Mini Mass Spectrometer Integrated with a Miniature Ion Funnel

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A Mini Mass Spectrometer Integrated with a Miniature Ion Funnel Yanbing Zhai, XiaoHua Zhang, Hualei Xu, Yongchang Zheng, Tao Yuan, and Wei Xu Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.7b00195 • Publication Date (Web): 02 Mar 2017 Downloaded from http://pubs.acs.org on March 2, 2017

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Analytical Chemistry

A Mini Mass Spectrometer Integrated with a Miniature Ion Funnel

Yanbing Zhai,1 Xiaohua Zhang,2 Hualei Xu,1 Yongchang Zheng,3 Tao Yuan4 and Wei Xu1*

1

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

Beijing Institute of Technology, Beijing 100081, China 2

Anyeep Instrumentation Company, Suzhou 215129, China

3

Department of Hepatic Surgery, Peking Union Medical College Hospital, Beijing

100032, China 4

College of Information Science, Shenzhen University, Shenzhen 518060, China

*Corresponding Author: Wei Xu School of Life Science Beijing Institute of Technology Haidian, Beijing, 100081, China Email: [email protected]

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ACS Paragon Plus Environment


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Abstract Previously, a continuous atmospheric pressure interfaced miniature mass spectrometer was developed in our lab. The continuous atmospheric pressure interface improves system robustness, stability and scan speed, but it also results in limited ion transfer efficiency and reduced mass resolution. To solve these problems, a miniature ion funnel was designed and integrated into the miniature mass spectrometer for the first time. Besides ion transfer efficiency, dimension and power consumption of the ion funnel also need to be considered throughout the design process. After a systematic optimization, the designed miniature ion funnel could increase ion transfer efficiency by more than 10 times; while lowering the background pressure of ion trap by ~2 times. As a result, sensitivity and mass resolution of the second generation miniature mass spectrometer were improved by 20 times and ~2 times respectively, while maintaining its high scan speed and stability. A sensitive and robust mini-MS, capable of coupling with ambient ionization sources would meet the needs of many on-site chemical analysis applications, such as in food, drug and agricultural administrations, forensic science, homeland security, and etc.

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Introduction Owing to its high sensitivity, specificity and generality, mass spectrometry (MS) has been widely applied for chemical and biological analyses.1-5 The development of miniature mass spectrometers is analogue to that of portable computing devices, system miniaturization would greatly expand their applications in the modern society, ranging from space exploration to personal usage. Miniaturization of a mass spectrometer is a systematic problem, which would involve customized and optimized designs of mass analyzers, ion transfer devices, electronic and vacuum systems.6,7 Since about fifteen years ago, MEMS8,9 and many other advanced fabrication techniques10-12 have been used to make miniaturized mass analyzers. For example, in an attempt to lower the rf voltage requirement, micrometer-sized ion traps13-15, quadrupole mass filters16,17 and their arrays18-21 have been fabricated. Miniaturized mass analyzers do help shrinking the electronic system, and could work at higher buffer gas pressures. However, there are also performance tradeoffs, especially in terms of mass resolution due to fabrication, assembly precisions and shallower potential well depth.22,23 The size and power consumption of a MS system are largely determined by the vacuum system. Thus, design of vacuum system and atmospheric pressure interface (API) is actually the key for miniaturizing a MS system as a whole. An API serves two purposes, which are introducing samples from atmosphere to vacuum and maintaining a high vacuum condition inside the instrument. Restricted by pumping power of a miniature system, the earliest miniature mass spectrometers adopt 3



