High-throughput miniature cylindrical ion trap array mass spectrometer

A fully multiplexed cylindrical ion trap (CIT) array mass spectrometer with four parallel ion source/mass analyzer/detector channels has been built to allow simultaneous high-throughput analysis of multiple samples. A multielement external chemical ionization/electron ionization source was coupled to a parallel array of CITs each of equal size (internal radius 2.5 mm), and the signal was recorded using an array of four miniature (2-mm inner diameter) electron multipliers. Using external electron ionization, the spectra of four separate samples were recorded simultaneously in real time using a four-channel preamplifier system and a data acquisition program written using LabVIEW software. These experiments mark the first demonstration of externally generated ions being successfully trapped in a miniature CIT mass analyzer. The instrument currently provides mass/charge range of approximately m/z 50-500. Average peak width is m/z 0.3, corresponding to a resolution of 1000 at m/z 300. The four-channel mass spectrometer is housed in a single vacuum manifold and operated with a single set of control electronics. The modular design of this instrument allows scale-up to many more channels of analysis for future applications in the areas of industrial process monitoring and combinatorial analysis and in the fields of proteomics and metabolomics.     

CHICSi—a compact ultra-high vacuum compatible detector system for nuclear reaction experiments at storage rings. II. Detectors

We describe the detectors for identification of charged particles and fragments in CHICSi, a large solid angle multi-telescope system mounted inside an ultra-high vacuum (UHV), cluster-jet target chamber. CHICSi performs nuclear reaction experiments at storage rings. The telescopes consist of a first very thin, 10–14 μm Si detector, a second 300 μm (or possibly 500 μm) ion implanted Si detector supplemented by a 6 mm GSO(Ce) scintillator read out by a photodiode (PD) or by a third 300 μm Si detector. The telescopes provide full charge separation up to Z=17 and mass resolution up to A=9 in the energy range 0.7–60A MeV. The thin p-i-n diode detector, etched out from a 280 μm Si wafer, and the GSO/PD detector, both exclusively developed for CHICSi, provide an energy resolution 8%, while the standard 300 μm detectors have 2% energy resolution. Radiation stability of the Si detectors is confirmed up to an integrated flux of 10¹⁰ alpha particles. The GSO detector has 70% light collection efficiency with the optical coupling to the PD a simple open, 0.2 mm, gap. A new method, developed to perform absolute energy calibration for the GSO/PD detector is presented.     

Achievement of energy focus for distance-of-flight mass spectrometry with constant momentum acceleration and an ion mirror

Distance-of-flight mass spectrometry (DOF-MS) has not yet been implemented, though it has many potential advantages in a variety of applications. Impeding the implementation of DOF-MS is the development of the required array detectors and working out the equivalents to the focusing methods now used in time-of-flight (TOF) mass analyzers. Ideally, a batch of ions composed of a variety of m/z values, despite initial distributions of space and energy, would be spatially focused at their respective flight distances at the same time. First-order energy focusing, including ion turnaround, is shown to be accomplished by the use of an ion mirror in conjunction with constant momentum acceleration of the initial ion packet. The initial spatial dispersion is maintained throughout the flight path. With zero initial spatial ion spread, energy focusing to achieve resolutions in the tens of thousands is shown to be feasible with ions from the elemental and isotope ratio mass regions through the extremely high m/z range. With moderate spatial spread taken into account, the DOF-MS approach is shown to achieve resolutions competitive with quadrupole and ion trap mass analyzers. Advantages of DOF-MS include all the advantages of TOF-MS plus simpler detector electronics and the improved signal-to-noise ratio and dynamic range afforded by array detection.     

