Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect
ACS Publications. Most Trusted. Most Cited. Most Read
Triboelectric Nanogenerators for the Masses: A Low-Cost Do-It-Yourself Pulsed Ion Source for Sample-Limited Applications
More

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Am. Soc. Mass Spectrom. 2024, 35, 5, 943-950
  • Open Access
Article

Triboelectric Nanogenerators for the Masses: A Low-Cost Do-It-Yourself Pulsed Ion Source for Sample-Limited Applications
Click to copy article linkArticle link copied!

  • Carter K. Asef
    Carter K. Asef
    School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
    More by Carter K. Asef
    Orcidhttps://orcid.org/0000-0002-5020-0583
  • Daniel D. Vallejo
    Daniel D. Vallejo
    School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
    More by Daniel D. Vallejo
    Orcidhttps://orcid.org/0000-0001-7617-0477
  • Facundo M. Fernández*
    Facundo M. Fernández
    School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
    Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
    *Phone: (404) 385-4432. Fax: (404) 894-7452. E-mail: [email protected]
    More by Facundo M. Fernández
Open PDFSupporting Information (2)

Journal of the American Society for Mass Spectrometry

Cite this: J. Am. Soc. Mass Spectrom. 2024, 35, 5, 943–950
Click to copy citationCitation copied!
https://doi.org/10.1021/jasms.4c00010
Published April 16, 2024

Copyright © 2024 The Authors. Published by American Chemical Society. This publication is licensed under

CC-BY 4.0 .

Abstract

Click to copy section linkSection link copied!
High Resolution Image
Download MS PowerPoint Slide

Triboelectric nanogenerators (TENG) are useful devices for converting mechanical motion into electric current using readily available materials. Though the applications for these devices span across many fields, TENG can be leveraged for mass spectrometry (MS) as inexpensive and effective power supplies for pulsed nanoelectrospray ionization (nESI). The inherently discontinuous spray provided by TENG is particularly useful in scenarios where high sample economy is imperative, as in the case of ultraprecious samples. Previous work has shown the utility of TENG MS as a highly sensitive technique capable of yielding quality spectra from only a few microliters of sample at low micromolar concentrations. As the field of miniaturized, fieldable mass spectrometers grows, it remains critical to develop advanced ion sources with similarly small power requirements and footprints. Here, we present a redesigned TENG ion source with a sub-1000 USD material cost, lower power consumption, reduced footprint, and improved capabilities. We validate the performance of this new device for a diverse set of applications, including lipid double bond localization and native protein analysis.

This publication is licensed under

CC-BY 4.0 .
  • cc licence
  • by licence
Copyright © 2024 The Authors. Published by American Chemical Society

Subjects

what are subjects

Introduction

Click to copy section linkSection link copied!
The fundamental operational principle of mass spectrometry (MS) involves the successful generation of gas-phase ions from the analytes of interest. Numerous ionization technologies have been developed that allow probing a diverse range of molecular classes in a variety of ways. Electrospray ionization (ESI) is one of the most widely used methods for investigating biological samples (e.g., metabolites, proteins, etc.), with refinements such as microelectrospray and nanoelectrospray (nESI) offering reduced sample consumption, improved sensitivity, and greatly enhanced ionization efficiency. (1,2) The majority of ESI approaches, however, rely on high-voltage DC power supplies that apply a constant voltage to the emitter, producing a continuous supply of ions. As a result, ions produced outside of the accumulation or pulsing periods of trapping or time-of-flight mass spectrometers may be wasted and not fully utilized. (3) Pulsed ESI approaches overcome this drawback, reducing sample consumption with minimal duty cycle losses by rapidly switching current on and off. (4) In addition, these pulsed techniques reduce emitter heating, allowing for higher voltages to be applied while decreasing the chances of clogging. (5)
Triboelectric nanogenerators (TENG) are intrinsically pulsed voltage generators (6) and have been previously deployed to improve upon DC nESI approaches. (7−9) TENG provide voltage to the nESI emitter by harvesting triboelectricity, the electrical potential generated when rubbing dissimilar materials against one another. (10) This harvested energy can generate very high voltages, on the order of several kilovolts, while delivering nanocoulombs of charge per pulse. (9) The high voltage/low charge nature of TENG combined with their pulsed implementation enables certain applications that are entirely unique to TENG nESI, such as improving sensitivity for subnanoliter metabolomics (11) and structural characterization of femtomole quanities of proteins neccessary for cultural heritage objects. (12) Ion–molecule reactions can also be conducted within the ionization region without damaging the emitter orifice, enabling lipid double bond epoxidation under standard nESI conditions. (13)
Due to their simplicity, TENG have also shown utility in ambient ionization, such as for driving toothpick-ESI to characterize falsified antimalarial medications (14) TENG are especially useful in this arena, as they preclude the necessity of a high-voltage DC power supply, one of the hurdles in the development of fieldable MS devices that might be operated by untrained personnel. (15) TENG ion sources use low-voltage power supplies to drive the necessary mechanical motion, with the generated high-voltage electricity presenting little more danger than static shock. As compared to other liquid ionization techniques which also do not require high-voltage power supplies such as atmospheric-pressure photoionization, vibrating sharp-edge spray ionization, and zero-voltage paperspray, TENG is unique in that it can preserve the high sensitivity and other traits associated with nESI when used with standard glass capillary nESI emitters. (11,16−19)
Despite the analytical benefits of TENG for nESI MS analysis, the construction of previous generation TENG nESI ion sources required costly and bulky equipment and materials, restricting their use in field applications and reducing their accessibility. Here, we describe a new TENG nESI ion source build that leverages consumer electronics, bulk materials, and 3D printing. This new construction provides a 20-fold decrease in cost and 30-fold decrease in size compared to previously reported TENG designs, putting it on par with the power supply equipment required for pulsed DC nESI in terms of footprint while maintaining a lower cost. (3−5) This signifcantly smaller device opens new opportunities for conducting nESI experiments in frugal academic settings, including mobile field demonstrations when powered by a small portable power station or battery. Additionally, this new portability lends well to the growing field of on-site and point of care mass spectrometry. (15,20−23) We demonstrate this new design is capable of reproducing previously reported data with high fidelity while unveiling new TENG nESI mechanisms not previously reported. We provide extensive step-by-step build instructions with the goal of democratizing TENG nESI for a wider audience in the MS field.

Materials and Methods

Click to copy section linkSection link copied!

Chemicals

Lipid standards were purchased through Avanti Lipids. Optima grade water, acetone, and methanol solvents were purchased from Fisher Scientific. LC MS grade ammonium acetate and NIST 1950 reference human blood plasma were purchased from MilliporeSigma. Protein samples were purchased from Sigma-Aldrich in lyophilized form. Cytochrome C (CytC), bovine serum albumin (BSA), concanavalin A (ConA), and alcohol dehydrogenase (ADH) were used as protein standards, and human serum albumin (HSA) was used as a positive control for collision cross-section (CCS) calibration purposes.

Triboelectric Nanogenerator Device

The sliding freestanding triboelectric nanogenerator (SF TENG) power source is composed of a stationary platform and a sliding platform (Figure 1). The sliding platform is constructed with a 120 mm × 97.5 mm rectangle of adhesive-backed 1/16′′ polyurethane foam (McMaster-Carr, 86375K162) mounted onto 1/4′′ cast acrylic (McMaster-Carr 8560K354). The stationary platform is a 120 mm × 200 mm rectangle of 1/4′′ cast acrylic covered on one side with adhesive copper foil tape (Amazon, ASIN B095SC3QR7). A 10 mm gap is cut into the copper foil to create two separate 95 mm × 120 mm electrodes at opposite ends of the platform. Small tabs of excess copper foil are left on each of the electrodes to allow for connection to wire leads. A film of 0.01′′ adhesive backed PTFE (McMaster-Carr, 2208T62) is used to cover the entire platform on top of the copper foil. Once both the adhesive and sliding elements are constructed, the sliding platform is mounted onto the moving platform of a belt drive linear actuator (Amazon, ASIN B081Z7S295) using 1/8′′ double-sided foam tape. A cage of 2020 aluminum extrusions is constructed around the actuator to hold the PTFE side of the stationary platform against the polyurethane side of the sliding platform, with uniform pressure. Double sided foam tape is used to mount the stationary platform to the aluminum cage. The linear actuator is controlled by an Arduino Uno R3 housed in a 3D-printed enclosure containing other necessary electrical components. A full list of components and a wiring diagram are shown in Table S1 and Figure S1, respectively. Arduino code, 3D files, and detailed assembly videos can be found on our GitHub (https://github.com/facundof2016/DIY-TENG). The device was powered either by a 24 V 5 A wall power supply or by a 156 Wh, 24 V lithium battery.

Figure 1

Figure 1. Schematic of the sliding freestanding TENG ion source interfaced with MS. Polyurethane padding is affixed to a rigid acrylic substrate mounted onto the moving platform of a belt drive actuator. The polyurethane film is pressed against a stationary platform of PTFE film and copper tape affixed to a rigid acrylic substrate. The copper tape has a 7.5 mm gap in the middle to form two distinct electrodes, one connected to an earth grounding pin on the mass spectrometer and the other connected to the nanoelectrospray emitter. The belt is driven by an Arduino-controlled stepper motor that slides the moving platform from one end of the stationary platform to the other. The moving platform pauses at each end and then reverses direction for the next stroke. The speed of the stroke and the delay between strokes is controlled by two potentiometer dials connected to the Arduino control board.

High Resolution Image
Download MS PowerPoint Slide

Nanoelectrospray Ionization (nESI) Conditions

Emitters for nESI experiments were produced in-house from borosilicate thin-wall glass capillaries with a starting outer diameter (OD) of 1 mm and an inner diameter (ID) of 0.78 mm (Harvard Apparatus, Holliston, MA). Borosilicate capillary emitters were pulled to ∼10 μm ID for lipid experiments and ∼1–2 μm ID for protein experiments using a Sutter Instruments P-97 Flaming Brown Puller (Novato, CA). Parameters for the puller programs are provided in Table S2. Samples were loaded into the nESI emitter (2–8 μL) using a gel loader pipet, and the emitters were mounted on an x, y, z manual linear stage (Thorlabs, Newton, NJ) to control their position relative to the inlet sampling cone. The emitter tip was held between 7–10 mm away from the inlet orifice. Ions were generated in positive ion mode in all cases, although negative ion mode is also possible.

Electrical Measurements and Spray Visualization

A Tektronix TDS3012B 1 MΩ oscilloscope was used to obtain waveform data for the TENG device. Due to the low charge generated by the TENG device, a 50 MΩ multimeter was used to better measure maximum voltages. A video (Supporting Information) of the electrospray plume was recorded on a Dino-Lite AM4012PTL microscope camera with illumination from a class 3B 432 nm laser.

Sample Preparation and MS Analysis

To extract the NIST 1950 standard, 50 μL of plasma was mixed with 150 μL of IPA, vortexed for 1 min, and centrifuged, and the supernatant was transferred to a LC MS vial. Plasma samples were analyzed by LC MS on an Accucore C30 150 × 2.1 mm, 2.6 μm column as previously described. (24) Collected fractions of reference plasma were dried in a Labconco CentriVap until completely dry and reconstituted at 1/20th the initial volume in 75:12.5:12.5 acetone:water:methanol (v:v:v) with 25 mM ammonium acetate. Lipid standards were first diluted in Optima-grade 2-propanol to concentrations ranging from 200 to 1000 μM and then diluted to their final concentrations of 20 μM in 75:12.5:12.5 acetone:water:methanol (v:v:v) with 25 mM ammonium acetate. Lipid samples were analyzed on a ThermoFisher Orbitrap ID-X tribrid mass spectrometer. Protein samples were analyzed on a Waters Synapt G2 mass spectrometer. All ID-X mass spectra were collected using the ion trap detector in normal scan mode unless otherwise noted. For both mass spectrometers, the standard ion sources were removed and interlocks temporarily defeated as shown in Figures S2–S4. Emitters were held to the inlet of the mass spectrometer using a 3D-printed holder and ring stand (see files in GitHub). Electricity was delivered to the emitters either directly through a platinum wire in contact with the liquid sample within the emitter (Figure 1) or inductively using a conductive graphite sleeve surrounding the emitter (Figure S3). Proteins samples were kept on ice and buffer exchanged into 200 mM ammonium acetate buffer at pH 7 using Micro Biospin columns with either a 6 or 30 kDa cutoff (Bio-Rad, Hercules, CA), based on the analyte protein molecular weight. Buffer-exchanged samples were then diluted to a working concentration of 10 μM prior to analysis.

