Use of a novel array detector for the direct analysis of solid samples by laser ablation inductively coupled plasma sector-field mass spectrometry

Barnes, James H.; Schilling, Gerhard; Hieftje, Gary M.; Sperline, Roger P.; Denton, M. Bonner; Barinaga, Charles J.; Koppenaal, David W.

doi:10.1016/j.jasms.2004.01.010

Cited by 41 publications

(33 citation statements)

References 32 publications

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“…The spatial focusing on the focal plane is proportional to the width of the opening slit (S) located at the analyzer entrance and to the ratio R m /R e (magnetic and electric radius described by the ion). Several types of detectors have been used with the MH-MS, such as: photographic plate [6], ion collectors coupled to electrometers [7], electro-optical imaging detector (EOID) [8,9], Spiraltron matrix coupled to a resistive anode [10], collector cups for linear mixture separation and material deposition (soft-landing) using a nonhomogeneous magnetic field [11,12], delta-doped CCD, [13] faraday-strip array detector [14][15][16][17][18][19][20][21][22][23], CMOS based pixilated array detector [24], and of course the modified CCD array detector (IonCCD) in early work [1]. Using an ESI source, we present results for the IonCCD coupled with a miniature MH-MS showing simultaneous biological mixture separation for potential micro-array ion deposition applications [25].…”

Section: Introductionmentioning

confidence: 99%

IonCCD™ for Direct Position-Sensitive Charged-Particle Detection: from Electrons and keV Ions to Hyperthermal Biomolecular Ions

Hadjar

Johnson

Laskin

et al. 2011

J. Am. Soc. Mass Spectrom.

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A novel, low-cost, pixel-based detector array (described elsewhere Sinha and Wadsworth (76 (2), 1) is examined using different charged particles, from electrons to hyperthermal (G100 eV) large biomolecular positive and negative ions, including keV small atomic and molecular ions. With this in mind, it is used in instrumentation design (beam profiling), mass spectrometry, and electron spectroscopy. The array detector is a modified light-sensitive charge-coupled device (CCD) that was engineered for direct charged-particle detection by replacing the semiconductor part of the CCD pixel with a conductor Sinha and Wadsworth (76(2), 1). The device is referred to as the IonCCD. For the first time, we show the direct detection of 250-eV electrons, providing linearity response of the IonCCD to the electron beam current. We demonstrate that the IonCCD detection efficiency is virtually independent from the particle energy (250 eV, 1250 eV), impact angle (45 o , 90 o ) and flux. By combining the IonCCD with a double-focusing sector field mass spectrometer (MS) of Mattauch-Herzog geometry (MH-MS), we demonstrate fast data acquisition. Detection of hyperthermal biomolecular ions produced using an electrospray ionization source (ESI) is also presented. In addition, the IonCCD was used as a beam profiler to characterize the beam shape and intensity of 15 eV protonated and deprotonated biomolecular ions at the exit of an rf-only collisional quadrupole. This demonstrates an ionbeam profiling application for instrument design. Finally, we present simultaneous detection of 140 eV doubly protonated biomolecular ions when the IonCCD is combined with the MH-MS. This demonstrates the possibility of simultaneous separation and micro-array deposition of biological material using a miniature MH-MS.

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Section: Introductionmentioning

confidence: 99%

IonCCD™ for Direct Position-Sensitive Charged-Particle Detection: from Electrons and keV Ions to Hyperthermal Biomolecular Ions

Hadjar

Johnson

Laskin

et al. 2011

J. Am. Soc. Mass Spectrom.

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“…After our MRI studies, we subjected DIV4 and DIV25 specimens to LA-ICP-MS, in which a laser ablation unit is coupled to the ICP-MS system to allow the generation of spatially dependent trace element maps [21]. Representative T1 maps of DIV4 and DIV25 specimens are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Spatial mapping of mineralization with manganese-enhanced magnetic resonance imaging

