1. Instituto Superior Técnico
2009/2010
Engenharia de Células e Tecidos
By: David Conceição nº64405 MBioNano
Johannes Österreicher nº68694 MEng.Quimica
2. 1. What is microfluidics?
2. Micro –fabrication process
3. Applications
3.1 State of the art
3.2 Case studies
4. Conclusions
Microfluidics for cell culture
3. 1. What is microfluidics?
The science and technology of systems that process or manipulate
small (sub-microliter-scale: nl, pl, fl and below) amounts of
fluids,using channels with dimensions of tens to hundreds of
micrometres or below.
I’m too big for
this stuff!
Microfluidic Chemostat
Microfluidics for cell culture
4. - Low sample consumption
- Fast analysis times
- High throughput screening
- Possibility of efficient data
- Allow single-use devices
- Incorporation of sample preparation and
product purification elements
- Massively parallel microfabrication Laminar flow
- Ease of making different designs
- Replicate essays in same device possible
The behaviour of fluids in the micro-scale is very different than in
the macro-scale
Microfluidics for cell culture
5. Turbulent flow
Mixing
Fluid behaviour depends on several parameters
-Reynolds number
- Navier Stokes equations
- Knudsen number
- Peclet number
Microfluidics for cell culture
6. Once upon a time…
Started in the 1980s in microanalytical chemistry and later in
biodefence, molecular biology and microelectronics
- gas-phase chromatography (GPC), high-pressure liquid
chromatography (HPLC) and capillary electrophoresis
(CE);
- detectors for chemical and biological threats;
- high-throughput DNA sequencing;
- microelectromechanical systems (MEMS)
Microfluidics for cell culture
7. 1. What is microfluidics?
2. Micro –fabrication method
3. Applications
3.1 State of the art
3.2 Case studies
4. Conclusions
Microfluidics for cell culture
8. 1. 2. Micro-fabrication process
UV light
Photomask
photoresist
Microchannel-
patterned mold
Pouring PDMS on
the patterned
mold
PDMS curing,
cutting, and
bonding
Microfluidics for cell culture
9. The ‘plumbing’
Microvalves
Micropumps
Microchannels
Microfluidics for cell culture
10. 1. What is microfluidics?
2. Micro –fabrication method
3. Applications
3.1 State of the art
3.2 Case studies
4. Conclusions
Microfluidics for cell culture
11. 1. 2. 3. Applications
Microfluidics for cell culture
Macro-scale systems are completely different from the
in vivo-environment : different behaviour of cells!
Microfluidics can mimic the in vivo-
environment of cells (channels, tissues,
membranes etc.)
Example: Human circulatory system to feed
the cells and remove waste products
Microfluidics for cell culture
13. Cell- on a chip
Microfluidics for cell culture
14. 1. 2. 3. 3.1 State of the art
Microfluidics for cell culture
15. Schematic suggesting the assembly of
modules in a microfluidic chip.
Schematic diagram of reversible sealing of
microfluidic arrays onto microwell patterned
substrates to fabricate multiphenotype cell
arrays.
Microfluidics for cell culture
16. 1. 2. 3. 3.1 3.2 Case studies
Two cell populations with intercellular
communication
System design
Microfluidics for cell culture
18. Experiments with living cells:
N9 Microglia
SY5Y Neuroblastoma
To study intracellular communication involved in
brain diseases
Microfluidics for cell culture
20. Cultured HeLa, MCF-7, Jurkat, and CHO-K1 cells for
up to five days and subsequently lysing the cells
without adding lysing reagents
Cell loading
Images of breast cancer cells (MCF-7)
cultured inside a device. After 72 h, the cells
have formed spheroids. Scale bar is 75 mm.
Microfluidics for cell culture
21. Dynamics of cell lysis by electrochemically
generated hydroxide
Microfluidics for cell culture
22. 1. What is microfluidics?
2. Micro –fabrication method
3. Applications
3.1 State of the art
3.2 Case studies
4. Conclusions
Microfluidics for cell culture
23. 1. 2. 3. 3.1 3.2 4. Conclusions
Microfluidic devices can be a start ing point for lab on a chip,
joining multiple operations.
It can simulate the in vivo conditions.
Microfluidic platforms are very useful
alternatives for future cell biology studies
and cell-based assays.
Most culture systems do not utilize a variety
of cellular analyses
Cross
High surface-to-volume ratio of microchannels enhances the contamination
adsorption of molecules onto channels walls, reducing the
effective concentration of reagents
Dificulty controlling fluid behaviour
Microfluidics for cell culture
24. Bibliography
- Bruzewicz, D., McGuigan, A. & Whitesides, G. Fabrication of a modular tissue construct in a microfluidic
chip Lab on a Chip, Royal Society of Chemistry, 2008, Vol. 8(5), pp. 663-671
- Khademhosseini, A., Yeh, J., Eng, G., Karp, J., Kaji, H., Borenstein, J., Farokhzad, O. & Langer, R. Cell
docking inside microwells within reversibly sealed microfluidic channels for fabricating multiphenotype cell
arrays Lab on a Chip, Royal Society of Chemistry, 2005, Vol. 5(12), pp. 1380-1386
- Lovchik, R., Tonna, N., Bianco, F., Matteoli, M. & Delamarche, E. A microfluidic device for depositing and
addressing two cell populations with intercellular population communication capability Biomedical
Microdevices, Springer, 2010, Vol. 12, pp. 275–-282
- Nevill, J., Cooper, R., Dueck, M., Breslauer, D. & Lee, L. Integrated microfluidic cell culture and lysis on a
chip Lab on a Chip, Royal Society of Chemistry, 2007, Vol. 7(12), pp. 1689-1695
- Wheeler, A., Throndset, W., Whelan, R., Leach, A., Zare, R., Liao, Y., Farrell, K., Manger, I., Daridon, A. &
others Microfluidic device for single-cell analysis Analytical Chemistry, ACS Publications, 2003, Vol. 75(14),
pp. 3581-3586
- Whitesides, G. The origins and the future of microfluidics Nature, Nature Publishing Group, 2006, Vol.
442(7101), pp. 368-373
- Young, E. & Beebe, D. Fundamentals of microfluidic cell culture in controlled microenvironments Chemical
Society Reviews, Royal Society of Chemistry, 2010, Vol. 39(3), pp. 1036-1048
Microfluidics for cell culture
25. The end
Any questions?
Microfluidics for cell culture
