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Modular microfluidics platform for POC system prototyping ... - CiPoC

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<strong>Modular</strong> <strong>microfluidics</strong> <strong>plat<strong>for</strong>m</strong> <strong>for</strong> <strong>POC</strong><br />

<strong>system</strong> <strong>prototyping</strong> and cell culturing<br />

Martin Dufva<br />

<br />

DTU Nanotech<br />

Technical University of Denmark<br />

martin.dufva@nanotech.dtu.dk


Do you have this in your lab<br />

3 DTU Nanotek, Danmarks Tekniske Universitet


Inspirations <strong>for</strong> <strong>plat<strong>for</strong>m</strong> design<br />

Standardized interface<br />

<strong>Modular</strong><br />

Highly integrated<br />

4 DTU Nanotek, Danmarks Tekniske Universitet


PoC <strong>prototyping</strong><br />

Materials<br />

Ability to use materials similar to those in final PoC device<br />

<br />

Per<strong>for</strong>mance<br />

Ability to drive 1 (simulating final PoC device) or up to 32 parallel assays<br />

(used in assay development)<br />

<br />

Usability<br />

Systems should be compatible with natural workflows<br />

<br />

<br />

Efficacy<br />

Minimize <strong>system</strong>/application specific development<br />

<br />

<br />

<br />

5 DTU Nanotek, Danmarks Tekniske Universitet


Connect hard chips to microfluidic ribbons<br />

Si/polymer hybrids Silicon Polymer<br />

6 DTU Nanotek, Danmarks Tekniske Universitet


Micropump per<strong>for</strong>mance<br />

Channel-to-channel (% CV): 6%<br />

Durability: >33 ml per channel<br />

Two-directional<br />

A few nL-80 microL/Min<br />

Pulsating flow<br />

No practical consequence<br />

<strong>for</strong> mixing and liquid<br />

switching operations on<br />

chip as compared with<br />

syringe pumps.<br />

1<br />

SKAFTE-PEDERSEN, P.*, SABOURIN, D.*, ET AL., MULTI-CHANNEL PERISTALTIC PUMP FOR MICROFLUIDIC<br />

APPLICATIONS FEATURING MONOLITHIC PDMS INLAY, LAB CHIP, VOL. 9, 2009.<br />

7 DTU Nanotek, Danmarks Tekniske Universitet


Valve<br />

8 DTU Nanotek, Danmarks Tekniske Universitet


Valve in action


Reagent vials integration<br />

10 DTU Nanotek, Danmarks Tekniske Universitet


Compatible with work flow and equipment<br />

11 DTU Nanotek, Danmarks Tekniske Universitet


Measurements of dopamine release in living<br />

neurones using a highly integrated <strong>system</strong><br />

400<br />

350<br />

300<br />

)<br />

A250<br />

(p<br />

t 200<br />

r<br />

e<br />

n<br />

150<br />

u<br />

C100<br />

50<br />

0<br />

-50<br />

-100<br />

PC12 cells<br />

Clean electrode<br />

0 20 40 60<br />

Time (sec)<br />

Electrochemical sensing integration:<br />

Prof Jenny Emneus, DTU Nanotech<br />

12 DTU Nanotek, Danmarks Tekniske Universitet


Microarray based genotyping<br />

13 DTU Nanotek, Danmarks Tekniske Universitet


Automated in situ hybridization<br />

Controller<br />

HistoFlex<br />

Tubing<br />

Connector<br />

Motor<br />

Merging<br />

Chip<br />

Valve<br />

Micro<br />

pump<br />

Waste<br />

Vial Rack<br />

Motor<br />

10 cm<br />

Together with Kim Holmstrøm, Bioneer A/S<br />

14 DTU Nanotek, Danmarks Tekniske Universitet<br />

7-6-2011


Online monitoring of pesticides<br />

Measure pesticides using an immunoassay with electrochemical detection<br />

Small enough to be put into a well (<strong>for</strong> onsite simulation)<br />

