Effect of test duration and sensor location on the reliability of standing balance parameters derived using body-mounted accelerometers.

BACKGROUND: Balance parameters derived from wearable sensor measurements during postural sway have been shown to be sensitive to experimental variables such as test duration, sensor number, and sensor location that influence the magnitude and frequency-related properties of measured center-of-mass (COM) and center-of-pressure (COP) excursions. In this study, we investigated the effects of test duration, the number of sensors, and sensor location on the reliability of standing balance parameters derived using body-mounted accelerometers. METHODS: Twelve volunteers without any prior history of balance disorders were enrolled in the study. They were asked to perform two 2-min quiet standing tests with two different testing conditions (eyes open and eyes closed). Five inertial measurement units (IMUs) were employed to capture postural sway data from each participant. IMUs were attached to the participants' right legs, the second sacral vertebra, sternum, and the left mastoid processes. Balance parameters of interest were calculated for the single head, sternum, and sacrum accelerometers, as well as, a three-sensor combination (leg, sacrum, and sternum). Accelerometer data were used to estimate COP-based and COM-based balance parameters during quiet standing. To examine the effect of test duration and sensor location, each 120-s recording from different sensor locations was segmented into 20-, 30-, 40-, 50-, 60-, 70-, 80-, 90-, 100-, and 110-s intervals. For each of these time intervals, time- and frequency-domain balance parameters were calculated for all sensor locations. RESULTS: Most COM-based and COP-based balance parameters could be derived reliably for clinical applications (Intraclass-Correlation Coefficient, ICC ≥ 0.90) with a minimum test duration of 70 and 110 s, respectively. The exceptions were COP-based parameters obtained using a sacrum-mounted sensor, especially in the eyes-closed condition, which could not be reliably used for clinical applications even with a 120-s test duration. CONCLUSIONS: Most standing balance parameters can be reliably measured using a single head- or sternum-mounted sensor within a 120-s test duration. For other sensor locations, the minimum test duration may be longer and may depend on the specific test conditions.

Phybrata Sensors and Machine Learning for Enhanced Neurophysiological Diagnosis and Treatment.

Concussion injuries remain a significant public health challenge. A significant unmet clinical need remains for tools that allow related physiological impairments and longer-term health risks to be identified earlier, better quantified, and more easily monitored over time. We address this challenge by combining a head-mounted wearable inertial motion unit (IMU)-based physiological vibration acceleration ("phybrata") sensor and several candidate machine learning (ML) models. The performance of this solution is assessed for both binary classification of concussion patients and multiclass predictions of specific concussion-related neurophysiological impairments. Results are compared with previously reported approaches to ML-based concussion diagnostics. Using phybrata data from a previously reported concussion study population, four different machine learning models (Support Vector Machine, Random Forest Classifier, Extreme Gradient Boost, and Convolutional Neural Network) are first investigated for binary classification of the test population as healthy vs. concussion (Use Case 1). Results are compared for two different data preprocessing pipelines, Time-Series Averaging (TSA) and Non-Time-Series Feature Extraction (NTS). Next, the three best-performing NTS models are compared in terms of their multiclass prediction performance for specific concussion-related impairments: vestibular, neurological, both (Use Case 2). For Use Case 1, the NTS model approach outperformed the TSA approach, with the two best algorithms achieving an F1 score of 0.94. For Use Case 2, the NTS Random Forest model achieved the best performance in the testing set, with an F1 score of 0.90, and identified a wider range of relevant phybrata signal features that contributed to impairment classification compared with manual feature inspection and statistical data analysis. The overall classification performance achieved in the present work exceeds previously reported approaches to ML-based concussion diagnostics using other data sources and ML models. This study also demonstrates the first combination of a wearable IMU-based sensor and ML model that enables both binary classification of concussion patients and multiclass predictions of specific concussion-related neurophysiological impairments.

Investigating the validity of a single tri-axial accelerometer mounted on the head for monitoring the activities of daily living and the timed-up and go test.

