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.

Public Health Relevance

Cutting-edge technologies enable breakthroughs in biomedical research. Developments of innovative silicon microfluidic chips for mass spectrometry analysis of proteins, peptides, and small molecules will accelerate the discovery and validation of biomarkers for Alzheimer's disease, thereby providing new strategies for its early diagnosis and targeted therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43AG046025-01A1
Application #
8779649
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hsiao, John
Project Start
2014-08-01
Project End
2016-04-30
Budget Start
2014-08-01
Budget End
2015-04-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Newomics, Inc
Department
Type
DUNS #
City
Emeryville
State
CA
Country
United States
Zip Code
94608
Chen, Yuchao; Mao, Pan; Wang, Daojing (2018) Quantitation of Intact Proteins in Human Plasma Using Top-Down Parallel Reaction Monitoring-MS. Anal Chem 90:10650-10653
Han, Yan; Zhao, Jinghua; Huang, Ruili et al. (2018) Omics-Based Platform for Studying Chemical Toxicity Using Stem Cells. J Proteome Res 17:579-589
Gil, Geuncheol; Mao, Pan; Avula, Bharathi et al. (2017) Proteoform-Specific Protein Binding of Small Molecules in Complex Matrices. ACS Chem Biol 12:389-397
Mao, Pan; Wang, Daojing (2015) Biomonitoring of perfluorinated compounds in a drop of blood. Environ Sci Technol 49:6808-14