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Improving the Performances of A “Brick Mass Spectrometer” by Quadrupole Enhanced Dipolar Resonance Ejection from the Linear Ion Trap Ting Jiang, Qian Xu, Hongjia Zhang, Dayu Li, and Wei Xu Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.8b03332 • Publication Date (Web): 30 Aug 2018 Downloaded from http://pubs.acs.org on September 1, 2018

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Analytical Chemistry

Improving the Performances of A “Brick Mass Spectrometer” by Quadrupole Enhanced Dipolar Resonance Ejection from the Linear Ion Trap

Ting Jiang,1 Qian Xu,1 Hongjia Zhang,2 Dayu Li2 and Wei Xu1*

1

State Key Laboratory Explosion Science and Technology, School of Life Science,

Beijing Institute of Technology, Beijing 100081, China 2

College of Information Science and Engineering, Northeastern University, Shenyang,

110819, China

*Corresponding Author: Wei Xu School of Life Science Beijing Institute of Technology Haidian, Beijing, 100081, China Email: [email protected] Web: http://www.escience.cn/people/weixu

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Analytical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Abstract Previously, a miniature mass spectrometer driven by a sinusoidal frequency scanning technique, named as Brick mass spectrometer was developed in our lab (Anal. Chem. 2017, 89, 5578). The frequency scanning technique enabled miniaturized electronics and broader mass range, but it was also limited in reduced mass resolution and sensitivity due to a relatively low operating rf voltage in comparison with the conventional voltage scanning technique. To improve performances of the Brick mass spectrometer, a quadrupole enhanced dipolar resonance ejection (QE-dipolar resonance ejection) method was proposed in this work. After optimization, mass resolution and sensitivity of the Brick mass spectrometer could be improved by no less than 2 times, and space charge effects within the ion trap could also be reduced. Furthermore, this QE-dipolar resonance ejection method is effective at elevated pressures, which would potentially allow us to further miniaturize the Brick mass spectrometer by operating it at higher pressures. This method is also applicable to any ion trap operated in either frequency scanning mode or voltage scanning mode, operated in either miniaturized instruments or bench top instruments.


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Introduction Miniaturization of mass spectrometry (MS) instruments could greatly expand the applications of MS into many field applications, such as environment monitoring,1 point-of-care testing,2,3 food safety4,5 and anti-terrorism.6,7 Over the past decades, great efforts have been made towards developing miniaturized mass spectrometers.8-10 Systems focusing on volatile sample analyses have been well developed and commercialized.11-14 Miniature mass spectrometers with atmospheric pressure interfaces have also been developed.12,15-18 By coupling with ambient ionization techniques,16,17,19-23 these miniature mass spectrometers not only reduce the total size and power consumption of the instrument, but also simplify the use of these instrument, which are critical for on-site applications. On the other hand, during the system miniaturization process, MS performance might be sacrificed with limited power and volume resources. For instance, the mass resolution would be reduced if air was used as the buffer gas or operating the mass analyzer at a higher buffer gas pressure.24-26 To miniaturize the vacuum system, MS sensitivity would be reduced by lowering the gas flow rate. To miniaturize the electronic system, mass range would be shrunk if the radio frequency (rf) generator of an ion trap was miniaturized. In facing these challenges, new techniques have been developed to counter-balance these effects. Discontinuous atmospheric pressure interface was developed to increase the gas flow rate, while maintaining a low enough pressure in an ion trap.16,19,27 Sinusoidal rf frequency scanning technique was developed to extend the mass range of a Brick mass spectrometer, while working at a



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relatively low rf voltage.28 Miniaturized ion traps29-32 and ion trap arrays33-35 have been developed to increase the working pressure of ion traps. New ion trap operation modes were proposed to further simplify a miniature MS system or to improve its quantitation precision.36-38 Even with these advancements, challenges still exist, and the performance of miniature mass spectrometers still needs to be improved to match the increasing demands in practical applications. To date, most of ion trap mass spectrometers employ a resonance ejection method to eject ions from the ion trap.39,40 In this way, ions will pick up energy from the excitation field and be ejected when their secular frequency approaches the excitation frequency. Typically, there are two resonance excitation methods, dipolar resonance excitation and quadrupolar resonance excitation methods. In dipolar excitation method, a supplementary alternating voltage was applied to one pair of the ion trap electrodes to produce a dipolar electric field.41,42 When ions are in resonance with the supplementary field, amplitude of ion motion will increase linearly with time (when ion-neutral collision was not considered) until being ejected. Ion ejection utilizing quadrupolar excitation could be carried out by the application of a supplementary alternating voltage applied in phase to one pair of the ion trap electrodes. Parametric resonant occurs when the ion frequency is one half of the supplementary

