The intense efforts for proteomics and biomarker discovery carried out by major research consortia such as EDRN (Early Detection Research Network) have generated many biomarkers, including those that are FDA-approved. However the transfer of biomarker detection and screening from research to clinical has been unsuccessful. The nanoLC-MS technique used in proteomic biomarker discovery is wrought with the inherent fragility and variability of the components of the experimental set-up. The weakest link in this transfer process is the fused silica spray emitter and columns which are easily clogged and damaged, and dead-volume must be painstaking eliminated because of the low flow-rate of sub- microliter/min to minimize peak broadening. Phoenix S&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 >100 uL/min. No fragile equipment is needed for use with these emitters. At flow-rates of a few microliters/min, the dead-volume elimination requirement is relaxed. The sensitivity obtained with these emitters at flow-rates less than 10 uL/min has been shown to be comparable to or exceeding that obtained with nanoLC-MS. These 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 feasible. The proposed research aims to characterize these emitters to optimize the performance and durability of the emitters and enable reproducible manufacturing, and also to create plastic spray emitters with the potential of having the additional benefits of a âsofterâ ionization that reduces in-source fragmentation and being disposable when used with dirty clinical samples. The learningâ from the proposed research on these emitters may also open up possibility of 2D electrospray-MS devices for high throughput analyses of cellular functions in the future.
Public Health Relevance Statement: 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 cancers. It is not possible at present because the nanoLC-MS (nano-liquid chromatography-mass spectrometry) method 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 patientsâ samples are not lost due to equipment failure. Phoenix S&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.
Project Terms: adduct; aqueous; Biological Markers; biomarker discovery; Blood capillaries; Buffers; Cell physiology; Clinic; Clinical; clinical application; clinical biomarkers; clinical decision-making; Collaborations; Complex; Cone; cost; Data; Decision Making; Delaware; Detection; Development; Devices; Disease; Doctor of Philosophy; Drops; Early Detection Research Network; Ensure; Environment; Equipment; Equipment Failure; Exhibits; Failure; FDA approved; Future; Gold; high throughput analysis; hydrophilicity; Hydrophobic Surfaces; Hydrophobicity; Injections; ionization; Ions; Laboratories; Lasers; Learning; Legal patent; Life; Link; Lipids; liquid chromatography mass spectrometry; Malignant Neoplasms; mass spectrometer; Mass Spectrum Analysis; Mechanics; Medical; metallicity; Metals; Methods; Microinjections; Molds; Molecular Analysis; nano-liquid chromatography; off-patent; Oligonucleotides; Patients; Pediatric Hospitals; Peptides; Performance; Phase; Philadelphia; Plasma; Polishes; Probability; Process; Production; Property; Proteins; Proteomics; Reproducibility; Research; research clinical testing; Resistance; Running; Sampling; screening; Serum; Services; Silicon Dioxide; Small Business Innovation Research Grant; small molecule; Source; success; Surface; Techniques; Universities; wasting; Wate
