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Active Digital Microfluidic Paper Chips with Inkjet-printed Patterned Electrodes and their Point-of Care Biomedical Application

Institute of Biological Interfaces, Department of Chemistry, Sogang University Kwanwoo Shin

BIOLOGICAL INTERFACE LAB · SOGANG UNIVERSITY

PAPER CHIP FOR CURES

Paper based digital fluidics Point-of Care devices Paper-electronics : Display & Camouflage

 Paper substrate:  Passive paper microfluidic chip:  Passive vs. Active paper microfluidic chips

• General: Abundant fiber, low-cost, writable, light, flexible, flammable
• Physical: Capillary force to wick a flow of liquid sample

 Flow channel: Patterned hydrophobic to confined the capillary fiber  Adjust drop speed by the wide or density of flow channel

Pregnancy test (1976) Litmus paper, Chromatography

ELISA paper chip

• G. Whiteside in

Harvard (2007)

• Flow-based, slow speed, sequential order
• Low-cost: Point-of-Care diagnosis test,

especially for resource limited people

• Flow in paper

Flow by capillary wicking

 Active paper open chip (APoC):

• Control by applying electric field
• No pump, pipe and pressurizer
• Drop-based, fast speed, randomly order
• Drop movement on paper

APoC, K. Shin in Sogang univ. (2013)

Digital drops actuated by electric field

Paper microfluidic chips

Properties Applications

qY

Solid substrate Liquid Vapor

glv gsl gsv

 Wetting condition of three phases: − Partial wetting, if 0 < q < p − Pseudo-partial wetting, if 0 < q < p − Complete wetting, if q = 0. Ex 1)  Wetting states:  The degree of wetting (wettability) is determined by a force balance between adhesive and cohesive forces.

Y lv sl sv

    cos  

Triple contact line (TCL)

Young’s equation:

Electrical double layer (EDL)

• + ++
• K. Shin et al. Langmuir 2007, 23, 12249

Wetting

Electrowetting on Dielectrics (EWOD)

d C

s

 0  Shin et al, J. Biomed. Nanotechnol. 2013, Vol. 9, No. 3 Shin et al, J. Nanosci. Nanotechnol. 2014, Vol. 14, No. 8

 Young-Lippmann's electrowetting equation:

lv ew Y L V

    / ) ( cos ) ( cos  

VdQ dA CV dA dA dA dG

sl sv sv sl sl lv lv

    

2

2 1    Minimization Thermodynamic approach: Gibb’s free energy,

Liquid Lenses

2012 International Special Awards-ASM Materials Education Foundation Award (Sogang R&E Team)

 Electrolyte properties of the electrowetting: Electrical double layer (EDL)

• W. C. Nelson, C.-J. Kim, J. Adhesion Sci. Technol. 2012, 26, 1747

EDL

i

n y

 In details,

r a ew

   cos cos  

 Furmidge’s model:

           AC for , 2 DC for , ) ( cos cos ) ( cos cos      

a a r r

EW force: the dynamic contact angle hysteresis where,

• F. Mugele et al.
• Statics: changing the drop shape  liquid lenses, e-papers

 How can we utilize these interesting phenomena ? DIGITAL ACTUATION

+V

ew



+V

Closed vs. Open  Two chips developed so far:

• Electrowetting force, i.e. ,

is not so strong.  Displacement, x: x < 5 mm for 5 mL  Need careful design for the shape and the dimension

• f a rail of electrodes

Electrowetting for drop actuation

Inkjet-printed CNT Electrodes on Paper

Hyojin, Kwon, Shin et al, Carbon 2013, 58, 116–127

After n=12 printing 760 Ohm/sq (lowest ever reported!)

(d)

Reacton Transporting Merging Mixing Detection Integration Fabrication

• Printed patterned CNT

electrodes

• Deposited functionalized films
• Plug in the electronic controller

Loading/creating a sample drop

• Using a syringe automatically or

manually

• Separating a drop from a

reservoir

• Programmable actuation digital drops
• Doing various possible lab. activities in chip-scale
• Potable lab. analyzers
• Potable PoC devices

Shin et al, Adv. Mater. 2014, 26 , 2335

Active Digital Microfluidic Paper Chips with Inkjet-printed Patterned Electrodes

Patents:

• PCT Patent, Inkjet Printable Paper based

Modular Microfluidic Chips and their Application PCT/KR2013/003815 (2013.05.02)

• Korea Patent Pending, 10-2012-0046284 (2012.
• 05. 02)

Papers:

• Adv. Mater. (2014), 26, 2335–2340, Selected as

a cover paper

• Fabrication and characterization of inkjet-printed

carbon nanotube electrode patterns on paper Carbon, (2013) 58, 116 –127, Selected as an prioritized fast-track paper

• Actuation of Digital Micro Drops by Electrowetting
• n Open Microfluidic Chips Fabricated in

photolithography, J. Nanosci. Nanotechnol. (2014) 14 (8)

• Analysis of Thickness of a Hydrophobic

Fluoropolymer Film Based on Electrowetting, J. Biomedical Nanotechnology, (2013) 9 (7), 1250- 1253.

