Surface modification of polydimethylsiloxane by the cataractous eye protein isolate.

Polydimethylsiloxane (PDMS), even though widely used in microfluidic applications, its hydrophobic nature restricts its utility in some cases. To address this, PDMS may be used in conjunction with a hydrophilic material. Herein, the PDMS surface is modified by plasma treatment followed by cross-linking with the cataractous eye protein isolate (CEPI). CEPI-PDMS composites are prepared at three pH and the effects of CEPI on the chemical, physical, and electrical properties of PDMS are extensively investigated. The cross-linking between PDMS and the protein are confirmed by FTIR, and the contact angle measurements indicate the improved hydrophilic nature of the composite films as compared to PDMS. Atomic Force Microscopy results demonstrate that the surface roughness is enhanced by the incorporation of the protein and is a function of the pH. The effective elastic modulus of the composites is improved by the incorporation of protein into the PDMS matrix. Measurements of the dielectric properties of these composites indicate that they behave as capacitors at lower frequency range while demonstrating resistive characteristics at higher frequency. These composites provide preliminary ideas in developing flexible devices for potential applications in diverse areas such as energy storage materials, and thermo-elective wireless switching devices.

Probing silver nanoparticle mediated mitigation of UV-photolysis in proteins by electrical impedance analysis.

The dynamic equilibrium between an array of molecular forces precisely organizes the native structure of the protein. The charge on the protein, an interconnected network continuum, is crucial in determining its secondary and tertiary structure. The photolysis of the protein by ultraviolet (UV) light occurs by generating reactive oxygen intermediates from the interaction of matter and light. Herein, we have investigated the photolysis of the protein and its prevention by the pre-treatment with silver nanoparticle (AgNP) using non-faradaic electrical impedance spectroscopy (Nf-EIS). Five microliters of protein solution are used to measure its impedimetric parameters via Nf-EIS. The photoionization process sparks off an altered surface charge continuum of the protein molecules in tandem with the genesis of solvated electrons and protons, spurring an upward shift in conductivity. The AgNP pre-treatment has reduced the damaging effects of the UV radiation, which is reflected as lesser conductivity in contrast to the photolyzed protein solution. Raman Spectroscopy and circular dichroism tests affirm the trend of Nf-EIS results. These results show that Nf-EIS can evaluate protein structure analysis utilized in quality assurance and toxicity analysis for biologics.

Early-Stage Liquid Infiltration in Nanoconfinements.

Liquid infiltration is one of the commonly adapted flow mechanisms in microscale/nanoscale heat-transfer applications. The theoretical modeling of dynamic infiltration profile in the microscale/nanoscale requires a deep study, because the acting forces are entirely different from those of a large-scale system. Herein, a model equation is developed from the fundamental force balance at the microscale/nanoscale level, to capture the dynamic infiltration flow profile. Molecular kinetic theory (MKT) is used to predict the dynamic contact angle. Molecular dynamics (MD) simulations are performed to study the capillary infiltration in two different geometries. The infiltration length is computed from the simulation results. The model is also evaluated over surfaces having different surface wettability. The generated model provides a better estimation of the infiltration length, compared to the well-established models. The developed model is expected to aid in the designing of microscale/nanoscale devices where liquid infiltration plays a key role.

Homocysteine thiolactone and H2 O2 induce amino acid modifications and alter the fibrillation propensity of the Aß25-35 peptide.

Of the proteinaceous ß-sheet-rich amyloid fibrillar structures, the Aß25-35 peptide, a component of the full-length Aß involved in Alzheimer's disease, has similar toxicity to the parent peptide. In this study, the effects of homocysteine thiolactone (HCTL) and hydrogen peroxide (H2 O2 ) on the conformation and fibrillation propensity of the Aß25-35 peptide were investigated. Both HCTL and H2 O2 induced amino acid modifications along with alteration in aggregation propensity. Methionine (Met)-35 was oxidized by H2 O2 and aggregation was attenuated following the increased hydrophilicity of the peptide due to sulfoxide/sulfone formation. The HCTL-modified lysine (Lys-28) residue destabilizes the structure of the peptide, which leads to fibrillation. Our studies provide important information regarding the relationship between amino acid modifications and the amyloid fibrillation process.

Thermally Programmable Dynamic Capillarity in Nanofluidic Channels Grafted with Smart Elastomeric Layers.

