Synthesis of Digital Microfluidic Biochips with Reconfigurable Operation Execution

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Synthesis of Digital Microfluidic Biochips with Reconfigurable Operation Execution Elena Maftei Technical University of Denmark DTU Informatics www.dreamstime.com

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Elena Maftei Technical University of Denmark DTU Informatics. Synthesis of Digital Microfluidic Biochips with Reconfigurable Operation Execution. www.dreamstime.com. Digital Microfluidic Biochip. Duke University. Applications. Sampling and real time testing of - PowerPoint PPT Presentation

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Page 1: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

Synthesis of Digital Microfluidic Biochips

with Reconfigurable Operation Execution

Elena MafteiTechnical University of Denmark

DTU Informatics

www.dreamstime.com

Page 2: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

2Duke University

Digital Microfluidic Biochip

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Applications

Sampling and real time testing of air/water for biochemical toxins Food testing DNA analysis and sequencing Clinical diagnosis Point of care devices Drug development

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Challenges: Design complexity Radically different design and test methods required Integration with microelectronic components in future SoCs

Advantages & Challenges

Advantages: High throughput (reduced sample / reagent consumption) Space (miniaturization) Time (parallelism) Automation (minimal human intervention)

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Outline

Motivation Architecture Operation Execution Contribution I

Module-Based Synthesis with Dynamic Virtual Devices

Contribution II Routing-Based Synthesis

Contribution III Droplet-Aware Module-Based Synthesis

Conclusions & Future Directions

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Architecture and Working Principles

Biochip architecture Cell architecture

Electrowetting-on-dielectric

Droplet

Top plate

Ground electrode

Control electrodes

InsulatorsFiller fluid

Bottom plate

S2

R

2

B

S3

S1 W

R

1

Reservoir

Detector

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S2

R

2

B

S3

S1 W

R

1

Dispensing Detection Splitting/Merging Storage Mixing/Dilution

Microfluidic Operations

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Reconfigurability

S2

R

2

B

S3

S1 W

R

1

Dispensing Detection Splitting/Merging Storage Mixing/Dilution

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Reconfigurability

S2

R

2

B

S3

S1 W

R

1

Dispensing Detection Splitting/Merging Storage Mixing/Dilution

Non-reconfigurable

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Reconfigurability

S2

R

2

B

S3

S1 W

R

1

Dispensing Detection

Splitting/Merging Storage Mixing/Dilution

Non-reconfigurable

Reconfigurable

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Module-Based Operation Execution

S2

R

2

B

S3

S1 W

R

1

2 x 4 module

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Module-Based Operation Execution

S2

R

2

B

S3

S1 W

R

1

Operation

Area (cells)

Time (s)

Mix 2 x 4 3

Mix 2 x 2 4

Dilution 2 x 4 4

Dilution 2 x 2 5Module library

2 x 4 module

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Module-Based Operation Execution

S2

R

2

B

S3

S1 W

R

1

2 x 4 module

segregation cells

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Module-Based Operation Execution

S2

R

2

B

S3

S1 W

R

1

Operations confined to rectangular, fixed modules

Positions of droplets inside modules ignored

Segregation cells

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Module-Based Synthesis with Dynamic Virtual Modules

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D1

tApplication graph

1 2

9

12

8

3 4

5 6

711

13

10

In S1

In B In S2 In R

1

Dilute Mix

In S3

In B

Dilute

In BIn R2

Dilute

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Example

Biochip

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D1

Application graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

t

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D1

D2(O

5)

Application graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D3

(O12

)

M1

(O6)

D4

(O13

)

store O5

t+4Application graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

Application graph

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D3

(O12

)

D4

(O13

)

M2(

O7)

t+8

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

Schedule

Mixer1

Mixer2

Diluter2

Diluter3

Diluter4

O5

O6

O12

O13

O7

store

t t+8 t+11Allocation

Application graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D2(O

5)