quadrupole

frequency.43,44

Ion

motion

amplitude

increases

exponentially with respect to time (when ion-neutral collision was not considered). However, the quadrupolar field has a zero value at center of the ion trap, when buffer gas is used to damp ion trajectories, quadrupolar excitation is not as effective as


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dipolar excitation. The double resonance ejection method was also developed,45 in which nonlinear resonance was used to achieve a rapid ion ejection. In this study, a new ion ejection method, the quadrupole enhanced dipolar resonance ejection method was proposed and implemented in our home-built Brick mass spectrometer. Performances of the Brick mass spectrometer, such as mass resolution, sensitivity and ion trapping capacity could be improved. This method could also extend the working pressure range of the instrument, potentially enabling the development of smaller MS instruments. Besides miniature MS instruments, this method is still applicable to bench top ion trap mass spectrometers.



Instrumentation Vacuum system. The Brick mass spectrometer developed in this study has a similar vacuum design to the previous version,28 which was designed based on the continuous atmospheric pressure interface (Figure 1f).17,23,46,47 A dual stage vacuum chamber was differentially pumped by the combination of a tunable turbo pump (70 L/s, KYKY Technology CO. LTD) and a scroll pump (0.18 m3/h, SVF-E0-50, Scroll Tech Inc., China). The first chamber and the atmosphere environment were connected by a stainless-steel capillary with a length of 10 cm and an inner diameter of 0.25 mm. A skimmer (diameter 0.5 mm) was used to connect these two vacuum stages. A linear ion trap (LIT) with hyperbolic electrodes (x0 = y0 = 4 mm, z0 = 40 mm) was placed in the second vacuum chamber to perform mass analysis. By default, the stainless-steel capillary was placed ~ 8 mm away from the skimmer, which results in a background pressure of 2.95 mTorr in the second vacuum chamber. Since no buffer gas was introduced in the system, air is used as the buffer gas in the ion trap. Control electronics. An enhanced version of the sinusoidal frequency scanning circuit was designed and applied to drive the LIT. Besides the rf driving signal, the QE-dipolar resonance ejection method developed in this study requires two supplementary resonance AC signals: the quadrupolar excitation signal and the dipolar excitation signal. Figure 1a plots the quadrupolar excitation field and the dipolar excitation field. To generate such fields, Figure 1b shows the schematic connection method of the rf (V cos(Ωt)), quadrupolar (Vq cos(ωqt)) and dipolar (Vd cos(ωdt)) excitation signals. As shown in Figure 1b, the quadrupolar excitation signal


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is coupled to the rf signal and applied on one pair of hyperbolic electrodes; while the dipolar excitation signal is applied on the other pair of hyperbolic electrodes. Figure 1c is a photo of the central control electronics (9.5 cm×2.5 cm×12.3 cm), which uses the Field-Programmable Gate Array (FPGA) technique to generate arbitrary waveforms. The central control electronics communicate with a PC via a high-speed USB port. This central control electronics would provide the required waveforms for the rf, quadrupolar and dipolar signals, as well as the DC signals supplied on the LIT endcaps. Figure 1d is the signal amplifier (2.2 cm in all dimensions) used to amplify the ion current signal from the electron multiplier. Figure 1e is the broadband rf amplifier (10 cm×5 cm×5 cm), which could sweep from 1 MHz to 200 kHz in frequency with a 500 Vp-p output voltage. With this circuit, frequency, phase and amplitude of both quadrupolar and dipolar excitation signals could be precisely controlled. In experiments, the rf signal with an amplitude of 500 Vp-p was swept from 1 MHz to 200 kHz linearly within the 100 ms mass scan period, unless otherwise specified. Sample preparation Reserpine (MW 608.68) was purchased from Organics (New Jersey), and the peptides Met-Arg-Phe-Ala (MRFA, MW 523.65), bradykinin (MW 1060.22) and PEG1500 were purchased from Sigma-Aldrich (St. Louis, MO). All samples were diluted in methanol-water (1:1 v/v).



