Method for generating filtered noise signal and braodband signal having ...

1 2

METHOD FOR GENERATING FILTERED having mass-to-charge ratios whose corresponding resonant

NOISE SIGNAL AND BRAODBAND SIGNAL frequencies fall within a notch region of the frequency

HAVING REDUCED DYNAMIC RANGE FOR amplitude spectrum of (he filtered noise signal.

USE IN MASS SPECTROMETRY U.S. Pat. No. 4,761,545. issued Aug. 2,1988, to Marshall,

s et al., also discloses application of a broadband signal to an

CROSS-REFERENCE TO RELATED ion trap during performance of a mass spectrometry opera

APPLICATION tion. Marshall et al. teach (at, for example, column 14, lines

m. . „„„ 12-14) application of a broadband signal having a notched

^Pf, ^T^TM?°f ... excitation profile to an ion trap during a mass storage step 505. filed Jul. 27,1994 now U S. Pat. No. 5 449,^5 which m to excitation of ^ of ^ for diction)

is a continuation ofU.S. apphcation Ser. No. 08/075,780 Ma[shail et ^ teach me foUowing multi-step process for

filed on Jun. 11. 1993 (now abandoned), which is a con- generatijlg Ae notched ^0^^ signais disclosed therein:

TT?"n*TM??? ^er- No. 0^28.262 filed on L of a ^ ^main excitation me (which

Aug. 11,1992 (issued as U.S. Pat. No. 5,256.875), which is ^ ^ Pledge ofthe of ^ ..desire<r

a contmuation-in-p^ of U S. apphcation Ser No 07/884, ions fo te retained m durin application of each

455 MedonMay 14,1992(issuedasU.S.Pat No. 5,274 233 notched exdta^on si ^d -^desired"

on Dec. 28 1993) which is a continuation of U-S appbca- { b ejected fr ± ^ application of each

tion Ser. No. 07/662,191 filed on Feb. 28, 1991 (now notched broadband excitation signal);

abandoned). 2. conversion of the mass domain excitation profile into a

FIELD OF THE INVENTION 20 frequency domain excitation spectrum;

3. optional "phase encoding" of the components of the The invention relates to a method for generating a filtered frequency domain excitation spectrum to reduce the noise signal by generating a broadband signal having dynamic range of the notched broadband excitation signal reduced dynamic range, and filtering the broadband signal in produced during the fourth step); a selected notch filter. In preferred embodiments, the inven- 25 4. application of an inverse-Fourier transform to convert the tion is a method for generating a filtered noise signal of a frequency domain excitation spectrum to a notched broadtype suitable for application in mass spectrometry, by gen- band time domain excitation signal; and erating a broadband signal having reduced dynamic range 5. optional weighting or shifting of the time domain exciand filtering the broadband signal in a selected notch filter. tation signal (as described in Marshall's column 3, lines

M 50-53).

BACKGROUND OF THE INVENTION Use and generation of time domain excitation signals as

In a class of conventional mass spectrometry techniques, b? M«shall is subject to several serious

ionshavmgmass-to-chargerauoswiWnaselectedrange(or ^vantages, including (he following. F^st Marshall s

setofranges)areisolatedinanionlrap,andthetrappedions technique for generating a notched broadband signal

are then excited for detection. In conventional variations on 35 PTMr knowledge of (he masses of both desired ions

such techniques, ions trapped during a first (mass storage) to be retafned m *e tiaP *TM* *PP^TM of ^ ^

step are allowed or induced to r«ict (or dissociate) to ...

produce other ions, and the other ions are excited for f ^gnal. Marshall s technique for generating a notched

detection during a second (mass analysis) step. broadband signal also requires construction of a complete

.„".,„.. , ,40 mass domain excitation profile waveform in order to gen

For example, U.S. Pat. No. 4,736,101, issued Apr. 5, wate a ^ domain excitation signal for each ^ spec.

