Electroless Ionization Mass Spectrometry Using a Compact Electrokinetic Ionization Source.

We introduce a new ionization technique for compact, portable mass spectrometers. It consists of a syringe with sample liquid capped by a self-ionizing spray nozzle containing a microfabricated nozzle chip. Interaction of the sample liquid with the nozzle wall results in electrical charging without the need for electronics. Elaborate cleaning procedures are redundant when disposable syringes and mass-fabricated spray nozzles are used. This self-named electroless spray ionization (ELI) technique shows comparable performance to conventional ionization techniques. In contrast to commonly used electrospray ionization, ELI exhibits excellent ionization efficiency for low-conductive solutions such as water or acetonitrile. Due to its compact size and the absence of high-voltage electronics, it can also be readily integrated in other ionization sources. Besides reviewing the main properties of ELI, we showcase the technique's potential for two on-site, ambient mass spectroscopy applications: perfume fingerprinting and fast screening of fungicides on citrus fruits.

Realizing Symmetry-Breaking Architectures in Soap Films.

We show here that soap films-typically expected to host symmetric molecular arrangements-can be constructed with differing opposite surfaces, breaking their symmetry, and making them reminiscent of functional biological motifs found in nature. Using fluorescent molecular probes as dopants on different sides of the film, resonance energy transfer could be employed to confirm the lack of symmetry, which was found to persist on timescales of several minutes. Further, a theoretical analysis of the main transport phenomena involved yielded good agreement with the experimental observations.

Co-current crossflow microfiltration in a microchannel.

Steady state crossflow microfiltration (CMF) is an important and often necessary means of particle separation and concentration for both industrial and biomedical processes. The factors controlling the performance of CMF have been extensively reviewed. A major factor is transmembrane pressure (TMP). Because microchannels have small height, they tend to have high pressure gradients in the feed-flow direction. In the extreme, these gradients may even reverse the pressure across the membrane (inciting backflow). It is therefore desirable to compensate for the effect of feed-flow on the TMP, aiming at constant transmembrane pressure (cTMP) at a value which maximizes filtrate flux. This is especially critical during filtration of deformable particles (e.g. erythrocytes) through low intrinsic resistance membranes. Filtration flux is generally taken to be directly proportional to TMP, with pressure drop along the channel decreasing in the flow direction. A co-current flow of filtrate in a suitably designed filtrate collecting channel is shown to allow the TMP to remain constant and permit the sieving surface to perform optimally, permitting up to twice as much filtration over that of a naïve configuration. Manipulation of the filtrate channel may be even more beneficial if it prevents backflow that might otherwise occur at the end of a sufficiently long channel. Experiments with erythrocyte suspensions, reported here, validate these concepts.

Erythrocyte fouling on micro-engineered membranes.

Crossflow microfiltration of plasma from blood through microsieves in a microchannel is potentially useful in many biomedical applications, including clinically as a wearable water removal device under development by the authors. We report experiments that correlate filtration rates, transmembrane pressures (TMP) and shear rates during filtration through a microscopically high channel bounded by a low intrinsic resistance photolithographically-produced porous semiconductor membrane. These experiments allowed observation of erythrocyte behavior at the filtering surface and showed how their unique deformability properties dominated filtration resistance. At low filtration rates (corresponding to low TMP), they rolled along the filter surface, but at higher filtration rates (corresponding to higher TMP), they anchored themselves to the filter membrane, forming a self-assembled, incomplete monolayer. The incompleteness of the layer was an essential feature of the monolayer's ability to support sustainable filtration. Maximum steady-state filtration flux was a function of wall shear rate, as predicted by conventional crossflow filtration theory, but, contrary to theories based on convective diffusion, showed weak dependence of filtration on erythrocyte concentration. Post-filtration scanning electron micrographs revealed significant capture and deformation of erythrocytes in all filter pores in the range 0.25 to 2 µm diameter. We report filtration rates through these filters and describe a largely unrecognized mechanism that allows stable filtration in the presence of substantial cell layers.

Emanating Jets As Shaped by Surface Tension Forces.

