Active Digital Microfluidic Paper Chips with Inkjet-printed Patterned - PowerPoint PPT Presentation

BIOLOGICAL INTERFACE LAB · SOGANG UNIVERSITY 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

PAPER CHIP FOR CURES Paper based digital fluidics Point-of Care devices Paper-electronics : Display & Camouflage

Paper microfluidic chips  Paper substrate: Applications Properties Litmus paper,  Chromatography 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)  Passive vs. Active paper microfluidic chips ELISA paper chip APoC, K. Shin G. Whiteside in in Sogang univ. Harvard (2007) (2013) Flow by capillary wicking Digital drops actuated by electric field  Passive paper microfluidic chip:  Active paper open chip (APoC):   Flow-based, slow speed, sequential order Control by applying electric field   Low-cost: Point-of-Care diagnosis test, No pump, pipe and pressurizer  especially for resource limited people Drop-based, fast speed, randomly order   Flow in paper Drop movement on paper

Wetting  The degree of wetting (wettability) is determined by a force balance between adhesive and cohesive forces.  Wetting condition of three phases: Young’s equation:       cos sv sl lv Y g lv Ex 1) Liquid Electrical double Vapor layer (EDL) q Y - - - + ++ g sv g sl Solid substrate Triple contact line (TCL)  Wetting states: − Partial wetting, if 0 < q < p − Pseudo-partial wetting, if 0 < q < p − Complete wetting, if q = 0. K. Shin et al. Langmuir 2007, 23 , 12249

Electrowetting on Dielectrics (EWOD) Shin et al, J. Biomed. Nanotechnol. 2013, Vol. 9, No. 3 Shin et al, J. Nanosci. Nanotechnol . 2014, Vol. 14, No. 8  0   s C d  Young-Lippmann's electrowetting equation: Thermodynamic approach: Gibb’s free energy, Minimization 1               2 cos L V ( ) cos ( 0 ) / dG dA dA dA CV dA VdQ Y ew lv lv lv sl sl sv sv sl 2 Liquid Lenses 2012 International Special Awards-ASM Materials Education Foundation Award (Sogang R&E Team)

 In details,  Electrolyte properties of the electrowetting: Electrical double layer (EDL)  Furmidge’s model: EW force: the dynamic contact angle hysteresis      cos cos ew a r y     cos cos ( 0 ) EDL n  r r i   where,  , for DC      cos cos ( 0 )   a a   2 , for AC F. Mugele et al. W. C. Nelson, C.-J. Kim, J. Adhesion Sci. Technol . 2012, 26 , 1747 - Statics: changing the drop shape  liquid lenses, e-papers

 How can we utilize these interesting phenomena ? DIGITAL ACTUATION

Electrowetting for drop actuation  Two chips developed so far:  ew Closed vs. Open +V +V  Electrowetting force, i.e.  , is not so strong.  Displacement, x : x < 5 mm for 5 m L  Need careful design for the shape and the dimension of a rail of electrodes

Inkjet-printed CNT Electrodes on Paper After n=12 printing 760 Ohm/sq (lowest ever reported!) Hyojin, Kwon, Shin et al, Carbon 2013, 58, 116 – 127

(d)

Active Digital Microfluidic Paper Chips with Inkjet-printed Patterned Electrodes 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 Transporting Merging Reacton Mixing Integration Detection   Programmable actuation digital drops Potable lab. analyzers   Doing various possible lab. activities in chip-scale Potable PoC devices Shin et al, Adv. Mater. 2014, 26 , 2335

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 on 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

Appropriate Technology for the Point of Care 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 oblems 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 ogy needed

Cure without vaccine

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

Indirect ELISA on APOC: Staphylococcus aureus Design strategies for detection Color image of strip sensor Schematic diagram of POC based ELISA Paper (test zone) 1. Immobilize antigen Substrates (TMB) are oxidized by HRP Antigen 2. Add antibody Y 3. Add labeled antibody 4. wash Y HRP Signal layer Y Flow layer TMB (non color) Blue precipitate Y HRP Substrate with Y absorption pad 5. Add enzyme substrate

P-Chip with ELISA Enzyme-linked immunosorbent assay Limitations  Large volume of sample Paper chips  Long analysis time New paper chips ELISA  Small volume of sample  Short analysis time  Automated method Paper-based devices  Reusable device

Optimization of ELISA Preechakasedkit (May), Nipapan Ruecha (Bank) ELISA procedure BCIP/NBT ENZ 1 st : Rabbit IgG immobilization Purple dot The effect of blocking time 2 nd : Blocking with BSA 3 rd : Anti-rabbit IgG-ALP 4 th : BCIP/NBT substrate 5 th : Reaction stopping Scanner and Image J *All steps need washing step The effect of concentration of anti-rabbit IgG-ALP The effect of reaction stopping time The effect of concentration of BSA The effect of immobilized time

Ultrafast, Cheap (~ free), and Sensitive Chip Summary of optimal parameters Parameters Optimal conditions Concentration of anti- 1:2,000 rabbit IgG-ALP Immobilized time 5 min Concentration of BSA 3% BSA Blocking time 5 min Reaction stopping time 5 min ELISA plate Paper chips ELISA Procedure 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 - Negative: Absence of rabbit IgG Positive: Presence of rabbit IgG Total 615 300 17 9

Potential lab-on-a-chip: Digital microfluidics a. Surface-based immunoassays Basic concept target merging Particles reactant Heating Target Optical detection b. PCR c. Latex immunoagglutination assay - Transport, merging, mixing, heating and optical detection of droplets. - Microfluidic techniques facilitate sample handling for platforms. Patent Pending

Active paper-chip for electrochemical multiprobe 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. (  4-7 mM) • Cobalt phthalocyanine (CoPc) as a mediator Preechakasedkit (May), Nipapan Ruecha (Bank) Chemical Reviews, 2008, Vol. 108, No. 2 815

Uric acid Dopamine  Dopamine is one of the most important  Uric acid is a chemical created when catecholamine neurotransmitters in mam the body breaks down substances called malian brain purines.  Abnormal level of DA results in neurol ogical disorders http://amal.net/?p=944  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 http://facts-fun.blogspot.kr/2013/08/uric-acid-level-diets.html http :// garylangephd . com / images / brain002 . jpg

Proto-type of Multipurpose Detection Unit Paper-chip with E-Chem  Low cost analysis WE1  for glucose detection  Portable device WE2  for simultaneous detection of dopamine, ascorbic acid and uric acid  Highly sensitive detection  Automated analysis

PAPER CIRCUITS

Paper electronics Perspective

Active Digital Microfluidic Paper Chips with Inkjet-printed Patterned Electrodes