IN-PLANE BANDPASS REGULATION CHECK VALVE IN HEAT-SHRINK
PACKAGING FOR DRUG DELIVERY
R. Lo and E. Meng
University of Southern California, Los Angeles, California, USA
ABSTRACT
The first check valve featuring dual regulation of in-
plane flow and heat-shrink tubing packaging is presented.
This modular design is optimized for integration into low-
profile fluidic devices requiring flow control, such as drug
delivery devices. Theoretical and finite-element-
modeling (FEM) analyses were performed to guide valve
design and these results were confirmed experimentally.
The valve regulates flow between 150-900 mmHg (20-
120 kPa) and withstands >500 mmHg (66.7 kPa) of
reverse pressure. The heat-shrink packaging scheme does
not require adhesives and is extremely robust (>2000
mmHg without leakage).
INTRODUCTION
The out-of-plane orientation of typical MEMS check
valves can complicate the process of fluidic packaging.
We previously presented an ocular drug delivery device
with a simple check valve [1]. The device comprised a
drug reservoir for storage of pharmaceutical solutions, a
flexible cannula for directed delivery to diseased tissues,
and a flow regulating check valve integrated at the tip of
the cannula. This check valve prevented bodily fluids
from backflowing into the drug reservoir but lacked over-
pressure protection to prevent accidental dosing. Also, its
out-of-plane orientation could result in contact with
tissues limiting its practical in vivo implementation.
Furthermore, the valve was integrated into a cannula
having rectangular geometry which prevented tight seals
with the tissue at the incision site after suturing.
Thus, we propose a new modular valve paradigm that
incorporates both a pressure limiting safety feature and
surgically-friendly medical grade heat-shrink tubing
packaging scheme. The round heat-shrink tubing is also
the durg delivery cannula (Figure :1). This valve
paradigm is easily adapted for use in other microfluidic
systems.
Figure :1 Surgical model of a MEMS ocular drug delivery
device featuring a valve packaged in a biocompatible
heat-shrink tube. The valve is comprised of four modular
components (inset): valve seat, pressure responsive valve
plate, a spacer, and pressure limiter.
DESIGN
The modular valve consists of four stacked disks:
valve seat, pressure responsive valve plate, spacer plate,
and pressure limiter (Figure 2).
Figure 2: Photo of the valve components (valve seat,
valve plate, spacer plate, and pressure limiter), heat–
shrink tube, and fully assembled valve (ruler divisions = 1
mm)
The valve operates in a manner analogous to a
bandpass filter and allows fluid flow when the forward
pressure exceeds the valve cracking pressure; flow ceases
when the closing pressure is reached. A SU-8 spacer plate
defines the distance between the movable valve plate and
pressure limiter plate and thus the operating pressure
range (opening and closing pressures). Valve components
are stacked together and packaged into a biocompatible
22G fluorinated ethylene propylene (FEP) heat-shrink
tube (Figure 3). The circular tube facilitates incision/tube
sealing with sutures. This packaging method is extremely
robust and does not require any adhesives.
Figure 3: a) Side view and b) top view of the packaged
valve in FEP heat-shrink tube. The valve was placed
inside the tube utilizing a custom-made jig and then
heated to 215 ºC at 1.5 ºC/min, and cooled at the same
rate to room temperature.
The valve dimensions were selected to meet the
surgical requirements; a 1 mm incision is permitted to
insert the cannula/valve. Therefore, a 900 μm diameter
valve was chosen leaving 100 μm for the packaging. The
thickness of the spacer and valve plates was determined
by FEM analysis and using the relationship governing
large-deflections in a flexible plate of uniform thickness
(eq. 1,2). Maximum deflection (w
max
) can be calculated
from plate thickness (t), applied pressure (p), plate radius
978-1-4244-2978-3/09/$25.00 ©2009 IEEE 236
(a), and flexural rigidity (D). Flexural rigidity is a
function of Young’s modulus (E), plate thickness (t), and
Poisson’s ratio (υ) [2].
D
pa
t
w
w
64
)486.01(
4
2
max
2
max
=+
(1)
)1(12
2
3
υ
−
=
Et
D
(2)
Three different valve plate designs (hole, straight
arm, and s-shape arm) were investigated (Figure 4). Each
design yielded different deflection behaviors and thus
differing bandpass flow regulating characteristics (e.g.
opening and closing pressure and flow resistance). FEM
estimations and theoretical analyses were used to assign
valve geometries such that the operational pressure range
would be limited at the lower bound by normal intraocular
pressure (IOP), <35 mmHg (4.67kPa), and an upper
bound of 1000 mmHg (133.3kPa) (Table 1).
Figure 4: Three different valve plate designs a) hole, b)
straight arm, and c) s-shape arm.
Table 1: Dimensions of valve components, including the
three valve designs (hole, straight arm, s-shape arm). All
components are 900
μ
m in diameter.