BACKGROUND: Quantitative assessments of activities of daily living (ADL) play an essential role in evaluating the impact of disease and interventions on people's quality of life. Motion capture systems traditionally used for quantitative assessments of postural transitions and movement associated with ADL are limited to the laboratory setting. Wearable accelerometers can remove these limitations and enable easier-to-use, longer-term, and remote functional evaluations. OBJECTIVE: To investigate the validity of a single tri-axial accelerometer mounted on the head for monitoring postural transition and the timed-up-and-go test. METHODS: Two accelerometers with a sampling frequency of 100 Hz were attached to twelve able-bodied study participants' sternum and right mastoid process. We developed algorithms for the functional calibration of accelerometers and the detection of the postural transitions by measuring the head inclination angle and variations of the gravitational components of the accelerometer readout. Participants performed a battery of ADL tests involving a wide variety of postural transitions. The head-mounted accelerometers results were compared with a sternum-mounted accelerometer and validated against a video motion capture system as a gold standard reference. RESULTS AND SIGNIFICANCE: The results indicate that, utilizing our proposed algorithm, a single tri-axial accelerometer mounted on the head can deliver high accuracy (>95 %), sensitivity (>90 %), and specificity (100 %) for detecting both postural transitions and walking events. Together with the small size and unobtrusive placement of the head-mounted accelerometer, these results demonstrate an attractive solution for the reliable assessment of ADLs and clinical evaluations based on functional tests such as the timed-up-and-go test.

Physiological Vibration Acceleration (Phybrata) Sensor Assessment of Multi-System Physiological Impairments and Sensory Reweighting Following Concussion.

OBJECTIVE: To assess the utility of a head-mounted wearable inertial motion unit (IMU)-based physiological vibration acceleration ("phybrata") sensor to support the clinical diagnosis of concussion, classify and quantify specific concussion-induced physiological system impairments and sensory reweighting, and track individual patient recovery trajectories. METHODS: Data were analyzed from 175 patients over a 12-month period at three clinical sites. Comprehensive clinical concussion assessments were first completed for all patients, followed by testing with the phybrata sensor. Phybrata time series data and spatial scatter plots, eyes open (Eo) and eyes closed (Ec) phybrata powers, average power (Eo+Ec)/2, Ec/Eo phybrata power ratio, time-resolved phybrata spectral density (TRPSD) distributions, and receiver operating characteristic (ROC) curves are compared for individuals with no objective impairments and those clinically diagnosed with concussions and accompanying vestibular impairment, other neurological impairment, or both vestibular and neurological impairments. Finally, pre- and post-injury phybrata case report results are presented for a participant who was diagnosed with a concussion and subsequently monitored during treatment, rehabilitation, and return-to-activity clearance. RESULTS: Phybrata data demonstrate distinct features and patterns for individuals with no discernable clinical impairments, diagnosed vestibular pathology, and diagnosed neurological pathology. ROC curves indicate that the average power (Eo+Ec)/2 may be utilized to support clinical diagnosis of concussion, while Eo and Ec/Eo may be utilized as independent measures to confirm accompanying neurological and vestibular impairments, respectively. All 3 measures demonstrate area under the curve (AUC), sensitivity, and specificity above 90% for their respective diagnoses. Phybrata spectral analyses demonstrate utility for quantifying the severity of concussion-induced physiological impairments, sensory reweighting, and subsequent monitoring of improvements throughout treatment and rehabilitation. CONCLUSION: Phybrata testing assists with objective concussion diagnosis and provides an important adjunct to standard concussion assessment tools by objectively ascertaining neurological and vestibular impairments, guiding targeted rehabilitation strategies, monitoring recovery, and assisting with return-to-sport/work/learn decision-making.

CO2-responsive surfactants with tunable switching pH.

HYPOTHESIS: One of the major challenges in applying CO2-responsive surfactants concerns their tunable switchability and robustness under operating conditions. We hypothesize that combining monoethanolamine (MEA) with long-chain fatty acids (LCFAs) of variable chain lengths through electrostatic attraction could develop a series of CO2-responsive surfactants with tunable switching pH. EXPERIMENTS: The tunability of switching pH for this group of surfactants was demonstrated by in situ probing of the CO2-responsive characteristics at the oil/water interface using dynamic interfacial tension (IFT) measurements. Two protocols were applied to distinguish interfacial response and solution response. The key importance of interfacial response was demonstrated by two essential applications of CO2-responsive surfactants: demulsification of stable emulsions, and alternation of the interfacial properties of ultra-heavy crude oil-water interfaces. FINDINGS: The switching pH of the CO2-responsive surfactants was controlled by the hydrocarbon chain length of LCFAs. More importantly, their switching behaviour was found to be different at the interface and in the bulk solution, which is attributed to the enhanced molecular interactions at the interface. Since most applications require surfactants to be switched at the interface, it is thereby most appropriate to determine the switching pH through their interfacial responses.

Monitoring of postural sway with a head-mounted wearable device: effects of gender, participant state, and concussion.

