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Frits Dijksman and Anke Pierik Philips Research Europe Eindhoven Workshop Contact Line Instabilities Lorentz Centre Leiden University January 4-8, 2010 Fluid dynamics of droplet impact on porous membranes. Molecular diagnostics Biomicrofluidics 2 044101 (2008) Slide 2 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 2 Trends in Molecular Diagnostics Multiple parameter testing on molecular level (DNA, RNA, proteins, enzymes, hormones, cells,) Point of Care Rapid Diagnostic Testing Sensitive Fast Integrated 24h/7d access Easy to use High multiplex grade Use of microarrays Slide 3 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 3 Microarrays Microarray: substrate containing multiple spots (DNA-fragments, proteins, ) that can each specifically capture a single target Advantages of microarrays Highly parallel, especially important for complex diseases low price per result Small sample volumes can be used More sensitive due to miniaturization Shorter reaction times due to shorter diffusion distances Slide 4 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 Use of microarrays in biomedical devices Developing very sensitive detection techniques for biomedical devices Sample preparation and detection equipment Sample Microarray containing ink jet printed capture probes Cartridge Measurement equipment Integrated systems Slide 5 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 Example of microarrays: DNA arrays Slide 6 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 Applications of microarrays Genotyping Identification: food, diagnostics Gene / protein expression Personalized prognosis, patient stratification Pharmacogenomics Personalized medicine Slide 7 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 7 Introduction on micro arrays Before hybridisation After hybridisation Microarray (5 by 6 mm) with capture probe spots Today: Dot size 150-200 m, Permeation depth 100 m Dot pitch 254-400 m Number of dots: 100-400 Near future: Dot size 50-100 m, Permeation depth 50 m Dot pitch 100-200 m Number of dots: > 1000 Slide 8 CONFIDENTIAL Nylon membranes, neutral or positively charged Average pore size: 450 nm Thickness of membranes: 150 m Cross-section Nytran membrane 3D distribution of probes depends on: Volume of droplet V droplet Total volume of dot V total Velocity of droplet v droplet Print frequency (Auto) diffusion of capture probes Surface properties membrane (charge) and properties solution and oligo-(dye) Manufacturing process of micro arrays Flow through direction Membrane with printed spots containing oligonucleotide probes Slide 9 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 9 Unit operations dot formation / capture probes Timing of: Droplet formation Flight Evaporation Spreading Penetration Diffusion Drying Velocity print head Slide 10 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 10 Issue: print heads Linear array 16 nozzle print head. Droplet volume: 10 pl Droplet speed: 5-10 m/s Max frequency: 4-6 kHz Cartridge volume: 1.5 ml Single nozzle pipette Droplet volume: 100-150 pl Droplet speed: 1-3 m/s Max frequency: 1 kHz Volume: 25 l Slide 11 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 11 Single nozzle printer: large droplets Total QC High speed multi-fluid printer: small droplets Issue: printers A. Pierik et al, J. Biotechnology Vol 3, 12, 2008 Slide 12 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 12 Main issue Are dot dimensions dependent on droplet size, jetting frequency and number? Wet dot size 500-1000 pl Dimatix: Droplet volume 10 pl 50-100 droplets, 4 kHz Microdrop: Droplet volume 120-150 pl 7-10 droplets, 100 Hz Is the capture probe distribution dependent on droplet size and number? Slide 13 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 13 Dot spreading upon impact Slide 14 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 14 Results Christophe Le Clerc and Michel Bruyninckx Impact of a water droplet with R = 42.3 m (317 pl) and velocity 5.1 m/s. The delay between each droplet is 3 sec. C. Le Clerc and D.B. van Dam Phys. Fluids 16, 3403 (2004) Slide 15 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 15 Results Christophe Le Clerc and Michel Bruyninckx Impact of a water droplet with R = 33 m (150 pl) and velocity 11.4 m/s. The delay between each droplet is 0.25 sec. Slide 16 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 16 Impacting droplets in a pixel. Movie made by Thijs van der Zanden Eindhoven University of Technology Slide 17 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 17 Results Bayer and Magarides (2004) Impact of a water droplet with R = 0.69 mm (1.38 l) and velocity 0.5 m/s. Ilker S. Bayer and Constantine M. Magarides at XXI ICTAM 15-21 August 2004 Warsaw Poland Neutral surface Wetting surface Anti-wetting surface Slide 18 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 18 Computational results Pasindideh et al 1996 Impact of a water droplet with R = 1mm and velocity = 1 m/s. M. Pasandideh-Fard, Y.M. Qiao, S. Chandra and J. Mostaghimi, Capillary effects during droplet impact on a solid surface: Physics of Fluids 8 (3), March 1996, 650-659. Slide 19 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 19 Static wetting Htte Mathematische Formeln und Tafeln I Szabo Berlin 1959 Slide 20 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 20 Definition of dynamic contact angle Jiang, Oh and Slattery formula Terence D. Blake and Kenneth J. Ruschak, Wetting: static and dynamic contact lines, Liquid Film Coating edited by Kistler and Schweitzer, Chapman & Hall 1997 U: velocity of moving contact line Slide 21 CONFIDENTIAL Dijksman/Pierik, Workshop Lorentz Centre January 4-8, 2010 21 Dimensionless numbers Volume [pl] Radius [ m] Velocity [m/s] WeReOhK