We show that emanating jets can be regarded as growing liquid towers, which are shaped by the twofold action of surface tension: first the emanated fluid is being accelerated back by surface tension force, herewith creating the boundary conditions to solve the shape of the liquid tower as a solution of an equation mathematically related to the hydrostatic Young-Laplace equation, known to give solutions for the shape of pending and sessile droplets, and wherein the only relevant forces are gravity g and surface tension γ. We explain that for an emanating jet under specific constraints all mass parts with density ρ will experience a uniform time dependent acceleration a( t). An asymptotic solution is subsequently numerically derived by making the corresponding Young-Laplace type equation dimensionless and by dividing all lengths by a generalized time dependent capillary length λc( t) = [Formula: see text]. The time dependent surface tension γ( t) can be derived by measuring both time dependent acceleration a( t) and time dependent capillary length λc( t). Jetting experiments with water and coffee show that the dynamic surface tension behavior according to the emanating jet method and with the well-known maximum bubble pressure method are the same, herewith verifying the proposed model.

Droplet Formation by Confined Liquid Threads inside Microchannels.

A confined liquid thread can form monodisperse droplets near the exit of a microchannel, provided the continuous phase is able to enter the microchannel. A general model that accurately predicts the droplet size including the breakup position inside the microchannel is presented and is verified with experimental observations; breakup occurs as long as the capillary number (Ca) of the liquid thread is below a critical capillary number (Cacr); for cylindrical microchannels, it is derived that Cacr = 1/16. Below Cacr, the formed droplets at the exit of the microchannel have a diameter approximately two times the diameter of the liquid thread; around and above Cacr, the liquid thread remains stable and the formed droplets grow infinitely large. The presented controlled droplet generation method is a useful tool for producing monodisperse emulsions and has great potential for the food and pharmaceutical industry.

Adhesion and friction properties of fluoropolymer brushes: on the tribological inertness of fluorine.

The effects of fluorination on the adhesion and friction properties of covalently bound poly(fluoroalkyl methacrylate) polymer brushes (thickness ∼80 nm) were systematically investigated. Si(111) surfaces were functionalized with a covalently bound initiator via a thiol-yne click reaction to have a high surface coverage for initiator immobilization. Surface-initiated atom-transfer radical polymerization (SI-ATRP) was employed for the synthesis of four different fluoropolymer brushes (SPFx, where x = 0, 3, 7, or 17 F atoms per monomer), based on fluoroalkyl methacrylates. All polymer brushes were characterized with static contact angle measurements, X-ray photoelectron spectroscopy (XPS), and infrared absorption reflection spectroscopy (IRRAS). The polymer brushes exhibited an excellent hydrophobicity, with static water contact angles of up to 121° depending on the number of fluorine atoms per side chain in fluoroalkyl methacrylate. The degree of swelling was precisely studied by using ellipsometry in different solvents such as acetone, hexadecane, hexafluoroisopropanol, nonafluorobutyl methyl ether, and Fluorinert FC-40. The polymer brushes have shown nanoscale swelling behavior in all solvents except hexadecane. The grafting density decreased upon increasing fluorine content in polymer brushes from 0.65 chains/nm(2) (SPF0) to 0.10 chains/nm(2) (SPF17) as observed in Fluorinert FC-40 as a good solvent. Adhesion and friction force measurements were conducted with silica colloidal probe atomic force microscopy (CP-AFM) under ambient, dry (argon), and lubricating fluid conditions. SPF17 showed the lowest coefficient of friction 0.005 under ambient condition (RH = 44 ± 2%) and a further decrease with 50% under fluidic conditions. These polymer brushes also showed adhesion forces as low as 6.9 nN under ambient conditions, which further went down to 0.003 nN under fluidic conditions (Fluorinert FC-40 and hexadecane) at 10 nN force.

Adhesion and friction properties of polymer brushes: fluoro versus nonfluoro polymer brushes at varying thickness.