This work demonstrates thermally programmable dynamic capillarity in exclusively engineered nanochannels functionalized by grafted smart elastomeric layers onto their inner surfaces. Tunable control of the capillarity is observed over the temperature window of 25-31 °C, deciphering the possibility of a sevenfold alteration in the rate of capillary flow. A simple theory explains the confluence of viscous and capillary interactions as mediated by the non-trivial interplay of the substrate wettability, confinement-induced surface layering of molecules, and thermally activated modulation of surface tension, to bring out this intriguing effect. The technology is demonstrated to be completely reconfigurable over the intended spatial and temporal regimes, via selective grafting of the channel surface and preferential choice of the activation temperature. Such favorable features as opposed to more complex yet non-reconfigurable flow manipulation strategies previously reported are likely to open up new possibilities of highly precise controlled nanofluidic manipulation of temperature-sensitive biological samples and chemical species on-demand, for applications ranging from biomedical technologies to energy harvesting and water purification.

Electro-osmosis Aided Thin-Film Evaporation from a Micropillar Wick Structure.

The heat-dissipating capacity of a surface having micropillar wick structures, which resembles the evaporator section of a vapor chamber, is mainly limited by the liquid flow rate through the porous structure (permeability) and the capillary pressure gradient. The efficacy of a regular vapor chamber is determined from two parameters, namely, the dry-out heat flux and temperature of the evaporator surface. These two parameters possess a counter relation to each other. The work described herein introduces and evaluates the performance of a novel idea of electro-osmosis-aided thin-film evaporation from a micropillar array structure. This study is conducted using a discretized approach that is validated against the thin-film evaporation model and additionally the electro-osmotic flow model with pre-existing pressure gradient conditions. The unique feature of this approach is that it results in an increment in the magnitude of dry-out heat flux without significantly changing the surface temperature, wherein the increase in permeability is due to the addition of electro-osmotic flow. This comprehensive model considers various geometries, zeta potentials, and extremal electric fields and establishes the beneficial effects of the application of an external electric field. The results are used to predict the sensitivity and the dependence of the dry-out heat flux and the evaporator surface temperature on these parameters. For a host of electro-osmotic parameters considered herein, a maximum increment of up to 320% in the dry-out heat flux is observed for an external electric field of 105 V/m. The study, therefore, conclusively demonstrates the beneficial impact of electro-osmosis in enhancing the dry-out heat flux without any significant Joule heating.

Mechanistic Underpinnings of Morphology Transition in Electrodeposition under the Application of Pulsatile Potential.

We quantitatively investigate the role of voltage fluctuation in terms of different waveforms on the electrodeposition dynamics and morphology for varying electrolyte concentrations. Dependent on the electrolyte concentration, a wide range of morphologies ranging from highly branched dendrites to comparatively closed packed electrodeposits has been captured. We mechanistically map the deposition dynamics by image analysis and demonstrate the highly porous dendritic dynamics to be independent of external perturbation. Additionally, comparatively closed packed morphological features show significant sensitivity toward the frequency and nature of the waveforms. The results provide fundamental insights into the correlation between the time scales of voltage fluctuation and growth dynamics. We comprehensively analyze the effect of the waveform nature on the average deposition height and show sinusoidal fluctuation to be preferred over square and pulse for metal batteries for lower deposition heights.

Molecular Investigation of the Actuation of Electrowetted Nanodroplets.

It is well known that the wettability of a droplet on a solid substrate can be modified by the application of an electric field. The phenomenon of electrowetting along with the associated physics of droplet shape change and dynamics has traditionally been studied at the micro-scale leading to exciting applications. The present work is undertaken to explore the physics of electrowetting actuation of droplet movement at the molecular level. Molecular simulations are performed to obtain the dynamic spreading of the droplet under the action of a radially symmetric electric field on a silica substrate. The dynamic behavior of the contact diameter is found to be qualitatively similar to that observed at the laboratory scale. Further simulations of droplet actuation across an array of electrodes illustrated the dynamics of the center of mass, which is then used to estimate the contact line friction and compared with the predictions from a reduced-order model. A scaling analysis is used to probe the physics of the problem correlating the contact line friction coefficient and the droplet velocity after actuation. The results and understanding elicited from the fundamental approach have the potential to guide the development of quick and precise control of nano-sized droplets and may prove to be pivotal in the development of future nanofluidic systems, nanomanufacturing methodologies, and high-resolution optoelectronic devices.