1988, to Syka, et al., discloses a mass spectrometry method trometry experiment

in which ions (having a mass-to-charge ratio within a Also, undesired missing frequency components ("holes") rffedetenmnedrange)aretrappedwitmnatnree-dimensional can resul, ^ conversion of Marshau>s mass domain quadrupole trapping field. The trapping field is then scanned 45 excitation into a frequency domain excitation specie eject unwanted parent ions (ions other than parent ions ^ The rfsk of such undeslred holes is enhanced due to me having a desired mass-to-charge ratio) consecutively from inverse relationship between mass and frequency (so that if the trap. The trapping field is then changed againto become Marshalrs ^ domain excitauon profile has closely capable of storing daughter ions of interest. The trapped spaced undesired mass components corresponding to undesparent ions are then induced to dissociate to produce daugh- 5Q ted ions havin M^ „ values me cotlespoa^ng fre. ter ions, and the daughter ions are ejected consecutively components of the frequency domain excitation (sequentially by m/z) from the (rap for detection. spectrum generated from the mass domain excitation profile

It is often useful to apply broadband voltage signals to an wj]] be widely separated). Undesired holes in a notched

ion trap to eject unwanted ions from the trap during perfor- broadband excitation signal resulting from Marshall's tech

mance of any (or all) of the ion storage, ion reaction or 55 nique can leave unwanted ions in the trap following appli

dissociation, and ion analysis steps of a mass spectrometry cation of Marshall's notched broadband excitation signal to

operation. the trap.

For example, U.S. Pat. No. 5,134,826, issued on Jul. 28, Conventional techniques for reducing dynamic range of a

1992 (based on U.S. application Ser. No. 662,217, filed Feb. broadband signal have selected a functional relationship

28, 1991), describes a mass spectrometry method in which 60 between phase and frequency, and assigned the phase of

a filtered noise signal (a broadband voltage signal which has each frequency component of the broadband signal in accor

been filtered in a notch-filter) is applied to electrodes of an dance with the selected functional relationship. For example,

ion trap. The filtered noise signal can be applied during the the phase encoding technique disclosed in Marshall (at

mass storage step to resonantly eject all ions except selected column 9) requires selection of a nonlinear functional rela

parent ions out of the region of the trapping field. After 65 tion between phase and frequency, and assignment of phases

application of the filtered noise signal, the only ions remain- of the frequency components in accordance with this func

ing (in significant concentrations) in the (rap are parent ions tional relation. Other conventional techniques for reducing a 3 4

broadband signal's dynamic range have randomly selected amplitude, and a known phase angle relative to the start

the phases of the frequency components of the broadband of the broadband waveform segment being constructed;

signal in an effort to randomly select a set of phases which (b) generating a trial signal by adding the first frequency

results in reduced dynamic range. Neither of these conven- component signal to a previously determined optimal

tional methods for generating a broadband signal with 5 frequency component set, and generating a dynamic range

reduced dynamic range is mathematically precise, and nei- signal indicative of the trial signal's dynamic range;

flier allows for true optimization (i.e., dynamic range (c) incrementally changing the phase angle (not the

minimization) of the resulting broadband signal. frequency) of the frequency component added to the

It would be desirable to generate notched broadband optimal frequency component set during step (b) ((he

signals, each having low (and preferably minimized) i0 "trial" frequency component) to generate a new trial

dynamic range and frequency-amplitude spectrum specifi- frequency component;

cally designed for a particular mass spectrometry operation, (d) subtracting the trial frequency component from the trial

in a manner enabling rapid generation (for example, real signal generated in step (b), and replacing said trial

time) of a sequence of such signals (for use in a sequence of frequency component by the new trial frequency compo

different mass spectrometry operations) without signifi- 15 nent to generate a new trial signal, and generating a new

cantly impeding the performance of such sequence of mass dynamic range signal indicative of me new trial signal's

spectrometry operations. It would also be desirable to gen- dynamic range (in preferred embodiments of the

erate such notched broadband signals without a need for invention, the value of the new trial signal's dynamic

prior knowledge of undesired ions to be ejected during range is recorded);

application of the notched broadband signals. It would also 2o (e) repeating steps (c) and (d) for each of M different phase

