Harnessing Standing Sound Waves to Treat Intraocular Blood Cell Accumulation.

Certain ocular conditions result from the non-physiological presence of intraocular particles, leading to visual impairment and potential long-term damage. This happens when the normally clear aqueous humor becomes less transparent, thus blocking the visual axis and by intraocular pressure elevation due to blockage of the trabecular meshwork, as seen in secondary open-angle glaucoma (SOAG). Some of these "particle-related pathologies" acquire ocular conditions like pigment dispersion syndrome, pseodoexfoliation and uveitis. Others are trauma-related, such as blood cell accumulation in hyphema. While medical and surgical treatments exist for SOAG, there is a notable absence of effective preventive measures. Consequently, the prevailing clinical approach predominantly adopts a "wait and see" strategy, wherein the focus lies on managing secondary complications and offers no treatment options for particulate matter disposal. We developed a new technique utilizing standing acoustic waves to trap and direct intraocular particles. By employing acoustic trapping at nodal regions and controlled movement of the acoustic transducer, we successfully directed these particles to specific locations within the angle. Here, we demonstrate control and movement of polystyrene (PS) particles to specific locations within an in vitro eye model, as well as blood cells in porcine eyes (ex vivo). The removal of particles from certain areas can facilitate the outflow of aqueous humor (AH) and help maintain optimal intraocular pressure (IOP) levels, resulting in a non-invasive tool for preventing secondary glaucoma. Furthermore, by controlling the location of trapped particles we can hasten the clearance of the AH and improve visual acuity and quality more effectively. This study represents a significant step towards the practical application of our technique in clinical use.

Acoustic Manipulation of Intraocular Particles.

Various conditions cause dispersions of particulate matter to circulate inside the anterior chamber of a human eye. These dispersed particles might reduce visual acuity or promote elevation of intraocular pressure (IOP), causing secondary complications such as particle related glaucoma, which is a major cause of blindness. Medical and surgical treatment options are available to manage these complications, yet preventive measures are not currently available. Conceptually, manipulating these dispersed particles in a way that reduces their negative impact could prevent these complications. However, as the eye is a closed system, manipulating dispersed particles in it is challenging. Standing acoustic waves have been previously shown to be a versatile tool for manipulation of bioparticles from nano-sized extracellular vesicles up to millimeter-sized organisms. Here we introduce for the first time a novel method utilizing standing acoustic waves to noninvasively manipulate intraocular particles inside the anterior chamber. Using a cylindrical acoustic resonator, we show ex vivo manipulation of pigmentary particles inside porcine eyes. We study the effect of wave intensity over time and rule out temperature changes that could damage tissues. Optical coherence tomography and histologic evaluations show no signs of damage or any other side effect that could be attributed to acoustic manipulation. Finally, we lay out a clear pathway to how this technique can be used as a non-invasive tool for preventing secondary glaucoma. This concept has the potential to control and arrange intraocular particles in specific locations without causing any damage to ocular tissue and allow aqueous humor normal outflow which is crucial for maintaining proper IOP levels.

Laser Printing of Multilayered Alternately Conducting and Insulating Microstructures.

Production of multilayered microstructures composed of conducting and insulating materials is of great interest as they can be utilized as microelectronic components. Current proposed fabrication methods of these microstructures include top-down and bottom-up methods, each having their own set of drawbacks. Laser-based methods were shown to pattern various materials with micron/sub-micron resolution; however, multilayered structures demonstrating conducting/insulating/conducting properties were not yet realized. Here, we demonstrate laser printing of multilayered microstructures consisting of conducting platinum and insulating silicon oxide layers by a combination of thermally driven reactions with microbubble-assisted printing. PtCl2 dissolved in N-methyl-2-pyrrolidone (NMP) was used as a precursor to form conducting Pt layers, while tetraethyl orthosilicate dissolved in NMP formed insulating silicon oxide layers identified by Raman spectroscopy. We demonstrate control over the height of the insulating layer between ∼50 and 250 nm by varying the laser power and number of iterations. The resistivity of the silicon oxide layer at 0.5 V was 1.5 × 1011 Ωm. Other materials that we studied were found to be porous and prone to cracking, rendering them irrelevant as insulators. Finally, we show how microfluidics can enhance multilayered laser microprinting by quickly switching between precursors. The concepts presented here could provide new opportunities for simple fabrication of multilayered microelectronic devices.

