Electrospray Emitter Research Articles

A monolithic microfluidic probe for ambient mass spectrometry imaging of biological tissues.

Ambient mass spectrometry imaging (MSI) is a powerful technique that allows for the simultaneous mapping of hundreds of molecules in biological samples under atmospheric conditions, requiring minimal sample preparation. We have developed nanospray desorption electrospray ionization (nano-DESI), a liquid extraction-based ambient ionization technique, which has proven to be sensitive and capable of achieving high spatial resolution. We have previously described an integrated microfluidic probe, which simplifies the nano-DESI setup, but is quite difficult to fabricate. Herein, we introduce a facile and scalable strategy for fabricating microfluidic devices for nano-DESI MSI applications. Our approach involves the use of selective laser-assisted etching (SLE) of fused silica to create a monolithic microfluidic probe (SLE-MFP). Unlike the traditional photolithography-based fabrication, SLE eliminates the need for the wafer bonding process and allows for automated, scalable fabrication of the probe. The chamfered design of the sampling port and ESI emitter significantly reduces the amount of polishing required to fine-tune the probe thereby streamlining and simplifying the fabrication process. We have also examined the performance of a V-shaped probe, in which only the sampling port is fabricated using SLE technology. The V-shaped design of the probe is easy to fabricate and provides an opportunity to independently optimize the size and shape of the electrospray emitter. We have evaluated the performance of SLE-MFP by imaging mouse tissue sections. Our results demonstrate that SLE technology enables the fabrication of robust monolithic microfluidic probes for MSI experiments. This development expands the capabilities of nano-DESI MSI and makes the technique more accessible to the broader scientific community.

Incorporation of a Disposable ESI Emitter into Inline Cartridge Extraction Mass Spectrometry Improves Throughput and Spectra Stability.

Rapid and reliable methods for detecting tumor margins are crucial for neuro-oncology. Several mass spectrometry-based methods have been recently proposed to address this problem. Inline Cartridge Extraction (ICE) demonstrates the potential for clinical application, based on ex-vivo analysis of dissected tissues, but requires time-consuming steps to avoid cross-contamination. In this work, a method of incorporating a disposable electrospray emitter into the ICE cartridge by PEEK sleeves melting is developed. It reduces total analysis time and improves throughput. The proposed setup also improves the robustness of the ICE molecular profiling as demonstrated with human glial tumor samples in that stability and reproducibility of the spectra were increased.

Laser Heating Nanoelectrospray Emitters for Fast Protein Melting Measurements with Mass Spectrometry.

Temperature-controlled nanoelectrospray ionization has been used to measure heat-induced conformational changes of biomolecules by mass spectrometry, but long thermal equilibration times associated with heating or cooling an entire emitter limit how fast these data can be acquired. Here, the tip of a borosilicate electrospray emitter is heated using 10.6 μm light from an unfocused CO2 laser. At 1.2 W, the solution inside the emitter tip can be heated from room temperature to a steady-state temperature of 78.2 ± 2.5 °C in less than 0.5 s and cools from 82.6 ± 0.6 °C back to room temperature within 4 s. The time required to establish a steady-state temperature is more than 100-fold faster than that required for a resistively heated emitter due to the low thermal mass. Protein unfolding curves measured as a function of laser power can be acquired in ∼40 s compared to a resistively heated apparatus that required ∼21 min to acquire similar data. Laser power is calibrated to temperature by comparisons of the average charge state of the protein cytochrome c measured with laser heating and with resistive heating. This laser heating method is applied to a three-component protein mixture to demonstrate the ability to rapidly acquire melting temperatures of proteins in mixtures. The ability to rapidly assess the thermal stabilities of multiple proteins simultaneously shows significant promise for coupling temperature-controlled electrospray ionization (ESI) to separation techniques, providing a high-throughput method for determining the effects of solution composition, drug binding, or sequence mutations on protein thermal stability.

Scalable Microfabrication of Multi-Emitter Arrays in Silicon for a Compact Microfluidic Electrospray Propulsion System.