Valve
Seat/
Pressure
Limiter
Hole
Valve
Plate
Straight
Arm
Valve
Plate
S-Shape
Arm
Valve
Plate
Spacer
Plate
Material
SU-8
MDX4-
4210
MDX4-
4210
MDX4-
4210
SU-8
Thickness
[µm]
200 75 75 75 40
FABRICATION
SU-8 Valve Seat and Pressure Limiter
The SU-8 valve seat and SU-8 pressure limiter were
fabricated using a two-layer SU-8 process (Figure 5).
First, a soda-lime wafer (Mark Optics, Santa Ana, CA)
was pretreated with Omnicoat (MicroChem, Newton,
MA), a SU-8 release layer. Three layers of Omnicoat
were applied (3000 rpm, 30 sec) with a bake step (1 min
at 200 ºC) performed after each coat (Figure 5a). Three
coats facilitated component release from the substrate;
these extra layers of Omnicoat resulted in a reduction in
the time and temperature necessary to release the SU-8. A
160 μm layer of SU-8 2100 (MicroChem, Newton, MA)
formed the base section (Figure 5b,c). A 40 μm layer was
added to form the features in the valve seat and pressure
limiter (Figure 5d-f). The wafer was immersed in
Remover PG (MicroChem, Newton, MA) for 5 minutes to
separate the SU-8 components from the wafer (Figure 5g).
The components were rinsed (IPA and DI H
2
O) and then
hardbaked at 215 ºC for 1 hour. This final step annealed
the SU-8 components to improve thermal resistance for
the subsequent heat-shrink packaging process.
Figure 5: Fabrication process for the valve seat and
pressure limiter plates.
SU-8 Spacer
The 40 μm thick spacer plate was also fabricated on
an Omnicoat-coated soda lime wafer using SU-9 2050
(Figure 6a-d). Spacer plates were released from the
substrate using Remover PG and rinsed using IPA and DI
H
2
O (Figure 6e).
Figure 6: Fabrication process for the SU-8 spacer plate.
Valve Plate
The valve plate was fabricated by casting medical
grade silicone (MDX4-4210, Dow Corning, Midland, MI)
against a SU-8 master. The SU-8 master was created on a
soda lime wafer using SU-8 2050. 4 μm of Parylene C
(Specialty Coating Systems, Inc., Indianapolis, IN) was
vapor deposited onto the wafer to prevent the SU-8 from
delaminating from the wafer due to thermal mismatch
with the substrate [3]. A 75 μm layer of SU-8 2050
defined the valve plate thickness (Figure 7a-c). MDX4-
4210 (10:1 base to curing agent ratio), was poured onto
the mold and degassed under vacuum. Excess silicone
was removed with a metal squeegee (Figure 7d) [4]. The
silicone was cured at room temperature for 48 hours to
minimize shrinkage. Then valve plates where separated
from the mold (Figure 7e).
Figure 7: Fabrication process for the valve plate using an
SU-8 master mold.
Valve Packaging in Heat-Shrink Tubing
The valve was packaged in the heat-shrink tubing
using a custom-made Teflon jig with a stainless steel post
(813 μm diameter). A 22G (inner diameter prior to
shrinkage: 914.4 μm, maximum wall thickness: 254 μm)
1.3:1 shrink ratio FEP heat-shrink tube (Zeus Industrial
Products Inc., Orangeburg, SC) was placed around the
post followed by the four valve components (valve seat,
valve plate, spacer plate, pressure limiter) (Figure 8a). A
second Teflon block with a matching and adjustable
stainless steel post was aligned and secured such that the
two posts held the valve assembly in place while the FEP
237
tubing was slipped it (Figure 8b). The entire jig was
placed in an oven and heated to 215 ºC at a rate of 1.5
ºC/min; baked for 30 minutes, and then cooled to room
temperature at the same rate to limit the thermally induced
stress on SU-8 (Figure 8c). The jig was disassembled and
the packaged valve was removed from the posts (Figure
8d).
The final outer diameter of the valve and packaging
was 1.23 ± 0.004 μm (n=7, mean ± SE); while the outer
diameter of the tube surrounding the valve was 1.04 ±
0.006 μm (n=21, mean ± SE). The post size was chosen
to provide the largest possible surface area on which to
balance the valve, however the final dimension for the
tube outer diameter was limited by the stainless steel post.
Figure 8: Process for packaging valve in heat-shrink
tubing.
EXPERIMENTS AND RESULTS
Valve Plate Deflection and Stress Analysis
Valve plate deflection and stress distribution for
various stages of valve operation were modeled using
FEM analysis (Figure 9). These stages include the valve
at rest, opening under application of forward pressure, and
closure at higher forward pressures.
Figure 9: FEM images of valve plate deflection under a)
negligible forward pressure, b) 100 mmHg, c) 500 mmHg,
and d) 10000 mmHg (used to visually exaggerate the
valve closing mechanism). Forces between the valve seat
and plate were not modeled; therefore the valve opened
for any non-zero applied forward pressure.
