The long-term goal of our efforts is to enable identification and mapping of every molecule in a cell. Such information is sought in many life-science disciplines including molecular biology, pathology, proteomics and for the pharmaceutical industry. It is critical information needed to underpin fundamental advances in our understanding of life processes. However, this vision will require development of a technology for efficient detection of molecules, that does not yet exist. Detectors for biomolecules are the foundation of analytical instruments such as mass spectrometers. We have developed and experimentally proven new concepts that will allow us to build and commercialize a detector technology enabling this grand vision. The technology is based on a new patented approach to using superconducting materials which can record 100% of the impinging molecules, even the heaviest proteins and protein complexes. Methods are now available to launch biomolecules of any mass from tissue and water solutions as ions into mass spectrometers with high efficiency and no fragmentation or denaturing. Such soft laser-ionization methods as MALDI (matrix-assisted laser desorption/ionization) and DIVE (desorption by impulsive vibrational excitation) open new opportunities for molecular analysis and mapping. We have designs for mass spectrometers that can deliver these ions onto a detector with very high mass resolving power (>200,000). However, the detector is currently the missing link in this exciting development. With the new detector technology, a whole new class of imaging mass spectrometers can be developed and brought to market. Our superconducting detector technology (a superconducting delay line or SCDL, pronounced skiddle) delivers 100% detection while capturing the high mass resolving power on unfragmented large-mass molecules like proteins. It is fast (>108 molecules/second) and expandable to large areas (>4 cm2). A proof-of-concept project was completed in the past year. We are commercializing this technology for biomolecule time-of-flight detection as part of our grand vision to spectroscopically map all molecules in a cell. We have built a team of academic and commercial experts in biological mass spectrometry (MS) and superconducting detectors and electronics. We will develop a highly parallel tessellated detector with integrated superconducting electronics on the detector wafer. The first step in commercialization, this Phase I program, is thorough simulation of the detector and its electronics in collaboration with SeeQC, Inc. (formerly Hypres, Inc.). When complete, we will have a high level of confidence in its expected performance. In our Phase II, we will fabricate a working detector with SeeQC and evaluate its performance in a test MS system on real biomolecular specimens. Commercializing the SCDL detector for high performance time-of-flight mass spectrometry is the first stage of our plans for this detector technology. In our second stage of development, we will design and build the technology for recording time-of-flight encoded images. In other words, the detector will be used to record megapixel stigmatic images that will allow us to push the spatial resolution of the imaging mass spectrometer to better than 100 nm. The proposed new detector technology will enable major advancements in life sciences and related industries.
Public Health Relevance Statement: Project Narrative This research will develop a detector for biomolecules needed to map the proteins, enzymes, etc. in the cells in our bodies. This information is used to develop more effective drug treatments, diagnose disease at the earliest stages, and generally develop a better understanding of how life functions. All branches of health and life science research and knowledge may be beneficially affected by the new information this detection capability brings.
Project Terms: Acceleration; Address; Affect; Area; Automobile Driving; base; Biological; Biological Sciences; Cells; Charge; Collaborations; commercialization; Complex; data acquisition; design; Detection; detector; Development; Disadvantaged; Discipline; disease diagnosis; Drug Industry; Electronics; Electrons; Engineering; Enzymes; Evaluation; Foundations; Fourier Transform; Goals; Government; Health Sciences; Heavy Ions; Image; Impulsivity; Industry; instrument; ion source; ionization; ionization technique; Ions; Isotopes; Kinetics; Knowledge; Lasers; Lead; Legal patent; Life; Link; Maps; mass analyzer; mass spectrometer; mass spectrometric imaging; Mass Spectrum Analysis; Methods; models and simulation; Molecular; Molecular Analysis; Molecular Biology; Pathology; Pattern; Performance; Persons; Pharmacotherapy; Phase; Process; Program Development; programs; protein complex; Proteins; Proteomics; Research; Resolution; simulation; single molecule; Specimen; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Speed; Statistical Distributions; Steam; System; tandem mass spectrometry; Technology; Testing; Time; time of flight mass spectrometry; Tissue Sample; Tissues; Variant; vibration; Vision; voltage; water solution; Work