The recent proliferation of SmallSats and their use in increasingly demanding applications require the development of onboard electric propulsion compatible with the power, mass, and volume constraints of these spacecraft. Electrospray propulsion is a promising technology for SmallSats due to its unique high efficiency and scalability across the wide power range of these platforms, for example, from a few watts available in a CubeSat to a few hundred watts in a MiniSat. The implementation of electrospray propulsion requires the use of microfabrication techniques to create compact arrays of thousands of electrospray emitters. This article demonstrates the microfabrication of multi-emitter electrospray sources of a scalable size for electrospray propulsion. In particular, a microfabrication and assembly process is developed and demonstrated by fabricating sources with arrays of 1, 64, and 256 emitters. The electrospray sources are tested in a relevant environment for space propulsion (inside a vacuum chamber), exhibiting excellent propulsive performance (e.g., absence of beam impingement in the extractor electrode, absence of hysteresis in the beam current versus propellant flow rate characteristic, proper operation in the cone-jet electrospraying mode, etc.) and nearly coincident output per emitter. Several design elements contribute to this performance: the even distribution of the propellant among all emitters made possible by the implementation of a network of microfluidic channels in the backside of the emitter array; the small dead volume of the network of microfluidic channels; the accurate alignment between the emitters and extractor orifices; and the use of a pipe-flow configuration to drive the propellant through closed conduits, which protects the propellant.

Shear‐Induced Macropore‐Infused Nanocomposite Emulsion Thermosets

AbstractTo create macropore‐infused nanocomposite emulsion thermosets (MINET), a mixing pathway is demonstrated in which a viscous fluid is kinetically trapped by high shear mixing of immiscible liquids, surfactant, and nanoparticles. The MINETs are prepared from common ingredients that are widely employed in industry, including epoxy resin, vegetable oil, epoxidized soybean oil, and different types of nanoparticles such as silica, activated carbon, alumina, and zinc oxide. MINETs prepared by the presented route are processed at ambient conditions and exhibit low shrinkage (<2%). Furthermore, they are suitable to form macro‐ to microscale structures with high precision and various controlled porosity. The interconnected porous architecture of MINET is even preserved in molded micrometer‐scale features and thus ensures mass transport through multiscale structures. In combination with standard microembossing or photolithography, the high throughput microfabrication of microstructured architectures with tunable pore sizes in a wide range (≈100 nm to ≈10 µm) is possible. As one application example, the parallel production of multiplexed electrospray emitters is demonstrated.

Polydopamine inner wall-coated hypodermic needle as microextraction device and electrospray emitter for the direct analysis of illicit drugs in oral fluid by ambient mass spectrometry

In this article, polydopamine inner wall-coated hypodermic needles (PDA-HNs) are evaluated as both microextraction devices and electrospray ionization (ESI) emitters for determining selected illicit drugs (methamphetamine, cocaine, and methadone) in oral fluid samples. The PDA film, located in the inner wall of the needle, allows the extraction of the analytes at alkaline pH, where their hydrophobic character is promoted. The extracted analytes are finally eluted in a methanol/formic acid mixture that also acts as ESI solution. For this purpose, a dedicated interface based on the connection of a PEEK tube with the needle hub is proposed. This assembly allows delivering the ESI solution by the infusion syringe pump of the mass spectrometer, providing an efficient ESI on the tip of the needle. The double use of the PDA-HNs as microextraction devices and ESI emitters permits the determination of the target analytes with limits of detection and precision (expressed as relative standard deviation) values better than 2.4 μg/L and 17.6%, respectively. The accuracy was evaluated by analyzing independent spiked oral fluid samples, obtaining good results.

Multiple Emission Sites on Porous Glass Electrospray Propulsion Emitters Using Dielectric Propellants

Spatially resolved emission current density maps are presented as a function of extraction voltage for two near-conical porous borosilicate glass electrospray emitters using a 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imid ionic liquid. The current measurements are complimented with time-of-flight measurements to characterize the charge-to-mass ratio of the beams. The spatial current probe measurements resolve individual beamlets associated with separate emission sites, allowing the observation of the growth of the number of emission sites as the extraction voltage is increased. The emitters are found to operate near the pure ionic regime, and no evidence of the transition to unstable emission is observed up to above onset. An empirical model is developed for the onset of emission sites that accounts for the changes in site hydraulic resistance with the number of emission sites. The model satisfactorily reproduces the experimental voltage–current curves and average beam charge-to-mass ratios after the adjustment of several empirical parameters.

Taking internally wetted capillary electrospray emitters to the sub-ten-micrometer scale with 3D microlithography

Electrospray emitters are an obvious choice for miniaturized thrusters for a variety of applications on small satellites (e. g., CubeSats), as well as for other micropropulsion purposes. They are inherently small and require a relatively low electric power for operation, and therefore, they fulfill the requirements imposed due to the small volume of CubeSats. Electrospray emitters of the internally wetted capillary type were fabricated by 3D microlithography in the SU-8 photopolymer down to capillary diameters of about 10 μm. Thus, the emitters are an order of magnitude smaller in lateral dimensions than those fabricated by advanced 3D printing methods and still half an order of magnitude smaller than those made by planar photolithography in SU-8. Fabrication methods and process parameters are presented. Furthermore, the preliminary results of the electric characterization of the emission behavior are shown. The experiments show promising results regarding the fabrication quality and extraction behavior.