Data Analysis

Experimental CCS values for the standard proteins were compared to the standard protein CCS Database. (25) Experimental CCS values for HSA were calibrated using the standard protein measurements. Percent differences were calculated between the CCS database values, and the average CCS experimental values were computed from intra- and interday CCS measurements. Root-square deviation values were computed for the intra- and interday CCS measurements. Drift time and CCS data were extracted at each collision voltage in DriftScope (Waters, Milford, MA) using TWIMExtract, (26) and CCS calibrations were conducted using the IMSCal software. (27)

Results and Discussion

Click to copy section linkSection link copied!
Our previously reported TENG ion source (8) relied on a linear motor (LinMot, Lake Geneva, WI) to drive the required back-and-forth motion of the sliding polyurethane platform. This design was not suitable for portable or fieldable applications due to the size and power consumption of the linear motor itself and the required ancillary equipment, which included a 72 V power supply, motor controller, and a desktop PC. The first step in reducing the size and increasing portability of this device was to choose a more suitable linear actuator. Belt drive actuators are inexpensive and available in a large number of configurations, making them excellent candidates. The necessary speeds and forces were easily met by a widely available NEMA 23 stepper motor powering the belt drive actuator. From here, the next design choice involved controlling the motor and packaging all ion source elements together. Control functions were accomplished with an Arduino UNO R3 and a mix of readily available electronic, structural, and 3D printed components (Table S1). A schematic of the new TENG ion source is given in Figure 1. Stroke speed and the delay between strokes were controlled using two potentiometer knobs, with the current settings being displayed on the small LCD screen.
Following its construction as documented on GitHub (https://github.com/facundof2016/DIY-TENG), the electrical performance of this new ion source was characterized, given the radically changed construction. Peak voltages were measured at 4.19 kV on the new ion source compared to 3.12 kV on the old source. Due to the low charge generated, it is likely that open circuit voltages are considerably higher than what can be measured on a 50 MΩ multimeter or 1 MΩ oscilloscope. (9) The reduced voltage of the “older” TENG device may be attributed to aging of the triboelectric materials caused by years of friction, highlighting the need for occasional refreshing of the electrically active layers. A 156 Wh, 24 V battery was able to power the new ion source continuously for ∼8 h at 100% stroke speed, with no delay between strokes. This run time is expected to be considerably longer when operating at reduced stroke speeds with a delay between strokes, as is typical for TENG operation. (28) Figure 2A shows that voltage is generated during the movement of the polyurethane platform, returning to baseline during pauses between motion and then reversing polarity when traveling in the opposite direction. When overlaying total ion counts (TIC) with measured voltage, as in Figure 2B, it was observed that electrospray continued for 3 scans (∼180 ms) after voltage generation had stopped, indicating some degree of accumulated charge in the system was still flowing. Lastly, Figure 2C demonstrates the ability to vary the maximum voltage by changing the sliding speed of the polyurethane platform. The reproducibility of this voltage generation and the correlation to stroke speed are shown in Table 1.
Table 1. Maximum Observed Voltage as Recorded for 20 Pulses at Three Speed Settingsa
 30% speed50% speed100% speed
mean potential (V)b182281481
standard deviation (V)b3.677.9311.0
RSD (%)2.02.82.3
percent max. potential37.858.4100.0
a

The mean, standard deviation, and RSD for these 20 pulses are reported above. The mean potential for 30% and 50% speeds are reported as a percentage of the mean potential at 100% speed in the “percent max potential” fields. A stroke speed of 100% represents a frequency of 1.87 Hz.

b

Voltage as measured by 1 MΩ oscilloscope. Voltages >4 kV measured using 50 MΩ multimeter. Emitter voltage is likely considerably higher. (9)

Figure 2

Figure 2. (A) Observed voltage vs slider position demonstrating voltage generation during ion source actuation. The polarity is determined by the direction of motion. (B) An overlay of total ion current vs observed voltage showing that ion signal continues for ∼180 ms after reversal of the electrode motion. (C) A comparison of observed voltages at different stroke speeds over 20 pulses. A stroke speed of 100% represents a frequency of 1.87 Hz. *Voltage as measured by 1 MΩ oscilloscope. Voltages >4 kV measured using a 50 MΩ multimeter. Emitter voltage is likely considerably higher. (9)

High Resolution Image
Download MS PowerPoint Slide
To demonstrate the utility of this new ion source build for bioanalytical purposes, we revisited the previously observed phenomenon of lipid double bond epoxidation during TENG nESI. (8,13) This epoxidation is caused by operating the TENG ion source in a dual atmospheric pressure chemical ionization (APCI)/nESI mode. APCI is triggered by a pulsed corona discharge that can be observed at the tip of a nESI emitter during negative TENG pulses, when using a platinum wire in direct contact with the liquid solution filling the emitter. When the corona discharge is produced in each cycle of TENG actuation, +16 Da oxidation shifts can be readily observed in the mass spectrum, indicating addition of atomic oxygen. Interestingly, the corona discharge was not observed when using a conductive carbon sleeve surrounding the emitter for inductive charging, indicating the glass emitter causes an effective electric field reduction preventing the breach of the air gap between the emitter and the inlet. Additionally, the low current and pulsed nature of this corona discharge avoids excessive heating of the emitter, therefore not damaging its orifice.
Oxidation reactions are commonly employed to provide fragmentation sites on unsaturated fatty acid chains, as these lipid C═C bonds do not regularly fragment during collision-induced dissociation. OzID is one such commonly cited technique, though it requires substantial modification to the inner components of the mass spectrometer and the use of hazardous ozone gas. (29) Other techniques require derivatization, such as Paterno–Büchi reactions, (30−32) unnecessarily complicating the workflow. TENG nESI is unique in that it requires no additional reagents or modifications to the mass spectrometer other than disconnecting and bypassing the manufacturer’s original ion source and replacing it with the TENG setup. Oxidation reactions are enabled by a specialized sample solvent composition, typically 75:12.5:12.5 acetone:water:methanol with 25 mM ammonium acetate, and direct electrical contact with the liquid sample. The epoxidation reaction can therefore be halted by using different solvents or by using a conductive graphite sleeve to inductively generate the electric field in lieu of the platinum wire. Three lipid standards were purchased with differing lipid class and chain composition as shown in Figure 3. Plots A–C show MS1 spectra for each individual standard as measured in negative ion mode using the ion trap detector. Though [M – H]− ions were the primary observed species, a singly oxidized [M + O – H]− feature was observed for all three standards at +16 Da from the primary ion. In both PG standards, which contained a total of two double bonds in their fatty acid chains, doubly oxidized ions were observed as well. Figure 3D–F shows the resulting MS2 spectra when isolating the singly oxidized species for each standard. The most intense fragments were the individual fatty acid chains, showing a mixture of oxidized and unoxidized fatty acids. For PE 18:0/18:1, the ratio of the unoxidized 18:1 fatty acid fragment at 281.3 Da to the oxidized fragment at 297.3 Da indicates that a majority of the singly oxidized precursor ion (760.8 Da) was oxidized along the fatty acid chain. These oxidized fatty acid chains were isolated for another round of fragmentation as shown in Figure 3G–I. Fragmentation occurred readily at the site of oxidation to generate aldehyde and aldehyde and terminal alkene fragment ions diagnostic of the double bond position. All annotated MS3 fragments aligned with the expected double bond positions for all the purchased standards.

Figure 3

Figure 3. (A–C) Full MS data for TENG nESI analysis of three different lipid standards. The primary observed species are labeled, including singly- and doubly oxidized ions. (D–F) MS2 spectra for the singly oxidized lipid species, indicating epoxide formation on unsaturated fatty acid chains. (G–I) MS3 spectra for the fragmentation of epoxide chain MS2 fragments. Annotated diagnostic fragments indicate the presence of double bonds at the Δ9 position on 18:1 chains, and Δ9 and Δ12 positions of the 18:2 chains.

High Resolution Image
Download MS PowerPoint Slide
Though standards are useful to validate new technologies, their analysis is rarely the end goal of any study. To test the ion source more thoroughly, we used NIST reference serum as a testbed to demonstrate a more biologically relevant application. A single serum sample was extracted with IPA for lipid metabolites and then analyzed by LC MS. Once the retention time was measured for a notable lipid species, PC(34:2), we employed one of the six-way valves of the LC system to divert flow to a collection vial during the elution time of this species. Figure 4A,B shows the XIC for this lipid species before and after employing the divert valve, indicating that the center of the peak was successfully cutoff. Ten injections of 2 μL were diverted for a total collection volume of 400 μL (0.1 min diversions @ 400 μL/min flow rate), which were then dried under vacuum and reconstituted at 1/20th the volume in the oxidation buffer solvent. This concentrated sample was then loaded into a glass capillary emitter and analyzed by TENG-nESI MS3. The observed fragments shown in Figure 4C were consistent for PC 16:0/18:2 with the double bonds of the 18:2 chain, identifying it as linoleic acid, a common biological fatty acid. The complete structural elucidation of this lipid from a biological sample shows the ability of TENG-nESI to integrate with traditional LC MS lipidomics studies to provide more detailed structural information on unknown lipids.

Figure 4

Figure 4. (A) Extracted ion chromatogram (XIC) at m/z = 802 for (PC 34:2) detected from the LC MS analysis of NIST SRM 1950 reference plasma. (B) A switching valve was employed during elution to divert the feature to a collection vial. (B) XIC of the same feature from a diverted run indicates successful capture of a majority of the feature. (C) MS3 spectrum from the collected fraction after drying and reconstituting into 75:12.5:12.5 acetone:water:methanol (v:v:v) with 25 mM ammonium acetate showing diagnostic fragments for double bonds at the Δ9 and Δ12 positions.

High Resolution Image
Download MS PowerPoint Slide
The sensitivity of these MS3 fragments is the current limiting factor of the technique, as it involves two rounds of fragmentation of a minor oxidation product. Though many parameters of the TENG-nESI experiment including solvent composition, emitter orifice diameter, and TENG stroke settings were optimized to promote oxidation, oxidation rates rarely exceeded 8% of the primary ion. As the number of double bonds in the molecule increases, the ion population becomes further split into more fragment ion channels. These effects ultimately limit the current version of this technology to fatty acid chains with fewer than four double bonds and concentrations in the low-micromolar range or higher.
A higher oxidation rate has the potential to increase sensitivity by 1 order of magnitude, greatly expanding the breadth of lipids which could be analyzed by this technique. The oxidation mechanism has been hypothesized to involve hydroxide radicals within the atmospheric pressure corona discharge, though a full investigation has not been performed. (8) During our analysis, we observed a period of high oxidation yields which occurred during the collapse of the Taylor cone at the end of each TENG pulse. To further investigate this phenomenon, we used the rapid scan rate of the ion trap detector while slowing down the speed of the TENG stroke to 20% with a 1 s delay between strokes (∼0.27 Hz). A recording of the resulting spray is shown in Video S1. Under these conditions, we were able to reproducibly observe [M + O – H]− oxidation products with >100% the abundance of the [M – H]− precursor lipid. The results of this experiment are shown in Figure 5. Though the overall oxidation yield was greatly increased (Figure 5F), the absolute abundance of the oxidized species did not significantly increase (Figure 5H). However, we hope to leverage this phenomenon in the future to better understand the effects of cone formation and collapse on the mechanism of oxidation, improving sensitivity.

Figure 5

Figure 5. (A) TENG driven spray dynamics earlier in the TENG cycle. (B) A distinct shift in spray mode is observed during the tail end of the voltage pulses when running at low stroke speeds. Regions of normal spray (C) and multijet spray (D) are highlighted with their associated mass spectra (E and F) when analyzing a pure PG(18:1/18:1) standard. Extracted ion chromatograms for [M – H], [MO – H]−, and [MOO – H]− are shown (G) and rescaled to oxidized species (H). Extreme ratios of oxidized/unoxidized ions are observed during the multijet regime, though absolute abundances did not increase significantly.

High Resolution Image
Download MS PowerPoint Slide
In addition to lipids, we also investigated the performance of this new TENG ion source for protein mass spectrometry. Previously, we reported on TENG-IM-MS approaches and their capability to generate native protein structures with collision cross-sections (CCS) measurements in agreement with community published values. The radically new design of the new TENG ion source warranted re-evaluating its capability to generate high fidelity native MS (nMS) measurements. Using BSA, a well validated protein standard for nMS experiments, the new TENG design resulted in excellent quality native BSA mass spectra (Figure 6A) that were qualitatively and quantitively indistinguishable from the previous TENG data (Figure S5). However, as noted previously, this approach used inductive emitter charging, which did not result in a corona discharge. When using the platinum wire, a mass spectrum that matched the charge state distribution for native BSA was generated but with a notable broadening of the peaks and a slight increase (∼2–3%) in the amount of dimer. These results suggest that the corona discharge is either leading to increased nonspecific oligomerization or to specific oligomerization due to slight protein unfolding. However, when calibrated for CCS we noted no major changes in CCS for BSA or HSA when comparing the conductive or platinum wire ionization approach (Figure 6C–E).

Figure 6

Figure 6. Mass spectra of native BSA under (A) inductive and (B) Pt wire-induced nESI resulting in qualitative differences in peak width (fwhm) and quantitative differences in nonspecific dimers. (C) CCS calibration indicates the new TENG ion source produces high fidelity native protein signals within (D) 3% of database reference values. (E) No quantitative difference in CCS of inductive vs Pt wire-generated protein ions, indicating that in both conditions proteins retain their native structure.

High Resolution Image
Download MS PowerPoint Slide

Conclusions

Click to copy section linkSection link copied!
We present a cost-effective ion source which operates on the triboelectric principle. Detailed instructions for assembly are included in the Supporting Information. This revised design of the TENG meets or exceeds the electrical characteristics of the previous design while reducing cost and footprint. Voltages upward of 4 kV could be measured, and the between-voltage pulse RSD was less than 3% across a range of parameters.
The unique capabilities and simplicity of this ion source make it well suited for its use in a wide range of academic and research environments. The device can interface with most mass spectrometers with atmospheric pressure inlets, ranging from research-grade tribrid Orbitrap systems to simpler quadrupole and ion trap instruments. Its low power consumption (less than 100W) makes it well suited for use with fieldable instruments.
Taken together, we present a cost-effective, field deployable ion source capable of structural characterization for biomolecules ranging from lipids to proteins. By democratizing this technology through build tutorials, we envision other research groups will not only further demonstrate its applications to a wide range of analytes but also innovate upon the technology with unique configurations of their own design.

Supporting Information

Click to copy section linkSection link copied!

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jasms.4c00010.

  • Video S1 visualizes nanoESI during the TENG pulses described in Figure 5 (MP4)

  • Detailed information is provided on the TENG hardware list, wiring diagram for assembly, MS inlet setup, and data comparison between old and new TENG designs (PDF)

Terms & Conditions

Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

Author Information

Click to copy section linkSection link copied!
  • Corresponding Author
    • Facundo M. Fernández - School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States;  Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, United States;  Email: [email protected]
  • Authors
  • Author Contributions

    These authors contributed equally. Carter K. Asef: Conceptualization, software, validation, formal analysis, narration and performing build videos, writing - original draft, writing - review and editing, visualization. Daniel D. Vallejo: Conceptualization, formal analysis, videography and editing of videos, writing- original draft, writing - review and editing, visualization. Facundo M. Fernandez: Writing - review and editing, supervision, funding. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

  • Notes
    The authors declare no competing financial interest.

Acknowledgments

Click to copy section linkSection link copied!

We thank the members of the Fernández lab for helping test the initial prototypes throughout the lifetime of this project. D.D.V. was supported by the National Science Foundation Mathematical and Physical Sciences divisions ASCEND program under grant award number CHE-2138107. We also acknowledge grant R01CA218664 to F.M.F. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. Figure 1 and TOC artwork were created with BioRender.com.

References

Click to copy section linkSection link copied!

This article references 32 other publications.