Assembly of Conductive Polyaniline Microstructures by a Laser-Induced Microbubble.

Micropatterns of conductive polymers are key for various applications in the fields of flexible electronics and sensing. A bottom-up method that allows high-resolution printing without additives is still lacking. Here, such a method is presented based on microprinting by the laser-induced microbubble technique (LIMBT). Continuous micropatterning of polyaniline (PANI) was achieved from a dispersion of the emeraldine base form of PANI (EB-PANI) in n-methyl-2-pyrrolidone (NMP). A focused laser beam is absorbed by the EB-PANI nanoparticles and leads to formation of a microbubble, followed by convection currents, which rapidly pin EB-PANI nanoparticles to the bubble/substrate interface. Micro-Raman spectra confirmed that the printed patterns preserve the molecular structure of EB-PANI. A simple transformation of the printed lines to the conducting emeraldine salt form of PANI (ES-PANI) was achieved by doping with various acid solutions. The hypothesized deposition mechanism was verified, and the resulting structures were characterized by microscopic methods. The microstructures displayed conductivities of 3.8 × 10-1 S/cm upon HCl doping and 1.5 × 10-1 S/cm upon H2SO4 doping, on par with state-of-the-art patterning methods. High fidelity control over the width of the printed lines down to ∼650 nm was accomplished by varying the laser power and microscope stage velocity. This straightforward bottom-up method using low-power lasers offers an alternative to current microfabrication techniques.

Microfluidic-based linear-optics label-free imager.

Linear optics based nanoscopy previously reached resolution beyond the diffraction limit, illuminating samples in the visible light regime while allowing light to interact with freely moving metallic nanoparticles. However, the hydrodynamics governing the nanoparticle motion used to scan the sample is very complex and has low probability of achieving appropriate and fast mapping in practice. Hence, an implementation of the technique on real biological samples has not been demonstrated so far. Moreover, a suitable way to perform controlled nanoparticle scanning of biological samples is required. Here we show a solution where a microfluidic channel is used to flow and trap biological samples inside a water droplet along with suspended nanoparticles surrounded by silicone oil. The evanescent light scattered from the sample and is rescattered by the nanoparticles in the vicinity. This encodes the sub-wavelength features of the sample which can later on be decoded and reconstructed from measurements in the far field. The microfluidic system-controlled flow allows better nanoparticle scanning of the sample and maintains an isolated system for each sample in each droplet. A more localized scan at the droplet water/oil interface is also conducted using amphiphilic nanoparticles where their hydrophilic side is constrained to the droplet and their hydrophobic side is constrained to the oil. This allows higher probability of capturing evanescent fields closer to their origin, yielding better resolution and a higher signal to noise ratio. Using this system, we obtained images of an E. coli sample and demonstrated how the method yield fine resolution of the sample contours. To the best of our knowledge, this is the first time that a linear and label free optics imaging process was performed using a micro-fluidic device.

Large-scale acoustic-driven neuronal patterning and directed outgrowth.

Acoustic manipulation is an emerging non-invasive method enabling precise spatial control of cells in their native environment. Applying this method for organizing neurons is invaluable for neural tissue engineering applications. Here, we used surface and bulk standing acoustic waves for large-scale patterning of Dorsal Root Ganglia neurons and PC12 cells forming neuronal cluster networks, organized biomimetically. We showed that by changing parameters such as voltage intensity or cell concentration we were able to affect cluster properties. We examined the effects of acoustic arrangement on cells atop 3D hydrogels for up to 6 days and showed that assembled cells spontaneously grew branches in a directed manner towards adjacent clusters, infiltrating the matrix. These findings have great relevance for tissue engineering applications as well as for mimicking architectures and properties of native tissues.

Simultaneous laser-induced synthesis and micro-patterning of a metal organic framework.

