Diffusion of Nanoparticles with Activated Hopping in Crowded Polymer Solutions.

A long-distance hop of diffusive nanoparticles (NPs) in crowded environments was commonly considered unlikely, and its characteristics remain unclear. In this work, we experimentally identify the occurrence of the intermittent hops of large NPs in crowded entangled poly(ethylene oxide) (PEO) solutions, which are attributed to thermally induced activated hopping. We show that the diffusion of NPs in crowded solutions is considered as a superposition of the activated hopping and the reptation of the polymer solution. Such activated hopping becomes significant when either the PEO molecular weight is large enough or the NP size is relatively small. We reveal that the time-dependent non-Gaussianity of the NP diffusion is determined by the competition of the short-time relaxation of a polymer entanglement strand, the activated hopping, and the long-time reptation. We propose an exponential scaling law τhop/τe ∼ exp(d/dt) to characterize the hopping time scale, suggesting a linear dependence of the activated hopping energy barrier on the dimensionless NP size. The activated hopping motion can only be observed between the onset time scale of the short-time relaxation of local entanglement strands and the termination time scale of the long-time relaxation. Our findings on activated hopping provide new insights into long-distance transportation of NPs in crowded biological environments, which is essential to the delivery and targeting of nanomedicines.

Electrothermal enrichment of submicron particles in an insulator-based dielectrophoretic microdevice.

Insulator-based dielectrophoresis (iDEP) exploits in-channel hurdles and posts etc. to create electric field gradients for various particle manipulations. However, the presence of such insulating structures also amplifies the Joule heating in the fluid around themselves, leading to both temperature gradients and electrothermal flow. These Joule heating effects have been previously demonstrated to weaken the dielectrophoretic focusing and trapping of microscale and nanoscale particles. We find that the electrothermal flow vortices are able to entrain submicron particles for a localized enrichment near the insulating tips of a ratchet microchannel. This increase in particle concentration is reasonably predicted by a full-scale numerical simulation of the mass transport along with the coupled charge, heat and fluid transport. Our model also predicts the electric current and flow pattern in the fluid with a good agreement with the experimental observations.

Picometer-resolution dual-comb spectroscopy with a free-running fiber laser.

Dual-comb spectroscopy holds the promise as real-time, high-resolution spectroscopy tools. However, in its conventional schemes, the stringent requirement on the coherence between two lasers requires sophisticated control systems. By replacing control electronics with an all-optical dual-comb lasing scheme, a simplified dual-comb spectroscopy scheme is demonstrated using one dual-wavelength, passively mode-locked fiber laser. Pulses with a intracavity-dispersion-determined repetition-frequency difference are shown to have good mutual coherence and stability. Capability to resolve the comb teeth and a picometer-wide optical spectral resolution are demonstrated using a simple data acquisition system. Energy-efficient, free-running fiber lasers with a small comb-tooth-spacing could enable low-cost dual-comb systems.

Hopping Behavior Mediates the Anomalous Confined Diffusion of Nanoparticles in Porous Hydrogels.

Diffusion is an essential means of mass transport in porous materials such as hydrogels, which are appealing in various biomedical applications. Herein, we investigate the diffusive motion of nanoparticles (NPs) in porous hydrogels to provide a microscopic view of confined diffusion. Based on the mean square displacement from particle tracking experiments, we elucidate the anomalous diffusion dynamics of the embedded NPs and reveal the heterogeneous pore structures in hydrogels. The results demonstrate that diffusive NPs can intermittently escape from single pores through void connective pathways and exhibit non-Gaussian displacement probability distribution. We simulate this scenario using the Monte Carlo method and clarify the existence of hopping events in porous diffusion. The resultant anomalous diffusion can be fully depicted by combining the hopping mechanism and the hydrodynamic effect. Our results highlight the hopping behavior through the connective pathways and establish a hybrid model to predict NP transport in porous environments.

Monitoring the Cleanliness of Reusable Surgical Instruments in Central Sterile Supply Department by Adenosine Triphosphate Method.

