Large biomolecules and bioparticles play a vital role in biology, chemistry, biomedical science and physics. Mass is a critical parameter for the characterization of large biomolecules and bioparticles. To achieve mass analysis, choosing a suitable ion source is the first step and the instruments for detecting ions, mass analyzers and detectors should also be considered. Abundant mass spectrometric techniques have been proposed to determine the masses of large biomolecules and bioparticles and these techniques can be divided into two categories. The first category measures the mass (or size) of intact particles, including single particle quadrupole ion trap mass spectrometry, cell mass spectrometry, charge detection mass spectrometry and differential mobility mass analysis; the second category aims to measure the mass and tandem mass of biomolecular ions, including quadrupole ion trap mass spectrometry, time-of-flight mass spectrometry, quadrupole orthogonal time-of-flight mass spectrometry and orbitrap mass spectrometry. Moreover, algorithms for the mass and stoichiometry assignment of electrospray mass spectra are developed to obtain accurate structure information and subunit combinations.

We adopt an orthogonal wavelet packet decomposition (OWPD) filtering approach to cancel harmonic interference noises arising from an AC power source in time domain and remove the resulting rf voltage interference noise from the mass spectra acquired by using a charge detection frequency-scan quadrupole ion trap mass spectrometer. With the use of a phase lock resampling technique, the transform coefficients of the rf interference in signals become a constant, exhibiting a shift of the baseline in different rf phases. The rf interference is therefore removable by shifting the baselines back to zero in OWPD coefficients. The approach successfully reduces the time-domain background noise from 1367 electrons (rms) to 408 electrons (rms) (an improvement of 70 %) and removes the high frequency noise components in the charge detection ion trap mass spectrometry. Unlike other smoothing or averaging methods commonly used in the mass-to-charge (m/Ze) domain, our approach does not cause any distortion of original signals.

A laser-induced rf plasma (LIRFP) ion source was developed to ionize submicrometer-sized particles for the first time. The LIRFP ion source can increase the charge of those particles to several thousand charges via charge exchange reactions so that those particles can be trapped and analyzed with a charge detection quadrupole ion trap-mass spectrometer (CD QIT-MS). Different reagent gases for charge exchange reaction were investigated, viz. argon, nitrogen, oxygen, methane, helium, krypton, xenon, argon/methane (with ratios of 10:1 and 2:1), argon/nitrogen (with a ratio of 1:1), nitrogen/oxygen (10:1), krypton/methane (10:1), and air. The average charge of 0.75 μm polystyrene particles could reach 1631 using an argon/methane mixture with a ratio of ∼10:1. The average charges for freeze-dried Escherichia coli EC11303, Escherichia coli strain W, and Staphylococcus aureus were 842, 1112, and 971, respectively, with a mass-to-charge ratio (m/z) range from 10 7 to 10 8 ; and the average masses were 3.5 × 10 10 Da, 6.0 × 10 10 Da, and 5.6 × 10 10 Da, respectively. The average mass and charge of the vaccinia virus were ∼9.1 × 10 9 Da and ∼708 with a m/z of ∼10 7 . This LIRFP CD QIT-MS method was rapid with only 20 min for each sample measurement.

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Conventional linear ion trap mass analyzers (LIT-MS) provide high ion capacity and show their MS ability; however, the detection of high mass ions is still challenging because LIT-MS with secondary electron detectors (SED) cannot detect high mass ions. To detect high mass ions, we coupled a charge detector (CD) to a rectilinear ion trap mass spectrometer (RIT-MS). Immunoglobulin G ions (m/z ~150,000) are measured successfully with controlled ion kinetic energy. In addition, when mass-to-charge (m/z) ratios of singly charged ions exceed 10 kTh, the detection efficiency of CD is found to be greater than that of SED. The CD can be coupled to LIT-MS to extend the detection mass range and provide the potential to perform MS of high mass ions inside the ion trap. Graphical Abstract ᅟ.