  1. 1
    Wilm, M.; Mann, M. Analytical Properties of the Nanoelectrospray Ion Source. Anal. Chem. 1996, 68 (1), 1– 8,  DOI: 10.1021/ac9509519
    Google Scholar
    1
    Analytical Properties of the Nanoelectrospray Ion Source
    Wilm, Matthias; Mann, Matthias
    Analytical Chemistry (1996), 68 (1), 1-8CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
    The nanoelectrospray ion source (nanoES) was recently developed and described theor. It is different from conventional electrospray sources and from other miniaturized electrospray sources by (1) its 1-2-μm spraying orifice achieved by pulling the spraying capillary to a fine tip, (2) its very low flow rate of ∼20 nL/min and the small size of droplets it generates, and (3) the absence of solvent pumps and inlet valves. The fabrication and operation of nanoES needles is described in detail. Solns. with up to 0.1M salt contents could be sprayed without sheath flow or pneumatic assist. Improved desolvation in nanoES led to instrument-limited resoln. of the signals of a glycoprotein and the ability to signal av. extensively allowed the C-terminal sequencing of a 40-kDa protein. Extensive mass spectrometric and tandem mass spectrometric investigation of the components of an unsepd. peptide mixt. was demonstrated by verification of 93% of the sequence of carbonic anhydrase. A rapid and robust desalting/concn. step coupled to the nanoES procedure allows the direct anal. of impure samples such as peptide mixts. extd. after in-gel digestion.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXpslSru7k%253D&md5=f396fcfc0b8effec0132e60a6267bfd3
  2. 2
    Emmett, M. R.; Caprioli, R. M. Micro-Electrospray Mass Spectrometry: Ultra-High-Sensitivity Analysis of Peptides and Proteins. J. Am. Soc. Mass Spectrom. 1994, 5 (7), 605– 613,  DOI: 10.1016/1044-0305(94)85001-1
    Google Scholar
    2
    Micro-electrospray mass spectrometry: Ultra-high-sensitivity analysis of peptides and proteins
    Emmett, Mark R.; Caprioli, Richard M.
    Journal of the American Society for Mass Spectrometry (1994), 5 (7), 605-13CODEN: JAMSEF; ISSN:1044-0305.
    A "micro-electrospray" ionization source has been developed that markedly increases the sensitivity of the conventional electrospray source. This was achieved by optimization of the source to accommodate nanoliter flow rates from 300 to 800 nL/min spraying directly from a capillary needle that, for the anal. of peptides, contained C18 liq. chromatog. packing as an integrated concn.-desalting device. Thus, a total of 1 fmol of methionine-enkephalin was desorbed from the capillary column spray needle, loaded as a 10-μL injection of 100-amol/μL soln. The mass spectrum showed the [M + H]+ ion at m/z 574.2 with a signal-to-noise ratio of better than 5:1 from a chromatog. peak with a width of about 12 s. A narrow range (15-u) tandem mass spectrum was obtained for methionine-enkephalin from the injection of 500 amol, and a full-scan tandem-mass spectrum was obtained from 50 fmol. For proteins, the av. mass measurement accuracy was approx. 100-200 ppm for the injection of 2.5 fmol of apomyoglobin and 20-40 ppm for 200 fmol. Carbonic anhydrase B and bovine serum albumin showed similar mass measurement accuracies.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXmt1Gmt74%253D&md5=4da21d48deaa122b197b42974e71e3f5
  3. 3
    Wei, Z.; Xiong, X.; Guo, C.; Si, X.; Zhao, Y.; He, M.; Yang, C.; Xu, W.; Tang, F.; Fang, X.; Zhang, S.; Zhang, X. Pulsed Direct Current Electrospray: Enabling Systematic Analysis of Small Volume Sample by Boosting Sample Economy. Anal. Chem. 2015, 87 (22), 11242– 11248,  DOI: 10.1021/acs.analchem.5b02115
    Google Scholar
    3
    Pulsed Direct Current Electrospray: Enabling Systematic Analysis of Small Volume Sample by Boosting Sample Economy
    Wei, Zhenwei; Xiong, Xingchuang; Guo, Chengan; Si, Xingyu; Zhao, Yaoyao; He, Muyi; Yang, Chengdui; Xu, Wei; Tang, Fei; Fang, Xiang; Zhang, Sichun; Zhang, Xinrong
    Analytical Chemistry (Washington, DC, United States) (2015), 87 (22), 11242-11248CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
    We had developed pulsed d.c. electrospray ionization mass spectrometry (pulsed-dc-ESI-MS) for systematically profiling and detg. components in small vol. sample. Pulsed-dc-ESI utilized const. high voltage to induce the generation of single polarity pulsed electrospray remotely. This method had significantly boosted the sample economy, so as to obtain several minutes MS signal duration from merely picoliter vol. sample. The elongated MS signal duration enable us to collect abundant MS2 information on interested components in a small vol. sample for systematical anal. This method had been successfully applied for single cell metabolomics anal. We had obtained 2-D profile of metabolites (including exact mass and MS2 data) from single plant and mammalian cell, concerning 1034 components and 656 components for Allium cepa and HeLa cells, resp. Further identification had found 162 compds. and 28 different modification groups of 141 saccharides in a single Allium cepa cell, indicating pulsed-dc-ESI a powerful tool for small vol. sample systematical anal.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhs1yltr3I&md5=bd117ff6a921704e0798d756e5d0f135
  4. 4
    McMahon, W. P.; Dalvi, R.; Lesniewski, J. E.; Hall, Z. Y.; Jorabchi, K. Pulsed Nano-ESI: Application in Ion Mobility-MS and Insights into Spray Dynamics. J. Am. Soc. Mass Spectrom. 2020, 31 (3), 488– 497,  DOI: 10.1021/jasms.9b00121
    Google Scholar
    There is no corresponding record for this reference.
  5. 5
    Xu, Z.; Wu, H.; Tang, Y.; Xu, W.; Zhai, Y. Electric Modeling and Characterization of Pulsed High-Voltage Nanoelectrospray Ionization Sources by a Miniature Ion Trap Mass Spectrometer. Journal of Mass Spectrometry 2019, 54 (7), 583– 591,  DOI: 10.1002/jms.4361
    Google Scholar
    There is no corresponding record for this reference.
  6. 6
    Liu, D.; Zhou, L.; Wang, Z. L.; Wang, J. Triboelectric Nanogenerator: From Alternating Current to Direct Current. iScience 2021, 24 (1), 102018  DOI: 10.1016/j.isci.2020.102018
    Google Scholar
    6
    Triboelectric nanogenerator: from alternating current to direct current
    Liu Di; Zhou Linglin; Wang Zhong Lin; Wang Jie; Liu Di; Zhou Linglin; Wang Zhong Lin; Wang Jie; Wang Zhong Lin
    iScience (2021), 24 (1), 102018 ISSN:.
    Triboelectric nanogenerator (TENG) is considered as a potential solution to harvest distributed energy for the sustainable and reliable power supply of the internet of things. Although numerous researches on alternating current (AC) output TENG from fundamental physics to potential applications have been widely promoted in recent years, the studies about direct current (DC) output TENG is just beginning, especially for a constant current output. This work gives the summary of recent key researches from AC-TENG to DC-TENG, especially a constant current TENG, as well as the design of AC/DC-TENG. In addition, some new DC generators will also be summarized toward a wide range of readers. This study presents the similarities and differences between AC-TENG and DC-TENG, so that their impact and uniqueness can be clearly understood. Finally, the major challenges and the future outlooks in this rapidly emerging research field will be discussed as a guideline for future research.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3srkslCrsQ%253D%253D&md5=5ef9c9b977a3d7310a02867af701e01d
  7. 7
    Ma, X.; Fernández, F. M. Triboelectric Nanogenerator-Coated Blade Spray Mass Spectrometry for Volume-Limited Drug Analysis. Int. J. Mass Spectrom. 2024, 495, 117164  DOI: 10.1016/j.ijms.2023.117164
    Google Scholar
    There is no corresponding record for this reference.
  8. 8
    Bouza, M.; Li, Y.; Wu, C.; Guo, H.; Wang, Z. L.; Fernández, F. M. Large-Area Triboelectric Nanogenerator Mass Spectrometry: Expanded Coverage, Double-Bond Pinpointing, and Supercharging. J. Am. Soc. Mass Spectrom. 2020, 31 (3), 727– 734,  DOI: 10.1021/jasms.0c00002
    Google Scholar
    There is no corresponding record for this reference.
  9. 9
    Li, A.; Zi, Y.; Guo, H.; Wang, Z. L.; Fernández, F. M. Triboelectric Nanogenerators for Sensitive Nano-Coulomb Molecular Mass Spectrometry. Nat. Nanotechnol. 2017, 12 (5), 481– 487,  DOI: 10.1038/nnano.2017.17
    Google Scholar
    9
    Triboelectric nanogenerators for sensitive nano-coulomb molecular mass spectrometry
    Li, Anyin; Zi, Yunlong; Guo, Hengyu; Wang, Zhong Lin; Fernandez, Facundo M.
    Nature Nanotechnology (2017), 12 (5), 481-487CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)
    Ion sources for mol. mass spectrometry are usually driven by d.c. power supplies with no user control over the total charges generated. Here, we show that the output of triboelec. nanogenerators (TENGs) can quant. control the total ionization charges in mass spectrometry. The high output voltage of TENGs can generate single- or alternating-polarity ion pulses, and is ideal for inducing nanoelectrospray ionization (nanoESI) and plasma discharge ionization. For a given nanoESI emitter, accurately controlled ion pulses ranging from 1.0 to 5.5 nC were delivered with an onset charge of 1.0 nC. Spray pulses can be generated at a high frequency of 17 Hz (60 ms in period) and the pulse duration is adjustable on-demand between 60 ms and 5.5 s. Highly sensitive (∼0.6 zeptomole) mass spectrometry anal. using minimal sample (18 pl per pulse) was achieved with a 10 pg ml-1 cocaine sample. We also show that native protein conformation is conserved in TENG-ESI, and that patterned ion deposition on conductive and insulating surfaces is possible.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXltVWnsbY%253D&md5=f7573097228d217ab623e80168ea9de4
  10. 10
    Wang, Z. L. Triboelectric Nanogenerators as New Energy Technology for Self-Powered Systems and as Active Mechanical and Chemical Sensors. ACS Nano 2013, 7 (11), 9533– 9557,  DOI: 10.1021/nn404614z
    Google Scholar
    10
    Triboelectric Nanogenerators as New Energy Technology for Self-Powered Systems and as Active Mechanical and Chemical Sensors
    Wang, Zhong Lin
    ACS Nano (2013), 7 (11), 9533-9557CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)
    A review. Tribo-electrification is an effect that is known to each and every one probably since ancient Greek time, but it is usually taken as a neg. effect and is avoided in many technologies. The authors have recently invented a triboelec. nanogenerator (TENG) that is used to convert mech. energy into electricity by a conjunction of tribo-electrification and electrostatic induction. As for this power generation unit, in the inner circuit, a potential is created by the triboelec. effect due to the charge transfer between 2 thin org./inorg. films that exhibit opposite tribo-polarity; in the outer circuit, electrons are driven to flow between 2 electrodes attached on the back sides of the films to balance the potential. Since the most useful materials for TENG are org., it is also named org. nanogenerator, which is the 1st using org. materials for harvesting mech. energy. The authors review the fundamentals of the TENG in the 3 basic operation modes: vertical contact-sepn. mode, in-plane sliding mode, and single-electrode mode. Ever since the 1st report of the TENG in Jan. 2012, the output power d. of TENG was improved 5 orders of magnitude within 12 mo. The area power d. reaches 313 W/m2, vol. d. reaches 490 kW/m3, and a conversion efficiency of ∼60% was demonstrated. The TENG can be applied to harvest all kinds of mech. energy that is available but wasted in the daily life, such as human motion, walking, vibration, mech. triggering, rotating tire, wind, flowing H2O, and more. Alternatively, TENG can also be used as a self-powered sensor for actively detecting the static and dynamic processes arising from mech. agitation using the voltage and current output signals of the TENG, resp., with potential applications for touch pad and smart skin technologies. To enhance the performance of the TENG, besides the vast choices of materials in the triboelec. series, from polymer to metal and to fabric, the morphologies of their surfaces can be modified by phys. techniques with the creation of pyramid-, square-, or hemisphere-based micro- or nano-patterns, which are effective for enhancing the contact area and possibly the triboelectrification. The surfaces of the materials can be functionalized chem. using various mols., nanotubes, nanowires, or nanoparticles, to enhance the triboelec. effect. The contact materials can be composites, such as embedding nanoparticles in a polymer matrix, which may change not only the surface electrification but also the permittivity of the materials so that they can be effective for electrostatic induction. Therefore, there are numerous ways to enhance the performance of the TENG from the materials point of view. This gives an excellent opportunity for chemists and materials scientists to do extensive study both in the basic science and in practical applications. The authors anticipate that a better enhancement of the output power d. will be achieved in the next few years. The TENG is possible not only for self-powered portable electronics but also as a new energy technol. with potential to contribute to the world energy in the near future.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsFelsb%252FF&md5=0c5e218d8e55cbb48a6454c8cf0479a5
  11. 11
    Li, Y.; Bouza, M.; Wu, C.; Guo, H.; Huang, D.; Doron, G.; Temenoff, J. S.; Stecenko, A. A.; Wang, Z. L.; Fernández, F. M. Sub-Nanoliter Metabolomics via Mass Spectrometry to Characterize Volume-Limited Samples. Nat. Commun. 2020, 11 (1), 5625,  DOI: 10.1038/s41467-020-19444-y
    Google Scholar
    11
    Sub-nanoliter metabolomics via mass spectrometry to characterize volume-limited samples
    Li, Yafeng; Bouza, Marcos; Wu, Changsheng; Guo, Hengyu; Huang, Danning; Doron, Gilad; Temenoff, Johnna S.; Stecenko, Arlene A.; Wang, Zhong Lin; Fernandez, Facundo M.
    Nature Communications (2020), 11 (1), 5625CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)
    The human metabolome provides a window into the mechanisms and biomarkers of various diseases. However, because of limited availability, many sample types are still difficult to study by metabolomic analyses. Here, we present a mass spectrometry (MS)-based metabolomics strategy that only consumes sub-nanoliter sample vols. The approach consists of combining a customized metabolomics workflow with a pulsed MS ion generation method, known as triboelec. nanogenerator inductive nanoelectrospray ionization (TENGi nanoESI) MS. Samples tested with this approach include exhaled breath condensate collected from cystic fibrosis patients as well as in vitro-cultured human mesenchymal stromal cells. Both test samples are only available in min. amts. Expts. show that picoliter-vol. spray pulses suffice to generate high-quality spectral fingerprints, which increase the information d. produced per unit sample vol. This TENGi nanoESI strategy has the potential to fill in the gap in metabolomics where liq. chromatog.-MS-based analyses cannot be applied. Our method opens up avenues for future investigations into understanding metabolic changes caused by diseases or external stimuli.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitlWgu7fF&md5=c26617ccf1bd401456f2b038df5176b7
  12. 12
    Vallejo, D. D.; Popowich, A.; Arslanoglu, J.; Tokarski, C.; Fernández, F. M. Native Triboelectric Nanogenerator Ion Mobility-Mass Spectrometry of Egg Proteins Relevant to Objects of Cultural Heritage at Picoliter and Nanomolar Quantities. Anal. Chim. Acta 2023, 1269, 341374  DOI: 10.1016/j.aca.2023.341374
    Google Scholar
    There is no corresponding record for this reference.
  13. 13
    Bouza, M.; Li, Y.; Wang, A. C.; Wang, Z. L.; Fernández, F. M. Triboelectric Nanogenerator Ion Mobility–Mass Spectrometry for In-Depth Lipid Annotation. Anal. Chem. 2021, 93 (13), 5468– 5475,  DOI: 10.1021/acs.analchem.0c05145
    Google Scholar
    There is no corresponding record for this reference.
  14. 14
    Bernier, M. C.; Li, A.; Winalski, L.; Zi, Y.; Li, Y.; Caillet, C.; Newton, P.; Wang, Z. L.; Fernández, F. M. Triboelectric Nanogenerator (TENG) Mass Spectrometry of Falsified Antimalarials. Rapid Commun. Mass Spectrom. 2018, 32 (18), 1585– 1590,  DOI: 10.1002/rcm.8207
    Google Scholar
    14
    Triboelectric nanogenerator (TENG) mass spectrometry of falsified antimalarials
    Bernier, Matthew C.; Li, Anyin; Winalski, Laura; Zi, Yunlong; Li, Yafeng; Caillet, Celine; Newton, Paul; Wang, Zhong Lin; Fernandez, Facundo M.
    Rapid Communications in Mass Spectrometry (2018), 32 (18), 1585-1590CODEN: RCMSEF; ISSN:0951-4198. (John Wiley & Sons Ltd.)
    An epidemic of low-quality medicines continues to endanger patients worldwide. Detection of such 'medicines' requires low cost, ambient ionization sources coupled to fieldable (portable) mass spectrometers for optimum sensitivity and specificity. With the use of triboelec. nanogenerators (TENGs), the charge required to produce gas-phase ions for mass spectral anal. can be obtained without the need for high-voltage elec. circuitry, thus simplifying and lowering the cost of next-generation mass spectrometry instruments. A sliding freestanding (SF) TENG was coupled to a toothpick electrospray setup for the purposes of testing if falsified medicines could be fingerprinted by this approach. Exts. from both genuine and falsified medicines were deposited on the toothpick and the SF TENG actuated to generate elec. charges, resulting in gas-phase ions for both active pharmaceutical ingredients and excipients. Our previous work had shown that direct anal. in real time (DART) ambient mass spectrometry can identify the components of multiple classes of falsified antimalarial medicines. Expts. performed in this study show that a simple extn. into methanol along with the use of a SF TENG-powered toothpick electrospray can provide similar detection capabilities, but with much simpler and rugged instrumentation, and without the need for compressed gases or high-voltage ion source power supplies. TENG toothpick MS allows for rapid analyte ion detection in a safe and low-cost manner, providing robust sampling and ionization capabilities.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsV2lurrF&md5=d9136d6c8ae58d782303ff5f2743d94d
  15. 15
    Snyder, D. T.; Pulliam, C. J.; Ouyang, Z.; Cooks, R. G. Miniature and Fieldable Mass Spectrometers: Recent Advances. Anal. Chem. 2016, 88 (1), 2– 29,  DOI: 10.1021/acs.analchem.5b03070
    Google Scholar
    15
    Miniature and Fieldable Mass Spectrometers: Recent Advances
    Snyder, Dalton T.; Pulliam, Christopher J.; Ouyang, Zheng; Cooks, R. Graham
    Analytical Chemistry (Washington, DC, United States) (2016), 88 (1), 2-29CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
    A review. This review emphasizes advances in the miniaturization of mass spectrometers which have taken place since an extensive review was published in 2009. During this time, reviews on ambient ionization and miniature mass analyzers have appeared, but an integrated treatment of miniature mass spectrometers (mini MS) and ambient ionization is now needed.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFyrurbP&md5=3ca4f74190326e7d9de2a2ec1efc4636
  16. 16
    Li, X.; Attanayake, K.; Valentine, S. J.; Li, P. Vibrating Sharp-Edge Spray Ionization (VSSI) for Voltage-Free Direct Analysis of Samples Using Mass Spectrometry. Rapid Commun. Mass Spectrom. 2021, 35 (S1), e8232  DOI: 10.1002/rcm.8232
    Google Scholar
    16
    Vibrating Sharp-edge Spray Ionization (VSSI) for voltage-free direct analysis of samples using mass spectrometry
    Li, Xiaojun; Attanayake, Kushani; Valentine, Stephen J.; Li, Peng
    Rapid Communications in Mass Spectrometry (2021), 35 (S1), e8232CODEN: RCMSEF; ISSN:0951-4198. (John Wiley & Sons Ltd.)