Objective: To assess the utility of a head-mounted wearable inertial motion unit (IMU)-based sensor and 3 proposed measures of postural sway to detect outliers in athletic populations at risk of balance impairments. Methods: Descriptive statistics are used to define a normative reference range of postural sway (eyes open and eyes closed) in a cross-sectional sample of 347 college students using a wireless head-mounted IMU-based sensor. Three measures of postural sway were derived: linear sway power, eyes closed vs eyes open sway power ratio (Ec/Eo ratio), and weight-bearing asymmetry (L-R ratio), and confidence intervals for these measures were calculated. Questionnaires were used to identify potentially confounding state variables. A prospective study of postural sway changes in 47 professional, college, and high school athletes was then carried out in on-field settings to provide estimates of session-to-session variability and the influence of routine physical activity on sway measures. Finally, pre-post-injury changes in sway are measured for a participant who was diagnosed with a concussion. Results: Despite the heterogenous population and sampling environments, well-defined confidence intervals were established for all 3 sway measures. Men demonstrated significantly greater sway than women. Two state variables significantly increased sway: the use of nicotine and prescription medications. In the athletes, session-to-session variability and changes due to routine physical activity remained well within 95% confidence intervals defined by the cross-sectional sample for all 3 sway measures. The increase in sway power following a diagnosed concussion was more than an order of magnitude greater than the increases due to session-to-session variability, physical activity, or other participant state variables. Conclusion: The proposed postural sway measures and head-mounted wearable sensor demonstrate analytic utility for on-field detection of abnormal sway that could be potentially useful when making remove-from-activity and return-to-activity decisions for athletes at risk of impact-induced balance impairments.

Spectroscopic study of ionic liquid adsorption from solution onto gold.

Gold was exposed to ethanol solutions containing 0.1 wt% 1-hexyl-3-methyl-imidazolium bis(trifluoromethanesulfonyl)imide (HMIM NTf2), an ionic liquid (IL). The resulting adsorbed layers were interrogated using X-ray photoelectron spectroscopy (XPS - both conventional and synchrotron-based) and spectroscopic ellipsometry. Ellipsometry indicated that the adsorbed layer thickness was smaller than the size of an IL ion pair, with an average determined layer thickness of 0.15 nm. This value indicates that the adsorbed layer on gold is most likely patchy. Conventional XPS revealed that the IL adsorbs irreversibly to gold, with equal amounts of anion and cation in the adsorbed layer. High signal-to-noise synchrotron XPS spectra permitted detailed deconvolution of the S 2p and N 1s peaks for the IL-treated gold, providing more information on adsorbed layer composition and structure. Spectra acquired as a function of X-ray exposure time indicate that non-interacting physisorbed IL components are preferentially removed at the expense of surface bound components, and that anion and cation are both present in the surface bound layer, and also in the layer above. A model structure for the IL adsorbed on gold is proposed.

Static and dynamic wetting behaviour of ionic liquids.

Ionic liquids (ILs) are a unique family of molecular liquids ('molten salts') that consist of a combination of bulky organic cations coupled to inorganic or organic anions. The net result of steric hindrance and strong hydrogen bonding between components results in a material that is liquid at room temperature. One can alter the properties of ionic liquids through chemical modification of anion and cation, thus tailoring the IL for a given application. One such property that can be controlled or selected is the wettability of an IL on a particular solid substrate. However, the study of wetting of ionic liquids is complicated by the care required for accurate and reproducible measurement, due to both the susceptibility of the IL properties to water content, as well as to the sensitivity of wettability measurements to the state of the solid surface. This review deals with wetting studies of ILs to date, including both static and dynamic wetting, as well as issues concerning line tension and the formation of precursor and wetting films.

High throughput prediction of the long-term stability of pharmaceutical macromolecules from short-term multi-instrument spectroscopic data.

Changes in the measurements of a macromolecular biopharmaceutical's physical form are often used to predict changes in the drug's long-term stability. These can in turn be used as important markers of changes to a drug's efficacy and safety. Such stability estimates traditionally require human judgment and are frequently tentative. We introduce methods for developing mathematical models that predict a drug's long-term storage stability profile from measurements of short-term physical form and behavior. We measured the long-term (2 year) chemical and colloidal stability of Granulocyte Colony Stimulating Factor (GCSF) in 16 different liquid formulations. Shortly after formulations were placed on stability, we also employed various spectroscopic techniques to characterize the short-term thermal unfolding response of GCSF in the 16 formulations. The short-term data were processed using several data reduction methods, including reduction to spectra at low temperature, to melt curves, and to transition temperatures. Least squares fitting was used to predict the long-term stability measurements from the reduced short-term spectroscopic measurements. On the basis of the cross-validation and a permutation test, many of the long-term stability predictions have less than 1% probability of occurring by chance.

