Digital Microfluidic Diagnostic Devices
Transcript of Digital Microfluidic Diagnostic Devices
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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
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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?
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State-of-the-art Liquid Handling Workstation (TECAN F500)
• High-throughput sample-processing
• Large scale
• $40k to >$100k
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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
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Example of Digital Microfluidics Platform
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“Two-plate digital microfluidics for dispensing, mixing, and merging droplets”http://www.youtube.com/watch?v=hVAa41qTIqg
1 mm
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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
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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
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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
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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
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Hardware Components of our Digital Microfluidics System
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DMF Control board
Power Supply
High-Voltage Switching Board
High-Voltage Amplifier
Arduino (under control board)
1 in.
Power Supply
ITO glassµElectrode
array
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High Voltage Amplifier Design
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Input: 2 Vpp and required output: 200 VppSignal frequency: 18 kHzPCB Design Software: Eagle CADPCB fabricated by Advanced Circuits
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Electrode Array Layout
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Design and Fabrication of Electrode Array
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1 cmContact Trace
Electrodes with 50µm spacing
5 mm
Photolithography Mask
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Glass
ITOPositive Photoresist
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1) Spin Coat Photoresist
UV Exposure Develop HCL Etch Strip Photoresist
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Glass
Mask
ITO
UV Light
Positive Photoresist
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Spin Coat Photoresist UV Exposure Develop HCL Etch Strip Photoresist
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Glass
ITO
Spin Coat Photoresist UV Exposure Develop HCL Etch Strip Photoresist
Positive Photoresist
ExposedPhotoresist
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Positive Photoresist
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Spin Coat Photoresist UV Exposure Develop HCL Etch Strip Photoresist
Glass
ITOPositive Photoresist
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Spin Coat Photoresist UV Exposure Develop HCL Etch Strip Photoresist
Glass
ITOPositive Photoresist
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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
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µElectrode Droplet Operations
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µPrinted System Control Platform
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5 cm
10 cm
• Can droplets be manipulated by tilting?
• First version – too heavy, slow
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Revised µPrinted System Control Platform
May 14-26 215 cm
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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
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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
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Quick “Pulses” Prevent High Threshold-Angle Problem
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0° angle 10° angle 30° angle
Rapid, movement at threshold angle
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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
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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
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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
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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
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Questions?
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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
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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
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Hours/feet*12inches/60 minutes
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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
1. 2.
3.
4.
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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