Multistage Transversal Modulation Ion Mobility Spectrometry: Reducing the Voltage Required for High Resolution IMS for pre-existing mass spectrometers

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1 Multistage Transversal Modulation Ion Mobility Spectrometry: Reducing the Voltage Required for High Resolution IMS for pre-existing mass spectrometers 1

2 Summary Introduction IMS-MS current technology. TMIMS principle of operation. Previous prototype. Objectives. Architecture definition. Results. Conclusions. 2

3 IMS-MS current technology Ion Mobility (K) IMS MS current systems in market Based on Drift-tube or Travelling Wave Waters SYNAPT Pulsed output of ions (Waters Synapt, Agilent IM-QTOF): - Peaks duration in the ms scale Only compatible with fast MS Careful integration required Commercialized systems integrate IMS and MS in a single system Not modular Very expensive systems Limited to Q-TOF Agilent IM-QTOF To expand IMS possibilities to all kind of existing MS IMS continuous output of ions 3

4 TMIMS principle of operation TMIMS provides continuous output of ions Deflector electrode Axial electrode Inlet slit Outlet slit Selection criterion: Not selected ions G. Vidal de Miguel, "Method and apparatus to produce steady beams of mobility selected ions via time-dependent electric fields", 61/211,111 (USPTO) G. Vidal, M. Macia, J. Cuevas, Transversal Modulation Ion Mobility Spectrometry (TM-IMS), A New Mobility Filter Overcoming Turbulence Related Limitations, Anal. Chem,

5 Previous prototype IMS-MS: Tetraalkylammonium ions Architecture: TMIMS-LTQ assembly Previous prototype demonstrated the viability of the technology. Still need to be improved to meet final user requirements. G. Vidal, M. Macia, J. Cuevas, Transversal Modulation Ion Mobility Spectrometry (TM-IMS), A New Mobility Filter Overcoming Turbulence Related Limitations, Anal. Chem, G. Vidal, M. Macia, C. Barrios, J. Cuevas, Transversal Modulation Ion Mobility coupled with Mass Spec.: Exploring the IMS-IMS-MS Possibilities of the Instrument, Anal. Chem,

6 Objectives Ion Source TMIMS API - MS Add-On IMS cell Requirements: One ion One peak (overtones, secondary peaks) Inlet voltage reduction (16kV to 0V) Reduce oscillating voltage Improve robustness Improve desolvation capacity Previous TMIMS 6

7 Summary Introduction. Architecture definition. - TMIMS ladder - New architecture. - New prototype. Results. Conclusions. 7

8 TMIMS ladder: principle of operation Ladder of small TMIMS stages Each stage operates with a fraction of the total voltage Ions of interest Selected ions sequentially focused at slits Lateral displacements accumulated Total resolving power of TMIMS ladder equals conventional TMIMS (same voltage) Unwanted ions With 6 stages: oscillating voltage 1.5kV pp Solvation and space charge affect only to first stages G. Vidal de Miguel, Transversal Modulation Ion Mobility Spectrometer with reduced voltage and improved robustness and resolving power, 62/114,601 (UPSTO), Feb. 11,

9 TMIMS ladder: simulations Overtone Simulated spectrum and trajectories Secondary Main 9

10 New Architecture Desolvation TMIMS cell TMIMS ladder Resistive capillary Ion Source API - MS Grounded 1.5 kvpp -2 kv -10 kv MS inlet voltage TMIMS ladder Reduces Oscillating Voltage. Solvation and space charge only affect first stages. Resistive capillary Couple TMIMS and MS. Inlet grounded. 10

11 New Prototype Control module Detail: TMIMS core TMIMS cell nanoesi LTQ Adjacent module 11

12 Summary Introduction. Architecture definition. Results. - Proof of concept tests. - Tuning tests. - Validation tests. Conclusions. 12

13 First tests: C 28 H 60 BrN Nominal operation nanoesi: C 28 H 60 BrN 100µM ; Temperature = 25 C Oscillating Voltage applied: Saturating stage 1 13

14 Temperature effect (C 28 H 60 BrN) nanoesi: C 28 H 60 BrN 100µM 14

15 Assembling Ion Max Source (ESI probe) Detail: IonMax - TMIMS Cell inlet IonMax (ESI) Control module TMIMS cell LTQ Adjacent module 15

16 Desolvation capacity (C 28 H 60 BrN) ESI: C 28 H 60 BrN 1µM ; Temperature = 130 C 16

17 LTQ ESI (+ ion) Calibration Solution ESI: Pierce LTQ ESI Pos. Ion Calibration Solution ; Temperature = 130 C MRFA (m/z Da) Ultramark Caffeine (m/z Da) 17

18 Cytochrome C ESI: Cytochrome C 10µM (denatured) ; Temperature = 130 C 18

19 Relative Abundance Relative Abundance Relative Abundance Separation of isomers: HOBP-PEG400 ESI: HOBP-PEG400 (5 µm : 100µM) ; Temperature = 130 C 2-hydroxy-4-octyloxybenzophenone (HOBP) & PEG-400 Unresolved HOBP - PEG400 (n=7) m/z Da m/z m/z Da Fragmentation (NCE 50) HOBP fragments Normalized m/z Da fragments m/z 19

20 Summary TMIMS technology & Background. Problems-Requirements. Aim of the project. New Architecture. Results. Conclusions. 20

21 Conclusions Add-on IMS cell TMIMS cell Control module Compatible with: Standard Ion Sources, Pre-existing API-MS. IonMax (ESI) LTQ Grounded inlet. Reduced voltage. Improved desolvation capacity. Improved robustness. Overtones & Secondary peaks have to be eliminated. Adjacent module 21

22 Many thanks! Dr. G. Vidal G. Arranz A. Tejero C. Barrios Laboratory of Organic Chemistry Dr. A. Makarov Dr. D. Nolting The Eurostars Programme (European Commission) Prof. R. Zenobi 22

23 ISIMS 2015 Thanks for your attention! 23

24 Drifting Gate: principle of operation Set of pair of electrodes ladder of slits Sequentially applying transversal E. Field Drifting Gate travels at fixed speed Drifting Gate ion transmission diagram G. Vidal de Miguel, "Method and apparatus to generate beams of ions with controlled ranges of mobilities", 62/077,412 (UPSTO), Nov. 10,

25 Drifting Gate: simulations Simulated spectrum and trajectories Overtone DG ion transmission diagram Secondary Main DG DG + TMIMS ladder 25

26 Future Architecture DG TMIMS cell TMIMS ladder Resistive capillary Ion Source API - MS Grounded 1.5 kvpp -2 kv -10 kv MS inlet voltage DG sync. TMIMS ladder Eliminates overtones & secondary peaks. Helps to desolvate ions. TMIMS ladder Reduces Oscillating Voltage. Solvation and space charge only affect first stages. Resistive capillary Couple TMIMS and MS. Inlet grounded. 26

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