IMPLANTABLE DRUG DELIVERY SYSTEM WITH AN IN-PLANE MICROPUMP By AMIT A

81 Pages·2006·1.15 MB·English

IMPLANTABLE DRUG DELIVERY SYSTEM WITH AN

IN-PLANE MICROPUMP

By

AMIT A. MHATRE

Presented to the Faculty of the Graduate school of

The University of Texas at Arlington in Partial Fulfillment

of the Requirements

for the Degree of

MASTER OF SCIENCE IN BIOMEDICAL ENGINEERING

THE UNIVERSITY OF TEXAS AT ARLINGTON
MAY 2006
Copyright © by Amit A. Mhatre 2006

All rights reserved.
ACKNOWLEDGEMENTS

I would like to thank my research advisor Dr. Dan Popa for giving me the
opportunity to work on the IDDS project. This enabled me to work at the Automation
and Research Robotics Institute (ARRI) in a research lab and on real world engineering
problems. His help and guidance is the primary reason for the materialization of this
thesis.
I would also like to thank Dr. Jeongsik Sin for his support and help throughout
the project particularly in the issues relating to the in-plane micropump.
I am thankful to Dr.J.C.Chiao for his constant guidance during this research
work. I benefited a lot from his mentorship and helpful insights through the project.
I would like to thank all the wonderful staff and student co-workers at ARRI
for their help and support especially Mr. Srikar Paruchuri and Ms. Smitha Rao.
I would also like to thank my committee members Dr. Behbehani and Dr. Liu
for their valuable inputs which led to great improvement in my thesis.
I would like to thank my parents and sister for their infinite love and support.
Every passing day makes me realize how truly amazing they are.

December 21, 2005

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ABSTRACT

IMPLANTABLE DRUG DELIVERY SYSTEM WITH AN

IN-PLANE MICROPUMP

Publication number_____.

Amit A.Mhatre, M.S.

The University of Texas at Arlington, 2006

Supervising professor: Dr. Dan Popa

A MEMS based Implantable Drug Delivery System (IDDS) is discussed. The heart of
the system is an in-plane MEMS micropump enables us to make a compact, inexpensive
system. A conceptual IDDS design is proposed. This design consists of an implantable
unit which houses the micropump, electronic and power circuitry. This implantable unit
is connected to a subcutaneous port via a silicone catheter. The subcutaneous port acts
as a refillable reservoir. This leads to a reduction in unit volume and makes the system
customizable. The IDDS pumps drug into surrounding tissue with the help of a MEMS-
based micropump. The force generated by the MEMS actuator and the displacement of
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the tip is determined with the help of FEM simulations using ANSYS. The results from
the displacement were verified experimentally. A lumped parameter model was made to
estimate the flow rate through the outlet of the IDDS.
Microfluidic interconnects to the micropump were fabricated and packaged. Packaging
of interconnects uses processes like anodic bonding, microdrilling and fibre alignment.
Future work will be focused on refining the IDDS model, conducting experiments to
measure tip-force of pump actuators, experimental measurement of the flow generated,
and implementation of electronic, RF and power components of the IDDS.

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TABLE OF CONTENTS

ACKNOWLEDGEMENTS....................................................................................... iii

ABSTRACT ............................................................................................................. iv

LIST OF ILLUSTRATIONS..................................................................................... ix

LIST OF TABLES…………………………………………………………………. xi

Chapter

1. INTRODUCTION………………………………………………………. 1

1.1 Motivation……………..……………………………………………. 1

1.2 Contribution of this thesis………….……………………………….. 3

2. BACKGROUND……..………………………………………………… 5

2.1 Field of controlled Drug Delivery………………………………… 5
2.1.1 Transdermal patches...…………………………………… 7
2.1.2 Polymer implants....……………………………………… 7
2.1.3 Bioadhesives.....………………………………………….. 7
2.1.4 Microencapsulation………………………………………. 8
2.1.5 Some important passive devices…….…………………… 8
2.1.5.1 Microchip drug reservoirs..……………………... 9
2.1.5.2 Immuno-isolating capsules….………………….. 10
2.1.5.3 Diffusion chambers……………………………. 12
2.1.5.4 Diffusion controlled implanted tubes ………… 12
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2.2 Implantable pump systems ………………………………………. 13