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membrane inlets24-26 or inlets with ultra-low gas flow rate27,28 Based on these APIs, hand-held mass spectrometers have been developed and applied for in situ analyses of volatile samples.27,29-31 To analyze non-volatile samples, discontinuous atmospheric pressure interface (DAPI)32-34 and pulsed pinhole atmospheric pressure interface (PP-API)35 were developed. By introducing ions into the vacuum chamber in a pulsed fashion, DAPI has enabled the coupling of ambient ionization techniques with mini-MS systems.36-39 In 2015, a miniature mass spectrometer with continuous API (CAPI) was developed by using high pressure ion trap operation and the differential pumping system design.40 System stability, robustness and scan speed were improved with this CAPI design, and ppbv level detection sensitivity could be achieved for volatile samples using an internal plasma ionization source41 However, only ppm level detection sensitivity was achieved when coupling with ambient ionization sources. Therefore, it is demanding to boost the analytical performances of the continuous atmospheric pressure interfaced miniature mass spectrometer (CAPI mini-MS). In fact, many ion transfer devices have been designed for lab-scale MS instruments, such as quadrupole,42,43 hexapole,44 octopole ion guides,45,46 einzel lens47 and ion funnels48,49. These ion transfer devices could effectively increase the ion transfer efficiency in a lab-scale instrument. Among these devices, an ion funnel could work at high pressure regions, such as the first vacuum stage of the CAPI mini-MS (1~10 Torr). However, conventional ion funnels are typically large in size, since its analytical performances instead of dimension are the main concern in its design 4


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process. A miniature planar ion funnel that works in low-pressure regions was designed and tested in terms of ion currents at 5.5×10-6 Torr.50 However, there has been no report of applying ion funnels in mini-MS systems. In this study, a second generation CAPI mini-MS system was developed, in which a miniature ion funnel was designed and integrated. Integration of this ion funnel could not only improve the detection sensitivity but also improve mass resolution of the mini-MS system. Ion trajectory simulations and experiments were carried out to optimize the design and operating parameters of the ion funnel. After optimization, a 20-fold sensitivity improvement was achieved due to increased ion transfer efficiency. Mass resolution was also improved by ~ 2 times, since background pressure in the ion trap was decreased from ~6 mTorr to ~3.4 mTorr by removing neutral molecules from ion beams in the ion funnel region. In addition, the architecture of the instrument was redesigned as well for enhanced system stability and robustness.

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Experimental section Chemical samples. Rhodamine b (MW 479.01), vitamin B (VB, MW 300.81), reserpine (MW 608.68) were purchased from Acros Organics (New Jersey, USA), the peptides Met-Arg-Phe-Ala (MRFA, MW 523.65) and Gly-Pro-Arg-Pro (GPRP, MW 425.48), were purchased from Sigma Aldrich (St. Louis, MO, USA). High performance liquid chromatography (HPLC)-grade methanol (Methanol) was purchased from Fisher Scientific (Fairlawn, NJ, USA).The samples used in experiments were all diluted in methanol–water (1:1 v/v). Instrumentation As shown in Figure 1a, a dual stage vacuum chamber was designed, which was differentially pumped by the combination of a turbo pump (10 L/s, Hipace 10, Pfeiffer Inc., Germany) and a diaphragm pump (0.18 m3/h, SVF-E0-50，Scroll Tech Inc.， China). A linear ion trap with hyperbolic electrodes (x0 = y0 = 4 mm, z0 = 40 mm) was placed in the second vacuum stage. An electron multiplier (Model 2500, Detech Inc., USA) integrated with a home-built dynode was used as the ion detector. Similar to the first generation the CAPI mini-MS, a 20 cm long stainless steel capillary with an inner diameter (i.d.) of 0.25 mm was used to connect the atmosphere with the first vacuum stage, and a skimmer (or pinhole) with an i.d. of 0.4 mm (Figure S1) was used to connect the first and the second vacuum stages. Different from the first generation CAPI mini-MS, the capillary in this generation was pulled away from the skimmer to allow the placement of the ion funnel, and the skimmer was isolated from the vacuum chamber, so that a DC voltage could be applied on it. Glass capillaries 6


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with tip diameters of 2-4 µm with a platinum electrode inserted inside were used as Nano

electrospray

ionization

(Nano-ESI)

sources.

