A Mechanical Nanomembrane Detector for Time-of-Flight Mass Spectrometry

Park, Jonghoo; Qin, Hua; Scalf, Mark; Hilger, Ryan T.; Westphall, Michael S.; Smith, Lloyd M.; Blick, Robert H.

doi:10.1021/nl201645u

Cited by 44 publications

(60 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the old-generation TOF detectors, such as electron multipliers and microchannel plates, are suboptimal for the detection of high MW proteins due to the low kinetic energy of these molecules in the drift tube, which decreases the probability of generating secondary electrons and dramatically reduces the detection efficiency of high MW molecules [59]. With the nanomembrane TOF detector developed recently, the kinetic energy of the ions generates mechanical oscillations in the nanomembrane thereby significantly improving the detection of large proteins or protein assemblies [60]. In addition, the hybridization of TOF instruments with quadrupole mass analyzers (q-TOF), which can act as a mass filter or collision cell, has greatly improved the capabilities of these instruments [31].…”

Section: Top-down Proteomics Methodologymentioning

confidence: 99%

Top-down Proteomics: Technology Advancements and Applications to Heart Diseases

Cai

Tucholski

Gregorich

et al. 2016

Expert Review of Proteomics

129

View full text Add to dashboard Cite

Introduction Diseases of the heart are a leading cause of morbidity and mortality for both men and women worldwide, and impose significant economic burdens on the healthcare systems. Despite substantial effort over the last several decades, the molecular mechanisms underlying diseases of the heart remain poorly understood. Areas covered Altered protein post-translational modifications (PTMs) and protein isoform switching are increasingly recognized as important disease mechanisms. Top-down high-resolution mass spectrometry (MS)-based proteomics has emerged as the most powerful method for the comprehensive analysis of PTMs and protein isoforms. Here, we will review recent technology developments in the field of top-down proteomics, as well as highlight recent studies utilizing top-down proteomics to decipher the cardiac proteome for the understanding of the molecular mechanisms underlying diseases of the heart. Expert commentary Top-down proteomics is a premier method for the global and comprehensive study of protein isoforms and their PTMs, enabling the identification of novel protein isoforms and PTMs, characterization of sequence variations, and quantification of disease-associated alterations. Despite significant challenges, continuous development of top-down proteomics technology will greatly aid the dissection of the molecular mechanisms underlying diseases of the hearts for the identification of novel biomarkers and therapeutic targets.

show abstract

Section: Top-down Proteomics Methodologymentioning

confidence: 99%

Top-down Proteomics: Technology Advancements and Applications to Heart Diseases

Cai

Tucholski

Gregorich

et al. 2016

Expert Review of Proteomics

129

View full text Add to dashboard Cite

show abstract

“…In the human proteome, for example, more than a third of proteins have masses over 50 kDa [3], and thus the issue of ion detection sensitivity for these large macromolecular species is critical. It is important to characterize the performance of these existing detectors in order to be able to evaluate their merits relative to potential alternative detection modalities [20–22]. …”

Section: Introductionmentioning

confidence: 99%

Detection of Large Ions in Time-of-Flight Mass Spectrometry: Effects of Ion Mass and Acceleration Voltage on Microchannel Plate Detector Response

Liu

Smith

2014

J. Am. Soc. Mass Spectrom.

Self Cite

View full text Add to dashboard Cite

In time-of-flight mass spectrometry (TOF-MS), ion detection is typically accomplished by the generation and amplification of secondary electrons produced by ions colliding with a microchannel plate (MCP) detector. Here, the response of an MCP detector as a function of ion mass and acceleration voltage is characterized, for peptide/protein ions ranging from 1 kDa to 290 kDa in mass, and for acceleration voltages from 5 kV to 25 kV. A non-destructive inductive charge detector (ICD) employed in parallel with MCP detection provides a reliable reference signal to allow accurate calibration of the MCP response. MCP detection efficiencies were very close to unity for smaller ions at high acceleration voltages (e.g. angiotensin, 1,046.5 Da, at 25 kV acceleration voltage), but decreased to ~11% for the largest ions examined (Immunoglobulin G (IgG) dimer, 290 kDa) even at the highest acceleration voltage employed (25 kV). The secondary electron yield γ (average number of electrons produced per ion collision) is found to be proportional to mv3.1 (m: ion mass, v: ion velocity) over the entire mass range examined, and inversely proportional to the square root of m in TOF-MS analysis. The results indicate that although MCP detectors indeed offer superlative performance in the detection of smaller peptide/protein species, their performance does fall off substantially for larger proteins, particularly under conditions of low acceleration voltage.

show abstract

“…They are used as micro hotplates for gas sensors, 1 as vacuum windows for ion beams, x rays, and ultraviolet radiation, 2 and as an electronpermeable substrate for transmission-electron microscopy. 3 In fundamental research they are used as building blocks for photonic crystals, 4,5 as an elastic substrate for mechanically controlled metallic contacts, 6 as temperature sensors with high thermal, spacial and temporal resolution, 7 as ion detectors for mass spectrometry, 8 and as a sieve on a molecular length scale. 9 Membranes inside an optical cavity allow coherent coupling of optical and mechanical degrees of freedom.…”

Section: Introductionmentioning

confidence: 99%

Mode shape and dispersion relation of bending waves in thin silicon membranes

et al. 2012

View full text Add to dashboard Cite

We study the vibrational behavior of silicon membranes with a thickness of a few hundred nanometers and macroscopic lateral size. A piezo is used to couple in transverse vibrations, which we monitor with a phase-shift interferometer using stroboscopic light. The observed wave pattern of the membrane deflection is a superposition of the mode corresponding to the excitation frequency and several higher harmonics. Using a Fourier transformation in time, we separate these contributions and image up to the eighth harmonic of the excitation frequency. With this method we determine the dispersion relation of membrane oscillations in a frequency range up to 12 MHz. We develop a simple analytical model combining stress of a membrane and bending of a thin plate that describes both the experimental data and finite-elements simulations very well. We derive correction terms to account for a finite curvature of the membrane and for the inertia of the surrounding atmosphere. A simple criterion for the transition between stressed membrane and thin plate behavior is presented.

show abstract

A Mechanical Nanomembrane Detector for Time-of-Flight Mass Spectrometry

Cited by 44 publications

References 28 publications

Top-down Proteomics: Technology Advancements and Applications to Heart Diseases

Top-down Proteomics: Technology Advancements and Applications to Heart Diseases

Detection of Large Ions in Time-of-Flight Mass Spectrometry: Effects of Ion Mass and Acceleration Voltage on Microchannel Plate Detector Response

Mode shape and dispersion relation of bending waves in thin silicon membranes

Contact Info

Product

Resources

About