Mass flux and current density distributions of electrospray plumes

Performance and lifetime analysis of electrospray thrusters requires accurate knowledge of the mass and charge distributions of the plume. Mass flux and current density distributions were measured for a single capillary electrospray emitter using EMI-Im and found to be substantially different across a wide range of flow rates and emission voltages. Mass flux measurements yield an n∼3 super-Gaussian profile across all flow rates and voltages, while current density measurements change shape from n∼1.5–2.5 super-Gaussian profiles monotonically with decreasing flow rate, where n=1 is Gaussian and higher n values correspond to increasingly more flat-top “super-Gaussian” profiles with steeper drop-off toward higher angles. For increasing flow rate, the mass flux profile grows while maintaining its shape, whereas the current density profile exhibits higher kurtosis, i.e., plumes that distribute proportionately more charge to higher angles. Additionally, higher extraction voltages exhibited tilted emission that led to highly off-axis plumes, ∼10°, for both mass flux and current density. Lifetime and performance assessments of electrospray thrusters must consider that mass flux and current density in the plume display different distribution shapes and trends in shape across changes in extraction voltage and flow rate.

Rapid Analysis of Biological Samples Using Monolithic Polymer-Based In-Tube Solid-Phase Microextraction with Direct Mass Spectrometry.

Online coupling in-tube solid-phase microextraction (SPME) with mass spectrometry (MS) was achieved by directly utilizing a monolithic SPME capillary as the electrospray emitter. A porous organic polymer with a highly porous structure can not only provide excellent extraction efficiency due to its high specific surface area but also increase the ionization efficiency and stability by producing smaller electrospray droplets. This online coupling strategy significantly simplifies the device as well as the operation process. The whole analytical process only takes about 12 min with a sample amount of 100 μL. By choosing an ionic liquid-based organic polymer with high extraction ability and good stability and adjusting a suitable porous structure for better electrospray, the developed in-tube SPME-MS method showed excellent extraction performance and good reusability without clogging events. As a proof of concept, the proposed method was applied for the analysis of non-steroid anti-inflammatory drugs in plasma and urine samples. The method showed a wide linear range (0.1-200 ng/mL), good linearity (R2 ≥ 0.99), and good reproducibility (intra-day relative standard deviations (RSDs) <3.00% and inter-day RSDs <6.29%).

Plume Composition Measurements of a High-Emission-Density Electrospray Thruster

An electrospray thruster designed for nanosatellites is introduced in this paper. The thruster has a compact size featuring a passive propellant transport method through the use of porous materials. Porous electrospray emitters with 1, 25, and 100 emission tips were fabricated using conventional machining techniques. The geometrical features of the emission tips were measured using a high-precision laser profilometer. Thruster prototypes fitted with different emitters were tested in a bipolar operation mode. The emission currents and voltage characteristics were studied, which demonstrated a wide range of operational voltage with relatively high emission currents. The maximum overall emission currents were and achieved using a 100-tip emitter at , and the maximum per-tip emission currents were and achieved using a 25-tip emitter at , respectively. Time-of-flight systems were used to characterize the mass and velocity distribution of the charged particles in the thruster plume, and the results suggest that the electrospray emission were highly ionic, containing mostly monomer ions and dimer ions. The thruster performance was conservatively estimated, with the thrust ranging from approximately 0.92 to , and the specific impulse ranging from 2733 to 5550 s. The maximum thrust per emission tip was approximately in a purely ionic emission regime, which is considerably high in this type of technology.

A Robust Method for Packing High Resolution C18 RP-nano-HPLC Columns.

The high complexity prevalent in biological samples requires chromatographic separations with high sensitivity and resolution to be effectively analyzed. Here we introduce a robust, reproducible and inexpensive protocol for preparation of a nano-flow reversed phase high performance liquid chromatography (RP-HPLC) columns for on-line separation of analytical peptides before introduction into and detection by a mass-spectrometer in traditional bottom-up proteomics workflows. Depending on the goal of the experiment and the chemical properties of the analytes being separated, optimal column parameters may differ in their internal or outer diameters, length, particle size, pore size, chemistry of stationary phase particles, and the presence or absence of an integrated electrospray emitter at the tip. An in-house column packing system not only enables the rapid fabrication of columns with the desired properties but also dramatically reduces the cost of the process. The optimized protocol for packing a C18 AQ (aqueous) fused silica column discussed here is compatible with a wide range of liquid chromatographic instruments for achieving effective separation of analytes.

