IMPROVED MICRO-FLOW REGULATOR FOR DRUG DELIVERY SYSTEMS

P. Cousseau, R. Hirschi, B. Frehner, S. Gamper, D. Maillefer

Debiotech S.A., Av. de Sévelin 28, CH-1004 Lausanne, Switzerland
Email: p.cousseau@debiotech.com, Website: www.debiotech.com

ABSTRACT micromachined flow restrictors have been studied for medical

infusion therapy [2]. The major difference between a flow
restrictor and a pressure compensating flow regulator is that flow
The paper reports on the design, manufacturing, and
restrictors do not compensate the flow rate for pressure variations.
experimental testing of a micromachined pressure compensating
flow regulator. This device was designed to provide a constant
liquid flow rate of 1 ml/hr within a pressure difference of 100 to
600 mbar. At pressures higher than 600 mbar the device is
designed to block the flow, preventing an over-delivery of
medicine. Structural and fluidic simulations were used to design
the geometry of the device before manufacturing. After
manufacturing, over 50 devices have been characterized
experimentally. The experimental results demonstrate the
credibility of the design, the accuracy of the flow rate and the long-
term stability of the device. One application of this device is the
replacement of the flow restrictor in an elastomeric infusion
system, which will increase the accuracy and safety of the drug
delivery system. This pressure compensating flow regulator is
passive, hence it needs no external energy source. The device is
relatively inexpensive to manufacture and is therefore, potentially a
disposable unit in a microfluidic system. Finally, it is small and
lightweight, ideal for portable applications.

INTRODUCTION
Figure 1. Diagram showing the 3-layer architecture of the
A pressure compensating flow regulator maintains a micromachined flow regulation device.
constant flow rate for pressure differences within the operational
pressure range of the device. The work presented in this paper is an
extension of the flow regulator reported at Eurosensors XII [1].
The flow regulator presented here has been independently designed
and manufactured. The flow rate of the realized devices is
approximately twice as accurate as has been previously reported.
Figure 1 shows a diagram of the device’s geometry. The device is
a stack of 3 layers. The center layer is a silicon micromachined
membrane with a through hole in the center. A spiral channel is
micromachined in the bottom layer; the start of the spiral is directly
below the hole in the membrane. This layer has been made from
silicon or glass. The top layer is a micropackaging layer of glass
with inlet and outlet holes ultrasonically drilled. Figures 2 and 3
show photographs of a realized device.
The working principle of the device is as follows: as the
pressure difference across the device increases, the deformation of
the silicon membrane increases which covers more of the channel
beneath the membrane. The increase in channel length, and
therefore flow resistance, balances the increase in pressure and
thus, a constant flow rate is maintained. Changing the depth and
width of the channel alters the flow rate. Changing the thickness of
the membrane modifies the operational pressure range.
Debiotech is interested in developing this technology to
improve the accuracy and safety of drug delivery for elastomeric
drug infusion systems. This is not the first time a micromachined Figure 2. Bottom view of a realized device showing the spiral
device has been proposed for infusion systems. Precision, silicon channel etched in glass.