Micro-patterning of a metal organic framework (MOF) from a solution of precursors is achieved by local laser heating. Nano-sized MOFs are formed, followed by rapid assembly due to convective flows around a heat-induced micro-bubble. This laser-induced bottom-up technique is the first to suggest simultaneous synthesis and micro-patterning of MOFs, alleviating the need for pre-preparation and stabilization.

Drag controlled formation of polymeric colloids with optical traps.

Optical trapping is a powerful optical manipulation technique for controlling various mesoscopic systems that allows formation of tailor-made polymeric micro-sized colloids by directed coalescence of nucleation sites. However, control over the size of a single colloid requires constant monitoring of the growth process and deactivation of the optical trap once it reaches the required dimensions. Moreover, producing more than one colloid requires moving the sample to a pristine location where the process must be repeated. Here, we present a novel method for continuous control over formation of polydimethylsiloxane colloids based on directed coalescence induced by optical traps under flow inside microfluidic channels. Once the drag force on a growing colloid exceeds the trapping force, it leaves the optical trap, and a new colloid starts to form at the same location. We demonstrate repeatability of the process and selectively produce colloids with radii of ∼1-14 µm by controlling the laser intensity and flow rate. In addition, holographic optical tweezers are used to show how multiple optical traps in 3D could be used to influence a significant cross section of the micro-channel, thus forming a light-controlled assembly line for colloidal formation.

Controlled Shape and Porosity of Polymeric Colloids by Photo-Induced Phase Separation.

The shape and porosity of polymeric colloids are two properties that highly influence their ability to accomplish specific tasks. For micro-sized colloids, the control of both properties was demonstrated by the photo-induced phase separation of droplets of NOA81-a thiol-ene based UV-curable adhesive-mixed with acetone, water, and polyethylene glycol. The continuous phase was perfluoromethyldecalin, which does not promote phase separation prior to UV activation. A profound influence of the polymer concentration on the particle shape was observed. As the photo-induced phase separation is triggered by UV radiation, polymerization drives the extracted solution out of the polymeric matrix. The droplets of the extracted solution coalesce until they form a dimple correlated to the polymer concentration, significantly changing the shape of the formed solid colloids. Moreover, control could be gained over the porosity by varying the UV intensity, which governs the kinetics of the reaction, without changing the chemical composition; the number of nanopores was found to increase significantly at higher intensities.

Imaging of nanoparticle dynamics in live and apoptotic cells using temporally-modulated polarization.

Gold nanoparticles are widely exploited in phototherapy. Owing to their biocompatibility and their strong visible-light surface plasmonic resonance, these particles also serve as contrast agents for cell image enhancement and super-resolved imaging. Yet, their optical signal is still insufficiently strong for many important real-life applications. Also, the differentiation between adjacent nanoparticles is usually limited by the optical resolution and the orientations of non-spherical particles are unknown. These limitations hamper the progress in cell research by direct optical microscopy and narrow the range of phototherapy applications. Here we demonstrate exploiting the optical anisotropy of non-spherical nanoparticles to achieve super-resolution in live cell imaging and to resolve the intracellular nanoparticle orientations. In particular, by modulating the light polarization and taking advantage of the polarization-dependence of gold nanorod optical properties, we realize the 'lock-in amplification', widely-used in electronic engineering, to achieve image enhancement in live cells and in cells that undergo apoptotic changes.

Microfluidic Devices Containing ZnO Nanorods with Tunable Surface Chemistry and Wetting-Independent Water Mobility.

Interest in polydimethylsiloxane (PDMS) microfluidic devices has grown dramatically in recent years, particularly in the context of improved performance lab-on-a-chip devices with decreasing channel size enabling more devices on ever smaller chips. As channels become smaller, the resistance to flow increases and the device structure must be able to withstand higher internal pressures. We report herein the fabrication of microstructured surfaces that promote water mobility independent of surface static wetting properties. The key tool in this approach is the growth of ZnO nanorods on the bottom face of the microfluidic device. We show that water flow in these devices is similar whether the textured nanorod-bearing surface is hydrophilic or superhydrophobic; that is, the device tolerates a wide range of surface wetting properties without changing the water flow within the device. This is not the case for smooth surfaces with different wetting properties, wherein hydrophilic surfaces result in slower flow rates. The ability to create monolayer-coated ZnO nanorods in a PDMS microfluidic device also allows for a variety of surface modifications within standard mass-produced devices. The inorganic ZnO nanorods can be coated with alkyl phosphonate monolayers. These monolayers can be used to convert hydrophilic surfaces into hydrophobic and even superhydrophobic surfaces that provide a platform for further surface modification. We also report photopatterned biomolecule immobilization within the channels on the monolayer-coated ZnO rods.