Creation of electrospray emitters from a flat polytetrafluoroethylene sheet through the use of laser micro-manufacturing

Electrospray propulsion is a form of electrostatic propulsion that shows potential for use as a thruster on small satellites. Electrospray emitters traditionally use arrays of capillaries, however, this paper investigates the suitability of manufacturing an emitter by laser drilling holes in sheets of polytetrafluoroethylene (PTFE), also known as Teflon. This is done by examining factors such as the machining time, hole shape and degree of taper in holes drilled through different methods. Experimental work was done to determine the shape of holes drilled in a flat sheet, and a computational model was used to simulate the performance of these drilled holes. These results were used to judge if this would be a valid method to manufacture electrospray thrusters, and how these thrusters would compare to more traditional emitters. Based on these results, it was concluded that a PTFE sheet with a width of 0.81 mm would be sufficient to achieve electrospray at voltages lower than those needed for traditional emitters.

Multiplexed electrospray emission on a porous wedge

Linear porous wedge electrospray emitters exhibit a discrete number of emission sites that naturally form during operation. An analytical model is developed to examine the behavior and spacing of these emission sites via the pressure variation in the porous fluid flow associated with the flow focusing on each emission site, which is coupled with the local electric field. The solution for site spacing and current is informed by empirical results with support from electric field modeling and investigation of porous media parameters. Emission site currents of up to 500 nA and site spacings of roughly 50 µm–300 µm are predicted. Results from the model match well with experimental trends and provide further insights into the current and spacing of the discrete emission sites. These insights include the following: (1) for the investigated geometry, the total current can be estimated without taking into account the effects local to each emission site, (2) the wedge hydraulic resistance shows how the emitter output scales with emitter geometry and propellant properties, and (3) the emitted charge to mass ratio increases with the applied electric field. Last, we present a physical description of how specific charge increases with the restorative pressure from the reservoir.

Direct analysis of naphthenic acids in produced water and crude oil by NH2-surface-modified wooden-tip electrospray ionization mass spectrometry.

This work describes the surface coating of wooden toothpicks with amino groups (NH2) for electrospray ionization mass spectrometry (MS) analysis of naphthenic acids (NAs) in produced water samples and crude oil fractions. NH2 was introduced into the cellulosic material through a silanization reaction using aminopropyltriethoxysilane. An NH2-modified toothpick was inserted into the analyte extraction sample and was subsequently used as an electrospray emitter for MS analysis. The extraction conditions were optimized by analyzing NAs (benzoic acid, 1-naphthoic acid, decanoic acid, 3,5-dimethyladamantane-1-carboxylic acid, and 3,5-dimethyladamantane-1-acetic acid) in pure water, and the best condition was using 5 min of extraction time with the samples under agitation. Modified and unmodified wooden toothpicks were compared, and the intensities of all NAs were higher when using the modified substrates than when using the unmodified ones. Limit of detection (LOD), limit of quantification (LOQ), linearity, precision, and recovery were determined by analyzing decanoic acid in seawater samples. The LOD and LOQ were 2 and 5 μg mL-1, respectively, and a linear correlation (R2 = 0.9927) was obtained with concentrations ranging from 5 to 250 μg mL-1. Precision values ranged from 6 to 13% and recoveries from 89 to 106%. The technique was also employed to analyze three produced water samples, in which decanoic acid was semi-quantified, and the concentrations ranged from 10 to 13 μg mL-1. High abundances of acidic compounds of class O2 with DBEs (double bond equivalents) ranging from 1 to 3 and carbon numbers going from 8 to 12 were detected in the produced water samples. The results suggest that the modification of wooden toothpicks with NH2 might offer a significant advancement in the knowledge of cheap substrates that can improve the sensitivity of analysis of NAs in water samples.

Fabrication and characterization of laser-heated, multiplexed electrospray emitter.

We present a one-step fabrication method for a new multiplexed electrospray emitter with nine parallel micronozzles. The nozzles were formed by wet chemical etching of the end of a microstructured silica fiber containing nine 10 μm flow channels. By carefully adjusting the water flow through the channels while etching, we controlled the shape of the conical micronozzles and were able to obtain conditions under which the micronozzles, together with the flow channels, formed optical micro-axicon lenses. When 1064 nm light was guided through the flow channels and focused by the micro-axicon lenses into the Taylor cones, we were able to increase the desolvation of a model analyte and thereby increased the spray current produced by the emitter. This work paves the way towards a rapidly modulated mass-spectrometry source having a greatly enhanced throughput.

