Patent Application
20080067356
It is initially noted that reference to a singular item herein includes the possibility that there are plural of the same items present. More specifically, as used herein and in the appended claims, the singular forms “a”, “an”, “said” and “the” include plural referents unless the context clearly dictates otherwise.
The term “adjacent” means near, next to or adjoining. Something adjacent may also be in contact with another component, surround (i.e. be concentric with) the other component, be spaced from the other component or contain a portion of the other component.
The apparatus 1 includes an ionization chamber 10 that comprises an enclosure in which ions are generated. An ionization device 15, which may comprise an electrospray tip, for example, extends into (or is enclosed by) the ionization chamber 10 and generates primary ions by mechanisms well known in the art from a gas/liquid aerosol that is present within the ionization chamber or supplied to the ionization chamber via a first passageway 12. The primary ions may include ions generated from a neutral analyte sample delivered to the ionization chamber through the first passageway and/or ions generated from other reactive substances provided or present within the ionization chamber such as water (hydronium and hydroxyl ions) or ammonia in vapor or liquid form, beta particles, Ni63, etc.
The space within the ionization chamber 10 in which primary ions are generated is termed the ionization region. It is noted that while electrospray is a particularly suitable ionization technique, other ionization modes can also be used to generate primary ions such as high-velocity gas impact, electron capture or impact and photoionization. The primary ions may be generated continuously or periodically during operation of the ionization device 15 to maintain a desired concentration of primary ions within the ionization region. A portion of the primary ions may be directed by electric fields towards an orifice 22 that leads downstream to a mass spectrometer 40 via a second passageway 20. However, the concentration of primary ions within the ionization region is maintained such that a sufficient number of primary ions can interact with neutral molecules as described below.
A third passageway 30 extends from the ionization chamber 10 and has an orifice 38 at its distal end. Gas-borne molecules can enter the apparatus 1 by entering the orifice 22 and diffusing through the length of the first passageway 30 into the ionization chamber 10. A sample 5 may thus be placed adjacent to coupled to the orifice 38 in order to introduce gas-borne neutral sample molecules into the ionization chamber 10 via such diffusion. In the example embodiment depicted, the sample in condensed phase is placed onto a sample support 8 (in solution or otherwise) positioned adjacent to the orifice 38. Volatilization and diffusion of neutral sample molecules may occur even though the sample 5 is prepared in condensed phase since some amount, albeit a small concentration thereof, is volatized from the sample at room temperature by evaporation or sublimation. Heat may also be applied to the sample 5 to promote volatilization and to speed up the ionization and detection process as will be discussed below. The concentration of gaseous neutral molecules that diffuse through the third passageway can be limited using plugged stoppers, microvalves, etc. (not shown) positioned within the third passageway 30.
In the depicted embodiment, the third passageway 30 may also serve as a passageway for the release of exhaust gases such as N2 purge gas emanating from the apparatus 1 into the ambient atmosphere. In some embodiments, exhaust gases may be expelled through an exhaust conduit 32 that extends for some length in the third passageway 30. An interesting feature of the apparatus disclosed herein is that the flow of exhaust gas through the third passageway 30 does not eliminate the back diffusion of gaseous molecules in the opposite direction. It has been found that the length of the exhaust conduit 32 and the associated exhaust flow rate affects the rate of back diffusion from the environment into the ion source; greater vent lengths increase resistance and thus decrease the back diffusion rate, but do not affect the signal response.
When the gaseous neutral molecules diffuse through the length of the third passageway 30 into the ionization chamber 10 they pass into the ionization region and encounter primary ions present within the ionization region. A portion of the neutral molecules are ionized by charge transfer and possibly other electro-physical interactions with the primary ions. A neutral molecule [M] either obtains a proton though charge transfer with a positive (or negative) primary ion such as a hydronium ion:
M°+HA+→[M+H]++A°
or the neutral molecule loses a proton through charge transfer with a negative primary ion such as a hydroxyl ion:
M°+HB−→[M−H]−+B°
It is emphasized that the charge transfer process whereby the neutral molecules are ionized by charge transfer with primary ions is a low-energy ‘soft ionization’ process in which energy interactions are typically on the order of 2-20 eV (electron volts). This is in contrast to ‘hard’ ionization techniques such as occur in Atmospheric Pressure Chemical Ionization (APCI) in which molecules are ionized by intense energy fields on the order of 100-1000 eV which are generated by corona discharge. By employing a soft ionization technique to produce secondary ions, ion suppression that can arise when dual ‘hard’ ionization sources are employed is largely avoided.