Additionally,

the

inner

infrastructure of the instrument was also redesigned to improve instrument portability. Figure 1b shows the overview photograph of the CAPI mini-MS redesigned in this work with dimensions of 38 cm×26 cm×24 cm. Design of a miniature ion funnel Since the pressure in the first vacuum stage of the CAPI mini-MS is 1-10 Torr, which is the typical operation pressure range of an ion funnel. Therefore, it is logical to place an ion funnel in the first vacuum chamber to improve ion transfer efficiency from capillary exit to the ion trap. Conventionally, ion funnels are used in lab-scale MS instruments, which have no critical requirements for their sizes, shapes and power consumptions. On the contrary, these aspects must be taken into account when designing an ion funnel for miniature mass spectrometers. In this study, limited by the space inside the first vacuum chamber, the total length of the miniature ion funnel should be less than 40 mm. Each electrode should be as small as possible to minimize the whole dimension of the ion funnel, as well as the power consumption, which is proportional to its capacitance. In an ion funnel design, the spacing between electrodes (s, as shown in Figure 1c), the diameter of last electrode (dmin) and the electrode number (N) are important parameters affecting ion transmission efficiency through the ion funnel. Considering the limited total length of the ion funnel in this work, effects of s and dmin on ion transmission efficiencies were studied and optimized through simulations. As listed in 7



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Table 1, six ion funnels with different configurations were simulated. For all these ion funnels, the electrode thickness (t) and diameter of the first electrode (dmax) were set at 0.3 mm and 8.8 mm, respectively. Ion funnel 1-4 have the same electrode spacing (s = 1 mm) but different diameters of the last electrode (dmin), ranging from 0.5 mm to 2 mm. In comparison, Ion funnel 2, 5 and 6 have the same dmin (1 mm) but different electrode spacings, ranging from 1 mm to 2 mm. The electrode number of these ion funnels were controlled to ensure their total length were less than 40 mm. As shown in Figure 1c, two radio frequency (RF) signals with opposite phase were coupled to the electrodes through capacitances, and two DC signals (DC 1 and DC 2 in Figure 1c) were applied to each electrode by resistances, forming DC potential gradient along the ion funnel x axis. As shown in Figure 1a, the skimmer separating these two vacuum stages has a cone shape with its entrance (vertex) facing the ion funnel. Actually, both orientations (with vertex facing the ion funnel or the ion trap) have been tested, and it is found the current orientation has better signal intensity (details could be found in a later section). All simulations were performed using SIMION 8.0 with an embedded hard-sphere, elastic, ion-neutral collision model to calculate ion trajectories under different conditions. As shown in Figure 2a, the simulation environment was divided into two regions by the skimmer electrode. Ion funnels were located in the first region with a background pressure of 4.3 Torr, and the ion trap was located in the second region with a background pressure of 3.4 mTorr (Note: these pressure values were based on measurements, which will be further discussed in the later section.). The 8


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other parameters configured in simulations are listed in Table 2. Ions were initially positioned in a circular disk (3 mm in radius) with a uniform distribution. Based on an estimation of gas volume removed by the first two pumping stages and the gas flow simulations reported by others,51-53 an estimated average gas flowing speed of 100 m/s was used in the ion funnel region throughout all simulations. The ion transmission efficiencies from plane A to plane B were measured and recorded. Typical ion trajectories were shown in Figure 2a which are the simulation results for ion funnel 2. It should be noticed that simplified fluid dynamic model was used in this study, since the non-uniform pressure distribution in the ion funnel region, as well as supersonic expansion effects and possible turbulences, were not considered. Therefore, simulation results in this study could only be used as guidance in the design process, and more accurate simulation results are expected using realistic fluid dynamic simulation methods.54 Figure 2b shows the simulation results of ion funnel 1-4. Given the diameters of the first and last electrode were dmax and dmin respectively, the diameter of arbitrary electrode (electrode i) could be expressed as di = dmax – (dmax – dmin)/N-1. With the same electrode spacing, the four ion funnels have different ion transmission efficiencies at different RF amplitudes. At any given RF amplitude, ion funnel 2 with dmin = 1 mm is found to be the optimized configuration. With larger openings of the last electrode (dmin), the ion focusing effect may not be strong enough to guide ions through the skimmer (i.d. 0.4 mm) right after the ion funnel. With smaller openings, this last electrode itself blocked ions from passing through the ion funnel. 9



