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

描述（由申请人提供）：阿尔茨海默病（AD）是一种毁灭性的神经退行性疾病，影响全球超过3500万人（包括500万美国人），预计到2050年这一数字将超过1.15亿。最近巴哌珠单抗和索拉单抗在阿尔茨海默病治疗中的临床试验令人失望，进一步加剧了这个问题。目前还没有明确的生物标志物用于阿尔茨海默病的早期诊断或治疗。该领域正在呼唤变革性的技术和方法。针对PA-11-335， Newomics公司提出开发集成硅微流控芯片，称为AD- ms芯片，作为快速、敏感和特异性基于生物流体的AD早期诊断的革命性平台。核心技术将基于Newomics突破性的硅微流体芯片，即多喷嘴发射器阵列芯片（MEA芯片-2012 R&D100奖），该芯片可实现基于液相色谱-纳米电喷雾电离质谱（LC-nanoESI/MS）的、高灵敏度、高特异性、高通量和多重测量的多类分析物（多肽、蛋白质和代谢物），从小批量样品中提取。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可能作为AD生物标志物的蛋白质形态。在这个SBIR项目中，我们将开发AD-MS芯片作为高通量和多路多组学平台。AD- ms芯片将能够从少量人血浆和脑脊液（CSF）样本中对“多类”分析物（肽、蛋白质和代谢物）进行高通量和多重测量，从而大大加快AD诊断“多类生物标志物面板（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芯片将实现快速、敏感和经济实惠的基于生物流体的AD早期诊断。

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.