D1

tApplication graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D2(O

5)

tApplication graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D2(O

5)

tApplication graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D2(O

5)

tApplication graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D2(O

5)

tApplication graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D2(O

5)

tApplication graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D2(O

5)

tApplication graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D2(O

5)

tApplication graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D2(O

5)

tApplication graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D2(O

5)

tApplication graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D2(O

5)

tApplication graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D2(O

5)

D1

tApplication graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

D2(O

5)

D1

t

M1

(O6)

Application graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

t+4

D3

(O12

)

S

1

S

2

S

3

B

1

R

2

R

1

WB

2

M2 (O

7)

D4

(O13

)

Application graph

2 x 22 x 2

2 x 4

2 x 22 x 4

S1

B1

S2 R

1

R2 B

2 B

1 S

3

1 2

9

12

8

3 4

5 6

711

13

10

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Example

Schedule – operation execution with dynamic virtual modules

O6Mixer

1

Mixer2

Diluter2

Diluter3

Diluter4

O5

t t+9

O12

O13

O7

t+4Allocation

Mixer1

Mixer2

Diluter2

Diluter3

Diluter4

O5

O6

O12

O13

O7

store

t t+8 t+11Allocation

Schedule – operation execution with fixed virtual modules

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Solution

Tabu Search

List Scheduling

Maximal Empty Rectangles

Binding of modules to operations

Schedule of the operations Placement of modules performed inside scheduling

Placement of the modules Free space manager based on [Bazargan et al. 2000]

thatdivides free space on the chip into overlapping rectangles

Page 38: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

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Dynamic Placement Algorithm

S

1

S

2

S

3

B

1

R

1

R

2

WB

2

Rect2

Rec

t 1 Rec

t 3

(0,0) (7,0)

(0,4)

(3,8) (8,8)

D1

Page 39: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

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Dynamic Placement Algorithm

S

1

S

2

S

3

B

1

R

1

R

2

WB

2

D1

Rect2

Rec

t 1 Rec

t 3

(0,0)

D2(O

5)

(6,4)

(3,4)

(8,8)

(7,0)

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Dynamic Placement Algorithm

Rect2

(4,0)

Rect1

(8,4)

(6,0)

S

1

S

2

S

3

B

1

R

1

R

2

WB

2

D2(O

5)

D1

(8,8)

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Experimental Evaluation

Tabu Search-based algorithm implemented in Java Benchmarks

Real-life applications Colorimetric protein assay In-vitro diagnosis Polymerase chain reaction – mixing stage

Synthetic benchmarks 10 TGFF-generated benchmarks with 10 to 100

operations

Comparison between: Module-based synthesis with fixed modules (MBS) T-Tree [Yuh et al. 2007] Module-based synthesis with dynamic modules (DMBS)

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Experimental EvaluationBest-, average schedule length and standard

deviation out of 50 runs for MBS

Area Time limit (min)

Best (s) Average (s)

Standard dev. (%)

13 x 13 60 182 189.99 2.90

10 182 192.00 3.64

1 191 199.20 4.70

12 x 12 60 182 190.86 3.20

10 185 197.73 6.50

1 193 212.62 10.97

60 184 192.50 3.78

10 194 211.72 14.37

1 226 252.19 15.76

Colorimetric protein assay

Colorimetric protein assayColorimetric protein assayColorimetric protein assay

Page 43: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

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Experimental Evaluation

Colorimetric protein assayColorimetric protein assay

Best schedule length out of 50 runs for MBS vs. T-Tree

10 x 10 10 x 9 9 x 90

50

100

150

200

250

300

MBS

T-Tree

Area (cells x cells)

Be

st s

che

du

le le

ng

th (

s)Colorimetric protein assayColorimetric protein assayColorimetric protein assay

Colorimetric protein assayColorimetric protein assay22.91 % improvement for 9 x 9

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Experimental EvaluationAverage schedule length out of 50 runs for DMBS vs. MBS

Colorimetric protein assayColorimetric protein assayColorimetric protein assay

Colorimetric protein assayColorimetric protein assay7.68 % improvement for 11 x 12

13 x 13 12 x 12 11 x 120

50

100

150

200

250

DMBS

MBS

Area (cells x cells)

Ave

rag

e s

che

du

le le

ng

th (

s)

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Routing-Based Operation Execution

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Module-Based vs. Routing-Based Operation Execution

S

2

R

2

B

S

3

S

1

W

R

1

S

2

R

2

B

S

3

S

1

W

R

1

c

2

c

1

Page 47: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

47

Operation Execution Characterization

S

2

R

2

B

S

3

S

1

W

R

1

c

2

90◦90◦

0◦

180◦c

1

p90, p180, p0 ?

