Acquisition of a Timstof Pro LC-MS System (Mass Spectrometer)

We wish to purchase a timsTOF Pro mass spectrometer with trapped ion mobility which allows Parallel Accumulation Serial Fragmentation (PASEF) acquisition method to provide extremely high speed and sensitivity proteomics. Bruker is the only provider of such instruments.

We wish to purchase a timsTOF Pro mass spectrometer with trapped ion mobility which allows Parallel Accumulation Serial Fragmentation (PASEF) acquisition method to provide extremely high speed and sensitivity proteomics. Bruker is the only provider of such instruments. The laboratory of Prof. Mann at the Centre for Protein Research, KU and also the Max Planck Institute for Biochemistry, Munich have tested this technology and have demonstrated more than 800 000 fragmentation spectra in standard 120 min LC runs, which can be used for near exhaustive precursor selection in the complex mixtures we examine. Online PASEF achieves remarkable sensitivity with more than 2 900 proteins identified in 30 min runs with 10 ng of material. This technology is essential for our research.

1) The instrument must be able to synchronise the quadrupole with the IMS elution time to allow for a high MS/MS acquisition speed, leading to an increased fragmentation depth and there must be algorithms for intelligent targeting of low-level precursors.

2) The MS instrument must be capable of real-time data acquisition and processing, enabling a high spectrum repetition rate of > 100 Hz in MS/MS mode (including ion mobility separation and without sacrificing sensitivity) to obtain highest possible identification of both peptides and proteins, i.e. high sequence coverage of the identified proteins.

3) Mass resolution 60 000 independent of MS or MS/MS sequencing speed.

4) Reproducibility of Collisional Cross Section (CCS) value determination < 0.5 % RSD.

5) Pre-defined methods for DDA, DIA, PRM delivered, where both m/z and ion mobility are used for selectivity (i.e. window selection in DIA and PRM, and possibility to integrate various LC vendors into the instrument control software and the data-file format must be open architecture to enable easy input for various bioinformatics approaches.

The timsTOF Pro system comes with a dual-TIMS (trapped ion mobility spectrometry) analyser optimised for high-speed shotgun proteomics. It has nearly 100 % duty cycle, making this parallel accumulation serial fragmentation technique (PASEF) perfectly suited for nanoflow LC-MS analysis of enzymatically-digested complex protein mixtures. The timsTOF Pro from Bruker is the only instrument in the market that has TIMS technology allowing PASEF, DIA-PASEF and PRM-PASEF acquisition methods.

Patent:

TIMS

— TIMS cell

Title: ‘Apparatus and method for parallel flow ion mobility spectrometry combined with mass spectrometry’

Issued: US7838826B1; US 8288717B2

— IMEX, temporal zoom

Title: ‘Spectrum Acquisition Modes For Ion Mobility Spectrometers Using Trapped Ions’

Issued: US8766176B2; GB2490387B

Pending: DE102012004398A1

— Parallel Accumulation TIMS

Ion Guide System:

— High Precision Multipole Rod Ion Guides

Title: ‘Multiple rod systems produced by wire erosion’

Issued: DE102004037511B4; GB2416915B; US7351963B2

— Ion Beam Conditioning

Title: ‘Conditioning of an ion beam for injection into a time-of-flight mass spectrometer’

Issued: GB2361803B; US6700117B2

TOF Mass Analyser:

Gridless Orthogonal Accelerator and Ion Optics for Focus Mode

Title: ‘Gridless time-of-flight mass spectrometer for orthogonal ion injection’

Issued: DE10005698B4; GB2361353B; US6717132B2

Title: ‘Pulsers for time-of-flight mass spectrometers with orthogonal ion injection’

Issued: DE10158924B4; GB2386751B; US6903332B2

— Reflector Design

Title: ‘Reflectors for time-of-flight mass spectrometers’

Issued: DE102014009900B4; CN105244242B

Pending: GB2530840A; US20160005583A1

— Auto-Calibration of Detector

Title: ‘Method of adjusting the detector amplification in mass spectrometers’

Issued: DE102008010118B4; GB2457559B; US8536519B2

— Advanced Mass Band-Width

Title: ‘Method of operating a time-of-flight mass spectrometer with orthogonal ion pulsing’

Issued: DE102011100525B4; GB2490577B; US8927928B2

Electro-Spray Ion Source with Ion Funnel

Title: ‘Ion guide for mass spectrometers’

Issued: CA2463433C; CA2747956C; US7495212B2; US7851752B2; US8222597B2; EP1465234B1 (DE, GB)

Title: ‘Ion funnel with improved ion screening’

Issued: GB2402261B; US7064321B2.