Expanding the molecular-ruler process through vapor deposition of hexadecanethiol.

The development of methods to produce nanoscale features with tailored chemical functionalities is fundamental for applications such as nanoelectronics and sensor fabrication. The molecular-ruler process shows great utility for this purpose as it combines top-down lithography for the creation of complex architectures over large areas in conjunction with molecular self-assembly, which enables precise control over the physical and chemical properties of small local features. The molecular-ruler process, which most commonly uses mercaptoalkanoic acids and metal ions to generate metal-ligated multilayers, can be employed to produce registered nanogaps between metal features. Expansion of this methodology to include molecules with other chemical functionalities could greatly expand the overall versatility, and thus the utility, of this process. Herein, we explore the use of alkanethiol molecules as the terminating layer of metal-ligated multilayers. During this study, it was discovered that the solution deposition of alkanethiol molecules resulted in low overall surface coverage with features that varied in height. Because features with varied heights are not conducive to the production of uniform nanogaps via the molecular-ruler process, the vapor-phase deposition of alkanethiol molecules was explored. Unlike the solution-phase deposition, alkanethiol islands produced by vapor-phase deposition exhibited markedly higher surface coverages of uniform heights. To illustrate the applicability of this method, metal-ligated multilayers, both with and without an alkanethiol capping layer, were utilized to create nanogaps between Au features using the molecular-ruler process.

1-Adamantanethiol as a versatile nanografting tool.

Strategies to regulate the self-assembly of adsorbates to create surface structures with molecular-scale features and organization are of broad interest to nanoscience, biochemistry, and engineering. One approach utilizes molecules with tailored intermolecular interaction strengths and topologies to direct molecular self-assembly as exemplified by the adsorption of 1-adamantanethiol molecules on Au{111} substrates. 1-Adamantanethiolate self-assembled monolayers exhibit decreased packing densities and weaker intermolecular interaction strengths than n-alkanethiolate self-assembled monolayers, which result in their complete displacement upon exposure to n-alkanethiol molecules. Herein, we explore the capabilities of the atomic force microscopy-based lithographic technique, nanografting, to fabricate chemical patterns comprised of 1-adamantanethiolate monolayers. Positive 1-adamantanethiolate patterns are generated by nanografting 1-adamantanethiol molecules into preexisting n-alkanethiolate self-assembled monolayers, and negative 1-adamantanethiolate patterns are created by nanografting n-alkanethiol molecules into preexisting 1-adamantanethiolate self-assembled monolayers. The patterned 1-adamantanethiolate regions are displaced upon exposure to solutions of n-alkanethiol molecules. This two-step nanografting-displacement strategy minimizes pattern dissolution as 1-adamantanethiol molecules do not intercalate into the preexisting self-assembled monolayer during nanografting. 1-Adamantanethiol can be utilized create high-resolution sacrificial chemical patterns with feature sizes beyond those afforded other 1-adamantanethiol patterning strategies for applications such as resists for metallic and organic structures.

Atomic force microscopy characterization and lithography of Cu-ligated mercaptoalkanoic acid "molecular ruler" multilayers.

Hybrid chemical patterning strategies that combine the sophistication of lithography with the intrinsic precision of molecular self-assembly are of broad interest for applications including nanoelectronics and bioactive surfaces. This approach is exemplified by the molecular-ruler process where the sequential deposition of mercaptoalkanoic acid molecules and coordinated metal ions is integrated with conventional lithographic techniques to fabricate registered, nanometer-scale spacings. Herein, we illustrate the capabilities of atomic force microscopy characterization and lithography to investigate the morphology, quality, and local thickness of Cu-ligated mercaptohexadecanoic acid multilayers on Au{111} substrates. These multilayers are a key component utilized in the molecular-ruler process. The rich and varied topographic features of each layer are investigated via contact-mode atomic force microscopy. Using nanoshaving, an atomic force microscopy lithographic strategy that reveals the underlying Au{111} substrate via tip-induced desorption of a molecular film, the local thicknesses of these multilayers are ascertained; these thicknesses are consistent with the anticipated heights for Cu-ligated mercaptohexadecanoic acid multilayers as well as previous ensemble surface analytical measurements. By regulating the force set point utilized during nanoshaving, the upper layer of a Cu-ligated mercaptohexadecanoic acid bilayer is removed, revealing the carboxyl moiety of the lower mercaptohexadecanoic acid layer. This selective nanoshaving demonstrates a simple and practical means to generate three-dimensional multilayers and to reveal buried chemical functionalities within metal-ligated multilayers.

