Microfluidics: introduction sami.franssila@aalto.fi

Why miniaturize ? because it is possible? because it is improves performance ? because it opens up new possibilities ? "Courtesy Sandia National Laboratories, SUMMiTTM Technologies, www.mems.sandia.gov"

Start of an era: Gas chromatograph on silicon wafer (1979): -injector -separation channel -thermal conductivity detector Gas fluidics minor activity compared to liquid fluidics (which started in 1990)

Drug delivery 100 identical drug chambers Drug release by electrical puncturing of a gold membrane

APCI-MS, Atmospheric Pressure Chemical Ionization Mass Spectrometry

Protein interaction chip 256-mixer Radiolabeling synthesis reactor for PET S. Quake

Is microfluidics different ?

Channels by embossing Bonding a cover slip

Closed channels: bonding One wafer holds channel; other is planar Both wafers hold structures; need alignment Misalignment ! Is channel cross section important ?

Laminar vs. turbulent flow

Reynolds number (Re) ratio of inertial to viscous forces Re = ρνD/η ρ = density of fluid (kg/m3) ν = linear velocity (m/s) D = dimension of the system, diameter (m) η = viscosity of the fluid (Pa*s = kg/m*s) viscosity is the quantity that describes a fluid's resistance to flow small Re means large viscous forces

Reynolds number Microchannel: ρ = 1 kg/l (= 1000 kg/m3) v = 1mm/s (=10-3 m/s) D = 100 µm diameter (=10-4 m) η = 0.001 kg/m*s Re = 1000* 0.001 * 10-4/0.001 (all in SI units) Re = 1 If Re < 2300, flow is laminar (microfluidics always)

“Swimming” at high Reynolds: streamlined shape; yet turbulence Re = ρνD/η = 1000 * 10 *10/ 0.001 = 100 000 000

Swimming at low Reynolds: shape does not matter Swimming movements of CR (Chlamydomonas Reinhardtii) Cell size ca. 10 µm, flagella 12 µm Flagella shown at different stages of the stroke (1-7 power stroke) 40-60 Hz frequency 100-200 µm/s speed (One stroke 2-4 µm, or 20-40% of CR size)

Slow mixing in laminar flow v ~ 100 m/year V ~ 1 µm/s  Re ~ 100 In laminar flow the streamlines do not mix. Mixing is predominantly by diffusion.

Sperm selection

Cell/bead sorter (1) sample flow in hydrodynamic focusing fluorescence detection electrokinetic actuation separated streams

Cell/bead sorter (2)

Nanofabrication Microfabrication

Microfabricated sizes Linewidth 10-100 µm typical Channel depths 1-100 µm typical Gaps 10 nm and up, by bonding or sacrificial etching

Nanofluidics: molecular size equals channel size Side view Top view

Diffusion d = √2Dt distance travelled Object Size Diffusion constant Distance in 1000 s small ion r=0.1 nm D=2*103 µm2/s 2000 µm small protein r=5 nm D=40 µm2/s 280 µm virus r=100 nm D=2 µm2/s 63 µm bacterium r=1 µm D=0.2 µm2/s 20 µm mammalian cell r=10 µm D=0.02 µm2/s 6.3 µm hemoglobin: D = 7*10-7 cm2/s = 70 µm2/s

Macroscopic vs. atomistic Diffusion constants can be measured in macroscopic experiments Theory developed by Einstein in 1905 established a connection between atomic size (RH= hydrodynamic radius) and diffusion constant D = kT/ 6ηRH  RH= kT/ 6η D where η =viscosity; kT = thermal energy r small protein = 1.38*10-23 *300/6*3.14*1*10-3*40*10-12 r small protein = 5.5*10-9 m

Scaling: diffusion & detection Cube volume 1 µL 1 nL 1 pL 1 fL Cube edge 1 mm 100 µm 10 µm 1 µm Diffusion time 500 s 5 s 0.05 s 0.5 ms #molecules (1 µM) 6*1011 6*108 6*105 600

Detection limits vs. volume Sabeth Verpoorte, IMT Neuchatel

Chemical microfluidics -separation systems (CE, LC, GC,...) -detectors (microelectrodes, MS, photodiodes,...) -droplet generators (ESI) -ionization systems (corona, UV, ...) -synthesis reactors -gradient generators -crystallization chips -...

Physical microfluidics cooling ICs and high power lasers power-MEMS: combustion engines, fuel atomizers, fuel cells fluidic optical switching fluid sensors (rate, viscosity, shear, ...) MAVs = Micro Air Vehicles microrockets fluidic logic

Electronic paper by electrowetting

Microfluidic benefits Many functions can be integrated in a single device Small volumes lead to fast reactions Sensitivity is enhanced because of high surface-to-volume ratios Laminar flow easy to control