Properly simulating an in vivo biological environment in vitro generally leads to increased clinical trial
success and more rapid access to effective treatments. Microfluidics are a primary means of simulating
biological environments in clinical and pharmaceutical laboratory research; however, the current utility of
microfluidics is limited by materials and manufacturing challenges. Additive manufacturing (3D printing) has
been heralded as the solution to these challenges, but it also faces hurdles, such as a relatively large
minimum feature size and difficulty in removing excess build material from internal passages. Additive
manufacturing has the potential to build complex, 3D, bio-mimicking structures and solve key challenges in
microfluidics such as fabricating efficient mixing elements, incorporating of membranes or electrodes,
providing integrated valving, and simplifying the connection between the micro-and macro-scales.
However, the most promising and widely used material in microfluidics, PDMS, is currently not available for
additive manufacturing. Phase, Inc. has developed a proprietary additive manufacturing technology termed
electric field fabrication (EFF) based on liquid dielectrophoresis that shapes uncured PDMS into prescribed
cross-sections which can be cured and bonded in succession to build a 3D microfluidic device. As opposed
to other 3DP modalities, our patented approach offers unique control over the 3D printing process, opening
the door to print new materials such as elastomerics with unprecedented resolution and no post-
processing. This technology offers the potential to increase the design space of PDMS microfluidics to
more closely match the in vivo environment enabling future advances in technologies such as organ-on-a-
chip. Commercialization of an additive manufacturing platform for complex 3D PDMS microfluidic devices
will enable broad access to 3D bio-mimicking structures which result in more effective treatments. The
microfluidics market is now valued at $14 billion and is expected to grow to $31 billion by 2027. PDMS
based products make up approximately 30% of the microfluidics market—the largest share of the market.
The proposed Phase I effort will further enhance the fidelity of the EFF process for additively manufacturing
PDMS devices through refinement of the overall platform and specifically address two aims which are
foundational to the commercial viability of the process. The Phase I effort will 1) demonstrate the functional
performance of a representative device and 2) demonstrate the ability to successfully incorporate a
membrane into a microfluidic device.
The aims of this Phase 1 SBIR proposal are to:
Aim 1. Fabricate a representative 3D microfluidic device in PDMS. To demonstrate the broad ranging utility
of the EFF process, a representative microfluid device will be fabricated in PDMS with two inlets, a passive
mixing element, an observation/measurement channel and an outlet. Successful demonstration of
additively manufacturing these basic microfluidic building blocks in a PDMS device will be the launching
point for fabrication of specific devices for trial studies and further commercialization.
Aim 2. Fabricate a PDMS device with an integrated track-etched membrane for simulation of the blood
brain barrier. Incorporation of membranes, electrodes and other elements in PDMS is key to building
functionality into microfluidic devices and is a key feature of EFF. Our additively manufactured model will be
comprised of brain endothelial cells cultured on a porous membrane (polyester track etch membrane, pores
0.4 µm) sandwiched between two additively manufactured PDMS layers. Human cerebral endothelial cells
(hCMEC/D3) will be used, as these cells have been demonstrated to recapitulate key phenotypic
characteristics of the BBB such as permeability, expression of junctional proteins and transendothelial
electrical resistance. Physiological shear stress will be applied on the cells by flow (~4 Dyn/cm2) to
encourage tight junction formation. Demonstration of the blood brain barrier device in Phase I will be
followed in Phase II with development of an advanced device.
Project summary/abstract