Improving Hematite's Solar Water Splitting Efficiency by Incorporating Rare-Earth Upconversion Nanomaterials.

Confounded by global energy needs, much research has been devoted to convert solar energy to various usable forms, such as chemical energy in the form of hydrogen via water splitting. Most photoelectrodes, such as hematite, utilize UV and visible radiation, whereas ∼40% infrared (IR) energy remains unconverted. This work represents our initial attempt to utilize IR radiation, that is, adding rare-earth materials to existing photoelectrodes. A simple substrate composed of hematite film and rare-earth nanocrystals (RENs) was prepared and characterized. Spectroscopy evidence indicates that the RENs in the composite absorb IR radiation (980 nm) and emit at 550 and 670 nm. The emitted photons are absorbed by surrounding hematite films, leading to improvement of water splitting efficiency as measured by photocurrent enhancement. This initial work demonstrates the feasibility and concept of using RENs for utilizing more solar radiation, thus improving the efficiency of existing solar materials and devices.

Fabrication and characterization of rare-earth-doped nanostructures on surfaces.

This article presents a simple and practical means to produce rare-earth-based nanostructures, as well as a combined characterization of structure and optical properties in situ. A nanosphere lithography strategy combined with surface chemistry enables the production of arrays of ß-NaYF(4):Yb,Er nanorings inlaid in an octadecyltrichlorosilane matrix. These arrays of nanorings are produced over the entire support, such as a 1 cm(2) glass coverslip. The dimension of nanorings can be varied by changing the deposition conditions. A home-constructed, multifunctional microscope integrating atomic force microscopy, near-field scanning optical microscopy, and far-field optical microscopy and spectroscopy is utilized to characterize the nanostructures. This in situ and combined characterization is important for rare-earth-containing nanomaterials in order to correlate local structure with upconversion photoluminescence. Knowledge gained from the investigation should facilitate materials design and optimization, for instance, in the context of photovoltaic devices and biofluorescent probes.

Regulation of local structure and composition of binary disulfide and thiol self-assembled monolayers using nanografting.

Nanografting is used to create spatial confinement, which enables regulation of self-assembly reaction pathways and outcome. The degree and outcome of this regulation is revealed using binary self-assembled monolayers (SAMs) of organothiols and disulfides. In naturally grown systems, these SAMs have more complex morphology when compared with corresponding binary alkanethiol SAMs. Taller molecules form nanodomains of ellipsoidal cap in shape. These domains arrange in various irregular geometries, including 1D worm-like and 2D branches. This observation differs from binary alkanethiol SAMs, where nanodomains are separated and randomly dispersed. During nanografting, more homogeneous morphology was observed compared with naturally grown layers. By varying nanoshaving speed, the nanodomain structure can be regulated from randomly dispersed to more heterogeneous and, finally, to near natural growth. This trend is very similar to mixed alkanethiol systems, where the domain size and separation increase with increasing speed. Different from the alkanethiol systems, the observed structural variations are due to the changes in surface composition, in addition to domain size, shape, and arrangement.

Bradycardia pacing-induced short-long-short sequences at the onset of ventricular tachyarrhythmias: a possible mechanism of proarrhythmia?