On-Line Coupling of Chip-Electrochromatography and Ion Mobility Spectrometry.

We report the first hyphenation of chip-electrochromatography (ChEC) with ion mobility spectrometry (IMS). This approach combines the separation power of two electrokinetically driven separation techniques, the first in liquid phase and the second in gas phase, with a label-free detection of the analytes. For achieving this, a microfluidic glass chip incorporating a monolithic separation column, a nanofluidic liquid junction for providing post-column electrical contact, and a monolithically integrated electrospray emitter was developed. This device was successfully coupled to a custom-built high-resolution drift tube IMS with shifted potentials. After proof-of-concept studies in which a mixture of five model compounds was analyzed in less than 80 s, this first ChEC-IMS system was applied to a more complex sample, the analysis of herbicides spiked in the wine matrix. The use of ChEC before IMS detection not only facilitated the peak allocation and increased the peak capacity but also enabled analyte quantification. As both, ChEC and IMS work at ambient conditions and are driven by high voltages, no bulky pumping systems are needed, neither for the hydrodynamic pumping of the mobile phase as in high-performance liquid chromatography nor for generating a vacuum system as in mass spectrometry. Accordingly, the approach has great potential as a portable analytical system for field analysis of complex mixtures.

Integration of 3D-printing for a desorption electrospray ionization source for mass spectrometry.

The field of ambient ionization mass spectrometry has witnessed the development of many novel and capable methods for the analysis and imaging of surfaces, with desorption electrospray ionization being a prominent technique that has been commercialized. The adaptation of this technique to existing mass spectrometry platforms requires a laboratory-built solution manufactured with the capability of fine, stable adjustments of the electrospray emitter for liquid or solid sampling purposes. The development, fabrication, and machining require tens of hours of labor for many custom solutions. Herein described is a highly modifiable alternative approach for the fabrication of a desorption electrospray ionization source, using computer-aided design and fused deposition modeling to three-dimensionally print a source platform that utilizes standard accessories of a commercial Bruker Daltonics mass spectrometer. Three-dimensional printing allows for the inexpensive, rapid development of highly modifiable plastic parts, with the total printing time of the apparatus requiring a singular day and only a few dollars of material using a consumer grade printer. To demonstrate the utility of this printed desorption electrospray ionization source, it was fitted on an unmodified Fourier transform ion cyclotron resonance mass spectrometer for a lipid fingerprint analysis in serial sections of rat brain tissue, with the acquisition of line scans of dye-coated slides for the demonstration of serial acquisition.

Numerical investigation of the effects of geometry and materials on the onset voltage of electrospray emitters

Guidelines for the design of 2D electrospray emitter arrays that operate at minimal emission onset voltage are established by analyzing the dependence of the emission onset voltage on key emitter dimensions. The electrostatic field, and resulting onset voltage, are determined numerically for different configurations. The relative permittivity of the medium surrounding the emitters is varied between 1 and 10 to consider two types of emitters: capillary emitters standing in vacuum, and capillary emitters embedded in a dielectric material. Results for single electrospray emitters are compared to those of an analytical model. Trends in the data imply minimal onset voltage when using dielectrics with low relative permittivity, small-diameter emitters tall enough to escape shielding from the surrounding features of the device, and a small extractor distance. However, these relationships are complex and are discussed in detail. The data also agrees with previous numerical research into arrays of emitters showing that at an emitter spacing of approximately 2.5 times the emitter height, shielding effects become negligible. These design guidelines and the specific results reported herein are particularly relevant to the rapid development of miniaturized electrospray chips holding hundreds, or even thousands, of emitters that are expected to reach market in the near future.

Accelerating Electrochemical Reactions in a Voltage‐Controlled Interfacial Microreactor

AbstractMicrodroplet chemistry is attracting increasing attention for accelerated reactions at the solution–air interface. We report herein a voltage‐controlled interfacial microreactor that enables acceleration of electrochemical reactions which are not observed in bulk or conventional electrochemical cells. The microreactor is formed at the interface of the Taylor cone in an electrospray emitter with a large orifice, thus allowing continuous contact of the electrode and the reactants at/near the interface. As a proof‐of‐concept, electrooxidative C−H/N−H coupling and electrooxidation of benzyl alcohol were shown to be accelerated by more than an order of magnitude as compared to the corresponding bulk reactions. The new electrochemical microreactor has unique features that allow i) voltage‐controlled acceleration of electrochemical reactions by voltage‐dependent formation of the interfacial microreactor; ii) “reversible” electrochemical derivatization; and iii) in situ mechanistic study and capture of key radical intermediates when coupled with mass spectrometry.