Time Evolution of Electric Fields in CDMS Detectors

The Cryogenic Dark Matter Search (CDMS) utilizes large mass, 3″?diameter×1″ thick target masses as particle detectors. The target is instrumented with both phonon and ionization sensors, the later providing a ～1?V?cm^?1 electric field in the detector bulk. Cumulative radiation exposure which creates ～200×10⁶ electron-hole pairs could be sufficient to produce a comparable reverse field in the detector thereby degrading the ionization channel performance, if it was not shielded by image charges on the electrodes. To study this, the existing CDMS detector Monte Carlo has been modified to allow for an event by event evolution of the bulk electric field, in three spatial dimensions. Surprisingly, this simple model is not sufficient to explain the degradation of detector performance. Our most recent results and interpretation are discussed.     

Multiplexed rectilinear ion trap mass spectrometer for high-throughput analysis

A multichannel mass spectrometer based on the rectilinear ion trap (RIT) analyzer was designed and constructed for simultaneous high-throughput analysis of multiple samples. The instrument features four parallel ion source/mass analyzer/detector channels assembled in a single vacuum chamber and operated using a common set of control electronics, including a single rf amplifier and transformer coil. This multiplexed RIT mass spectrometer employs an array of four millimeter-sized ion traps (x(o) = 5.0 mm and y(o) = 4.0 mm, where x(o) and y(o) are the half-distances in the x and y dimensions, respectively). Mass spectra are acquired from four different samples simultaneously. The available mass/charge range is m/z 15-510 with excellent linearity of the mass calibration (R2 = 0.999 999). The peak width is less than 0.3 mass/charge units at m/z 146, corresponding to a resolution of approximately 500. Simultaneous MS/MS of ions due to four compounds (3-fluoroanisole, 4-fluoroanisole, 2-fluorobenzyl alcohol, 2,6-dimethylcyclohexanone) with the same nominal molecular radical cation but distinctive fragmentation patterns was demonstrated. Isolation and fragmentation efficiencies were approximately 25 and approximately 75%, respectively, measured in the typical case of the molecular radical cation of acetophenone. Preacquisition differential data were obtained by real-time subtraction of the ion signals from two channels of the multiplexed mass spectrometer. The differential experiment presented offers proof of principle of comparative mass spectra in high-throughput screening applications while reducing data storage requirements.     

A tandem mass spectrometer for improved transmission and analysis of large macromolecular assemblies

We report the design and first applications of a tandem mass spectrometer (a quadrupole time-of-flight mass spectrometer) optimized for the transmission and analysis of large macromolecular assemblies. Careful control of the pressure gradient in the different pumping stages of the instrument has been found to be essential for the detection of macromolecular particles. Such assemblies are, however, difficult to analyze by tandem-MS approaches, because they give rise to signals above m/z 3,000-4,000, the limit for commercial quadrupoles. By reducing the frequency of the quadrupole to 300 kHz and using it as a narrow-band mass filter, we show that it is possible to isolate ions from a single peak at m/z 22,000 in a window as narrow as 22 m/z units. Using cesium iodide cluster signals, we show that the mass range in the time-of-flight (TOF) analyzer extends beyond m/z 90,000, in theory to more than m/z 150,000. We also demonstrate that the resolution of the instrument is greater than 3,000 at m/z 44,500. Tandem-MS capabilities are illustrated by separating components from heterooligomeric assemblies formed between tetrameric transthyretin, thyroxine, retinol-binding protein, and retinol. Isolation of a single charge state at m/z 5,340 in the quadrupole and subsequent collision-induced dissociation (CID) in the gas-filled collision cell leads to the formation of ions from individual subunits and subcomplexes, identified by their mass and charge in the TOF analyzer.     

MALDI ion trap mass spectrometer with charge detector for large biomolecule detection

Up to now, all commercial matrix-assisted laser desorption/ionization (MALDI) mass spectrometers still can not efficiently analyze very large biomolecules. In this work, we report the development of a novel MALDI ion trap mass spectrometer which can enrich biomolecular ions to enhance the detection sensitivity. A charge detector was installed to measure the large ions directly. With this design, we report the first measurement of IgM with the mass-to-charge ratio (m/z) at 980?000. In addition, quantitative measurements of the number of ions can be obtained. A step function frequency scan was first developed to get a clear signal in the m/z range from 200,000 to 1,000,000.     

