Nanowire Sensor Array-based Assay for Early Diagnosis of Alzheimer's Disease

基于纳米线传感器阵列的阿尔茨海默病早期诊断检测

• 批准号: 9353280
• 负责人: Maksudul Alam
• 金额: $ 76.96万
• 依托单位: INNOSENSE, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9353280
• 关键词: Affect; Age; Algorithmic Software; Alzheimer' s Disease; American; Amyloid beta-Protein; Anguish; Antibodies; Antigens; Autopsy; Back; Benchmarking; Biochemical; Biochemistry; Biological Assay; Biological Markers; Biometry; Biosensor; Blood; Brain; California; Capital; Caregivers; Caring; Cerebrospinal Fluid; Characteristics; Chemistry; Clinical; Clinical Data; Clinical Research; Clinical Trials; Collaborations; Complex; Computer software; Data; Dementia; Deposition; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; Disease Progression; Dot Immunoblotting; Early Diagnosis; Elderly; Electronics; Engineering; Enzyme-Linked Immunosorbent Assay; Evaluation; Family; Future; Genotype; Health Care Costs; Healthcare; Healthcare Systems; Human Resources; Image; In Vitro; Incidence; Intervention; Laboratories; Lead; Letters; Methods; Microbiology; Modeling; Molecular Biology; Molecular Conformation; Monitor; Neurodegenerative Disorders; Neurofibrillary Tangles; Neurology; Pathologic; Patients; Performance; Pharmaceutical Preparations; Phase; Phosphate Buffer; Polymers; Principal Investigator; Process; Production; Protein Analysis; Proteins; Reproducibility; Research; Resistance; Saline; Saliva; Sampling; Secure; Senile Plaques; Sensitivity and Specificity; Specificity; Staging; Surface; Symptoms; Synapses; System; Technology; Testing; Time; Universities; Urine; Work; accurate diagnosis; assay development; base; biomarker panel; cognitive function; cognitive testing; cost; cost effective; cross reactivity; design; disease diagnosis; effective therapy; experience; experimental study; improved; interest; monitoring device; nanomolar; nanowire; neuron loss; phase 2 study; point of care; point-of-care diagnostics; prognostic; prototype; rapid diagnosis; research and development; response; sensor; specific biomarkers; targeted biomarker; tau Proteins; tau conformation; tau-1; theranostics; tool; waiver

PROJECT SUMMARY Alzheimer’s disease (AD) is a complex and severe neurodegenerative disorder. AD is characterized by synapse and neuron loss in the brain with the accumulation of senile plaques (protein containing deposits) and neurofibrillary tangles. Approximately 5.4 million Americans and globally 30 million people are affected and this number is growing rapidly. In 2015, the cumulative cost of care for AD and other dementia was estimated at $226 billion. Yet, there is no definitive point-of-care (POC) diagnostic for AD. Current standard methods of AD diagnosis involve a combination of imaging and cognitive tests which are expensive and require complicated, time-consuming laboratory-based analysis while definitive diagnosis is made postmortem. Because early diagnosis could enable better planned and coordinated care, there is an urgent need to develop a cost-effective, highly sensitive and selective diagnostic tool for pre-symptomatic AD diagnosis which could also be used as a convenient monitoring device for bedside or primary POC use. In Phase I, InnoSense LLC (ISL) developed a conducting polymer nanowire-based biosensor, Adnos, for detecting AD biomarkers. ISL constructed a working model and demonstrated its capability for detecting AD-associated biomarkers in spiked solutions with phosphate buffered saline and artificial cerebrospinal fluid (aCSF) as well as CSF samples from patients. ISL demonstrated that Adnos devices had an average limit of detection of 100 fM for AD-specific biomarkers. The results indicate that Adnos has better sensitivity than standard laboratory tests such as Enzyme-Linked Immunosorbent Assay (ELISA) (nanomolar) for AD protein analysis. In Phase II, ISL will further develop, fine tune, and rigorously evaluate Adnos performance for detecting AD-specific biomarkers. ISL will: (1) optimize the Adnos nanowire sensor fabrication process, (2) toward assay development construct a prototype with necessary electronics and software, (3) fine-tune the prototype performance for accurate detection and monitoring of AD-specific biomarkers with a limit of detection of 100 fM in less than 30 min, (4) demonstrate ability of a prototype Adnos to detect AD biomarkers in clinical CSF samples and compare the performance with standard ELISA and dot blot tests, and (5) prepare to secure CLIA waiver while we explore commercial options. The ability to detect the earliest stages of AD, prior to onset of symptoms, could potentially have a powerful impact on families to: (1) plan for future healthcare needs, (2) development of early stage intervention strategies, and (3) gain the ability to understand and manage the entire lifecycle of the disease. Use of the Adnos system will be highly valuable as a tool providing monitoring data for clinical studies in search of effective treatments for AD.

项目摘要 阿尔茨海默氏病（AD）是一种复杂而严重的神经退行性疾病。广告的特征是 随着老年斑块的积累（含有蛋白质的沉积物）和 神经纤维缠结。大约有540万美国人和全球3000万人受到影响，这 数字正在迅速增长。 2015年，估计AD和其他痴呆症的护理成本 2260亿美元。但是，AD没有确定的护理点（POC）诊断。当前的AD标准方法 诊断涉及成像和认知测试的组合，这些测试昂贵且需要复杂， 耗时的基于实验室的分析，而确定性诊断则是验尸。因为很早 诊断可以实现更好的计划和协调护理，迫切需要开发 具有成本效益，高度敏感和选择性的诊断工具，用于止痛药诊断，这也可以 用作床旁或主要POC的方便监控设备。 在第一阶段，Innosense LLC（ISL）开发了一个基于聚合物纳米线的导电生物传感器ADNOS，用于 检测广告生物标志物。 ISL构建了一个工作模型，并证明了其检测能力 与磷酸盐缓冲盐和人造脑脊液的尖刺溶液中的广告相关生物标志物 （ACSF）以及患者的CSF样品。 ISL证明ADNOS设备的平均限制为 用于AD特异性生物标志物的100 FM检测。结果表明，ADNO具有比 用于AD蛋白的标准实验室测试，例如酶联免疫吸附测定（ELISA）（纳摩尔） 分析。 在第二阶段，ISL将进一步发展，微调和严格评估ADNOS性能以检测 广告特异性生物标志物。 ISL Will：（1）优化ADNOS纳米线传感器制造过程，（2）to Assay 开发构建具有必要电子和软件的原型，（3）微调原型 用于准确检测和监测AD特异性生物标志物的性能，并限制为100 FM 在不到30分钟的时间内，（4）证明了原型ADNO在临床CSF中检测AD生物标志物的能力 样品并将性能与标准ELISA和DOT印迹测试进行比较，（5）准备确保Clia 放弃时，我们探索商业选择。 在症状发作之前检测最早的AD的能力可能具有强大的功能 对家庭的影响：（1）未来医疗保健需求计划，（2）开发早期干预 策略以及（3）获得理解和管理疾病整个生命周期的能力。使用 ADNOS系统将是一种工具，作为为临床研究提供监视数据的工具，以寻找 广告的有效治疗方法。