Continuous flow microfluidics for colloidal particle assembly on porous substrates.

Self-assembly of colloidal particles for 'bottom-up' fabrication of various patterns and structures is critical for a range of applications including, but not limited to, energy generation and storage, nanomaterial structures, biomimetics, and biosensing. Multiple self-assembly techniques, such as substrate templating-via topological or chemical patterning-and solvent evaporation were discussed in our previous papers and have been developed for the deposition of patterned self-assembled structures, such as bands of colloidal particles, on various substrates. While the templating techniques are limited in applications due to the requirements for pattern-specific prior substrate engineering to fabricate the desired structure, solvent evaporation requires longer assembly times and precise control over environmental conditions. In this paper, a template-free, continuous flow process, which is facilitated by continuous solvent drainage through porous substrates, is demonstrated for the self-assembly of colloidal particles into high-aspect ratio (>103, length to width) structures, such as linear arrays or grid structures. Colloidal particles were assembled both on polymeric and metallic porous membranes, with rapid assembly times.

Differential clock comparisons with a multiplexed optical lattice clock.

Rapid progress in optical atomic clock performance has advanced the frontiers of timekeeping, metrology and quantum science1-3. Despite considerable efforts, the instabilities of most optical clocks remain limited by the local oscillator rather than the atoms themselves4,5. Here we implement a 'multiplexed' one-dimensional optical lattice clock, in which spatially resolved strontium atom ensembles are trapped in the same optical lattice, interrogated simultaneously by a shared clock laser and read-out in parallel. In synchronous Ramsey interrogations of ensemble pairs we observe atom-atom coherence times of 26 s, a 270-fold improvement over the measured atom-laser coherence time, demonstrate a relative instability of [Formula: see text] (where τ is the averaging time) and reach a relative statistical uncertainty of 8.9 × 10-20 after 3.3 h of averaging. These results demonstrate that applications involving optical clock comparisons need not be limited by the instability of the local oscillator. We further realize a miniaturized clock network consisting of 6 atomic ensembles and 15 simultaneous pairwise comparisons with relative instabilities below [Formula: see text], and prepare spatially resolved, heterogeneous ensemble pairs of all four stable strontium isotopes. These results pave the way for multiplexed precision isotope shift measurements, spatially resolved characterization of limiting clock systematics, the development of clock-based gravitational wave and dark matter detectors6-12 and new tests of relativity in the lab13-16.

Combined electrokinetic and shear flows control colloidal particle distribution across microchannel cross-sections.

Recent experimental observations on combined electrokinetic and shear flows of colloidal suspensions in rectangular cross-section microfluidic channels have shown unusual cross-stream colloidal particle migration and dynamic assembly. Although a new electrophoresis-induced lift force has been postulated to cause the lateral migration of colloidal particles, little is known about how fluid properties and flow conditions impact this force and therefore subsequent colloidal particle migration. Furthermore, no experimental quantification of this electrophoresis-induced lift force is available. We report several key advances by demonstrating that the kinematic viscosity of the fluid can be used to modulate the spatial distribution of particles over the entire microchannel cross-section, with suppression of the colloidal particle migration observed with increase in fluid kinematic viscosity. Colloidal particle migration of ∼10 µm from not only the top and bottom microchannel walls but also from the side walls is shown with the corresponding electrophoresis-induced lift force of up to ∼30 fN. The breadth of flow conditions tested capture the channel Reynolds number in the 0.1-1.1 range, with inertial migration of colloidal particles shown in flow regimes where the migration was previously thought to be ineffective, if not for the electrophoresis-induced lift force. The ability of the electrophoresis-induced lift force to migrate colloidal particles across the entire microchannel cross-section establishes a new paradigm for three-dimensional control of colloidal particles within confined microchannels.

Evaluation of electrical properties of ex vivo human hepatic tissue with metastatic colorectal cancer.

OBJECTIVE: To probe the distribution of electrical properties in tumor-bearing human hepatic tissues with metastatic colorectal cancer. APPROACH: Electrochemical impedance spectroscopy (EIS) and a non-contact electromagnetic probe were used for distinguishing spatial heterogeneities in fresh, unfixed human hepatic tissues ex vivo from patients with metastatic colorectal cancer (CRC). MAIN RESULTS: Point-wise EIS measurements reported over a frequency range of 100 Hz-1 MHz showed that the interface tissue between visible tumor and normal tissue exhibits an electrically different domain (p < 0.05) from both normal tissue (over 100 Hz-100 kHz) and tumor tissue (over 100 Hz-1 MHz). Observations of the microstructure on tumor-bearing hepatic tissue from hematoxylin and eosin stained images and the equivalent circuit modelling were used to validate the impedance measurements and characterize previously unidentified interfacial domain between normal and tumor tissue. Lastly, in a proof of concept study, a new in-house designed non-contact electromagnetic probe, as opposed to the invasive EIS measurements, was demonstrated for distinguishing tumor tissue from the normal tissue in a hepatic tissue specimen from a patient with metastatic CRC. SIGNIFICANCE: EIS measurements, correlated with histological observations, show potential for mapping electrical properties in tumor-bearing human hepatic tissue.

Ultrastructure imaging of Pseudomonas aeruginosa lawn biofilms and eradication of the tobramycin-resistant variants under in vitro electroceutical treatment.

