PFI-TT: Cell Culture System with Enzyme-based Control of Oxygen Concentration to Enhance Biomedical Research

该创新-技术转化伙伴关系（PFI-TT）项目的更广泛影响/商业潜力是通过控制细胞培养中的氧气来加强生物医学研究。细胞培养是生物医学研究中最有用的技术之一，科学家们试图在体内培养细胞。然而，氧，细胞行为和生理学的关键因素，在标准细胞培养过程中不受控制。事实上，实验室细胞培养中的细胞经历的氧气浓度比体内高50倍。通过将细胞培养的现状从无氧控制改变为氧控制，所提出的技术可以促进对氧在疾病发展、生物过程和人体组织中的作用的科学理解。此外，该技术还可以通过以下方式改善人类健康：（i）促进新药和药物靶点的发现，（ii）提高药物筛选过程的准确性，降低失败药物的损耗率，成本和时间，以及（iii）加速基于细胞的癌症治疗和再生医学疗法的商业化。拟议的项目将开发氧控制细胞培养（OCC）系统，这是一种基于酶的方法，适用于已经用于细胞培养的容器。 与目前通过减少细胞培养容器周围气相中的氧气来发挥作用的氧气控制产品不同，OCC系统采用了一种创新方法，即利用酶直接在细胞环境中局部控制氧气浓度。这种方法提高了数据的准确性、一致性和再现性。OCC系统将通过测试将酶化学附着到细胞培养容器的多种策略来开发。通过控制容器内的酶消耗速率和氧转移速率，将氧浓度调节至特定值。将通过检查对干细胞和癌细胞行为和生理的影响来验证系统性能。通过这项提案，预计OCC系统原型将为下一阶段的商业化做好准备。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Partnerships for Innovation - Technology Translation (PFI-TT) project is to enhance biomedical research by controlling oxygen in cell culture. Cell culture, in which scientists attempt to grow cells in conditions like those in the body, is one of the most useful techniques in biomedical research. However, oxygen, a critical factor for cell behavior and physiology, is not controlled during standard cell cultures. In fact, cells in laboratory cell culture experience up to 50-fold higher oxygen concentrations than they do in the body. By changing the status quo of cell culture from non-oxygen-controlled to oxygen-controlled, the proposed technology can advance the scientific understanding of oxygen’s role in disease development, biological processes, and human tissues. In addition, the technology can improve human health by (i) fueling the discovery of new drugs and drug targets, (ii) improving the accuracy of the drug screening process, reducing the attrition rate, cost and time spent on failed drugs, and (iii) accelerating the commercialization of cell-based therapies for cancer treatment and regenerative medicine. The proposed project will develop the Oxygen-Controlling Cell Culture (OCC) system, an enzyme-based approach adaptable to the vessels already in use for cell culture. Unlike current oxygen-controlling products that function by reducing oxygen in the gas phase surrounding cell culture vessels, the OCC system takes an innovative approach by harnessing enzymes to locally control oxygen concentration directly in the cellular environment. This approach improves data accuracy, consistency, and reproducibility. The OCC system will be developed by testing a number of strategies to chemically attach enzymes to cell culture vessels. The oxygen concentration will be tuned to specific values by controlling the enzymatic depletion rates and oxygen transfer rates within the vessels. System performance will be validated by examining the impact on stem cells and cancer cell behavior and physiology. Through this proposal, it is anticipated that an OCC system prototype will be ready for the next stage of commercialization.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.