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

描述（由申请人提供）：骨是一种动态组织，它自然地、持续地经历着新生骨的形成和破骨细胞以平衡的速率吸收旧骨的过程；这两种比率之间的任何不平衡都会导致不同的异常骨转换状态，如骨质疏松症，并伴有骨脆性和骨折风险增加。虽然骨质疏松症是一种常见疾病，特别是在老年妇女中，但通常只有在出现脊柱或髋部骨折等病态症状时才会被诊断出来。目前，最可靠的骨矿物质密度（BMD）测量方法是成像技术，如双光子吸收仪（DPA）、定量计算机断层扫描（QCT）和双能x射线吸收仪（DEXA）。虽然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，因为它们昂贵，与护理点测试相比，相对时间和劳动力密集，并且通常无法用于骨质疏松症高危人群的常规筛查。目前基于实验室的检测，如酶联免疫测定（ELISA）试剂盒，用于检测血液或尿液中的个体生物标志物，通常不提供筛查和治疗随访应用，因为它们是侵入性的和昂贵的。已经研究了可靠的骨转换标记物的测量，以评估其在骨恶化的诊断和预测中的作用；这些研究评估了它们与骨密度测量的相关性，以t评分值表示，结果非常一致。骨转换标志物可以从血液或尿液中检测，然而，由于其方便和非侵入性采样，最近的注意力集中在唾液诊断上。Intelligent Optical Systems （IOS）提出基于IOS先前开发的横向流动测试条（LFTS）技术，开发一种具有成本效益，易于使用，无创的骨转换唾液标志物筛查平台。该平台将评估两个关键的骨活动：骨形成，表现为骨钙素（OC），骨吸收，表现为胶原交联脱氧吡啶啉（D-PYR）。高度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水平可重复、敏感测量的可行性。与密西西比大学医学中心牙周病和预防科学系的Roger B. Johnson教授合作，一项简单的前瞻性研究将包括人类唾液样本测试，与尿液/血液水平和骨密度测量进行比较。II期将在使用唾液样本的大规模人群研究中证明LFTS的敏感性和可靠性，以验证检测的准确性并满足临床要求。

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.