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Polymeric nanoparticles have been studied for gene and drug delivery. These nanoparticles can be modified to utilize a targeted delivery approach to selectively deliver their payload to specific cells, while avoiding unwanted delivery to healthy cells. One commonly over-expressed receptor which can be targeted by ligand-conjugated nanoparticles is the folate receptor alpha (FRα). The ability to target FRα remains a promising concept, and therefore, understanding the binding dynamics of the receptor with the ligand of the nanoparticle therapeutic can provide valuable insight. This manuscript focuses on the interaction between self-assembled nanoparticles decorated with a folic acid (FA) ligand and FRα. The nanoparticles consist of micelles formed with a FA conjugated triblock copolymer (PEI-g-PCL-b-PEG-FA) which condensed siRNA to form micelleplexes. By combining biological and biophysical approaches, this manuscript explores the binding kinetics and force of the targeted siRNA containing nanoparticles to FRα in comparison with free FA. We demonstrate via flow cytometry and atomic force microscopy that multivalent micelleplexes bind to FRα with a higher binding probability and binding force than monovalent FA. Furthermore, we revisited why competitive inhibition studies of binding of multivalent nanoparticles to their respective receptor are often reported in literature to be inconclusive evidence of effective receptor targeting. In conclusion, the results presented in this paper suggest that multivalent targeted nanoparticles display strong receptor binding that a monovalent ligand may not be able to compete with under in vitro conditions and that high concentrations of competing monovalent ligands can lead to measurement artifacts.

Understanding the dynamics of water under nanoscale confinement is important for biology, geology, tribology, and nanotechnology. In many naturally occurring situations, ions are present in water at various concentrations. Here we report on how the addition of sodium ions alters the squeeze-out behavior of water nanoconfined between a mica surface and silicon oxide tip. We find that Na+ ions enhance molecular ordering and lead to longer mechanical relaxation times. We also observed a critical ion concentration, above which the confined water switches from a viscous to an elastic (solid-like) response at very slow, quasistatic compression speeds.

Background Discoidin Domain Receptors (DDRs) are membrane-tethered proteins of the receptor tyrosine kinase family, which signal in response to collagen. DDR expression is associated with human diseases, including fibrosis and cancer. The role of DDRs in human pathogenesis is mediated by dysregulated receptor function in response to the collagenous milieu. Thus, understanding DDR-collagen interactions is important for developing novel therapeutic strategies against DDRs. Methods We developed a biophysical method to isolate and measure specific interactions between DDR1 and collagen in live cells at the single molecule level using atomic force microscopy. This new method is capable of providing density and kinetics of membrane receptors in live cells. Results We isolated DDR1-collagen interactions and quantified the association and dissociation rates of the DDR1-collagen I complex. We estimated separate binding probabilities of collagen I to DDR and integrin, and by combining kinetic and binding probability data, we were able to estimate the density of receptors in two cancer cell types. We also tested the viability of a DDR1 blocking antibody and determined its efficacy in suppressing DDR1-collagen binding. Conclusions The new method shows promise in quantifying receptor-ligand kinetics and receptor density on live cells. General significance The new approach is applicable to other receptor-ligand systems and allows the determination of critical parameters at the single cell/single molecule level – in particular, the direct determination of kinetic and density differences of receptors in different cell types. This capability should prove to be useful in cancer research and drug design.

Nanofluids exhibit some intriguing thermal properties, and have great potential to increase efficiency in various heat technological applications in micro- and nano-technology. Recent studies on mass transport in nanofluids yielded some interesting but controversial results. In this communication, we report the tracer diffusion of fluorescent dye in different nanofluids. Measurements were performed using fluorescence correlation spectroscopy (FCS). Nanoparticle concentration in the nanofluid varied up to 1.7 vol%, and the diffusion coefficient of fluorescent dye was measured. Our results showed no significant changes in diffusion of dyes in the concentration range used, and the results indicate that more research is needed to completely understand the diffusion in nanofluids. This communication brings upon the powerful FCS technique for the first time to study the dynamics of nanofluids.