    Rationale : The development of miniaturized and field portable mass spectrometers could not succeed without a simple, compact, and robust ionization source. Here the authors present a voltage-free ionization method, Vibrating Sharp-edge Spray Ionization (VSSI), which can generate a spray of liq. samples using only one std. microscope glass slide to which a piezoelec. transducer is attached. Compared with existing ambient ionization methods, VSSI eliminates the need for a high elec. field (∼5000 V·cm-1) for spray generation, while sharing a similar level of simplicity and flexibility with the simplest direct ionization techniques currently available such as paper spray ionization (PSI) and other solid substrate-based electrospray ionization methods. Methods : The VSSI device was fabricated by attaching a piezoelec. transducer onto a std. glass microscope slide using epoxy glue. Liq. sample was aerosolized by either placing a droplet onto the vibrating edge of the glass slide or touching a wet surface with the glass edge. Mass spectrometric detection was achieved by placing the VSSI device 0.5-1 cm from the inlet of the mass spectrometer (Q-Exactive, ThermoScientific). Results : VSSI is demonstrated to ionize a diverse array of chem. species, including small org. mols., carbohydrates, peptides, proteins, and nucleic acids. Preliminary sensitivity expts. show that high-quality mass spectra of acetaminophen can be obtained by consuming 100 fmol of the target. The dual spray of VSSI was also demonstrated by performing in-droplet denaturation of ubiquitin. Finally, due to the voltage-free nature and the direct-contact working mode of VSSI, it has been successfully applied for the detection of chems. directly from human fingertips. Conclusions : Overall, the authors report a compact ionization method based on vibrating sharp-edges. The simplicity and voltage-free nature of VSSI make it an attractive option for field portable applications or analyzing biol. samples that are sensitive to high voltage or difficult to access by conventional ionization methods.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsFeqtbrE&md5=d60a60f74698c56fb14c158c952a2521
  17. 17
    Wleklinski, M.; Li, Y.; Bag, S.; Sarkar, D.; Narayanan, R.; Pradeep, T.; Cooks, R. G. Zero Volt Paper Spray Ionization and Its Mechanism. Anal. Chem. 2015, 87 (13), 6786– 6793,  DOI: 10.1021/acs.analchem.5b01225
    Google Scholar
    17
    Zero Volt Paper Spray Ionization and Its Mechanism
    Wleklinski, Michael; Li, Yafeng; Bag, Soumabha; Sarkar, Depanjan; Narayanan, Rahul; Pradeep, T.; Cooks, R. Graham
    Analytical Chemistry (Washington, DC, United States) (2015), 87 (13), 6786-6793CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
    The anal. performance and a suggested mechanism for zero volt paper spray using chromatog. paper are presented. A spray is generated by the action of the pneumatic force of the mass spectrometer (MS) vacuum at the inlet. Pos. and neg. ion signals are obsd., and comparisons are made with std. kV paper spray (PS) ionization and nanoelectrospray ionization (nESI). While the range of analytes to which zero volt PS is applicable is very similar to kV PS and nESI, differences in the mass spectra of mixts. are interpreted in terms of the more significant effects of analyte surface activity in the gentler zero volt expt. than in the other methods due to the significantly lower charge. The signal intensity of zero volt PS is also lower than in the other methods. A Monte Carlo simulation based on statistical fluctuation of pos. and neg. ions in soln. was implemented to explain the prodn. of ions from initially uncharged droplets. Uncharged droplets 1st break up due to aerodynamics forces until they are in the 2-4 μm size range and then undergo Coulombic fission. A model involving statistical charge fluctuations in both phases predicts detection limits similar to those obsd. exptl. and explains the effects of binary mixt. components on relative ionization efficiencies. The proposed mechanism may also play a role in ionization by other voltage-free methods.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXptF2murk%253D&md5=bf3501d7ebb38bdc3c5e712c13391258
  18. 18
    Neumann, A.; Tiemann, O.; Hansen, H. J.; Rüger, C. P.; Zimmermann, R. Detailed Comparison of Xenon APPI (9.6/8.4 eV), Krypton APPI (10.6/10.0 eV), APCI, and APLI (266 Nm) for Gas Chromatography High Resolution Mass Spectrometry of Standards and Complex Mixtures. J. Am. Soc. Mass Spectrom. 2023, 34 (8), 1632– 1646,  DOI: 10.1021/jasms.3c00085
    Google Scholar
    There is no corresponding record for this reference.
  19. 19
    Robb, D. B.; Covey, T. R.; Bruins, A. P. Atmospheric Pressure Photoionization: An Ionization Method for Liquid Chromatography-Mass Spectrometry. Anal. Chem. 2000, 72 (15), 3653– 3659,  DOI: 10.1021/ac0001636
    Google Scholar
    19
    Atmospheric pressure photoionization: an ionization method for liquid chromatography-mass spectrometry
    Robb, Damon B.; Covey, Thomas R.; Bruins, Andries P.
    Analytical Chemistry (2000), 72 (15), 3653-3659CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
    Atm. pressure photoionization ( APPI) was successfully demonstrated to provide high sensitivity to LC-MS anal. A vacuum-UV lamp designed for photoionization detection in gas chromatog. was used as a source of 10-eV photons. The mixt. of samples and solvent eluting from an HPLC is fully evapd. prior to introduction into the photoionization region. In the new method, large quantities of an ionizable dopant are added to the vapor generated from the LC eluant, allowing for a great abundance of dopant photoions to be produced. Because the ion source is at atm. pressure, and the collision rate is high, the dopant photoions react to completion with solvent and analyte mols. present in the ion source. Using APPI, at an LC flow rate of 200 μL/min, it is possible to obtain analyte signal intensities 8 times as high as those obtainable with a com. available corona discharge-atm. pressure chem. ionization source.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXksFOrurg%253D&md5=9e8f4169a51e6c3ed9fa507704aaf6f0
  20. 20
    Keating, M. F.; Zhang, J.; Feider, C. L.; Retailleau, S.; Reid, R.; Antaris, A.; Hart, B.; Tan, G.; Milner, T. E.; Miller, K.; Eberlin, L. S. Integrating the MasSpec Pen to the Da Vinci Surgical System for In Vivo Tissue Analysis during a Robotic Assisted Porcine Surgery. Anal. Chem. 2020, 92 (17), 11535– 11542,  DOI: 10.1021/acs.analchem.0c02037
    Google Scholar
    20
    Integrating the MasSpec Pen to the da Vinci Surgical System for In Vivo Tissue Analysis during a Robotic Assisted Porcine Surgery
    Keating, Michael F.; Zhang, Jialing; Feider, Clara L.; Retailleau, Sascha; Reid, Robert; Antaris, Alexander; Hart, Bradley; Tan, Gina; Milner, Thomas E.; Miller, Kyle; Eberlin, Livia S.
    Analytical Chemistry (Washington, DC, United States) (2020), 92 (17), 11535-11542CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
    Minimally invasive robotic-assisted surgeries have been increasingly used as a first-line of treatment for patients undergoing oncol. surgeries. In-situ tissue identification is crit. to guide tissue resection and assist decision-making. Traditional intraoperative histopathol. anal. of frozen tissue sections can be time-consuming and present logistical challenges which interrupt surgical workflows. The authors report the development and implementation of a laparoscopic, drop-in version of the MasSpec Pen device integrated into the da Vinci Xi Surgical system for in vivo tissue anal. in a robotic-assisted porcine surgery. The authors evaluated the performance of the drop-in MasSpec Pen during surgery by introducing the device into the animal upper gastrointestinal system and performing in vivo analyses of the stomach and liver, including charred and bloody tissues after electrocauterization. The mol. profiles obtained included ions tentatively identified as metabolites and lipids typically obsd. with MasSpec Pen anal., without causing observable tissue damage. Statistical classifiers built to distinguish porcine liver and stomach tissues using the in vivo data yielded an overall tissue identification accuracy of 98% (n = 53 analyses). The results provide evidence that the drop-in MasSpec Pen developed can be used to acquire mass spectra in vivo during a robotic-assisted surgery and might be used as an in vivo tissue assessment tool to help guide surgical resections and streamline surgical workflows.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVygsrjE&md5=3ead28c68b812f4feeaf7a15ec15f024
  21. 21
    Zhai, Y.; Fu, X.; Xu, W. Miniature Mass Spectrometers and Their Potential for Clinical Point-of-Care Analysis. Mass Spectrometry Reviews 2023, 21867,  DOI: 10.1002/mas.21867
    Google Scholar
    There is no corresponding record for this reference.
  22. 22
    Liu, J.; Tang, W.; Meng, X.; Zhan, L.; Xu, W.; Nie, Z.; Wang, Z. Improving the Performance of the Mini 2000 Mass Spectrometer with a Triboelectric Nanogenerator Electrospray Ionization Source. ACS Omega 2018, 3 (9), 12229– 12234,  DOI: 10.1021/acsomega.8b01777
    Google Scholar
    There is no corresponding record for this reference.
  23. 23
    Zhou, X.; Li, S.; Ouyang, Z. Miniature Mass Spectrometers for On-Site Chemical Analysis. 2023 IEEE 36th International Vacuum Nanoelectronics Conference (IVNC); IEEE: Cambridge, MA, 2023; pp 157– 159.  DOI: 10.1109/IVNC57695.2023.10189017 .
    Google Scholar
    There is no corresponding record for this reference.
  24. 24
    Asef, C. K.; Rainey, M. A.; Garcia, B. M.; Gouveia, G. J.; Shaver, A. O.; Leach, F. E.; Morse, A. M.; Edison, A. S.; McIntyre, L. M.; Fernández, F. M. Unknown Metabolite Identification Using Machine Learning Collision Cross-Section Prediction and Tandem Mass Spectrometry. Anal. Chem. 2023, 95, 1047  DOI: 10.1021/acs.analchem.2c03749
    Google Scholar
    There is no corresponding record for this reference.
  25. 25
    Allen, S. J.; Giles, K.; Gilbert, T.; Bush, M. T. Ion Mobility Mass Spectrometry of Peptide, Protein, and Protein Complex Ions Using a Radio-Frequency Confining Drift Cell. Analyst 2016, 141 (3), 884– 891,  DOI: 10.1039/C5AN02107C
    Google Scholar
    25
    Ion mobility mass spectrometry of peptide, protein, and protein complex ions using a radio-frequency confining drift cell
    Allen, Samuel J.; Giles, Kevin; Gilbert, Tony; Bush, Matthew F.
    Analyst (Cambridge, United Kingdom) (2016), 141 (3), 884-891CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)
    Ion mobility mass spectrometry expts. enable the characterization of mass, assembly, and shape of biol. mols. and assemblies. Here, a new radio-frequency confining drift cell is characterized and used to measure the mobilities of peptide, protein, and protein complex ions. The new drift cell replaced the traveling-wave ion mobility cell in a Waters Synapt G2 HDMS. Methods for operating the drift cell and detg. collision cross section values using this exptl. set up are presented within the context of the original instrument control software. Collision cross sections for 349 cations and anions are reported, 155 of which are for ions that have not been characterized previously using ion mobility. The values for the remaining ions are similar to those detd. using a previous radio-frequency confining drift cell and drift tubes without radial confinement. Using this device under 2 Torr of helium gas and an optimized drift voltage, denatured and native-like ions exhibited av. apparent resolving powers of 14.2 and 16.5, resp. For ions with high mobility, which are also low in mass, the apparent resolving power is limited by contributions from ion gating. In contrast, the arrival-time distributions of low-mobility, native-like ions are not well explained using only contributions from ion gating and diffusion. For those species, the widths of arrival-time distributions are most consistent with the presence of multiple structures in the gas phase.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhtl2jsg%253D%253D&md5=e7ad7e451d070ecbb377484dee0d598f
  26. 26
    Haynes, S. E.; Polasky, D. A.; Dixit, S. M.; Majmudar, J. D.; Neeson, K.; Ruotolo, B. T.; Martin, B. R. Variable-Velocity Traveling-Wave Ion Mobility Separation Enhancing Peak Capacity for Data-Independent Acquisition Proteomics. Anal. Chem. 2017, 89 (11), 5669– 5672,  DOI: 10.1021/acs.analchem.7b00112
    Google Scholar
    26
    Variable-Velocity Traveling-Wave Ion Mobility Separation Enhancing Peak Capacity for Data-Independent Acquisition Proteomics
    Haynes, Sarah E.; Polasky, Daniel A.; Dixit, Sugyan M.; Majmudar, Jaimeen D.; Neeson, Kieran; Ruotolo, Brandon T.; Martin, Brent R.
    Analytical Chemistry (Washington, DC, United States) (2017), 89 (11), 5669-5672CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
    High mass accuracy, data-dependent acquisition is the current std. method in mass spectrometry-based peptide annotation and quantification. In high complexity samples, limited instrument scan speeds often result in under-sampling. In contrast, all-ion data-independent acquisition methods bypass precursor selection, alternating high and low collision energies to analyze product and precursor ions across wide mass ranges. Despite capturing data for all events, peptide annotation is limited by inadequate alignment algorithms or overlapping ions. Ion mobility sepn. can add an orthogonal anal. dimension, reducing ion interference to improve reproducibility, peak capacity, and peptide identifications to rival modern hybrid quadrupole orbitrap systems. Despite the advantages of ion mobility sepn. in complex proteomics analyses, there has been no quant. measure of ion mobility resoln. in a complex proteomic sample. Here, the authors present TWIMExt., a data extn. tool to export defined slices of liq. chromatog./ion mobility/mass spectrometry (LC-IM-MS) data, providing a route to quantify ion mobility resoln. from a com. traveling-wave ion mobility time-of-flight mass spectrometer. Using std. traveling-wave ion mobility parameters (600 m/s, 40 V), 90% of the annotated peptides occupied just 23% of the ion mobility drift space, yet inclusion of ion mobility nearly doubled the overall peak capacity. Relative to fixed velocity traveling-wave ion mobility settings, ramping the traveling-wave velocity increased drift space occupancy, amplifying resoln. by 16%, peak capacity by nearly 50%, and peptide/protein identifications by 40%. Overall, variable-velocity traveling-wave ion mobility-mass spectrometry significantly enhances proteomics anal. in all-ion fragmentation acquisition.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXntFarurY%253D&md5=82324095a4f44bc40a0a0a90a958844a
  27. 27
    Sergent, I.; Adjieufack, A. I.; Gaudel-Siri, A.; Siri, D.; Charles, L. The IMSCal Approach to Determine Collision Cross Section of Multiply Charged Anions in Traveling Wave Ion Mobility Spectrometry. Int. J. Mass Spectrom. 2023, 492, 117112  DOI: 10.1016/j.ijms.2023.117112
    Google Scholar
    27
    The IMSCal approach to determine collision cross section of multiply charged anions in traveling wave ion mobility spectrometry
    Sergent, Isaure; Adjieufack, Abel Idrice; Gaudel-Siri, Anouk; Siri, Didier; Charles, Laurence
    International Journal of Mass Spectrometry (2023), 492 (), 117112CODEN: IMSPF8; ISSN:1387-3806. (Elsevier B.V.)
    The need for appropriate stds. to calibrate ion arrival times in traveling wave ion mobility (TWIM) remains an issue for collision cross section (CCS) measurements, particularly in the case of multiply charged anions due to the scarcity of calibrants in the neg. ion mode. In order to circumvent constraints raised for stds. in the conventional power law calibration, the new approach recently implemented in the IMSCal software (Anal. Chem. 93 (2021) 3542-3550) has been evaluated here to derive CCS of multiply charged anions measured by TWIM. The math. model developed in IMSCal to describe ion motion in the TWIM cell was trained with different combinations of phosphoric acid clusters and deprotonated polyalanine stds. and performance of so-obtained calibrations was evaluated for multiply deprotonated oligothymidine 10mers used as control analytes. Although optimal compn. of the calibrant set could not be fully rationalized, one mandatory condition for best CCS accuracy is to include stds. of different charge states to properly model the effects of radial distribution of ions in the TWIM cell. Further improvement of calibration robustness requires that one of these charge states equals that of the analytes to account for the effects of velocity relaxation also incorporated in the IMSCal model. Doing so, exptl. CCS values could be readily obtained with relative error below ±5% for anions of charge state up to 6-.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhs1CntLrK&md5=77fe72716bea1a313f1e4f432a12dd4f
  28. 28
    Vallejo, D. D.; Corstvet, J. L.; Fernández, F. M. Triboelectric Nanogenerators: Low-Cost Power Supplies for Improved Electrospray Ionization. Int. J. Mass Spectrom. 2024, 495, 117167  DOI: 10.1016/j.ijms.2023.117167
    Google Scholar
    There is no corresponding record for this reference.
  29. 29
    Brown, S. H. J.; Mitchell, T. W.; Blanksby, S. J. Analysis of Unsaturated Lipids by Ozone-Induced Dissociation. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 2011, 1811 (11), 807– 817,  DOI: 10.1016/j.bbalip.2011.04.015
    Google Scholar
    There is no corresponding record for this reference.
  30. 30
    Ma, X.; Xia, Y. Pinpointing Double Bonds in Lipids by Paternò-Büchi Reactions and Mass Spectrometry. Angew. Chem., Int. Ed. Engl. 2014, 53 (10), 2592– 2596,  DOI: 10.1002/anie.201310699
    Google Scholar
    30
    Pinpointing double bonds in lipids by Paterno-Buchi reactions and mass spectrometry
    Ma Xiaoxiao; Xia Yu
    Angewandte Chemie (International ed. in English) (2014), 53 (10), 2592-6 ISSN:.
    The positions of double bonds in lipids play critical roles in their biochemical and biophysical properties. In this study, by coupling Paterno-Buchi (P-B) reaction with tandem mass spectrometry, we developed a novel method that can achieve confident, fast, and sensitive determination of double bond locations within various types of lipids. The P-B reaction is facilitated by UV irradiation of a nanoelectrospray plume entraining lipids and acetone. Tandem mass spectrometry of the on-line reaction products via collision activation leads to the rupture of oxetane rings and the formation of diagnostic ions specific to the double bond location.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cvisVyltQ%253D%253D&md5=f02d31d6cdd460c4490bc0324c9391b0
  31. 31
    Murphy, R. C.; Okuno, T.; Johnson, C. A.; Barkley, R. M. Determination of Double Bond Positions in Polyunsaturated Fatty Acids Using the Photochemical Paternò-Büchi Reaction with Acetone and Tandem Mass Spectrometry. Anal. Chem. 2017, 89 (16), 8545– 8553,  DOI: 10.1021/acs.analchem.7b02375
    Google Scholar
    31
    Determination of Double Bond Positions in Polyunsaturated Fatty Acids Using the Photochemical Patern´o-B.ovrddot.uchi Reaction with Acetone and Tandem Mass Spectrometry
    Murphy, Robert C.; Okuno, Toshiaki; Johnson, Christopher A.; Barkley, Robert M.
    Analytical Chemistry (Washington, DC, United States) (2017), 89 (16), 8545-8553CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
    The positions of double bonds along the carbon chain of methylene interrupted polyunsatd. fatty acids are unique identifiers of specific fatty acids derived from biochem. reactions that occur in cells. It is possible to obtain direct structural information as to these double bond positions using tandem mass spectrometry after collisional activation of the carboxylate anions of an acetone adduct at each of the double bond positions formed by the photochem. Patern´o-B.ovrddot.uchi reaction with acetone. This reaction can be carried out by exposing a small portion of an inline fused silica capillary to UV photons from a mercury vapor lamp as the sample is infused into the electrospray ion source of a mass spectrometer. Collisional activation of [M - H]- yields a series of reverse Patern´o-B.ovrddot.uchi reaction product ions that essentially are derived from cleavage of the original carbon-carbon double bonds that yield an isopropenyl carboxylate anion corresponding to each double bond location. Aldehydic reverse Patern´o-B.ovrddot.uchi product ions are much less abundant as the carbon chain length and no. of double bonds increase. The use of a mixt. of D0/D6-acetone facilitates identification of these double bonds indicating product ions as shown for arachidonic acid. If oxygen is present in the solvent stream undergoing UV photoactivation, ozone cleavage ions are also obsd. without prior collisional activation. This reaction was used to det. the double bond positions in a 20:3 fatty acid that accumulated in phospholipids of RAW 264.7 cells cultured for 3 days.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtFyqs7fK&md5=e617889c2776d5106a7a0b7c35f81c3e
  32. 32
    Zhao, J.; Xie, X.; Lin, Q.; Ma, X.; Su, P.; Xia, Y. Next-Generation Paternò-Büchi Reagents for Lipid Analysis by Mass Spectrometry. Anal. Chem. 2020, 92 (19), 13470– 13477,  DOI: 10.1021/acs.analchem.0c02896
    Google Scholar
    There is no corresponding record for this reference.

