VIII. QUADRUPOLE ION TRAPS: AN ION TRAPPING INST. A. BASIC DESIGN (REF: JMS, 1997, 32, 351)

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1 VIII. QUADRUPOLE ION TRAPS: AN ION TRAPPING INST. A. BASIC DESIGN (REF: JMS, 1997, 32, 351) The trap consists of a ring electrode (internal radius is r 0 ) and two end caps separated by z 0.; all internal surfaces are hyperbolic. RF (and sometimes DC) voltages are applied to the ring electrode, establishing a quadrupolar electric field. Force on the ion increases as displacement from trap center increases; i.e., there is a restoring force along r when there is a repelling force along the z axis. Buffer gas (~ 1 mtorr) is added to damp stable ion motions and bunch ions at the center of the trap, where ejection occurs by increasing the rf amplitude, pushing ions in increasing m/z through the end-cap holes. Typical operating conditions: r 0 ~ 1 cm; f ~ 1 MHz (applied to ring electrode) Amplitude of rf (V) in range of 1000 to 10,000 V f 0 = 0.5 to 1 MHz Scan rate 5000 u/sec (normal); 500 u/sec (zoom scan) He press: 1 mtorr CI gas (if used):.01 mtorr Ionization gate: I ms and adjustable Ion source: both internal (EI and CI) and external (ESI). 43

2 B. ELECTRIC FIELD P = P 0 2 (x r 2 + y 2 2z 2 ) 0 Since x = r cos, y = r sin, and z = z, then P = P 0 r 0 2 (r 2 cos 2 + r 2 sin 2 2z 2 ) Since cos 2 + sin 2 = 1, then P = P 0 2 (r r 2 2z 2 ) 0 Where r 0 is internal radius of the ring electrode. This equation gives the potential for any point within the quadrupolar field of the trap. In the ideal trap r 2 0 = 2z 2 0 C. EQUATIONS OF MOTION Since P 0 = U + V cos t as defined previously for the quadrupole, then Fz = m Ø2 z Øt 2 = q ØP Øz =+q 4z r 0 2 (U Vcos t) Fr = m Ø2 r Øt 2 = q ØP Ør 0 = q 2r r 0 2 (U V cos t) and m Ø 2 z, and Øt 4q 2 2 (U V cos t)z = 0 r 0 m Ø 2 r Øt 2 + 2q r 0 2 (U V cos t)r = 0 In a manner identical to that of the quadrupole mass analyzer, we can obtain solutions for the equations of motion and determine: az = 16qU and m(r z 02 ) = 2a r qz = 2 8qV m(r z 02 ) 2 = 2q r Usually, we can ignore az and ar because all commercial ion traps do not use any DC potential, which is proportional to U. The operation of the ion trap is along the qz axis. Note that commercial traps are stretched such that the value of z 0 is increased by ~10% or more so that there is no longer a purely quadrupolar geometry. The equations cannot be simplified further as r 2. 0! 2z

3 D. STABILITY DIAGRAMS As for the linear quadrupole, the solutions to the Mathieu equation are of two classes: (1) periodic and stable and (2) periodic and unstable. Note the strong similarity of this stability diagram with that of the linear quadrupole. Ions can be stored in the trap if their trajectories are stable in r and z simultaneously; that is where the r-stable and z-stable regions overlap, as seen in the next figure. Here one sees the two regions where ion trajectories are stable (labeled A and B). Region A is chosen because it allows for U to be zero or nearly so and for V to have reasonable values (not excessively high voltages). Blow up of region A is shown in the next figure. 45

4 This is the stability region in (a z, q z ) for region A in the previous figure. The iso z and r are shown and explained below. The q z axis intersects the z = 1 where q z = 0.908, which is q max in the mass-selective instability mode. This means that stored ions can be scanned out (from low to high m/z) by raising V (moving along the q z axis). Upper m/z for 1-cm trap at q z = is 650 and if r 0 is decreased to 7 mm, the value is 850. Improvements in upper m/z are described later. E. SECULAR FREQUENCIES The 3-D representation of an ion trajectory has the appearance of a Lissajous curve. There are not only fundamental frequencies but also higher order (n) frequencies. These frequencies are given by the eqns below: u,n =(n u) for pos values of n where a u + q u

5 E. OBTAINING SPECTRA: ION MOTION SIMULATION 1.To manipulate the ions, one must be able to store them in the trap. (Taken from web site of R.G. Cooks at Purdue) 2. The ions are then cooled by collisions with helium gas and focused to the center of the trap. This focusing is very important as when ions are ejected, they start from a relatively sharp point, where they are bunched. 47

