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Automated Design of Digital Automated Design of Digital Automated Design of Digital Automated Design of Digital Microfluidic Lab Microfluidic Lab- -on on- -Chip under Chip under Pin Pin- -Count Constraints Count Constraints Krishnendu Chakrabarty Krishnendu Chakrabarty Department of Electrical and Computer Engineering Department of Electrical and Computer Engineering Duke University Duke University Durham, North Carolina Durham, North Carolina D D h h N N th C th C li li USA USA

Acknowledgments Acknowledgments � Students: Tianhao Zhang, Fei Su, William Hwang, Phil Paik, Tao Xu, Students: Tianhao Zhang, Fei Su, William Hwang, Phil Paik, Tao Xu, Vijay Srinivasan, Yang Zhao Vijay Srinivasan, Yang Zhao � Post Post- -docs, colleagues, and collaborators: Dr. Vamsee Pamula, Dr. docs, colleagues, and collaborators: Dr. Vamsee Pamula, Dr. Michael Pollock, Prof. Richard Fair, Dr. Jun Zeng (Coventor, HP) Michael Pollock, Prof. Richard Fair, Dr. Jun Zeng (Coventor, HP) � Duke University Duke University ’ ’ s Microfluidics Research Lab s Microfluidics Research Lab (http://www.ee.duke.edu/research/microfluidics/) (http://www.ee.duke.edu/research/microfluidics/) � Advanced Liquid Logic ( Advanced Liquid Logic (http://www.liquid http://www.liquid- -logic.com/ logic.com/): Start ): Start-up up company spun out off Duke University company spun out off Duke University ’ ’ s microfluidics research s microfluidics research project project project project

Talk Outline Talk Outline Talk Outline Talk Outline � Motivation � Motivation Motivation Motivation � Technology overview Technology overview gy gy � Design of high Design of high- -throughput pin throughput pin- - constrained lab constrained lab on constrained lab constrained lab-on on-chip on chip chip chip � Array partitioning Array partitioning � Cross Cross- -referencing referencing- -based biochip based biochip � High High- g -throughput droplet manipulation throughput droplet manipulation g p g p p p p p � Conclusions Conclusions

Applications and Advantages Applications and Advantages of Lab of Lab on of Lab of Lab-on on Chip on-Chip Chip Chip Applications Applications � Point Point- -of of- -care clinical diagnostics, care clinical diagnostics, newborn screening newborn screening � Environmental monitoring E Environmental monitoring E i i t l t l it it i i � Massively Massively- -parallel DNA parallel DNA sequencing sequencing q q g g � Automated drug discovery Automated drug discovery Conventional Biochemical Analyzer Advantages Advantages Shrink � Automated Automated uto uto ated ated � Small sample/reagent cost Small sample/reagent cost Microfluidic Lab- on-Chip � High sensitivity � High sensitivity High sensitivity High sensitivity 20nl sample

Why Do We Care? Why Do We Care? System Driver for 2009: “Medical” Intel Research Day 2007: Biochip prototype demonstrated for Final Draft 2007 point-of-care diagnostics and lab testing

Motivation for Microfluidics Motivation for Microfluidics Automation Test tubes Test tubes Integration Integration Miniaturization Automation Robotics Integration Integration Miniaturization Automation Microfluidics Integration Miniaturization

Microfluidics Microfluidics � Continuous Continuous- -flow lab flow lab- -on on- -chip: Permanently chip: Permanently- -etched microchannels, etched microchannels, micropumps and microvalves, electrokinetics, etc. micropumps and microvalves, electrokinetics, etc. � Digital microfluidic lab Digital microfluidic lab- -on on- -chip: Manipulation of liquids as discrete chip: Manipulation of liquids as discrete droplets droplets Multiplexing Multiplexing Mixing: Static, Diffusion Limited Diffusion Limited Biosensors : Optical: SPR, Fluorescence etc. Electrochemical: Amperometric, Potentiometric etc.

