Agilent Time-of-Flight Mass Spectrometry Manual
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1. 10 100 1000 10000 Sample Amount pg Figure 5 lons per transient as a function of sample amount showing TDC limitations Time of Flight Mass Spectrometry resolving power then unless the signal from the detector has returned to below the threshold point the second ion is unable to trigger the dis criminator see Figure 6 This phenomenon and the associated reset time of the discriminator and counter are called TDC dead time TDC dead time can have a significant effect in attempts to accurately measure average ion arrival times If a significant number of ions arrive at the detector during the TDC dead time then a shift in the average of the arrival distribution occurs The shift in the measured ion arrival time is always to shorter arrival times because it is always the sec ond ion to arrive in a given transient that is dropped The shift towards shorter apparent arrival time directly translates to a smaller mass value When attempting to measure mass values to the part per million accuracy even a few ions missed can have a substantial effect The discriminator used on TDC systems also introduces a third problem The arrival of each ion produces a peak with measurable width With an ADC system the peak is profiled with multiple points within a single transient These points can be subjected to mathematical centroiding to cal culate the arrival time with high accuracy Cen troiding allows calculation of the ion a2. 1 2 3 4 5 Agilent Technologies voltage applied to the rods creates electromag netic fields that confine ions above a particular mass to the open center of the rod set The ions are propelled through this first octopole ion guide by the momentum retained from being drawn from atmospheric pressure through the sampling capillary As the ions transit the first octopole they also pass into the third stage of the vacuum sys tem where the pressure is now low enough that there are few collisions between the ions and gas molecules Ions exiting the first octopole ion guide immediately enter the second octopole ion guide in the fourth vacuum stage The second octopole ion guide is similar to the first but carries a lower direct cur rent DC potential It accelerates the ions The second ion guide is driven by an RF power ampli fier operated at 5 MHz The high 5 MHz frequency is key to achieving maximum ion transmission over a wide gt m z 100 m z 3000 mass range Vacuum stages Figure 1 lon source ion optics and mass filter from the Agilent LC MSD TOF an API oa TOF mass spectrometer Time of Flight Mass Spectrometry In the fourth vacuum stage the ion beam leaves the second octopole ion guide and enters the beam shaping optics An ion focus lens and DC quadrupole shape the beam to achieve optimal parallelism and size before it enters the time of flight mass anal yzer The more parallel the ion beam the higher
3. at various flow rates e Atmospheric pressure chemical ionization APCI e Atmospheric pressure photoionization APPI e Atmospheric pressure matrix assisted laser desorption ionization AP MALDI a Agilent Technologies Time of Flight Mass Spectrometry Ions from these sources can be introduced into the mass spectrometer vacuum system via a common atmospheric sampling interface Figure 1 depicts the Agilent LC MSD TOF an oa TOF mass spectrometer Ions produced in the source are electrostatically drawn through heated drying gas and then through a sampling capillary into the first stage of the vacuum system Near the exit of the capillary is a metal skimmer with a small hole Heavier ions with greater momentum pass through the skimmer aperture Most of the lighter drying gas nitrogen molecules are pumped away by a vacuum pump The ions that pass through the skimmer and enter the second stage of the vacuum system are imme diately focused by the first of two octopole ion guides An octopole ion guide is a set of small par allel metal rods with a common open axis through which the ions can pass Radio frequency RF lon mirror SSS Ct m Vacuum HPLC walls m inlet Skimmer Nebulizer gas inlet Octopole Capillary ion uides DC Nebulizer quad Focus lens Slits Detector Analyte lon pulser N Heated Signal drying gas Flight tube
4. the resolving power that can be achieved After the ions have been shaped into a parallel beam they pass through a pair of slits into the fifth and last vacuum stage where the time of flight mass analysis takes place Because the mass of each ion is assigned based on its flight time the background gas pressure in this stage must be very low Any collision of an ion with residual back ground molecules will alter the flight time of the ion and affect the accuracy of its mass assignment In the time of flight mass analyzer the nearly par allel beam of ions first passes into the ion pulser The pulser is a stack of plates each except the back plate with a center hole The ions pass into this stack from the side just between the back plate and the first plate Scintillator hv es Optical lens 700V Overall gain 2x10 Photomultiplier tube PMT Ground Agilent Technologies To start the ion s flight to the detector a high voltage HV pulse is applied to the back plate This accelerates the ions through the stack of pulser plates The ions leave the ion pulser and travel through the flight tube which is about one meter in length At the opposite end of the flight tube is a two stage electrostatic ion mirror that reverses the direction of the ions back towards the ion pulser The two stage mirror has two distinct potential gradients one in the beginning section and one deeper in the mirror This i