In this study, we present a detailed analysis of the squeeze-out dynamics of nanoconfined water confined between two hydrophilic surfaces measured by small-amplitude dynamic atomic force microscopy. Explicitly considering the instantaneous tip-surface separation during squeeze-out, we confirm the existence of an adsorbed molecular water layer on mica and at least two hydration layers. We also confirm the previous observation of a sharp transition in the viscoelastic response of the nanoconfined water as the compression rate is increased beyond a critical value (previously determined to be about 0.8 nm/s). We find that below the critical value, the tip passes smoothly through the molecular layers of the film, while above the critical speed, the tip encounters "pinning" at separations where the film is able to temporarily order. Preordering of the film is accompanied by increased force fluctuations, which lead to increased damping preceding a peak in the film stiffness once ordering is completed. We analyze the data using both Kelvin-Voigt and Maxwell viscoelastic models. This provides a complementary picture of the viscoelastic response of the confined water film.

Small amplitude Atomic Force Microscopy (AFM) is a relatively new AFM technique which was specifically developed to perform linear measurements of nanomechanical phenomena. This is achieved by using ultra-small cantilever amplitudes and very high sensitivity deflection sensors. Recently this technique has been used in ultra-high vacuum (UHV) and liquid environments to measure atomic and molecular forces and dynamics with high precision. Here we focus on three examples which are interesting from a nanoengineering standpoint: Atomic energy dissipation (atomic friction), atomic-scale contact mechanics, and nanotribology/molecular ordering in confined liquid films.

Most current non-contact-atomic force microscopy (nc-AFM) techniques rely on vibrating the measuring lever at resonance using amplitudes that are large compared to typical interaction length scales. Here we present results of simulations that show that off-resonance, small amplitude AFM provides an alternative non-contact technique in which force gradients can be measured directly without the need of mathematical de-convolution. We show that under a wide range of reasonable conditions the measurements are linear and quantitative.

Charged surfaces and electrolytes play an important role in many scientific and technological applications such as molecular friction, transport through bio-membranes, and generation of electrochemical energy. Using a home-built ultra-sensitive atomic force microscope, we have measured the stiffness, damping coefficient, and Maxwell’s relaxation time of a few molecular layers thin film of electrolytic water against atomically smooth mica surface. Water containing NaCl and CsCl have been compared with ultrapure water. The viscoelastic properties of the nanoconfined film exhibit a strong dependence on the compression rate of the film as well as the type of electrolyte present. The increase in Maxwell’s relaxation time as a function of NaCl concentration gives rise to a solidlike dynamic mechanical response under quasi-static conditions (compression rate = 0.2 nm/s). In contrast, the CsCl containing electrolytic water seems to suppress the solidlike dynamic mechanical behavior, which results from an apparent jamming of the molecules during a squeeze-out, as suggested elsewhere (Khan et al., Phys. Rev. Lett. 2010). These results suggest that the size and hydration number of ions play an important role in nanoconfined water.

Interatomic force gradients between a W tip and a 7 × 7 reconstructed Si(111) surface were measured using an off-resonance, ultra-low-amplitude atomic force microscope (AFM) technique. The amplitudes used were less than 1 Å (peak-to-peak), which allowed direct measurement of the interaction force gradients as a function of separation. The force gradient curves are shown to consist of an attractive van der Waals part and short-range attractive and repulsive interactions. The van der Waals background can be subtracted, leaving a short-range interaction with an energy parameter of 1.9-3.4 eV and an interaction length-scale of 0.54-1.26 Å, characteristic of a single atomic bond. This correlates well with our observation of single-atom resolved force gradient images. In general, the interaction is reversible up to the zero intercept of the force gradient (inflection point of the energy). Beyond this point hysteresis tends to be observed and the onset of inelastic deformation can be clearly discerned. An analysis of the atomic scale contact gives reasonable values for the interfacial energy, yield strength, and the energy per atom needed to initiate plastic deformation.

The immersion of Si surfaces in fluoride solutions results in the formation of a hydrogen passivated surface. The resulting surface morphology is dependent on the solution composition and the crystallographic orientation of the surface. Etching of miscut Si(111) in fluoride solutions can lead to the formation of mesa-like features. In this article we show that these features are due to the formation of step bunches during the etching process. The density of these features is dependent on the etch rate, the applied potential, and the fluoride ion concentration of the etching solution.