2.2.1 Clinical conditions that can be treated………………….... 15

2.2.2 Examples of important devices currently in use………… 16

2.2.2.1 Medtronic Synchromed...…………………...... 16

2.2.2.2 Debiotech…………………………………….. 17

3. THE IDDS SYSTEM …......................................................................... 18

3.1 Conceptual Design……………………………………………….. 18

3.2 Components of IDDS……………………………………………. 18

3.2.1 Micropump………………………………………………. 18

3.2.2 Reservoir. ………………………………………. ……… 19

3.2.3 Power management..……………………………………. 20

3.2.4 Control and telemetry circuitry..………………………... 21

4. MODELING AND SIMULATION...…………………………..…… 24

4.1 The electrothermal actuator..……………………………………. 24

4.2 Closed-form calculation of actuator-force ……………………... 26

4.3 Analysis and simulation of actuator using FEA…..………….... 32

4.4 Tip-Force determination with the help of ANSYS 9.0……........ 36

4.5 Experimental results for the displacement of the actuator…….... 39

4.6 Lumped-parameter modeling of the IDDS.…………………….... 42

4.7 Conclusions of chapter….………………………………………. 53

5. MICROFLUIDIC INTERCONNECTS ……………………….…… 55

5.1 Background …………………………………………………… 55

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5.2 Fabrication ………………………………………………......... 55

5.2.1 Microchannels……………………………………...... 55

5.2.2 Drilling of holes on glass wafer...……........................ 56

5.2.3 Anodic bonding..…………………………………….. 57

5.2.4 Attachment of capillaries……………………………... 59

6. CONCLUSION AND FUTURE WORK. …………………………………. 61

6.1 Conclusions…………………………………………………… 61

6.2 Future work and challenges…………………………………. 62

REFERENCES ………………………………………………………………... 65

BIOGRAPHICAL INFORMATION ………………………………………….. 70

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LIST OF ILLUSTRATIONS
Figure Page
2.1 Drug dosage to maintain therapeutic level ………………………………….. 5

2.2 Microchip drug reservoir ……………………………………………………. 9

2.3 Micrograph of a biocapsule membrane with 25-nm pores ……………….. 11

2.4 Diffusion chamber (Debiotech-Lausanne, Switzerland)………………........ 11

2.5 Duros osmotic pump (Alza-Mountain View, CA, USA) ………………… 13

2.6 Minimed pump and external communicator (Medtronic-MN, USA)……… 16

2.7 MIP implantable MEMS pump (Debiotech-Lausanne, Switzerland)……… 17

3.1 Conceptual design…………………………………………………………. 18

3.2 In-plane micropump……………………………………………………….. 19

3.3 Subcutaneous ports as reservoir (INSTECH-SOLOMON, PA, USA)……. 20

3.4 (a) Telemetry set up (b) transmitted and (c) received signal ……………... 21

3.5 Block diagram.………….………………………………………………… 22

3.6 Internal arrangement of components (proposed)..………………………..... 23

4.1 SEM photograph of a Chevron-type actuator…..………………………… 24

4.2 Electrothermal actuator (present design).…………………………………. 26

4.3 Boundary conditions for the beams..……………………………………... 29

4.4 Force-balance diagram for the v Beam…………………………………….. 31

4.5 FEA simulated Y-Displacement of the electrothermal actuator in microns… 34

4.6 FEA simulated Y-displacement of tip at various input voltages ….…….….. 35
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4.7 Temperature distribution at 14V….…………………………………………. 35

4.8 Plot of Temperature Vs input Voltage………………………………………. 36

4.9 Method to determine force using FEA………………………………………. 38

4.10 Picture of the tip of the actuator..……..…………………………………….. 40

4.11 Experimental value of displacement ………………………………………... 41

4.12 Comparison of simulation and experimental results for displacement……… 41

4.13 Probe station ……………………………………………………………….. . 42

4.14 The representation of the pump system as a piston-cylinder model ………… 43

4.15 Displacement of liquid at piston..………………………………………….... 47

4.16 Flow rate through the outlet for a quarter pumping cycle. ………………...… 48

4. 17 Model with a leak……………………………………………………………. 49

4.18 Displacement with leak ……………………………………………………... 51

4.19 Flow rate with leak...………………………………………………………... 51

4.20 Model when drug escapes in the surrounding space which is at P =0……… 52
3

5.1 Drill bit and the diamond tip (Ukam, Valencia, Calfornia, USA) ………….. 56

5.2 Setup for microdrilling located at ARRI…….……………………………… 57

5.3 Schematic diagram-Anodic Bonding…..……………………………………. 58

5.4 Glass and Silicon sample after anodic bonding ……………………………... 58

5.5 Set up for alignment and curing of epoxy located at ARRI………………….. 59

5.6 The resulting microfluidic interconnect……………………………................ 60

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