5. expected mass The magnitude of this effect can be estimated by using a simple weighted average calculation 1 Aobs a Acontaminant 2Abd contaminant Abd contaminant Abdsample where Aobs is the observed shift in mass in ppm Acontaminant iS the mass difference between the sample and contaminant in ppm Abdcontaminant and Abdsampie are the mass peak heights or areas of the contaminant and sample By way of example for a resolving power of 10 000 a mass difference between the sample and contaminant of 50 ppm and relative mass peak heights of 10 1 sample vs background the observed mass shift would be 50 x 1 1 10 or about 5 ppm There are a number of ways to minimize chemical background First the Agilent LC MSD TOF has a sealed ion source design that minimizes contami nation from the laboratory air Second very high purity HPLC solvents should always be used Third a regular systematic cleaning program for the HPLC and the MS ion source should be fol lowed These precautions help ensure the highest quality mass measurements Agilent Technologies Dynamic Range Dynamic range can be measured in various ways Probably the most exacting definition for mass spectrometry is the in scan condition This is the dynamic range within a single spectrum defined as the ratio in signal abundance of the largest and smallest useful mass peaks Even when restricted to the in scan definition of dynamic range t
6. Time of Flight Mass Spectrometry Technical Overview John Fjeldsted Agilent Technologies Introduction Time of flight mass spectrometry TOF MS was developed in the late 1940 s but until the 1990 s its popularity was limited Recent improvements in TOF technology including orthogonal accelera tion ion mirrors reflectrons and high speed electronics have significantly improved TOF resolution This improved resolution combined with powerful and easy to use electrospray ESI and matrix assisted laser desorption ionization MALDD ion sources have made TOF MS a core technology for the analysis of both small and large molecules This overview describes e Basic theory of operation for an orthogonal acceleration time of flight oa TOF mass spectrometer e Flight time and the fundamental equations for TOF mass analysis e TOF measurement cycle e Relative advantages of the two most common TOF digitizers analog to digital converter ADC and time to digital converter TDC e Theoretical and practical limits to mass accuracy e Dynamic range considerations Basic oa TOF MS Theory of Operation While an orthogonal acceleration time of flight mass spectrometer can be interfaced with many types of ion sources this discussion will focus on the use of an oa TOF MS with atmospheric pres sure ionization API sources There are several types of API sources that can be used including e Electrospray ionization ESI
7. a given mass in a single transient The LC MSD TOF auto tune software targets the detector gain for a mean ion response of five counts In a single transient the ADC with 8 bits or 255 counts can therefore measure up to 50 ions for a given mass Time of Flight Mass Spectrometry Practical considerations limit both TDC and ADC systems with regards to the upper limit for which accurate mass measurements can be achieved For a TDC system long before the level of one ion for a given mass per transient is reached substantial mass shifts are observed Deadtime correction algorithms compensate for this but these correc tions are effective only up to some fraction of this theoretical limit typically 0 2 to 0 5 ions tran sient Both ADC and TDC systems when used to make measurements on rising and falling chro matographic peaks need to allow for a safety buffer of a factor of two This is because the chromatographic peak may be rising into satura tion even while the average of the 10 000 tran sients used to make the final mass measurement is at only the 50 level Table 3 summarizes both theoretical and practical dynamic range limits for ADC and TDC based oa TOF mass spectrometers based on single spectrum in scan dynamic range Depending on the application it is sometimes pos sible to extend the practical dynamic range One approach is to sum average multiple spectra together This improves ion statistics and allows for incre
8. analysis condi tions By understanding the concepts of oa TOF mass spectrometry it is possible to achieve the ultimate in performance with the Agilent LC MSD TOF system LC MSD Hypothetical TOF TDC System 1 1 50 1 500 000 10 000 500 000 10 000 200 200 25 0 1 0 25 250 000 1000 2500 1 250 10 25 Time of Flight Mass Spectrometry Agilent Technologies Author John Fjeldsted is an R amp D project manager at Agilent Technologies in Santa Clara California U S A www agilent com chem Agilent Technologies Inc 2003 Information descriptions and specifications in this publication are subject to change without notice Agilent Technologies shall not be liable for errors contained herein or for incidental or consequential damages in connection with the furnishing performance or use of this material Printed in the U S A December 11 2003 5989 0373EN j Agilent Technologies
