says. “That’s where this photobioreactor and cell detachment comes into the picture.”

Photobioreactors are used to develop carbon-absorbing algae cells by creating tightly managed environments involving water and daylight. They function lengthy, winding tubes with clear surfaces to let within the gentle algae have to develop. When algae persist with these surfaces, they block out the sunshine, requiring cleansing.

“You have to shut down and clean up the entire reactor as frequently as every two weeks,” Varanasi says. “It’s a huge operational challenge.”

The researchers realized different industries have related drawback as a result of many cells’ pure adhesion, or stickiness. Each trade has its personal resolution for cell adhesion relying on how essential it’s that the cells survive. Some individuals scrape the surfaces clear, whereas others use particular coatings which might be poisonous to cells.

In the pharmaceutical and biotech industries, cell detachment is usually carried out utilizing enzymes. However, this methodology poses a number of challenges — it could actually injury cell membranes, is time-consuming, and requires giant quantities of consumables, leading to hundreds of thousands of liters of biowaste.

To create a greater resolution, the researchers started by finding out different efforts to clear surfaces with bubbles, which primarily concerned spraying bubbles onto surfaces and had been largely ineffective.

“We realized we needed the bubbles to form on the surfaces where we don’t want these cells to stick, so when the bubbles detach it creates a local fluid flow that creates shear stress at the interface and removes the cells,” Varanasi explains.

Electric currents generate bubbles by splitting water into hydrogen and oxygen. But earlier makes an attempt at utilizing electrical energy to detach cells had been hampered as a result of the cell tradition mediums include sodium chloride, which turns into bleach when mixed with an electrical present. The bleach damages the cells, making it impractical for a lot of functions.

“The culprit is the anode — that’s where the sodium chloride turns to bleach,” Vandereydt defined. “We figured if we could separate that electrode from the rest of the system, we could prevent bleach from being generated.”

To make a greater system, the researchers constructed a 3-square-inch glass floor and deposited a gold electrode on prime of it. The layer of gold is so skinny it doesn’t block out gentle. To maintain the opposite electrode separate, the researchers built-in a particular membrane that solely permits protons to move by way of. The arrange allowed the researchers to ship a present by way of with out producing bleach.

To take a look at their setup, they allowed algae cells from a concentrated resolution to stay to the surfaces. When they utilized a voltage, the bubbles separated the cells from the surfaces with out harming them.

The researchers additionally studied the interplay between the bubbles and cells, discovering the upper the present density, the extra bubbles had been created and the extra algae was eliminated. They developed a mannequin for understanding how a lot present can be wanted to take away algae in numerous settings and matched it with outcomes from experiments involving algae in addition to cells from ovarian most cancers and bones.

“Mammalian cells are orders of magnitude more sensitive than algae cells, but even with those cells, we were able to detach them with no impact to the viability of the cell,” Vandereydt says.

Getting to scale

The researchers say their system might characterize a breakthrough in functions the place bleach or different chemical substances would hurt cells. That consists of pharmaceutical and meals manufacturing.

“If we can keep these systems running without fouling and other problems, then we can make them much more economical,” Varanasi says.

For cell tradition plates used within the pharmaceutical trade, the staff envisions their system comprising an electrode that could possibly be robotically moved from one tradition plate to the following, to detach cells as they’re grown. It is also coiled round algae harvesting programs.

“This has general applicability because it doesn’t rely on any specific biological or chemical treatments, but on a physical force that is system-agnostic,” Varanasi says. “It’s also highly scalable to a lot of different processes, including particle removal.”

Varanasi cautions there may be a lot work to be achieved to scale up the system. But he hopes it could actually at some point make algae and different cell harvesting extra environment friendly.

“The burning problem of our time is to somehow capture CO₂ in a way that’s economically feasible,” Varanasi says. “These photobioreactors could be used for that, but we have to overcome the cell adhesion problem.”

The work was supported, partially, by Eni S.p.A by way of the MIT Energy Initiative, the Belgian American Educational Foundation Fellowship, and the Maria Zambrano Fellowship.