Silicon Photonic Detection of anti-ABO Antibodies

Summary Problem: Detecting and quantifying Anti-ABO antibodies is essential for some medical procedures, such as whole blood transfusion and ABO-incompatible solid organ transplant and could greatly impact patient care for other indications, such as hemolytic disease of the fetus and newborn. However, current testing methods are encumbered by the need for large blood samples, transportation to centralized laboratories, time to centrifuge and perform testing of serial dilutions, specialized reagents and technical training needs, and technical variability between users and sites. Thus, there is a need for antibody detection and quantification that is standardized, multiplexed, and automated while simultaneously providing for speed and lower cost. Solution: SiDx has demonstrated the promise of our technology in proof-of-concept studies to detect A, B, RhD (D), C, E, and Kell blood group antigens in small volume blood samples and is working to multiplex these assays for commercialization. However, detection and quantification of anti-ABO antibodies presents further technical challenges. This SBIR application is seeking SBIR support to determine the feasibility of detecting and semi- quantitatively characterizing isotype-specific anti-ABO antibodies using silicon photonic biosensors. We propose to do this in two aims: In Aim 1, we propose developing proof-of-concept assays for IgG, IgM, and total anti- ABO antibodies. In Aim 2, we propose detecting and semi-quantitatively characterizing anti-ABO IgG antibodies in O-type samples over a physiologic range of titers. This work will provide data to support a SBIR phase II application in which we will propose optimization of the assays developed in phase I and quantitative analysis of IgG and IgM antibodies as well as providing a road map for future work on detection and quantification of other antibodies on our platform. Impact: This silicon photonic blood typing platform holds the promise to modernize blood group testing with simple, fast, fully automated, multiplexed blood group testing in small volume blood samples. The addition of quantitative and isotype-specific information about anti-ABO antibodies will increase the value of the SiDx platform by providing more actionable information in an easy to use automated test. We predict that this product will transform both blood group testing and transfusion medicine through small sample volume, fully automated testing, and rapid time to results.NARRATIVE Anti-ABO antibody detection and quantification is necessary in multiple medical indications, including ABO- incompatible transplantation and whole blood transfusion, and could be used to screen for pregnancies at risk for ABO-mediated hemolytic disease of the fetus and newborn if it were not cost-prohibitive. However, current antibody isotype identification and quantification methods require large volume blood samples, must be sent to a specialized laboratory where processing and testing is performed by trained laboratory staff, and have a great deal of technical variability between measurements. We propose to determine the feasibility of using a silicon photonic blood group testing chip assay that can detect and quantify isotype-specific anti-ABO antibodies using a small sample quickly, easily, and near the patient, without the need for specialized laboratory methods.