9. ased mass accuracy at lower sample levels Table 3 Single spectrum in scan dynamic range Theoretical Limit Minimum detectable per spectrum ions spectrum Maximum detectable per transient ions transient Maximum detectable per spectrum X 10 000 transients Dynamic range Practical Limit while achieving accurate mass Lower limit per spectrum ions spectrum Upper limit per transient ions transient Upper limit per spectrum x 10 000 transients Dynamic range Agilent Technologies To extend the dynamic range on the high end the opposite approach is taken and spectra from the apex of a chromatographic peak are excluded from the average Intelligent spectral averaging is an important function of the automated accurate mass report generation software of the LC MSD TOF Together these techniques can extend the practical limit of dynamic range 10 by a factor of 100 achieving effective dynamic ranges of 10 for ADC based systems in accurate mass applica tions Conclusion Over the past few years there has been substan tial progress in technologies that take the oa TOF to new performance levels High efficiency ion optics and vacuum system designs have given rise to greater sensitivities High speed ADC based acquisition systems have made greater mass accuracy and wider dynamic range possible The addition of sophisticated data systems and data processing algorithms has enabled outstanding mass accuracies under routine
10. ass spectrometer that does not have an ion mirror Time of Flight Mass Spectrometry Combining the first and second equations yields m 2E d t This gives us the basic time of flight relationship For a given energy E and distance d the mass is proportional to the square of the flight time of the ion In the design of an oa TOF mass spectrometer much effort is devoted to holding the values of the energy E applied to the ions and the distance d the ion travels constant so that an accurate mea surement of flight time will give an accurate mass value As these terms are held constant they are often combined into a single variable A so m At This is the ideal equation that determines the rela tionship between the flight time of an ion and its mass Because the relationship is a squared rela tionship if the observed flight time of the ion is doubled the resulting mass is not doubled but rather it is four times greater In practice there is a delay from the time the con trol electronics send a start pulse to the time that high voltage is present on the rear ion pulser plate There is also a delay from the time an ion reaches the front surface of the ion detector until the signal generated by that ion is digitized by the acquisition electronics These delays are very short but significant Because the true flight time cannot be measured it is necessary to correct the measured time tm by subtracting the sum o
11. asses should bracket the masses of analytical interest The reference mass correction algorithm for the LC MSD TOF requires that one mass be at or below m z 330 and that a second mass be at least 500 m z above the low mass ion If these condi tions are not satisfied but at least one reference mass is found then only the A term is recalculated TOF Measurement Cycle TOF measurements do not rely on the arrival times of ions coming from just a single pulse applied to the ion pulser but instead are summa tions of the signals resulting from many pulses Each time a high voltage is applied to the plates of the ion pulser a new spectrum called a single transient is recorded by the data acquisition sys tem This is added to previous transients until a predetermined number of sums has been made For analyses requiring a scan speed of one spec trum per second approximately 10 000 transients can be summed before transferring the data from the instrument back to the host computer to be written to disk If the target application involves high speed chromatography then fewer transients are summed increasing the scan speed The mass range limits the number of times per second that the ion pulser can be triggered and transients recorded Once the ion pulser fires it is necessary to wait until the last mass of interest arrives at the ion detector before the ion pulser is triggered again Otherwise light ions triggered from the second transient
12. ce mass correction is a technique that has been automated on the Agilent LC MSD TOF mass spectrometer To introduce reference compounds a second nebulizer has been integrated into the ESI ion source This reference nebulizer is con nected to the A bottle of the calibrant delivery system CDS which is controlled via software Bottle A contains the reference compounds The mass spectrometer control software has an editable table that contains the exact masses of these reference compound ions During the acqui sition of each spectrum from the time of flight analyzer these known masses are identified and the A and t values are re optimized Each stored spectrum has its own A and t values so that the software can adjust for even the smallest instru ment variation Each spectrum is then corrected using these values and using the correction equation the higher order polynomial function determined in the second calibration step described previously The correction equation needs to be determined only once because the small deviations across the mass range are nearly constant over time To determine the two unknowns A and t the reference compounds must contain at least two Agilent Technologies components of known mass In order to achieve a good fit for both A and te at least one reference mass needs to be a low mass value and at least one needs to be a higher mass value For best results the low m z and high m z reference m