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Theory and simulation In the presence of both quadrupolar and dipolar resonance excitations, after applying the pseudo-potential approximation ion motion in a linear ion trap could be described as,

d 2u du +c + (a − 2q cos(2ξ ) − 2q 'cos(2v ' ξ ))u = A cos(2vξ ) 2 dξ dξ

(1)

with the parameters defined as,

a=

ωq ωd 4 zVq Vq zVd 8eU 4 zV v = , v ' = , q = , q ' = = q , A = , Ω Ω mr02Ω2 mr0 2Ω2 mr02Ω2 V 2mr0Ω2

(2)

where Vq is the amplitude of quadrupolar excitation signal, Vd is the amplitude of dipolar excitation signal, V is the amplitude of the rf signal, Ω is the frequency of the rf signal, ωd defines the frequency of dipolar excitation signal, ωq defines the frequency of quadrupolar excitation signal, m is the mass of the ion, z is the charge an ion possess, r0 is the radius of the ion trap and c is the damping factor due to ion-neutral collisions. It is known that resonance occurs when frequency of the applied dipolar signal ( ωd ) matches ion secular frequency ( ωu ,n ).42,48,49 That is

ωd = ωu , n = (2n ± βu )Ω / 2, n = 0,1, 2,...

(3)

where u denotes the direction of interest (x or y direction) in the linear ion trap and

βu is a dimensionless parameter. In the case of quadrupolar excitation, the strongest resonance appears at twice of the secular frequency, high-order quadrupolar resonances were predicted to occur when the frequency ( ωq ) of the applied quadrupole signal and ion secular frequency coincides with following equation44,50,51


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ωq = ωu ,n =| n + β u | Ω / K, n = 0, ±1, ±2,...

(4)

where K is the order of resonance. The presence of quadrupolar excitation field leads to instability bands in the stability diagram along iso-βu lines. With a fixed v ' value, the instable βu values in the first stability region could be calculated using the following expression:52-55

Kv ' =| n + βu |, n = 0, ±1,...,K = 1,2,...

(5)

For example, when v ' =1/3, two instability bands close to β=1/3 and β=2/3 across the first stability region could be obtained from Equation 5. It should be noticed that high-order electric fields, such as hexapole and octupole fields, were not considered in this study. Appropriate high-order field components are known to help the ion ejection process.45,56,57 However, precise control of high-order fields are not easy, since high-order fields are typically due to non-ideal physical geometry of the ion trap. In this work, enhanced ion ejection could also be achieved using quadrupole fields, and the operating ion ejection point could be controlled and tuned by selecting appropriate quadrupole and dipole excitation frequencies (as shown in Figure 3 in later text). Therefore, high-order fields were not utilized in this work. Numerical simulations were also carried out to map the stability diagram of the LIT with the presence of quadrupolar excitation signals. A fourth order Runge-Kutta method was used to solve the ion motion equation (Mathieu equation).58,59 Figure 2a is the simulated stability diagram with the presence of a quadrupolar excitation signal ( v ' =1/3). The stability region is plotted at a resolution of 301×10001 pixels in the (a, q) plane with q’ = 0.01q. The instability bands corresponding to β=1/3 and β=2/3



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could be well observed. Width of the unstable bands introduced by the quadrupolar excitation field is determined by the quadrupolar signal amplitude. With the presence of only a dipolar excitation signal, ion motions in a LIT would have the following frequency components:60

kΩ±nωd ±ω0,k =0,1,2,...n =1,2,...

