Hydrophobic spray emitters for ultrahigh sensitivity microLC-MS for clinical biomarker analysis

Abstract The intense efforts for proteomics and biomarker discovery carried out by major research consortia such as EDRNEarly Detection Research Networkhave generated many biomarkersincluding those that are FDA approvedHowever the transfer of biomarker detection and screening from research to clinical has been unsuccessfulThe nanoLC MS technique used in proteomic biomarker discovery is wrought with the inherent fragility and variability of the components of the experimental set upThe weakest link in this transfer process is the fused silica spray emitter and columns which are easily clogged and damagedand dead volume must be painstaking eliminated because of the low flow rate of submicroliter min to minimize peak broadeningPhoenix Sandamp T has discovered patent pending and patented metallic and plastic spray emitters with reduced surface interactions with the aqueous component of the buffer such that the cone jet mode spray with high ion production efficiency are consistently and robustly produced at flow rates from sub microliter min up to andgtuL minNo fragile equipment is needed for use with these emittersAt flow rates of a few microliters minthe dead volume elimination requirement is relaxedThe sensitivity obtained with these emitters at flow rates less thanuL min has been shown to be comparable to or exceeding that obtained with nanoLC MSThese attributes offered by the new spray emitters make the transfer of the methods for biomarker screening into the clinics for medical decision making much more feasibleThe proposed research aims to characterize these emitters to optimize the performance and durability of the emitters and enable reproducible manufacturingand also to create plastic spray emitters with the potential of having the additional benefits of asofterionization that reduces in source fragmentation and being disposable when used with dirty clinical samplesThe learningfrom the proposed research on these emitters may also open up possibility ofD electrospray MS devices for high throughput analyses of cellular functions in the future Narrative The use of FDA approved protein and peptide biomarkers discovered in proteomics research has the potential to contribute significantly to aid clinical decision making on serious diseases such as cancersIt is not possible at present because the nanoLC MSnano liquid chromatography mass spectrometrymethod and equipment used in the biomarker discovery process are fragile and error prone so that they are not amenable for the transfer into the clinical laboratory where robustness of the method and the reliability of the equipment are paramount to make sure that patientssamples are not lost due to equipment failurePhoenix Sandamp T has discovered and wishes to further develop new spray emitters that are much more robust and yet delivery the same high sensitivity as the existing unreliable spray emitters and also at a more clinical environment friendly flow rates so that the major hurdles for the method transfer to the clinical setting will be largely overcome