A series of different thicknesses of fluoro poly(2,2,2-trifluoroethyl methacrylate) and its analogous nonfluoro poly(ethyl methacrylate) polymer brushes were prepared via surface-initiated ATRP (SI-ATRP) on Si(111) surfaces. The thiol-yne click reaction was used to immobilize the SI-ATRP initiator with a high surface coverage, in order to achieve denser polymer brushes (grafting density from ~0.1 to 0.8 chains/nm(2)). All polymer brushes were characterized by static water contact angle measurements, infrared absorption reflection spectroscopy, and X-ray photoelectron spectroscopy. Adhesion and friction force measurements were conducted with silica colloidal probe atomic force microscopy (CP-AFM) under ambient and dry (argon) conditions. The fluoro poly(2,2,2-trifluoroethyl methacrylate) polymer showed a decrease in adhesion and friction with increasing thickness. The analogous nonfluoro poly(ethyl methacrylate) polymer brushes showed high adhesion and friction under ambient conditions. Friction coefficients down to 0.0057 (ambient conditions) and 0.0031 (dry argon) were obtained for poly(2,2,2-trifluoroethyl methacrylate) polymer brushes with 140 nm thickness, which are the lowest among these types of polymer brushes.

Covalently attached organic monolayers onto silicon carbide from 1-alkynes: molecular structure and tribological properties.

In order to achieve improved tribological and wear properties at semiconductor interfaces, we have investigated the thermal grafting of both alkylated and fluorine-containing ((C(x)F(2x+1))-(CH2)n-) 1-alkynes and 1-alkenes onto silicon carbide (SiC). The resulting monolayers display static water contact angles up to 120°. The chemical composition of the covalently bound monolayers was studied by X-ray photoelectron spectroscopy (XPS), infrared reflection-absorption spectroscopy (IRRAS), and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. These techniques indicate the presence of acetal groups at the organic-inorganic interface of alkyne-modified SiC surfaces. The tribological properties of the resulting organic monolayers with fluorinated or nonfluorinated end groups were explored using atomic force microscopy (AFM). It was found that the fluorinated monolayers exhibit a significant reduction of adhesion forces, friction forces, and wear resistance compared with non-fluorinated molecular coatings and especially bare SiC substrates. The successful combination of hydrophobicity and excellent tribological properties makes these strongly bound, fluorinated monolayers promising candidates for application as a thin film coating in high-performance microelectronic devices.

Efficient functionalization of oxide-free silicon(111) surfaces: thiol-yne versus thiol-ene click chemistry.

Thiol-yne click (TYC) chemistry was utilized as a copper-free click reaction for the modification of alkyne-terminated monolayers on oxide-free Si(111) surfaces, and the results were compared with the analogous thiol-ene click (TEC) chemistry. A wide range of thiols such as 9-fluorenylmethoxy-carbonyl cysteine, thio-ß-d-glucose tetraacetate, thioacetic acid, thioglycerol, thioglycolic acid, and 1H,1H,2H,2H-perfluorodecanethiol was immobilized using TYC under photochemical conditions, and all modified surfaces were characterized by static water contact angle measurements, X-ray photoelectron spectroscopy (including a simulation thereof by density functional calculations), and infrared absorption reflection spectroscopy. Surface-bound TYC proceeds with an efficiency of up to 1.5 thiols per alkyne group. This high surface coverage proceeds without oxidizing the Si surface. TYC yielded consistently higher surface coverages than TEC, due to double addition of thiols to alkyne-terminated monolayers. This also allows for the sequential and highly efficient attachment of two different thiols onto an alkyne-terminated monolayer.

Mono-fluorinated alkyne-derived SAMs on oxide-free Si(111) surfaces: preparation, characterization and tuning of the Si workfunction.

Organic monolayers derived from ω-fluoro-1-alkynes of varying carbon chain lengths (C(10)-C(18)) were prepared on Si(111) surfaces, resulting in changes of the physical and electronic properties of the surface. Analysis of the monolayers using XPS, Infrared Reflection Absorption Spectroscopy, ellipsometry and static water contact angle measurements provided information regarding the monolayer thickness, the tilt angle, and the surface coverage. Additionally, PCFF molecular mechanics studies were used to obtain information on the optimal packing density and the layer thickness, which were compared to the experimentally found data. From the results, it can be concluded that the monolayers derived from longer chain lengths are more ordered, possess a lower tilt angle, and have a higher surface coverage than monolayers derived from shorter chains. We also demonstrate that by substitution of an H by F atom in the terminal group, it is possible to controllably modify the surface potential and energy barrier for charge transport in a full metal/monolayer-semiconductor (MOMS) junction.