(6)

With the presence of both quadrupolar and dipolar excitation signals, ion motions would have a more complicated frequency spectrum as shown in Figure 2b (obtained from the Fourier transform of a simulated ion trajectory). Besides the ion secular motion frequency components ( 2n ± β0 , marked in red) and the frequency components related to dipolar excitations ( 2n ± βd , marked in purple), there are also frequency components resulting from quadrupolar excitation harmonics superimposed on ion secular frequencies ( 2n ± β0 ± mβq , marked in green), as well as frequency components resulting from quadrupolar excitation harmonics superimposed on dipolar excitation harmonics ( 2n ± βd ± mβq , marked in black). Among these frequency components, the ones related to ion secular frequency would decay with respect to time due to ion-neutral collisions.60 Furthermore, the frequency components far away from ion fundamental secular frequency would have much less effect than those close to ion secular frequency. Therefore, the frequency components at 2-βd -βq , 2βd -βq , βd should be a focus. When these frequencies are close to or exactly matches to that of the ion secular frequency (β0), ions would quickly absorb energies from excitation signals and getting ejected. Figure 2c-e are ion trajectories calculated by solving Equation 1 with different


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quadrupolar and dipolar excitation signals. An ion (m/z 524 Th) was placed close to center of the ion trap (0.01 mm off-center) at time zero. A rf voltage of 250 volts (pk-pk) and 460 kHz was applied during ion trajectory simulation. A buffer gas N2 with a pressure of 5 mTorr was applied. As shown in Figure 2c, a 2.5 V0-p quadrupolar excitation signal (126.8 kHz) itself is not sufficient to excite the ion, since a quadrupolar electric field has zero field strength at the center of the ion trap. By increasing the quadrupolar excitation voltage to 4 V0-p, an exponential increase of ion motion amplitude could be observed in Figure 2d. In the case of QE-dipolar resonance, ions could obtain energy from both quadrupolar and dipolar excitation fields. As plotted in Figure 2e (quadrupolar and dipolar signal frequency 126.8 and 126.8 kHz, respectively), the ion motion amplitude increases linearly at the beginning. When ions have been displaced from the center, it could also absorb energy from the additional quadrupolar field, leading to a steeper increase in ion motion amplitudes as shown in Figure 2f. As ions ejected rapidly from the ion trap, it would suffer fewer collisions, and the mass resolution could therefore be improved.



Results and Discussion Experimental evidence of QE-dipolar resonance ejection. In order to verify the effectiveness of QE-dipolar resonance ejection, experiments were performed at three different dipolar excitation frequency points, in which the dipolar excitation signal has an amplitude of 1.5 V and its frequency v = 0.334, 0.376 and 0.249, respectively. Figure 3a(1), 3b(1) and 3c(1) are the mass spectra of MRFA using the corresponding dipolar resonance ejection. Figure 3a(2) and 3a(3) are the mass spectra of MRFA at the same rf working condition, but with the superposition of an additional quadrupolar excitation (v’=1/3 and v’=2/3, respectively). Figure 3a(2) and 3a(3) insets are the stability diagrams with the addition of quadrupolar excitations, and the red arrow indicates the frequency point of the dipolar excitation. In both cases, the quadrupolar field induced instability lines would approach or overlap with the dipolar excitation frequency point. As a result, both the mass peak intensity and resolution of MRFA were improved. It should be noticed that the quadrupolar excitation signal with v’=1/3 and v’=2/3 would both produce two unstable iso-β lines (β=1/3 and β=2/3) across the stability region, and there are two unstable points (β=1/3 and 2/3) at the a=0 mass scan line. However, amplitude of quadrupole field is far below the ejection threshold, no ions would be ejected from the β=1/3 point without the help of dipolar field. Similarly, quadrupolar excitations with frequencies of v’=1/4 and v’=3/4 produce three unstable iso-β lines at β=1/4, 1/2 and 3/4, as shown in Figure 3b(2) and 3b(3). QE-dipolar excitation could also improve the peak intensity and resolution. When v’=1/2 as shown in Figure 3c(2), there is only one unstable iso-β lines at β=1/2.