OBJECTIVES: The purpose of this study was to characterize interactions between normal pacing system operation and the initiating sequence of ventricular tachycardia (VT)/ventricular fibrillation (VF). BACKGROUND: Abrupt changes in ventricular cycle lengths (short-long-short, S-L-S) might initiate VT/VF. The S-L-S sequences might be passively permitted or actively facilitated by bradycardia pacing. METHODS: Initiating sequences of 1,356 VT/VF episodes in the PainFree Rx II (n = 634) and EnTrust Trial (n = 421) were analyzed with stored electrograms and by pacing mode (DDD/R, VVI/R, and Managed Ventricular Pacing [MVP]). Interactions between pacing and VT/VF initiation were classified as: non-pacing associated, pacing associated, pacing permitted, and pacing facilitated. RESULTS: Non-pacing associated (no pacing, no S-L-S) and pacing associated (ventricular pacing without S-L-S) onset accounted for 44.0% and 29.8% of all VT/VF, respectively. Pacing permitted (S-L-S sequences without ventricular pacing) episodes accounted for 6.4% (DDD/R), 20.0% (MVP), and 25.6% (VVI/R) of 1,356 VT/VF episodes. Pacing facilitated onset (S-L-S sequences actively facilitated by ventricular pacing including the terminal beat after a pause) accounted for 8.2% (MVP), 9.4% (VVI/R), and 14.8% (DDD/R) of 1,356 VT/VF episodes. Pacing facilitated S-L-S VT/VF occurred in 2.6% (MVP), 3.3% (VVI/R), and 5.2% (DDD/R) of patients with episodes and was the sole initiating sequence in approximately 1% of patients. Pause durations during pacing facilitated S-L-S differed between modes (DDD/R 793 +/- 172 ms vs. MVP 865 +/- 278 ms vs. VVI/R 1180 +/- 414 ms, p = 0.002). The majority of these episodes were monomorphic VT. CONCLUSIONS: Ventricular tachycardia/VF in some implantable cardioverter-defibrillator patients might be initiated by S-L-S sequences that are actively facilitated by bradycardia pacing operation and might constitute an important mechanism of ventricular proarrhythmia.

1-Adamantanethiolate monolayer displacement kinetics follow a universal form.

Alkanethiol molecules in solution displace 1-adamantanethiolate self-assembled monolayers on Au{111}, ultimately leading to complete molecular exchange. Specifically, here, fast insertion of n-dodecanethiolate at defects in the original 1-adamantanethiolate monolayer nucleates an island growth phase, which is followed by slow ordering of the n-dodecanethiolate domains into a denser and more crystalline form. Langmuir-based kinetics, which describe alkanethiolate adsorption on bare Au{111}, fail to model this displacement reaction. Instead, a Johnson-Mehl-Avrami-Kolmogorov model of perimeter-dependent island growth yields good agreement with kinetic data obtained by Fourier transform infrared spectrometry over 100-fold variation in n-dodecanethiol concentration. Rescaling the growth rate at each concentration collapses all the data onto a single universal curve, suggesting that displacement is a scale-free process. The rate of displacement varies as the square-root of the n-dodecanethiol concentration across the 0.01-1.0 mM range studied.

Avoidance of right ventricular pacing in cardiac resynchronization therapy improves right ventricular hemodynamics in heart failure patients.

BACKGROUND: Cardiac resynchronization therapy (CRT) applied by pacing the left and right ventricles (BiV) has been shown to provide synchronous left ventricular (LV) contraction in heart failure patients. CRT may also be accomplished through synchronization of a properly timed LV pacing impulse with intrinsically conducted activation wave fronts. Elimination of right ventricular (RV) pacing may provide a more physiological RV contraction pattern and reduce device current drain. We evaluated the effects of LV and BiV pacing over a range of atrioventricular intervals on the performance of both ventricles. METHODS: Acute LV and RV hemodynamic data from 17 patients with heart failure (EF = 30 +/- 1%) and a wide QRS (138 +/- 25 msec) or mechanical dyssynchrony were acquired during intrinsic rhythm, BiV, and LV pacing. RESULTS: The highest LV dP/dt(max) was achieved during LV pre- (LV paced prior to an RV sense) and BiV pacing, followed by that obtained during LV post-pacing (LV paced after an RV sense) and the lowest LV dP/dt(max) was recorded during intrinsic rhythm. Compared with BiV pacing, LV pre-pacing significantly improved RV dP/dt(max) (378 +/- 136 mmHg/second vs 397 +/- 136 mmHg/second, P < 0.05) and preserved RV cycle efficiency (61.6 +/- 14.6% vs 68.6 +/- 11.4%, P < 0.05) and stroke volume (6.6 +/- 4.4 mL vs 9.0 +/- 6.3 mL, P < 0.05). Based on LV dP/dt(max), the optimal atrioventricular interval could be estimated by subtracting 30 msec from the intrinsic atrial to sensed RV interval. CONCLUSIONS: Synchronized LV pacing produces acute LV and systemic hemodynamic benefits similar to BiV pacing. LV pacing at an appropriate atrioventricular interval prior to the RV sensed impulse provides superior RV hemodynamics compared with BiV pacing.