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Subsequently, the effects of electrode spacing were also comparably studied by simulating ion funnel 2, 5 and 6. Compared with ion funnel 2, as shown in Figure 2c, the other two ion funnels have lower ion transmission efficiencies at any given rf amplitude. This could be explained by the fact that ion funnels with larger electrode spacing have weaker ion focusing capability at the same rf voltage. Consequently, ion funnel 2 was chosen as the optimized configuration for the miniature ion funnel, which was then fabricated and used in later experiments. The fabricated miniature ion funnel has 27 electrodes with holes having different inner diameters, decreasing from 8.8 mm (dmax) to 1 mm (dmin), the thickness of each electrode (t) was 0.3 mm and the spacing between neighbor electrodes (s) was 1 mm. All electric signals applied on the ion funnel were provided by a homebuilt electronic board integrated in the mini-MS instrument. Figure 1d shows the overview photograph of the miniature ion funnel, the total length of the ion funnel is only about 35 mm, which could fit well into the first vacuum stage of the mini-MS. As shown in Figure 1d, electrodes of the miniature ion funnel made of stainless steel were mounted on two PEEK bolts and separated from each other by PEEK spacers (1 mm in thickness). A printed circuit board (PCB) was also mounted on the miniature ion funnel to supply all required signals for the ion funnel. Ion funnel capacitance was minimized by cutting out redundant metal materials from the electrodes as shown in Figure 1d insert. With these considerations, the fabricated miniature ion funnel has a capacitance of ~40 pF at a measured frequency of 930 kHz.

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Results and Discussions Experimental optimization of the miniature ion funnel. After geometry optimization through simulation, the fabricated ion funnel was then optimized with respect to the applied electric signals, including the rf signal and DC voltage gradient along the ion funnel x axis. Determined by ion funnel capacitance, the rf signal applied on the miniature ion funnel has a frequency of 930 kHz, at which the ion funnel consume the lowest power consumption of 0.42 W ( rf amplitude = 100 Vpp). DC voltage gradient along the ion funnel was firstly optimized by experiments, in which the DC voltage applied on DC 2 was varied while DC 1 was set at ground. Figure 3a plots the normalized ion abundances of GPRP (m/z 426, 100 µg/mL) at different DC voltage gradients with an rf amplitude of 60 Vpp (solid black line) and 30 Vpp (dashed red line) respectively. Results indicate that a DC voltage gradient of ~10 V/cm could be used as the optimized working parameter for the DC voltage. Effects of rf amplitude on ion transmission efficiency were then investigated using three different analytes: vitamin B (m/z 265), GPRP (m/z 426) and reserpine (m/z 609). All samples were prepared at the same concentration (100 µg/mL), and ionized using nano-ESI. The DC gradient voltage was set at the optimized value of 10 V/cm. Figure 3b plots the relative abundance of ion peaks at m/z 265 (black line), m/z 426 (red line) and m/z 609 (blue line) as a function of the rf amplitude. Ions with different m/z ratios had very similar trends in terms of transmission efficiency at different rf voltages. The increase of ion abundance with increasing rf voltage could 11



