Collaborative Research: Chemo-Physics and Molecular Design of In-situ Hydrogel-MXene Biosensors

结直肠癌（CRC）具有重大的全球影响，影响全球200万人，并成为美国癌症相关死亡的第三大原因。能够原位监测与CRC的发展和进展密切相关的生物标志物的技术对于CRC的及时诊断、早期干预和个性化治疗是非常理想的。然而，复杂的生理环境中复杂的化学、生物和机械因素对实现CRC的特异性、灵敏性和持久性早期检测提出了实质性挑战。在化学、生物工程、环境与运输系统系生物传感项目和化学系化学测量与成像项目的支持下，（密歇根州立大学），吴成林教授（密苏里州科技大学），和Xinyue Liu教授（密歇根州立大学）旨在通过开发能够检测低水平CRC生物标志物（例如，癌胚抗原（CEA））。原位水凝胶-MXene生物传感器将可能导致生物电子学的巨大飞跃，为疾病诊断提供变革性影响，并为个性化医疗保健铺平道路。此外，本发明还提供了一种方法，该项目旨在通过多机构和跨学科的努力，包括在本科课程中整合新课题，以及促进STEM领域，以鼓励更多学生从事这些领域的研究，促进新兴生物技术的下一代劳动力的发展。该项目的目标是将选择性渗透水凝胶与MXene基领域相结合，用于开发高性能水凝胶-MXene生物传感器的效应晶体管，所述水凝胶-MXene生物传感器可以实现低水平结肠直肠癌（CRC）生物标志物（例如，癌胚抗原（CEA）），同时减轻移动的离子的影响。为了实现这一目标，该项目将利用水凝胶中可逆相互作用、网络拓扑结构和固定电荷的分子设计来调节水凝胶与肠道的相互作用，以实现选择性生物分子运输，并调节水凝胶与MXene的相互作用，以提高场效应传感性能。具体而言，该项目将利用水凝胶中网络弹性和可逆相互作用的协同作用，独立调节靶和非靶生物分子的运输，从而实现选择性和增强的运输。此外，该项目将利用分子设计，原子模拟和DFT计算的综合努力来优化水凝胶的网络拓扑结构和固定电荷密度的设计，从而最大化德拜长度，降低电容，并调整水凝胶-MXene界面的带隙。最后，该项目将结合探索的水凝胶设计原则，构建一种高性能的水凝胶-MXene生物传感器，能够在模拟肠道环境中量化CRC生物标志物。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。

Colorectal cancer (CRC) has a significant global impact, affecting 2 million people worldwide and standing as the third leading cause of cancer-related deaths in the United States. Technologies that enable in-situ monitoring of biomarkers closely related to the development and progression of CRC are highly desirable for timely diagnosis, early intervention, and personalized treatment of CRC. However, the complicated chemical, biological, and mechanical factors within complex physiological environments present substantial challenges in achieving specific, sensitive, and durable early detection of CRC. With support from the Biosensing Program in the Division of Chemical, Bioengineering, Environmental and Transport Systems and the Chemical Measurement and Imaging Program in the Division of Chemistry, the research groups of Prof. Shaoting Lin (Michigan State University), Prof. Chenglin Wu (Missouri University of Science and Technology), and Prof. Xinyue Liu (Michigan State University) aim to overcome these challenges by developing in-situ hydrogel-MXene biosensors capable of detecting low-level CRC biomarkers (e.g., carcinoembryonic antigen (CEA)) in simulated intestinal environments. The in-situ hydrogel-MXene biosensor will potentially lead to a big leap in bioelectronics, offering transformative impacts in disease diagnostics and paving the way for personalized healthcare. In addition, this project is expected to foster the development of the next-generation workforce in emerging biotechnologies through multi-institutional and interdisciplinary efforts including the integration of new topics in undergraduate courses and the promotion of STEM fields to encourage more students to engage in these areas of study.The goal of this project is to integrate selective-permeable hydrogels with MXene-based field-effect transistors for developing high-performance hydrogel-MXene biosensors that can achieve in-situ detection of low-level colorectal cancer (CRC) biomarkers (e.g., carcinoembryonic antigen (CEA)) in simulated intestinal environments while mitigating the influence of mobile ions. To achieve this, this project will leverage molecular design of reversible interaction, network topology, and fixed charge in hydrogels to modulate hydrogel-intestine interactions for selective biomolecular transport and to regulate hydrogel-MXene interactions for improved field-effect sensing performance. Specifically, this project will leverage the synergy of network elasticity and reversible interaction in hydrogels to independently modulate the transport of target and non-target biomolecules, thereby enabling selective and enhanced transport. In addition, this project will harness the combined efforts of molecular design, atomic simulation, and DFT calculation to optimize the design of network topology and fixed charge density of hydrogels, thus maximizing the Debye length, reduce the capacitance, and tune the bandgap at the hydrogel-MXene interface. Finally, this project will incorporate the explored hydrogel design principles to build a high-performing hydrogel-MXene biosensor capable of quantifying CRC biomarkers in simulated intestinal environments.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.