VALUE

The chips should be inexpensive, accurate, reliable and suited to the medical conditions in developing countries : Appropriate technology for Portable PoC diagnosis

example) Portable water filter

Proble

• blems

ms in cur urre rent nt tec echnolo nology gy Unique, Versatile & Economical In comparison, paper-based chips are,

• the most abundant resources (PDMS-chip)
• Simple preparation and detection
• Versatile design and easy process
• No need for additional equipment

( pressure driven fluidic system)

• Various chemical processes

New idea, novel technolog

• gy needed

Appropriate Technology for the Point of Care

Cure without vaccine

$$$ $$$ $$$ $$$ $$$ $$$ $$$ $$$ $$$ $$$ $$$ $$$ $$$ $$$ $$$ $$$ $$$ $$$ $$$ $$$

Schematic diagram of POC based ELISA

Paper (test zone) Antigen

• 1. Immobilize antigen

Y Y

HRP

Y Y

HRP

Y

TMB (non color) Blue precipitate

• 2. Add antibody
• 3. Add labeled antibody
• 4. wash
• 5. Add enzyme substrate

Substrates (TMB) are oxidized by HRP Design strategies for detection

Indirect ELISA on APOC:Staphylococcus aureus

Color image of strip sensor Flow layer Signal layer Substrate with absorption pad

Enzyme-linked immunosorbent assay

Limitations  Large volume of sample  Long analysis time

New paper chips ELISA

 Small volume of sample  Short analysis time  Automated method  Reusable device

Paper-based devices Paper chips

P-Chip with ELISA

The effect of reaction stopping time The effect of blocking time The effect of concentration of BSA

ENZ

BCIP/NBT Purple dot

ELISA procedure

1st: Rabbit IgG immobilization 2nd: Blocking with BSA 3rd: Anti-rabbit IgG-ALP 4th: BCIP/NBT substrate 5th: Reaction stopping

*All steps need washing step

Scanner and Image J The effect of immobilized time

Optimization of ELISA

The effect of concentration of anti-rabbit IgG-ALP

Preechakasedkit (May), Nipapan Ruecha (Bank)

Parameters Optimal conditions Concentration of anti- rabbit IgG-ALP 1:2,000 Immobilized time 5 min Concentration of BSA 3% BSA Blocking time 5 min Reaction stopping time 5 min

Negative: Absence of rabbit IgG Positive: Presence of rabbit IgG

Procedure ELISA plate Paper chips ELISA Time (min) Volume (µL) Time (min) Volume (µL) Rabbit IgG immobilization 480 100 5 3 Blocking with BSA 60 100 5 3 Anti-rabbit IgG-ALP 60 100 2 3 Reaction stopping 15

• 5
• Total

615 300 17 9

Summary of optimal parameters

Ultrafast, Cheap (~ free), and Sensitive Chip

• b. PCR
• Transport, merging, mixing, heating and optical detection of droplets.
• Microfluidic techniques facilitate sample handling for platforms.

Potential lab-on-a-chip: Digital microfluidics

Particles target Heating merging Optical detection

Basic concept

• a. Surface-based immunoassays

Target reactant

• c. Latex immunoagglutination assay

Patent Pending

Chemical Reviews, 2008, Vol. 108, No. 2 815

Glucose, a carbohydrate, is the most important sugar in human metabolism. Glucose is a major source of energy for most cells of the human body.

Active paper-chip for electrochemical multiprobe

(4-7 mM)

• Cobalt phthalocyanine (CoPc) as a mediator

Preechakasedkit (May), Nipapan Ruecha (Bank)

Dopamine

http://garylangephd.com/images/brain002.jpg

• Dopamine is one of the most important

catecholamine neurotransmitters in mam malian brain

• Abnormal level of DA results in neurol
• gical disorders

Uric acid

http://amal.net/?p=944

 Uric acid is a chemical created when the body breaks down substances called purines.

http://facts-fun.blogspot.kr/2013/08/uric-acid-level-diets.html

 Most uric acid dissolves in blood and travels to the kidneys, where it passes o ut in urine.  A high level of uric acid in the body is called hyperuricemia.

8

Proto-type of Multipurpose Detection Unit

 Low cost analysis  Portable device  Highly sensitive detection  Automated analysis Paper-chip with E-Chem

WE1 for glucose detection WE2 for simultaneous detection of dopamine, ascorbic acid and uric acid

PAPER CIRCUITS

Paper electronics Perspective

Active Digital Microfluidic Paper Chips with Inkjet-printed Patterned Electrodes

BIOLOGICAL INTERFACE LAB · SOGANG UNIVERSITY Paper Chip

• Dr. Oh-Sun Kwon

Hyojin Ko Seunghwi Beak Youngjun Kim Heeju Kim Heedo Chae ELISA Jumi Lee Artificial Cells Heesuk Kim Kilyong Lee Sojung Nam Serin Lee Taewoo Moon Siyeon Baek Phan Dan Minh 3D Printing Aeree Cho Daehyung Cho Minjung Kim FT-IR Imaging

• Dr. Su Ryon Ryu

Wonhyung Jang Chulalongkorn University

• Prof. Orawan Chailapakul
• Dr. N. Rodthongkum

Pattarachaya Preechakasedkit (May) Nipapan Ruecha (Bank)