3 research outputs found
VARIABLE FENESTRATION OF A 3D NANOPRINTED LIVER SINUSOID ON A CHIP
Gemstone Team MICROHere we report a novel strategy for engineering liver sinusoids with designed
fenestrae that yield near uniform microfuidic flow conditions along
the length of the microstructure - capabilities enabled by the use two-photon
direct laser writing (DLW). To better model organ systems, researchers
have increasingly investigated the use of DLW as a promising
means for mimicking both architectures and length scales of physiological
components. DLW-based approaches could enable liver sinusoids to be
recreated in vitro; however, recent efforts to construct permeated tubules
exhibit dramatic decreases in fluid
flow through the pores downstream. To
overcome such issues, here we applied microfluidic circuit theory and in-situ
DLW (isDLW) to manufacture liver sinusoids that included fenestrae with
distinct sizes to better maintain a consistent fenestra-specifi c
flow profi le.
Specifically, fenestrae radii were increased from 0.75 μm to 2.01 μm over
the length of a 510-μm sinusoid. Theoretical results revealed that the
flow
rate through the fenestrae could be more maintained along the length of the
optimized sinusoid versus the unoptimized sinusoid with uniform fenestrae
which results in inconsistent
fluid
flow. Preliminary results revealed successful
isDLW fabrication of the optimized sinusoid, with proof-of-concept
microfluidic
flow demonstrations that suggest that the presented strategy
could benefit numerous biomedical applications. These results suggest the
potential of this design strategy for liver on-a-chip modeling, and given the
numerous anatomical structures similar to the presented fenestrated sinusoid,
this approach could be extended to model additional organ systems
of the body for disease modeling and drug screening
The Use of Minimal RNA Toeholds to Trigger the Activation of Multiple Functionalities
Current work reports the use of single-stranded
RNA toeholds of different lengths to promote the reassociation of
various RNA–DNA hybrids, which results in activation of multiple
split functionalities inside human cells. The process of reassociation
is analyzed and followed with a novel computational multistrand secondary
structure prediction algorithm and various experiments. All of our
previously designed RNA/DNA nanoparticles employed single-stranded
DNA toeholds to initiate reassociation. The use of RNA toeholds is
advantageous because of the simpler design rules, the shorter toeholds,
and the smaller size of the resulting nanoparticles (by up to 120
nucleotides per particle) compared to the same hybrid nanoparticles
with single-stranded DNA toeholds. Moreover, the cotranscriptional
assemblies result in higher yields for hybrid nanoparticles with ssRNA
toeholds