Once the neutral molecules derived from the sample are ionized in the ionization region they become subjected to an electric field produced in this region by the combined action of several electrodes 15, 17, 18 maintained at different voltages. The electric field guides the ions in the ionization region toward a low pressure region in front of the orifice 22 of the second passageway 20 that leads toward the mass spectrometer 40. In the example embodiment, a first electrode 15 is positioned above the ionization region, a second electrode 17 is positioned opposite the orifice of the second passageway 20, and a third electrode 18 is positioned adjacent to the orifice 22 of the second passageway. It is noted however, that the configuration of the electrodes 15, 17, 18 is merely exemplary and other configurations, and a different number of electrodes, may be employed to create electric fields suitable for directing ions in the ionization region toward the orifice 22 of the second passageway 20. Ions that reach the orifice 22 are pulled through into the second passageway by the pressure differential between the second passageway 20 and the ionization chamber 10.
Ions guided into the orifice 22 of the second passageway 20 are guided further downstream by pressure differentials, electrodes and other ion optics into the mass spectrometer 40, which may comprise any known mass analyzer devices, including but not limited to: quadrupole, ion trap (linear or two-dimensional), time-of-flight (TOF), orbitrap, and FT-ICR (Fourier Transform Ion Cyclotron Resonance) devices. The spectrometer may comprise single mass analyzer or a tandem (MS/MS) configuration including more than one mass analyzer arranged in sequence. The ions guided into the mass spectrometer 40 are filtered and detected within the mass spectrometer. A mass spectrum indicating abundance of detected ions according to mass/charge ratio is generated thereby.
One of the advantages of the above-described ion source and associated ionization method is that it is capable of providing extremely small concentrations of sample ions to the mass spectrometer that are detectable. If an extremely sensitive mass analyzer is employed, such as a time-of-flight (TOF), it is possible for sample levels on the order of 1 part per 1015 to be detected and identified.
A sample of a known chemical having isotopic molecular weight of approximately 303 was introduced by way of the third passageway of an ionization apparatus according to the present invention. During monitoring the detected masses in scan mode at m/z of 304 (indicating the addition of a proton), the level detected increased whenever the sample was placed near the orifice, indicating that the chemical was diffusing into the apparatus against the exhaust flows and being ionized therein.
As shown, the apparatus 100 includes an ionization chamber 110 having an ionization region 112 in which primary ions are generated. A first passageway (not depicted in
One of the useful features of the embodiment depicted in
While a portion of the gaseous neutral molecules (M) released from the sample diffuse toward the exit orifice 143, the low volume gas flow enhances the egress of the gaseous molecules from the sample chamber 142 to a third passageway 130 coupled to the exit orifice 143. The third passageway 130 extends from the exit orifice 143 of the sample chamber 142 at a first end to the ionization region 112 within the ionization chamber 110 at its second end. As depicted, both gaseous sample molecules (M) and nitrogen molecules (N2) flow through the third passageway 130 into the ionization region 112.
Within the ionization region, a portion of the sample molecules (M) encounter primary ions (HA+) and are ionized thereby, in this case taking on a proton and converting to positive ion (M+H)+ as discussed above. A substantial portion of the primary ions and secondary ions derived from the gaseous neutral molecules are guided into a low pressure region in front of an entrance to the second passageway 120 leading to a mass spectrometer by electric fields generated by electrodes 115, 117 coupled to respective power supplies HV 1, HV 2. The neutral molecules sample molecules (M) may constitute an unknown analyte sample to be determined, but in some applications (M) may instead comprise a source mass calibrant molecules of known mass.
To accommodate the low volume gas flow passed through the sampling region 140, the embodiment shown in
The embodiment of
The ionization apparatuses discussed in
This method of ionizing mass calibrant molecules within an ion source is easy to implement and does not require ionizing the mass calibrant molecules externally from the ion source or an additional ionization device, as is often provided in multimode ionization sources, because the mass calibrant ions are generated by interaction with the primary ions, rather than by an independent ionization mechanism.
The primary ions and the mass calibrant ions within the ionization region of the ion source 210 and are then guided by electrostatic forces along with the primary ions into a conduit 220 leading to the mass analyzer 240 via a transport region 230 which may include ion optics such as a multipole guide. The mass analyzer may comprise a TOF analyzer having a flight tube and other components such as an equalizer and a reflectron (both not shown). Packets of ions are released into the flight tube of a TOF analyzer in pulses; the kinetic energies of the ions are substantially equalized so that the flight times of different ion species through the chamber up to the detector 250 reflect the difference in their masses. The flight time of the mass calibrant is then used as a standard measurement for the correction of the detected flight times of the primary ions.
It is to be understood that the depiction of the molecules and ions herein is simplified for illustrative purposes and do not reflect their actual numbers and dimensions.
Having described the present invention with regard to specific embodiments, it is to be understood that the description is not meant to be limiting since further modifications and variations may be apparent or may suggest themselves to those skilled in the art. It is intended that the present invention cover all such modifications and variations as fall within the scope of the appended claims.
