Digital Microfluidic Diagnostic Devices
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Digital Microfluidic Diagnostic Devices May 14-26B Advisor/Clients: Dr. Santosh Pandey, Dr. Rebecca Cademartiri, Dr. Ludovico Cademartiri Members: Riley Brien (EE), Jared Anderson (EE), Taejoon Kong (EE), Chee Kang Tan (EE) Website Password may0526
Transcript of Digital Microfluidic Diagnostic Devices
Digital Microfluidic Diagnostic Devices
May 14-26BAdvisor/Clients: Dr. Santosh Pandey, Dr. Rebecca Cademartiri, Dr. Ludovico Cademartiri
Members: Riley Brien (EE), Jared Anderson (EE), Taejoon Kong (EE), Chee Kang Tan (EE)
Website Password may0526
Standard Liquid Handling Steps in Biology
• Example: PCR Purification
– Up to 10 manual pipetting steps
– Different reagents in each step
May 14-26 2www.beckmancoulter.com
Is it possible to automate the different steps using a portable, low cost system to minimize human intervention?
State-of-the-art Liquid Handling Workstation (TECAN F500)
• High-throughput sample-processing
• Large scale
• $40k to >$100k
May 14-26 3
Digital Microfluidic Systems
New automated liquid-handling systems
• Using published methods
– µElectrode system – Electrostatic forces
drive droplet movement on electrode array
• Using novel techniques– µPrinted system – Gravity and mechanical
oscillations drive droplet movement on inkjet-printed surface
May 14-26 4http://www.sciencedirect.com/science/article/pii/S1367593110000955
discrete droplets µL scale
Example of Digital Microfluidics Platform
May 14-26 5
“Two-plate digital microfluidics for dispensing, mixing, and merging droplets”http://www.youtube.com/watch?v=hVAa41qTIqg
1 mm
Overview of Digital Microfluidics
• Controlled droplet movement (actuation) on electrode array
• Electrowetting theory
– 𝑐𝑜𝑠𝜃 = 𝑐𝑜𝑠𝜃0 +𝜀0𝜀𝑟𝑉
2
2𝛾𝑑, 𝜃0-Initial contact angle 𝜃-contact angle,
𝛾-surface tension, 𝑑-dielectric thickness
– Requires high voltage >50V
May 14-26 6http://loolab.chem.ucla.edu/research/proteomics.htmlhttp://gozips.uakron.edu/~aaa80/research.html
Project Goals
• Build a prototype digital microfluidic system
– Implement “Dropbot” hardware
– Fabricate electrode arrays
• Demonstrate key droplet operations:
If possible, design and implement a new droplet-manipulation system
May 14-26 7
Transport
Dispensing
Merging
Splitting
http://cjmems.seas.ucla.edu/?p=fbizqheqoqvthp&paged=2
– Dispensing
– Transport
– Merging
– Mixing
– Splitting
– Parallel control of multiple droplets
– Low voltage (<12V)
– Easy to build
– Low cost (<$100)
– Easy-to-use graphical user interface
Electrical Connectivity of µElectrode System
Modified from Wheeler lab May 14-26 8
PC
ITO Electrodes Array
Arduino
HV Switching Board
Control Board
HV Amplifier
Serial BusFeedback
2Vpp Square wave
100Vpp Square wave
Serial Bus
USB
Edge connector
Hardware Components of our Digital Microfluidics System
May 14-26 9
DMF Control board
Power Supply
High-Voltage Switching Board
High-Voltage Amplifier
Arduino (under control board)
1 in.
Power Supply
ITO glassµElectrode
array
High Voltage Amplifier Design
May 14-26 10
Input: 2 Vpp and required output: 200 VppSignal frequency: 18 kHzPCB Design Software: Eagle CADPCB fabricated by Advanced Circuits
Electrode Array Layout
May 14-26 11
Design and Fabrication of Electrode Array
May 14-26 12
1 cmContact Trace
Electrodes with 50µm spacing
5 mm
Photolithography Mask
Glass
ITOPositive Photoresist
May 14-26 13
1) Spin Coat Photoresist
UV Exposure Develop HCL Etch Strip Photoresist
Glass
Mask
ITO
UV Light
Positive Photoresist
May 14-26 14
Spin Coat Photoresist UV Exposure Develop HCL Etch Strip Photoresist
Glass
ITO
Spin Coat Photoresist UV Exposure Develop HCL Etch Strip Photoresist
Positive Photoresist
ExposedPhotoresist
May 14-26 15
Positive Photoresist
Spin Coat Photoresist UV Exposure Develop HCL Etch Strip Photoresist
Glass
ITOPositive Photoresist
May 14-26 16
Spin Coat Photoresist UV Exposure Develop HCL Etch Strip Photoresist
Glass
ITOPositive Photoresist
May 14-26 17
Applying Dielectric and Hydrophobic Layers
• Parylene C
– High dielectric constant
– Chemical vapor deposition
• Teflon AF 1600
– Hydrophobic layer1 cm
http://pubs.rsc.org/en/content/articlehtml/2008/lc/b803827a
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Shortedtraces
5mm
µElectrode Droplet Operations
May 14-26 19
µPrinted System Control Platform
May 14-26 20
5 cm
10 cm
• Can droplets be manipulated by tilting?