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Figure 3. Top view of the device showing the top of the silicon
membrane with the outlet connector glued on the bottom left.
DEVICE DESIGN
Before drawing the masks for the device, extensive computer
simulations were performed to establish the appropriate geometry
of the device. Theoretically, the geometry of the device can be
scaled to provide any desirable flow rate, therefore, a target flow
rate of 1 ml/hr was chosen because of its suitability for infusion
drug delivery. Two types of simulations were performed: structural
and fluidic. The structural simulations were used to predict the
radius of contact between the membrane and the channel wafer as a
function of the pressure difference across the device. The fluidic
simulations were used to verify the flow rate through the device for
specific membrane deflections.
The structural simulations were preformed using the
commercially available software package ANSYS, version 5.3. An
axially symmetric model of the membrane was used. The boundary
of the membrane was considered clamped. A pressure was applied
normal to the upper surface of the membrane. This pressure
corresponds to the pressure difference across the whole device.
The channel wafer was modeled by rigid contact elements, i.e., the
membrane deflection was constrained to be less than or equal to the
gap between the membrane and channel wafer. The nonlinear
effects of stress stiffening and geometric nonlinearities were
included in the simulations. For the simulated geometry, it was
found that these nonlinear effects are important, with up to a 25%
difference between the simulated results and a linear analytic
solution. Different mesh densities and different values for the
convergence criteria were used to verify the stability of the
simulated results. The contact radius between the membrane and
the bottom wafer was solved for several different pressures. With
this data the shape of the spiral channel was calculated.
After completing the structural simulations, the deflected shape
of the membrane is known for a given pressure difference and
therefore the complete geometry of the fluidic path of the device is
known. Using this information, a three-dimensional fluidic model
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was created. The CAD software Catia was used to construct the
mesh of the flow path, which included the volume above the
membrane, the through hole in the membrane, the micro-channel,
the space between the bottom of the membrane and the spiral
wafer, and the outlet hole. The program TASCflow was used to
solve the incompressible Navier-Stokes equations for the above
geometry. The fluidic simulations were necessary to verify that the
pressure drop of the device was mainly in the micro-channel and
that there were no other unforeseen large pressure drops, for
example at the small gap where the bottom of the membrane comes
in contact with the channel wafer or through the small through hole
in the membrane. The fluidic simulations showed that the other
pressure drops in the device (excluding the micro-channel)
amounted to less than 2% of the total pressure loss and hence did
not affect the flow rate.
FABRICATION
The flow regulator is a stack of three wafers (Fig. 1). The
central wafer is the silicon membrane made with a three masks
process (shown in Fig. 4). First, the silicon oxide is dry etched
(Fig. 4b) on the bottom in order to pattern the membrane area. A
photolithography step is then processed, followed by dry etching of
the central hole (Fig. 4c) in the membrane. It is important that the
depth of this step be deeper (by at least 15%) than the final
membrane thickness to end with a through hole in the membrane.
After removing the photoresist, the membrane area is patterned by
fluorine-based plasma techniques (Fig. 4d). The upper part is then
processed after an oxide has been grown on the wafer. For this
purpose we pattern (Fig. 4e) the oxide by dry etching, using TMAH
to etch the silicon (Fig. 4f). First, a timed-etch is used to roughly
reach the membrane thickness. Additional small duration etches
were used each followed by measurement to reach a precise
membrane thickness.
For the spiral wafer, we use only a dry etching step (Fig. 5) in
silicon. The purpose is to pattern a spiral channel. And we chose
plasma etching in order to keep a maximum design freedom. The
oxide layer is removed from both silicon wafers (membrane and
spiral) that are then bonded together (Fig. 5c) using Silicon-Direct-
Bonding. The alignment accuracy is ±5 µ m in order to guarantee
that the through hole in the membrane is directly above the start of
the micro-channel. The top wafer is in fact only a Pyrex wafer with
the inlet and outlet holes drilled by ultrasound, which is bonded to
the stack of membrane and spiral wafers using anodic bonding.
The Pyrex wafer allows for metallic fluid connects to be glued
directly onto the device. The majority of the wafer processing for
these devices was done at microFAB in Bremen, Germany;
additional processing was done at the CMI (Center of
Microtechnology) at the EPFL (Swiss Federal Institute of
Technology) in Lausanne, Switzerland.
EXPERIMENTAL RESULTS
Several different batches of devices with different membrane
thicknesses and channel profiles have been realized. Over 50
devices have been characterized experimentally. For measuring the
flow rate of the device as a function of pressure, the gravimetric
method was used. The standard test setup consist of a bottle of
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application, a small membrane filter can be included in the system
or an on-chip particle filter can be added to the device, for example
the particle filter reported in MEMS-99 [3].
Figure 7. Comparison of the flow rate from a pressure
compensating flow regulator (nominal flow rate of 1.3 ml/hr) and a
flow restrictor for a sinusoidal pressure between 200 and 400 mbar
with a period of 300 s.
Figure 8. Long-term stability of the flow rate of the flow
regulator (nominal flow rate of 0.54 ml/hr) over a 26 day period.
If a valve is placed in series with the flow regulator, then a
dosing system independent of the reservoir pressure is created.
Figure 9 shows the amount of liquid dosed when the valve is open
for 100 s for different pressures. Within the operating pressure
range of the flow regulator, the amount of liquid dosed is
independent of pressure. This is not the case when a flow restrictor
is used; the amount of liquid dosed varies linearly with pressure.
Using this system, a lightweight portable dosing system can be
realized which dispenses a predicable volume of liquid without the
need to measure the pressure in the reservoir or the outlet flow rate
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Figure 9. Comparison of the amount of liquid dosed in 100 s
between a pressure compensating flow regulator and a flow
restrictor for different reservoir pressures.
CONCLUSIONS
This paper has presented a realized and fully operational
microfluidic pressure compensating flow regulator. It has been
demonstrated that this device maintains a constant flow rate for
pressures between 200 and 500 mbar. Also, the long-term stability
of the device has been demonstrated by 26 days of continuous
operation with no degradation of the flow rate. The device can be
used with a valve for liquid dosing applications. Also, the valve
could be duty cycled to generate a variable flow rate device. In the
future, manufacturing the device in plastic and reducing the size in
silicon will be studied. It is believed that flow regulators could
potentially have a place next to microvalves, channels, mixers and
pumps in µTas applications and drug delivery systems, especially
portable devices, which would benefit from the lightweight and
small size. Debiotech is interested in using this micromachined
flow regulator to replace the less accurate conventional glass
capillary flow restrictors used in portable elastomeric drug infusion
systems
REFERENCES
[1] Ch. Amacker, Y.-S. Leungki, V. Pasquier, Ch. Madore, M.
Haller, and Ph. Renaud, “Passive Micro-Flow Regulator for
Drug Delivery System”, Proceedings of Eurosensors XII,
September 13-16, 1998, pp. 591-594.
[2] J. Drake, and H. Jerman, “A Precision Flow Restrictor for
Medical Infusion Therapy”, Proceeding of the 8th International
Conference on Solid-State Sensors and Actuators and
Eurosensors IX, Stockholm, Sweden, June 25-29, 1995, pp.
373-376.
[3] D. Maillefer, H. van Lintel, G. Rey-Mermet, and R. Hirschi, “A
High-Performance Silicon Micropump for an Implantable Drug
Delivery System”, Proceedings of the 12th IEEE Internal
Conference on Micro Electro Mechanical Systems, Orlando,
Florida, USA, January 17-21, 1999, pp. 541-546.