2005 TexMEMS, VII International Conference on Micro Electro Mechanical Systems, Sept. 21-22, 2005.

El Paso, TX, USA and Ciudad Jurez, Mexico.

MEMS-based Implantable Drug Delivery System

Smitha M. N. Rao, Amit Mhatre, Dan O. Popa, J. -C. Chiao, Thermpon Ativanichayaphong,
Jeongsik Sin, Harry E. Stephanou
Automation & Robotics Research Institute
The University of Texas at Arlington, Arlington, Texas
Email: smitha@arri.uta.edu

Abstract Implantable devices are currently used regularly for

chronic pain relief, cardiac pacemakers, arterial infusion for cancer
and insulin delivery. A MEMS based implantable drug delivery
system (IDDS) integrating a subcutaneous reservoir, an in plane
silicon pump and associated circuitry for local or centralized
delivery of therapeutic agents for chemotherapy is proposed.
System configurations, flow rate analysis and applications are
presented. There are many advantages to the MEMS based IDDS
employing the well established techniques of intravenous therapy.
The reservoir can be customized providing flexibility. This
combined with the small size of the pump provides workable
solution for implantable drug delivery systems. Telemetry allows
wireless monitoring and control of the drug flow rate, reservoir
levels and battery recharging. The flow rate capability of the pump
is evaluated in the presence of venous pressure. A combination of
finite element analysis and lumped model approximations show
that the average flow rates up to 85 l/min are achievable.
I. INTRODUCTION
In recent years there has been an increased effort to improve
the efficiency of drug delivery. It is estimated that demand for
drug delivery systems will grow nine percent annually through
2007 in United States alone [1]. Although controlled release pills
remain the single most dominant drug delivery method, there has
been an increased interest in miniature drug delivery systems for
delivery of hormones, anticancer agents and vaccines. Rapid
advances in medicine call for rapid changes in drug delivery
mechanisms. Lower side effects, effective drug delivery, ease of
use, lower cost and maintenance and patient comfort assume
highest priority. Pumps are routinely used in drug infusion. The
types of pumps explored in the past are Peristaltic, Osmotic and
Pneumatic pumps [2-4]. Peristaltic pumps are employed in
biomedical applications, since the fluid path is completely
isolated from the electrical path and is free of any form of
contamination due to interaction with the pump components. Our
goal is to realize these requirements with a MEMS-based
Implantable Drug Delivery System.
II. IDDS COMPONENTS
The IDDS is composed of (a) micropump (b) reservoir (c)
delivery assembly (d) electronic circuitry and (e) power
management as shown in Fig. 1. A catheter delivers controlled
doses of drug from the micropump output to the target vein.
Power module
Electronics
RF Module
Micropump
Figure 1. Implantable drug delivery system module
A. Micropump
The micropump is an on-demand active device that can be
electrically controlled to deliver specific volumes of therapeutic
agents. The micropump provides the driving mechanism to
deliver the drug from the reservoir to the catheter. The
requirements for drug delivery include a minimum flow rate in
the order of 10l per minute or more, small size and high
reliability. The IDDS should be capable of delivering drugs
against a back pressure of blood in the range of 8mmHg to
12mmHg in the veins or greater than 120mmHg in the arteries.
The IDDS uses an in-plane silicon pump fabricated from
silicon-on-insulator (SOI) wafer using deep reactive ion etching
(DRIE) process.
1) Fabrication
In contrast to traditional peristaltic micropump designs [5-8],
which use an out-of plane pumping diaphragm, we fabricate the
actuators, diaphragms, reservoir and I/O fluidic valves in a single
layer.
The micropump is a DRIE machined monolithic structure
fabricated on 4 inch 100 m SOI wafer. The functional modules
of the micropump such as actuator, stoke amplifier, diaphragm
and valves are all fabricated on a single layer by a single
fabrication step. Joule heating of the V-beams and lever
mechanism amplifies the stroke of the pump. The fluidic path is
enclosed by anodic bonding of a Pyrex glass to the pump die.
The size of the actuator is 12x100x1200 m with a rib angle of
5.7o [9]. Preliminary experiments performed to characterize the
actuation of the pump show diaphragm deflection of 30 m at 12
V corresponding to a pumping volume in the range of 3.6 ~ 12.6
nl and compression ratio of 3.5 [9].
 An in plane micropump design reduces the fabrication time
and complexity and offers advantages of embedded actuation.
Figure 2. Micropump fabricated on a 100 m SOI wafer by DRIE
B. Reservoir
The reservoir plays an important role in determining the size
of the implantable device. Our reservoir is similar in design to the
vascular access ports. These ports have been demonstrated to