Cited By

Click to copy section linkSection link copied!

This article has not yet been cited by other publications.

Download PDF
Open PDF
Go to Journal of the American Society for Mass Spectrometry
Get e-Alerts
Get e-Alerts

Journal of the American Society for Mass Spectrometry

Cite this: J. Am. Soc. Mass Spectrom. 2024, 35, 5, 943–950
Click to copy citationCitation copied!
https://doi.org/10.1021/jasms.4c00010
Published April 16, 2024

Copyright © 2024 The Authors. Published by American Chemical Society. This publication is licensed under

CC-BY 4.0 .

Article Views

983

Altmetric

-

Citations

-
Learn about these metrics

Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.

  • Abstract

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 1

    Figure 1. Schematic of the sliding freestanding TENG ion source interfaced with MS. Polyurethane padding is affixed to a rigid acrylic substrate mounted onto the moving platform of a belt drive actuator. The polyurethane film is pressed against a stationary platform of PTFE film and copper tape affixed to a rigid acrylic substrate. The copper tape has a 7.5 mm gap in the middle to form two distinct electrodes, one connected to an earth grounding pin on the mass spectrometer and the other connected to the nanoelectrospray emitter. The belt is driven by an Arduino-controlled stepper motor that slides the moving platform from one end of the stationary platform to the other. The moving platform pauses at each end and then reverses direction for the next stroke. The speed of the stroke and the delay between strokes is controlled by two potentiometer dials connected to the Arduino control board.

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 2

    Figure 2. (A) Observed voltage vs slider position demonstrating voltage generation during ion source actuation. The polarity is determined by the direction of motion. (B) An overlay of total ion current vs observed voltage showing that ion signal continues for ∼180 ms after reversal of the electrode motion. (C) A comparison of observed voltages at different stroke speeds over 20 pulses. A stroke speed of 100% represents a frequency of 1.87 Hz. *Voltage as measured by 1 MΩ oscilloscope. Voltages >4 kV measured using a 50 MΩ multimeter. Emitter voltage is likely considerably higher. (9)

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 3

    Figure 3. (A–C) Full MS data for TENG nESI analysis of three different lipid standards. The primary observed species are labeled, including singly- and doubly oxidized ions. (D–F) MS2 spectra for the singly oxidized lipid species, indicating epoxide formation on unsaturated fatty acid chains. (G–I) MS3 spectra for the fragmentation of epoxide chain MS2 fragments. Annotated diagnostic fragments indicate the presence of double bonds at the Δ9 position on 18:1 chains, and Δ9 and Δ12 positions of the 18:2 chains.