6 3. A mass spectrum is then scanned: Ions of increasing mass are successively made unstable and ejected from the trap owing to an increase in V (the amplitude of the rf). With a standard sized trap, this gives an upper m/z limit of 650. Higher m/z limits can be achieved by using resonant excitation (see below). 4. MS/MS and extended mass use resonant excitation: Ions can be transl. excited by applying a suppl. oscillating potential (up to 7 V) across the end caps. This excites the axial motion, ejecting ions from the trap in precursor-ion selection for MS/MS, collisionally exciting (lower amplitude) for MS/MS, or exciting to promote endothermic ion-molecule rxs. MS/MS can be done to MS

7 Resonant excitation at lower frequencies also extends the m/z range of the ion trap (see below). F. CALCULATIONS 1. q z determines lower mass limit: For ions of m/z 200 in a trap where r 0 = 1.0 cm and z 0 = cm, U = 0, V = 1130 V (0-p), and f = 1.05 MHz, 8qV q z = m(r z 0 2 ) 2 Or q z = The low mass (LM) cut off is given by: m LM m = q z q z LM = since q z is proportional to m. m LM = 99. This means that when 1130 V are applied to the trap, only ions with m/z > 99 will be stored. This shows a limitation of the method: in MS/MS, not all ions will be stored in the trap, and the lower mass region of the product-ion spectrum will be missing. 2. β z and ω z : a u + q u 2 From 2, a q z of 0.45, β z = 0.32 (recall that a z is zero). For m/z 2000, q z =.045 and β z = Where are these on the stability diagram? Now we can calculate a fundamental( n= 0) axial secular frequency, ω z. Recall that u,n =(n u). Therefore, when β z =0.32, ω z = 1,050,000 rad/s or 167 khz. 3. Upper m/z: The upper m/z limit will be for an ion having a q z of 0.90 for the maximum rf amplitude (V = 7340 V), or m/z ~ Extended m/z range: Obviously, for LC/MS, we need an upper m/z > 650. An ion of m/z 1300 will have a q z of 0.45 and remain trapped. The ω z for this ion is 167 khz (see #2 above). If we excite with a low amplitude oscillating voltage of 167 khz applied to end caps, then this ion could be ejected if the maximum rf amplitude (V) is applied to the ring. If one used a q z of (ω z = 16.7 khz), the upper m/z limit would be 13,000. The ac applied to the end caps causes new regions of instability to be 8qV created, thus extending the mass range. Given that m max = can also extend the m/z range by: lowering, 49 q eject (r z 0 2 ) 2, one

8 increasing V, reducing r 0 (smaller trap). Recall the is fixed at q eject 5. Mass Resolving Power: The narrowest peak width in commercial instruments is ~0.2 Da, obtained by a slow ( zoom ) scan (rate can be 1000 times slower). G. EXTERNAL SOURCES The most successful instrument has been a trap with an external ESI source: The quadrupoles thermalize ions and focus them to a center trajectory so that they can be injected into the trap. This also has been done with MALDI, but only in a research setting. Note that high vacuum is not needed. H. AUTOMATIC GAIN CONTROL Space charge and unwanted ion-molecule reactions in trapping instruments can be a problem. To control number of ions for each scan (called a micro scan), two ionization stages are used. The first is of a fixed duration (e.g., 0.2 ms), and the ions detected. This ion signal is then used to calculate an optimization ionization (or admittance) time to fill the trap. The computer system keeps track of these times so the spectra can be normalized. I. SUMMARY Simple, robust, relatively inexpensive, easy to operate Fast scanning, detects sequentially all ions (except low m/z) upper m/z limit on commercial instruments Capable of Ms n but low m/z ions not trapped Commercially available as GC/MS and LC/MS (low voltage) Sensitivity comparable to that of most contemporary instruments Medium RP available but no exact mass Fourier transform possible. 50