be desirable to generate many different notched broadband angles which span a desired range, to identify one of the

signals for many different mass spectrometry experiments, trial signal and the new trial signals which has minimum

by performing rapid processing operations (for example, in dynamic range as an optimal trial signal, and identifying

real time) on a single broadband signal (having optimized the frequency components of the optimal trial signal as an

dynamic range). 25 expanded optimal frequency component set (in preferred

SUMMARY OF THE INVENTION embodiments of the invention, the frequency, amplitude,

,„ . t. . it , . . „ . and phase of the frequency components of the optimal

• f mu-l n I5,3 &***>*6 a m*C*TS': nial signal are recorded); and

signal which includes the steps of generating a broadband (f) d (aHe) fa M addidonal sinusoidal (or

signal having optimized (reduced or minimized) dynamic 30 otnef fr component having a frequency

range, and filtering (he broadband signal in a notch filter to meKnt man mat Qf fr component generated

generate a broadband signal whose frequency-ampktade imin a ^ tition of ^ (a).

spectrum has one or more notches (the lUtered noise s (f) can ^ ^ fQf each sinusoidal (or ^

signal). In preferred embodiments the filtered noise signalis fr component to be included in the opti

a voltage signal suitable for application to an ion trap (or 35 ... broadband signal (i.e., for aU frequencies necessary to

other applicable mass spectrometer) during a mass spec- exdte in ... ... ^ h ical ^ tQ whfch ^

trometry operaUon. If applied to, for example, a quadruple broadband signal ^ be applied)( of for only a

ion trap, the filtered noise signal creates a field which subse, of such fr components The latter embodi

combmes with the quadrupole field (having parameters U V, ments rf me m a ^ optimi2ed

and Q), to create a new field called a filtered noise field. ^ band signal including one or more frequency components

The invention enables rapid generation of different fil- on whicn steps (aHe) have been prf^^ as weU as other

tered noise signals (for use in different mass spectrometry frequency components on which steps (a)-(e) have not been

experiments) by filtering a single common broadband signal performed, one embodiment, an analog version of the

(having optimized dynamic range) using a set of different partially optimized broadband signal is generated, and the

notch filters, each having a simple, easily implementable 45 time-averaged energy of this analog signal is determined

design- over intervals of the analog signal's total duration, T. in

The invention enables rapid generation of filtered noise order to identify one or more "flat" intervals over which the

signals (for example, in real time during mass spectrometry time-averaged energy is substantially constant (either

experiments) without prior knowledge of the mass spectrum throughout the interval or at least over beginning and ending

of unwanted ions to be ejected from a trap during application 50 portions of the interval). By storing a portion of the partially

of the filtered noise signal to the trap. The invention also optimized broadband signal having duration U (where U<T)

enables rapid generation of a filtered noise signal having no and corresponding to at least one of the flat intervals, a better

missing frequency components outside the notches of the optimized broadband signal (having lower dynamic range

notch filter employed to generate such filtered noise signal. than the above-mentioned partially optimized signal) can be

In a class of preferred embodiments, two steps are per- 55 generated from the stored flat interval signal by repeatedly

formed to generate the inventive broadband signal (which is clocking the flat interval signal out from storage or other

to be subsequently notch-filtered). The first step is to itera- wise concatenating several identical copies of the flat inter

tively generate digital values indicative of the amplitude val signal.

(typically voltage), frequency, and phase of each frequency Throughout the specification, the expression "optimized

component of a broadband signal having optimized dynamic eo broadband signal" will be employed to denote not only fully

range. The second step is to process these digital values to optimized broadband signals (having minimized dynamic

generate an analog, optimized broadband signal. range), but also "partially optimized" and "better optimized"

In a preferred embodiment, the iterative digital value broadband signals of the types mentioned above,

generation is performed in a digital processor, and includes Each optimized broadband signal should contain all fre

the following steps: 65 quencies necessary to excite the physical system to which it

(a) generating a first sinusoidal (or other periodic) frequency will be applied (for example, all undesired trapped ions to

component signal having a first frequency, a first which a notch-filtered version of the optimized broadband