Directed assembly of nanoparticles into continuous microstructures by standing surface acoustic waves.

Directed-assembly by standing surface acoustic waves (SSAWs) only requires an acoustic contrast between particles and their surrounding medium. It is therefore highly attractive as this requirement is fulfilled by almost all dispersed systems. Previous studies utilizing SSAWs demonstrated mainly reversible microstructure arrangements from nanoparticles. The surface chemistry of colloids dramatically influences their tendency to aggregate and sinter; therefore, it should be possible to form permanent microstructures with intimate contact between nanoparticles by controlling this property. Dispersed silver nanoparticles in a microfluidic channel were exposed to SSAWs and reversibly accumulated at the pressure nodes. We show that addition of chloride ions that remove the polyacrylic capping of the nanoparticles trigger their sintering and the formation of stable conducting silver microstructures. Moreover, if the destabilizing ions are added prior to nanoparticle assembly while continuously streaming the dispersion through the acoustic aperture, the induced aggregation leads to formation of significantly thinner microstructures, which are (for the first time) unlimited in length by the acoustic apparatus. This new approach overcomes the discrepancy between the need for organic dispersants to prevent unwanted aggregation in the dispersion, and the end product's requirement for intimate contact between the colloidal particles.

Self-faceting of emulsion droplets as a route to solid icosahedra and other polyhedra.

HYPOTHESIS: Temperature-controlled self-faceting of liquid droplets has been recently discovered in surfactant-stabilized alkane-in-water emulsions. We hypothesize that similar self-faceting may occur in emulsion droplets of UV-polymerizable linear hydrocarbons. We further hypothesize that the faceted droplet shapes can be fixed by UV-initiated polymerization, thus providing a new route towards the production of solid polyhedra. EXPERIMENTS: Temperature-induced shape variations were studied by optical microscopy in micron-size emulsion droplets of UV-polymerizable alkyl acrylate. When polymerized, the resultant solid particles' 3D shape and internal structure were determined by combined scanning electron microscopy (SEM) and focused ion beam (FIB) slicing. The SEM and FIB nanoscale resolution provided a far greater detail imaging than that achievable for the liquid droplets, which could only be studied by optical microscopy, severely limiting their 3D shape determination. FINDINGS: We demonstrate the formation of solid icosahedra, polyhedral platelets, and rods of hitherto-unreported sizes, well below the 3D-printing resolution (∼20µm). The presence of icosahedral shapes and the absence of any resolvable internal structure at sub-µm length scales, are in line with the surface-freezing-driven mechanism proposed for the faceting phenomenon. Further development of the method presented here may allow large-quantity production of shaped micron- to nano- sized colloidal building blocks for 3D metamaterials and other applications.

Continuous Nanoparticle Assembly by a Modulated Photo-Induced Microbubble for Fabrication of Micrometric Conductive Patterns.

The laser-induced microbubble technique (LIMBT) has recently been developed for micro-patterning of various materials. In this method, a laser beam is focused on a dispersion of nanoparticles leading to the formation of a microbubble due to laser heating. Convection currents around the microbubble carry nanoparticles so that they become pinned to the bubble/substrate interface. The major limitation of this technique is that for most materials, a noncontinuous deposition is formed. We show that continuous patterns can be formed by preventing the microbubble from being pinned to the deposited material. This is done by modulating the laser so that the construction and destruction of the microbubble are controlled. When the method is applied to a dispersion of Ag nanoparticles, continuous electrically conductive lines are formed. Furthermore, the line width is narrower than that achieved by the standard nonmodulated LIMBT. This approach can be applied to the direct-write fabrication of micron-size conductive patterns in electronic devices without the use of photolithography.

Influencing colloidal formation with optical traps.

