Time-of-flight mass spectrometry

Time-of-flight mass spectrometry separates ions by measuring how long they take to reach a detector after a timed acceleration pulse. The simplest instrument has an ion source, an accelerating electric field, and a drift tube kept under vacuum. For ions of equal positive electric charge accelerated through the same electric potential difference, smaller mass gives greater speed and earlier arrival.^[ref]

Let $U$ be the accelerating electric potential difference, $q$ the positive electric charge, $m$ the mass, and $L$ the field-free drift length. Neglecting initial speed and the time spent accelerating, conservation of energy givesFor an ideal $1\mathrm{m}$ drift at $1000\mathrm{V}$, a singly charged ion of mass $100\mathrm{u}$ arrives after approximately $22.8\mu \mathrm{s}$; $400\mathrm{u}$ takes $45.5\mu \mathrm{s}$. Here $\mathrm{u}$ is the unified atomic mass unit. Quadrupling mass doubles the ideal flight time. A doubly charged $200\mathrm{u}$ ion has the same mass-to-charge ratio as the singly charged $100\mathrm{u}$ ion and therefore the same ideal arrival time.

Real peaks broaden because ions begin at different positions and with different kinetic energies. In 1955, W. C. Wiley and I. H. McLaren analysed these effects and demonstrated an ion gun with two accelerating regions that reduced timing differences caused by initial position. Comparing calculated focusing conditions with measured spectra turned a timing idea into a practical improvement in mass spectrometry.^[ref]

A time-of-flight mass spectrometer is a mass spectrometer whose analyzer infers mass-to-charge ratio from ion arrival times. A simple arrangement uses an ion source, pulsed acceleration, a drift region under vacuum and a mass spectrometer detector. The 1955 Wiley–McLaren instrument connected such an apparatus to calculations of how initial position and velocity spread affect resolution.^[ref]

In an ideal drift, $t_{\mathrm{drift}}=L\sqrt{m/(2qU)}$ for flight length $L$, positive charge $q$ and accelerating electric potential difference $U$. Recorded arrival time can also include a time-of-flight timing offset $t_0$. A useful ideal instrument calibration model iswhere $x$ is the numerical mass-to-charge coordinate in a declared unit and $k$ absorbs the instrument geometry and unit conversion.

For original invented standards, let $x=25$ arrive at $12\mu \mathrm{s}$ and $x=100$ at $22\mu \mathrm{s}$. Since the square roots are 5 and 10, $k=2\mu \mathrm{s}$ and $t_0=2\mu \mathrm{s}$. An unknown arriving at $17\mu \mathrm{s}$ then has $x=((17-2)/2{)}^2=56.25$. Ignoring the offset and scaling from the first standard alone would instead give $25(17/12{)}^2\approx 50.17$. A timing offset becomes a mass-assignment error when omitted from the model.

Real peaks have finite widths. Space focusing and time-lag focusing address specified sources of that spread; neither is simply a longer wait before detection. Calibration standards, acquisition timing and focusing conditions therefore belong in the interpretation of a measured spectrum.

A time-of-flight timing offset, $t_0$, is an additive time-origin parameter in a model connecting recorded ion arrival time with physical flight time. In a simple time-of-flight mass spectrometer calibration,where $x$ is the numerical mass-to-charge ratio in declared units. A 2017 instrument-analysis paper uses this equation and determines instrument-dependent constants from identified isotope peaks.^[ref]

An original error calculation shows why the offset matters. Suppose the physical flight contribution is $20\mu \mathrm{s}$ and $t_0=3\mu \mathrm{s}$, so the recorded time is $23\mu \mathrm{s}$. With $k_0$ held fixed, ignoring the offset multiplies the inferred coordinate bya $32.25\%$ overestimate. This deliberately large example isolates the effect; it does not describe a measured instrument error.

With $k_0$ fixed, a small error in the fitted offset propagates approximately asAn offset uncertainty of $0.05\mu \mathrm{s}$ at a corrected flight time of $20\mu \mathrm{s}$ therefore contributes about $0.5\%$ relative uncertainty in this approximation. The same absolute offset error has greater relative impact on earlier arrivals.

This parameter concerns timing, whereas time-lag focusing is a physical delayed-extraction technique affecting the ion packet. Fitting an offset does not by itself sharpen a peak. More detailed instruments can require additional calibration terms; the stated equation is a model, not a universal transfer function.

Time-lag focusing in time-of-flight mass spectrometry uses a controlled delay between creation of an ion packet and application of its extraction electric field. During this delay, different initial velocities produce different positions. The later extraction pulse can then give initially faster ions less accelerating work than initially slower ones, reducing their arrival-time spread at a chosen detector plane.^[ref]

Suppose two equal-mass, equal-electric charge ions differ in their initial forward velocity by $\Delta u$. A field-free delay $\tau$ creates a position differenceFor example, $\Delta u=100\mathrm{m}{\mathrm{s}}^{-1}$ and $\tau =1\mu \mathrm{s}$ give $\Delta x=100\mu \mathrm{m}$. In a subsequently applied uniform field, an ion farther toward the exit experiences a smaller remaining accelerating electric potential difference. Choosing the delay and fields appropriately allows the slower-starting ion to catch up later.

The delay creates a useful correlation between position and velocity; waiting alone does not focus the packet. Space focusing compensates an initial position distribution, whereas time-lag focusing exploits motion during the delay to address an initial velocity distribution. An instrument's focusing condition must state the geometry, fields, reference mass-to-charge ratio and initial-distribution assumptions.

Space focusing in time-of-flight mass spectrometry reduces differences in arrival time caused by the initial positions of otherwise equivalent ions. An ion starting farther from the exit of an accelerating region spends longer there but can acquire greater kinetic energy, allowing it to catch up during the drift. Electrode geometry and electric fields are chosen so that these effects compensate at the detector.^[ref]

A simple idealized derivation makes the compensation explicit. Consider positive ions of mass $m$ and electric charge $q$, initially at rest, with distance $a$ remaining in a uniform accelerating electric field $E$. Let $L$ be the field-free distance beyond its exit. Their total flight time isThe first term is acceleration time; the second is drift time. Setting the derivative $dt/da$ to zero at a reference position $a_0$ givesFor example, $a_0=1\mathrm{cm}$ gives a first-order space focus at $L=2\mathrm{cm}$ in this simplified single-field model. Nearby position errors then affect arrival time only at higher order in the Taylor expansion. Practical two-field sources allow the focus to be placed at more useful drift distances. Initial velocity spread is a separate contribution to peak width, motivating time-lag focusing.