Evaporation mediated translation and encapsulation of an aqueous droplet atop a viscoelastic liquid film.

HYPOTHESIS: Viscoelastic liquids could be used as potential substrates in the microfluidics paradigm. The theoretical and experimental investigation of an evaporating aqueous droplet, over a viscoelastic liquid substrate, could provide a fundamental perspective of the complex interplay amongst capillarity, viscosity, and elasticity, resulting in a wide array of intriguing dynamics, which could be important in several microscale processes. EXPERIMENTS: The evaporation dynamics of a water droplet atop an un-crosslinked polydimethylsiloxane film (polymeric liquid substrate) are examined using an optical goniometer and a laser scanning confocal microscopy, to discern the interfaces. The recorded videos were analyzed to estimate the contact angles, velocities, and other parameters of relevance. FINDINGS: The viscoelasticity of the film, in conjunction with evaporation, triggered a self-propulsion in the droplet, leading to crumpling of the polymeric film, and finally culminating in the encapsulation of the water drop by the polymer. The evaporation caused a dynamic variation in both the radius and contact angle of the droplet. The physics of the hitherto unreported phenomena is explained via the development of a semi-analytical model, considering all the relevant forces. We postulate that this symbiotic and self-sustained dynamics would pave the path towards the comprehension of micro-swimmers and surface encapsulation, to name a few.

Rapid determination of erythrocyte sedimentation rate (ESR) by an electrically driven blood droplet biosensor.

In healthcare practice, the sedimentation rate of red blood cells (erythrocytes) is a widely used clinical parameter for screening of several ailments such as stroke, infectious diseases, and malignancy. In a traditional pathological setting, the total time taken for evaluating this parameter varies typically from 1 to 2 h. Furthermore, the volume of human blood to be drawn for each test, following a gold standard laboratory technique (alternatively known as the Westergren method), varies from 4 to 5 ml. Circumventing the above constraints, here we propose a rapid (∼1 min) and highly energy efficient method for the simultaneous determination of hematocrit and erythrocyte sedimentation rate (ESR) on a microfluidic chip, deploying electrically driven spreading of a tiny drop of blood sample (∼8 µl). Our unique approach estimates these parameters by correlating the same with the time taken by the droplet to spread over a given radius, reproducing the results from more elaborate laboratory settings to a satisfactory extent. Our novel methodology is equally applicable for determining higher ranges of ESR such as high concentration of bilirubin and samples corresponding to patients with anemia and patients with some severe inflammation. Furthermore, the minimal fabrication steps involved in the process, along with the rapidity and inexpensiveness of the test, render the suitability of the strategy in extreme point-of-care settings.

Interfacial energy driven distinctive pattern formation during the drying of blood droplets.

HYPOTHESIS: Dried blood droplet morphology may potentially serve as an alternative biomarker for several patho-physiological conditions. The deviant properties of the red blood cells and the abnormal composition of diseased samples are hypothesized to manifest through unique cell-cell and cell-substrate interactions leading to different morphological patterns. Identifying distinctive morphological trait from a large sample size and proposing confirmatory explanations are necessary to establish the signatory pattern as a potential biomarker to differentiate healthy and diseased samples. EXPERIMENTS: Comprehensive experimental investigation was undertaken to identify the signatory dried blood droplet patterns. The corresponding image based analysis was in turn used to differentiate the blood samples with a specific haematological disorder "Thalassaemia" from healthy ones. Relevant theoretical analysis explored the role of cell-surface and cell-cell interactions pertinent to the formation of the distinct dried patterns. FINDINGS: The differences observed in the dried blood patterns, specifically the radial crack lengths, were found to eventuate from the differences in the overall interaction energies of the system. A first-generation theoretical analysis, with the mean field approximation, also confirmed similar outcome and justified the role of the different physico-chemical properties of red blood cells in diseased samples resulting in shorter radial cracks.

Biomimetic pulsatile flows through flexible microfluidic conduits.