13. could arrive before the heavier ions of the first transient resulting in overlapping spectra Table 2 shows some example masses with their approximate flight times and possible transient rates These are calculated for a flight length of two meters and a flight potential of 6 500 volts Under these conditions a ion with m z 3200 has a flight time of about 0 1 milliseconds msec or 100 microseconds usec Because there is essen Time of Flight Mass Spectrometry tially no delay time between transients this means that 10 000 transients per second correspond to a mass range of 3200 m z For a smaller mass range the ion pulser can be triggered at higher rates For example a mass of m z 800 one fourth of 3200 m z reduces the flight time to 0 1 msec V4 or 0 05 milliseconds allowing for 20 000 transients per second over an 800 m z mass range Con versely extending the transient to 0 141 milli seconds doubles the mass range to 6400 m z mass is a function of the time squared Table 2 Flight time and transients second as a function of mass m z Flight time psec Transients sec 800 50 20 000 3200 100 10 000 6400 141 7 070 Two meter flight tube flight potential 6500V The minimum allowed tran sient is 50 psec 50 000 points The maximum is 160 psec 160 000 points or about 8 000 m z Because transients are so short the number of ions of a specific mass from a particular com pound in any given transient is generally
14. efficients A and t have been determined a comparison is made between the actual mass values for the calibration masses and their calculated values from the equation These typically deviate by only a few parts per million ppm Because these deviations are small and relatively constant over time it is possible to perform a second pass correction to achieve an even better mass calibration This is done with an equation that corrects the small deviations across the entire mass range This correction equation a higher order polynomial function is stored as Time of Flight Mass Spectrometry part of the instrument calibration The remaining mass error after this two step calibration method neglecting all other instrumental factors is typi cally at or below 1 ppm over the range of calibra tion masses Reference mass correction Achieving an accurate mass calibration is the first step in producing accurate mass measurements When the goal is to achieve mass accuracies at or below the 3 ppm level even the most miniscule changes in energy applied to the ions can cause a noticeable mass shift It is possible however to cancel out these factors with the use of reference mass correction With this technique one or more compounds of known mass are introduced into the ion source at the same time as the samples The instrument software constantly corrects the measured masses of the unknowns using the known masses as reference Referen
15. f both the start and stop delay times which when added together are referred to as to t tm to By substitution the basic formula that can be applied for actual measurements becomes m A tm t0 Mass calibration To make the conversion from measured flight time tm to mass the values of A and to must be Agilent Technologies determined so a calibration is performed A solu tion of compounds whose masses are known with great accuracy is analyzed Then a simple table is established of the flight times and corresponding known masses It looks something like this Table 1 TOF mass calibration Calibrant compound Flight time mass u psec 118 0863 20 79841 322 0481 33 53829 622 029 46 12659 922 0098 55 88826 1521 971 71 45158 2121 933 84 14302 2721 895 95 13425 Now that m and tm are known for a number of values across the mass range the computer that is receiving data from the instrument does the calcu lations to determine A and to It employs nonlin ear regression to find the values of A and to so that the right side of the calibration equation m A tm to matches as closely as possible the left side of the equation m for all seven of the mass values in the calibration mix While this initial determination of A and t is highly accurate it is not accurate enough to give the best possible mass accuracy for time of flight analysis A second calibration step is needed So after the calibration co
16. he upper and lower limits must be defined There are both theoretical and practi cal limits to consider Theoretically it is possible to detect a single ion but practically chemical background would under most conditions obscure such a low level Practical limitations depend on the application For example when the instrument is used for accurate mass mea surement then the lower limit is set by the mini mum sample amount for which accurate mass measurements can be obtained To determine the minimum sample amount the limitations based on ion statistics must be consid ered Assuming a goal of 5 ppm mass accuracy achieved with 67 confidence 10 based on a sin gle unaveraged spectrum and allowing for 1 ppm of calibration error then lo 4 ppm Staying with the assumption of 10 000 resolving power then about 200 ions are required for the measurement This calculation is based on ion statistics and resolving power and is independent of acquisition technology This calculation does assume that there is significant sensitivity signal to noise so that the measurement is unaffected by back ground contamination To determine the highest level under which accu rate mass measurements can be obtained the type of acquisition system must be considered With a TDC system there is a theoretical limit at one ion per transient at a given mass With an ADC system depending on the detector gain many ions can be accurately measured for