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 4

    Figure 4. (A) Extracted ion chromatogram (XIC) at m/z = 802 for (PC 34:2) detected from the LC MS analysis of NIST SRM 1950 reference plasma. (B) A switching valve was employed during elution to divert the feature to a collection vial. (B) XIC of the same feature from a diverted run indicates successful capture of a majority of the feature. (C) MS3 spectrum from the collected fraction after drying and reconstituting into 75:12.5:12.5 acetone:water:methanol (v:v:v) with 25 mM ammonium acetate showing diagnostic fragments for double bonds at the Δ9 and Δ12 positions.

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 5

    Figure 5. (A) TENG driven spray dynamics earlier in the TENG cycle. (B) A distinct shift in spray mode is observed during the tail end of the voltage pulses when running at low stroke speeds. Regions of normal spray (C) and multijet spray (D) are highlighted with their associated mass spectra (E and F) when analyzing a pure PG(18:1/18:1) standard. Extracted ion chromatograms for [M – H], [MO – H]−, and [MOO – H]− are shown (G) and rescaled to oxidized species (H). Extreme ratios of oxidized/unoxidized ions are observed during the multijet regime, though absolute abundances did not increase significantly.

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 6

    Figure 6. Mass spectra of native BSA under (A) inductive and (B) Pt wire-induced nESI resulting in qualitative differences in peak width (fwhm) and quantitative differences in nonspecific dimers. (C) CCS calibration indicates the new TENG ion source produces high fidelity native protein signals within (D) 3% of database reference values. (E) No quantitative difference in CCS of inductive vs Pt wire-generated protein ions, indicating that in both conditions proteins retain their native structure.

    High Resolution Image
    Download MS PowerPoint Slide

  • References

    This article references 32 other publications.