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be attributed to the increased ion confinement of the ion funnel. However, energetic ions would experience significant collisional activation and get lost when the rf voltage was too high, which resulted in the decrease of ion abundance. Similar trends were observed in study by Richard D. Smith et al. and were discussed in detail.55 As a result, 60 Vpp was selected and used in later experiments as the optimized rf voltage of the miniature ion funnel. Effects of the skimmer with floated potential were also tested. Result shows (Figure S2) that the best performance was achieved when the skimmer was grounded, which was then chosen as the optimized voltage on the skimmer in later experiments. Sensitivity enhancement. By integrating this miniature ion funnel in the first vacuum stage, ion transfer efficiency from capillary exit to the linear ion trap was expected to increase, which would result in improved detection sensitivity. Rhodamine b samples in different concentrations were first used to characterize the ion focusing aspect of the miniature ion funnel. Ion intensities before and after using the ion funnel were compared, while other parameters of the instrument were kept unchanged. As shown in Figure 4a, more than 10 folds ion intensity enhancements were observed at all three concentrations: 1 µg/mL, 10 µg/mL and 100 µg/mL. Ion focusing effects for different ions were also explored with results shown in Figure 4b. Vitamin B (m/z 265, 100 µg/mL), GPRP (m/z 426, 100 µg/mL), rhodamin b (m/z 443, 100 µg/mL) and MRFA (m/z 524, 100 µg/mL) were tested, and ion intensity enhancements of 12-27 folds were obtained. As shown in Figure 4b, the miniature ion funnel has more ion intensity enhancement for 12


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ions with smaller m/z ratios. This might because lighter ions experience stronger supersonic expansion effect at the exit of the capillary when injected into the first vacuum stage.51,56 Without the help of this ion funnel, light ions would have lower ion transfer efficiency than that of heavier ions. It should be noticed that ion signal intensities were used to characterize the ion transfer efficiency enhancement. Although there might be extra ion losses in the ion trap during the ion trapping and ejection processes, it is reasonable to be used as long as the ion trap operation parameters were kept unchanged among measurements. The CAPI mini-MS integrated with the miniature ion funnel was then characterized in terms of limit of detections (LODs). In experiments, MRFA was tested in the tandem MS mode, and its precursor ions (m/z 524 for MRFA) prior to collision induced dissociation (CID) was used for quantitation. In this experiment, both orientations of the skimmer were tested. As shown in Figure 5, a better signal intensity and lower LOD could be achieved with the skimmer facing the ion funnel. Figure 5b and 5c plots the linear of quantitation curves of MRFA with the skimmer vertex facing the ion trap and facing the ion funnel, and LODs of 0.1 µg/mL and 0.05 µg/mL were obtained, respectively. Compared with the first generation CAPI mini-MS (LOD = 1 µg/mL), a 20 fold sensitivity improvement was achieved when coupling with nano-ESI sources for the mini-MS system. Figure 5d shows the CID mass spectra of MRFA ([M+H]+ 524) at 0.05 µg/mL. MS Resolution improvement. Besides increasing ion transfer efficiency, integration of the miniature ion funnel 13



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also helps improving the mass resolution of the CAPI mini-MS. This is because the background pressure in the second vacuum stage (where the linear ion trap was placed) could be reduced by placing the ion funnel in the first vacuum stage. In the first generation CAPI mini-MS, the distance of the capillary exit from the skimmer was kept at about 10 mm for maximized ion transfer to the linear ion trap. Since there is a pressure drop at the capillary exit, the pressure inside the first vacuum stage is not uniform distributed.57,58 The closer the skimmer is from the capillary exit, the higher pressure it will experience. In other words, more neutral molecules would pass through the skimmer and enter into the linear ion trap, which results in a relatively high background pressure. The background pressure in the linear ion trap was ~6 mTorr in the first generation CAPI mini-MS. Furthermore, it was not possible to lower this pressure using larger pumping system for a miniature mass spectrometer, and thus the instrument had a relatively low mass resolution as reported in our earlier work.40 By placing this miniature ion funnel in the first vacuum stage, the capillary in this study could be placed further away from the skimmer without sacrificing ion transfer efficiency. In fact, the distance between the capillary exit and the skimmer was kept around 30 mm in the second generation CAPI mini-MS. With this setup, background pressure in the second vacuum stage decreased from ~ 6 mTorr to ~ 3.4 mTorr. As a result, better mass resolution was observed. Full width at half maximum (FWHM) of an ion peak was measured to characterize the instrument resolution using GPRP. Figure 6a compares the FWHMs of GPRP at different rf scan rates acquired 14