17. mproves second order time focusing of the ions on the detector Because ions enter the ion pulser with a certain amount of horizontal momentum they continue to move hori zontally as well as vertically during their flight Thus they are not reflected directly back to the ion pulsar but instead arrive at the detector Figure 2 show a schematic of the detector The first stage of the detector is a microchannel plate MCP a thin plate perforated by many precise microscopic tubes channels When an ion with sufficient energy hits the MOP one or more elec Figure 2 TOF detector with potentials shown for positive ion operation Microchannel Plate MCP Time of Flight Mass Spectrometry trons are freed Each microchannel acts as an electron multiplier By the time the electrons exit the MCP there are roughly ten electrons for every incoming ion The electrons exiting the MCP are accelerated onto a scintillator that when struck by the elec trons emits photons The photons from the scintil lator are focused through optical lenses onto a photomultiplier tube PMT which amplifies the number of photons and then produces a electrical signal proportional to the number of photons The reason for this conversion of an electrical sig nal to an optical signal and back to an electrical signal is to electrically isolate the flight tube and the front of the detector which are at roughly 6 500 volts from the PMT whose signal out
18. ometry shown in Figure 4 Each successive transient builds the values in memory This accurately represents the detector output signal whether it is from a small or large ion current The next section will show why the TDC does not have this dynamic range Time to digital converter systems The time to digital converter TDC represents the second approach to digitizing a TOF signal A TDC acquisition system begins with a discriminator A discriminator is an electronic device that triggers when a particular signal level is reached This trig ger signal from the discriminator is registered by a counter which marks the flight time After a brief dead time the discriminator and counter are ready to record the next ion arrival Since the discriminator triggers on the leading edge of the mass peak the advantage of a TDC system is its ability to eliminate any broadening of the mass peak originating in the detector and amplifier One disadvantage is loss of dynamic range Since the discriminator triggers on the leading edge of the incoming ion signal it ignores the remainder of the detector signal and gives the same response regardless of whether the signal is the result of one ion or many ions The TDC sim ply marks ion arrival but cannot convey how Mass peak ADC sample Intensity of ions recorded at each arrival time lon arrival time Ne Figure 4 An ADC can record multiple ions per transient so it accu
19. put is at ground potential Flight Time and Its Relationship to Mass Equations for time of flight The flight time for each mass is unique It starts when a high voltage pulse is applied to the back plate of the ion pulser and ends when when the ion strikes the detector The flight time t is deter mined by the energy E to which an ion is accel Agilent Technologies erated the distance d it has to travel and its mass strictly speaking its mass to charge ratio There are two well know formulae that apply to time of flight analysis One is the formula for kinetic energy E Yemv which solved for m looks like m 2E v and solved for v looks like v 2E m The equation says that for a given kinetic energy E smaller masses will have larger velocities and larger masses will have smaller velocities That is exactly what takes place in the time of flight mass spectrometer Ions with lower masses arrive at the detector earlier as shown in Figure 3 Instead of measuring velocity it is much easier to measure the time it takes an ion to reach the detector The second equation is the familiar velocity v equals distance d divide by time t v d t Accelerating energy E lon source Flight path distance d Flight tube Detector Figure 3 Time of flight analysis of ions of various masses each with a single charge For clarity and simplicity this shown in a linear time of flight m
20. quite small For many oa TOF instruments this number averages to substantially less than one This fact plays an important role in the basic design of the data acquisition system of many of today s com mercial instruments Digitally Recording lon Arrival While there is an exact instant when each ion strikes the detector it is difficult to transfer this perfectly into the digital world There are two basic approaches used to translate a detector signal into a digital measurement the analog to digital converter ADC used in the Agilent LC MSD TOF and the time to digital converter used in many other commercial TOF systems The next two sections discuss these two approaches Agilent Technologies Analog to digital converter systems The function of an analog to digital converter ADC is to represent digitally the signal that comes from the ion detector An ADC does not attempt to determine the exact arrival time of the ions it is simply a data recorder As a data recorder it samples the amplified detector output at a fixed interval In the case of the LC MSD TOF this interval is 1 nanosecond 107 seconds This translates to a frequency of one gigahertz GHz or 1 billion cycles per second During each cycle the detector output signal intensity is converted into a digital value The digital value is represented by eight bits corresponding to a dynamic range of 28 counts or in decimal notation 0 to 255 counts When the acq
