Microfluidics Flashcards
Microfluidics advantages
compact
faster and more efficient
multifunctional
mass production
less materials
safer handling
disposable
Microfluidics Disadvantages
complex
things work differently at smaller scales
harder to detect
no defined standards
things don’t scale linearly
Reynolds Number
measures if laminar or turbulent
> 4000 turbulent
< 2000 laminar
Transport mechanisms
- diffusion
entropy driven molecular movement
- convection/direction
controlled by a force
bulk fluid motion
Peclets Number
Measure if diffusion or directed dominates
> 1: convection dominates
< 1: diffusion dominates
Directed Convection Transport kinds
- Hydrodynamic
parabolic flow profile
- Electroosmotic Flow
uniform flow profile
Flow Rate
proportional to pressure difference/drop
smaller dimensions = slower flow
How to mix in microchannel
- Diffusion
increase length
- Flow focussing
flow directed in to continuous flow
- Microstructures in microchannel
creates secondary flows that mix
Materials
Silicon and Glass
Elastomers and plastics
hydrogels
paper
Silicon/glass advantages
organic solvents
metal depositing
high thermo conductivity
stable electroosmotic flow
silicon/glass disadvantages
expensive
dangerous fabrication
difficult to bond layers
can’t do valves
not gas permaeble
Elastomers Plastics advantages
Inexpensive
easy fabrication
non toxic
high resolution
reversibly or irreversibly bonded
multilayer
can make valves
gas permeable
elastomers plastics disadvantages
no organic solvents
interact with analytes limiting quantification
Hydrogel benefits
3D networks of hydrophilic polymer
highly porous
permeability
good for cell culture
Paper pros
highly porous
easy to fabricate
wiking of ligands
no pump/power needed
low cost
filters particles
paper cons
not transparent
poor detection sensitivity
evaporation from open channels
Fabrication Methods
Photolithography
chemical Etching
Physical etching
deposition
replication/moulds
3D printing
micromilling
Photoresist kinds
positive:
regions exposed become soluble
negative:
regions not exposed become soluble
Etching details
subtractive process
wet etching with chemicals
dry etching with plasma
isotropic - spherical front, undercuts mask
ansiotropic - directed, straight edges
Physical etching pros and cons
pros
faster
no clean room
cons
surface roughness
lower accuracy
physical etching methods
powder blasting
electron discharge machining
laser abalation
Replication Techniques
create high precision mold
- micro moulding
apply pdms to mould and bake
- injection moulding
inject molten plastic in mould
- hot embossing
master pressed into soft plastic
Bonding layers
silicon to silicon - fusion bonding
silicon to glass - anodic bonding
pdms - reversible by contact, irreversible by oxygen plasma
3D printing
layer by layer fabrication
fast prototyping
from 3D model
micromilling
subtractive process
rapid prototyping
Paper fabrication methods
- photolithography
- paper cutting
- wax printing
- oragami 3D structures
- hydrogel driven
paper photolithography process
- soak in resist
- prebake
- mask
- expose to UV
- post bake
- wash away resist
- plasma oxidise residual
hydrophobic polymer creates channels
Paper cutting
cut out channels
arrange and set between two layers of plastic
wax printing
draw hydrophobic wax channels on paper
Hydrogel driven devices
release fluid with stimulus e.g. temp
hence can control fluid flow
Digital Droplet based devices
generate and manipulate drops of fluids in immiscible continuous phase
digital droplet advantages
high control over droplet size, frequency with uniform
higher surface area to volume means faster transfer and reaction times
each droplet can be individually transported, mixed, reacted and analysed
allows for parallel processing
high through put
much greater control/uniformity than traditional agitation
Droplet formation factors
flow rate
flow angle
controls size and frequency
Droplet formation methods
- T junction
- flow/shear focussing
- Dielectrophoresis (DEP)
- Electrowetting (EWOD)
- Pneumatic valve pump
Concentrating Sample
- Electrophoretic
- stacking
- isotachophoresis
- isoelectric focussing
- temperature gradient focussing - support based
- solid phase extraction
why microfluidics good for biology
- channels and chambers are same size as cells
- study cell interactions in controlled environment
- single cell handling
- real time observations
- continuous flow systems
- can sort cells e.g. DEP
biological applications
- mimick biological functions/organs
create microstructures for trapping cells and reducing shear stress
- bioreactor
chemical processes using arranged cells
- cell cultivation
trap cells in microstructures
- cell assays
create chemical gradients
- 3D hydrogel cell cultivation
contains water and forms 3D structures
Digital Droplet applications
cell encapsulation
mixing
drug delivery
T junction
cell size depends on flow rates and channel size
flow shear focussing
increasing dispersed phase flow creates smaller droplets at higher frequency
DEP details
polarisable fluid at higher dielectric permittivity
apply nnon-uniform elecric field generating droplets
magnitude of voltage and frequency determines size
electrowetting details
electric field reduces interfacial energy/contact angle
causes wetting of surface
when voltage turned off surface becomes hydrophobic again creating droplets
size dependent on field strength, frequency and channel size
higher frequency produces smaller droplets
Flow rate minimisation
rate decreases as fluidic resistance higher in microchannels
same time but lower reagent consumption
Analytical Applications
Isotachophoresis preconcentration
solid phase extraction
purification of DNA for pcr analysis
isoelectric focussing
Biological Applications
Replicating biological functions e.g. lung on a chip
Bioreactor
Cell cultures
PDMS soft lithography process
- coat silicon wafer with photoresist
- soft bake
- apply photo mask
- expose to uv
- post bake
- develop photoresist
- apply pdms over mould and bake to cure
- remove PDMS layer
- permanenly seal by oxygen plasma
Why Biological
Microchannels match cell size
study cell-cell/cell-matrix
trap cells in microstructures
can form complex cell structures/environments
gradients
sort cells
real time obserations
shear stress minimisation
microstructures reduce shear stress
improves cell growth and survivability