Responsible: Associate Professor Mogens Havsteen DTU Nanotech<br />

15 DTU Nanotek, Danmarks Tekniske Universitet


System stress test (cell culturing)<br />

MainSTREAM 1.0<br />

Chip and Syringe pump<br />

Setup<br />

Time<br />

Sites<br />

(No.)<br />

Culture<br />

Days<br />

Failures<br />

(%)<br />

Bubbles<br />

(%)<br />

Parts<br />

(No.)<br />

(h)<br />

16 DTU Nanotek, Danmarks Tekniske Universitet<br />

7-6-2011


MainSTREAM develoment<br />

MainSTREAM 1.0<br />

8-channel pumps


Acknowledgements<br />

MainSTREAM core components<br />

and <strong>system</strong>s design<br />

David Sabourin<br />

Peder Skafte-Pedersen<br />

Massimo Alberti<br />

Alvaro José Conde<br />

Maciek Skolimowski<br />

Stem cell biology<br />

Mette Hemmingsen<br />

Philippe Collas (Uni Oslo)<br />

Alberto Martínez-Serrano<br />

(Uni Madrid)<br />

DNA microarrays<br />

David Sabourin<br />

Sun Yi, Anders Wolff<br />

Jesper Pedersen (Uni Copenhagen)<br />

In situ hybridization<br />

Martin J Søe (Bioneer A/S)<br />

Kim Holmstrøm (Bioneer A/S)<br />

Electrochemistry on cells<br />

Arto Heiskanen, Vasile Coman<br />

Jenny Emneus, EU – FP7 consortia<br />

Tissue slices cultures<br />

Arto Heiskanen, Jenny Emneus<br />

Indumathi Vedarethinam<br />

Merab Kokaia (Lund University)<br />

Biocompatibility<br />

Joanna Lopacinska<br />

Theory and simulation<br />

Peder Skafte-Pedersen<br />

Søren Vedel, Henrik Bruus<br />

Circle to circle amplification<br />

Monica Brivio, Annika Alh<strong>for</strong>d<br />

Mats Nilsson<br />

Water quality control<br />

Mogens Havsteen Jacobsen<br />

Basil Uthuppu<br />

18 DTU Nanotek, Danmarks Tekniske Universitet<br />

Dufva LOECEC 2011


Literature<br />

David Sabourin, Peder Skafte-Pedersen, Martin Jensen Søe, Mette Hemmingsen, Massimo Alberti, Vasile Coman, Jesper<br />

Petersen, Jenny Emnéus, Jörg P. Kutter, Detlef Snakenborg, Flemming Jørgensen, Christian Clausen, Kim Holmstrøm,<br />

and Martin Dufva. The MainSTREAM Component Plat<strong>for</strong>m: A Holistic Approach to Microfluidic System Design. Journal of<br />

Laboratory 2012 as doi:10.1177/2211068212461445.<br />

Vergani, M, Carminati, M , Ferrari, G, Landini, E, Caviglia, C, Heiskanen, A, Zor, K, Sabourin, D, Dufva, M, Raiteri, R,<br />

Emnéus, J and Sampietro, M. Multichannel Bipotentiostat Integrated with a Microfluidic Plat<strong>for</strong>m <strong>for</strong> Electrochemical<br />

Real-Time Monitoring of Cell Cultures. 2012 accepted, IEEE Transactions on Biomedical Circuits and Systems journal.<br />

Skafte-Pedersen P, Hemmingsen M, Sabourin D, Blaga F, Bruus H, Dufva M. A self-contained, programmable<br />

microfluidic cell culture <strong>system</strong> with real-time microscopy access. Biomedical microdevices (2012), 14(2), 385-399.<br />

Søe M, Sabourin D, Alberti M, Holmstrøm K, Dufva M. HistoFlex – a microfluidic device providing uni<strong>for</strong>m flow<br />

conditions enabling highly sensitive, reproducible and quantitative in situ hybridizations. Lab on a chip journal 2011.<br />

Sabourin D, Petersen J, Dufva M. 2010. Microfluidic DNA microarrays in PMMA chips: streamlined fabrication via<br />

simultaneous DNA immobilisation and bonding activation by brief UV exposure. Biomed Microdevices. 2010 Aug;12(4):<br />

673-81.<br />

Sabourin D, Snakenborg, D and Dufva M. 2010, Interconnection blocks with minimal dead volumes permitting planar<br />

interconnection to thin microfluidic devices, Microfluidics and Nanofluidics. 9(1):87-93<br />

D Sabourin , M Dufva , T Jensen , J Kutter and D Snakenborg. et al. 2010, One-step fabrication of microfluidic chips<br />

with in-plane, adhesive-free interconnections. J. Micromech. Microeng. 20 (3): 037001.<br />

Sabourin D, Snakenborg D, Dufva M. Interconnection blocks: a method <strong>for</strong> providing reusable, rapid, multiple, aligned<br />

and planar microfluidic interconnections. Journal of micromechanics and microengineering. 2009;19:035021.<br />

Skafte-Pedersen, P., D. Sabourin, M. Dufva, and D. Snakenborg. 2009. Multi-channel peristaltic pump <strong>for</strong> microfluidic<br />

applications featuring monolithic PDMS inlay. Lab on a chip 9:3003-3006..<br />

<br />

19 DTU Nanotek, Danmarks Tekniske Universitet


PoC <strong>prototyping</strong><br />

Usability, interference<br />

Instrumentation<br />

development<br />

Input to hardware<br />

development<br />

Test bed<br />

Input to assay<br />

design<br />

Assay<br />

development<br />

<strong>POC</strong> device<br />

User experience<br />

Clinical tests<br />

2 DTU Nanotek, Danmarks Tekniske Universitet

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