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Man-Portable and Fieldable Mass Spectrometer for Sequencing Peptides

Description:

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Develop a new miniaturized multi-order (MSn) mass spectrometer that is man-portable and capable of detecting and sequencing peptides derived from biological agents including bacteria, viruses, and toxins.

DESCRIPTION: Currently our ability to detect biological threats in the field relies heavily upon immunological based assays which have limited robustness, specificity, and often generate false positive results. Although mass spectral techniques exist which have high sensitivity, high selectivity and are broadly applicable for detection and identification, the research grade instrumentation used has a large physical and logistical footprint making it impractical to bring into the field. Several efforts have been made over the last decade to miniaturize mass spectrometers for the detection of chemical warfare agents (CWA)3, toxic industrial chemicals (TICs), and illicit drugs4. From these investments, several portable mass spectrometry (MS) systems have been successfully commercialized demonstrating both the feasibility and utility of a miniaturized mass spectrometer. At present there is a need to develop a new portable multi-order mass spectrometry system that can sequence peptides derived from biological agents including bacteria, viruses, and toxins. Prototypes/designs of portable backpack systems have been published and tested, but a fully functional system with the specifications needed for peptide sequencing have not been realized1,2. This system should have a broad mass range (such as 300-1600 m/z), adequate mass resolution (~3000 >1.0 Da, FWHM; Full Width at Half Maximum), reasonable dynamic range with moderate sensitivity (detecting sub-ug amounts in complex matrixes) and it should be capable of performing multiple data dependent MS/MS scans. This type of new instrumentation should be flexible in design so that it can be coupled with the current state-of-the-art in sample preparation and/or liquid chromatography, ESI/ambient ionization, and data processing algorithms. Furthermore, the analysis and data handling systems should be designed in a way that, once completely mature, could be operated by a non-expert with minimal training. Should a system be successfully designed it could easily replace the current state-of-the-art MS-based chemical detection primarily due to its superior capabilities. Potential customers for a commercialized system span a wide range of government agencies and commercial entities including the military, the department of homeland security, first responders, and hospitals.

PHASE I: During Phase I performers will provide evidence that each of the principle components are physically validated or have been shown to work as proposed in a different instrument systems. This includes each critical component potentially including but not limited to the sampling, sample preparation, chromatographic, atmospheric MS inlet, ion optics design, mass analyzers, pumping system, and electrical/computer system (i.e. sampling through data interpretation). In addition, preliminary evidence using a simulation program such as SIMION should be provided supporting the feasibility of the overall marriage of all components. Initial efforts during the Phase I of this program should be focused on generating evidence that all components of the proposed system work together in unison. Less attention needs to be given to the strict logistical requirements of this breadboard instrument including weight and power requirements. However, performers that demonstrate the potential to acquire data that results in sequenced peptides from a complex mixture such as a tryptically digested cellular lysate will be preferred for transition from Phase I to Phase II.

PHASE II: Candidates that are awarded a Phase II proposal shall further develop the instrument into a pre-production prototype that can be tested in a relative environment outside of a laboratory setting. The pre-production prototype shall strive to meet the following criteria:

  • A complete system weighing approximately 40 lbs
  • Total volume/size is amenable to being carried on a backpack or a suitcase no larger than a “carry-on” bag. Battery pack could be designed so that it is in a separate case. Capable of operating or charging with solar power is a plus! Having the power supply designed as a separate module could allow for easy “upgrades” as the design (instrument and power supply) evolves and matures.
  • Minimal power requirements so that it is capable of running on battery power at least for a brief period of time. This is preferred, but not required.
  • MS resolution of ~3000 FWHM
  • Capable of multiple data dependent MS/MS scans
  • Sensitive enough to detect infectious dose quantities

PHASE III DUAL USE APPLICATIONS: Should the breadboard pre-production prototype successfully meet all criteria set forth during the Phase II effort, multiple prototypes shall be constructed and distributed to at least three different laboratories for independent validation. These independent groups could span both academia, government, and another potential commercial transition partners with significant resources and customer base amendable to launching a successful a production and marketing campaign. It is expected the bulk of the software development will be performed in this phase. Up to this point it is acceptable that the instrument control and data analysis be performed by highly trained personnel. However, in the final product sample gathering, preparation and analysis as well as spectral interpretation will need to be simplified for use after moderate training (2 weeks). Additionally, this phase can be used to improve logistical characteristics such as weight and power consumption. For example, weight could be reduced by replacing heavier but more inexpensive materials with lighter but expensive ones (stainless steel parts with titanium). This product would fulfill needs across a wide customer base including medical facilities, first responders, and private practices to aid in diagnosis. It would be extremely beneficial across all branches of the military for both threat detection and diagnosis. The FDA and EPA would find a high resolution mass spectrometer very useful for compliance regulations.

REFERENCES:

    • Chen, Chien-Hsun, et al. "Design of Portable Mass Spectrometers with Handheld Probes: Aspects of the Sampling and Miniature Pumping Systems." Journal of The American Society for Mass Spectrometry 26.2 (2015): 240-247.

 

    • Hendricks, Paul I., et al. "Autonomous in situ analysis and real-time chemical detection using a backpack miniature mass spectrometer: concept, instrumentation development, and performance." Analytical chemistry 86.6 (2014): 2900-2908.

 

    • Dumlao, Morphy, et al. "Real-time detection of chemical warfare agent simulants in forensic samples using active capillary plasma ionization with benchtop and field-deployable mass spectrometers." Analytical Methods 6.11 (2014): 3604-3609

 

  • Hall, Seth E., and Christopher C. Mulligan. "Application of Ambient Sampling Portable Mass Spectrometry Toward On-Site Screening of Clandestine Drug Operations." (2014).

KEYWORDS: Miniaturized, mass spectrometer, bio-detection, portable, chemical detection, MSMS, BW

  • TPOC-1: Dr. Trevor Glaros
  • Phone: 410-436-3616
  • Email: trevor.g.glaros.civ@mail.mil
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