Pulsed acceleration charge detection mass spectrometry: application to weighing electrosprayed droplets

We describe a new approach to measuring the masses of individual macroions. The method employs a pulsed acceleration tube located between two sensitive image charge detectors. The charge and velocity of the macroion are recorded with the first image charge detector. The ion is pulse accelerated through a known voltage drop, and then the charge and velocity are remeasured using the second image charge detector. The mass of the ion is deduced from its charge and its initial and final velocities. The approach has been used to measure masses in the 10(10)-10(14) Da range with z = 10(3)-10(6) and m/z = 10(6)-10(9). It should be extendable to masses of <10(6) Da. We have used the method to determine the size and charge of water droplets transmitted through a capillary interface and an aperture interface. The droplets detected from the aperture interface are approximately 1 order of magnitude smaller in mass than those detected from the capillary interface. The droplets from both interfaces have relatively low charges, particularly with the capillary interface where they are only charged to a small fraction of the Rayleigh limit. These results suggest that the aerodynamic breakup of the droplets plays a significant role in the mechanism of electrospray ionization.     

Study of the dead layer in germanium for the CDMS detectors

We present new measurements on a Cryogenic Dark Matter Search (CDMS) detector with electron, neutron, and gamma sources. The measurements have been performed to investigate the dead layer of one of the CDMS Z-dependent Ionization Phonon germanium detectors. The dead layer has been studied at both charge electrodes and at different electric field intensities. We also present a method to remove the dependence of athermal phonon measurements on event position.     

Compact Radiation Shield for a Superconducting Array Molecule Detector

Recent development on large-scale superconducting array detectors requires a large through hole along the molecular flight path in a cryostat. The through hole causes degradation of detector performance due to the 300 K radiation and a short holding time at the cryostat base temperature. To realize a compact detector system, we designed and fabricated infrared radiation shields with a fine-honeycomb collimator and a micro-structured metal-mesh. The infrared flux through the honeycomb collimator located at 50 K was 300–500 μW. A test run in a cryostat showed a holding time of 8 hours. We fabricated a metal-mesh consisting of a self standing Cr/Cu film with an array of 2.0 μm holes having a pitch of 3.5 μm. The metal-mesh was supported by a Si reinforce structure. Spectral measurement indicates that the transmission of the 300 K radiation is less than 1%.      

Detector Development for the Next Phases of the Cryogenic Dark Matter Search: Results from 1 Inch Ge and Si Detectors

The Cryogenic Dark Matter Search (CDMS) experiment is searching for Weakly Interacting Massive Particles (WIMPs) using detectors with the ability to discriminate between candidate (nuclear recoil) and background (electron recoil) events by measuring both phonon and ionization signals from recoils in the detector crystals. As CDMS scales up to greater WIMP sensitivity, it is necessary to increase the detector mass and further improve background discrimination. CDMS is engaged in ongoing fabrication and development of new detector designs in order to meet these criteria for the proposed SuperCDMS experiment. Thicker detector prototypes have been produced with new photolithographic masks. These masks have greater surface coverage of the quasi particle trap and transition edge sensor system to provide superior athermal phonon collection. Results from continuing laboratory tests are presented which already indicate improvement in discrimination parameters.      

Performance of a three-element thin film detector

A nuclear charged particle detector has been designed and fabricated at the University of Florida for use in identifying the nuclear charge Z and mass number A of low energy (1 MeV/amu) heavy mass ions. The detector consists of a stack of three sequential thin film detectors (made from NE-102A plastic scintillator) for three successive measurements of the specific luminescence ΔL/Δx and velocity of a transiting ion and a terminal surface barrier detector for measuring the ion residual energy. This detector assembly was tested by measuring its response to various isotopes of germanium and selenium ions accelerated to selected energies between 53 and 169 MeV and then scattered from a thin gold target foil. The tests were performed to obtain quantitative information on the ability of the detector system to identify the nuclear Z of an impinging ion and to test the 0810 1076 V 3 advantage of having three successive measurements of ΔL/Δx from three sequential and independent thin film detectors. It was determined that below 2 MeV/amu the detector response was dependent on particle velocity but independent of particle mass and below about 0.9 MeV/amu the detector was not able to distinguish between ions having two units difference in Z, probably due to similarities in ionic charge state distributions. It was also determined that the use of three detectors reduced the FWHM of the TFD response by 54%.     