have good bio-stability and bio-compatibility [10]. The reservoir
should have smooth contours, hold at least 5 ml of the drug and
be easily accessible for refilling. A subcutaneous position for the
port-like reservoir is targeted for the IDDS. The size of the
reservoir can be varied based on need at the same time retaining
the size of the pump. For reasons of biocompatibility, Titanium
and Silicone reservoir will be used. It must be noted that there is
no set dosage for continuous infusion for Chemotherapy. The
dosage, infusion rate and drug combination is varied depending
on the type of cancer, patient response to treatment and the
experience of the oncologist.
C. Delivery assembly
The method of delivery can affect efficacy and extent of the
side effects. Some studies suggest that delivery alone can
improve effectiveness by over 10%. Chemotherapeutic chemicals
have a half life that indicates the time period over which the drug
needs to be infused. This imposes a limit on the rate of infusion
in the drug delivery mechanism. For localized drug delivery, the
output of the pump needs to overcome higher pressure; however
the size of the reservoir can be smaller since concentrated drug
dosages can be employed.
For centralized drug delivery the reservoir is to be slightly
larger. Injecting the drug in a concentrated form into the
circulatory system is known to induce cardiac arrest and organ
failures.
Generally, all drugs are diluted with saline before infusion.
The dilution is accounted for in the drug flow rate to meet the
requirements for delivering the appropriate drug dosages. Low
dose of Heparin is injected through the infusion system to
improve drug delivery by preventing blood clots.
There is a demand for localized delivery of drug that is
minimally invasive. In localized delivery, a small area is exposed
to the drug minimizing damage to healthy cells and tissue. Care
should be taken to prevent hemorrhaging and clots.
The central idea of the MEMS IDDS is to utilize the well
established principles of intravenous therapy (IV) to deliver drug.
The reservoir, pump, catheter and associated circuitry will mimic
the intravenous fluid bags and catheter. Conventional intravenous
therapy relies on positioning the fluid bag to deliver the drug, as
in gravity drip or expensive Infusion pumps to pump the drug
into the circulatory system. These however limit patient mobility
by confining them to a bed side infusion set up. The MEMS
based IDDS aims to provide all the benefits of conventional IV
therapy with a small implantable pump and provide mobility. We
also intend to incorporate telemetry circuitry to control the pump
and obtain information from the pump.
The advantage of the IDDS is the flexibility offered in terms
of the various schemes for drug delivery. Localized delivery and
centralized delivery can be targeted with equal ease. The
reservoir may be integrated with the micropump or separated
from it, catheters or microneedles may be used for drug delivery.
Incorporating telemetry would provide additional features to
control, monitor and regulate drug delivery.
D. Electronic circuitry
Base Micro
Statio Pump
(a)
2.08 191
V mV
(b) (c)
Figure 3. (a) Telemetry set up (b) transmitted and (c) received signal from the
telemetry test setup placed 5m apart. The transmitted signal is a 1.2 mVp-p
amplified by a factor of 2000 and received signal is 191 mV. The modulated
signal is a 1 KHz sine wave with a 433 MHz carrier.
The telemetry module consists of a transmitter unit and a
receiver unit. The transmitter includes operational amplifiers,
amplifier circuit, a miniature antenna and a transmitter chip. The
receiver has a receiver chip and signal conditioning circuitry. The
antenna chosen is a Copper solenoid of 24 turns. The antenna is
soldered on a small printed circuit board with the transmitter chip
and lumped elements with operating frequency of 433 MHz. The
range of operation is sufficient for the proposed application since
the base station will be close to the patient when the physician
monitors and programs the implanted unit.
Fig. 3 shows the signal received from a transmitter-receiver
separated by a distance of 5 m. A 1 KHz sine wave was used to
modulate a carrier of 433 MHz. It demonstrated clear
communication between the transmitter and receiver. The
transmitted signal is 1.2 mVp-p amplified by a factor of 2000. The
received signal is filtered by a bandpass filter, 300 Hz 10 KHz,
to reduce noise, especially 60-Hz power line signals and
interference from other wireless instruments. The purpose of this
demonstration is to show feasibility of telemetry, hence the size
of the circuit board has not been optimized.
Our goal is to integrate the telemetry and microfluidic devices
to deliver a completely implantable drug delivery mechanism.
Several technical challenges are being investigated. These
include power management, size considerations, and control (a)
circuit integration.