9 IX. FOURIER TRANSFORM ION CYCLOTRON RESONANCE MS (FT-ICR-MS, FTMS) (MSR, 1998, 17, 1; JMS, 1996, 31, 1325; SCIENCE, 10/19/84) A. NATURAL MOTIONS OF IONS IN MAGNETIC TRAP Figure shows the motion of an ion in a B field in a plane perpendicular to the page. One motion is for + ions the other for - ions. Equating centrifugal force and that due v r = c = qb m where c = 2 f and f is in Hz. to the B field, we obtain: 2 mv r = qvb where v is the velocity (m/s) in xy plane. So we may write: 1. What is the radius of the circular Motion? mv 2 2 = kt r = qb 1 2mkT r Since r = mv and, then. At 3 tesla for m/z 100, qb 0.08 mm. Note that ions of greater m/z will have larger orbits at any T. 2. What is the KE of an ion for a given radius of trajectory? Since v = qbr and mv 2 m, 2 = KE KE = q 2 B 2 r 2 2m. If the radius is known, the KE of the ion can be calculated. Note that energy goes up with the square of radius and B field and decreases with increasing mass. For example, an ion of m/z 1000 orbiting at 1.0 cm in a B field of 7.00 Tesla has an energy of 240 ev (compare to ~50 ev for ions in quad.) 3. Ions stored and Detected in a Penning trap. Ions can be stored in a cubic trap, shown in the lower part of the figure on next page. Ions are constrained to the xy plane by the B field and are trapped in that plane. To contrain the ions along z, small trapping voltages (~ 1 V) or placed on the trapping plates. Ion excitation is done by applying to the excitation plates an alternating voltage with a frequency equal to the natural cyclotron frequency (qb/m) of the ion. This frequency is in the khz to low MHz range. The excitation imparts coherent motion to the ion packet. 51

10 Detection is done by using the receiver (detection) plates. As the ion packet nears the receiver plate, an image current is induced on the plates (electrons in the plate are attracted toward positive ions). That alternating image current across the shunt resistor give an image voltage (V = ir) for detection. 4. Three basic motions in the trap as result of E field: Because ions are held along the z axis by a small trapping field, they oscillate along z. The frequency in the trap field is that of a harmonic oscillator and given by: T = 2 fv T = Ez (Trapping) where a is the width along z axis, V T is the trapping voltage, and α is a geometric constant (1.3869), and Ez = 4qV T a. For an ion of m/z 100 in a m 3-T field and a 1-V, 1-cm cubic trap, T = 12 khz, whereas c = 460 khz. The three important forces on ions in a FT mass spectrometer cell are centrifugal (an outward force), magnetic (an inward force), and electric (due to the trap voltage--outward in the xy plane). We may balance these forces: 52

11 mv 2 r = qb 0 v qe 0 r The electric field complicates the cyclotron frequency: + = qb + q2 B 2 4mqE 0 2m (Cyclotron) Compute the value of + when the electric field goes to zero! When ions are off center, they are in a EXB field, and they will undergo a low frequency oscillation around the center of the trap: magnetron motion. = qb q2 B 2 4mqE 0 2m (Magnetron) Compute the value of when the electric field goes to zero. B. EVENT SEQUENCE AND FOURIER TRANSFORM 53 The quench is accomplished by raising the voltage on one trapping plate, causing ejection of any ions in the trap. Ionization could be an electron-beam pulse (EI), a laser beam pulse (MALDI, MPI), or injection of ions from external source. The time between ionization and

12 excite can be used by ion-molecule reactions, CID, ion spectroscopy, etc. Excitation is by a pulse at one frequency, a rapidly scanned frequency ( chirp ), or by selected waveform inverse FT. Figures a and b show that a rectangular waveform can be used by excitation. The narrower the waveform (pulse), the wider the range of excitation, as shown by the FT. Subfigure c shows a chirp, i.e., a rapid scan from low to high freqency, excited all ions have corresponding cyclotron frequencies. Figures d and e show a tailored excitation done by SWIFT. Figure e shows how ejection of some frequency (mass) range can be implemented. One could also use a single frequency to excite one ion only. The outcome of excitation can be a prelude to detection, MS/MS via collisional activation, or ejection (called double resonance). 54

13 C. MULTICHANNEL ADVANTAGE An important feature of FTMS is that the signal output (the sum of the cyclotron frequencies of all the excited ions) contains all the spectral information in the time domain. Transformation to the frequency domain gives a complete mass spectrum of all the excited ions (f = 2πqB/m). The signal decays (is transient) due to collisions of the excited ion packet with background gas. D. HIGH RESOLVING POWER AND RELATION TO S/N: Besides ion trapping, the most notable feature of FTMS is its high mass resolving power. Note that the longer the transient that is sampled, the higher the mass resolving power (the more certain is the frequency or the more narrow the peak width). Further, as resolving power increases, so does peak height, giving an interesting phenomenon that both resolving power and S/N are improved 55