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When the dipolar excitation is close to this β=1/2 point, enhanced peak intensity and resolution could be obtained (Figure 3c(2)). While no effect would be observed, when the dipolar excitation frequency is far away from this β=1/2 point (Figure 3c(3)). Parameter optimization. In QE-dipolar resonance ejection, parameters of both the dipolar and quadrupolar signal need to be optimized. Experiments have been carried out using MRFA. Amplitudes and frequencies of both the dipolar and quadrupolar signal were varied to find the optimal working condition (please refer to Figure S1 in the Supporting Information for details). Previous studies on dipolar resonance ejection have shown that there is an optimized amplitude value for the dipolar excitation signal at a given m/z ratio.24,61 In QE-dipolar resonance ejection, similar results were found. Optimal amplitude values exist for both the dipolar and quadrupolar excitation signals. When the quadrupolar excitation signal is too strong, ion ejections would happen at all the quadrupolar induced instability points (or the first point) at the a=0 MS scan line (Figure S1a). As discussed earlier in the theoretical analysis, frequency of the quadrupolar excitation signal needs to be close to that of the dipolar excitation signal. After optimization, it is found that an optimized ion ejection could be achieved at v’=1/3 and v=0.334 (Figure S1c and S1d). Phase differences among the rf, the dipolar and the quadrupolar excitation signals would also affect the mass peak (please refer to Figure S3 in the Supporting Information), which is similar to that in conventional dipolar resonance ejection method.62-64 To ensure stable and repeatable measurements, their initial phases were all set at zero at the beginning of the MS scanning period.



Resolution and sensitivity improvements of the Brick mass spectrometer. To characterize the performance enhancements of the Brick mass spectrometer, the instrument was operated in both the QE-resonance ejection mode and conventional dipolar resonance ejection mode with the results directly compared. First, PEG1500 with a concentration of 1000 ug/mL was tested. To reach a higher mass range, the instrument was operated in the following condition: rf frequency scans from 600 kHz to 200 kHz (nonlinearly to have a linear mass calibration curve as described in supporting information) in 100 ms (corresponding to a mass scan rate of 20000 Th/s) with an amplitude of 500 Vp-p; the dipolar excitation signal had an amplitude of 2.86 Vp-p, and its frequency was scanned from 150.6 kHz to 50.2 kHz, so that v=0.251. In the QE-resonance ejection mode, the additional quadrupolar excitation signal had an amplitude of 4.96 Vp-p, and its frequency was scanned from 150 kHz to 50 kHz, so that it was synchronized with the rf signal (v’=1/2). As shown in Figure 4a, doubly charged PEG1500 peaks could not be resolved using conventional dipolar resonance ejection mode, resulting in a big bump at the low mass range. However, they could be baseline resolved in the QE-dipolar resonance ejection mode, suggesting that QE-dipolar resonance ejection could effectively improve mass resolution of the Brick mass spectrometer. It should be noticed that amplitude optimization was also performed for the conventional dipolar resonance ejection experiments (Figure S2 in the Supporting Information). A systematic study was also performed to characterize the mass resolution enhancement effect of the QE-dipolar resonance ejection method. Figure 4b shows the


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mass peaks of MRFA (100 µg/mL) ions at different mass scan rates. In this experiment, the rf frequency was scanned from 1 MHz to 400 kHz with an amplitude of 500 Vp-p, and v and v’ were set at 0.334 and 1/3, respectively. To vary the mass scan rate, the scanning duration was tuned from 100 to 500 ms. Compared to dipolar resonance ejection, QE-dipolar resonance ejection could effectively narrow the peak width by about 3-6 times. Furthermore, a more symmetric mass peak could be observed using the QE-dipolar resonance ejection method (insets in Figure 4b). With narrower mass peaks, ion intensities of MRFA were also increased by about 2-3 times at different mass scan rates (Figure 4c). With increased ion intensity, the sensitivity of the Brick mass spectrometer could also be improved. Figure 4d compares the linear range of quantitation curves of MRFA with dipolar resonance and QE-dipolar resonance ejection methods. A limit of quantitation (LOQ) of 0.25 µg/mL was achieved with the QE-dipolar resonance ejection method, compared to 0.5 µg/mL with the conventional dipolar resonance ejection method. In dipolar-only resonance ejection experiments, amplitude of the excitation signal was also optimized during experiments, so that a fair comparison could be obtained. Signal intensity improvements is believed to be also a result of the narrower mass peak. For instance, similar or equal peak areas are expected if ion ejection efficiency approaches unity in both cases. However, since the QE-dipolar resonance ejection could narrow the peak width, a higher peak height would be observed. Furthermore, a mixture of MRFA (100 µg/mL) and reserpine (50 µg/mL), as well



