“`html
To assist in alleviating climate change, enterprises are employing bioreactors to cultivate algae and other microorganisms that are significantly more effective at sequestering CO2 than trees. Simultaneously, in the pharmaceutical sector, cell culture is utilized to produce biologic medications and other sophisticated therapies, including lifesaving gene and cell treatments.
Both methodologies face challenges due to cells’ inclination to adhere to surfaces, resulting in considerable waste and interruptions for cleanup. A comparable issue hinders biofuel generation, impacts biosensors and implants, and reduces efficiency in the food and drink sector.
Currently, MIT scholars have devised a method for detaching cells from surfaces as needed, by utilizing electrochemically produced bubbles. In an open-access article published in Science Advances, the researchers demonstrated their technique in a laboratory prototype and confirmed its effectiveness across various cells and surfaces without damaging the cells.
“We aimed to develop a technology that would be high-throughput and adaptable, enabling cells to attach and detach as required to enhance workflow in these industrial operations,” states Professor Kripa Varanasi, the senior author of the study. “This is a core challenge with cells, and we’ve addressed it with a scalable process. It is applicable to numerous different uses.”
Collaborating with Varanasi on the study are co-first authors Bert Vandereydt, a PhD candidate in mechanical engineering, and former postdoctoral researcher Baptiste Blanc.
Addressing a sticky challenge
The researchers commenced with a goal.
“We have been focused on discovering how we can effectively capture CO2 from various sources and transform it into valuable goods for several end markets,” Varanasi explains. “That’s where this photobioreactor and cell detachment become relevant.”
Photobioreactors are utilized to cultivate carbon-absorbing algae cells by establishing rigorously controlled environments that include water and sunlight. They comprise long, twisting tubes with transparent surfaces to allow light to reach the algae needed for growth. When algae adhere to these surfaces, they obstruct the light, necessitating cleaning.
“You have to pause and clean the entire reactor as often as every two weeks,” Varanasi notes. “It’s a significant operational challenge.”
The researchers recognized that other sectors face similar issues due to many cells’ inherent adhesive properties. Each sector has its own strategy for addressing cell adhesion, based on how crucial it is for cells to remain viable. Some individuals scrape the surfaces, while others apply special coatings that are detrimental to cells.
In the pharmaceutical and biotech sectors, cell detachment is generally performed using enzymes. However, this technique presents several difficulties — it can harm cell membranes, is labor-intensive, and requires substantial amounts of materials, yielding millions of liters of biowaste.
To engineer an improved solution, the researchers started by examining previous attempts to clear surfaces with bubbles, which primarily involved spraying bubbles onto surfaces and were largely ineffective.
“We understood that we required the bubbles to form on the surfaces where we do not want these cells to adhere; when the bubbles detach, it induces a localized fluid motion that applies shear stress at the interface and dislodges the cells,” Varanasi clarifies.
Electric currents produce bubbles by decomposing water into hydrogen and oxygen. However, earlier efforts to use electricity for cell detachment were obstructed because the cell culture media contain sodium chloride, which turns into bleach when mixed with an electric current. The bleach harms the cells, rendering it unsuitable for many applications.
“The issue lies with the anode — that’s where the sodium chloride converts into bleach,” Vandereydt elucidated. “We realized that if we could isolate that electrode from the rest of the system, we could stop bleach from being produced.”
To construct a more effective system, the researchers designed a 3-square-inch glass surface and placed a gold electrode atop it. The layer of gold is so thin it does not obstruct light. To keep the other electrode separate, the researchers incorporated a specialized membrane that permits only protons to pass through. This configuration enabled the researchers to send a current through without creating bleach.
To evaluate their system, they allowed algae cells from a concentrated solution to adhere to the surfaces. Upon applying a voltage, the bubbles facilitated the separation of the cells from the surfaces without causing any damage.
The researchers also investigated the interaction between the bubbles and cells, discovering that the greater the current density, the more bubbles were generated and the more algae was dislodged. They formulated a model to comprehend the amount of current required to detach algae in various environments and correlated it with findings from experiments involving algae as well as cells from ovarian cancer and bone tissues.
“Mammalian cells are orders of magnitude more delicate than algae cells, but even with those cells, we could detach them without affecting their viability,” Vandereydt remarks.
Scaling up
The researchers propose that their system could signify a breakthrough in scenarios where bleach or other chemicals could damage cells, including pharmaceutical and food production.
“If we can maintain these systems in operation without fouling and other complications, we can enhance their cost-effectiveness,” Varanasi states.
For cell culture plates utilized in the pharmaceutical industry, the team imagines their system consisting of an electrode that could be automatically transferred from one culture plate to another, detaching cells as they develop. It could also be wrapped around algae harvesting systems.
“This has broad applicability because it does not depend on any specific biological or chemical treatments but relies on a physical force that is system-agnostic,” Varanasi comments. “It’s also highly scalable to various processes, including particle removal.”
Varanasi cautions that much work remains to scale the system. However, he hopes it may one day enhance the efficiency of algae and other cell harvesting processes.
“The pressing issue of our time is to somehow capture CO2 in a manner that is economically viable,” Varanasi asserts. “These photobioreactors could facilitate that, but we need to resolve the cell adhesion challenge.”
The research received support, in part, from Eni S.p.A through the MIT Energy Initiative, the Belgian American Educational Foundation Fellowship, and the Maria Zambrano Fellowship.
“`