E. Power management
Without taking into account the power required by the RF
unit, the estimated power consumption for the target 10 l/min
delivery rate is in the range of 100-500 mW. This figure is
estimated based on the power consumption of the micropump
necessary to generate required diaphragm displacements.
As a result, commercially available miniature lithium-ion
batteries [11-12] would discharge in less than 48 hours of
operation. Therefore, a power management system employing (b)
recharging of the power source is necessary in the IDDS. One
possibility is recharging from outside of the body using through- Figure 5. (a) The displacement of the diaphragm in micrometers during the
pumping cycle, and (b) the corresponding flow rate at the catheter output in
skin electrical interconnects. A much better alternative would be l/min.
wireless power transmission using RF coils [13-14]. By writing the dynamic equations of motion and the
We are in the process of developing a combined miniature RF continuity and Bernoulli flow equations we obtain:
power recharging and telemetry system for the proposed IDDS.
mx1 + bx1 + kx1 + p1 A1 = F ,
III. FLOW MODELING A1 x1 = A2 x 2 , (1)

Actuator x 2 2 x1 2
Spring
Force p2 + = p1 + ,
2 2
Pumping in which x1 is displacement of piston, p1 is pressure below the
diaphragm
piston, A1 is cross-section of the piston equal to 1.44 mm2, x2 is
Cross-section I outlet flow velocity, A2 cross-section of outlet equal to 0.78 mm2,
is the density of the liquid, b is the diaphragm damping factor.
Catheter
Pb
In our simulations, b was chosen to critically damp the system:

L b = 2 km .
Cross-Section II
Figure 4. Lumped parameter model used to estimate flow rate of
the micropump.
In order to guide in the micropump design parameters, we
used a simple lumped dynamic model as shown in Fig. 4. Motion
obtained by flexing the diaphragm is simplified to the motion of a
piston of mass m = 3 g. Based on the finite element model of
the actuator and diaphragm [15] the stiffness is k = 200 N/m and
the actuator force F = 6 mN for a voltage input of 15 V.
(2)
The outlet of the pump chamber is connected to a catheter of
length L equal to 10 cm and diameter D equal to 500 m that
connects the pump to the vein. Based on physiological data we
assume that the back pressure at the end of the catheter is
Pb=8mmHg, therefore a pressure boundary condition for our
model is:
p 2 = pb + p, where the pressure drop across the catheter
of pipe friction coefficient is given by the Darcy-Weisbach
formula for pressure drop across circular pipes [16].
 l Acknowledgments
p =
2
x 2 , (3)
D 2
The resulting dynamical equations for the micropump takes
the form of a nonlinear lumped model approximate ODE:
2 with the simulation results presented in this paper.
mx1 + kx1 + ( pb + k 3 x1 )A1 =F. (4)
Flow simulations for a micropump/check-valve/catheter
system were carried out in MATLAB. Assuming a sinusoidal
signal to the MEMS actuator with frequency f = 50Hz (close to
the thermal bandwidth of the MEMS actuator), and amplitude F
= 6mN we obtain the output flow rate of the pump as shown in
Fig. 5. Simulation results indicate that an average flow rate of 85
l/min can be achieved against a venous pressure of 8 mmHg.
We will be experimentally validating the flow rate results and
characterize the operation of the micropump.
IV. DISCUSSION
A. Future applications and challenges
Recent research has been focused on MEMS based IDDS to
enable them to meet all biomedical needs. Some of the key areas
are treatment for cancer of colon, lungs, prostate and kidney,
diabetes, spinal cord injuries, spasticity, pain relief, hormone
therapy and release of growth factors.
MEMS has been successful in a large number of fields
however, MEMS based IDDS, although viable, is yet to be
demonstrated. There are a number of reasons for the slow
progress. MEMS based devices are prone to critical damage from
moisture and external influences and are required to be
hermetically sealed and protected. This restricts their
functionality. The stringent conditions required for biomedical
applications for reasons of biocompatibility impose constraints
on the materials and technologies and the power required to
operate the devices are expected to be low. Rapid development in
therapies such as nano-particles for drug delivery has improved
the chances of implementing IDDS. However owing to the
diversity in needs and features, a simple yet feasible IDDS is still
in its infancy.
B. Proposed plan
We have developed and demonstrated micro-fluidic
connections and multiple wafer stacking [reference]. We have
also demonstrated a wireless setup. We aim at miniaturization
and integration of these to demonstrate a truly MEMS based
IDDS. We are also testing the feasibility of realizing a peristaltic
in plane pump using a flexible material to form a microtube to
carry the drug while simultaneously isolating the fluidic and
electrical paths. We are investigating the properties of Parylene
[15] for this purpose and have some promising results. Intensive
testing and simulations will be carried out to characterize the
working of the device. Analysis of precise low rates and
mechanisms to determine them practically will be investigated.
This work has been supported in part by the U.S. Army
research grant W23RYX-3270-N770, Texas Higher Education
Board and by funds from the Automation & Robotics Research
Institute at UTA. We wish to thank Ashutosh Kole for his help
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