High-Throughput and Ultra-sensitive Multidimensional Analytical Platform Based on Multiplexed Ion Mobility Spectrometry/Mass Spectrometry

Battelle Number: 14158-E | N/A

Technology Overview

The integration of ion mobility spectrometry (IMS) with mass spectrometry (MS) has recently become a point-of-emphasis for instrument developers because of the potential it offers for improved identification of peptides and other compounds having similar atomic masses. Such an integrated system holds promise for biomolecule analysis and characterization, national security, advances in petroleum, and environmental monitoring. However, this potential has been hampered by the losses in sensitivity and mismatched duty cycles that are traditionally associated with combined IMS/MS systems.

PNNL has developed an integrated instrument platform that overcomes these problems. The system incorporates three innovations: 1) an ion funnel technology for increased sensitivity, 2) ion funnel trap advancements that provide more ion accumulation and precise release, and 3) a multiplexing feature for even greater sensitivity with better-aligned duty cycles. Together, these innovations can be easily coupled with liquid chromatography MS systems to enable efficient analysis, without losing ions or degrading IMS resolution.

PNNL’s multiplexing technique uses an extended pseudo-random gating procedure that separates ions into packets based on the timing of the gate openings and closings. After the ions travel through the drift cell of the IMS-time-of-flight (TOF) MS, the system intermingles ions from different packets at the detector based on differences in relative ion mobility. The system then uses algorithms to de-convolute the intermingled ions. This process yields a higher signal-to-noise ratio than can be produced by conventional techniques, resulting in greater sensitivity. Because ion packets can travel through the drift region simultaneously, rather than one at a time, the technique also increases analysis throughput.

Multiplexing is a technique related to and often confused with Hadamard transform. However, the multiplexing technique developed at PNNL is fundamentally different and provides several advantages over Hadamard transform. For a given sample, PNNL’s multiplexing decreases analysis time by 10-fold at the same signal-to-noise ratio as a conventional approach. At lower signal-to-nose ratio and increased sensitivity, the technique still maintains faster throughput than conventional methods. Although the algorithms behind multiplexing are relatively complex, implementation of the technique is relatively straightforward, involving the addition of electronic gating equipment and software to IMS systems or combinations of IMS and MS. A new method for reducing artifacts and substantially increasing the signal-to-noise ratio in multiplexed analyses is also part of the technology portfolio. The approach incorporates sophisticated software for integrating and controlling the new multidimensional system.

PNNL has also developed patented methods for interfacing IMS with ion trap MS systems such as Orbitrap (patent 9,939,409). The method provides similar benefits to multiplexed analysis using TOF MS in which the MS scan times are shorter than IMS times. Using a dual gating system, the method allows for analysis of complete samples using ion mobility in conjunction with the slower scan speeds of ion trap MS. The duty cycle and the sensitivity of the instrument benefit from a double multiplexing approach that delivers an order-of-magnitude better signal than traditional approaches. The algorithm developed to handle the convoluted data also efficiently removes the artifacts usually observed in conventional de-multipelxing schemes.The integration of ion mobility spectrometry (IMS) with mass spectrometry (MS) has recently become a point-of-emphasis for instrument developers because of the potential it offers for improved identification of peptides and other compounds having similar atomic masses. Such an integrated system holds promise for biomolecule analysis and characterization, national security, advances in petroleum, and environmental monitoring. However, this potential has been hampered by the losses in sensitivity and mismatched duty cycles that are traditionally associated with combined IMS/MS systems.

PNNL has developed an integrated instrument platform that overcomes these problems. The system incorporates three innovations: 1) an ion funnel technology for increased sensitivity, 2) ion funnel trap advancements that provide more ion accumulation and precise release, and 3) a multiplexing feature for even greater sensitivity with better-aligned duty cycles. Together, these innovations can be easily coupled with liquid chromatography MS systems to enable efficient analysis, without losing ions or degrading IMS resolution.

PNNL’s multiplexing technique uses an extended pseudo-random gating procedure that separates ions into packets based on the timing of the gate openings and closings. After the ions travel through the drift cell of the IMS-time-of-flight (TOF) MS, the system intermingles ions from different packets at the detector based on differences in relative ion mobility. The system then uses algorithms to de-convolute the intermingled ions. This process yields a higher signal-to-noise ratio than can be produced by conventional techniques, resulting in greater sensitivity. Because ion packets can travel through the drift region simultaneously, rather than one at a time, the technique also increases analysis throughput.

Multiplexing is a technique related to and often confused with Hadamard transform. However, the multiplexing technique developed at PNNL is fundamentally different and provides several advantages over Hadamard transform. For a given sample, PNNL’s multiplexing decreases analysis time by 10-fold at the same signal-to-noise ratio as a conventional approach. At lower signal-to-nose ratio and increased sensitivity, the technique still maintains faster throughput than conventional methods. Although the algorithms behind multiplexing are relatively complex, implementation of the technique is relatively straightforward, involving the addition of electronic gating equipment and software to IMS systems or combinations of IMS and MS. A new method for reducing artifacts and substantially increasing the signal-to-noise ratio in multiplexed analyses is also part of the technology portfolio. The approach incorporates sophisticated software for integrating and controlling the new multidimensional system.

PNNL has also developed patented methods for interfacing IMS with ion trap MS systems such as Orbitrap (patent 9,939,409). The method provides similar benefits to multiplexed analysis using TOF MS in which the MS scan times are shorter than IMS times. Using a dual gating system, the method allows for analysis of complete samples using ion mobility in conjunction with the slower scan speeds of ion trap MS. The duty cycle and the sensitivity of the instrument benefit from a double multiplexing approach that delivers an order-of-magnitude better signal than traditional approaches. The algorithm developed to handle the convoluted data also efficiently removes the artifacts usually observed in conventional de-multipelxing schemes.

Advantages

  • Increases sensitivity and throughput by integrating fast IMS separation with slower MS acquisition, solving the mismatched duty cycle issue of current systems
  • Can decrease analysis time by 10-fold
  • Works with IMS, TOF MS, and Orbitrap MS
  • Reduces artifacts and substantially increases signal-to-noise ratios in multiplexed analysis

Availability

Available for licensing in all fields

Keywords

ion mobility, analytical instrumentation, mass spectrometry, 14158-E, 15270-E, 15625-E, 15815-E, 16720-E, 30201-E; 6,818,890; 6,967,325; 9,939,409; hourglass electrodynamic funnel; fast separation; slow detection; internal ion funnel

Portfolio

AI-Other Analytical Instruments
AI-Mass Spectrometry

Market Sectors

Analytical Instruments