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Operation Execution Characterization

Type Area (cells)

Time(s)

Mix/Dlt 2 x 4 2.9

Mix/Dlt 1 x 4 4.6

Mix/Dlt 2 x 3 6.1

Mix/Dlt 2 x 2 9.9

Input - 2

Detect 1 x 1 30

0◦ 0◦

0◦0◦ 90◦90◦

90◦

90◦

0◦

0◦ 90◦90◦

90◦

90◦

0◦180◦ 0◦

180◦0◦0◦

90◦ 90◦90◦

90◦

p90, p180, p0

Electrode pitch size = 1.5 mm, gap spacing = 0.3 mm, average velocity rate = 20 cm/s.

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Operation Execution Characterization

Type Area (cells)

Time(s)

Mix/Dlt 2 x 4 2.9

Mix/Dlt 1 x 4 4.6

Mix/Dlt 2 x 3 6.1

Mix/Dlt 2 x 2 9.9

Input - 2

Detect 1 x 1 30

p90 = 0.1 %

p180 = - 0.5 %

p0 = 0.29 %

p0 = 0.58 %

Electrode pitch size = 1.5 mm, gap spacing = 0.3 mm, average velocity rate = 20 cm/s.

1

2

Page 50: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

50

Example

1 2

7

10

4In S

1In R

1

Mix

Mix

In R2

3In S

2

8Mix

Dilute 9

5 6In S

3In B

11

13 Waste

In R1 1

2Mix

Application graph

Biochip

S

2

R

2

B

R

1S

1

W

S

3

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Example

Application graph

1 2

7

10

43

8 9

5 6

11

13

12

S

2

R

2

B

R

1S

1

W

S

3

M2(

O7)

M1(

O8)

t = 2.04 s

1 x 41 x 4 2 x 4

2 x 41 x 4 W

R1

R2 S

3 B S

2 R

1 S

1

Page 52: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

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Example

t = 6.67 s

S

2

R

2

B

R

1S

1

W

S

3

M3(

O10

)

D1(

O9)

Application graph

1 2

7

10

43

8 9

5 6

11

13

12

1 x 41 x 4 2 x 4

2 x 41 x 4 W

R1

R2 S

3 B S

2 R

1 S

1

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Example

t = 9.5 s

S

2

R

2

B

R

1S

1

W

S

3

M4(

O12

)