Under forward applied pressure (1000 mmHg, 133.3
kPa), the maximum stress on the valve plate (0.99 MPa)
was concentrated at the outer edge of contact with the
valve seat. The stress was <20% of MDX4-4210 tensile
strength (5 MPa) and significantly less than the tensile
strength of SU-8 (60 MPa). Reverse pressure (500
mmHg, 66.7 kPa) analysis verified the stress on the valve
(0.46 MPa) was at least an order of magnitude less than
the tensile stress of MDX4-4210 or SU-8 (Figure 10b).
Additionally, the valve plate deflected <7 μm under
reverse pressure, maintaining an effective seal between
the valve plate and valve seat (Figure 10b). Normal IOP
ranges are 5-35 mmHg (4.67 kPa), thus the valve can
withstand reverse pressure conditions greater than 10
times the IOP without failing.
Figure 10: FEM analysis of 500 mmHg reverse pressure
on the assembled valve. a) Maximum stress (0.46 MPa)
was significantly lower than the tensile stress of the valve
materials. b) Deflection of the valve plate was <7µm.
The deflection for each valve plate design under
increasing forward pressure was measured using a
microscope. The valve plate was clamped along the outer
edge and pressurized air was applied to the plate. The
results were compared to the theory (large deflection
equations of a clamped membrane with uniform thickness
(eq. 1, 2)) (Figure 11).
Figure 11: Comparison of calculated valve deflection
values using theoretical equations versus experimentally
obtained values for all three designs (n=4, mean ± SE).
As expected, the hole and straight arm valves had
similar performance while the s-shaped arm valve had the
greatest deflection [5]. The s-shaped tethers allow the
valve plate to twist as it deflects away from the valve seat.
Furthermore, the s-shape arm valve presents less fluidic
resistance than the other two designs.
Heat-Shrink Tubing Packaging Method
The biocompatible heat-shrink tubing provides an
extremely robust package and eliminates the use of
adhesives [6, 7]. To ensure even shrinkage and prevent
cracking, the tube is uniformly heated and cooled to/from
215 ºC (1.5 ºC/min) and room temperature in a digitally-
controlled oven (Model VO914A, Lindberg/ Blue,
Asheville, NC).
To quantify the fluidic integrity of this packaging
method, a solid 200 μm thick SU-8 disk with the same
diameter as the valve (900 μm) was packaged in heat-
shrink tubing. Pressurized water was applied through the
heat-shrink tubing to one side of the packaged SU-8 disk.
A 100 μL calibrated pipette (Clay Adams, Parsippany, NJ,
USA) was placed at the outlet to measure leakage of water
between the disk and heat-shrink tubing. The disk
remained in its packaged position and the entire system
was leak-tight up to 2000 mmHg (266.6 kPa) which is the
pressure limit of our testing apparatus. Pressurized N
2
gas
was applied to the system, with the tubing outlet
immersed in water to visualize any bubbles due to
238
leakage. The packaged system was also able to withstand
up to 2000 mmHg (266.6 kPa).
Valve Operation
The behavior of a packaged valve (hole valve plate)
was determined using a custom-made jig and pressure
system. Pressurized water (0-1000 mmHg, 0-133.3 kPa)
was applied in incremental steps to the valve inlet. The
flow rate from the packaged valve was measured using a
100 μL calibrated pipette placed at the valve outlet. The
system was held at each test pressure set point for 5
minutes to allow the system to equilibrate.
The valve cracking pressure was 150 mmHg (20 kPa)
and closed at a pressure of 900 mmHg (120 kPa) for the
hole valve plate design (Figure 12). Minimal leakage, less
than 18 times peak flow, was observed after valve closure.
The valve was able to withstand reverse pressures in
excess of 500 mmHg (66.7 kPa) without leaking. The
valve operating range is much greater than normal and
abnormal IOP values, preventing the valve from opening
due to normal eye pressures or transient fluctuations (e.g.
as a result of flying or sneezing).
Figure 12: Bandpass regulation of fluid flow was verified
on a packaged valve (hole valve plate). Pressurized DI
water was applied to the inlet of a package valve and flow
rate was measured using a 100 µL calibrated pipette.
CONCLUSION
A bandpass regulation, in-plane check valve
packaged within biocompatible heat-shrink tubing without
the use of adhesives is presented. The valve achieved
bandpass regulation of pressurized water with a cracking
pressure of 150 mmHg (20 kPa) and closing pressure of
900 mmHg (120 kPa). The valve was able to withstand a
reverse pressure of 500 mmHg (66.7 kPa) without
leaking. The package is very robust and can withstand
water and N
2
gas pressures in excess of 2000 mmHg
(266.6 kPa). Packaged valves were incorporated into a
surgical model of the drug delivery device (made of
MDX4-4210 with a stainless steel ring and PEEK
baseplate) that will be used for ex vivo and in vivo
validation of valve operation (Figure 13).
Figure 13: The valve was incorporated into a surgical
model containing a drug reservoir for in vivo testing
(ruler divisions = 1 mm). The valve is modular and easily
replaced with another valve.
ACKNOWLEDGEMENTS
This work was funded by the NIH/NEI under award
number R21EY018490. The authors would like to thank
Dr. Donghai Zhu, Benjamin Lee, and the members of the
USC Biomedical Microsystems Laboratory for their
assistance with this project.
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