Picoelectrospray Ionization Mass Spectrometry for Top-down Proteomics

DESCRIPTION provided by applicant The proteome reflects the physiology and pathology states of a patient therefore proteomics is a powerful tool for early diagnostics of diseases and monitoring of therapeutic responses Mass spectrometry MS measures the mass to charge ratio of charged species and has become the enabling technology for proteomics However the majority of the current proteomics studies rely on bottom up shotgun approaches In this case mixtures of proteins are digested by one of the proteases e g trypsin separated by liquid chromatography LC and analyzed by electrospray mass spectrometry ESI MS Despite tremendous successes there remain two major limitations in bottom up proteomics first it is difficult to identify all protein isoforms or proteoforms including splicing modifications cleavages etc second the native state of proteins is always lost after digestion There is currently a great push to implement top down proteomics i e identification and characterization of full length proteins by LC MS Unfortunately top down proteomics proves to be much more challenging There are several bottlenecks first lower MS sensitivity of protein relative to peptides second limitation on detection of high molecular weight proteins third inefficient identification of proteins by MS MS fragmentation and fourth laborious multidimensional protein separation not suitable for small volumes of biological samples The field is calling for transformative technologies In response to PA Newomics Inc proposes to develop a new technology picoelectrospray ionization mass spectrometry picoESI MS based on our breakthrough multinozzle emitter array for top down proteomics of small volume samples The technology will be built on our microfabricated monolithic multinozzle emitters M emitters and multinozzle emitter array MEA chips for LC nanoESI MS which collectively offer a straightforward yet novel solution to the longstanding problem of the efficient coupling between silicon microfluidic chips and ESI MS and pave the way for the large scale integration on the proposed microfluidic chips for LC picoESI MS Our picoESI MS platform will directly address the aforementioned bottlenecks and thus enable high sensitivity high throughput and multiplex top down proteomics of small volumes of biological samples PUBLIC HEALTH RELEVANCE Cutting edge technologies enable breakthroughs in biomedical research Developments of innovative and integrated mass spectrometry based microfluidic chips will accelerate the discovery and validation of protein biomarkers thereby providing new strategies for early diagnosis and targeted therapy of diseases