M3(

O10

)Application

graph

1 2

7

10

43

8 9

5 6

11

13

12

1 x 41 x 4 2 x 4

2 x 41 x 4 W

R1

R2 S

3 B S

2 R

1 S

1

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54

Example

Mixer1

Mixer3

Mixer2

O8

O9

2.04 12.506.67

O12

O10

Diluter1

Mixer4

O7

ScheduleApplication graph

1 2

7

10

43

8 9

5 6

11

13

12

1 x 41 x 4 2 x 4

2 x 41 x 4 W

R1

R2 S

3 B S

2 R

1 S

1

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55

Example

t = 2.03 s

S

2

R

2

R

1S

1

B

W

83

4

4

4

9

6

6

6

5

1 1 1 227

Application graph

1 2

7

10

43

8 9

5 6

11

13

12

1 x 41 x 4 2 x 4

2 x 41 x 4 W

R1

R2 S

3 B S

2 R

1 S

1

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56

Example

t = 4.20 s

S

2

R

2

S

1

W

S

3

R

1

B

13.58 times

7

8

9

Application graph

1 2

7

10

43

8 9

5 6

11

13

12

1 x 41 x 4 2 x 4

2 x 41 x 4 W

R1

R2 S

3 B S

2 R

1 S

1

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57

Example

t = 4.28 s

R

2

WS

1

R

1

S

3

B

S

2

8

7

8

7

8810

7

7

7

e913 12e

13 13

13 13 13

13

13 11

11

11

11

Application graph

1 2

7

10

43

8 9

5 6

11

13

12

1 x 41 x 4 2 x 4

2 x 41 x 4 W

R1

R2 S

3 B S

2 R

1 S

1

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58

Example

t = 6.34 s

R

2

WS

1

R

1

S

3

B

S

2

10.33 times

10

12

Application graph

1 2

7

10

43

8 9

5 6

11

13

12

1 x 41 x 4 2 x 4

2 x 41 x 4 W

R1

R2 S

3 B S

2 R

1 S

1

Page 59: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

59

Example

Schedule – module-based operation execution

Schedule – routing-based operation execution

Mixer1

Mixer3

Mixer2

O8

O9

2.04 12.506.67

O12

O10

Diluter1

Mixer4

O7

2.03 6.354.20

O10

O7

O8

O9

O12

Page 60: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

60

Solution

1 2

7

10

4In S

1In R

1

Mix

Mix

In R2

Source

3In S

2

8Mix

Dilute

Sink

9

5 6In S

3In B

11

13 Waste

In R1 1

2Mix

Merge

Mix

Page 61: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

61

Solution

1 2

7

10

4In S

1In R

1

Mix

Mix

In R2

Source

3In S

2

8Mix

Dilute

Sink

9

5 6In S

3In B

11

13 Waste

In R1 1

2Mix

Merge

Mix Minimize the completiontime for the operation

Minimize the time until the droplets meet

Page 62: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

62

Solution

Greedy Randomized Adaptive Search Procedure (GRASP)

S

2

R

2

S

3

R

1S

1

B

W

3

3

3

2

1

Page 63: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

63

Solution

Greedy Randomized Adaptive Search Procedure (GRASP)

S

2

R

2

S

3

R

1S

1

B

W

3

3

3

2

1

For each droplet: Determine possible moves Evaluate each move

Merge: minimize Manhattan distance

Mix: maximize operation execution

Make a list of the best N moves Perform a random move from N

Page 64: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

64

Solution

Greedy Randomized Adaptive Search Procedure (GRASP)

S

2

R

2

S

3

R

1S

1

B

W

3

3

3

2

1

For each droplet: Determine possible moves Evaluate each move

Merge: minimize Manhattan distance

Mix: maximize operation execution

Make a list of the best N moves Perform a random move from N

Page 65: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

65

Solution

Greedy Randomized Adaptive Search Procedure (GRASP)

S

2

R

2

S

3

R

1S

1

B

W

3

3

3

2

1 1

For each droplet: Determine possible moves Evaluate each move

Merge: minimize Manhattan distance

Mix: maximize operation execution

Make a list of the best N moves Perform a random move from N

Page 66: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

66

Solution

Greedy Randomized Adaptive Search Procedure (GRASP)

S

2

R

2

S

3

R

1S

1

B

W

3

3

3

2

1 1

3

For each droplet: Determine possible moves Evaluate each move

Merge: minimize Manhattan distance

Mix: maximize operation execution

Make a list of the best N moves Perform a random move from N

Page 67: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

67

Experimental Evaluation

GRASP-based algorithm implemented in Java Benchmarks

Real-life applications Colorimetric protein assay

Synthetic benchmarks 10 TGFF-generated benchmarks with 10 to 100

operations

Comparison between: Routing-based synthesis (RBS) Module-based synthesis with fixed modules (MBS)

Page 68: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

68

Experimental Evaluation

Colorimetric protein assayColorimetric protein assay

44.95% improvement for 10 x 10

Colorimetric protein assayColorimetric protein assay

Average schedule length out of 50 runs for RBS vs. MBS

Colorimetric protein assay

11 x 11 11 x 10 10 x 10 0

50

100

150

200

250

RBS

MBS

Area (cells x cells)

Ave

rag

e s

che

du

le le

ng

th (

s)Colorimetric protein assayColorimetric protein assayColorimetric protein assay

Colorimetric protein assayColorimetric protein assay44.95 % improvement for 10 x 10