    1. 1
      Wilm, M.; Mann, M. Analytical Properties of the Nanoelectrospray Ion Source. Anal. Chem. 1996, 68 (1), 1– 8,  DOI: 10.1021/ac9509519
      1
      Analytical Properties of the Nanoelectrospray Ion Source
      Wilm, Matthias; Mann, Matthias
      Analytical Chemistry (1996), 68 (1), 1-8CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
      The nanoelectrospray ion source (nanoES) was recently developed and described theor. It is different from conventional electrospray sources and from other miniaturized electrospray sources by (1) its 1-2-μm spraying orifice achieved by pulling the spraying capillary to a fine tip, (2) its very low flow rate of ∼20 nL/min and the small size of droplets it generates, and (3) the absence of solvent pumps and inlet valves. The fabrication and operation of nanoES needles is described in detail. Solns. with up to 0.1M salt contents could be sprayed without sheath flow or pneumatic assist. Improved desolvation in nanoES led to instrument-limited resoln. of the signals of a glycoprotein and the ability to signal av. extensively allowed the C-terminal sequencing of a 40-kDa protein. Extensive mass spectrometric and tandem mass spectrometric investigation of the components of an unsepd. peptide mixt. was demonstrated by verification of 93% of the sequence of carbonic anhydrase. A rapid and robust desalting/concn. step coupled to the nanoES procedure allows the direct anal. of impure samples such as peptide mixts. extd. after in-gel digestion.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXpslSru7k%253D&md5=f396fcfc0b8effec0132e60a6267bfd3
    2. 2
      Emmett, M. R.; Caprioli, R. M. Micro-Electrospray Mass Spectrometry: Ultra-High-Sensitivity Analysis of Peptides and Proteins. J. Am. Soc. Mass Spectrom. 1994, 5 (7), 605– 613,  DOI: 10.1016/1044-0305(94)85001-1
      2
      Micro-electrospray mass spectrometry: Ultra-high-sensitivity analysis of peptides and proteins
      Emmett, Mark R.; Caprioli, Richard M.
      Journal of the American Society for Mass Spectrometry (1994), 5 (7), 605-13CODEN: JAMSEF; ISSN:1044-0305.
      A "micro-electrospray" ionization source has been developed that markedly increases the sensitivity of the conventional electrospray source. This was achieved by optimization of the source to accommodate nanoliter flow rates from 300 to 800 nL/min spraying directly from a capillary needle that, for the anal. of peptides, contained C18 liq. chromatog. packing as an integrated concn.-desalting device. Thus, a total of 1 fmol of methionine-enkephalin was desorbed from the capillary column spray needle, loaded as a 10-μL injection of 100-amol/μL soln. The mass spectrum showed the [M + H]+ ion at m/z 574.2 with a signal-to-noise ratio of better than 5:1 from a chromatog. peak with a width of about 12 s. A narrow range (15-u) tandem mass spectrum was obtained for methionine-enkephalin from the injection of 500 amol, and a full-scan tandem-mass spectrum was obtained from 50 fmol. For proteins, the av. mass measurement accuracy was approx. 100-200 ppm for the injection of 2.5 fmol of apomyoglobin and 20-40 ppm for 200 fmol. Carbonic anhydrase B and bovine serum albumin showed similar mass measurement accuracies.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXmt1Gmt74%253D&md5=4da21d48deaa122b197b42974e71e3f5
    3. 3
      Wei, Z.; Xiong, X.; Guo, C.; Si, X.; Zhao, Y.; He, M.; Yang, C.; Xu, W.; Tang, F.; Fang, X.; Zhang, S.; Zhang, X. Pulsed Direct Current Electrospray: Enabling Systematic Analysis of Small Volume Sample by Boosting Sample Economy. Anal. Chem. 2015, 87 (22), 11242– 11248,  DOI: 10.1021/acs.analchem.5b02115
      3
      Pulsed Direct Current Electrospray: Enabling Systematic Analysis of Small Volume Sample by Boosting Sample Economy
      Wei, Zhenwei; Xiong, Xingchuang; Guo, Chengan; Si, Xingyu; Zhao, Yaoyao; He, Muyi; Yang, Chengdui; Xu, Wei; Tang, Fei; Fang, Xiang; Zhang, Sichun; Zhang, Xinrong
      Analytical Chemistry (Washington, DC, United States) (2015), 87 (22), 11242-11248CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
      We had developed pulsed d.c. electrospray ionization mass spectrometry (pulsed-dc-ESI-MS) for systematically profiling and detg. components in small vol. sample. Pulsed-dc-ESI utilized const. high voltage to induce the generation of single polarity pulsed electrospray remotely. This method had significantly boosted the sample economy, so as to obtain several minutes MS signal duration from merely picoliter vol. sample. The elongated MS signal duration enable us to collect abundant MS2 information on interested components in a small vol. sample for systematical anal. This method had been successfully applied for single cell metabolomics anal. We had obtained 2-D profile of metabolites (including exact mass and MS2 data) from single plant and mammalian cell, concerning 1034 components and 656 components for Allium cepa and HeLa cells, resp. Further identification had found 162 compds. and 28 different modification groups of 141 saccharides in a single Allium cepa cell, indicating pulsed-dc-ESI a powerful tool for small vol. sample systematical anal.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhs1yltr3I&md5=bd117ff6a921704e0798d756e5d0f135
    4. 4
      McMahon, W. P.; Dalvi, R.; Lesniewski, J. E.; Hall, Z. Y.; Jorabchi, K. Pulsed Nano-ESI: Application in Ion Mobility-MS and Insights into Spray Dynamics. J. Am. Soc. Mass Spectrom. 2020, 31 (3), 488– 497,  DOI: 10.1021/jasms.9b00121
      There is no corresponding record for this reference.
    5. 5
      Xu, Z.; Wu, H.; Tang, Y.; Xu, W.; Zhai, Y. Electric Modeling and Characterization of Pulsed High-Voltage Nanoelectrospray Ionization Sources by a Miniature Ion Trap Mass Spectrometer. Journal of Mass Spectrometry 2019, 54 (7), 583– 591,  DOI: 10.1002/jms.4361
      There is no corresponding record for this reference.
    6. 6
      Liu, D.; Zhou, L.; Wang, Z. L.; Wang, J. Triboelectric Nanogenerator: From Alternating Current to Direct Current. iScience 2021, 24 (1), 102018  DOI: 10.1016/j.isci.2020.102018
      6
      Triboelectric nanogenerator: from alternating current to direct current
      Liu Di; Zhou Linglin; Wang Zhong Lin; Wang Jie; Liu Di; Zhou Linglin; Wang Zhong Lin; Wang Jie; Wang Zhong Lin
      iScience (2021), 24 (1), 102018 ISSN:.
      Triboelectric nanogenerator (TENG) is considered as a potential solution to harvest distributed energy for the sustainable and reliable power supply of the internet of things. Although numerous researches on alternating current (AC) output TENG from fundamental physics to potential applications have been widely promoted in recent years, the studies about direct current (DC) output TENG is just beginning, especially for a constant current output. This work gives the summary of recent key researches from AC-TENG to DC-TENG, especially a constant current TENG, as well as the design of AC/DC-TENG. In addition, some new DC generators will also be summarized toward a wide range of readers. This study presents the similarities and differences between AC-TENG and DC-TENG, so that their impact and uniqueness can be clearly understood. Finally, the major challenges and the future outlooks in this rapidly emerging research field will be discussed as a guideline for future research.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3srkslCrsQ%253D%253D&md5=5ef9c9b977a3d7310a02867af701e01d
    7. 7
      Ma, X.; Fernández, F. M. Triboelectric Nanogenerator-Coated Blade Spray Mass Spectrometry for Volume-Limited Drug Analysis. Int. J. Mass Spectrom. 2024, 495, 117164  DOI: 10.1016/j.ijms.2023.117164
      There is no corresponding record for this reference.
    8. 8
      Bouza, M.; Li, Y.; Wu, C.; Guo, H.; Wang, Z. L.; Fernández, F. M. Large-Area Triboelectric Nanogenerator Mass Spectrometry: Expanded Coverage, Double-Bond Pinpointing, and Supercharging. J. Am. Soc. Mass Spectrom. 2020, 31 (3), 727– 734,  DOI: 10.1021/jasms.0c00002
      There is no corresponding record for this reference.
    9. 9
      Li, A.; Zi, Y.; Guo, H.; Wang, Z. L.; Fernández, F. M. Triboelectric Nanogenerators for Sensitive Nano-Coulomb Molecular Mass Spectrometry. Nat. Nanotechnol. 2017, 12 (5), 481– 487,  DOI: 10.1038/nnano.2017.17
      9
      Triboelectric nanogenerators for sensitive nano-coulomb molecular mass spectrometry
      Li, Anyin; Zi, Yunlong; Guo, Hengyu; Wang, Zhong Lin; Fernandez, Facundo M.
      Nature Nanotechnology (2017), 12 (5), 481-487CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)
      Ion sources for mol. mass spectrometry are usually driven by d.c. power supplies with no user control over the total charges generated. Here, we show that the output of triboelec. nanogenerators (TENGs) can quant. control the total ionization charges in mass spectrometry. The high output voltage of TENGs can generate single- or alternating-polarity ion pulses, and is ideal for inducing nanoelectrospray ionization (nanoESI) and plasma discharge ionization. For a given nanoESI emitter, accurately controlled ion pulses ranging from 1.0 to 5.5 nC were delivered with an onset charge of 1.0 nC. Spray pulses can be generated at a high frequency of 17 Hz (60 ms in period) and the pulse duration is adjustable on-demand between 60 ms and 5.5 s. Highly sensitive (∼0.6 zeptomole) mass spectrometry anal. using minimal sample (18 pl per pulse) was achieved with a 10 pg ml-1 cocaine sample. We also show that native protein conformation is conserved in TENG-ESI, and that patterned ion deposition on conductive and insulating surfaces is possible.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXltVWnsbY%253D&md5=f7573097228d217ab623e80168ea9de4
    10. 10
      Wang, Z. L. Triboelectric Nanogenerators as New Energy Technology for Self-Powered Systems and as Active Mechanical and Chemical Sensors. ACS Nano 2013, 7 (11), 9533– 9557,  DOI: 10.1021/nn404614z
      10
      Triboelectric Nanogenerators as New Energy Technology for Self-Powered Systems and as Active Mechanical and Chemical Sensors
      Wang, Zhong Lin
      ACS Nano (2013), 7 (11), 9533-9557CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)
      A review. Tribo-electrification is an effect that is known to each and every one probably since ancient Greek time, but it is usually taken as a neg. effect and is avoided in many technologies. The authors have recently invented a triboelec. nanogenerator (TENG) that is used to convert mech. energy into electricity by a conjunction of tribo-electrification and electrostatic induction. As for this power generation unit, in the inner circuit, a potential is created by the triboelec. effect due to the charge transfer between 2 thin org./inorg. films that exhibit opposite tribo-polarity; in the outer circuit, electrons are driven to flow between 2 electrodes attached on the back sides of the films to balance the potential. Since the most useful materials for TENG are org., it is also named org. nanogenerator, which is the 1st using org. materials for harvesting mech. energy. The authors review the fundamentals of the TENG in the 3 basic operation modes: vertical contact-sepn. mode, in-plane sliding mode, and single-electrode mode. Ever since the 1st report of the TENG in Jan. 2012, the output power d. of TENG was improved 5 orders of magnitude within 12 mo. The area power d. reaches 313 W/m2, vol. d. reaches 490 kW/m3, and a conversion efficiency of ∼60% was demonstrated. The TENG can be applied to harvest all kinds of mech. energy that is available but wasted in the daily life, such as human motion, walking, vibration, mech. triggering, rotating tire, wind, flowing H2O, and more. Alternatively, TENG can also be used as a self-powered sensor for actively detecting the static and dynamic processes arising from mech. agitation using the voltage and current output signals of the TENG, resp., with potential applications for touch pad and smart skin technologies. To enhance the performance of the TENG, besides the vast choices of materials in the triboelec. series, from polymer to metal and to fabric, the morphologies of their surfaces can be modified by phys. techniques with the creation of pyramid-, square-, or hemisphere-based micro- or nano-patterns, which are effective for enhancing the contact area and possibly the triboelectrification. The surfaces of the materials can be functionalized chem. using various mols., nanotubes, nanowires, or nanoparticles, to enhance the triboelec. effect. The contact materials can be composites, such as embedding nanoparticles in a polymer matrix, which may change not only the surface electrification but also the permittivity of the materials so that they can be effective for electrostatic induction. Therefore, there are numerous ways to enhance the performance of the TENG from the materials point of view. This gives an excellent opportunity for chemists and materials scientists to do extensive study both in the basic science and in practical applications. The authors anticipate that a better enhancement of the output power d. will be achieved in the next few years. The TENG is possible not only for self-powered portable electronics but also as a new energy technol. with potential to contribute to the world energy in the near future.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsFelsb%252FF&md5=0c5e218d8e55cbb48a6454c8cf0479a5
    11. 11
      Li, Y.; Bouza, M.; Wu, C.; Guo, H.; Huang, D.; Doron, G.; Temenoff, J. S.; Stecenko, A. A.; Wang, Z. L.; Fernández, F. M. Sub-Nanoliter Metabolomics via Mass Spectrometry to Characterize Volume-Limited Samples. Nat. Commun. 2020, 11 (1), 5625,  DOI: 10.1038/s41467-020-19444-y
      11
      Sub-nanoliter metabolomics via mass spectrometry to characterize volume-limited samples
      Li, Yafeng; Bouza, Marcos; Wu, Changsheng; Guo, Hengyu; Huang, Danning; Doron, Gilad; Temenoff, Johnna S.; Stecenko, Arlene A.; Wang, Zhong Lin; Fernandez, Facundo M.
      Nature Communications (2020), 11 (1), 5625CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)
      The human metabolome provides a window into the mechanisms and biomarkers of various diseases. However, because of limited availability, many sample types are still difficult to study by metabolomic analyses. Here, we present a mass spectrometry (MS)-based metabolomics strategy that only consumes sub-nanoliter sample vols. The approach consists of combining a customized metabolomics workflow with a pulsed MS ion generation method, known as triboelec. nanogenerator inductive nanoelectrospray ionization (TENGi nanoESI) MS. Samples tested with this approach include exhaled breath condensate collected from cystic fibrosis patients as well as in vitro-cultured human mesenchymal stromal cells. Both test samples are only available in min. amts. Expts. show that picoliter-vol. spray pulses suffice to generate high-quality spectral fingerprints, which increase the information d. produced per unit sample vol. This TENGi nanoESI strategy has the potential to fill in the gap in metabolomics where liq. chromatog.-MS-based analyses cannot be applied. Our method opens up avenues for future investigations into understanding metabolic changes caused by diseases or external stimuli.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitlWgu7fF&md5=c26617ccf1bd401456f2b038df5176b7
    12. 12
      Vallejo, D. D.; Popowich, A.; Arslanoglu, J.; Tokarski, C.; Fernández, F. M. Native Triboelectric Nanogenerator Ion Mobility-Mass Spectrometry of Egg Proteins Relevant to Objects of Cultural Heritage at Picoliter and Nanomolar Quantities. Anal. Chim. Acta 2023, 1269, 341374  DOI: 10.1016/j.aca.2023.341374
      There is no corresponding record for this reference.
    13. 13
      Bouza, M.; Li, Y.; Wang, A. C.; Wang, Z. L.; Fernández, F. M. Triboelectric Nanogenerator Ion Mobility–Mass Spectrometry for In-Depth Lipid Annotation. Anal. Chem. 2021, 93 (13), 5468– 5475,  DOI: 10.1021/acs.analchem.0c05145
      There is no corresponding record for this reference.
    14. 14
      Bernier, M. C.; Li, A.; Winalski, L.; Zi, Y.; Li, Y.; Caillet, C.; Newton, P.; Wang, Z. L.; Fernández, F. M. Triboelectric Nanogenerator (TENG) Mass Spectrometry of Falsified Antimalarials. Rapid Commun. Mass Spectrom. 2018, 32 (18), 1585– 1590,  DOI: 10.1002/rcm.8207
      14
      Triboelectric nanogenerator (TENG) mass spectrometry of falsified antimalarials
      Bernier, Matthew C.; Li, Anyin; Winalski, Laura; Zi, Yunlong; Li, Yafeng; Caillet, Celine; Newton, Paul; Wang, Zhong Lin; Fernandez, Facundo M.
      Rapid Communications in Mass Spectrometry (2018), 32 (18), 1585-1590CODEN: RCMSEF; ISSN:0951-4198. (John Wiley & Sons Ltd.)
      An epidemic of low-quality medicines continues to endanger patients worldwide. Detection of such 'medicines' requires low cost, ambient ionization sources coupled to fieldable (portable) mass spectrometers for optimum sensitivity and specificity. With the use of triboelec. nanogenerators (TENGs), the charge required to produce gas-phase ions for mass spectral anal. can be obtained without the need for high-voltage elec. circuitry, thus simplifying and lowering the cost of next-generation mass spectrometry instruments. A sliding freestanding (SF) TENG was coupled to a toothpick electrospray setup for the purposes of testing if falsified medicines could be fingerprinted by this approach. Exts. from both genuine and falsified medicines were deposited on the toothpick and the SF TENG actuated to generate elec. charges, resulting in gas-phase ions for both active pharmaceutical ingredients and excipients. Our previous work had shown that direct anal. in real time (DART) ambient mass spectrometry can identify the components of multiple classes of falsified antimalarial medicines. Expts. performed in this study show that a simple extn. into methanol along with the use of a SF TENG-powered toothpick electrospray can provide similar detection capabilities, but with much simpler and rugged instrumentation, and without the need for compressed gases or high-voltage ion source power supplies. TENG toothpick MS allows for rapid analyte ion detection in a safe and low-cost manner, providing robust sampling and ionization capabilities.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsV2lurrF&md5=d9136d6c8ae58d782303ff5f2743d94d
    15. 15
      Snyder, D. T.; Pulliam, C. J.; Ouyang, Z.; Cooks, R. G. Miniature and Fieldable Mass Spectrometers: Recent Advances. Anal. Chem. 2016, 88 (1), 2– 29,  DOI: 10.1021/acs.analchem.5b03070
      15
      Miniature and Fieldable Mass Spectrometers: Recent Advances
      Snyder, Dalton T.; Pulliam, Christopher J.; Ouyang, Zheng; Cooks, R. Graham
      Analytical Chemistry (Washington, DC, United States) (2016), 88 (1), 2-29CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
      A review. This review emphasizes advances in the miniaturization of mass spectrometers which have taken place since an extensive review was published in 2009. During this time, reviews on ambient ionization and miniature mass analyzers have appeared, but an integrated treatment of miniature mass spectrometers (mini MS) and ambient ionization is now needed.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFyrurbP&md5=3ca4f74190326e7d9de2a2ec1efc4636
    16. 16
      Li, X.; Attanayake, K.; Valentine, S. J.; Li, P. Vibrating Sharp-Edge Spray Ionization (VSSI) for Voltage-Free Direct Analysis of Samples Using Mass Spectrometry. Rapid Commun. Mass Spectrom. 2021, 35 (S1), e8232  DOI: 10.1002/rcm.8232
      16
      Vibrating Sharp-edge Spray Ionization (VSSI) for voltage-free direct analysis of samples using mass spectrometry
      Li, Xiaojun; Attanayake, Kushani; Valentine, Stephen J.; Li, Peng
      Rapid Communications in Mass Spectrometry (2021), 35 (S1), e8232CODEN: RCMSEF; ISSN:0951-4198. (John Wiley & Sons Ltd.)
