BM658 Biomedical Microsystems Course Project A Piezoelectric micropump integrated with a Silicon Microneedle array for Transdermal drug

delivery
Under the guidance of Dr. Rohit Srivastava Bioschool, IIT Bombay

Joaquim Ignatious Monteiro (08330301)

Outline
Rationale Brainstorming/ approaches Customer requirements Functional requirements Fabrication Packaging Testing Summary

Rationale for the project

Drugs delivery systems
Site specific delivery Therapeutic range Toxic levels

MEMS technology & drug delivery

Site-specific drug delivery Reduced side effects Increased therapeutic effectiveness
Microneedles based transdermal devices Osmosis based devices Micropump based devices Micro reservoir based devices Biodegradable MEMS devices

Problem definition & Objectives

Transdermal drug delivery system
Minimal trauma Precise control of drug volume

Integrated Drug delivery system

Fluidics
Microneedle(s) Drug reservoir(s)

Actuation device

Brain storming Silicon hollow microneedle array

Stoeber and Liepmann (2000)
combination of DRIE and isotropic etching techniques 200 um long with a wide base and a channel diameter of 40 um.

Mukerjee et al. (2005)

Combination of DRIE, blade circular sawing and isotropic etching. shank height:140 um, channel diameter:25 um

Jing Ji, Francis et al. (2006)

Combination of isotropic etching using ICP and DRIE 20 x 20 array, height of 250 m lumen diameter: 30 m

Brain storming Piezoelectric micropump

Schabmueller et al. (2002)
Structure: SiSi, Nozzle/diffuser,Voltage:190V Frequency: 2400Hz Flow rate 1500ul/min

Geipel et al. (2006)

Structure: SiSi ,Silicon membrane Active valves,Voltage:100V Frequency: <1Hz, Flow rate:10- 50 ul/min

Y.H.Guu et al. (2008)

Structure: SiSi ,Silicon membrane Nozzle/ diffuser,Voltage:140V Frequency: 20Hz, Flow rate:91ul/min

Customer Requirements
Sl. No Requirement Importance

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Minimal trauma, painless delivery of drug into the body Precise control of drug volume. Smaller holes in the skin during injection Microneedles should not break during injection Minimise drug wastage Parts of the system which come in contact with the drug should not react with the drug, cause corrosion of device structures or release toxic products into the drug Actuation mechanism of the micro pump should not damage or electrolyze the drug Drug should not be contaminated by external particles Leak proof interfaces Needle(s) should not get clogged by cells High flow rate Small size Ease of operation The system should have reliability and redundancy The system should be robust

1 1 4 1 1 1 1 2 2 3 4 4 4 4 5

Functional specifications
Sl. No. Metric Details The hollow microneedles are of 200m in length so they do not reach the dermis layer of the skin which contains the nerve endings hence there is no sensation of pain. Additional anisotropic wet etching during fabrication to obtain microneedles to have sharp tips. Materials in contact with the drug are Si, SiO2, Brass and Silicon epoxy all of which are biocompatible. Micropump size reduced hence the dead volume is also reduced. Rubber seal between micropump electrodes. Micropump enclosed in a protective shell covering. Lid seal at the common syringe pipe-micropump interface. Size of packaged micropump is 5024 mm3 Values Microneedle length: 200m Needs Priority

Minimally invasive painless drug delivery

1,3

Drug Biocompatibility

6,7

Reduction of drug wastage

2,5,12

Leak proof interfaces

8,9

Functional specifications
Sl. No. Metric Details Array of microneedles ensures redundancy in case of failure due to needle clogging. Microneedle lumen of 30m to avoid channel clogging by cells. Microneedle shaft is designed to withstand bending moments during injection which can cause breakage. Polyimide outer frame for micro array to provide additional support. Micropump enclosed in a protective shell covering. Piezoelectric micropump has a high flow rate. Drug delivery rate can be controlled by varying the actuation voltage of the piezoelectric micropump. 1800l/s Values Needs Priority

Redundancy

4,10

Reliability

14,15

Drug delivery rate

11,13

Microneedle Fabrication Process Process

SiO2 layer is grown by Thermal Oxidation at 1100oC. silicon layer thickness 250um SiO2 layer 30um

Side View

Top/Bottom View

Mask

Photoresist Coating Positive Photoresist:DQN

Photoresist Exposure & Developing

Sio2 Lithography: Buffered Oxide etch in HF to remove the SiO2 from exposed regions.

a) Photoresist stripping b) Tetra Methyl Ammonium Hydroxide (TMAH) etching of Si. Mask : Si02 Sio2 mask later removed by buffered oxide etch in HF

Steps 2 to 5 are repeated for the top side.