Page 69: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

69

Routing-Based Operation Execution - Conclusions

Improved completion time compared to module-based synthesis

Challenge: contamination

Page 70: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

70

Routing-Based Operation Execution - Conclusions

Improved completion time compared to module-based synthesis

Challenge: contamination

S

1 R

1

W

S

3

B

1

B

2

S

2

R

3

R

21

residues

Page 71: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

71

Routing-Based Operation Execution - Conclusions

Improved completion time compared to module-based synthesis

Challenge: contamination

S

1 R

1

S

3

B

1

B

2

S

2

R

2

WR

3

1

w1

Page 72: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

72

Routing-Based Operation Execution - Conclusions

Improved completion time compared to module-based synthesis

Challenge: contamination

S

1 R

1

S

3

B

1

B

2

S

2

R

2

WR

3

1

w1

Page 73: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

73

Routing-Based Operation Execution - Conclusions

Improved completion time compared to module-based synthesis

Challenge: contamination

S

1 R

1

S

3

B

1

B

2

S

2

R

2

WR

3

1

w1

Page 74: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

74

Routing-Based Operation Execution - Conclusions

Improved completion time compared to module-based synthesis

Challenge: contamination

S

1 R

1

S

3

B

1

B

2

S

2

R

2

WR

3

1

w1

Partition1

Partition2

w2

Page 75: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

75

Routing-Based Operation Execution - Conclusions

Improved completion time compared to module-based synthesis

Challenge: contamination

S

1 R

1

S

3

B

1

B

2

S

2

R

2

WR

3

1

w1

Partition1

Partition2

w2

S

1 R

1

S

3

B

1

B

2

S

2

R

2

1

WR

3

Page 76: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

76

Routing-Based Operation Execution - Conclusions

Improved completion time compared to module-based synthesis

Challenge: contamination

S

1 R

1

S

3

B

1

B

2

S

2

R

2

WR

3

1

w1

Partition1

Partition2

w2

S

1 R

1

S

3

B

1

B

2

S

2

R

2

1

WR

3

w2

w1

Page 77: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

77

Droplet-Aware Operation Executionwithout Contamination

Page 78: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

78

Example

Biochip

1 2

9

12

In S1

In B

8In S

3

3 4 In R1

5 6

7

In B

11

13

10In R

2

Dilute Dilute

MixDilute

In S2

Mix

In B

Application graph

S

1

R

2

W

S

3

B

1

S

2

R

1

B

2

Page 79: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

79

Example

S

1

R

2

W

S

3

B

1

S

2

R

1

B

2

1 2

9

12

In S1

8In S

3

3 4 In R1

5 6

711

13

10

Dilute Dilute

MixDilute

In S2

Mix

2 x 42 x 4

1 x 4

R2

B2

2 x 32 x 3

S3

B1

S1

S2

Application graph

Biochip

B1

R1

Page 80: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

80

Example

S

1

R

2

W

S

3

B

1

S

2

R

1

B

2

M1

(O6)D1

(O5)

t = 2 sApplication graph

1 2

9

12

In S1

8In S

3

3 4 In R1

5 6

711

13

10

Dilute Dilute

MixDilute

In S2

Mix

2 x 42 x 4

1 x 4

R2

B2

2 x 32 x 3

S3

B1

S1

S2

B1

R1

Page 81: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

81

Example

t = 4.9 s

D3(O13)

D2(O12)M2 (

O7)

S

1

R

2

W

S

3

B

1

S

2

R

1

B

2

Application graph

1 2

9

12

In S1

8In S

3

3 4 In R1

5 6

711

13

10

Dilute Dilute

MixDilute

In S2

Mix

2 x 42 x 4

1 x 4

R2

B2

2 x 32 x 3

S3

B1

S1

S2

B1

R1

Page 82: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

82

Example

Diluter1

O5

O12

2 114.9

O7

O6

O13

Diluter2

Diluter3

Mixer1

Mixer2

ScheduleApplication graph

1 2

9

12

In S1

8In S

3

3 4 In R1

5 6

711

13

10

Dilute Dilute

MixDilute

In S2

Mix

2 x 42 x 4

1 x 4

R2

B2

2 x 32 x 3

S3

B1

S1

S2

B1

R1

Page 83: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

83

Example

S

1

R

2

W

S

3

B

1

S

2

R

1

B

2

M1

(O6)D1

(O5)