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using the first and second generations CAPI mini-MS. As plotted in Figure 6, the mass resolution of this second generation CAPI mini-MS was improved by nearly 2 times compared to that of the first generation. As mass spectra shown in Figure 6b, a FWHM of 1.7 was improved to 0.8 at a normal scan mode (4773-4877 Da/s), and from 0.5 to 0.27 at an ultra-scan mode (1590-1625 Da/s). Except buffer gas pressure and MS scan rate, other parameters that would also affect the mass resolution of an ion trap were kept the same, and both instruments (first and second generations of CAPI mini-MS) were working at optimized conditions. For example, rf frequency and MS scan function were not changed between experiments, and high-order fields of the ion trap were kept the same by using the same ion trap.

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Conclusions In this work, a second generated CAPI mini-MS was developed, in which a miniaturized ion funnel was designed to improve both instrument sensitivity and mass resolution. Systematic optimization processes were carried out through simulation and experiments. This miniature ion funnel increased the ion transfer efficiency by more than 10 times, and a LOD of 0.05 µg/mL was achieved when working with nano-ESI sources. With the help of this miniature ion funnel, MS resolution was also improved by about two times by lowering the background pressure in the linear ion trap region. Sensitivity and resolution improvement in this study is an important step towards the practical applications of CAPI mini-MS in the near future.

Acknowledgements This work was supported by MOST instrumentation program of China (2012YQ040140-07), NSF (21475010), BNSF (16L00065) and State Key Laboratory Explosion Science and Technology (YBKT16-17).