Improved Olfactory Deposition of Theophylline Using a Nanotech Soft Mist Nozzle Chip.

Currently, nasal administration of active pharmaceutical ingredients is most commonly performed using swirl-nozzle-based pump devices or pressurized syringes. However, they lead to limited deposition in the more active regions of the nasal cavity, especially the olfactory region, which is crucial for nose-to-brain drug delivery. This research proposes to improve deposition in the olfactory region by replacing the swirl nozzle with a nanoengineered nozzle chip containing micrometer-sized holes, which generates smaller droplets of 10-50 µm travelling at a lower plume velocity. Two nanotech nozzle chips with different hole sizes were tested at different inhalation flow rates to examine the deposition patterns of theophylline, a hyposmia treatment formulation, using a nasal cavity model. A user study was also conducted and showed that the patient instructions influenced the inhalation flow rate characteristics. Targeted flow rates of between 0 and 25 L/min were used for the in vitro deposition study, yielding 21.5-31.5% olfactory coverage. In contrast, the traditional swirl nozzle provided only 10.8% coverage at a similar flow rate. This work highlights the potential of the nanotech soft mist nozzle for improved intranasal drug delivery, particularly to the olfactory region.

Low energy nebulization preserves integrity of SARS-CoV-2 mRNA vaccines for respiratory delivery.

Nebulization of mRNA therapeutics can be used to directly target the respiratory tract. A promising prospect is that mucosal administration of lipid nanoparticle (LNP)-based mRNA vaccines may lead to a more efficient protection against respiratory viruses. However, the nebulization process can rupture the LNP vehicles and degrade the mRNA molecules inside. Here we present a novel nebulization method able to preserve substantially the integrity of vaccines, as tested with two SARS-CoV-2 mRNA vaccines. We compare the new method with well-known nebulization methods used for medical respiratory applications. We find that a lower energy level in generating LNP droplets using the new nebulization method helps safeguard the integrity of the LNP and vaccine. By comparing nebulization techniques with different energy dissipation levels we find that LNPs and mRNAs can be kept largely intact if the energy dissipation remains below a threshold value, for LNP integrity 5-10 J/g and for mRNA integrity 10-20 J/g for both vaccines.

The emerging role of circulating tumor cell detection in genitourinary cancer.

PURPOSE: Circulating tumor cells are malignant cells in peripheral blood that originate from primary tumors or metastatic sites. The heterogeneous natural history and propensity for recurrence in prostate, bladder and kidney cancers are well suited for improved individualization of care using circulating tumor cells. The potential clinical applications of circulating tumor cells include early diagnosis, disease prediction and prognosis, and selection of appropriate therapies. MATERIALS AND METHODS: The PubMed® and Web of Science® databases were searched using the key words circulating tumor cells, CTC, prostate, kidney, bladder, renal cell carcinoma and transitional cell carcinoma. Relevant articles and references from 1994 to 2011 were reviewed for data on the detection and significance of circulating tumor cells in genitourinary cancer. RESULTS: Technical challenges have previously limited the widespread introduction of circulating tumor cell detection in routine clinical care. Recently novel platforms were introduced to detect these cells that offer the promise of overcoming these limitations. We reviewed the current state of circulating tumor cell capture technologies and their clinical applications for genitourinary cancers. CONCLUSIONS: In genitourinary cancer circulating tumor cell enumeration has been useful for prognosis in patients with castration resistant prostate cancer. Soon characterizing individual circulating tumor cells in blood will serve as a noninvasive real-time liquid biopsy to monitor molecular changes in cancer, allowing clinicians to custom tailor treatment strategies. Circulating tumor cells will serve as a treatment response biomarker. Finally, circulating tumor cell detection promises to assist in the early detection of clinically localized cancers, facilitating curative therapy.

Bioconjugation of protein-repellent zwitterionic polymer brushes grafted from silicon nitride.