t = 2 sApplication graph

1 2

9

12

In S1

8In S

3

3 4 In R1

5 6

711

13

10

Dilute Dilute

MixDilute

In S2

Mix

2 x 42 x 4

1 x 4

R2

B2

2 x 32 x 3

S3

B1

S1

S2

B1

R1

Page 84: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

84

Example

t = 2 s

S

1

R

2

W

S

3

B

1

S

2

R

1

B

2

M1(O6)D1(O5)

65

Application graph

1 2

9

12

In S1

8In S

3

3 4 In R1

5 6

711

13

10

Dilute Dilute

MixDilute

In S2

Mix

2 x 42 x 4

1 x 4

R2

B2

2 x 32 x 3

S3

B1

S1

S2

B1

R1

Page 85: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

85

Example

t = 4.17 s

S

1

R

2

W

S

3

B

1

S

2

R

1

B

2

D3(O13)

M2(O7)D2(O12)

7 12

13

Application graph

1 2

9

12

In S1

8In S

3

3 4 In R1

5 6

711

13

10

Dilute Dilute

MixDilute

In S2

Mix

2 x 42 x 4

1 x 4

R2

B2

2 x 32 x 3

S3

B1

S1

S2

B1

R1

Page 86: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

86

Example

Schedule

Diluter1

O5

O

12

2 4.17

O7

O6

O

13

Diluter2

Diluter3

Mixer1

Mixer2

6.67

Application graph

1 2

9

12

In S1

8In S

3

3 4 In R1

5 6

711

13

10

Dilute Dilute

MixDilute

In S2

Mix

2 x 42 x 4

1 x 4

R2

B2

2 x 32 x 3

S3

B1

S1

S2

B1

R1

Page 87: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

87

Example

Schedule – module-based operation execution

Schedule – droplet-aware operation

execution

Diluter1

O5

O

12

2 4.17

O7

O6

O

13

Diluter2

Diluter3

Mixer1

Mixer2

6.67

Diluter1

O5

O12

2 114.9

O7

O6

O13

Diluter2

Diluter3

Mixer1

Mixer2

Page 88: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

88

Solution

Location of modules determined using Tabu Search

Greedy movement of droplets inside modules Routing of droplets between modules and

between modules and I/O ports determined using GRASP

Page 89: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

89

Droplet-Aware Operation Execution

S

1

R

2

W

S

3

B

1

S

2

B

2

R

1

M2(O

7)

D3(O

13)

D2(O

12)

Page 90: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

90

Droplet-Aware Operation Execution

S

1

R

2

W

S

3

B

1

S

2

B

2

R

1

13 13 13 13

12

12

12 12

777

7

Page 91: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

91

Droplet-Aware Operation Execution

S

1

R

2

W

S

3

B

1

S

2

B

2

R

1

13 13 13 13

12

12

12 12

777

7

Page 92: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

92

Droplet-Aware Operation Execution

S

1

R

2

W

S

3

B

1

S

2

B

2

R

1

13 13 13 13

12

12

12 12

7

777

7

Page 93: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

93

Experimental Evaluation

Algorithm implemented in Java Benchmarks

Real-life applications In-vitro diagnosis Colorimetric protein assay

Synthetic benchmarks 3 TGFF-generated benchmarks with 20, 40, 60

operations

Comparison between: Droplet-aware module-based synthesis (DAS) Module-based synthesis (MBS)

Page 94: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

94

Experimental Evaluation

21.55% improvement for 13 x 13

Colorimetric protein assayColorimetric protein assayColorimetric protein assayColorimetric protein assay

Average schedule length out of 50 runs for DAS vs. MBS

Colorimetric protein assayColorimetric protein assay

15 x 15 14 x 14 13 x 130

20

40

60

80

100

120

140

DAS

MBS

Area (cells x cells)