14 simultaneously, but at the expense of time of observation. Besides long observation time, one needs low pressure. High resolving power detection of gramicidin S for ions produced by ESI. Usually resolving power is computed by m/ m where m is the width at half height (peak shapes tend to be Lorenzian, and broadened artificially at the base). Note the wide separation of isotopic peaks. E. FACTORS DETERMINING RESOLVING POWER The length of the transient is the principal factor that determines RP. One wishes to have a long transient--therefore, low pressure and long observation time are needed. 1. Pressure in the trap: R [ k qb mp( /n) where k is 8.6x10-10 u. cm 3 torrt -1 s -1 and /n is 1x10-9 cm 3 s -1 molecule -1, q is mrp expressed as units of charge (1, 2,...), and m as u. The term B 0.86 for +1 or -1 ions. For example, if a resolving power (R) of 50,000 is sought at 1.2 T for m/z 200, then P ~ 1x10-7 torr. 2. Observation time: R [ kqbt m Where k = 1.3x10 7 u.t -1 s -1 and charge is +1, 2,... Note that R is inverse to pressure and directly proportional to observation time. For example, if R = 1,000,000 is sought for an ion of m/z 100 at 3 T, 56

15 then t > 2.6 s, provided the pressure is sufficiently low to allow the transient decay to last for the required time. 3. Computer limitations: How many data points are needed if R = 1,000,000 is sought for an ion of m/z 100 (f = 460,000 Hz)? 920,000 points are needed to satisfy the Nyquist theorem: 920,000 pts/s x 2.5 s (see #2 above) = 2.3 million points or 2.3 Mbytes of fast memory. If we start the scan at m/z 50, then we need 4.6 million points (the number of points is determined by the lowest m/z, which has the highest frequency). If computer memory size becomes a problem, then turn to the heterodyne detection. Consider f 1 = 461,000 Hz and f 2 = 460,000 Hz. The difference frequency is 1000 Hz, and multiplied by 2 is 2000 Hz (to satisfy Nyquist) pts x 2.5 s = 5000 pts or 5K of memory. What is sacrificed is mass range. 57

16 F. UPPER MASS LIMIT (CRITICAL MASS) mc = qb 2 a 2 8V eff Where a is the width of a cubic trap, V eff is the effective trap voltage, and is a geometry constant depending on trap design (1.3869). For a 2.5-cm trap in a 13-T field, and a trapping voltage of 1 V, the critical m/z is ~920,000. Thermal motions of ions also determine the upper m/z (no consideration of trap field), and this is more limiting: mupper = q2 B 2 r 2 2kT G. DYNAMIC RANGE Dynamic range is always a problem with trapping instruments, owing to space charge. In FTMS, image current can be detected for ions. The trap saturates at ions (depending on trap volume and B). Therefore, the dynamic range is Improvements can be made for minor ions by ejecting major ones and repeating the experiment. H. ION STORAGE TIME t 1/2 = (ab) 2 P(V T ) Where is polarizability, is reduce mass (m 1 m 2 /(m 1 + m 2 ). We can detect 30% of the ions after 13.5 hr at P = 10-8 torr, 4.7 T, and ion m/z of 18. I. EXACT MASS MEASUREMENT One can measure frequency to 1 ppb. In principle, m/z measurements should be equally precise and accurate. Problem is the trap field, which affects ion frequency in ways not yet completely understood. The calibration is two-point, and state-of-the-art is ppm (at best 0.1 ppm) although a thorough evaluation has not been done (can be derived from the equation showing balance of electrical, magnetic, and centrifugal forces. 58

17 J. MS/MS IN FTMS ( TANDEM IN TIME ) Translational excitation is simply another event in the FTMS sequence. Instead of translational excitation, one can also add internal energy via an IR or UV laser or via collisions with surfaces. 1. Collisions via cyclotron excitation: Excitation makes use of ω = qb/m. Problem is that the laboratory energy varies with m/z of parent and decreases as m/z increases. 2. Sustained off resonance irradiation and related methods: SORI uses an excitation frequency that is slightly off resonance, allowing ions to be excited in deexcited--the ion orbit repeatedly increases then decreases In very-low-energy excitation, the excitation is on resonance but the phase alternates between 0 and 180 o. In multiple excitation for collisional activation, the parent ions are excited briefly and then allowed to relax by collisions. In each method, a collision gas (He, Ne, etc) is pulsed to the torr range and then turned off for mass analysis. SORI is most common. 3. IR Multiphoton Dissociation (IRMPD). An IR laser dumps in many photons as the internal energy is raised slowly by a ladder-climbing means. Available on commercial instruments. 59