The influence of topography on dynamic wetting.

The paramount importance of wetting applications and the significant economic value of controlling wetting-based industrial processes has stimulated a deep interest in wetting science. In many industrial applications the motion of a complex liquid front over nano-textured surfaces controls the fate of the processes. However our knowledge of the impact of nano-heterogeneities on static and dynamic wetting is very limited. In this article, the fundamentals of wetting are briefly reviewed, with a particular focus on hysteresis and roughness issues. Present knowledge and models of dynamic wetting on smooth and rough surfaces are then examined, with particular attention devoted to the case of nano-topographical heterogeneities and solid-fluid-fluid systems.

Patterning of wettability for controlling capillary-driven flow in closed channels.

Glass capillaries are prepared with well-defined regions of tuneable wettability on the interior walls using an inexpensive and simple approach. A homogeneous layer of hydrophilic TiO2 nanoparticles is adsorbed on the capillary wall and chemically hydrophobized using octadecyltrihydrosilane (OTHS). The hydrophobic OTHS monolayer is then patterned by spatially-selective removal of the OTHS via TiO2-catalysed decomposition by ultraviolet irradiation. By patterning the capillaries with hydrophilic-hydrophobic rings, modulated penetration of a liquid (glycerol, in this study) can be achieved. For given wettability contrast, the penetration dynamics and equilibrium rise heights are very sensitive to the characteristic length-scale of the pattern, and may offer greater, time-dependent sampling control in fluidic devices.

Contact line motion on nanorough surfaces: a thermally activated process.

The motion of a solid-liquid-liquid contact line over nanorough surfaces is investigated. The surface nanodefects are varied in size, density, and shape. The dynamics of the three-phase contact line on all nanorough substrates studied is thermally activated. However, unlike the motion of a liquid-vapor interface over smooth surfaces, this thermally activated process is not adequately described by the molecular kinetic theory. The molecular parameters extracted from the experiments suggest that on the nanorough surfaces, the motion of the contact line is unlikely to simply consist of molecular adsorption-desorption steps. Thermally activated pinning-depinning events on the surface nanodefects are also important. We investigate the effect of surface nanotopography on the relative importance of these two mechanisms in governing contact line motion. Using a derivation for the hysteresis energy based on Joanny and de Gennes's model, we evaluate the effect of nanotopographical features on the wetting activation free energy and contact line friction. Our results suggest that both solid-liquid interactions and surface pinning strength contribute to the energy barriers hindering the three-phase contact line motion. For relatively low nanodefect densities, the activation free energy of wetting can be expressed as a sum of surface wettability and surface topography contributions, thus providing a direct link between contact line dynamics and roughness parameters.

Dynamic electrowetting and dewetting of ionic liquids at a hydrophobic solid-liquid interface.

The dynamic electrowetting and dewetting of ionic liquids are investigated with high-speed video microscopy. Five imidazolium-based ionic liquids ([BMIM]BF(4), [BMIM]PF(6), [BMIM]NTf(2), [HMIM]NTf(2), and [OMIM]BF(4)) are used as probe liquids. Droplets of ionic liquids are first spread on an insulated electrode by applying an external voltage (electrowetting) and then allowed to retract (dewetting) when the voltage is switched off. The base area of the droplet varies exponentially during both the electrowetting and retraction processes. The characteristic time increases with the viscosity of the ionic liquid. The electrowetting and retraction kinetics (dynamic contact angle vs contact line speed) can be described by the hydrodynamic or the molecular-kinetic model. Energy dissipation occurs by viscous and molecular routes with a larger proportion of energy dissipated at the three-phase contact line when the liquid meniscus retracts from the solid surface. The outcomes from this research have implications for the design and control of electro-optical imaging systems, microfluidics, and fuel cells.

Femtoliter droplet handling in nanofluidic channels: a Laplace nanovalve.

Analytical technologies of ultrasmall volume liquid, in particular femtoliter to attoliter liquid, is essential for single-cell and single-molecule analysis, which is becoming highly important in biology and medical diagnosis. Nanofluidic chips will be a powerful tool to realize chemical processes for such a small volume sample. However, a technical challenge exists in fluidic control, which is femtoliter to attoliter liquid generation in air and handling for further chemical analysis. Integrating mechanical valves fabricated by MEMS (microelectric mechanical systems) technology into nanofluidic channels is difficult. Here, we propose a nonmechanical valve, which is a Laplace nanovalve. For this purpose, a nanopillar array was embedded in a nanochannel using a two-step electron beam lithography and dry-etching process. The nanostructure allowed precise wettability patterning with a resolution below 100 nm, which was difficult by photochemical wettability patterning due to the optical diffraction. The basic principle of the Laplace nanovalve was verified, and a 1.7 fL droplet (water in air) was successfully generated and handled for the first time.

