microfluidics: introduction [email protected]
TRANSCRIPT
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
Radiolabeling synthesis reactor for PETS. Quake
256-mixer
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 numberMicrochannel:
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
In laminar flow the streamlines do not mix.
Mixing is predominantly by diffusion.
v ~ 100 m/year
V ~ 1 µm/s
Re ~ 100
Sperm selection
Cell/bead sorter (1)sample flow in
hydrodynamic focusing
fluorescence detection
electrokinetic actuation
separated streams
Cell/bead sorter (2)
MicrofabricationNanofabrication
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
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
d = √2Dt distance travelled
Macroscopic vs. atomisticDiffusion 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/ 6ηRH RH= kT/ 6η 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