Optically Induced Measurement of Electron and Hole Drift Velocities in a Germanium 〈100〉 CDMS Detector at 50 mK

We report on precise drift velocity measurements of electrons and holes in 50 mK, ultrapure (≈10¹⁰ net shallow impurities per?cm³) germanium 〈100〉 CDMS dark matter detectors as a function of electric field up to 4?V/cm. A laser diode connected to an optical fiber extending from room-temperature to the detector creates electron-hole pairs on one surface of the crystal. High-speed electronics measure the drift current as the generated carriers travel to the opposite face of the crystal. CDMS detectors measure the ionization and phonon response of particle interactions within the crystal. Stable charge collection is necessary for successful background discrimination when looking for a possible dark matter signal. While biased, however, ionization performance degrades over time due to the build-up of space charge. Free electrons and holes created by particle interactions are subject to drift-diffusion dynamics occurring simultaneously with the trapping of carriers to localized surface and bulk states. The combination of these processes determine the evolution of space charge within the crystal, making it important that we understand carrier transport under our unique operating condition of low-temperature and low-field. We find good agreement between our measured drift velocities and our theoretical predictions, indicating carrier scattering is dominated by spontaneous phonon emission. In addition, we present preliminary measurements of effective longitudinal carrier trapping lengths for both n-type and p-type crystals at 50?mK.     

Rectilinear ion trap mass spectrometer with atmospheric pressure interface and electrospray ionization source

A rectilinear ion trap (RIT) mass analyzer was incorporated into a mass spectrometer fitted with an electrospray ionization source and an atmospheric pressure interface. The RIT mass spectrometer, which was assembled in two different configurations, was used for the study of biological compounds, for which performance data are given. A variety of techniques, including the use of a balanced rf, elevated background gas pressure, automatic gain control, and resonance ejection waveforms with dynamically adjusted amplitude, were applied to enhance performance. The capabilities of the instrument were characterized using proteins, peptides, and pharmaceutical drugs. Unit resolution and an accuracy of better than m/z 0.2 was achieved for mass-to-charge (m/z) ratios up to 2000 Th at a scan rate of approximately 3000 amu/(charge.s) while reduced scan rates gave greater resolution and peak widths of less than m/z 0.5 over the same range. The mass discrimination in trapping externally generated ions was characterized over the range m/z 190-2000 and an optimized low mass cutoff value of m/z 120-140 was found to give equal trapping efficiencies over the entire range. The radial detection efficiency was measured as a function of m/z ratio and found to rise from 35% at low m/z values to more than 90% for ions of m/z 1800. The way in which the ion trapping capacity depends on the dc trapping potential was investigated by measuring the mass shift due to space charge effects, and it was shown that low trapping potentials minimize space charge effects by increasing the useful volume of the device. The collision-induced dissociation (CID) capabilities of the RIT instrument were evaluated by measuring isolation efficiency as a function of mass resolution as well as measuring peptide CID efficiencies. Overall CID efficiencies of more than 60% were easily reached, while isolation of an ion with unit resolution at m/z 524 was achieved with high rejection (>95%) of the adjacent ions. The overall analytical capabilities of the ESI-RIT instrument were demonstrated with the analysis of a mixture of pharmaceutical compounds using multiple-stage mass spectrometry.     

