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.     

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.     

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.     

Halo ion trap mass spectrometer

We describe a novel radio frequency ion trap mass analyzer based on toroidal trapping geometry and microfabrication technology. The device, called the halo ion trap, consists of two parallel ceramic plates, the facing surfaces of which are imprinted with sets of concentric ring electrodes. Radii of the imprinted rings range from 5 to 12 mm, and the spacing between the plates is 4 mm. Unlike conventional ion traps, in which hyperbolic metal electrodes establish equipotential boundary conditions, electric fields in the halo ion trap are established by applying different radio frequency potentials to each ring. The potential on each ring can be independently optimized to provide the best trapping field. The halo ion trap features an open structure, allowing easy access for in situ ionization. The toroidal geometry provides a large trapping and analyzing volume, increasing the number of ions that can be stored and reducing the effects of space-charge on mass analysis. Preliminary mass spectra show resolution (m/Deltam) of 60-75 when the trap is operated at 1.9 MHz and 500 Vp-p.     

Development of a multiplexed interface for capillary electrophoresis-electrospray ion trap mass spectrometry

A four-channel multiplexed electrospray capillary electrophoresis interface has been developed. This new interface permits up to four capillary electrophoresis columns to be sampled sequentially by means of a stepper motor and a notched rotating plate assembly, which at any instant occludes all but a single sprayer. In this design, four sheath liquid electrospray probes are oriented in a circular array situated 90 degrees relative to one another. The rotating metal disk, which contains a one-quarter notch, is mounted to the stepper motor assembly and is located between the sprayers and the entrance aperture of an ion trap mass spectrometer. By using the data acquisition signal from the ion trap mass spectrometer, the scan event is synchronized with the rotation of the metal disk. With this device, four discrete sample streams can be simultaneously analyzed, resulting in a 4-fold increase in analytical throughput.     

Miniaturization and geometry optimization of a polymer-based rectilinear ion trap

The fabrication, operation, and characterization of a polymer-based rectilinear ion trap mass analyzer is discussed. A novel, fast prototyping technique, stereolithography (SLA)-based fabrication, traditionally reserved for end use production parts and to fabricate master molds for rubber products, is applied here as a tool to create precise, arbitrary geometries. Taking full advantage of the SLA methodology, an open corner, polymer-based ion trap has been fabricated and tested. The use of a custom resin, Nanoform 15120 (DSM Somos, New Castle, DE), has resulted in a polymer with high heat deflection temperature and greater structural stability at higher temperatures and lower capacitance. The mass analyzer was mounted in a polymer holder and tested in a custom vacuum system using modified LCQ Duo (Thermo Fisher Corp.) electronics. The resolution, mass/charge range, and MS/MS capabilities were examined using electrospray ionization as well as atmospheric pressure chemical ionization. In the course of this study, three traps of different sizes were fabricated, beginning with a "full size" device measuring 10 x 8 x 50 mm. The next two traps were scaled down by linear factors of a half and a third. SLA is shown to allow fabrication of light, small rectilinear ion traps, which are less expensive and have the same performance as traditional machined devices of the same size. In addition, smaller traps can be built just as easily, and they show unit mass resolution to mass 300, tandem mass spectrometry capabilities, and low power consumption.     

High-throughput mass spectrometer using atmospheric pressure ionization and a cylindrical ion trap array

The analytical performance of an atmospheric pressure sampling, multiple-channel, high-throughput mass spectrometer was investigated using samples of a variety of types. The instrument, based on an array of cylindrical ion traps, was built with four independent channels and here is operated using two fully multiplexed channels (sources, ion optics, ion traps, detectors) capable of analyzing different samples simultaneously. Both channels of the instrument were incorporated within the same vacuum system and operated using a common set of control electronics. A multichannel electrospray ionization source was assembled and used to introduce samples including solutions of organic compounds, peptides, and proteins simultaneously into the instrument in a high-throughput fashion. Cross-talk between the channels of the instrument occurred in the detection system and could be minimized to 1-2% using shielding between detector channels. In this initial implementation of the instrumentation, an upper mass/charge limit of approximately 1300 Th was observed (+13 charge state of myoglobin) and unit mass/charge resolution was achieved to approximately 800 Th. The rather limited dynamic range (2-3 orders of magnitude for low-concentration analytes) is due to cross-talk contributions from more concentrated species introduced into a different channel. Analysis of mixtures of alkylamines and peptides is demonstrated, but analysis of mixtures with a wide spread in mass/charge ratios was not possible due to mass discrimination in the ion optics. Further refinement of the vacuum system and ion optics will allow the addition of more channels of parallel mass analysis and facilitate applications in fields such as proteomics and metabolomics.     