• First version – too heavy, slow
Revised µPrinted System Control Platform
May 14-26 215 cm
Surface-Tension-Confined Tracks Theory
• Droplet is confined to hydrophilic track
• Superhydrophobic surface provides high contact angle
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Superhydrophobic Substrate
Hydrophilic TrackDroplet
µPrinted System Substrate Fabrication and Patterning
• Superhydrophobic Coating –Rust-Oleum NeverWet™
• Transparency Sheets
• Inkjet-printer patterned hydrophilic channels
May 14-26 23http://www.epson.comhttp://www.homedepot.com/catalog/productImages
Quick “Pulses” Prevent High Threshold-Angle Problem
May 14-26 24
0° angle 10° angle 30° angle
Rapid, movement at threshold angle
Droplet Movement on Cross, Ladder, and Line Patterns
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Characterizing Droplet Movement on Cross, Ladder, and Line Patterns
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-0.1
0
0.1
0.2
0.3
0.4
0.5
0.6
0 5 10 15 20
Dro
ple
t m
ove
me
nt
[cm
]
Cycle of stimulation
Droplet movement per cycle of stimulationCross Ladder Line
0
0.1
0.2
0.3
0.4
0.5
0.6
Cross Ladder Line
Dro
ple
t m
ove
me
nt
[cm
]
Average droplet movement per cycle of stimulation
Cross Ladder Line
µPrinted System GUI Controls
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µPrinted System Droplet Manipulation
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Dispensing
Simultaneous loading and mixing
Simultaneous transport
Merging and Mixing
Summary of µElectrode and µPrinted Systems
• µElectrode
– Implemented controller hardware and amplifier
– Fabricated electrode arrays
– Demonstrated droplet operations
• µPrinted
– Developed novel digital microfluidic system
– Demonstrated droplet operations
May 14-26 29
Acknowledgments
• Zach Njus (Graduate student, Dr. Pandey’s group)
• Dr. Wai Leung (Assistant Scientist III, DOE Ames Lab)
• Lee Harker (Electronics Technician II, Coover Hall)
• Dr. Liang Dong (Associate Professor, ECpE)
• Dr. Jaeyoun Kim (Associate Professor, ECpE)
May 14-26 30
Questions?
May 14-26 31
Biological Applications and Advantages
EWOD System RDS System Pipetting robot Manual pipetting
Cost
Speed
Accuracy
Flexibility
Ease of Use
May 14-26 32
Standard methods
http://photos.uc.wisc.edu/photos/3525/view
Digital microfluidics
http://www.ehs.iastate.edu/sites/default/files/uploads/images/pipetting.jpg
ITO Patterning– Problems and Solutions
• Problems
– Shorted traces: many electrodes are actuated at the same time
– Broken traces: can not supply the potential
• Solutions
– Get rid of dust
– Improve mask alignment
May 14-26 33
Hours/feet*12inches/60 minutes
Evolution of DMF Platforms
• 2001 – Duke University and UCLA– First prototypes (1.)
• 2004 – Advanced Liquid Logic– First digital microfluidics company (2.)
• 2011 – Sandia National Lab– First integrated inlet/outlet ports (3.)
• 2012 – University of Toronto – First Open-Source digital microfluidics
system, “Dropbot” (4.)
May 14-26 34http://i1.ytimg.com/vi/9GInRQYzSJg/maxresdefault.jpg
http://www.biw.kuleuven.be/biosyst/mebios/biosensors-home/droplet/image_previewhttp://microfluidics.utoronto.ca/dropbot/media/DropBot_system-labelled.jpg
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Project Costs for DMF system
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• Cost– Control board - $150– Switching board - $300– Amplifier - $800– Indium Tin Oxide (ITO) glass - $1500 (100 pcs.) – Teflon AF 1600 - $1800*– Reagents (photoresist, developer, HCL, Acetone, Methanol,
etc) - Lab supply