      Rationale : The development of miniaturized and field portable mass spectrometers could not succeed without a simple, compact, and robust ionization source. Here the authors present a voltage-free ionization method, Vibrating Sharp-edge Spray Ionization (VSSI), which can generate a spray of liq. samples using only one std. microscope glass slide to which a piezoelec. transducer is attached. Compared with existing ambient ionization methods, VSSI eliminates the need for a high elec. field (∼5000 V·cm-1) for spray generation, while sharing a similar level of simplicity and flexibility with the simplest direct ionization techniques currently available such as paper spray ionization (PSI) and other solid substrate-based electrospray ionization methods. Methods : The VSSI device was fabricated by attaching a piezoelec. transducer onto a std. glass microscope slide using epoxy glue. Liq. sample was aerosolized by either placing a droplet onto the vibrating edge of the glass slide or touching a wet surface with the glass edge. Mass spectrometric detection was achieved by placing the VSSI device 0.5-1 cm from the inlet of the mass spectrometer (Q-Exactive, ThermoScientific). Results : VSSI is demonstrated to ionize a diverse array of chem. species, including small org. mols., carbohydrates, peptides, proteins, and nucleic acids. Preliminary sensitivity expts. show that high-quality mass spectra of acetaminophen can be obtained by consuming 100 fmol of the target. The dual spray of VSSI was also demonstrated by performing in-droplet denaturation of ubiquitin. Finally, due to the voltage-free nature and the direct-contact working mode of VSSI, it has been successfully applied for the detection of chems. directly from human fingertips. Conclusions : Overall, the authors report a compact ionization method based on vibrating sharp-edges. The simplicity and voltage-free nature of VSSI make it an attractive option for field portable applications or analyzing biol. samples that are sensitive to high voltage or difficult to access by conventional ionization methods.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsFeqtbrE&md5=d60a60f74698c56fb14c158c952a2521
    17. 17
      Wleklinski, M.; Li, Y.; Bag, S.; Sarkar, D.; Narayanan, R.; Pradeep, T.; Cooks, R. G. Zero Volt Paper Spray Ionization and Its Mechanism. Anal. Chem. 2015, 87 (13), 6786– 6793,  DOI: 10.1021/acs.analchem.5b01225
      17
      Zero Volt Paper Spray Ionization and Its Mechanism
      Wleklinski, Michael; Li, Yafeng; Bag, Soumabha; Sarkar, Depanjan; Narayanan, Rahul; Pradeep, T.; Cooks, R. Graham
      Analytical Chemistry (Washington, DC, United States) (2015), 87 (13), 6786-6793CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
      The anal. performance and a suggested mechanism for zero volt paper spray using chromatog. paper are presented. A spray is generated by the action of the pneumatic force of the mass spectrometer (MS) vacuum at the inlet. Pos. and neg. ion signals are obsd., and comparisons are made with std. kV paper spray (PS) ionization and nanoelectrospray ionization (nESI). While the range of analytes to which zero volt PS is applicable is very similar to kV PS and nESI, differences in the mass spectra of mixts. are interpreted in terms of the more significant effects of analyte surface activity in the gentler zero volt expt. than in the other methods due to the significantly lower charge. The signal intensity of zero volt PS is also lower than in the other methods. A Monte Carlo simulation based on statistical fluctuation of pos. and neg. ions in soln. was implemented to explain the prodn. of ions from initially uncharged droplets. Uncharged droplets 1st break up due to aerodynamics forces until they are in the 2-4 μm size range and then undergo Coulombic fission. A model involving statistical charge fluctuations in both phases predicts detection limits similar to those obsd. exptl. and explains the effects of binary mixt. components on relative ionization efficiencies. The proposed mechanism may also play a role in ionization by other voltage-free methods.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXptF2murk%253D&md5=bf3501d7ebb38bdc3c5e712c13391258
    18. 18
      Neumann, A.; Tiemann, O.; Hansen, H. J.; Rüger, C. P.; Zimmermann, R. Detailed Comparison of Xenon APPI (9.6/8.4 eV), Krypton APPI (10.6/10.0 eV), APCI, and APLI (266 Nm) for Gas Chromatography High Resolution Mass Spectrometry of Standards and Complex Mixtures. J. Am. Soc. Mass Spectrom. 2023, 34 (8), 1632– 1646,  DOI: 10.1021/jasms.3c00085
      There is no corresponding record for this reference.
    19. 19
      Robb, D. B.; Covey, T. R.; Bruins, A. P. Atmospheric Pressure Photoionization: An Ionization Method for Liquid Chromatography-Mass Spectrometry. Anal. Chem. 2000, 72 (15), 3653– 3659,  DOI: 10.1021/ac0001636
      19
      Atmospheric pressure photoionization: an ionization method for liquid chromatography-mass spectrometry
      Robb, Damon B.; Covey, Thomas R.; Bruins, Andries P.
      Analytical Chemistry (2000), 72 (15), 3653-3659CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
      Atm. pressure photoionization ( APPI) was successfully demonstrated to provide high sensitivity to LC-MS anal. A vacuum-UV lamp designed for photoionization detection in gas chromatog. was used as a source of 10-eV photons. The mixt. of samples and solvent eluting from an HPLC is fully evapd. prior to introduction into the photoionization region. In the new method, large quantities of an ionizable dopant are added to the vapor generated from the LC eluant, allowing for a great abundance of dopant photoions to be produced. Because the ion source is at atm. pressure, and the collision rate is high, the dopant photoions react to completion with solvent and analyte mols. present in the ion source. Using APPI, at an LC flow rate of 200 μL/min, it is possible to obtain analyte signal intensities 8 times as high as those obtainable with a com. available corona discharge-atm. pressure chem. ionization source.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXksFOrurg%253D&md5=9e8f4169a51e6c3ed9fa507704aaf6f0
    20. 20
      Keating, M. F.; Zhang, J.; Feider, C. L.; Retailleau, S.; Reid, R.; Antaris, A.; Hart, B.; Tan, G.; Milner, T. E.; Miller, K.; Eberlin, L. S. Integrating the MasSpec Pen to the Da Vinci Surgical System for In Vivo Tissue Analysis during a Robotic Assisted Porcine Surgery. Anal. Chem. 2020, 92 (17), 11535– 11542,  DOI: 10.1021/acs.analchem.0c02037
      20
      Integrating the MasSpec Pen to the da Vinci Surgical System for In Vivo Tissue Analysis during a Robotic Assisted Porcine Surgery
      Keating, Michael F.; Zhang, Jialing; Feider, Clara L.; Retailleau, Sascha; Reid, Robert; Antaris, Alexander; Hart, Bradley; Tan, Gina; Milner, Thomas E.; Miller, Kyle; Eberlin, Livia S.
      Analytical Chemistry (Washington, DC, United States) (2020), 92 (17), 11535-11542CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
      Minimally invasive robotic-assisted surgeries have been increasingly used as a first-line of treatment for patients undergoing oncol. surgeries. In-situ tissue identification is crit. to guide tissue resection and assist decision-making. Traditional intraoperative histopathol. anal. of frozen tissue sections can be time-consuming and present logistical challenges which interrupt surgical workflows. The authors report the development and implementation of a laparoscopic, drop-in version of the MasSpec Pen device integrated into the da Vinci Xi Surgical system for in vivo tissue anal. in a robotic-assisted porcine surgery. The authors evaluated the performance of the drop-in MasSpec Pen during surgery by introducing the device into the animal upper gastrointestinal system and performing in vivo analyses of the stomach and liver, including charred and bloody tissues after electrocauterization. The mol. profiles obtained included ions tentatively identified as metabolites and lipids typically obsd. with MasSpec Pen anal., without causing observable tissue damage. Statistical classifiers built to distinguish porcine liver and stomach tissues using the in vivo data yielded an overall tissue identification accuracy of 98% (n = 53 analyses). The results provide evidence that the drop-in MasSpec Pen developed can be used to acquire mass spectra in vivo during a robotic-assisted surgery and might be used as an in vivo tissue assessment tool to help guide surgical resections and streamline surgical workflows.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVygsrjE&md5=3ead28c68b812f4feeaf7a15ec15f024
    21. 21
      Zhai, Y.; Fu, X.; Xu, W. Miniature Mass Spectrometers and Their Potential for Clinical Point-of-Care Analysis. Mass Spectrometry Reviews 2023, 21867,  DOI: 10.1002/mas.21867
      There is no corresponding record for this reference.
    22. 22
      Liu, J.; Tang, W.; Meng, X.; Zhan, L.; Xu, W.; Nie, Z.; Wang, Z. Improving the Performance of the Mini 2000 Mass Spectrometer with a Triboelectric Nanogenerator Electrospray Ionization Source. ACS Omega 2018, 3 (9), 12229– 12234,  DOI: 10.1021/acsomega.8b01777
      There is no corresponding record for this reference.
    23. 23
      Zhou, X.; Li, S.; Ouyang, Z. Miniature Mass Spectrometers for On-Site Chemical Analysis. 2023 IEEE 36th International Vacuum Nanoelectronics Conference (IVNC); IEEE: Cambridge, MA, 2023; pp 157– 159.  DOI: 10.1109/IVNC57695.2023.10189017 .
      There is no corresponding record for this reference.
    24. 24
      Asef, C. K.; Rainey, M. A.; Garcia, B. M.; Gouveia, G. J.; Shaver, A. O.; Leach, F. E.; Morse, A. M.; Edison, A. S.; McIntyre, L. M.; Fernández, F. M. Unknown Metabolite Identification Using Machine Learning Collision Cross-Section Prediction and Tandem Mass Spectrometry. Anal. Chem. 2023, 95, 1047  DOI: 10.1021/acs.analchem.2c03749
      There is no corresponding record for this reference.
    25. 25
      Allen, S. J.; Giles, K.; Gilbert, T.; Bush, M. T. Ion Mobility Mass Spectrometry of Peptide, Protein, and Protein Complex Ions Using a Radio-Frequency Confining Drift Cell. Analyst 2016, 141 (3), 884– 891,  DOI: 10.1039/C5AN02107C
      25
      Ion mobility mass spectrometry of peptide, protein, and protein complex ions using a radio-frequency confining drift cell
      Allen, Samuel J.; Giles, Kevin; Gilbert, Tony; Bush, Matthew F.
      Analyst (Cambridge, United Kingdom) (2016), 141 (3), 884-891CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)
      Ion mobility mass spectrometry expts. enable the characterization of mass, assembly, and shape of biol. mols. and assemblies. Here, a new radio-frequency confining drift cell is characterized and used to measure the mobilities of peptide, protein, and protein complex ions. The new drift cell replaced the traveling-wave ion mobility cell in a Waters Synapt G2 HDMS. Methods for operating the drift cell and detg. collision cross section values using this exptl. set up are presented within the context of the original instrument control software. Collision cross sections for 349 cations and anions are reported, 155 of which are for ions that have not been characterized previously using ion mobility. The values for the remaining ions are similar to those detd. using a previous radio-frequency confining drift cell and drift tubes without radial confinement. Using this device under 2 Torr of helium gas and an optimized drift voltage, denatured and native-like ions exhibited av. apparent resolving powers of 14.2 and 16.5, resp. For ions with high mobility, which are also low in mass, the apparent resolving power is limited by contributions from ion gating. In contrast, the arrival-time distributions of low-mobility, native-like ions are not well explained using only contributions from ion gating and diffusion. For those species, the widths of arrival-time distributions are most consistent with the presence of multiple structures in the gas phase.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhtl2jsg%253D%253D&md5=e7ad7e451d070ecbb377484dee0d598f
    26. 26
      Haynes, S. E.; Polasky, D. A.; Dixit, S. M.; Majmudar, J. D.; Neeson, K.; Ruotolo, B. T.; Martin, B. R. Variable-Velocity Traveling-Wave Ion Mobility Separation Enhancing Peak Capacity for Data-Independent Acquisition Proteomics. Anal. Chem. 2017, 89 (11), 5669– 5672,  DOI: 10.1021/acs.analchem.7b00112
      26
      Variable-Velocity Traveling-Wave Ion Mobility Separation Enhancing Peak Capacity for Data-Independent Acquisition Proteomics
      Haynes, Sarah E.; Polasky, Daniel A.; Dixit, Sugyan M.; Majmudar, Jaimeen D.; Neeson, Kieran; Ruotolo, Brandon T.; Martin, Brent R.
      Analytical Chemistry (Washington, DC, United States) (2017), 89 (11), 5669-5672CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
      High mass accuracy, data-dependent acquisition is the current std. method in mass spectrometry-based peptide annotation and quantification. In high complexity samples, limited instrument scan speeds often result in under-sampling. In contrast, all-ion data-independent acquisition methods bypass precursor selection, alternating high and low collision energies to analyze product and precursor ions across wide mass ranges. Despite capturing data for all events, peptide annotation is limited by inadequate alignment algorithms or overlapping ions. Ion mobility sepn. can add an orthogonal anal. dimension, reducing ion interference to improve reproducibility, peak capacity, and peptide identifications to rival modern hybrid quadrupole orbitrap systems. Despite the advantages of ion mobility sepn. in complex proteomics analyses, there has been no quant. measure of ion mobility resoln. in a complex proteomic sample. Here, the authors present TWIMExt., a data extn. tool to export defined slices of liq. chromatog./ion mobility/mass spectrometry (LC-IM-MS) data, providing a route to quantify ion mobility resoln. from a com. traveling-wave ion mobility time-of-flight mass spectrometer. Using std. traveling-wave ion mobility parameters (600 m/s, 40 V), 90% of the annotated peptides occupied just 23% of the ion mobility drift space, yet inclusion of ion mobility nearly doubled the overall peak capacity. Relative to fixed velocity traveling-wave ion mobility settings, ramping the traveling-wave velocity increased drift space occupancy, amplifying resoln. by 16%, peak capacity by nearly 50%, and peptide/protein identifications by 40%. Overall, variable-velocity traveling-wave ion mobility-mass spectrometry significantly enhances proteomics anal. in all-ion fragmentation acquisition.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXntFarurY%253D&md5=82324095a4f44bc40a0a0a90a958844a
    27. 27
      Sergent, I.; Adjieufack, A. I.; Gaudel-Siri, A.; Siri, D.; Charles, L. The IMSCal Approach to Determine Collision Cross Section of Multiply Charged Anions in Traveling Wave Ion Mobility Spectrometry. Int. J. Mass Spectrom. 2023, 492, 117112  DOI: 10.1016/j.ijms.2023.117112
      27
      The IMSCal approach to determine collision cross section of multiply charged anions in traveling wave ion mobility spectrometry
      Sergent, Isaure; Adjieufack, Abel Idrice; Gaudel-Siri, Anouk; Siri, Didier; Charles, Laurence
      International Journal of Mass Spectrometry (2023), 492 (), 117112CODEN: IMSPF8; ISSN:1387-3806. (Elsevier B.V.)
      The need for appropriate stds. to calibrate ion arrival times in traveling wave ion mobility (TWIM) remains an issue for collision cross section (CCS) measurements, particularly in the case of multiply charged anions due to the scarcity of calibrants in the neg. ion mode. In order to circumvent constraints raised for stds. in the conventional power law calibration, the new approach recently implemented in the IMSCal software (Anal. Chem. 93 (2021) 3542-3550) has been evaluated here to derive CCS of multiply charged anions measured by TWIM. The math. model developed in IMSCal to describe ion motion in the TWIM cell was trained with different combinations of phosphoric acid clusters and deprotonated polyalanine stds. and performance of so-obtained calibrations was evaluated for multiply deprotonated oligothymidine 10mers used as control analytes. Although optimal compn. of the calibrant set could not be fully rationalized, one mandatory condition for best CCS accuracy is to include stds. of different charge states to properly model the effects of radial distribution of ions in the TWIM cell. Further improvement of calibration robustness requires that one of these charge states equals that of the analytes to account for the effects of velocity relaxation also incorporated in the IMSCal model. Doing so, exptl. CCS values could be readily obtained with relative error below ±5% for anions of charge state up to 6-.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhs1CntLrK&md5=77fe72716bea1a313f1e4f432a12dd4f
    28. 28
      Vallejo, D. D.; Corstvet, J. L.; Fernández, F. M. Triboelectric Nanogenerators: Low-Cost Power Supplies for Improved Electrospray Ionization. Int. J. Mass Spectrom. 2024, 495, 117167  DOI: 10.1016/j.ijms.2023.117167
      There is no corresponding record for this reference.
    29. 29
      Brown, S. H. J.; Mitchell, T. W.; Blanksby, S. J. Analysis of Unsaturated Lipids by Ozone-Induced Dissociation. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 2011, 1811 (11), 807– 817,  DOI: 10.1016/j.bbalip.2011.04.015
      There is no corresponding record for this reference.
    30. 30
      Ma, X.; Xia, Y. Pinpointing Double Bonds in Lipids by Paternò-Büchi Reactions and Mass Spectrometry. Angew. Chem., Int. Ed. Engl. 2014, 53 (10), 2592– 2596,  DOI: 10.1002/anie.201310699
      30
      Pinpointing double bonds in lipids by Paterno-Buchi reactions and mass spectrometry
      Ma Xiaoxiao; Xia Yu
      Angewandte Chemie (International ed. in English) (2014), 53 (10), 2592-6 ISSN:.
      The positions of double bonds in lipids play critical roles in their biochemical and biophysical properties. In this study, by coupling Paterno-Buchi (P-B) reaction with tandem mass spectrometry, we developed a novel method that can achieve confident, fast, and sensitive determination of double bond locations within various types of lipids. The P-B reaction is facilitated by UV irradiation of a nanoelectrospray plume entraining lipids and acetone. Tandem mass spectrometry of the on-line reaction products via collision activation leads to the rupture of oxetane rings and the formation of diagnostic ions specific to the double bond location.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cvisVyltQ%253D%253D&md5=f02d31d6cdd460c4490bc0324c9391b0
    31. 31
      Murphy, R. C.; Okuno, T.; Johnson, C. A.; Barkley, R. M. Determination of Double Bond Positions in Polyunsaturated Fatty Acids Using the Photochemical Paternò-Büchi Reaction with Acetone and Tandem Mass Spectrometry. Anal. Chem. 2017, 89 (16), 8545– 8553,  DOI: 10.1021/acs.analchem.7b02375
      31
      Determination of Double Bond Positions in Polyunsaturated Fatty Acids Using the Photochemical Patern´o-B.ovrddot.uchi Reaction with Acetone and Tandem Mass Spectrometry
      Murphy, Robert C.; Okuno, Toshiaki; Johnson, Christopher A.; Barkley, Robert M.
      Analytical Chemistry (Washington, DC, United States) (2017), 89 (16), 8545-8553CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
      The positions of double bonds along the carbon chain of methylene interrupted polyunsatd. fatty acids are unique identifiers of specific fatty acids derived from biochem. reactions that occur in cells. It is possible to obtain direct structural information as to these double bond positions using tandem mass spectrometry after collisional activation of the carboxylate anions of an acetone adduct at each of the double bond positions formed by the photochem. Patern´o-B.ovrddot.uchi reaction with acetone. This reaction can be carried out by exposing a small portion of an inline fused silica capillary to UV photons from a mercury vapor lamp as the sample is infused into the electrospray ion source of a mass spectrometer. Collisional activation of [M - H]- yields a series of reverse Patern´o-B.ovrddot.uchi reaction product ions that essentially are derived from cleavage of the original carbon-carbon double bonds that yield an isopropenyl carboxylate anion corresponding to each double bond location. Aldehydic reverse Patern´o-B.ovrddot.uchi product ions are much less abundant as the carbon chain length and no. of double bonds increase. The use of a mixt. of D0/D6-acetone facilitates identification of these double bonds indicating product ions as shown for arachidonic acid. If oxygen is present in the solvent stream undergoing UV photoactivation, ozone cleavage ions are also obsd. without prior collisional activation. This reaction was used to det. the double bond positions in a 20:3 fatty acid that accumulated in phospholipids of RAW 264.7 cells cultured for 3 days.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtFyqs7fK&md5=e617889c2776d5106a7a0b7c35f81c3e
    32. 32
      Zhao, J.; Xie, X.; Lin, Q.; Ma, X.; Su, P.; Xia, Y. Next-Generation Paternò-Büchi Reagents for Lipid Analysis by Mass Spectrometry. Anal. Chem. 2020, 92 (19), 13470– 13477,  DOI: 10.1021/acs.analchem.0c02896
      There is no corresponding record for this reference.

  • Supporting Information

    Supporting Information

    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jasms.4c00010.

    • Video S1 visualizes nanoESI during the TENG pulses described in Figure 5 (MP4)

    • Detailed information is provided on the TENG hardware list, wiring diagram for assembly, MS inlet setup, and data comparison between old and new TENG designs (PDF)


    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.