A "screened" electrostatic ion trap for enhanced mass resolution, mass accuracy, reproducibility, and upper mass limit in Fourier transform ion cyclotron resonance mass spectrometry

Until now, it was thought that the optimal static electromagnetic ion trap for Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry should be designed to produce a quadrupolar electrical potential, for which the ion cyclotron frequency is independent of the ion's preexcitation location within the trap. However, a quadrupolar potential results in a transverse (to the magnetic field) electric field that increases linearly with distance from the center of the trap. That radially linear electric field shifts the observed ICR frequency, increases the ICR orbital radius, and ultimately limits the highest mass-to-charge ratio ion that can be contained within the trap. In this paper, we propose a new static electromagnetic ion "trap" in which grounded screens placed just inside the usual "trapping" plates produce a good approximation to a "particle-in-a-box" potential (rather than the quadrupolar "harmonic oscillator" potential). SIMION calculations confirm that the electric potential of the screened trap is near zero almost everywhere within the trap. For our screened orthorhombic (2.5 in. X 2 in. X 2 in.) trap, the experimental ICR frequency shift due to trapping voltage is reduced by a factor of approximately 100, and the experimental variation of ICR frequency with ICR radius is reduced by a factor of approximately 10 compared to a conventional (unscreened) 2-in. cubic ion trap.(ABSTRACT TRUNCATED AT 250 WORDS)     

Polymer-Based Ion Trap Chemical Sensor

Ion traps are widely used in chemical analysis, and they are especially important in current attempts to miniaturize mass spectrometers to create portable instruments. The ultimate aim is to build a handheld device that would require a smaller mass analyzer. To accomplish this task, a robust precision fabrication procedure is desired. In this paper, the authors report a new approach to fabricating ion traps using stereolithography apparatus (SLA), which provides precision monolithic fabrication. An SLA-fabricated rectilinear ion trap, which employs a very simple electrode geometry, is shown to provide detection capabilities within a useful mass range encompassing that of interest in the detection of numerous volatile organic compounds, including those relevant to homeland security applications. Single small ion traps and integrated trap arrays can be made through this approach, which allows higher operating pressures and reduced power requirements     

Infrared microspectroscopic imaging using a large radius germanium internal reflection element and a focal plane array detector

Previously, we established the ability to collect infrared microspectroscopic images of large areas using a large radius hemisphere internal reflection element (IRE) with both a single point and a linear array detector. In this paper, preliminary work in applying this same method to a focal plane array (FPA) infrared imaging system is demonstrated. Mosaic tile imaging using a large radius germanium hemispherical IRE on a FPA Fourier transform infrared microscope imaging system can be used to image samples nearly 1.5 mm x 2 mm in size. A polymer film with a metal mask is imaged using this method for comparison to previous work. Images of hair and skin samples are presented, highlighting the complexity of this method. Comparisons are made between the linear array and FPA methods.     

A monolithic array of three-dimensional ion traps fabricated with conventional semiconductor technology

The coherent control of quantum-entangled states of trapped ions has led to significant advances in quantum information, quantum simulation, quantum metrology and laboratory tests of quantum mechanics and relativity. All of the basic requirements for processing quantum information with arrays of ion-based quantum bits (qubits) have been proven in principle. However, so far, no more than 14 ion-based qubits have been entangled with the ion-trap approach, so there is a clear need for arrays of ion traps that can handle a much larger number of qubits. Traps consisting of a two-dimensional electrode array have undergone significant development, but three-dimensional trap geometries can create a superior confining potential. However, existing three-dimensional approaches, as used in the most advanced experiments with trap arrays, cannot be scaled up to handle greatly increased numbers of ions. Here, we report a monolithic three-dimensional ion microtrap array etched from a silica-on-silicon wafer using conventional semiconductor fabrication technology. We have confined individual (88)Sr(+) ions and strings of up to 14 ions in a single segment of the array. We have measured motional frequencies, ion heating rates and storage times. Our results demonstrate that it should be possible to handle several tens of ion-based qubits with this approach.     

