SBIR Phase I: Sensitive and Rapid Endotoxin Assays via a Unique Optical Biosensor-Based Limulus Amoebocyte Lysate Test

这个小型企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力是探索一种创新的，高灵敏度，快速，紧凑和廉价的系统，用于检测称为内毒素的污染物。如果被内毒素污染的药品或植入式医疗器械与血液接触，它们可能会导致核心体温迅速上升，随后发生严重休克，甚至在诊断出问题之前就可能致命。据估计，仅在美国每年就进行7000万次内毒素检测。然而，常规方法遭受有限的灵敏度和速度或化学干扰问题。该项目将推进使用新型光学生物传感器的内毒素检测系统的开发，以快速，精确地检测低水平。该系统可应用于急性败血症的诊断。SBIR第一阶段项目将致力于内毒素检测在药品质量控制中的应用。所提出的方法将使用不同的物理参数，折射率（RI），灵敏地监测分析物溶液和鲎变形细胞溶解物（LAL）混合物中凝胶形成过程的早期发生。内毒素浓度将与由于LAL凝固引起的RI变化相关。一种独特的光子晶体生物传感器将用于监测RI的变化与高速（5分钟）。灵敏度高（0.000025 EU/mL），比实际水平高200倍。该晶体将用于全内反射（PC-TIR）配置，并带有成像系统以监控传感器的状态。该项目将通过3D打印进行快速原型迭代。技术目标包括：（1）设计和构建原型;（2）在存在典型干扰物质的情况下进行验证和确认;（3）评估半衰期短的放射性药物的检测速度。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 Small Business Innovation Research (SBIR) Phase I project is to explore an innovative, highly sensitive, rapid, compact and inexpensive system for detection of contaminants known as endotoxins. If pharmaceutical products or implantable medical devices contaminated with endotoxins come into contact with the bloodstream, they can cause a rapid rise in core body temperature followed by a severe shock, possibly fatal even before the problem is diagnosed. An estimated 70 million endotoxin tests are performed each year in the US alone. However, the conventional methods suffer from limited sensitivity and speed or chemical interference issues. The proposed project will advance the development of an endotoxin detection system using a novel optical biosensor for quick, precise detection of low levels. The proposed system can potentially be applied to sepsis diagnosis in acute care.The proposed SBIR Phase I project will address endotoxin testing for pharmaceutical quality control. The proposed approach will use a different physical parameter, refractive index (RI), to sensitively monitor the early onset of the gel-forming process in a mixture of analyte solution and Limulus Amoebocyte Lysate (LAL). Endotoxin concentrations will be correlated with the changes in RI due to the coagulation of LAL. A unique photonic-crystal biosensor will be used to monitor changes in RI with high speed (5 min.) and high sensitivity (0.000025 EU/mL), 200 times higher than the state of practice. This crystal will be used in a total internal reflection (PC-TIR) configuration, with an imaging system to monitor the sensor's state. The project will conduct rapid prototype iterations through 3D printing. Technical objectives include: (1) design and construct a prototype; (2) conduct verification and validation in the presence of typical interfering species; (3) evaluate assay speeds for testing of radiopharmaceuticals with a short half-life.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.