I-Corps: Cell-free Biosensors

I-Corps项目更广泛的影响/商业潜力是开发一个分离和测量跨膜蛋白（TMPs）活性的平台。跨膜蛋白是生物学中最强大的传感元件之一，因为它们几乎可以检测到任何化学或生物化合物。由于这个原因，它们在检测和开发新疗法方面受到高度追捧。大约60%的候选药物靶向跨膜蛋白，包括病毒、疼痛和免疫受体蛋白等靶标。不幸的是，tmp在研究和使用方面具有挑战性。目前，研究跨膜蛋白的科学家和工程师依赖于劳动密集型的程序，需要高度专业化的设备和试剂。这些要求导致了昂贵和漫长的研究和开发，限制了这些重要生物分子的全面应用。拟议中的技术可能提供一种加速这项研究的方法，并允许科学家更快地将治疗方法推向市场。I-Corps项目的基础是开发一种快速组装的生物传感平台，该平台使用无细胞技术将跨膜蛋白整合到仿生传感设备中。众所周知，跨膜蛋白是一类难以研究的蛋白质，但它是细胞中许多生物功能的催化剂，因此也是缓解疾病的药物靶点。该平台采用特定的基因序列，直接将跨膜蛋白合成为脂质膜。这个提议的过程既提供了一个类似天然的环境来模拟细胞，又避免了传统上难以合成的问题。这种提出的无细胞合成方法允许开箱反应，可以在广泛的环境中设计和控制快速生产定制蛋白质。此外，这使得它非常适合开发高度可扩展和可调的传感平台，例如与微流体技术的集成。目前，这项技术已经被证明是通过将离子通道合成到生物膜传感器中，并使用该传感器来检测基于电子变化的小分子化学物质。所提出的技术利用了生物技术和生物电子学的进步，并有潜力为膜蛋白生物传感提供下一步。该奖项反映了美国国家科学基金会的法定使命，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 I-Corps project is the development of a platform to isolate and measure activity of transmembrane proteins (TMPs). Transmembrane proteins are one of biology’s most powerful sensing elements as they can detect nearly any chemical or biological compound. For this reason, they are highly sought after for both detection and development of new therapeutics. Roughly 60% of all drug candidates are targeted against transmembrane proteins, including targets such as viral, pain, and immune receptor proteins. Unfortunately, TMPs are challenging to study and use. Currently, scientists and engineers working with transmembrane proteins rely on labor-intensive procedures that require highly specialized equipment and reagents. These requirement result in costly and lengthy research and development that limits the full-scale application of these important biomolecules. The proposed technology may provide a way to expedite this research and allow scientists to bring therapies to market more rapidly.This I-Corps project is based on the development of a rapidly assembled, biosensing platform that uses cell-free technologies to integrate transmembrane proteins into a biomimetic sensing device. Transmembrane proteins are a notoriously difficult class of proteins to study but are catalysts of many biological functions in cells and, therefore, also pharmaceutical targets for disease mitigation. The proposed platform takes a specific gene sequence and directly synthesizes transmembrane proteins into a lipid membrane. This proposed process both provides a native-like environment to mimic the cell and circumvents traditionally difficult synthesis. This proposed cell-free synthesis method allows for an open-box reaction that may be engineered and controlled to produce customized proteins rapidly in a wide range of environments. In addition, this makes it ideal to develop sensing platforms that are highly scalable and tunable, such as integration with microfluidic technologies. Currently, this technology has been demonstrated by synthesizing an ion channel into a biomembrane sensor and using this sensor to detect a small-molecule chemical based on electronic changes. The proposed technology uses advancements in biotechnology and bioelectronics and has the potential to provide the next step in membrane protein biosensing.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.