tDDA: A Targeted Data-Dependent Acquisition Mode for Rapid Screening of Targets in Complex Matrices

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Instrumentation

Background:

• Miniaturized mass spectrometers are valuable for in situ analysis due to portability and specificity.
• Traditional data-dependent acquisition (DDA) in complex samples is hindered by chemical noise and matrix effects, leading to false negatives.
• In situ applications often lack extensive sample pretreatment, exacerbating challenges with complex matrices.

Purpose of the Study:

• To develop and validate a targeted data-dependent acquisition (tDDA) mode for miniaturized mass spectrometers.
• To enhance the accurate detection of target compounds in complex matrices, minimizing false negatives.
• To improve the capability of in situ analysis for challenging samples like blood and saliva.

Main Methods:

• Implementation of a novel targeted data-dependent acquisition (tDDA) mode, bypassing reliance on full-scan mass spectra.
• Leveraging sine amplitude modulation of sinusoidal frequency modulated (SAM-SFM) waveforms for real-time waveform generation and parallel, high-speed screening.
• Integration of targeted automatic gain control (AGC) technology to improve detection of low-concentration analytes.
• Validation of the tDDA mode on a modified "Brick" miniaturized ion trap mass spectrometer.

Main Results:

• The tDDA mode successfully reduced the impact of chemical noise and matrix effects common in complex samples.
• Targeted automatic gain control significantly enhanced the detection sensitivity for low-concentration analytes.
• The tDDA method demonstrated effective detection of illicit drugs spiked in blood and saliva samples at low concentrations.

Conclusions:

• The developed tDDA mode offers a substantial improvement over conventional DDA for in situ analysis of complex samples.
• This technology effectively minimizes false negatives, increasing the accuracy of target compound detection.
• The tDDA mode shows significant promise for real-world applications requiring rapid and reliable in situ screening, such as forensic analysis.