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

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.