We bring out unique aspects of the pulsatile flow of a blood analog fluid (Xanthan gum solution) in a biomimetic microfluidic channel. Pressure waveforms that mimic biologically consistent pulsations are applied on physiologically relevant cylindrical microchannels fabricated using polydimethylsiloxane. The in vivo features of the relevant waveforms like peak amplitude and dicrotic notch are reproduced in vitro. The deformation profiles exhibit viscoelastic behavior toward the end of each cycle. Further, the time-varying velocity profiles are critically analyzed. The local hydrodynamics within the microchannel is found to be more significantly affected by pressure waveform rather than the actual wall deformation and the velocity profile. These results are likely to bear far-reaching implications for assessing micro-circulatory dynamics in lab on a chip based microfluidic platforms that to a large extent replicate physiologically relevant conditions.

Patterned surface charges coupled with thermal gradients may create giant augmentations of solute dispersion in electro-osmosis of viscoelastic fluids.

Augmenting the dispersion of a solute species and fluidic mixing remains a challenging proposition in electrically actuated microfluidic devices, primarily due to an inherent plug-like nature of the velocity profile under uniform surface charge conditions. While a judicious patterning of surface charges may obviate some of the concerning challenges, the consequent improvement in solute dispersion may turn out to be marginal. Here, we show that by exploiting a unique coupling of patterned surface charges with intrinsically induced thermal gradients, it may be possible to realize giant augmentations in solute dispersion in electro-osmotic flows. This is effectively mediated by the phenomena of Joule heating and surface heat dissipation, so as to induce local variations in electrical properties. Combined with the rheological premises of a viscoelastic fluid that are typically reminiscent of common biofluids handled in lab-on-a-chip-based micro-devices, our results demonstrate that the consequent electro-hydrodynamic forcing may open up favourable windows for augmented hydrodynamic dispersion, which has not yet been unveiled.

Collective dynamics of red blood cells on an in vitro microfluidic platform.

Understanding the dynamics of blood flow in physiologically relevant confinements turns out to be an outstanding proposition in biomedical research. Despite the large number of studies being reported to theoretically elucidate the dynamics of red blood cells (RBCs) in confined geometries, in vitro experimental studies unveiling the implications of the collective dynamics of red blood cells in physiologically relevant bio-mimetic microfluidic channels remain elusive. Here, we investigate the implications of complex dynamvic interactions between the whole blood and a deformable channel wall fabricated using a hydrogel matrix. For a range of flow rates, we map the trajectories of the RBCs for varying levels of softness of the microchannel wall. We compare these scenarios with the reference cases of rigid polydimethylsiloxane (PDMS) channels. Our results reveal that the smallest channels investigated herein exhibit the most intricate interactions between the collective dynamics of the RBC and the wall flexibility, attributable to confinement-induced hydrodynamic interactions in the presence of spatially varying shear rates. These results may open up new paradigms in conceptual understanding of in vivo dynamics of blood flow through simple in vitro experiments on a simple microfluidic platform.

Analysis of the Distinct Pattern Formation of Globular Proteins in the Presence of Micro- and Nanoparticles.

Pattern formation during evaporation of biofluids has numerous biomedical applications, e.g., in disease identification. The drying of a bidisperse colloidal droplet involves formation of coffee ring patterns owing to the deposition of constituent particles. In the present study, we examine the distinctly different pattern formations during the drying of a colloidal solution depending on the nature of the constituent proteins. The pattern formations of two oppositely charged proteins, namely HSA and lysozyme, have been studied in the presence of fluorescence polystyrene beads of two different sizes (providing better image contrast for further analysis). The variation of pattern formation has been studied by varying the concentrations of the proteins as well as the particles. Furthermore, using image analysis, the patterns are segmented into different regions for quantification. To explain the variations in the patterns, we delve into the interplay of the interactions, especially the capillary and the DLVO forces (between the particles and the substrate). The developed methodology based on the coffee ring effect may be used to identify individual proteins.

Tailored topography: a novel fabrication technique using an elasticity gradient.