Result of Step 6

<111>

Anisotropic wet etching: <100> surface orientation Etchant:TMAH Mask: SiO2

Deep Reactive Ion Etching: Gas: Flourine Plasma (CF4) Mask:Cr Needle inner dia 30um Needle outer dia. 90um Needle length 250um

Si SiO2 Photoresist Cr

Piezoelectric Micropump Fabrication Process Process Side View Top/Bottom View Mask

a) SiO2 layer grown by Thermal oxidation. b) Photoresist coating 1 silicon layer thickness 1000um SiO2 layer 30um Photoresist : 40um

4.5mm

a)Photoresist exposure and developing b) Si02 layer lithography

Anisotropic wet etching of Si. Etchant : TMAH. Sio2 mask later removed by buffered oxide etch in HF

Anisotropic etching: <100> surface orientation Etchant:TMAH Mask: SiO2

<111>

Silicon Nitride layer deposition LPCVD

a) SiO2 layer grown by Thermal oxidation. b) Photoresist coating

Buffered Oxide etch in HF to remove the SiO2 from exposed regions.

10m

Anisotropic wet etching: Etchant:TMAH 8

1.15 mm

Anisotropic wet etching: Etchant:TMAH

10

Metallization for the electrodes. Sputtering with Gold. Metal mask

11

Bonding of the two structures by fusion bonding.

12

Piezoelectric crystal is bonded by using epoxy adhesive.

Packaging
Electrical interconnections to the micropump Lid seal Drug reservoir assembly Microneedle array packaging

o Electrical interconnections to the micropump

Packaging
o Lid seal Prevent entry of external contaminants Common syringe pipe connects micropump assembly with microneedle array

Packaging
o Drug reservoir assembly Shell is covered on the pump as the protective shield.

Packaging
o Microneedle array packaging
Substrate is less than 100 m in thickness Polyimide membrane backing

Packaging
o Microneedle array packaging

Integrated Drug delivery system

Testing
Fluidic tests Flexibility tests of the Si microneedle array

o Fluidic Tests
Effect of back pressure on flow rate Effect of drive voltage on flow rate Effect of drive frequency on flow rate

Set-up of flow rate measurement.

Fluidic Tests

Flexibility tests of the Si microneedle array

silicon needle array was adhered on the annular clamp Chamber vacuumized => array deforms 9mm9mm array, 1515 needles, thickness<100m, degree of vacuum 500 Torr. (appx. 10N pressure on Si needle array) 15o bend Broken needles or cracks were not detected

Summary
The integration of piezoelectric micropump with Silicon microneedle array for drug delivery. Good compatibility with drug delivery requirements
Minimally invasive Minimal trauma Control of drug volume Non toxic components

References
A. Nisar et al.,MEMS-based micropumps in drug delivery and biomedical applications, Sensors and Actuators B 130 (2008) 917942 Bin Ma, E. Sheng Liu, A PZT insulin pump integrated with a silicon microneedle array for transdermal drug delivery, Microfluid Nanofluid (2006) 2: 417423 M.R. Prausnitz, Microneedles for transdermal drug delivery, Advanced Drug Delivery Reviews 56 (2004) 581587 B. Stoeber, D. Liepmann, Fluid injection through out-of-plane microneedles, Journal Of Microelectromechanical Systems, Vol. 14, No. 3, June 2005 Y.H.GUU et al., Study of Piezoelectrically Actuated Micropumps with Multiple Parallel Chambers Materials and Manufacturing Processes, 23: 16, 2008 E.V. Mukerjee et al., Microneedle array for transdermal biological fluid extraction and in situ analysis, Sensors and Actuators A 114 (2004) 267275 C G J Schabmueller et al., Self-aligning gas/liquid micropump, 2002 J. Micromech. Microeng. 12, 420-424 Jing Ji et al.,Microfabricated Hollow Microneedle Array Using ICP Etcher, Journal of Physics: Conference Series 34 (2006) 11321136 A. Geipel et al.,Pressure-independent micropump with piezoelectric valves for low flow drug delivery systems,MEMS 2006,Istanbul

Thank You