Electrochemically generated bactericidal compounds have been shown to eradicate bacterial lawn biofilms through electroceutical treatment. However, the ultrastructure of biofilms exposed to these species has not been studied. Moreover, it is unknown if the efficacy of electroceutical treatment extends to antibiotic-resistant variants that emerge in lawn biofilms after antibiotic treatment. In this report, the efficacy of the in vitro electroceutical treatment of Pseudomonas aeruginosa biofilms is demonstrated both at room temperature and in an incubator, with a ~4 log decrease (p < 0.01) in the biofilm viability observed over the anode at both conditions. The ultrastructure changes in the lawn biofilms imaged using transmission electron microscopy demonstrate significant bacterial cell damage over the anode after 24 h of electroceutical treatment. A mix of both damaged and undamaged cells was observed over the cathode. Finally, both eradication and prevention of the emergence of tobramycin-resistant variants were demonstrated by combining antibiotic treatment with electroceutical treatment on the lawn biofilms.

Printed Electroceutical Dressings for the Inhibition of Biofilms and Treatment of Chronic Wounds.

We report on an innovative, fabric-based conformable, and easily fabricated electroceutical wound dressing that inhibits bacterial biofilm infections and shows significant promise for healing chronic wounds. Cyclic voltammetry demonstrates the ability of the electroceutical to produce reactive oxygen species, primarily HOCl that is responsible for bacterial inhibition. In vitro investigation with the lawn biofilm grown on a soft tissue mimic assay shows the efficacy of the dressing against both gram-positive and gram-negative bacteria in the biofilm form. In vivo, the printed electroceutical dressing was utilized as an intervention treatment for a canine subject with a non-healing wound due to a year-long persistent polymicrobial infection. The clinical case study with the canine subject exhibited the applicability in a clinical setting with the results showing infection inhibition within 11 days of initial treatment. This printed electroceutical dressing was integrated with a Bluetooth® enabled circuit allowing remote monitoring of the current flow within the wound bed. The potential to monitor wounds remotely in real-time with a Bluetooth® enabled circuit proposes a new physical biomarker for management of infected, chronic wounds.

Disposable Patterned Electroceutical Dressing (PED-10) Is Safe for Treatment of Open Clinical Chronic Wounds.

Objective: To evaluate if patterned electroceutical dressing (PED) is safe for human chronic wounds treatment as reported by wound care providers. Approach: This work reports a pilot feasibility study with the primary objective to determine physically observable effects of PED application on host tissue response from a safety evaluation point of view. For this pilot study, patients receiving a lower extremity amputation with at least one open wound on the part to be amputated were enrolled. Patients were identified through the Ohio State University Wexner Medical Center (OSUWMC) based on inclusion and exclusion criteria through prescreening through the Comprehensive Wound Center's (CWC) Limb Preservation Program and wound physicians and/or providers at OSUWMC. Wounds were treated with the PED before amputation surgery. Results: The intent of the study was to identify if PED was safe for clinical application based on visual observations of adverse or lack of adverse events on skin and wound tissue. The pilot testing performed on a small cohort (N = 8) of patients showed that with engineered voltage regulation of current flow to the open wound, the PED can be used with little to no visually observable adverse effects on chronic human skin wounds. Innovation: The PED was developed as a second-generation tunable electroceutical wound care dressing, which could potentially be used to treat wounds with deeper infections compared with current state of the art that treats wounds with treatment zone limited to the surface near topical application. Conclusion: Technology advances in design and fabrication of electroceutical dressings were leveraged to develop a tunable laboratory prototype that could be used as a disposable low-cost electroceutical wound care dressing on chronic wounds. Design revisions of PED-1 (1 kΩ ballast resistor) circumvented previously observed adverse effects on the skin in the vicinity of an open wound. PED-10 (including a 10 kΩ ballast resistor) was well tolerated in the small cohort of patients (N = 8) on whom it was tested, and the observations reported here warrant a larger study to determine the clinical impact on human wound healing and infection control.

Electroceutical Treatment of Pseudomonas aeruginosa Biofilms.

Electroceutical wound dressings, especially those involving current flow with silver based electrodes, show promise for treating biofilm infections. However, their mechanism of action is poorly understood. We have developed an in vitro agar based model using a bioluminescent strain of Pseudomonas aeruginosa to measure loss of activity and killing when direct current was applied. Silver electrodes were overlaid with agar and lawn biofilms grown for 24 h. A 6 V battery with 1 kΩ ballast resistor was used to treat the biofilms for 1 h or 24 h. Loss of bioluminescence and a 4-log reduction in viable cells was achieved over the anode. Scanning electron microscopy showed damaged cells and disrupted biofilm architecture. The antimicrobial activity continued to spread from the anode for at least 2 days, even after turning off the current. Based on possible electrochemical ractions of silver electrodes in chlorine containing medium; pH measurements of the medium post treatment; the time delay between initiation of treatment and observed bactericidal effects; and the presence of chlorotyrosine in the cell lysates, hypochlorous acid is hypothesized to be the chemical agent responsible for the observed (destruction/killing/eradication) of these biofilm forming bacteria. Similar killing was obtained with gels containing only bovine synovial fluid or human serum. These results suggest that our in vitro model could serve as a platform for fundamental studies to explore the effects of electrochemical treatment on biofilms, complementing clinical studies with electroceutical dressings.