Dynamic aspects of small bubble and hydrophilic solid encounters.

The capture of solid particles suspended in aqueous solution by rising gas bubbles involves hydrodynamic and physicochemical processes that are central to colloid science. Of the collision, attachment and aggregate stability aspects to the bubble-particle interaction, the crucial attachment process is least understood. This is especially true of hydrophilic solids. We review the current literature regarding each component of the bubble-particle attachment process, from the free-rise of a small, clean single bubble, to the collision, film drainage and interactions which dominate the attachment rate. There is a particular focus on recent studies which employ single, very small bubbles as analysis probes, enabling the dynamic bubble-hydrophilic particle interaction to be investigated, avoiding complications which arise from fluid inertia, deformation of the liquid-vapour interface and the possibility of surfactant contamination.

Multidimensional methods for the formulation of biopharmaceuticals and vaccines.

Determining and preserving the higher order structural integrity and conformational stability of proteins, plasmid DNA, and macromolecular complexes such as viruses, virus-like particles, and adjuvanted antigens are often a significant barrier to the successful stabilization and formulation of biopharmaceutical drugs and vaccines. These properties typically must be investigated with multiple lower resolution experimental methods because each technique monitors only a narrow aspect of the overall conformational state of a macromolecular system. This review describes the use of empirical phase diagrams (EPDs) to combine large amounts of data from multiple high-throughput instruments and construct a map of a target macromolecule's physical state as a function of temperature, solvent conditions, and other stress variables. We present a tutorial on the mathematical methodology, an overview of some of the experimental methods typically used, and examples of some of the previous major formulation applications. We also explore novel applications of EPDs including potential new mathematical approaches as well as possible new biopharmaceutical applications such as analytical comparability, chemical stability, and protein dynamics.

Shear-induced coalescence of oil-in-water Pickering emulsions.

This work reports on coalescence in oil-in-water Pickering emulsions subjected to simple shear flow. The emulsions were stabilized by silanized fumed silica particles forming layers a few hundred nanometers thick around drops that are tens of micrometers in size. The drop size and particle concentration in the emulsions were fixed, while the salt concentration was varied to adjust the colloidal interactions between the drops and particles. At rest the oil drops do not coalesce. The susceptibility of the drops to orthokinetic coalescence was found to depend on the extent of particle flocculation in the attached particle layer. The evolution of the drop size with time and shear rate was consistent with phenomenological models used to describe the behavior of emulsions under shear.

A distribution-based method to resolve single-molecule Förster resonance energy transfer observations.

We introduce a new approach to analyze single-molecule Förster resonance energy transfer (FRET) data. The method recognizes that FRET efficiencies assumed by traditional ensemble methods are unobservable for single molecules. We propose instead a method to predict distributions of FRET parameters obtained directly from the data. Distributions of FRET rates, given the data, are precisely defined using Bayesian methods and increase the information derived from the data. Benchmark comparisons find that the response time of the new method outperforms traditional methods of averaging. Our approach makes no assumption about the number or distribution of underlying FRET states. The new method also yields information about joint parameter distributions going beyond the standard framework of FRET analysis. For example, the running distribution of FRET means contains more information than any conceivable single measure of FRET efficiency. The method is tested against simulated data and then applied to a pilot-study sample of calmodulin molecules immobilized in lipid vesicles, revealing evidence for multiple dynamical states.

Cells as factories for humanized encapsulation.

Biocompatibility is of paramount importance for drug delivery, tumor labeling, and in vivo application of nanoscale bioprobes. Until now, biocompatible surface processing has typically relied on PEGylation and other surface coatings, which, however, cannot minimize clearance by macrophages or the renal system but may also increase the risk of chemical side effects. Cell membranes provide a generic and far more natural approach to the challenges of encapsulation and delivery in vivo. Here we harness for the first time living cells as "factories" to manufacture cell membrane capsules for encapsulation and delivery of drugs, nanoparticles, and other biolabels. Furthermore, we demonstrate that the built-in protein channels of the new capsules can be utilized for controlled release of encapsulated reagents.