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(32) Gao, L.; Cooks, R. G.; Ouyang, Z. Anal. Chem. 2008, 80, 4026-4032. (33) Xu, W.; Charipar, N.; Kirleis, M. A.; Xia, Y.; Ouyang, Z. Anal. Chem. 2010, 82, 6584-6592. (34) Xue, Z.; Chen, Y.; He, M.; Xiong, X.; Fang, X.; Zhao, Y.; Xu, W. Int. J. Mass spectrom. 2016, 397, 1-5. (35) Wei, Y.; Bian, C.; Ouyang, Z.; Xu, W. Rapid Commun. Mass Spectrom. 2015, 29, 701-706. (36) Gao, L.; Sugiarto, A.; Harper, J. D.; Cooks, R. G.; Ouyang, Z. Anal. Chem. 2008, 80, 7198-7205. (37) Li, L.; Chen, T.-C.; Ren, Y.; Hendricks, P. I.; Cooks, R. G.; Ouyang, Z. Anal. Chem. 2014, 86, 2909-2916. (38) Hendricks, P. I.; Dalgleish, J. K.; Shelley, J. T.; Kirleis, M. A.; McNicholas, M. T.; Li, L.; Chen, T.-C.; Chen, C.-H.; Duncan, J. S.; Boudreau, F. Anal. Chem. 2014, 86, 2900-2908. (39) He, M.; Xue, Z.; Zhang, Y.; Huang, Z.; Fang, X.; Qu, F.; Ouyang, Z.; Xu, W. Anal. Chem. 2015, 87, 2236-2241. (40) Zhai, Y.; Feng, Y.; Wei, Y.; Wang, Y.; Xu, W. Analyst 2015, 140, 3406-3414. (41) Zhai, Y.; Jiang, T.; Huang, G.; Wei, Y.; Xu, W. Analyst 2016, 141, 5404-5411. (42) Dodonov, A.; Kozlovsky, V.; Loboda, A.; Raznikov, V.; Sulimenkov, I.; Tolmachev, A.; Kraft, A.; Wollnik, H. Rapid Commun. Mass Spectrom. 1997, 11, 1649-1656. (43) Javahery, G.; Thomson, B. J. Am. Soc. Mass. Spectrom. 1997, 8, 697-702. (44) Guzowski Jr, J. P.; Hieftje, G. M. J. Anal. At. Spectrom. 2001, 16, 781-792. (45) Röttgen, M. A.; Judai, K.; Antonietti, J.-M.; Heiz, U.; Rauschenbach, S.; Kern, K. Rev. Sci. Instrum. 2006, 77, 013302. (46) Voyksner, R. D.; Lee, H. Rapid Commun. Mass Spectrom. 1999, 13, 1427-1437. (47) Liebl, H. Applied charged particle optics; Springer, 2008; Vol. 2012. (48) Shaffer, S. A.; Tolmachev, A.; Prior, D. C.; Anderson, G. A.; Udseth, H. R.; Smith, R. D. Anal. Chem. 1999, 71, 2957-2964. (49) Shaffer, S. A.; Tang, K.; Anderson, G. A.; Prior, D. C.; Udseth, H. R.; Smith, R. D. Rapid Commun. Mass Spectrom. 1997, 11, 1813-1817. (50) Chaudhary, A.; van Amerom, F. H.; Short, R. Rev. Sci. Instrum. 2014, 85, 105101. (51) Gimelshein, N.; Gimelshein, S.; Lilly, T.; Moskovets, E. J. Am. Soc. Mass. Spectrom. 2014, 25, 820-831. (52) Zhou, X.; Ouyang, Z. Analyst 2014, 139, 5215-5222. (53) Zhou, X.; Ouyang, Z. Anal. Chem. 2016, 88, 7033-7040. (54) Mayer, T.; Borsdorf, H. Rapid Commun. Mass Spectrom. 2016, 30, 372-378. (55) Kim, T.; Tolmachev, A. V.; Harkewicz, R.; Prior, D. C.; Anderson, G.; Udseth, H. R.; Smith, R. D.; Bailey, T. H.; Rakov, S.; Futrell, J. H. Anal. Chem. 2000, 72, 2247-2255. (56) Lin, B.; Sunner, J. J. Am. Soc. Mass. Spectrom. 1994, 5, 873-885. (57) Garimella, S.; Zhou, X.; Ouyang, Z. J. Am. Soc. Mass. Spectrom. 2013, 24, 1890-1899. (58) Hagena, O.; Obert, W. J. Chem. Phys. 1972, 56, 1793-1802.

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Figure 1

Figure 1. (a) Schematic and (b) overview photograph of the continuous atmospheric pressure interfaced mini-MS equipped with a miniature ion funnel. (c) Schematic depiction of the miniature ion funnel, and (d) photograph of the fabricated miniature ion funnel.

19



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

Figure 2

Figure 2. (a) Ion trajectories in ion funnel 2 simulated by SIMION 8.0. Ion transmission efficiencies at different rf amplitudes with respect to (b) different diameters of the last electrode (dmin) and (c) different spacing (s).

20


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Figure 3 (b)

Relative Abundance (%)

(a)


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


RF 60 Vpp RF 30 Vpp

100 75 50 25 0

0

3

6

9

12

15

18

100

m/z 265 m/z 426

75

m/z 609

50 25 0

0

30

60

90

120

150

180

RF amplitude (Vpp)

DC voltage gradient (V/cm)

Figure 3. (a) DC voltage gradient effects on ion transmission efficiency. GPRP (m/z 426) was used as the model ion. (b) RF amplitude effects on ion transmission efficiency for ions with different m/z ratios. Vitamin B (m/z 265), GPRP (m/z 426) and reserpine (m/z 609) were used as the model ions.