A new method for attaching antibodies to protein-repellent zwitterionic polymer brushes aimed at recognizing microorganisms while preventing the nonspecific adsorption of proteins is presented. The poly(sulfobetaine methacrylate) (SBMA) brushes were grafted from α-bromo isobutyryl initiator-functionalized silicon nitride (Si(x)N(4), x ≥ 3) surfaces via controlled atom-transfer radical polymerization (ATRP). A trifunctional tris(2-aminoethyl)amine linker was reacted with the terminal alkylbromide of polySBMA chains. N-Hydroxysuccinimide (NHS) functionalization was achieved by reacting the resultant amine-terminated polySBMA brush with bifunctional suberic acid bis(N-hydroxysuccinimide ester). Anti-Salmonella antibodies were subsequently immobilized onto polySBMA-grafted Si(x)N(4) surfaces through these NHS linkers. The protein-repellent properties of the polySBMA-grafted surface after antibody attachment were evaluated by exposing the surfaces to Alexa Fluor 488-labeled fibrinogen (FIB) solution (0.1 g·L(-1)) for 1 h at room temperature. Confocal laser scanning microscopy (CLSM) images revealed the minimal adsorption of FIB onto the antibody-coated polySBMA in comparison with that of antibody-coated epoxide monolayers and also bare Si(x)N(4) surfaces. Subsequently, the interaction of antibodies immobilized onto polySBMA with SYTO9-stained Salmonella solution without using blocking solution was examined by CLSM. The fluorescent images showed that antibody-coated polySBMA efficiently captured Salmonella with only low background noise as compared to antibody-coated monolayers lacking the polymer brush. Finally, the antibody-coated polySBMA surfaces were exposed to a mixture of Alexa Fluor 647-labeled FIB and Salmonella without the prior use of a blocking solution to evaluate the ability of the surfaces to capture bacteria while simultaneously repelling proteins. The fluorescent images showed the capture of Salmonella with no adsorption of FIB as compared to antibody-coated epoxide surfaces, demonstrating the potential of the zwitterionic layer in preventing the nonspecific adsorption of the proteins during the detection of bacteria in complex matrices.

Ultralow adhesion and friction of fluoro-hydro alkyne-derived self-assembled monolayers on H-terminated Si(111).

New fluorine-containing terminal alkynes were synthesized and self-assembled onto Si(111) substrates to obtain fluorine-containing organic monolayers. The monolayers were analyzed in detail by ellipsometry, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared reflection absorption spectroscopy (FT-IRRAS), static water contact angle measurements (CA), and atomic force microscopy (AFM). The SAMs exhibit excellent hydrophobicity, with static water contact angles of up to 119° and low critical surface tensions of 5-20 mN/m depending on the number of F atoms per molecule. IRRAS confirmed the formation of highly ordered monolayers, as indicated by the antisymmetric and symmetric stretching vibrations of the CH(2) moieties at 2918-2920 and 2850-2851 cm(-1), respectively. Upon increasing the number of fluorine atoms in the alkyne chains from 0 to 17, the adhesion of bare silica probes to the SAMs in air decreases from 11.6 ± 0.20 mJ/m(2) for fluorine-free (F0) alkyne monolayers to as low as 3.2 ± 0.03 mJ/m(2) for a heptadecafluoro-hexadecyne (F17)-based monolayer. Likewise, the friction coefficient decreases from 5.7 × 10(-2) to 1.2 × 10(-2). The combination of high ordering, excellent hydrophobicity, low adhesion, and low friction makes these fluoro-hydro alkyne-derived monolayers highly promising candidates for use in high-performance microelectronic devices.

Hexadecadienyl monolayers on hydrogen-terminated Si(111): faster monolayer formation and improved surface coverage using the enyne moiety.