18 4. Electron-Capture Dissociation (ECD) Low energy electrons for a filament (as in EI) are captured by multiply charged ions (e.g., from proteins) to form a hypervalent species. Fragmentation occurs at many sites of the multiply protonated species and is thought to be nonergodic (not governed by QET). K. IMPROVING PERFORMANCE Current research is directed at: making the electric fields in the cell more ideal for both excitation and detection, using external sources and intermediate storage devices to decouple ion source and mass analyzer, cooling ions for focusing to center of cell and for ion-molecule reactions and improved mass analysis, developing new means of MS/MS. 1. Lowering background pressure with dual cell: Ions are made in the high pressure region on left, where ion-molecule reactions or CAD are conducted. The low-pressure region on the right is for high RP mass analysis. Just prior to mass analysis, ions are allowed to partition on both sides of the trap (conductance limit at zero volts), and then the voltage on the conductance limit is increased, isolating half the ions in the low-pressure trap on the right, where mass analysis takes place. The ions left on the left are discarded. 2. External ion source. Here the source and mass analysis are nearly completely decoupled. Any ion source can be used, and the ions are transmitted via quadrupole or electrostatic lens into the ion trap. Ions are stopped in the cell by gated trapping. Once the ions are stored, mass analysis or other experiments 60

19 (MS/MS, ion-molecule reactions) can be conducted. Most commercial instrument now use this strategy--see figure below. Notice that the single magnet can be equipped with MALDI (on left) and ESI (on right) simultaneously, although the two ionization modes are used separately and independently. 3. Increasing inward force on ion (minimize trap field): The magnet force is inward but the trapping electric field provides an outward force, which works against B and leads to poor performance (note the radial force in the equipotential field lines). Ion a is subjected to only an inward trapping force whereas ion b experiences an upward and inward force. Problem with cubic and cylindrical traps. Efforts are underway to minimize upward or radial forces. Elongated cells (McIver) Screened cells (Marshall) 61

20 Hyperbolic cell (like ion trap) (Rempel and Gross) Example cells (traps) used in FTMS. (a) cubic, (b) cylindrical (can also be open with trapping plates replaced by trapping rings), (c) hyperbolic, (d) multisection (e.g., dual), (e) elongated and screened. E = excitation plate or electrode, D = detector plate, T = trap plate, S = screen. 62

21 Compensated cell (Rempel and Gross) Exploded view of compensated trap. 1.7 V is applied to outer trapping electrode whereas 1.0 V is applied to inner electrode. The field lines from 1.7 to 1.0 give a compensating inward force for ions such as b in the previous drawing. 4. Cooling ions translationally and internally: Especially needed for MALDI-produced ions formed at high translational energy (750 m/s, in a micro supersonic expansion), and for remeasurement strategies to relax excited ions to center of trap for re excitation. Gas pulsing (limited to 10-5 torr) Comatrix that decomposes to give high local P for MALDI Active cooling by quadrupole axialization: Use the four, nontrapping plates. Ions absorb at 2ω +, 2ω -, and (ω + + ω - ). At the latter frequency, ion motion is converted between pure cyclotron and pure magnetron. During the cyclotron mode, collisions with buffer gas cause motion to damp and ion cloud collapses. Mass range is a factor of 2 times. Active cooling by rf-only mode event: By applying 1 MHz to the trap plates, the Penning trap is converted into a Paul trap (ion trap). In the Paul mode, pressure can be increase to mtorr range, promoting ion collisions and collapse of ion cloud to center of trap. Useful for ion chemistry studies where intermediates can be stabilized by collisions. 63

22 More on Compensated traps Below is the cyclindrical cell used in the Ion Spec FT mass spectrometer. The end cylinders serve the same function as flat trapping plates in the cubic or rectangular traps. The center section is comprised of four segments: two excitation electrodes and two receiver electrodes. Note how laser and electron beams can be easily admitted to the trap from the right and intersect in the center the trapped ions. Below is the compensated cylindrical trap, designed by D. Rempel. The center section is as before except slightly shorter. Three addn ring electrodes are added, as per the design, and to these electrodes are applied voltages, also calculated according to the design, to shim the electric fields in the trap. The outcome is higher RP (3-5 X) and sensitivity (10 X)