Ave

rag

e s

che

du

le le

ng

th (

s)

Colorimetric protein assayColorimetric protein assay21.55 % improvement for 13 x 13

Colorimetric protein assayColorimetric protein assayColorimetric protein assay

Page 95: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

95

Experimental Evaluation

Algorithm implemented in Java Benchmarks

Real-life applications Colorimetric protein assay

Synthetic benchmarks 3 TGFF-generated benchmarks with 20, 40, 60

operations

Comparison between: Droplet-aware module-based synthesis (DASC) Routing-based synthesis (RBSC)with contamination avoidance

Page 96: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

96

Experimental Evaluation

11.19% improvement for 14 x 14

Colorimetric protein assayColorimetric protein assay

Average schedule length out of 50 runs for DASC vs. RBSC

15 x 15 14 x 14 13 x 13 0

50

100

150

200

250

DASC

RBSC

Area (cells x cells)

Ave

rag

e s

che

du

le le

ng

th (

s)

Colorimetric protein assayColorimetric protein assay11.19 % improvement for 14 x 14

Colorimetric protein assayColorimetric protein assayColorimetric protein assay

Page 97: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

97

Contributions

Tabu Search-based algorithm for the module-based synthesis with fixed devices [CASES09]

Module-based synthesis with virtual devices [CASES09] Module-based synthesis with non-rectangular virtual

devices [DAEM10] Analytical method for operation execution

characterization [CASES10] Routing-based synthesis [CASES10] + contamination

[DAEM, submitted] Droplet-aware module based synthesis [JETC,

submitted] ILP formulation for the synthesis of digital biochips

[VLSI-SoC08]

Page 98: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

98

Conclusions

Proposed several synthesis techniques for DMBs Considered the reconfigurability characteristic of

DMBs Shown that by considering reconfigurability during

operation execution improvements in the completion time of applications can be obtained

Page 99: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

99

Future Directions

S

1

R

2

W

S

3

B

1

S

2

R

1

B

2

M1

M2

Page 100: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

100

Future Directions

S

1

R

2

W

S

3

B

1

S

2

R

1

B

2

M1

M2

M1

M2

S

1

R

2

W

S

3

B

1

S

2

R

1

B

2

Module-Based Synthesis with Overlapping Devices

Page 101: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

101

Future Directions

S

1

R

2

W

S

3

B

1

S

2

R

1

B

2

Fault-Tolerant Module-Based Synthesis

M1

(O1)

M2

(O2) Faulty cell

S

1

R

2

W

S

3

B

1

S

2

R

1

B

2

M1

(O1)

M2

(O2)

M3(

O3)

Page 102: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

102

Future Directions

S

1

R

2

W

S

3

B

1

S

2

R

1

B

2

Fault-Tolerant Module-Based Synthesis

Faulty cellS

1

R

2

W

S

3

B

1

S

2

R

1

B

2

M1

(O1)

M2

(O2)

M3(

O3)

M2

(O2)

M1

(O1) M

3(O

3)

Page 103: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

103

Page 104: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

104

Back-up slides

Page 105: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

105

Electrowetting

Page 106: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

106

Surface Tension

Imbalance of forces between moleculesat an interface (gas/liquid, liquid/liquid,gas/solid, liquid/solid)

Page 107: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

107

Dispensing

Page 108: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

108

Dispensing

Page 109: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

109

Dispensing

Page 110: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

110

Splitting

Page 111: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

111

Mixing

Page 112: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

112

Capacitive sensor

Page 113: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

113

Design Tasks

Operation Area(cells) Time(s)

Mix 2 x 2 10

Mix 1 x 3 5

Dilute 1 x 3 8

Dilute 2 x 5 3

Page 114: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

114

Design Tasks

Operation Area(cells) Time(s)

Mix 2 x 2 10

Mix 1 x 3 5

Dilute 1 x 3 8

Dilute 2 x 5 3

S

1

S

2

S

3

B

R

1

R

2

Page 115: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

115

Experimental EvaluationQuality of the solution compared to classical operation execution