BACKGROUND: Cleaning is very important in reusable surgical instruments (RSI) reprocessing. The adenosine triphosphate (ATP) method is widely used to assess cleanliness, but few studies focus on using this method on RSIs. OBJECTIVE: To assess the effectiveness of the ATP Bioluminescence Assay for monitoring the cleanliness of RSIs. METHODS: The study was conducted in three central sterile supply departments (CSSD) from 2015 to 2020. Surgical scissors, hemostatic forceps, and other non-lumen instruments were sampled after cleaning. The surface of each instrument was swabbed in a uniform manner, including hinged joints and teeth, and the amount of ATP (amol) was calculated. RESULTS: A total of 871 RSIs were tested, the mean ATP lg (amol) was 2.829 ± 0.539 and the qualified rate was 80.57%. Washer-disinfector cleaning was more efficient than manual cleaning, the mean ATP lg (amol) were 2.776 ± 0.513 and 2.948 ± 0.575, respectively; the qualified rates were 84.97% and 70.59%, respectively. With the time of bare instruments expose to environment increased, the qualified rate was decreased (Ptrend = 0.044). CONCLUSION: ATP levels are stable and repeatable for continuous monitoring of the cleanliness of RSIs. It is a rapid and viable method for assessing the cleanliness of RSIs. Washer-disinfector cleaning is recommended and cleaned instruments should be placed in sterile packaging in good time. HIGHLIGHTS: The ATP method is viable for assessing the cleanliness of RSI in CSSDs.

Nanoparticle translocation across the lung surfactant film regulated by grafting polymers.

Nanoparticle-based pulmonary drug delivery has gained significant attention due to its ease of administration, increased bioavailability, and reduced side effects caused by a high systemic dosage. After being delivered into the deep lung, the inhaled nanoparticles first interact with the lung surfactant lining layer composed of phospholipids and surfactant proteins and then potentially cause the dysfunction of the lung surfactant. Conditioning the surface properties of nanoparticles with grafting polymers to avoid these side effects is of crucial importance to the efficiency and safety of pulmonary drug delivery. Herein, we perform coarse-grained molecular simulations to decipher the involved mechanism responsible for the translocation of the polymer-grafted Au nanoparticles across the lung surfactant film. The simulations illustrate that conditioning of the grafting polymers, including their length, terminal charge, and grafting density, can result in different translocation processes. Based on the energy analysis, we find that these discrepancies in translocation stem from the affinity of the nanoparticles with the lipid tails and heads and their contact with the proteins, which can be tuned by the surface polarity and surface charge of the nanoparticles. We further demonstrate that the interaction between the nanoparticles and the lung surfactant is related to the depletion of the lipids and proteins during translocation, which affects the surface tension of the surfactant film. The change in the surface tension in turn affects the nanoparticle translocation and the collapse of the surfactant film. These results can help understand the adverse effects of the nanoparticles on the lung surfactant film and provide guidance to the design of inhaled nanomedicines for improved permeability and targeting.

Field-Free Isolation of Exosomes from Extracellular Vesicles by Microfluidic Viscoelastic Flows.

Exosomes, molecular cargos secreted by almost all mammalian cells, are considered as promising biomarkers to identify many diseases including cancers. However, the small size of exosomes (30-200 nm) poses serious challenges in their isolation from complex media containing a variety of extracellular vesicles (EVs) of different sizes, especially in small sample volumes. Here we present a viscoelasticity-based microfluidic system to directly separate exosomes from cell culture media or serum in a continuous, size-dependent, and label-free manner. Using a small amount of biocompatible polymer as the additive in the media to control the viscoelastic forces exerted on EVs, we are able to achieve a high separation purity (>90%) and recovery (>80%) of exosomes. The proposed technique may serve as a versatile platform to facilitate exosome analyses in diverse biochemical applications.

A microfluidic fluorous solid-phase extraction chip for purification of amino acids.

