Showing papers by "Deyu Li published in 2015"

Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor

Abstract: The blood-brain barrier (BBB) is a critical structure that serves as the gatekeeper between the central nervous system and the rest of the body. It is the responsibility of the BBB to facilitate the entry of required nutrients into the brain and to exclude potentially harmful compounds; however, this complex structure has remained difficult to model faithfully in vitro. Accurate in vitro models are necessary for understanding how the BBB forms and functions, as well as for evaluating drug and toxin penetration across the barrier. Many previous models have failed to support all the cell types involved in the BBB formation and/or lacked the flow-created shear forces needed for mature tight junction formation. To address these issues and to help establish a more faithful in vitro model of the BBB, we have designed and fabricated a microfluidic device that is comprised of both a vascular chamber and a brain chamber separated by a porous membrane. This design allows for cell-to-cell communication between endothelial cells, astrocytes, and pericytes and independent perfusion of both compartments separated by the membrane. This NeuroVascular Unit (NVU) represents approximately one-millionth of the human brain, and hence, has sufficient cell mass to support a breadth of analytical measurements. The NVU has been validated with both fluorescein isothiocyanate (FITC)-dextran diffusion and transendothelial electrical resistance. The NVU has enabled in vitro modeling of the BBB using all human cell types and sampling effluent from both sides of the barrier.

TDP-43 is intercellularly transmitted across axon terminals

Abstract: Transactive response DNA-binding protein 43 kD (TDP-43) is an aggregation-prone prion-like domain-containing protein and component of pathological intracellular aggregates found in most amyotrophic lateral sclerosis (ALS) patients. TDP-43 oligomers have been postulated to be released and subsequently nucleate TDP-43 oligomerization in recipient cells, which might be the molecular correlate of the systematic symptom spreading observed during ALS progression. We developed a novel protein complementation assay allowing quantification of TDP-43 oligomers in living cells. We demonstrate the exchange of TDP-43 between cell somata and the presence of TDP-43 oligomers in microvesicles/exosomes and show that microvesicular TDP-43 is preferentially taken up by recipient cells where it exerts higher toxicity than free TDP-43. Moreover, studies using microfluidic neuronal cultures suggest both anterograde and retrograde trans-synaptic spreading of TDP-43. Finally, we demonstrate TDP-43 oligomer seeding by TDP-43-containing material derived from both cultured cells and ALS patient brain lysate. Thus, using an innovative detection technique, we provide evidence for preferentially microvesicular uptake as well as both soma-to-soma "horizontal" and bidirectional "vertical" synaptic intercellular transmission and prion-like seeding of TDP-43.

Thermal conductivity of electrospun polyethylene nanofibers

Abstract: We report on the structure-thermal transport property relation of individual polyethylene nanofibers fabricated by electrospinning with different deposition parameters. Measurement results show that the nanofiber thermal conductivity depends on the electric field used in the electrospinning process, with a general trend of higher thermal conductivity for fibers prepared with stronger electric field. Nanofibers produced at a 45 kV electrospinning voltage and a 150 mm needle-collector distance could have a thermal conductivity of up to 9.3 W m−1 K−1, over 20 times higher than the typical bulk value. Micro-Raman characterization suggests that the enhanced thermal conductivity is due to the highly oriented polymer chains and enhanced crystallinity in the electrospun nanofibers.

Stretching Fibroblasts Remodels Fibronectin and Alters Cancer Cell Migration

Abstract: Most investigations of cancer-stroma interactions have focused on biochemical signaling effects, with much less attention being paid to biophysical factors. In this study, we investigated the role of mechanical stimuli on human prostatic fibroblasts using a microfluidic platform that was adapted for our experiments and further developed for both repeatable performance among multiple assays and for compatibility with high-resolution confocal microscopy. Results show that mechanical stretching of normal tissue-associated fibroblasts (NAFs) alters the structure of secreted fibronectin. Specifically, unstretched NAFs deposit and assemble fibronectin in a random, mesh-like arrangement, while stretched NAFs produce matrix with a more organized, linearly aligned structure. Moreover, the stretched NAFs exhibited an enhanced capability for directing co-cultured cancer cell migration in a persistent manner. Furthermore, we show that stretching NAFs triggers complex biochemical signaling events through the observation of increased expression of platelet derived growth factor receptor α (PDGFRα). A comparison of these behaviors with those of cancer-associated fibroblasts (CAFs) indicates that the observed phenotypes of stretched NAFs are similar to those associated with CAFs, suggesting that mechanical stress is a critical factor in NAF activation and CAF genesis.