Ion soft landing using a rectilinear ion trap mass spectrometer

A new ion soft landing instrument has been built for the controlled deposition of mass selected polyatomic ions. The instrument has been operated with an electrospray ionization source; its major components are an electrodynamic ion funnel to reduce ion loss, a 90-degree bent square quadrupole that prevents deposition of fast neutral molecules onto the landing surface, and a novel rectilinear ion trap (RIT) mass analyzer. The ion trap is elongated (inner dimensions: 8 mm x 10 mm x 10 cm). Three methods of mass analysis have been implemented. (i) A conventional mass-selective instability scan with radial resonance ejection can provide a complete mass spectrum. (ii) The RIT can also be operated as a continuous rf/dc mass filter for isolation and subsequent soft landing of ions of the desired m/ z value. (iii) The 90-degree bent square quadrupole can also be used as a continuous rf/dc mass filter. The mass resolution (50% definition) of the RIT in the trapping mode (radial ion ejection) is approximately 550. Ions from various test mixtures have been mass selected and collected on fluorinated self-assembled monolayers on gold substrates, as verified by analysis of the surface rinses. Desorption electrospray ionization (DESI) has been used to confirm intact deposition of [Val (5)]-Angiotensin I on a surface. Nonmass selective currents up to 1.1 nA and mass-selected currents of up to 500 pA have been collected at the landing surface using continuous rf/dc filtering with the RIT. A quantitative analysis of rinsed surfaces showed that the overall solution-to-solution soft landing yields are between 0.2 and 0.4%. Similar experiments were performed with rf/dc isolation of both arginine and lysine from a mixture using the bent square quadrupole in the rf/dc mode. The unconventional continuous mass selection methods maximize soft landing yields, while still allowing the simple acquisition of full mass spectra.     

Collision-activated infrared multiphoton dissociation in a quadrupole ion trap mass spectrometer

We propose and demonstrate a new method for multiple-stage mass spectrometry (MSn), collision-activated infrared multiphoton dissociation (CA-IRMPD), which is very effective for the quadrupole ion trap mass spectrometer (QITMS). CA-IRMPD uses a combination of focused laser irradiation (beam radius, approximately 0.4 mm) and collisional activation by a supplemental AC voltage between endcap electrodes. This combination enables IRMPD, which has conventionaLly been ineffective above 10(-4) Torr, to be used under a standard bath gas pressure of 2-8 mTorr. CA-IRMPD can produce richer spectra of product ions than CID or IRMPD while maintaining high sensitivity and mass resolution; thus, it will contribute to an accurate determination of peptide sequences.     

High-efficiency on-line solid-phase extraction coupling to 15-150-microm-i.d. column liquid chromatography for proteomic analysis

The ability to manipulate and effectively utilize small proteomic samples is important for analyses using liquid chromatography (LC) in combination with mass spectrometry (MS) and becomes more challenging for very low flow rates due to extra column volume effects on separation quality. Here we report on the use of commercial switching valves (150-microm channels) for implementing the on-line coupling of capillary LC columns operated at 10,000 psi with relatively large solid-phase extraction (SPE) columns. With the use of optimized column connections, switching modes, and SPE column dimensions, high-efficiency on-line SPE-capillary and nanoscale LC separations were obtained demonstrating peak capacities of approximately 1000 for capillaries having inner diameters between 15 and 150 microm. The on-line coupled SPE columns increased the sample processing capacity by approximately 400-fold for sample solution volume and approximately 10-fold for sample mass. The proteomic applications of this on-line SPE-capillary LC system were evaluated for analysis of both soluble and membrane protein tryptic digests. Using an ion trap tandem MS it was typically feasible to identify 1100-1500 unique peptides in a 5-h analysis. Peptides extracted from the SPE column and then eluted from the LC column covered a hydrophilicity/hydrophobicity range that included an estimated approximately 98% of all tryptic peptides. The SPE-capillary LC implementation also facilitates automation and enables use of both disposable SPE columns and electrospray emitters, providing a robust basis for automated proteomic analyses.     

Single-particle mass spectrometry of polystyrene microspheres and diamond nanocrystals.