An electrokinetically-driven microfluidic chip was developed to realize beads-based solid-phase extraction (SPE) of amino acids. This chip uses a two-level (deep/shallow) poly(dimethylsiloxane) (PDMS) microchannel network to confine the fluorous reversed-phase silica beads within the SPE chamber. The mixture of fluorous tagged and non-tagged amino acids was carried into the fluorous solid-phase extraction (F-SPE) chamber by electrokinetic pumping and was successfully separated and extracted. By adding a reference material to the sample, the extraction efficiency of the eluted fluorous-tagged amino acid was calculated using the detection results from mass spectrometry (MS). The F-SPE microchips showed good reproducibility and efficiency, yielding an average extraction efficiency of 55% with a RSD of 10.6% under the typical experimental conditions.

Effects of graphene oxide nanosheets on the ultrastructure and biophysical properties of the pulmonary surfactant film.

Graphene oxide (GO) is the most common derivative of graphene and has been used in a large range of biomedical applications. Despite considerable progress in understanding its cytotoxicity, its potential inhalation toxicity is still largely unknown. As the pulmonary surfactant (PS) film is the first line of host defense, interaction with the PS film determines the fate of the inhaled nanomaterials and their potential toxicity. Using a coarse-grained molecular dynamics model, we reported, for the first time, a novel mechanism of toxicity caused by the inhaled GO nanosheets. Upon deposition, the GO nanosheets induce pores in the PS film and thus have adverse effects on the ultrastructure and biophysical properties of the PS film. Notably, the pores induced by GO nanosheets result in increasing the compressibility of the PS film, which is an important indication of surfactant inhibition. In vitro experiments have also been conducted to study the interactions between GO and animal-derived natural PS films, qualitatively confirming the simulation results.

A microfluidic tubing method and its application for controlled synthesis of polymeric nanoparticles.

This report describes a straightforward but robust tubing method for connecting polydimethylsiloxane (PDMS) microfluidic devices to external equipment. The interconnection is irreversible and can sustain a pressure of up to 4.5 MPa that is characterized experimentally and theoretically. To demonstrate applications of this high-pressure tubing technique, we fabricate a semicircular microfluidic channel to implement a high-throughput, size-controlled synthesis of poly(lactic-co-glycolic acid) (PLGA) nanoparticles ranging from 55 to 135 nm in diameter. This microfluidic device allows for a total flow rate of 410 mL h(-1), resulting in enhanced convective mixing which can be utilized to precipitate small size nanoparticles with a good dispersion. We expect that this tubing technique would be widely used in microfluidic chips for nanoparticle synthesis, cell manipulation, and potentially nanofluidic applications.

Physicochemical properties of nanoparticles regulate translocation across pulmonary surfactant monolayer and formation of lipoprotein corona.

Interaction with the pulmonary surfactant film, being the first line of host defense, represents the initial bio-nano interaction in the lungs. Such interaction determines the fate of the inhaled nanoparticles and their potential therapeutic or toxicological effect. Despite considerable progress in optimizing physicochemical properties of nanoparticles for improved delivery and targeting, the mechanisms by which inhaled nanoparticles interact with the pulmonary surfactant film are still largely unknown. Here, using combined in vitro and in silico methods, we show how hydrophobicity and surface charge of nanoparticles differentially regulate the translocation and interaction with the pulmonary surfactant film. While hydrophilic nanoparticles generally translocate quickly across the pulmonary surfactant film, a significant portion of hydrophobic nanoparticles are trapped by the surfactant film and encapsulated in lipid protrusions upon film compression. Our results support a novel model of pulmonary surfactant lipoprotein corona associated with inhaled nanoparticles of different physicochemical properties. Our data suggest that the study of pulmonary nanotoxicology and nanoparticle-based pulmonary drug delivery should consider this lipoprotein corona.

A microfluidic origami chip for synthesis of functionalized polymeric nanoparticles.

This report demonstrates a microfluidic origami chip to synthesize monodisperse, doxorubicin-loaded poly(lactic-co-glycolic acid) nanoparticles with diameters of ~100 nm, a size optimized for cellular uptake and anticancer efficacy, but difficult to achieve with existing approaches. This three-dimensional design in a microchannel may allow for the fabrication of polymeric nanoparticles in this size regime with ease.