Electronic surface states at semiconductor/solution interfaces can mediate processes such as trapping and detrapping of majority and minority charge carriers, recombination, or charge transfer to or from the solution. We have calculated the complete impedance response due to these processes using a kinetic approach. Specific cases are discussed and diagnostic parameters for the capacitance and conductance are presented. Experimental results on n-Si(111) in fluoride solutions are used to illustrate the obtained expressions.

The properties of n-type (111) Si surfaces in aqueous 0.1 M K 4 Fe(CN) 6 + 0.5 M KCl at pH 9 were studied both in the dark and under illumination. In this solution, oxide passivation of the surface gives rise to a variety of electrically active interface states. Both in the dark and under illumination, interface states interacting with the conduction band are present at an energy of about 0.36 eV below the conduction bandedge, giving rise to a characteristic impedance at potentials close to the flatband potential. Furthermore, interface states which act as recombination centers are observed when the surface is illuminated. The density of recombination centers was found to be a function of the light intensity, ranging from 1 x 10 12 to 3 x 10 12 cm -2 , indicating that these states are related to oxidation intermediates. The rate constant for recombination was determined to be about 3 x 10 -9 cm 3 s -1 .

Electrochemical impedance spectroscopy (EIS) was used to analyze the energetics and kinetics of processes occurring at n-type silicon (111) surfaces in 1 M NH4F solutions in the pH range 3−11 in the dark. An additional impedance parallel to that of the space charge layer was observed due to electrically active surface states. The surface states are located energetically at about 0.38 eV below the conduction band and have a capture cross section of 1 × 10-16 cm2. The rate constant for thermal excitation of electrons from the surface states into the conduction band is essentially independent of pH, indicating the surface states are physically the same on both hydrogen terminated and oxidized silicon surfaces. The density of surface states is 2 × 1010 cm-2 at pH 3, characteristic of the hydrogen terminated surface, and increases to 1 × 1012 cm-2 at pH 11, corresponding to an oxide passivated surface.

Purpose: Discoidin domain receptors (DDR) have recently been recognized as important players in cancer progression. DDRs are cell receptors that interact with collagen, an extracellular matrix (ECM) protein. However the detailed mechanism of their interaction is unclear. Here we attempted to examine their interaction in terms of structural (surface topography), mechanical (rupture force), and kinetic (binding probability) information on the single molecular scale with the use of atomic force microscopy (AFM). Methods: The Quantitative Nano-mechanical property Mapping (QNM) mode of AFM allowed to assess the cells in liquid growth media at their optimal physiological while being viable. Human benign prostate hyperplasia (BPH-1) cell line was genetically regulated to suppress DDR expression (DDR- cells) and was compared with naturally DDR expressing cells (DDR+). Results: Binding force measurements (n = 1000) were obtained before and after the two groups were treated with fibronectin (FN), an integrin-inhibiting antibody to block the binding of integrin. The quantification indicates that cells containing DDR bind with collagen at a most probable force of 80.3–83.0 ±7.6 pN. The probability of them binding is 0.167 when other interactions (mainly due to integrin-collagen binding) are minimized. Conclusion: Together with further force measurements at different pulling speeds will determine dissociation rate, binding distance and activation barrier. These parameters in benign cells provides some groundwork in understanding DDR's behavior in various cell microenvironments such as in malignant tumor cells. Funding supported by Richard Barber Interdisciplinary Research Program of Wayne State University

Pyrophosphate solutions are commonly used in the electronics industry for copper deposition on printed circuit boards. This paper reports on the growth kinetics for copper deposition on silicon from pyrophosphate solution. It is shown that complexation shifts the energetic position of the copper ions in solution with respect to the bandedges for silicon such that deposition occurs via the conduction band. It is shown that the growth kinetics for low Cu(II) concentrations are consistent with progressive nucleation of hemispherical clusters followed by diffusion-limited growth.

The mechanical properties of nanoconfined water layers are still poorly understood and continue to create considerable controversy, despite their importance for biology and nanotechnology. Here, we report on dynamic nanomechanical measurements of water films compressed down to a few single molecular layers. We show that the mechanical properties of nanoconfined water layers change dramatically with their dynamic state. In particular, we observed a sharp transition from viscous to elastic response even at extremely slow compression rates, indicating that mechanical relaxation times increase dramatically once water is compressed to less than 3-4 molecular layers.