High-resolution mass spectra of single submicrometer-sized particles are obtained using an electrospray ionization source in combination with an audio frequency quadrupole ion-trap mass spectrometer. Distinct from conventional methods, light scattering from a continuous Ar-ion laser is detected for particles ejected out of the ion trap. Typically, 10 particles are being trapped and interrogated in each measurement. With the audio frequency ion trap operated in a mass-selective instability mode, analysis of the particles reveals that they all differ in mass-to-charge ratio (m/z), and the individual peak in the observed mass spectrum is essentially derived from one single particle. A histogram of the spectra acquired in 10(2) repetitions of the experiment is equivalent to the single spectrum that would be observed when an ion ensemble of 10(3) particles is analyzed simultaneously using the single-particle mass spectrometer (SPMS). To calibrate such single-particle mass spectra, secular frequencies of the oscillatory motions of the individual particle within the trap are measured, and the trap parameter qz at the point of ejection is determined. A mass resolution exceeding 10(4) can readily be achieved in the absence of ion ensemble effect. We demonstrate in this work that the SPMS not only allows investigations of monodisperse polystyrene microspheres, but also is capable of detecting diamond nanoparticles with a nominal diameter of 100 nm, as well.     

Rectilinear ion trap: concepts, calculations, and analytical performance of a new mass analyzer

A mass analyzer based on a rectilinear geometry ion trap (RIT) has been built, and its performance has been characterized. Design concepts for this type of ion trap are delineated with emphasis on the effects of electrode geometry on the calculated electric field. The Mathieu stability region was mapped experimentally. The instrument can be operated using mass-selective instability scans in both the boundary and resonance ejection versions. Comparisons of performance between different versions of the device having different dimensions allowed selection of an optimized geometry with an appropriate distribution of higher-order electric fields. Comparisons made under the same conditions between the performance of a conventional cylindrical ion trap and a RIT of 4 times greater volume show an improvement of 40 times in the signal-to-noise ratio resulting from the higher ion trapping capacity of the RIT. The demonstrated capabilities of the RIT include tandem mass spectrometry, a mass resolution in excess of 1000, and a mass/charge range of 650 Th, all in a simple structure that is only 3.5 cm(3) in internal volume.     

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.     

Atmospheric pressure ionization in a miniature mass spectrometer

A miniature cylindrical ion trap mass spectrometer featuring an atmospheric pressure interface allowing atmospheric pressure chemical ionization and electrospray ionization is described together with its analytical performance characteristics. The vacuum system, ion optics, mass analyzer, control electronics system, and detection system have all been designed and built in-house. The design is based upon a three-stage, differentially pumped vacuum system with the instrument capable of being interfaced to many types of atmospheric pressure ionization sources. Ions are transferred through home-built ion optics, and instrument control is achieved through custom-designed electronics and LabView control software. Corona discharge ionization and electrospray ionization sources are implemented and used to allow the analysis of both gaseous- and solution-phase samples during the characterization of the instrument. An upper mass/charge limit of approximately 450 Th with unit resolution was achieved using a 2.5-mm-internal radius cylindrical ion trap as the mass analyzer. The specificity of the instrument can be increased by employing the MS/MS capabilities of the ion trap and has been demonstrated for nitrobenzene. Limits of detection for the trace analysis in air of the chemical warfare agent simulant methyl salicylate (1.24 ppb) and for nitrobenzene (629 pptr) are achieved. The dynamic range of the instrument is currently limited to approximately 2 orders of magnitude by saturation of the detection electronics. Isolation and collision-induced dissociation efficiencies in MS/MS experiments both greater than 50% are reported. Electrospray/nanospray data are presented on solutions including 100 microM (D,L)-arginine, 10 microM (-)-ephedrine, and 10 microM lomefloxacin.     

Planar geometry for trapping and separating ions and charged particles

A planar quadrupole ion trap is proposed. We have demonstrated an extremely large operating range by trapping ions and particles with mass-to-charge ratio ranging from 10(2) to 10(9) at frequencies from 2.8 x 10(6) to 60 Hz at an operating pressure of 1.1 x 10(-4) to 760 Torr, respectively, using a trap radius of r1 = 1 mm. We have also performed mass spectrometry with a resolution of 1.2 amu with mass-to-charge range from 50 to 150. Our geometry is simple enough to be integrated into existing integrated circuits and microelectromechanical system devices, opening up the possibility of many novel hybrid applications and experiments.     

Field-emission cold-cathode el source for a microscale ion trap mass spectrometer

A cold-cathode electron impact ionization source based on field emission from an array of diamond-coated silicon whiskers is described. The source is coupled to a microscale ion trap mass spectrometer (r0 = 0.50 mm, z0 = 0.50 mm). An electron beam of 250 nA could be obtained through the 0.45-mm diameter opening in the end cap electrode.