SBIR Phase I: All-Carbon, Chemically Cross-Linked 3D Nano Assemblies for Liquid Chromatography

该小型企业创新研究（SBIR）项目的更广泛影响/商业潜力将是开发高性能全碳反相高效液相色谱（HPLC）柱填料。每年13亿美元的HPLC色谱柱市场的客户包括生命科学、生物化学、工业、营养安全、环境、农业、工艺工程、学术和政府组织。反相色谱柱占HPLC色谱柱市场的大部分。进入市场后，我们的技术将吸引那些分析要求超出当前二氧化硅（通常由18个碳原子（C18）键合到二氧化硅载体上的疏水烷基链）或石墨碳基柱能力的客户，以及那些寻求以更低成本进行更快更有效分析的客户。它还将吸引寻求下一代性能能力的客户，用于分离结构相似的化合物、生物制剂、生物优化剂或生物仿制药。分子将包括几何异构体和非对映异构体（例如，手性药物如沙利度胺），生物源的（例如，在许多神经系统疾病如阿尔茨海默病中调节的儿茶酚胺或其它激素）。大分子包括结构相似的化合物（例如，镰状细胞性贫血中的血红蛋白变体）和许多药物代谢物（例如，阿片代谢物中的葡糖苷酸）和滥用药物（例如，该SBIR第一阶段项目提出建立用于反相HPLC的化学交联的全碳柱材料的技术可行性。 色谱技术在开发拯救生命的药物产品和医疗方法、确保我们的食品和水的安全、保护我们的环境和保护公众健康方面发挥着关键作用。反相HPLC色谱柱采用疏水固定相。典型的基于二氧化硅的反相HPLC柱不耐用，受到升高的pH和温度的挑战，并且对于高极性和密切相关的结构缺乏足够的保留。较新的石墨碳HPLC柱非常昂贵，并且既不能扩展也不能功能化以提高选择性。我们的技术的关键区别在于分子表面水平，我们新颖的专有制造技术直接将碳纳米材料与共价键连接起来，生产可扩展的全碳柱材料。我们在第一阶段的总体目标是确定最佳的色谱柱填充条件，并表征色谱柱的色谱性能，作为pH值和温度的函数，以及分离结构相似的小分子化合物和生物制剂的能力。成功完成拟议的研发计划将使我们能够最终确定高度差异化的全碳纳米材料色谱柱原型，这些色谱柱将提供无与伦比的化学和热稳定性、一流的回收率、出色的分离效率和更长的色谱柱寿命，同时成本显著降低。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be the development of high-performance all-carbon reverse-phase high-performance liquid chromatography (HPLC) column packing material. Customers of the $1.3 Billion/year HPLC column market include life science, biochemical, industrial, nutritional safety, environmental, agricultural, process engineering, academic and governmental organizations. Reversed-phase columns account for the majority of HPLC column market. Upon market entry, our technology will attract customers whose analysis requirements fall outside the capabilities of current silica- (Hydrophobic alkyl chains typically comprising of 18 carbon atoms (C18) bonded to silica support) or graphitic carbon-based columns as well as those who are seeking faster more efficient analysis at a lower cost. It will also attract customers seeking next-generation performance capabilities for separation of structurally similar compounds, biologics, biobetters or biosimilars. Molecules would include geometric isomers and diastereoisomers (e.g., chiral drugs such as thalidomide), biogenic (e.g., catecholamines or other hormones that are modulated in many neurologic disorders such as Alzheimer Disease). Macromolecules include structurally similar compounds (e.g., hemoglobin variants in sickle cell anemia) and many drug metabolites (e.g., glucuronide in opioid metabolites) and drugs of abuse (e.g., cannabis).This SBIR Phase I project proposes to establish the technical feasibility of a chemically-crosslinked all carbon column material for reverse phase HPLC. Chromatography technology plays a key role in the development of life-saving pharmaceutical products and medical therapies, ensuring the safety of our food and water, protection of our environment and guarding public health. Reversed-phase HPLC columns employ a hydrophobic stationary phase. Typical silica-based reverse phase HPLC columns are not durable, are challenged by elevated pH and temperature and lack sufficient retention for highly polar and closely related structures. The newer graphitic carbon HPLC columns are prohibitively expensive and neither scalable nor functionalizable for improved selectivity. Our technology's key differentiator is at the molecular surface level, where our novel proprietary fabrication technology directly connect carbon nanomaterials with covalent bonds, producing scalable all-carbon column materials. Our overall objective during Phase I is to identify the optimal column packing conditions and characterize the chromatographic performance of the columns as a function of pH and temperature and ability to separate structurally similar small compounds and biologics. Successful completion of the proposed research and development plan will allow us to finalize highly differentiated all-carbon nanomaterial column prototypes that will offer unparalleled chemical and thermal stability, best-in-class recovery, excellent separation efficiency and increased column longevity at a significantly lower cost.