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Technical Program TRACK 3

of active and passive components that not only remove all backflow but larized liver and cardiac platforms to assess the interaction of fluorescently
also allows for control over dispersed volume. labeled nanoparticles and chemotherapies (cisplatin, doxorubicin) with the
endothelium in these models as well as the transport and biodistribution of
A passive microfluidic rectifier in the shape of a triangle with a base of 198 particles through these systems independently and in an integrated, plug-N-
micrometers and a height of 210 micrometers and an active microfluidic rec- play fashion. Using our high-resolution confocal imaging system, we imaged
tifier along with three consecutive microfluidic valves were fabricated using long-term growth of cells in each tissue platform (tumor, liver, heart) and the
soft lithography technique. Two polydimethylsiloxane (PDMS) layers, which effects of cell seeding density, cell composition (co-cultures of various cell
are pneumatic and fluidic structures, were designed and manufactured types), matrix composition, and flow conditions on the growth and remodel-
with 10:1 PDMS and then these layers were bonded after an oxygen plasma ing of each tissue platform.
treatment. As a final step, this assembled PDMS structure was bonded on an
oxygen plasma treated glass slide. Pneumatic actuation of lifting gate struc- Results: Cell growth and behavior were assessed, using a combination
tures was used to create pulsatile flow and a diodic pump with differential of fluorescently labeled cells and membrane and nuclear staining (DAPI,
voltage control supplied pneumatic actuation to the active rectifier. A flow calceinAM), following perfusion of chemotherapeutic drugs, at clinically
sensor was used to generate flow profiles of each micropump and rectifier relevant dosages, through each collagen platform. Real-time confocal im-
structure. aging recorded the distribution of fluorescent nanoparticles in each tissue
compartment, focusing specifically on the effect of tumor cells on increasing
This microfluidic rectifier was then tested under various pulsatile flow con- the permeability of the endothelium, and aggregation of particles in the
ditions which were generated by the three microfluidic valves. Different endothelium and surrounding tissues, dependent on the properties of each
pressures which were used to optimize flow patterns and characterization. individual tissue platform. Using our plug-N-play format, we observed the
Outflow profiles from the microfluidic rectifier were then compared with the time-lapse biodistribution of labeled nanoparticles flowing through each of
output profiles which were obtained from the microfluidic channel without the three vascularized tissue compartments in series.
the rectifier structure. Flow data that was collected from both was compared
after normalization. Decrease in backflow was observed when using the flu-
idic diode. When flow profiles were generated backflow in the straight chan- 3-3
nel was 40.00% out of total volumetric flow per cycle. The passive rectifier
was able to reduce the backflow to 25.34% out of total volumetric flow, and DETECTION SYSTEMS
with the addition of the active microfluidic rectifier there was no backflow on
the pulsatile flow profile. Using this microfluidic rectifier, a droplet generation Navarro 11:30 AM - 1:00 PM
requiring a continuous forward flow was demonstrated and quality of drops
were characterized by measuring polydispersity index. By comparison of
this index, we found that the index from the microfluidic rectifier show a sim- Session Organizer: Gabe Kwong, Georgia Tech, Atlanta, GA, United
ilar index from the index acquired from syringe pump based droplet genera- States
tor. This microfluidic rectifier can be used in any fluidic system requiring zero
backflow, which can be a substitute for syringe pumps. This zero backflow 11:30am Microfluidics for Digital Biological Measurements
platform can also be used for a portable droplet generator which would sim-
plify the complexity of current droplet platforms.
Keynote. NEMB2016-6138

12:40pm 3D Integrated Vascularized Tumor, Liver, and Heart Mi-
crofluidic Platforms for In Vitro Transport and Toxicity Studies Daniel Chiu, University of Washington, Seattle, WA, United States

Digital measurements report the presence and activity of the individual
Technical Presentation. NEMB2016-6126 building blocks of biological systems, such as individual molecules and sin-
gle cells. This presentation describes microfluidic devices and instruments
Jeehyun Park, Nichole Rylander, University of Texas at Austin, we have developed for carrying out digital biological measurements. As one
Austin, TX, United States example, this presentation will describe a simple and robust microfluidic de-
vice for digitizing samples into a large array of discrete volumes for carrying
Introduction: Chemotherapeutic drug development typically involves the use out digital PCR. An another example, I will discuss a platform we developed
of 2D in vitro cell cultures or in vivo animal models. 2D models are insuffi- for isolated single rare cells from peripheral blood, which we have employed
cient for studying cell response to therapies, as cell cultures in 3D matrices for isolating circulating tumor cells from peripheral blood of cancer patients.
have shown decreased responses to drugs compared to similar 2D dos-
ages, and the incorporation of altered intratumoral flow conditions further 12:00pm Mathematical framework for activity-based biomarkers
decreases uptake and efficacy. Though animal models provide more physi-
ologically accurate environments for toxicity studies, the sheer volume of an- Technical Presentation. NEMB2016-6007
imal specimens required for validation can quickly become cost-prohibitive.
3D in vitro platforms overcome these issues by recreating physiologically Gabe Kwong, Georgia Tech, Atlanta, GA, United States, Jaideep
relevant cell microenvironments for cost-effective, high throughput drug
screening capability. Chemotherapy development and dose optimization Dudani, Emmanuel Carrodeguas, Eric Mazumdar, Seyedeh M.
must also include drug effects on and interactions with the endothelium, me- Zekavat, MIT, Cambridge, MA, United States, Sangeeta Bhatia,
tabolism by the liver, and toxicity in the liver and the heart. Certain therapies Koch Institute/Mit, Cambridge, MA, United States
require activation by metabolism in the liver, and combination liver-tumor
microfluidic platforms are needed to assess the effects of chemotherapeutic Advances in nanomedicine are providing sophisticated functions to precise-
drugs post-liver metabolism. ly control the behavior of nanoscale drugs and diagnostics. Strategies that
coopt protease activity as molecular triggers are increasingly important in
Methods: The Rylander group has designed and validated a 3D vascularized nanoparticle design, yet the pharmacokinetics of these systems are chal-
microfluidic platform mimicking the breast tumor microenvironment using lenging to understand without a quantitative framework to reveal nonintui-
type I collagen from rat tails to study nanoparticle transport and therapeutic tive associations. We describe a multicompartment mathematical model to
efficacy. Each platform was cultured in FEP tubing implementing a subtrac- predict strategies for ultrasensitive detection of cancer using synthetic bio-
tive needle method to form vasculature. Endothelial cells were seeded in markers, a class of activity-based probes that amplify cancer-derived signals
34 the resulting channels, and flow protocols optimized by the Rylander group into urine as a noninvasive diagnostic. Using a model formulation made of a
were used to induce formation of a confluent endothelial layer around the PEG core conjugated with protease-cleavable peptides, we explore a vast
channels. We have adapted this tumor platform to create microfluidic vascu- design space and identify guidelines for increasing sensitivity that depend