Salivary-based Bone-loss Marker Detection Platform for Point-of-Care Screening

描述(申请人提供)：骨是一种动态的组织，它自然并持续地经历周转，成骨细胞以平衡的速度形成新骨，破骨细胞以平衡的速度吸收旧骨；两者之间的任何不平衡都会导致不同状态的异常骨周转，如骨质疏松，并伴随骨脆性和骨折风险增加。尽管骨质疏松症是一种常见的疾病，尤其是在老年女性中，但它通常只有在出现脊柱或髋部骨折等病态症状的后期才被诊断出来。目前，骨密度(BMD)测量最可靠的方法是成像技术，如双光子吸收法(DPA)、定量计算机断层摄影术(QCT)和双能X射线吸收法(DEXA)。尽管这些诊断技术是准确的，但它们并不是常规骨密度筛查的最佳选择，因为与护理点测试相比，它们昂贵、相对耗时和劳力密集，而且通常无法用于对大量有骨质疏松风险的人群进行常规筛查。目前以实验室为基础的检测，如用于检测血液或尿液中单个生物标记物的酶联免疫分析(ELISA)试剂盒，通常不能用于筛查和治疗后续应用，因为它们具有侵入性且价格昂贵。对骨转换标志物的可靠测量进行了研究，以评估它们在诊断和预测骨恶化中的作用；这些研究评估了它们与骨密度测量的相关性，以T分值表示，非常一致。骨转换标志物可以从血液或尿液中检测，然而，最近的注意力集中在唾液诊断上，因为它们的采样方便和非侵入性。智能光学系统公司(IOS)建议开发一种经济高效、易于使用、非侵入性的骨转换唾液标志物筛查平台，该平台基于iOS先前开发的横向流动测试条(LFTS)技术。该平台将评估两个关键的骨活动：以骨钙素(OC)为代表的骨形成和以胶原交联脱氧吡啶(D-PYR)为代表的骨吸收。高稳定的量子点标记技术将通过荧光测量提供检测，并将允许使用相同的样品、测试条和激发光源进行多路检测。第一阶段将重点展示实现缓冲液和模拟唾液中OC和PYR/D-PYR水平的可重复、灵敏测量的可行性。与密西西比大学医学中心牙周病和预防科学系的罗杰·B·约翰逊教授合作，一项简单的前瞻性研究将包括人类唾液样本检测与尿液/血液水平和骨密度测量的比较。第二阶段将在大规模人群研究中展示LFTS的敏感性和可靠性，使用唾液样本来验证检测准确性并满足临床要求。 公共卫生相关性：智能光学系统公司建议开发一种基于唾液的非侵入性骨丢失标志物检测平台的新技术。该检测器的设计具有筛查应用所需的测量精度，而无需血液或尿液采样和测试，因此将有助于快速诊断和适当的治疗。建议的检测平台将通过一种廉价的非侵入性方法实现对骨丢失生物标志物的常规筛选，该方法可用于护理点(POC)测试。常规筛查将导致更早发现骨丢失，这反过来将导致更有效的治疗选择，改善骨质疏松症患者的生活质量。在减少与骨质疏松相关的骨折和相关治疗方面，将实现显著的成本节约。

DESCRIPTION (provided by applicant): Bone is a dynamic tissue that naturally and continually undergoes turnover with new bone formation by osteoblasts and old bone resorption by osteoclasts at a balanced rate; any imbalance between the two rates results in varying states of abnormal bone turnover such as osteoporosis, with accompanying bone fragility and increased risk of fracture. Although osteoporosis is a common condition, particularly in older women, it is usually only diagnosed at a later stage when morbid symptoms, such as spine or hip fractures, have occurred. Currently, the most reliable methods for bone mineral density (BMD) measurements are imaging techniques such as dual photon absorptiometry (DPA), quantitative computed tomography (QCT), and dual energy X-ray absorptiometry (DEXA). Although these diagnostic techniques are accurate, they are not optimal for routine screening of bone density because they are expensive, relatively time- and labor-intensive compared to point- of-care tests, and often unavailable to for routine screening of the large population at risk for osteoporosis. Current laboratory-based tests such as enzyme linked immunoassay (ELISA) kits for the detection of individual biomarkers in either blood or urine are generally not offered for screening and treatment follow-up applications because they are invasive and expensive. Reliable measurements of bone turnover markers have been studied to evaluate their role in the diagnosis and prediction of bone deterioration; these studies assessed their correlation to BMD measurements, presented in T-score values, with great agreement. Bone turnover markers can be assayed from blood or urine, however, recent attention has focused on salivary diagnostics because of their convenient and non-invasive nature of sampling. Intelligent Optical Systems (IOS) proposes to develop a cost-effective, easy-to-use, non-invasive screening platform for bone turnover salivary markers based on a lateral flow test strip (LFTS) technique previously developed by IOS. This platform will assess two key bone activities: bone formation, presented in osteocalcin (OC), and bone resorption, presented in collagen crosslink deoxypyridinoline (D-PYR). Highly stable quantum dot labeling techniques will provide detection via fluorescence measurements, and will allow multiplexed detection using the same sample, test strip, and excitation light source. Phase I will focus on demonstrating the feasibility of achieving reproducible, sensitive measurements of OC and PYR/D-PYR levels in buffer and modeled saliva. In collaboration with Prof. Roger B. Johnson of the University of Mississippi Medical Center, Department of Periodontics and Preventive Sciences, a simple prospective study will include human saliva sample testing in comparison with urine/blood levels and BMD measurements. Phase II will demonstrate LFTS sensitivity and reliability in a large population study using salivary samples to validate detection accuracy and meet clinical requirements. PUBLIC HEALTH RELEVANCE: Intelligent Optical Systems proposes to develop a new technique for a non-invasive salivary-based bone-loss marker detection platform. The detector is designed to have the measurement accuracy required for screening applications without the need for blood or urine sampling and testing, and will therefore contribute to a quick diagnosis and appropriate treatment. The proposed detection platform will enable routine screening of bone loss biomarkers via an inexpensive, non-invasive method that can be employed in point-of-care (POC) testing. Routine screening will result in an earlier detection of bone loss, which in turn will result in more effective treatment options, improving the quality of life of osteoporotic patients. Significant cost savings will be realized in the reduction of osteoporosis-related fractures and associated treatment.