as another sample, bradykinin (100 µg/mL) were also analyzed using the Brick mass spectrometer. Figure 5 compares the mass spectra obtained using QE-dipolar resonance ejection method with those obtained using dipolar resonance ejection method. The rf scan rate was fixed at ~ 3000 Th/s in both methods. Results show that the QE-dipolar resonance ejection is still effective for mixture analysis, and the peak width of MRFA and reserpine were decreased from 3.3 to 0.65 Th, 3.75 to 1.38 Th, respectively. Besides the ion intensity enhancement, mass peak of the doubly charged bradykinin ion was also narrowed from 0.84 to 0.46 Th. High pressure operations. For portable mass spectrometers, the capability of mass analysis at high pressures would have big impacts on the vacuum system miniaturization. For example, mass analysis at hundreds of mTorr would potentially allow the dispense of turbo pumps when designing a miniature mass spectrometer, which could significantly reduce the power consumption and volume of the system. However, the pressure induced peak broadening effect would also degrade mass resolution.25,65 At higher pressures, ion-neutral collisions could better help ion cooling to the center of the ion trap during the ion trapping process, but the increased number of ion-neutral collisions would also randomize and delay the ion ejection process. In the QE-dipolar resonance ejection method, ions could gain extra energy from the quadrupolar excitation field, thus achieve faster ejections (Figure 2e). With a smaller number of ion-neutral collisions, mass resolution is also expected to be improved at higher pressures with this QE-dipolar resonance ejection method. To test this hypothesis, background pressure in the second vacuum chamber of the Brick mass


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spectrometer was increased by lowering the rotation rate of the turbo pump. Limited by the operation pressure of the electron multiplier, a highest pressure of 6.44 mTorr was achieved in the experiments. MRFA was then tested using both dipolar and QE-enhanced dipolar resonance ejection methods. As shown in Figure 6, QE-dipolar resonance ejection method could effectively improve mass resolution at the tested pressure region (from 2.95 to 6.44 mTorr). It can be observed that the peak width of MRFA ions decreased from 3.65 to 1.58 Th at 2.95 mTorr, from 4.23 to 2.19 Th at 6.44 mTorr in comparison with dipolar resonance ejection. Reduction of space charge effects. Charge capacity, the number of ions that can be trapped simultaneously without leading to peak distortions, is one of the most important figure-of-merits of an ion trap mass spectrometer. Space charge effects would cause the broadening and shift of a mass peak.66-68 Therefore, techniques such as automatic gain control (AGC)69 are typically used to prevent space charge effects. However, larger ion trapping capacity is still desired to extend the dynamic range of an ion trap mass spectrometer. Previous study has shown that space charge effects could be reduced by lowering the Coulomb interaction between ions.70 The faster ion ejection in QE-dipolar resonance ejection process could shortening the Coulomb interaction duration within the ion ejection process. To test this hypothesis, the ion introduction time was increased from 50 to 600 ms, so that more and more ions could be introduced into the ion trap. Figure 7 shows the results by using 100 µg/mL MRFA as the analyte. When using conventional dipolar resonance ejection method, strong space charge effects were observed. The peak width broadened from 3.43 to 6.12 Th



as the ion introduction time was increased from 50 to 600 ms (Figure 7a). While the peak width was almost kept the same when using the QE-dipolar resonance ejection method (Figure 7b and 7c). The mass shift was also below 0.5 Th within 400 ms ion introduction durations, while a ~1.5 Th mass shift was observed when using dipolar resonance ejection method. Figure 7d compares the ion intensities of MRFA under different ion injection times and using different resonance ejection methods. A ~2 time improvement in ion intensity was observed with a 50 ms ion injection duration; while ~6 time with a 600 ms ion injection duration. Ion intensity of MRFA has a close to linear relationship with the ion introduction duration under the QE-dipolar resonance ejection mode. In contrast, ion intensity first increases, then decreases due to the peak broadening effect under the dipolar resonance ejection mode.


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Conclusion Facing the contradiction between MS miniaturization and performance degradation, a new ion ejection method, quadrupole enhanced dipolar resonance ejection was proposed. Theory and its implementation in the Brick mass spectrometer were shown in this study. By accelerating the ion ejection process, mass resolution of the system could be improved by more than 2 times. With narrower peak width, ion peak intensity could also be increased, which results in about a 2-fold improved detection sensitivity. This method could also reduce the space charge effects in an ion trap, and broadly applicable to both bench top and miniature ion trap mass spectrometers.