Chesnick

Centeno

Todorov

et al. 2011

Bone

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Paramagnetic manganese can be employed as a calcium surrogate to sensitize the magnetic resonance imaging (MRI) technique to the processing of calcium during the bone formation process. At low doses, after just 48 h of exposure, osteoblasts take up sufficient quantities of manganese to cause marked reductions in the water proton T1 values compared with untreated cells. After just 24 h of exposure, 25 μM MnCl2 had no significant effect on cell viability. However, for mineralization studies 100 μM MnCl2 was used to avoid issues of manganese depletion in calvarial organ cultures and a post-treatment delay of 48 h was implemented to ensure that manganese ions taken up by osteoblasts is deposited as mineral. All specimens were identified by their days in vitro (DIV). Using inductively coupled plasma optical emission spectroscopy (ICP-OES), we confirmed that Mn-treated calvariae continued to deposit mineral in culture and that the mineral composition was similar to that of age-matched controls. Notably there was a significant decrease in the manganese content of DIV18 compared with DIV11 specimens, possibly relating to less manganese sequestration as a result of mineral maturation. More importantly, quantitative T1 maps of Mn-treated calvariae showed localized reductions in T1 values over the calvarial surface, indicative of local variations in the surface manganese content. This result was verified with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). We also found that ΔR1 values, calculated by subtracting the relaxation rate of Mn-treated specimens from the relaxation rate of age-matched controls, were proportional to the surface manganese content and thus mineralizing activity. From this analysis, we established that mineralization of DIV4 and DIV11 specimens occurred in all tissue zones, but was reduced for DIV18 specimens because of mineral maturation with less manganese sequestration. In DIV25 specimens, active mineralization was observed for the expanding superficial surface and ΔR1 values were increased due to the mineralization of small, previously unmineralized areas. Our findings support the use of manganese-enhanced MRI (MEMRI) to study well-orchestrated mineralizing events that occur during embryonic development. In conclusion, MEMRI is more sensitive to the study of mineralization than traditional imaging approaches.

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“…With an atomic mass spectrometry history of nearly a decade, multicollector mass spectrometry 71 offers the potential to measure up to 9 mass channels simultaneously; indeed, the instrumentation has found important use in isotope ratio analysis. The extension to allow many simultaneous channels was further developed by Hieftje and colleagues [72][73][74] . Assuming that technological developments (not yet in sight) will allow analyses on the time scale of single-cell ionization events, we believe this could be a technology to eventually rival CyTOF's foreseen applications.…”

Section: Single-cell Dna and Rna Sequencingmentioning

confidence: 99%

From single cells to deep phenotypes in cancer

2012

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In recent years, major advances in single-cell measurement systems have included the introduction of high-throughput versions of traditional flow cytometry that are now capable of measuring intracellular network activity, the emergence of isotope labels that can enable the tracking of a greater variety of cell markers and the development of super-resolution microscopy techniques that allow measurement of RNA expression in single living cells. These technologies will facilitate our capacity to catalog and bring order to the inherent diversity present in cancer cell populations. Alongside these developments, new computational approaches that mine deep data sets are facilitating the visualization of the shape of the data and enabling the extraction of meaningful outputs. These applications have the potential to reveal new insights into cancer biology at the intersections of stem cell function, tumor-initiating cells and multilineage tumor development. In the clinic, they may also prove important not only in the development of new diagnostic modalities but also in understanding how the emergence of tumor cell clones harboring different sets of mutations predispose patients to relapse or disease progression.

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Use of a novel array detector for the direct analysis of solid samples by laser ablation inductively coupled plasma sector-field mass spectrometry

Cited by 41 publications

References 32 publications

IonCCD™ for Direct Position-Sensitive Charged-Particle Detection: from Electrons and keV Ions to Hyperthermal Biomolecular Ions

IonCCD™ for Direct Position-Sensitive Charged-Particle Detection: from Electrons and keV Ions to Hyperthermal Biomolecular Ions

Spatial mapping of mineralization with manganese-enhanced magnetic resonance imaging

From single cells to deep phenotypes in cancer

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