Silicon Photonic Blood Typing

摘要 每年对数以百万计的血液样本进行检测，以确定献血者和 接受输血的人。然而，目前的检测方法受到大血样需求的阻碍， 运输到中央实验室，离心机和测试的时间，专门的试剂，以及 技术培训需求，给医疗系统带来了昂贵的负担。特别是，减少了血液采样 容量是可取的，以避免加重可能需要输血的患者的贫血， 儿科和危重病人。此外，当前的测试时间需要维护通用单元以 当病人的血型尚不清楚时，提供紧急输血，使血液受到影响。 供给。因此，需要更小、更快、更好、更便宜的血型检测。我们建议的解决方案 将在一种多路、低成本和可扩展的硅纳米光子生物芯片上进行血型测试。这 概念验证研究已经证明了检测A、B和RhD(D)血型和 小容量血样中的抗A和抗B抗体。SiDx，Inc.已授权核心知识产权， 聘请了一位经验丰富的FDA监管顾问，并获得了种子资金，将这项技术商业化。 这个应用程序正在为SiDx寻求SBIR支持，以推动这项血型检测技术走向 为FDA的研究做好准备，未来的目标是FDA监管部门的批准和产品的商业化 作为医学诊断。在此SBIR Fast Track阶段I/II应用中，我们为每个 两个阶段：在第一阶段，我们提出了一个目标：开发概念验证分析来使硅光子功能 用于检测C、E和K血型的生物传感器。这些血型是关键的次要血型 可引发严重的、可能危及生命的免疫反应的抗原，并在扩大 未来产品的多路血型检测能力。在第二阶段，我们提出了两个目标：目标II.1： 研究链霉亲和素的表面官能化条件并优化其通过共价(硅烷)和 非共价(物理吸附)手段在硅光子表面上用于血型抗原和抗体检测 验证；以及目标II.2：在优化的基础上对ABO、D、C、E和K血型分析(和对照)进行多重 功能表面使用喷墨阵列和测试化验性能。这一目标还将评估以下样本 可以挑战临床实验室的常规检测方法，如弱D和混合现场反应 这种硅光子血型芯片有望实现血型检测的现代化，实现简单、快速、全面 在小容量血液样本中进行自动多路血型检测。我们预测，如果成功，这将是 该产品具有通过小样本改变血型检测和输血医学的潜力 批量要求、全自动测试和快速得出结果。这应该会减少医源性失血， 延迟输血，最大限度地减少通用装置的使用，并改善目前有 支持血型检测能力的资源有限。

SUMMARY Millions of blood samples are tested annually to establish blood type compatibility between blood donors and transfusion recipients. However, current testing methods are encumbered by the need for large blood samples, transportation to centralized laboratories, time to centrifuge and perform testing, specialized reagents, and technical training needs, placing a costly burden on the medical system. In particular, reduced blood sampling volumes are desirable to avoid exacerbating anemia in patients who may require transfusion, particularly pediatric and critically ill patients. Additionally, current test times create the need to maintain universal units to provide emergency transfusions when the blood type of the patient is not yet known, placing a strain on the blood supply. Thus, there is a need for smaller, faster, better, and cheaper blood group testing. Our proposed solution will perform blood group testing on a multiplexed, low-cost, and scalable silicon nanophotonic biochip. This technology has been demonstrated in proof-of-concept studies to detect A, B, and RhD (D) blood groups and anti-A and anti-B antibodies in small volume blood samples. SiDx, Inc. has licensed the core intellectual property, engaged an experienced FDA regulatory consultant, and secured seed funding to commercialize this technology. This application is seeking SBIR support for SiDx to advance this blood group testing technology towards readiness for FDA studies, with the future goal of FDA regulatory approval and commercialization of the product as a medical diagnostic. In this SBIR Fast Track Phase I/II application, we propose specific aims for each of the two Phases: In Phase I we propose one aim: to develop proof-of-concept assays to functionalize silicon photonic biosensors for the detection of blood groups C, E, and K. These blood groups are critical minor blood group antigens that can provoke severe, potentially life-threatening immune reactions and bring value in expanding the multiplexed blood group testing capabilities of the future product. In Phase II, we propose 2 aims: Aim II.1: to study surface functionalization conditions and optimize surface capture of streptavidin via covalent (silane) and non-covalent (physisorption) means on silicon photonic surfaces for blood group antigen and antibody assay validation; and Aim II.2: to multiplex ABO, D, C, E, and K blood group assays (and controls) on optimized functional surfaces using an inkjet arrayer and test assay performance. This aim will also assess samples that can challenge conventional testing methods in the clinical laboratory, such as weak D and mixed field reactions This silicon photonic blood typing chip holds the promise to modernize blood group testing with simple, fast, fully automated multiplexed blood group testing in small volume blood samples. We predict that, if successful, this product holds the potential to transform both blood group testing and transfusion medicine through small sample volume requirements, fully automated testing, and rapid time to results. This should reduce iatrogenic blood loss, delays in transfusion, minimize the use of universal units, and improve access in hospitals that currently have limited resources to support blood group testing capabilities.