A facile methodology to create a wrinkled surface with a tailored topography is presented herein. The dependency of the elasticity of poly(dimethyl)siloxane (PDMS) on the curing temperature has been exploited to obtain a substrate with an elasticity gradient. The temperature gradient across the length of PDMS is created by a novel set-up consisting of a metal and insulator connected to a heater and the highest usable (no degradation of PDMS) temperature gradient is used. The time-dependent temperature distributions along the substrate are measured and the underlying physics of the dependence of the PDMS elasticity on the curing temperature is addressed. The PDMS substrate with the elasticity gradient is first stretched and subsequently oxidized by oxygen plasma. Upon relaxation, an ordered wrinkled surface with continuously varying wavelength and amplitude along the length of PDMS is obtained. The extent of hydrophobicity recovery of this plasma oxidized PDMS with varying elasticity has been studied. The change in the wavelength and amplitude of the regular patterns on the substrate can be controlled by varying operational parameters like applied pre-strain, plasma power and the heater temperature. It has been found that the spatial distributions of the topography and the hydrophobicity collectively decide the resultant wettability of the substrate. Such surfaces with gradients in the substructure dimensions demonstrate different wetting characteristics that may lead to a wide gamut of applications including droplet movement, cell adhesion and proliferation, diffraction grating etc.

Flow-induced deformation in a microchannel with a non-Newtonian fluid.

In this work, we have fabricated physiologically relevant polydimethylsiloxane microfluidic phantoms to investigate the fluid-structure interaction that arises from the interaction between a non-Newtonian fluid and the deformable wall. A shear thinning fluid (Xanthan gum solution) is used as the blood analog fluid. We have systematically analyzed the steady flow characteristics of the microfluidic phantom using pressure drop, deformation, and flow visualization using micro-PIV (Particle Image Velocimetry) to identify the intricate aspects of the pressure as well as the velocity field. A simple mathematical formulation is introduced to evaluate the flow induced deformation. These results will aid in the design and development of deformable microfluidic systems and provide a deeper understanding of the fluid-structure interaction in microchannels with special emphasis on biomimetic in-vitro models for lab-on-a-chip applications.

Electrodewetting and Wetting of an Extended Meniscus.

Here, we report the intriguing movements of an extended liquid meniscus on a silicon substrate under the influence of sinusoidal alternating current (AC) voltages at different operating frequencies. As opposed to droplet electrowetting, wherein the droplet spreads and experiences oscillations at the free surface, the application of AC voltage to a thin liquid film results in distinct and uniform dewetting, in conjunction with augmented wetting. Image analyzing interferometry is used for the precise measurement of the film thickness profile and other associated parameters. We postulate that the classic Young-Lippmann equation fails to explain the dynamics of an extended meniscus and evince that the dynamics of film displacement could be successfully explained by considering the product of the applied electric field and its gradient, as opposed to the existing consideration of a square dependence on the applied voltage. The physics of the hitherto unreported phenomena is elucidated by developing a mathematical model, taking into consideration all of the germane forces governing the dynamics of the thin liquid film. We affirm that the present study would serve as a fundamental background for a fascinating mode of liquid actuation, with inherent application potential in several existing and novel microfluidic systems.

Surface property induced morphological alterations of human erythrocytes.

Microscopic investigations of any abnormality associated with erythrocyte/red blood cell morphology constitute an important segment of the age-old peripheral smear test. Though the test is conducted on a glass slide, the effect of glass and similar other solid substrates on erythrocyte morphology remained majorly unexplored. In the first of its kind investigation, we have outlined the effect of varying the substrate surface potential on erythrocyte morphology. Such a substrate induced phenomenon has been quantified for two distinctly different drying configurations (droplets and film) upon systematically varying the cell concentration. Experimental results and supporting theoretical analysis unambiguously show the surface potential of the solid substrate to be the most influential parameter in the process of morphological alteration. The findings of the present investigation may be utilized to formulate an error-free protocol for the baseline peripheral smear test of hematological diagnosis.

Fractal Dimension of Erythrocyte Membranes: A Highly Useful Precursor for Rapid Morphological Assay.

Morphology of erythrocyte membrane has been recognized as an alternative biomarker of several patho-physiological states. Numerous attempts have been made to upgrade the existing method of primitive manual counting, particularly exploring the light scattering properties of erythrocyte. All the techniques are at best semi-empirical and heavily rely on the effectiveness of the statistical correlations. Precisely, this is due to the lack of a non-empirical scale of the so-called "morphological scores". In this article, fractal dimension of erythrocyte membrane has been used to formulate a suitable scoring scale. Subsequently, the rapid experimental output of flow-cytometry has been functionally related to the mean morphological quantifier of the whole cell population via an optimum neural network model (R2 = 0.98). Moreover, the fractal dimension has been further demonstrated to be an important parameter in early detection of an abnormal patho-physiological state, even without any noticeable poikilocytic transformation in micrometric domain.