Scanning electron microscopy of nanoscale chemical patterns.

A series of nanoscale chemical patterning methods based on soft and hybrid nanolithographies have been characterized using scanning electron microscopy with corroborating evidence from scanning tunneling microscopy and lateral force microscopy. We demonstrate and discuss the unique advantages of the scanning electron microscope as an analytical tool to image chemical patterns of molecules highly diluted within a host self-assembled monolayer and to distinguish regions of differential mass coverage in patterned self-assembled monolayers. We show that the relative contrast of self-assembled monolayer patterns in scanning electron micrographs depends on the operating primary electron beam voltage, monolayer composition, and monolayer order, suggesting that secondary electron emission and scattering can be used to elucidate chemical patterns.

Directed assembly and separation of self-assembled monolayers via electrochemical processing.

Separated domains of 1-dodecanethiolate were fabricated via solution displacement of preformed 1-adamantanethiolate self-assembled monolayers on Au{111}. Subsequently, the 1-adamantanethiolate domains were desorbed selectively, and the substrate was exposed to a 1-octanethiol solution, creating artificially separated self-assembled monolayers of 1-dodecanethiolate and 1-octanethiolate. The molecular order of each lattice type and the apparent height differences imaged with scanning tunneling microscopy and the two distinct cathodic peaks observed with cyclic voltammetry indicated distinct separated domains of each lattice type in the separated self-assembled monolayers. By manipulating the intermolecular interaction strengths of the patterned molecules, we are able to control the structure and properties of the separated self-assembled monolayers via the exploitation of competitive adsorption and the utilization of electrochemical processing, which can be extended to other self-assembly patterning techniques such as microdisplacement printing.

System identification: a multi-signal approach for probing neural cardiovascular regulation.

Short-term, beat-to-beat cardiovascular variability reflects the dynamic interplay between ongoing perturbations to the circulation and the compensatory response of neurally mediated regulatory mechanisms. This physiologic information may be deciphered from the subtle, beat-to-beat variations by using digital signal processing techniques. While single signal analysis techniques (e.g., power spectral analysis) may be employed to quantify the variability itself, the multi-signal approach of system identification permits the dynamic characterization of the neural regulatory mechanisms responsible for coupling the variability between signals. In this review, we provide an overview of applications of system identification to beat-to-beat variability for the quantitative characterization of cardiovascular regulatory mechanisms. After briefly summarizing the history of the field and basic principles, we take a didactic approach to describe the practice of system identification in the context of probing neural cardiovascular regulation. We then review studies in the literature over the past two decades that have applied system identification for characterizing the dynamical properties of the sinoatrial node, respiratory sinus arrhythmia, and the baroreflex control of sympathetic nerve activity, heart rate and total peripheral resistance. Based on this literature review, we conclude by advocating specific methods of practice and that future research should focus on nonlinear and time-varying behaviors, validation of identification methods, and less understood neural regulatory mechanisms. Ultimately, we hope that this review stimulates such future investigations by both new and experienced system identification researchers.

Randomized pilot study of a new atrial-based minimal ventricular pacing mode in dual-chamber implantable cardioverter-defibrillators.