To further improve the coverage of organic monolayers on hydrogen-terminated silicon (H-Si) surfaces with respect to the hitherto best agents (1-alkynes), it was hypothesized that enynes (H-C≡C-HC═CH-R) would be even better reagents for dense monolayer formation. To investigate whether the increased delocalization of ß-carbon radicals by the enyne functionality indeed lowers the activation barrier, the kinetics of monolayer formation by hexadec-3-en-1-yne and 1-hexadecyne on H-Si(111) were followed by studying partially incomplete monolayers. Ellipsometry and static contact angle measurements indeed showed a faster increase of layer thickness and hydrophobicity for the hexadec-3-en-1-yne-derived monolayers. This more rapid monolayer formation was supported by IRRAS and XPS measurements that for the enyne show a faster increase of the CH2 stretching bands and the amount of carbon at the surface (C/Si ratio), respectively. Monolayer formation at room temperature yielded plateau values for hexadec-3-en-1-yne and 1-hexadecyne after 8 and 16 h, respectively. Additional experiments were performed for 16 h at 80° to ensure full completion of the layers, which allows comparison of the quality of both layers. Ellipsometry thicknesses (2.0 nm) and contact angles (111-112°) indicated a high quality of both layers. XPS, in combination with DFT calculations, revealed terminal attachment of hexadec-3-en-1-yne to the H-Si surface, leading to dienyl monolayers. Moreover, analysis of the Si2p region showed no surface oxidation. Quantitative XPS measurements, obtained via rotating Si samples, showed a higher surface coverage for C16 dienyl layers than for C16 alkenyl layers (63% vs 59%). The dense packing of the layers was confirmed by IRRAS and NEXAFS results. Molecular mechanics simulations were undertaken to understand the differences in reactivity and surface coverage. Alkenyl layers show more favorable packing energies for surface coverages up to 50-55%. At higher coverages, this packing energy rises quickly, and there the dienyl packing becomes more favorable. When the binding energies are included the difference becomes more pronounced, and dense packing of dienyl layers becomes more favorable by 2-3 kcal/mol. These combined data show that enynes provide the highest-quality organic monolayers reported on H-Si up to now.

Stable protein-repellent zwitterionic polymer brushes grafted from silicon nitride.

Zwitterionic poly(sulfobetaine acrylamide) (SBMAA) brushes were grafted from silicon-rich silicon nitride (SixN4, x > 3) surfaces by atom transfer radical polymerization (ATRP) and studied in protein adsorption experiments. To this aim ATRP initiators were immobilized onto SixN4 through stable Si-C linkages via three consecutive reactions. A UV-induced reaction of 1,2-epoxy-9-decene with hydrogen-terminated SixN4 surfaces was followed by conversion of the epoxide with 1,2-ethylenediamine resulting in primary and secondary amine-terminated surfaces. A reaction with 2-bromoisobutyryl bromide led to ATRP initiator-covered surfaces. Zwitterionic polymer brushes of SBMAA were grown from these initiator-coated surfaces (thickness ∼30 nm), and the polymer-coated surfaces were characterized in detail by static water contact angle measurements, X-ray photoelectron spectroscopy (XPS), and an atomic force microscope (AFM). The adsorption of proteins onto zwitterionic polymer coated surfaces was evaluated by in situ reflectometry, using a fibrinogen (FIB) solution of 0.1 g·L(-1), and compared to hexadecyl-coated SixN4 surfaces (C16-SixN4), uncoated air-based plasma oxidized SixN4 surfaces (SiOy-SixN4), and hexa(ethylene oxide)-coated SixN4 surfaces (EO6-SixN4). Excellent protein repellence (>99%) was observed for these zwitterionic polymer-coated SixN4 surfaces during exposure to FIB solution as compared to C16-SixN4 surfaces. Furthermore, the stability of these zwitterionic polymer-coated SixN4 surfaces was surveyed by exposing the surfaces for 1 week to phosphate buffered saline (PBS) solution at room temperature. The zwitterionic polymer-coated SixN4 surfaces before and after exposure to PBS solution were characterized by XPS, AFM, and water contact angle measurements, and their protein-repelling properties were evaluated by reflectometry. After exposure to PBS solution, the zwitterionic polymer coating remained intact, and its thickness was unchanged within experimental error. No hydrolysis was observed for the zwitterionic polymer after 1 week exposure to PBS solution, and the surfaces still repelled 98% FIB as compared to C16-SixN4 surfaces, demonstrating the long-term efficiency of these easily prepared surface coatings.

Measurement of small droplet aerosol concentrations in public spaces using handheld particle counters.

We measure aerosol persistence to assess the risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in public spaces. Direct measurement of aerosol concentrations, however, has proven to be technically difficult; we propose the use of handheld particle counters as a novel and easily applicable method to measure aerosol concentrations. This allows us to perform measurements in typical public spaces, each differing in volume, the number of people, and the ventilation rate. These data are used to estimate the relation between the aerosol persistence time and the risk of infection with SARS-CoV-2.