21. rately tracks ion signal intensity Agilent Technologies many ions Because the repetition rate for tran sients is high and the average number of ions for any given mass has been substantially less than one per transient this has generally been an acceptable solution However as ion sources and ion optics become more efficient the number of ions of a given mass in a single transient increases to the point of significance To illustrate this consider a hypothetical instru ment equivalent to the LC MSD TOF that uses a TDC acquisition system Figure 5 shows the num ber of ions for a single compound that arrive in a single transient as a function of sample amount At sample concentrations above 1000 picograms the hypothetical TDC system no longer gives an increased signal response because the TDC cannot reflect the fact that multiple ions of a given mass are arriving in each transient A second problem associated with TDC acquisi tion systems is an observed shift in measured ion arrival time at high ion currents When less than one ion for any given mass arrives at the detector per transient the TDC accurately records arrival time to within the limit of the counter s resolu tion If ions arrive for a given mass just slightly sep arated in time as determined by the instrument s Arb Units 1E 6 lons per Transient Mean response using oa TOF with ADC 1E 5 1 Predicted limit for the same 1E 4 oa TOF with TDC 01
22. rrival time to a resolution beyond that given by the original data points With a TDC system the arrival of the ion is captured by a single value This means the time between data acquisitions must be shorter to achieve the same time resolution Because of the loss of the arrival profile information TDC sys tems must operate at higher sampling rates to achieve equivalent mass accuracy even when saturation effects are not present Theoretical and Practical Limits to Mass Accuracy Whether the acquisition system is a TDC or an ADC the arrival time for the accumulated signal in memory is determined by centroiding the mass measurements from the individual transients Even though the focus of the design of the TDC was to specifically measure the arrival time of Agilent Technologies S Mass peak Second ion of same nominal mass arrives at detector during TDC dead time and is not recorded First ion arrives at detector and is recorded threshold Intensity of ions recorded at each arrival time lon arrival time 50 000000 usec J Figure 6 TDC dead time causes shift to shorter arrival times for higher signal levels each ion the nominal arrival time must be the average centroid of the population for the summed transients There are limits to how pre cisely this centroid can be determined lon statistics The first theoretical limit is set by the number of ions measured and their time di
23. stribution If the distribution is narrow and well populated result ing in a quiet and stable signal then the centroid or average can be precisely determined The expression is o 106 2 4 R Vn where o is the standard deviation of the resulting measurement R is the resolving power often called resolution of the mass spectrometer and n is the number of ions that are detected in the mass peak Suppose one desires 95 confidence 20 mass accuracy at 3 ppm Then with a resolving power of 10 000 and 1o 1 5 ppm it is necessary to have approximately 1000 ions To increase the number of ions in a centroided spectrum it is general practice to use the data analysis software to average spectra across the width of the eluting chromatographic peak Time of Flight Mass Spectrometry It should be noted that while oa TOF has the potential for fast scan cycles reducing the scan time reduces the number of transients which reduces the integration of ions required to achieve accurate mass measurements Fast scanning and accurate mass are opposing performance goals The most accurate mass measurements are achieved under slower scanning conditions Chemical background The second significant factor that limits mass accuracy is chemical background The high resolv ing power of a TOF system helps to reduce the chances of having the peak of interest merged with background yet even a small unresolved impurity can shift the centroid of the
24. uisition system signals the pulser to fire the ADC begins to convert the signal arriving from the detector amplifier It stores each succes sive conversion in memory Each time the pulser fires the ADC adds the new measurement to those already recorded in memory from the previ ous transients When an ADC is used in this way it is called an integrating transient recorder With an ADC some care must be used to bias the detector amplifier Amp Offset to a value close to zero so that when no ion signal is present zero signal is recorded Otherwise the signal present in the absence of an ion signal would add to sys tem noise The gain of the detector and amplifier must be sufficient so that an individual ion regis ters at least one count In practice the gain is normally set so that the average number of counts per ion is greater than one The LC MSD TOF autotune routine automatically sets the detector gain and Amp Offset parameters to satisfy these conditions The advantage of the ADC acquisition system rela tive to the TDC acquisition system discussed in the next section becomes apparent when multiple ions of a given mass arrive at the detector within a single transient The detector is an analog device and amplifies the combined signal from the several nearly simultaneous ion arrivals An ADC with its eight bits can translate this rising and falling sig nal into a digital profile of the mass peak as Time of Flight Mass Spectr
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Agilent Time of Flight Mass Spectrometry Manual