Acknowledgements This work was supported by National Key research and development plan (2018YFF0212500),

NNSF

(21827810,

201475010,

(16L00065). Supporting Information Supporting Information is available via the internet.


61635003)

and

BNSF


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Figure 1

Figure 1. (a) Quadrupolar excitation field and dipolar excitation field distributions in x-y plane of an ion trap. (b) Schematic connections of the rf signal, quadrupolar excitation signal and dipolar excitation signal. Photos of (c) the center control electronics, (d) the signal amplifier, and (e) the broadband rf amplifier. (f) Schematic of the Brick mass spectrometer with the continuous atmospheric pressure interface.



Figure 2

Figure 2. (a) The simulated stability diagram of a linear ion trap with the presence of a quadrupolar excitation signal (v’=1/3 and q’=0.01q). (b) Frequency spectrum obtained by Fast Fourier Transform analysis of the ion motion trajectory under a = 0, q = 0.585, v’ = 1/3, v = 0.32 , Vd = 1 V0-p, Vq = 4 V0-p, buffer gas pressure 5 mTorr, nitrogen. Ion secular motion harmonics, dipolar harmonics, quadrupole superposed ion secular harmonics, quadrupole superimposed dipolar harmonics are marked by red, purple, green, and black colors, respectively. Note: is used to represent ion motion frequencies since they have the relationship of ω = βΩ /2 . (c) Simulated ion motion trajectory of an ion (m/z 524 Th) with a quadrupolar resonance excitation, Vq = 2.5 V0-p, . (d) Simulated ion trajectory with a quadrupolar resonance excitation, Vq = 4 V0-p. (e) Comparison of ion trajectories under QE-dipolar resonance (Vq = 2.5 V0-p, Vd = 0.6 V0-p,) and dipolar resonance (Vd = 0.6 V0-p) excitations.


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Figure 3

Figure 3. (a)(1) (b)(1) (c)(1) the mass spectra of MRFA using dipolar resonance ejection with a frequency of v=0.334, 0.376, 0.249, respectively. (a)(2)-(3) the mass spectra of MRFA with an additional quadrupolar excitation at frequencies of v’=1/3 and 2/3, respectively. (b)(2)-(3) the mass spectra of MRFA with an additional quadrupolar excitation at frequencies of v’=1/4 and 3/4, respectively. (c)(2)-(3) the mass spectra of MRFA using QE-dipolar excitation ejection with the quadrupole frequency at v’=1/2, and dipolar frequencies at v=0.249 and 0.334, respectively. Insets are the first stability diagrams with the addition of a quadrupolar resonance signal, and the red arrow indicates the frequency point of the dipolar excitation.



Figure 4

Figure 4. (a) Mass spectra of PEG1500 using dipolar resonance and QE-dipolar resonance ejection methods, and the rf has a scan rate of 20000 Th/s. (b) Resolution improvements at different rf scan rates for MRFA (m/z 524 Th). (c) Ion intensity enhancement at different rf scan rates for MRFA (m/z 524 Th). (d) The linear of quantitation curves of the BMS for MRFA with dipolar resonance and QE-dipolar resonance ejections, respectively.


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Figure 5

Figure 5. Typical mass spectra using dipolar resonance and QE-dipolar resonance ejection methods with a scan rate of ~3000 Th/s. (a) mixture sample of MRFA (m/z 524 Th) and Reserpine (m/z 609 Th). (b) bradykinin (m/z 1060 Th, +1 charge, m/z 530 Th, +2 charges). Inset are the zoomed in mass peaks.



Figure 6

Figure 6. Resolution improvements at different pressures for MRFA (m/z 524 Th).


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Figure 7

Figure 7. (a) (b) Mass spectra of MRFA (100 µg/mL) at different injection times using dipolar resonance and QE-dipolar resonance ejection methods. (c) Mass resolution degradations of MRFA in terms of the increased ion injection time. (d) Comparison of ion intensity under different ion injection times with dipolar resonance and QE-dipolar resonance ejection methods.



TOC


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