Experimental evidence of very long intrinsic phonon mean free path along the c-axis of graphite

Abstract: We report on experimental studies of the average phonon mean free path in the c-axis direction of graphite Through systematically measuring the cross-plane thermal conductivity of thin graphite flakes with thickness ranging from 24 nm to 714 nm via a differential three omega method, we demonstrate that the average phonon mean free path in the c-axis direction of graphite is around 200 nm at room temperature, much larger than the commonly believed value of just a few nanometers This study provides direct experimental evidence for the recently projected very long phonon mean free path along the c-axis of graphite

Retina-on-a-chip: a microfluidic platform for point access signaling studies.

Abstract: We report on a microfluidic platform for culture of whole organs or tissue slices with the capability of point access reagent delivery to probe the transport of signaling events. Whole mice retina were maintained for multiple days with negative pressure applied to tightly but gently bind the bottom of the retina to a thin poly-(dimethylsiloxane) membrane, through which twelve 100 μm diameter through-holes served as fluidic access points. Staining with toluidine blue, transport of locally applied cholera toxin beta, and transient response to lipopolysaccharide in the retina demonstrated the capability of the microfluidic platform. The point access fluidic delivery capability could enable new assays in the study of various kinds of excised tissues, including retina.

Phonon Dynamics at Surfaces and Interfaces and Its Implications in Energy Transport in Nanostructured Materials—An opinion Paper

Abstract: Nanoscale thermal transport has attracted considerable attention because of both fundamental scientific interest and important engineering applications. For semiconductors and insulators, energy transport is dominated by phonons, whose behavior at surfaces and interfaces plays a significant role in energy transport processes. In this article, we present opinions on phonon dynamics at surfaces and interfaces and the implications on nanoscale thermal transport. The effects of roughness, bonding strength, coherence, and nanoscale constrictions are discussed. The existence of two specularity parameters at an interface (separate values for transmitted and reflected phonons) and the implications of phonon reflection at free surfaces to the thermal conductance of nearby interfaces are two concepts that have not been previously discussed in the literature. We provide some outlook and potential topics for future studies.

Detection of short single-strand DNA homopolymers with ultrathin Si3N4 nanopores.

Abstract: A series of nanopores with diameters ranging from 2.5 to 63 nm are fabricated on a reduced Si3N4 membrane by focused ion beam and high energy electron beam. Through measuring the blocked ionic currents for DNA strands threading linearly through those solid-state nanopores, it is found that the blockade ionic current is proportional to the square of the hydrodynamic diameter of the DNA strand. With the nanopore diameter reduced to be comparable with that of DNA strands, the hydrodynamic diameter of the DNA becomes smaller, which is attributed to the size confinement effects. The duration time for the linear DNA translocation events increases monotonically with the nanopore length. By comparing the spatial configurations of DNA strands through nanopores with different diameters, it is found that the nanopore with large diameter has enough space to allow the DNA strand to translocate through with complex conformation. With the decrease of the nanopore diameter, the folded part of the DNA is prone to be straightened by the nanopore, which leads to the increase in the occurrence frequency of the linear DNA translocation events. Reducing the diameter of the nanopore to 2.5 nm allows the detection and discrimination of three nucleotide "G" and three nucleotide "T" homopolymer DNA strands based on differences in their physical dimensions.

A microfluidic device for generation of chemical gradients

Abstract: A microfluidic device was developed for generating chemical concentration gradients by integrating PEG-diacrylate (PEGDA) hydrogel separators in a Polydimethylsiloxane (PDMS) chamber. In this device, the linear chemical gradient in the central culture channel is achieved by the diffusion of two side flow streams which are separated by hydrogel separators. Two long serpentine channels feed into a transition zone to balance the pressure of both streams insuring a stable gradient is formed and maintained before it reaches the central culture channel. This device provides a reproducible, controllable, long-term steady and linear chemical concentration gradient without complex supports. Additionally, the concentration gradient can be controlled by varying the hydrogel thickness, thereby changing the amount of diffusion through the hydrogels. This device can be modified to create different chemical gradients for a variety of cell culture applications.

Thermal Conductivity of Individual Electrospun Polymer Nanofibers

Abstract: In this work, the thermal conductivity of individual polyethylene (PE) nanofibers fabricated by electrospinning was experimental measured. Our results show that polyethylene nanofibers can have a thermal conductivity up to 2.6 Wm−1K−1, (more than 9 times higher than the bulk PE value) and that the thermal conductivity is strongly correlated with the electric field intensity used in electrospinning. This, combined with micro-Raman characterization of individual nanofibers, suggests that the enhanced thermal conductivity is due to the high degree of orientation of the polymer chains. The stronger elongational forces experienced by the jet at higher electrospinning voltage result in the formation of nanofibers with a higher degree of molecular orientation. Similar thermal conductivity enhancement is also observed with other polymer nanofibers including polyethylene oxide (PEO), Nylon-6, and polyvinylidene fluoride (PVDF). Collectively, our results indicate that electrospinning could be an effective approach to produce polymer nanofibers with enhanced thermal conductivity.Copyright © 2015 by ASME