Overview: Tackling a universal bottleneck in cell-based production
Bioreactors are central to modern manufacturing, from growing algae that aggressively absorb CO2 to producing biologic drugs and cell therapies. But a stubborn challenge—cells sticking to surfaces—limits performance across industries. This adhesion reduces light exposure in photobioreactors, disrupts harvesting, and triggers costly downtime for cleaning. A new MIT approach promises to detach cells on demand using electrochemically generated bubbles, offering a scalable, non-destructive solution with broad applicability.
In a study published in Science Advances, MIT researchers demonstrated a lab-scale system that detaches cells from surfaces without harming them. The team believes the method can be adopted across photobioreactors, pharmaceutical cell cultures, and even food and biosensor industries, where fouling and adhesion impede throughput and efficiency.
The science behind the stickiness
Cell adhesion is a natural property that helps organisms attach to surfaces for growth. In bioreactors, however, sticking means light-blocking films in photobioreactors and clogging when attempting to harvest or refresh surfaces. Traditional detachment methods in pharma rely on enzymes, which can damage membranes, add cost, and generate waste. The MIT team sought a physical, scalable alternative that could work with diverse cell types and materials.
The core idea is to generate bubbles directly at the surfaces where cells tend to adhere. When bubbles form, they create local fluid flow and shear forces strong enough to dislodge cells. Importantly, this method avoids chemical treatments that could harm cells or contaminate processes.
A clever separation of electrodes to prevent bleach formation
One major obstacle in electrochemical approaches is the formation of bleach from sodium chloride in cell culture media, which can damage cells. The MIT group solved this by separating the electrode that drives bubble formation from the rest of the system with a proton-permeable membrane. This design prevents bleach generation while still delivering current to produce the detaching bubbles.
The researchers fabricated a compact 3-square-inch glass surface with a thin gold electrode to stay optically transparent for light-dependent growth. The membrane ensures protons pass through, while the adjacent electrode remains isolated from the culture medium. The result is a controllable detachment tool that preserves cell viability.
Evidence across multiple cell types
In experiments, algae grown in contact with the treated surfaces detached as current was applied, with higher current density producing more bubble formation and more detachment. The team developed a model to predict the required current for different settings and validated it against experiments using algae and mammalian cells, including ovarian and bone-derived lines. Even with mammalian cells, the researchers observed detachment without compromising viability, suggesting broad applicability across industries.
Scaling potential for industry
The beauty of the approach lies in its generality and scalability. It does not rely on cell-type-specific chemical treatments or coatings, but on a physical mechanism—bubble-induced shear—that can be integrated into existing workflows. For photobioreactors, a moving or modular electrode could detach adherent algae as harvests occur. In pharmaceutical manufacturing, detachable cells could reduce downtime and cut waste and costs associated with enzymes and buffers. The team envisions robotic electrode movement across culture plates or coils around harvesting lines to keep surfaces clean and productive.
“This is a high-throughput, plug-and-play solution,” said senior author Prof. Kripa Varanasi. “It’s scalable and system-agnostic, offering a path to more economical bioproduction, especially where chemical treatments are detrimental.”
Implications for climate and health
If bioreactors can run longer between cleanings and harvests, CO2-to-value pathways—like algae-based carbon capture—could become more economically viable. Similarly, robust, non-enzymatic detachment in cell culture could streamline biologics manufacturing, gene and cell therapies, and biosensor devices, reducing waste and downtime while protecting cell integrity.
Next steps and collaboration
The MIT team acknowledges that scaling from lab prototypes to industrial systems will require engineering refinements and pilot demonstrations. They plan to explore automated, scalable configurations that can adapt to various reactor geometries and production scales. The research was supported by Eni S.p.A through the MIT Energy Initiative, along with fellowships supporting the team’s investigators.