Broad ion beams in the energy range of 0.2 to 1.5 keV originating from a filament source with argon as feed gas have been analyzed by high‐resolution emission spectroscopy. The Doppler structure of Ar+ emissions reveals the existence of different velocity classes. Besides slow ions and ions possessing the main beam energy, electronically excited Ar+ ions with twice the main beam energy are detected which are attributed to a single‐electron capture process in Ar++/Ar collisions. As a preliminary result from a reactive beam extracted from a microwave CF4 source plasma fast F atoms are detected which are attributed to charge exchange and dissociative collisions in the process chamber.

The influence of a magnetic volume field B on the chemical and physical properties of a 13.56‐MHz CF4 plasma was studied by laser‐induced fluorescence (LIF) and by optical emission spectroscopy (OES) at typical low‐pressure etching conditions. The measurements were carried out in a commercial magnetron with a modified magnetic field configuration allowing a continuous variation of B up to a maximum field strength of 80 G. As indicated by LIF the densities of the CF2 radicals in the electronic and vibrational ground state increased by about a factor of 3 when the maximum B field was applied. No concentration gradients were detected by spatially resolved LIF. A similar increase as for CF2 was observed for actinometrically normalized F emission intensities. The ratios of CF2 LIF and CF2 OES signals are compared with the emission intensity behavior of argon, admixed to a small percentage, which suggest an increase of the electron induced production rates (electron densities) significantly stronger than that o...

Fiber-optic based interferometers are used to detect small displacements, down to the subnanometer range. Coating the end of the optical fiber with a partially reflecting thin film greatly improves the resolution of interferometers by increasing the multiple reflections between the fiber end and the measured object. In this work, we present a quick and easy thin film deposition technique to coat the end of a single optical fiber by dip-coating a metal-organic precursor, which is then decomposed in a propane flame. The coated fiber was tested for morphology and usefulness for interferometric application. We found that this coating technique is much faster and easier than conventional thin coating techniques, and yields results that are comparable or better than can be achieved with sputtering or thermal evaporation.

We have developed an atomic force microscopy (AFM) technique that can perform simultaneous normal and shear stiffness measurements of nanoconfined liquids with angstrom-range amplitudes. The AFM technique is based on a fiber-interferometric, small-amplitude, off-resonance AFM. This AFM is capable of providing linear quasistatic measurements of the local mechanical properties of confined liquid layers while only minimally disturbing the layers themselves. A detailed analysis of the measurement geometry reveals that shear stiffness measurements are extremely challenging, as even small deviations from perfect orthogonality can lead to data that is very difficult to interpret. We will show ways out of this dilemma and present results that show simultaneous measurement of the shear and normal stiffness of confined liquid layers.

Molecular motors are the workhorses of living cells. Seemingly by 'magic', these molecules are able to complete purposeful tasks while being immersed in a sea of thermal chaos. Here, we review the current understanding of how these machines work, present simple models based on thermal ratchets, discuss implications for statistical physics, and provide an overview of ongoing research in this important and fascinating field of study.

Optical emission spectroscopy has been established as a valuable method for the analysis of broad oxygen ion beams. The ion beams used for reactive ion‐beam etching have been investigated in the energy range of 300–1500 eV. From survey spectra O+2 molecules and neutral O atoms are identified as main emitting species. Concerning the occurrence of emission lines the beam spectrum resembles that obtained from an O2 rf plasma. The intensity ratios however are strongly different within both spectra. Whereas electron impact is the main source for electronic excitation in ordinary etch plasmas, heavy particle collisions are suggested to play an important role in the investigated ion beams. Beam‐induced emissions of atomic oxygen neutrals were recorded at high resolution of 0.1 A. The O emission lines were found to be triple peaked. One peak at the unshifted wavelength and two Doppler‐shifted peaks could be resolved. The absolute values of the wavelength shifts are well correlated to the energies of the initial i...

The sections in this article are 1 Energy Band Structure 2 Semiconductor/Solution Interface 3 Modulation Techniques 4 Summary Keywords: space charge layer capacitance; interface states; recombination; modulation techniques; electrochemical impedance spectroscopy; intensity modulated photocurrent spectroscopy; potential modulated microwave reflectivity spectroscopy; silicon electrochemistry; current-potential characteristics; photocurrent-potential characteristics