Scale-up production and application of graphene oxide as nanocarriers

纳米材料正在被纳入产品和设备，提供了一个转型变革的一瞥，使包括先进制造，纳米医学，可持续资源开发和清洁能源生产在内的广泛领域成为可能。当前的挑战包括创造新的和改进的测量方法，具有更高的空间分辨率、精度和灵敏度，制备具有纳米尺度特征的标准和参考材料，以及将纳米材料的特性和功能联系起来的能力。能否获得准确、快速和成本有效的方法来确保纳米材料的质量和可重复性是发展纳米材料应用的另一个关键障碍。氧化石墨烯（GO）是一种二维（2D）纳米材料，具有大表面积、高柔韧性和稳定性以及在水溶液中的分散性等优异性能。氧化石墨烯具有很强的络合能力和与dna和rna的相互作用，在一系列应用中具有很高的潜力，特别是在基因治疗中作为纳米载体。然而，尽管有广泛的策略，但没有一种石墨烯衍生物被考虑用于临床试验，这主要是由于在解决氧化石墨烯生产的可重复性、样品处理过程中物理化学性质的变化以及石墨烯材料潜在的细胞毒性方面提供的证据不足。我们建议在交叉流过滤系统中开发一种自动化和潜在机器学习控制的新方法，以生成可扩展的单层氧化石墨烯产品，具有可控制和可复制的纯度，形态和理化性质。我们还将使用这些可重复的产品创建氧化石墨烯缀合物的新配方，以解决有效靶向和将核酸递送到模型细胞系统中的挑战，作为氧化石墨烯应用概念的证明。同时，将使用新开发的配方和表征方法评估氧化石墨烯纳米载体的毒性，并结合传统的基于细胞的测定，以提供具有特殊研究设计的氧化石墨烯纳米载体的验证过程，强调基于性别的评估。提出的创新使二维纳米材料生产的工业规模成为可能，并为新型测量方法的发展和纳米材料的标准化提供了基础流。这些强大而标准的方法为纳米材料的发展带来了革命性的变化，这将确保纳米材料在广泛领域的应用。培训计划为学生和学员提供了一个多元化和包容性的研究环境，特别强调为代表性不足的小组成员提供公平的机会，并提高他们在表面化学，材料科学，多模态成像，纳米尺度测量和纳米技术领域的知识和技能。

Nanoscale materials are being incorporated into products and devices, offering a glimpses of transformational change that have enabled a broad range of sectors including advanced manufacturing, nanomedicine, sustainable resource development and clean energy production. Current challenges include creating new and improved measurement approaches with higher spatial resolution, accuracy and sensitivity, preparation of standards and reference materials with nanoscale features and the ability to correlate properties and functions for nanomaterials. Availability of accurate, rapid and cost effective methods to ensure the quality and reproducibility of nanomaterials is another key obstacle to the development of their applications. Graphene oxide (GO), a two-dimensional (2D) nanomaterial, has exhibited exceptional properties such as large surface area, high flexibility and stability, as well as dispersibility in aqueous solutions. GO has high potential in a range of applications, particularly in gene therapy serving as a nanocarrier for its strong complexation ability and interactions with DNAs and RNAs. However, despite the broad range of strategies, none of the graphene derivatives have been considered for clinical trials, largely due to the insufficient evidence provided in addressing the reproducibility of GO production, the variations of physicochemical properties across sample processing, and the potential cytotoxicity of the graphene materials. We propose to develop a novel approach with automation and potential machine-learning control in cross flow filtration system to generate scalable single layered GO products, with controlled and reproducible purity, morphology and physiochemical properties. We will also create novel formulations of GO conjugates using these reproducible product, to address the challenge of efficient targeting and delivery of nucleic acids into model cell systems as a proof of concept of GO application. At the same time, the toxicity of the GO nanocarriers will be evaluated using newly developed formulations and characterization methods, combined with traditional cell based assays, to offer a proof-of-process of GO nanocarriers with special research designs underline the gender based evaluations. The proposed innovation enables an industrial scale of 2D nanomaterial production, and provides fundamental stream for the developments of novel measurement methods and standardization for nanomaterials. These robust and standard methodologies delivers a transformative change on the development of nanomaterials that will ensure the applications in a broad range of sectors. The training program offers a diverse and inclusive research environment for students and trainees with particular emphasis to provide equitable opportunities to the under-representative group members and advance their knowledge and skills in the areas of surface chemistry, material sciences, multimodal imaging, nanoscale measurements and nanotechnology.