23 L. TRAP/FTMS: Ions are stored in linear ion trap (similar to quadrupole ion trap but with 10X more capacity). There they can be thermally relaxed, focussed to trap center, and made ready for injection into FTMS trap for high resolving power and accurate mass. Following injection into FTMS, the linear trap is filled again, and MS/MS experiments can be done in a data-dependent manner, giving 5 product-ion spectra per second. FTMS is used for accurate mass measurements with a transient just under 1 sec, giving a RP of 100,000 at m/z 400. RP can be increased by increasing the observation time for transient. M. SUMMARY Works at low pressure (10-8 torr) Relatively simple mass analyzer but complicated by external sources and high-pumping demands Traps ions for minutes; good for ion chemistry, spectroscopy Nondestructive detection (remeasurement) Interfaces well with pulsed ionization (lasers)--multichannel Highest mass resolving power, but needs time for transient Requires expensive and maintenance-demanding magnet High mass limit (critical mass) Subject to space-charge effects, giving low dynamic range (improvable by ejecting unwanted ions) Highest accuracy m/z and can be improved (improvement not likely for sectors or TOFs) 64

24 X. ORBITRAP (A. Makarov, Anal Chem, 2006, 2113; rev JMS, 40, 430) A. DESIGN OF KINGDOM TRAP The ions are injected with velocity perpendicular to long axis of the Orbitrap (z-axis). Injection at a point displaced from z = 0 gives ions pot energy in z. Injection at this pt on the z-potential analogous to pulling back a pendulum bob and then releasing it to oscillate... Ion motion along z is an harmonic oscillator and is completely independent of radial (r) and angular (w) motion. Ion mass/charge ratio m/z is simply related to the frequency of ion oscillation along the z-axis. = [(z/m) k]

25 B. DESIGN OF INSTRUMENT The instrument is coupled with a linear ion trap to produce a high resolving power tandem instrument, interfaced to ESI. C. ACQUISITION OF MASS SPECTRUM Mass spectra are found in a time-domain, transient decay that contains all the ion frequencies. When transformed to the frequency domain, one has a mass spectrum. 66

26 Figure. Transient and mass spectrum of bovine insulin (MW ~5700). Mass calibrants, separated by 100 m/z, are also seen in the spectrum. D. MASS RESOLVING POWER RP determined by acquisition time (like FTMS). Commercial instrument has RP of 40,000 at m/z 400. Limited by pressure and imperfections in the machining. In MS/MS mode, can obtain high RP for precursor and product ions and accurate m/z in both modes! The spectrum is that of vancomycin. Note good agreement between calc and exp 67

27 isotope patterns. High RP and accurate m/z available for product ions in fast scanning. E. ACCURATE MASS Accurate m/z with a two point calibration is ~ 2 ppm. Long-term (days) is ~ 5 ppm, indicating that calibration is not needed for every spectrum. The accuracy remain high for 1,000,000 ions stored in trap (good dynamic range) F. S/N, TRANSMISSION, & DETECTION LIMIT Transmission from linear ion trap to orbitrap is 30-50%, lower for higher m/z ions. S/N = 4 for ~ 20 ions stored in the orbitrap. Detection limit for bradykinin (peptide) ~ 4 attomol--see figure; [Bradykinin] = 3 nm. G. APPLICATIONS LC/MS/MS for proteomics, metabolomics, std mass spectrometry. Various modes of ion activation--in ion trap or in the C trap. High RP for product ions (RP ~ 40,000 at m/z 400), but the RP is inverse to m/z and time of acquisition just like the FTICR. Question: is this the instrument to couple with high performance UPLC where, in peptide analysis, the chromatographic peaks are a few secs wide? 68

28 Hyperbolic quadrupole mass filter precise selection of precursor ions and outstanding ion transmission Q-Exactive Orbitrap Mass Spectrometer Orbitrap mass analyzer unrivaled mass resolution and unmatched spectrum quality S-lens ion source excellent ion transmission for enhanced sensitivity C-trap premier in-spectrum dynamic range HCD collision cell higher fragmentation efficiency for unsurpassed MS/MS spectra quality Carbofuran Formetanate 100 C12H15NO3 C11H15N3O2 M+H+ = M+H+ = R=17,500 R=35,000 R=70,000 R=140, Relative Abundance m/z m/z m/z m/z Nominally isobaric pesticides carbofuran and formetanate are unresolved or only poorly resolved at the highest resolutions available in Q-TOF instruments. The higher resolutions easily achieved by the Q Exactive instrument clearly resolve analytes from complex matrix interferences without sacrificing sensitivity. 3