We present a novel concept where optical traps are used to influence an ongoing polymerization process of emulsion droplets. By directed coalescence and partial fusion of intermediate nucleation sites, spherical and elongated colloids with specific dimensions are formed. The strength of this approach lies in its versatility and ease of making various changes to the end product without the need for chemical modifications.

Celebrating Soft Matter's 10th Anniversary: monitoring colloidal growth with holographic microscopy.

Holographic video microscopy offers valuable and previously unavailable insights into the progress of colloidal synthesis by providing measurements of the size and refractive index of individual colloidal particles in the dispersion. These measurements are precise enough to track subtle changes in particles' properties and rapid enough for real-time process control. We demonstrate this technique by applying it to the synthesis of monodisperse samples of crosslinked polydimethysiloxane (PDMS) spheres. The measured time dependence of these spheres' most probable radius is consistent with the LaMer model for colloidal growth. The joint distribution of size and refractive index, however, also reveals a small proportion of undersize, lower-density spheres. Trends in the distribution's time evolution offer insights into their origin. Applied over longer time periods, holographic characterization also tracks how the newly-synthesized spheres age, and illuminates the aging mechanism.

A novel method for investigating electrical breakdown enhancement by nm-sized features.

Electrical transport studies across nm-thick dielectric films can be complicated, and datasets compromised, by local electrical breakdown enhanced by nm-sized features. To avoid this problem we need to know the minimal voltage that causes the enhanced electrical breakdown, a task that usually requires numerous measurements and simulation of which is not trivial. Here we describe and use a model system, using a "floating" gold pad to contact Au nanoparticles, NPs, to simultaneously measure numerous junctions with high aspect ratio NP contacts, with a dielectric film, thus revealing the lowest electrical breakdown voltage of a specific dielectric-nanocontact combination. For a 48 ± 1.5 Å SiO(2) layer and a ∼7 Å monolayer of organic molecules (to link the Au NPs) we show how the breakdown voltage decreases from 4.5 ± 0.4 V for a flat contact, to 2.4 ± 0.4 V if 5 nm Au NPs are introduced on the surface. The fact that larger Au NPs on the surface do not necessarily result in significantly higher breakdown voltages illustrates the need for combining experiments with model calculations. This combination shows two opposite effects of increasing the particle size, i.e., increase in defect density in the insulator and decrease in electric field strength. Understanding the process then explains why these systems are vulnerable to electrical breakdown as a result of spikes in regular electrical grids. Finally we use XPS-based chemically resolved electrical measurements to confirm that breakdown occurs indeed right below the nm-sized features.

Molecular electronics at metal/semiconductor junctions. Si inversion by sub-nanometer molecular films.

Electronic transport across n-Si-alkyl monolayer/Hg junctions is, at reverse and low forward bias, independent of alkyl chain length from 18 down to 1 or 2 carbons! This and further recent results indicate that electron transport is minority, rather than majority carrier dominated, occurs via generation and recombination, rather than (the earlier assumed) thermionic emission, and, as such, is rather insensitive to interface properties. The (m)ethyl results show that binding organic molecules directly to semiconductors provides semiconductor/metal interface control options, not accessible otherwise.

Radiation damage to alkyl chain monolayers on semiconductor substrates investigated by electron spectroscopy.

Monolayers of alkyl chains, attached through direct Si-C bonds to Si(111), via phosphonates to GaAs(100) surfaces, or deposited as alkyl-silane monolayers on SiO2, are investigated by ultraviolet and inverse photoemission spectroscopy and X-ray absorption spectroscopy. Exposure to ultraviolet radiation from a He discharge lamp, or to a beam of energetic electrons, leads to significant damage, presumably associated with radiation- or electron-induced H-abstraction leading to carbon-carbon double-bond formation in the alkyl monolayer. The damage results in an overall distortion of the valence spectrum, in the appearance of (occupied) states above the highest occupied molecular orbital of the alkyl molecule, and in a characteristic (unoccupied state) pi resonance at the edge of the carbon absorption peak. These distortions present a serious challenge for the interpretation of the electronic structure of the monolayer system. We show that extrapolation to zero damage at short exposure times eliminates extrinsic features and allows a meaningful extraction of the density of state of the pristine monolayer from spectroscopy measurements.