What is Digital Microfluidics? What is Digital Microfluidics? g � Droplet actuation is Droplet actuation is achieved through achieved through an hi hi d th d th h h an effect called effect called electrowetting electrowetting electrowetting electrowetting ⎯ Electrical modulation Electrical modulation of the solid of the solid- -liquid liquid interfacial tension interfacial tension No Potential Applied Potential

Demonstrations Demonstrations Demonstrations Demonstrations Video source: www.ee.duke.edu/research/microfluidics

Some Basic Operations Some Basic Operations Some Basic Operations Some Basic Operations Transport Transport p Splitting/Merging Splitting/Merging p p g g g g g g 25 cm/s flow rates, order of magnitude higher than continuous-flow methods

Current Capabilities Current Capabilities � Digital microfluidic lab Digital microfluidic lab- -on on- -chip chip TRANSPORT DISPENSING MIXERS REACTORS DETECTION Basic microfluidic functions (transport, splitting, � merging, and mixing) have already been demonstrated on a 2-D array y INTEGRATE Highly reconfigurable system � Di it l Mi Digital Microfluidic fl idi Lab-on-Chip Protein crystallization chip (under development) (under development)

Emerging Trends and Needs for Emerging Trends and Needs for Lab L b L b Lab-on on- -Chip Chi Chi Chip � High throughput � High throughput High throughput High throughput DNA sequencing, 10 6 base pairs � DNA sequencing, 10 base pairs Protein crystallization, 10 3 3 candidate conditions � Protein crystallization, 10 � Protein crystallization, 10 Protein crystallization, 10 candidate conditions candidate conditions candidate conditions � Low cost Low cost � Disposable low � Disposable, low Disposable low-cost less than $1/chip Disposable, low cost, less than $1/chip cost less than $1/chip cost, less than $1/chip � PCB design PCB design � Rapid prototyping and inexpensive mass Rapid prototyping and inexpensive mass- -fabrication fabrication � Copper layer for electrodes (coplanar grounding rails) Copper layer for electrodes (coplanar grounding rails) � Solder mask for insulator Solder mask for insulator � Teflon AF coating for hydrophobicity T fl Teflon AF coating for hydrophobicity T fl AF AF i i f f h d h d h bi i h bi i � Disposable PCB device plugged into controller circuit board, Disposable PCB device plugged into controller circuit board, p programmed and powered with USB port p programmed and powered with USB port g g p p p p

Electrode Electrode- -Addressing Problem Addressing Problem Direct Addressing: Direct Addressing: � Each electrode connected to an independent pin Each electrode connected to an independent pin � For larger arrays (e.g., > 100 x 100 electrodes) For larger arrays (e.g., > 100 x 100 electrodes) F F l l ( ( 100 100 100 100 l l d d ) ) Too many control pins � high fabrication cost � Too many control pins high fabrication cost � Complicated wiring, too many PCB layers, high cost Complicated wiring, too many PCB layers, high cost PCB design: 250 um via hole, 500 um x 500 um electrode PCB design: 250 um via hole, 500 um x 500 um electrode PCB design 250 PCB design 250 m ia hole 500 m ia hole 500 m m 500 500 m electrode m electrode Via Holes Via Holes Wires Wires

Solution Based on Array Partitioning y g � Pin Pin- -constrained array design constrained array design � Advantage Ad Ad Advantage : Reduce number of independent pins for : Reduce number of independent pins for n x R d R d b b f i d f i d d d i i f f x m m array array from from n x m n x m to to k ≤ n x m k ≤ n x m � k = 5 is fewest # of control pins to control single droplet � k = 5 is fewest # of control pins to control single droplet = 5 is fewest # of control pins to control single droplet = 5 is fewest # of control pins to control single droplet � Disadvantage Disadvantage : Potential for unintentional interference between : Potential for unintentional interference between multiple droplets: no way to concurrently move D i to position multiple droplets: no way to concurrently move multiple droplets: no way to concurrently move D i to position multiple droplets: no way to concurrently move to position to position (1,2) and (1,2) and D j j to position (4,4) to position (4,4) � Solution Solution Solution Solution � Single droplet: Single droplet: Addressing each electrode Addressing each electrode and its neighbors with distinct pins and its neighbors with distinct pins g g p p � Multiple droplets: Multiple droplets: Partition the chip Partition the chip � Need for stall cycles? � Need for stall cycles? Need for stall cycles? Need for stall cycles?

Partitioning for Pin Partitioning for Pin- -Constrained Constrained Designs Designs � Droplet Trace Droplet Trace � all the cells traversed by a all the cells traversed by a droplet in its lifetime droplet in its lifetime droplet in its lifetime droplet in its lifetime � Scheduling and placement Scheduling and placement information needed information needed � Partitioning rules Partitioning rules � non non- -overlapping partitions overlapping partitions � spatially overlapping partitions spatially overlapping partitions � temporally overlapping temporally overlapping partitions partitions partitions partitions