OBJECTIVE: We hypothesized that a new minimal ventricular pacing mode (MVP) that provides AAI/R pacing with ventricular monitoring and back-up DDD/R pacing as needed during AV block (AVB) would significantly reduce cumulative percent ventricular pacing compared to DDD/R. BACKGROUND: Conventional DDD/R mode often results in high cumulative percent ventricular pacing that may adversely affect ventricular function and increase risk of heart failure and atrial fibrillation. METHODS: MVP was made operational in 30 patients with DDD/R implantable cardioverter-defibrillators (ICDs) and no history of AVB. Patients were randomized to one week each in DDD/R and MVP. Holter monitor recordings (ECG, intracardiac electrograms, and event markers) and device diagnostics were analyzed for cumulative % atrial paced (Cum%AP), cumulative percent ventricular pacing, and frequency and duration of DDD/R pacing back-up. Diaries were used to report symptoms. RESULTS: Age of the study population was 61 years +/- 12 years and 83% were male. Baseline PR interval was 204 ms +/- 32 ms and programmed AV intervals (DDD/R) were 200 ms +/- 50 ms (paced)/167 ms +/- 54 ms (sensed). Cum%AP was similar between MVP and DDD/R (47.9 +/- 37 vs 46.3 +/- 36). Cumulative percent ventricular pacing was significantly lower in MVP vs DDD/R (3.79 +/- 16.3 vs 80.6 +/- 33.8, P < .0001). Back-up DDD/R pacing during MVP operation due to transient AVB occurred in 10% of patients (9.3 +/- 7.4 [range 1-15] episodes/patient-day, duration 39.7 minutes +/- 156 minutes). Fifteen percent of AV intervals during MVP operation exceeded 300 ms. No significant symptoms were reported during MVP operation. CONCLUSIONS: MVP dramatically reduced cumulative percent ventricular pacing compared to DDD/R while maintaining AV synchrony and providing sensor-modulated atrial pacing support. Intermittent oscillations between MVP and DDD/R during transient AV block appeared safe and well tolerated.

Effects of simulated microgravity on closed-loop cardiovascular regulation and orthostatic intolerance: analysis by means of system identification.

Microgravity-induced orthostatic intolerance (OI) continues to be a primary concern for the human space program. To test the hypothesis that exposure to simulated microgravity significantly alters autonomic nervous control and, thus, contributes to increased incidence of OI, we employed the cardiovascular system identification (CSI) technique to evaluate quantitatively parasympathetic and sympathetic regulation of heart rate (HR). The CSI method analyzes second-to-second fluctuations in noninvasively measured HR, arterial blood pressure, and instantaneous lung volume. The coupling mechanisms between these signals are characterized by using a closed-loop model. Parameters reflecting parasympathetic and sympathetic responsiveness with regard to HR regulation can be extracted from the identified coupling mechanisms. We analyzed data collected from 29 human subjects before and after 16 days of head-down-tilt bed rest (simulated microgravity). Statistical analyses showed that parasympathetic and sympathetic responsiveness was impaired by bed rest. A lower sympathetic responsiveness and a higher parasympathetic responsiveness measured before bed rest identified individuals at greater risk of OI before and after bed rest. We propose an algorithm to predict OI after bed rest from measures obtained before bed rest.

Statistical accuracy of a moving equivalent dipole method to identify sites of origin of cardiac electrical activation.

While radio frequency (RF) catheter ablation (RCA) procedures for treating ventricular arrhythmias have evolved significantly over the past several years, the use of RCA has been limited to treating slow ventricular tachycardias (VTs). In this paper, we present preliminary results from computer and animal studies to evaluate the accuracy of an algorithm that uses the single equivalent moving dipole (SEMD) model in an infinite homogeneous volume conductor to guide the RF catheter to the site of origin of the arrhythmia. Our method involves measuring body surface electrocardiographic (ECG) signals generated by arrhythmic activity and by bipolar current pulses emanating from a catheter tip, and representing each of them by a SEMD model source at each instant of the cardiac cycle, thus enabling rapid repositioning of the catheter tip requiring only a few cycles of the arrhythmia. We found that the SEMD model accurately reproduced body surface ECG signals with a correlation coefficients > 0.95. We used a variety of methods to estimate the uncertainty of the SEMD parameters due to measurement noise and found that at the time when the arrhythmia is mostly localized during the cardiac cycle, the estimates of the uncertainty of the spatial SEMD parameters (from ECG signals) are between 1 and 3 mm. We used pacing data from spatially separated epicardial sites in a swine model as surrogates for focal ventricular arrhythmic sources and found that the spatial SEMD estimates of the two pacing sites agreed with both their physical separation and orientation with respect to each other. In conclusion, our algorithm to estimate the SEMD parameters from body surface ECG can potentially be a useful method for rapidly positioning the catheter tip to the arrhythmic focus during an RCA procedure.