Toward artifact-free data in Hadamard transform-based double multiplexing of ion mobility-Orbitrap mass spectrometry

The integration of ion mobility spectrometry (IMS) with a trap-based mass spectrometer (MS) such as Orbitrap using the dual gate approach suffers from low duty cycle. Efforts to improve the duty cycle involve the utilization of Hadamard transform-based double multiplexing which significantly improves the signal-to-noise ratio and duty cycle of the ion mobility-Orbitrap mass spectrometry (IM-Orbitrap MS) platform. However, artifacts and noise in the demultiplexed data significantly reduce the data quality and negate the benefits of multiplexing. We propose a new approach that identifies the true IM peaks and helps in eliminating the artifacts in the demultiplexed data leading to a decrease in false identifications in subsequent data processing. After the application of the algorithm, the quality of the IM-Orbitrap MS measurements was greatly improved because of the reduction in artifacts.