Introduction to Microfluidics

C. Ftterer,
Institut Curie & Fluigent SA, Paris

Miniaturisation &
Integration

Micro-Pipettes
Problems:
Minimal volume: 1l
Samples unprotected
against evaporation &
contamination (dust)
Slow and tedious operation
Manipulation errors
Difficult automation
through expensive robots

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Why Traditional Instruments are

Unsufficient
Complexity: 100.000 genes
and more than 106 proteins in
human body.
Spatio-temporal dynamics of
cellular/molecular processes.
Big volumes: low speed of
thermal and molecular diffusion
and reactions.

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Size of Biological Objects

pl

nl

?
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ml

Solution: Microfluidics
Come Closer to Cells and Molecules!

Institut Curie
Smallest fluid quantities (single cell)
High throughput (statistics)
Faster physico-chemical processes (diffusion more efficient)

Towards quantitative biology!

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Pioneer Publication
Electronic Chips

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Chips are not Chips...

Electronic Chips

Microfluidic Chips

DNA-Chips

Institut Curie
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Many Advantages of Miniaturisation

Size: nanoliters, single cell and molecule

manipulations,
Superior flow control (no mixing),
Speed: diffusion: 1mm -> 15 min, 10m -> 100ms),
Integration & parallelisation,
Protection against contamination and evaporation,
Kinetics easy to study.

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Microfluidics is Not New

- Arteria and venes in animals
- Capillaries in plants

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How to Make it:

Microfabrication

Photolithography

Mask:

PROTOCOL
Spincoat photosensitive solution,
Dry
Put mask on top
Expose to UV
Wash
Heat
Master

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Rapid Prototyping: Principle

Chip-Fabrication
Master

Chip (PDMS)

Master

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Surface-Patterning
by Contact Printing

Rapid Prototyping: Mask and Mould

Chip-Fabrication

Chip (PDMS)

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Rapid Prototyping: Mould

Chip-Fabrication

Chip (PDMS)

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Mould: Vials
Reproducible and clean vials

Polymer
Chip (PDMS)

Air
Microstructure

Master

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Rapid Prototyping: Master I

Chip-Fabrication

Chip (PDMS)

Much more stable!

Pallandre, Ftterer et al., 2006

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Rapid Prototyping: Master II

Chip-Fabrication

Chip (PDMS)

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Rapid Prototyping: Polyester Master

Chip (PDMS)

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Taylored Channel Systems, Integration

Quake et al.
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Flow Control

Micro-Fluidics: Defined Flow Profile

Laminar profile

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Difficulty: Flow Control through Interfacing

(Contraction)

1cm

10m

Human
scale

Ratio: 106 !!!

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Molecules and
Cells

Flow Control: Syringe Pumps

Syringe pumps:
Long response time
Strong hysteresis
Limited volume
Stopped-flow/flow inversion difficult

Slow
Bubbles
Mechanical drive

Bending of tubes
Atmospheric Pressure
Elasticity

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Flow Control: Electroosmotic Pumps

-+ +- +- +- +- +- +- +- +- +- +- +- +- +- ++++++++++++++++

---------------

Reproducibility problems with

biological fluids
Time consuming preparation

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Flow Control: AC-Electroosmotic Pumps

Reproducibility problems with

biological fluids
Time consuming preparation
Electrodes are consumed
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muTAS 2005

Flow Control: Microfabricated Pumps

Pressure
Pulsed flow
Complex Microfabrication
Objects are squeezed (Cells!)

Quake et al.
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Flow Control
Peristaltic pumps

Pulses
Long time constant
Objects are squeezed
Tubes have to be exchanged

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Capillary Forces or Centrifugal Systems

Blood test

Separation of blood plasma

(Zengerle et al. IMTEK)

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Pumping through Moving Objects

Optical
tweezer

Optical
tweezer

Leach et al. Lab Chip 2006

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New Principle for Microfluidics Flow Control

Semi-open pneumatic pressure control

Pneumatic
Wheatstone bridge
Microchannel
Microchannel

Calibrated
Calibrated leaks
leaks

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New Principle for Microfluidics Flow Control

Semi-open pneumatic pressure control
Very short response time (< 1s),
No pulsations,
Symmetry: flow in both directions,
Dynamic pressure feedback:
automated compensation of
- back pressures,
- bubbles,
- environmental pressure
changes.

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Vision of the Lab

tomorrow

today

Microfluidic Chip:

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MicroFluidic Control System

Start-up Fluigent
Industrial prototype
20cm

Pressure output

www.fluigent.com
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Very Fast Response in Microchannel

single T4 DNA
molecule

playing with sliding knob

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Applications

Low Dispersion Suspensions

Joanicot, Ajdari, Science, 2005

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Nano-Pores: DNA-Positioning and

Pressure Control Winterhalter group, CF,...
Channel 1

Channel 2

Pore

Channel 1

Channel 2
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Pore

Micro Patterning for Cell Assays

Piel & Bornens, Institut Curie

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Cells Adapt Strongly to External Conditions

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Cell Assay on Patterned Surfaces

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Cells on L-Substate Close to Migrating Cell

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Cell Cycle Becomes Reproducible

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2-Dimensional Gradients

Hung, Lee, et al. 2004

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Symmetry

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Magnetic Bead Micro Reactors

Slovacova Futterer et al., Lab Chip 2005

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Fast Protein Digestion in Microchannels

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Rapid Cancer Diagnosis

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Nano Transport

Hess et al. 2006

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