21



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

Figure 4

Figure 4. (a) Signal intensity enhancement for rohdamine B (m/z 443) at different concentrations. (b) Signal intensity enhancement for ions with different m/z ratios at the same concentration (100 µg/mL).

22


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Page 23 of 26

20000

(a)

(b) Facing ion trap Facing ion funnel

Abundance

15000 10000 5000 0

100 75 50

0.1 µg/ml 25

y = 753.89x + 23.58 R² = 0.9999

0 0

1 µg/ml

10 µg/ml

5

10

15

(d)

100

90

m/z 524

50 25

25

MRFA 0.05 µg/ml

288

75

0.05 µg/ml

20

Concentration (ug/ml)

Abundance

(c)


Figure 5

Relative abundance (%)

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


y = 1057.9x - 83.34

60

271

376

30

489 524 435 453

R² = 0.9987

0 0

2

4

6

8

0 100

10

200

Concentration (ug/ml)

300

400

500

m/z

Figure 5. (a) Ion abundances of MRFA (m/z 524) comparatively recorded with the skimmer assembled at two different skimmer orientations. The linear quantitation curves for MRFA with a LOD of (b) 0.1 µg/mL and (c) 0.05 µg/mL when the skimmer vertex facing the ion trap and ion funnel, respectively. (d) Tandem mass spectrum of MRFA ([M+H]+ 524) at 0.05 µg/mL.

23



Figure 6

2

1

GPRP (m/z 426) 0

0

2000

4000

6000

8000

100

4773 Da/s

0.5

50

1625 Da/s 0.27

50

422

424

426

428

430

m/z

Scan rate (Da/s)

1.7

0 100

0

10000

1590 Da/s

6 mTorr

(b)

3.4 mTorr 6 mTorr

4877 Da/s

3.4 mTorr

3


(a)

FWHM (Da)

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

Page 24 of 26

0.8

422

424

426

428

430

m/z

Figure 6. Mass resolution enhancement by the miniature ion funnel. (a) The FWHMs of GPRP (m/z 426) at different rf scan rates acquired using the first and the second generation CAPI mini-MS. (b) Typical mass spectra recorded in the normal scan mode (4773-4877 Da/s) and the ultra-scan mode (1590-1625 Da/s).

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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


Table 1: The geometrical parameters of different simulated ion funnel configurations Ion Funnel configurations

t (mm)

dmax (mm)

dmin (mm)

S (mm)

N

Total length (mm)

IF 1

0.3

8.8

0.5

1

27

35

IF 2

0.3

8.8

1

1

27

35

IF 3

0.3

8.8

1.5

1

27

35

IF 4

0.3

8.8

2

1

27

35

IF 5

0.3

8.8

1

1.5

20

36

IF 6

0.3

8.8

1

2

13

30

Table 2 The parameters used in SIMION simulation Related Conditions Pinhole parameters

Environmental parameters

Simulated ions initial conditions

Electrical parameters

Detail Description Inner diameters Thickness Distance from IT endcap Ion funnel pressure Ion trap pressure Temperature Gas mass (amu) Gas velocity Ion source Radius Particles number Particles mass (amu) Particles charge Initial kinetic energy RF frequency RF amplitude DC potential gradient

Values 0.4 mm 2 mm 3 mm 3.7 Torr 3.7 mTorr 273 28 100 m/s Circle distribution 3 mm 200 500 +1 0.1–1.9 eV (uniform distribution) 900 kHz 40, 60, 80 V0p 10 V/cm

25



TOC only

Mini-MS with Continuous API

1

without ion funnel

LOD (µg/ml)

LIT

with ion 0.05 funnel

Nano-ESI Skimmer

Diaphragm Pump

3

Turbo pump 10 l/s

FWHM (Da)

Mini Ion Funnel

Detector

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

Page 26 of 26

without ion funnel 2

1

with ion funnel 0

0

2000

4000

6000

8000 10000

Scan rate (Da/s)

26


Mini Mass Spectrometer Integrated with a Miniature Ion Funnel

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