Ultra-sensitive magnetic assays for rapid detection of stroke biomarkers

描述（由申请人提供）：MagneSensors, Inc。快速确定谁可以安全地从治疗干预中获益的需求阻碍了目前中风的治疗。FDA批准的溶栓治疗对于最常见的中风——急性缺血性中风是有效的，只要在最初的3-4.5小时内给药。许多医生不愿意使用溶栓治疗，因为如果对脑出血患者进行溶栓治疗可能是致命的。对血液中的中风生物标志物进行快速而简单的诊断测试，可能会提供有价值的诊断信息，帮助区分哪些人应该接受治疗，哪些人不应该接受治疗。许多研究表明，胶质原纤维酸性蛋白（GFAP）是一种很有前景的生物标志物。不幸的是，现有的GFAP测试缺乏足够的灵敏度，变化很大（不是直接定量的），而且耗时太长。因此，它们甚至不足以用于旨在评估生物标志物的临床研究，也不适合随后的临床应用。我们假设一种快速、灵敏、定量的GFAP血液检测可以为包括排除在内的特定临床应用提供重要的诊断信息

DESCRIPTION (provided by applicant): MagneSensors, Inc. Phase I SBIR Ultra-sensitive magnetic assays for rapid detection of stroke biomarkers Project Summary Current treatment of stroke is hampered by the need to rapidly determine who can safely benefit from therapeutic intervention. FDA approved thrombolytic therapy can be effective for acute ischemic stroke, the most common stroke, as long as it is administered within the first 3-4.5 hours. Many doctors are reluctant to use thrombolytic therapy since it can be lethal if administered to patients with intracerebral hemorrhage (ICH). A rapid and simple diagnostic test for stroke biomarkers in blood might provide valuable diagnostic information, helping to sort out who should and should not receive therapy. A number of studies have shown glial fibrillary acidic protein (GFAP) to be a promising biomarker. Unfortunately, existing GFAP tests lack adequate sensitivity, are highly variable (not directly quantitative), and take too long. As such, they are inadequate even for clinical studies designed to evaluate the biomarker as well as unsuitable for subsequent clinical application. We hypothesize that a rapid, sensitive, and quantitative blood test for GFAP could provide important diagnostic information for specific clinical applications that include ruling out ICH. Our Phase I goal is to develop such a test to overcome the shortcomings of existing tests. We propose a new approach that is centered on the use of new magnetic nanoparticle labels and ultra-sensitive magnetic sensors, which together offer a unique combination of benefits. To our knowledge, magnetic detection assays have never been applied to the detection of stroke biomarkers. The Phase I specific aim is to demonstrate a magnetic immunoassay for the GFAP stroke biomarker that has: 1) high analytical sensitivity, 2 pg/ml in blood, and 2) rapid turnaround time, 50 minutes total that includes both preparation and measurement. We will also measure GFAP levels in thirty clinical blood specimens collected from ischemic stroke and ICH patients by our UCSD Stroke Center collaborator. The development of the GFAP magnetic test in Phase I will employ a model system where GFAP is spiked into whole blood and captured on microspheres coated with anti-GFAP. Magnetic nanoparticles coated with detect anti-GFAP antibodies then bind to the captured GFAP. The magnetic signal from bound magnetic nanoparticle labels is measured with our latest generation magnetic detection instrument, which is designed for use in a clinical setting. The novel "mix and measure" format eliminates the need for wash steps to remove unbound magnetic nanoparticle labels or red blood cells, thereby enabling rapid and sensitive tests of blood biomarkers. In Phase II we plan to conduct a much larger prospective clinical study on specimens provided by our UCSD collaborator. We expect to reduce the total test time to 15 minutes or less, which is very important for this time critical application. We also plan to evaluate additional biomarkers to improve clinical sensitivity and specificity. The Phase II goal is to collect convincing data to recruit additional luminary sites t enable multi-center clinical studies in Phase III. Ultimately, we plan to team with a larger company to bring these tests to market. PUBLIC HEALTH RELEVANCE: Nearly 800,000 people have strokes annually in the U.S. leading to 140,000 deaths, making stroke the third leading cause of mortality and the number one cause of long term disability. Proven therapy can significantly reduce damage to brain cells if given in time, but it is currently underutilized as it is difficult to quickly determine when itcan most safely be used. The rapid, sensitive detection of stroke biomarkers in blood could assist early diagnosis to improve patient treatment.