AD-MS Chips for Biofluids-Based Diagnosis of Alzheimer's Disease

描述(申请人提供)：阿尔茨海默病(AD)是一种破坏性的神经退行性疾病，全球有超过3500万人(包括500万美国人)受到影响，预计到2050年，这一数字将超过1.15亿。最近治疗AD的bapineuzumab和solanezumab令人失望的临床试验进一步加剧了这一问题。目前尚无明确的生物标志物可用于AD的早期诊断或治疗。该领域正在呼唤变革性的技术和方法。作为对PA-11-335的响应，Neomeics Inc.建议开发集成的硅微流控芯片，称为AD-MS芯片，作为基于特定生物流体的快速、敏感和特定的AD早期诊断的革命性平台。核心技术将基于Neomeics的突破性硅微流控芯片-多喷嘴发射器阵列芯片(MEA芯片-2012 R&D100奖)，该芯片实现了基于液相色谱-纳米电喷雾电离质谱仪(LC-NanESI/MS)的、高灵敏度、高特异性、高通量和多路测量的多类别分析物(肽、蛋白质和代谢物)在OMICS水平上的小批量样品测量。该项目还基于我们最近通过使用我们的MEA芯片进行自上而下的蛋白质组学研究，在人类血浆中发现了几种蛋白质形式作为潜在的AD生物标记物。在这个SBIR项目中，我们将开发AD-MS芯片作为高通量和多元化的多组学平台。AD-MS芯片将实现从少量人类血浆和脑脊液(CSF)样本中高通量和多路测量“多类别”分析物(肽、蛋白质和代谢物)，从而极大地加快AD诊断“多类别生物标志物小组(MBP)”的发现、验证和临床应用。如果在未来的前瞻性临床研究中得到验证，AD-MS芯片将使基于生物流体的AD快速、敏感和负担得起的早期诊断成为可能。

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 35 million people (including 5 million Americans) worldwide, and this number is expected to reach more than 115 million by the year 2050. Recent disappointing clinical trials of bapineuzumab and solanezumab in AD treatment further aggravate the problem. There is currently no definitive biomarker for early diagnosis or therapy of AD. The field is calling for transformative technologies and approaches. In response to PA-11-335, Newomics Inc. proposes to develop integrated silicon microfluidic chips, termed AD-MS chips, as a revolutionary platform for rapid, sensitive, and specific biofluids-based early diagnosis of AD. The core technology will be based on Newomics' breakthrough silicon-microfluidic-chip, the multinozzle emitter array chip (MEA chip-2012 R&D100 award), which enables liquid chromatography-nanoelectrospray ionization mass spectrometry (LC-nanoESI/MS)-based, highly sensitive, highly specific, high-throughput, and multiplex measurements of multiclass analytes (peptides, proteins, and metabolites) at the Omics level, from small volumes of samples. The project is also based on our recent discovery of several proteoforms in human plasma as potential AD biomarkers through top-down proteomics studies using our MEA chips. In this SBIR project, we will develop AD-MS chips as a high-throughput and multiplex multi-omics platform. AD-MS chips will enable high-throughput and multiplex measurements of "multiclass" analytes (peptides, proteins, and metabolites), from small volumes of human plasma and cerebrospinal fluid (CSF) samples, thereby dramatically accelerating the discovery, validation, and clinical application of "Multiclass Biomarker Panel (MBP)" for AD diagnosis. If validated in future prospective clinical studies, AD-MS chips will enable rapid, sensitive, and affordable biofluids-based early diagnosis of AD.