Best out of 50

Colorimetric protein assayColorimetric protein assay9.73% improvement for 11 x 12

Colorimetric protein assayColorimetric protein assayColorimetric protein assay

13 x 13 12 x 12 11 x 120

50

100

150

200

250

DMBS vs. FMBS

DMBS

FMBS

Area (cells x cells)

Be

st s

che

du

le le

ng

th (

s)

Page 116: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

116

Experimental EvaluationQuality of the solution compared to classical operation execution

Best out of 50

11 x 11 11 x 10 10 x 10 0

50

100

150

200

250

RBS vs. MBS

RBS

MBS

Area (cells x cells)

Be

st s

che

du

le le

ng

th (

s)Colorimetric protein assayColorimetric protein assayColorimetric protein assay

Colorimetric protein assayColorimetric protein assay44.63% improvement for 10 x 10

Page 117: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

117

Experimental EvaluationQuality of the solution compared to classical operation execution

Best out of 50

Colorimetric protein assayColorimetric protein assayColorimetric protein assay

Colorimetric protein assayColorimetric protein assay15.76% improvement for 13 x 13

15 x 15 14 x 14 13 x 130

20

40

60

80

100

120

140

DAS vs. MBS

DAS

MBS

Area (cells x cells)

Be

st s

che

du

le le

ng

th (

s)

Page 118: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

118

Future Directions

S

1

R

2

W

S

3

B

1

S

2

B

2

R

1

3

2

1

Pin-Constrained Routing-Based Synthesis

Page 119: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

119

Future Directions

S

1

R

2

W

S

3

B

1

S

2

B

2

R

1

3

2

1

Pin-Constrained Routing-Based Synthesis

Page 120: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

120

Future Directions

S

1

R

2

W

S

3

B

1

S

2

B

2

R

1

3

2

1

Pin-Constrained Routing-Based Synthesis

Page 121: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

121

Microfluidic Operations

S2

R

2

B

S3

S1 W

R

1

Dispensing

Dispensing

Page 122: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

122

Microfluidic Operations

S2

R

2

B

S3

S1 W

R

1

Dispensing Detection

Page 123: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

123

S2

R

2

B

S3

S1 W

R

1

Page 124: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

124

S2

R

2

B

S3

S1 W

R

1

Dispensing Detection Splitting/Merging

Microfluidic Operations

Page 125: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

125

S2

R

2

B

S3

S1 W

R

1

Dispensing Detection Splitting/Merging Storage

Microfluidic Operations

Page 126: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

126

Motivational Example (for the first contrib)

Application graph

Operation Area(cells) Time(s)

Mix 2 x 4 3

Mix 2 x 2 4

Dilution 2 x 4 4

Dilution 2 x 2 5

Dispense - 2

Module library

1 2

9

12

In S1

In B

8In S

3

3 4 In R1

5 6

7

In B

11

13

10In R

2

Dilute Dilute

MixDilute

In S2

Mix

In B

Page 127: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

127

Motivational Example(for the 2nd contrib)

1 2

7

10

4In S

1In R

1

Mix

Mix

In R2

Source

3In S

2

8Mix

Dilute

Sink

9

5 6In S

3In B

11

13 Waste

In R1 1

2Mix

Application graph

Type Area (cells)

Time(s)

Mix/Dlt 2 x 4 2.9

Mix/Dlt 1 x 4 4.6

Mix/Dlt 2 x 3 6.1

Mix/Dlt 2 x 2 9.9

Input - 2

Detect 1 x 1 30

Module library

Page 128: Synthesis of Digital Microfluidic Biochips  with Reconfigurable Operation Execution

128

Example(for the 3rd contrib)

Type Area (cells)

Time(s)

Mix/Dlt 2 x 4 2.9

Mix/Dlt 1 x 4 4.6

Mix/Dlt 2 x 3 6.1

Mix/Dlt 2 x 2 9.9

Input - 2

Detect 1 x 1 30

Module libraryApplication graph

1 2

9

12

In S1

In B

8In S

3

3 4 In R1

5 6

7

In B

11

13

10In R

2

Dilute Dilute

MixDilute

In S2

Mix

In B