A team of researchers from the Massachusetts Institute of Technology (MIT) has introduced an innovative enzyme-free approach for detaching anchorage-dependent cells from culture surfaces. This method, detailed in the journal ACS Nano, promises to enhance cell viability and streamline processes in biomanufacturing and biomedical applications.
Anchorage-dependent cells, essential in various fields including pharmaceuticals and biotechnology, require attachment to a solid surface for survival and growth. Traditional techniques for detaching these cells often involve enzymatic treatments, which can damage cell membranes and introduce complications in workflows. According to Kripa Varanasi, a professor of mechanical engineering at MIT, these processes can be labor-intensive and generate significant waste, with an estimated 300 million liters of cell culture waste produced annually.
The newly developed method utilizes alternating electrochemical current on a conductive biocompatible polymer nanocomposite surface. Varanasi explains that applying low-frequency alternating voltage can effectively disrupt cell adhesion within minutes while preserving over 90 percent cell viability. This approach addresses the limitations of existing enzymatic and mechanical methods, significantly reducing the risk of cell damage and waste production.
Implications for Biomanufacturing and Medicine
The implications of this enzyme-free detachment method extend beyond routine cell culture. It has the potential to revolutionize large-scale biomanufacturing by facilitating automated workflows for cell therapies, tissue engineering, and regenerative medicine. The platform enables the safe expansion and harvesting of sensitive immune cells, which is crucial for applications such as CAR-T therapies.
Wang Hee (Wren) Lee, a postdoctoral researcher at MIT and co-first author of the study, emphasizes the broader applications of their work. “Our electrically tunable interface can dynamically shape the ionic microenvironment around cells,” he states. This capability allows researchers to control ion channels and explore signaling pathways, which can be integrated into bioelectronic systems for drug screening and personalized medicine.
Co-first author Bert Vandereydt, a mechanical engineering researcher at MIT, highlights the scalability of this method. “Because this technique can be uniformly applied across large areas, it is ideal for high-throughput applications,” he explains. The team envisions automated, closed-loop cell culture systems becoming a reality in the near future.
Streamlining Cell Culture Processes
The versatility of this platform is underscored by Yuen-Yi (Moony) Tseng, principal investigator at the Broad Institute and collaborator on the project. “This advancement opens new doors for culturing and harvesting delicate primary or cancer cells,” Tseng remarks. The method has the potential to enhance workflows in both research and clinical biomanufacturing, reducing variability while preserving cell functionality for therapeutic use.
In their study, the researchers tested the enzyme-free method on human cancer cells, specifically osteosarcoma and ovarian cancer cells. After determining the optimal frequency for detachment, the efficiency increased from 1 percent to 95 percent, with cell viability maintained above 90 percent.
This breakthrough reflects a significant advancement in cell culture technology, with the promise of fostering new industries focused on sustainable and efficient biomanufacturing practices. The findings underscore the importance of innovation in the intersection of biotechnology and engineering, paving the way for future research and applications in the field.