Tandem ion trap design with enhanced mass analysis capabilities for large populations of ions

A new arrangement consisting of two separate radio frequency (rf) quadrupole ion traps is used to analyze large populations of ions over a wide mass-to-charge (m/z) range. The setup consists of an "accumulation" trap that is maintained at a higher pressure than the second high-performance "analyzer" trap. The two traps are scanned simultaneously, with a mass difference between that determines the residence time and mass range of ions in the analytical trap. Initially, all ions are trapped in the accumulation trap and then mass-selectively ejected into the analyzer trap. As ions arrive in the analyzer trap, they cool through collisions with the buffer gas and then are mass selectively ejected toward the detector. This concurrent linked mass scanning reduces the total number of ions present in the analyzer trap during mass analysis, thereby reducing space charge effects and leading to improved resolution and mass accuracy of analytical spectra.     

Tandem infrared multiphoton dissociation and collisionally activated dissociation techniques in a quadrupole ion trap

Tandem infrared multiphoton dissociation and collisionally activated dissociation methods are implemented in a quadrupole ion trap mass spectrometer and used to characterize an array of antibiotic ions generated by electrospray ionization. The tandem methods prove useful for probing fragmentation genealogies, evaluating the structures of lower mass fragment ions produced from higher mass molecular ions, and differentiating isobaric ions. The infrared multiphoton dissociation method is more efficient for producing an array of fragment ions over a large mass range, whereas collisionally activated dissociation is preferable for the analysis of lower m/z ions.     

Ultrahigh Mass Accuracy in Isotope-Selective Collision-Induced Dissociation Using Correlated Sweep Excitation and Sustained Off-Resonance Irradiation: A Fourier Transform Ion Cyclotron Resonance Mass Spectrometry Case Study on the [M + 2H](2+) Ion of Bradykinin

Using electrospray ionization with a 9.4 T Fourier transform mass spectrometer, fragment ion spectra were acquired for a single isotopomer of doubly protonated bradykinin (molecular mass, 1059.6 Da). Correlated sweep excitation methods were applied to mass-select the single isotopomer (m/z = 530.8). Sustained off-resonance irradiation was used to activate and fragment the ions. The accuracy (in terms of m/z) in detection of the fragment ions was on average 1.2 ppm, making the assignments unambiguous. The methods employed would be generally applicable to ions in the mass range of approximately 50 Da to 50 kDa.     

Cylindrical ion trap array with mass selection by variation in trap dimensions

A mass spectrometer array is described in which each array element is a cylindrical ion trap (CIT) within which an approximately quadrupolar, time-varying, field is established. The individual traps are of different sizes, so that when the array is operated with a fixed rf potential, ions of different masses (or mass ranges) are stored in each trap. By choosing the dimensions of each CIT element in the array, a multiple ion monitoring experiment can be performed. For example, in a two-element array with elements having internal radii of 5 and 4 mm, the smaller trap selects for m/z 91 and the larger for m/z 57, corresponding to characteristic aromatic and aliphatic hydrocarbon ions. Ion storage using both rf/dc (apex) isolation and the stored waveform inverse Fourier transform method is demonstrated.The array reduces the complexity of the electronics needed to operate the ion trap, which should make it suitable for use in a miniature mass spectrometer system.     

Development of a TES-Based Anti-coincidence Detector for Future x-Ray Observatories

Microcalorimeters onboard future x-ray observatories require an anti-coincidence detector to remove environmental backgrounds. In order to most effectively integrate this anti-coincidence detector with the main microcalorimeter array, both instruments should use similar read-out technology. The detectors used in the Cryogenic Dark Matter Search (CDMS) use a phonon measurement technique that is well suited for an anti-coincidence detector with a microcalorimeter array using SQUID readout. This technique works by using a transition-edge sensor (TES) connected to superconducting collection fins to measure the athermal phonon signal produced when an event occurs in the substrate crystal. Energy from the event propagates through the crystal to the superconducting collection fins, creating quasiparticles, which are then trapped as they enter the TES where they produce a signal. We are currently developing a prototype anti-coincidence detector for future x-ray missions and have recently fabricated test devices with Mo/Au TESs and Al collection fins. We present results from the first tests of these devices which indicate a proof of concept that quasiparticle trapping is occurring in these materials.