MEMS: Micro Electro Mechanical Systems Flashcards
http://www.zyvex.com/nanotech/feynman.html 1) Jurgen Fritz. Cantilever biosensors. Analyst, 2008, 133, 855-863. 2) Kyo Seon Hwang et. al. Micro and nanocantilever devices and systems for biomolecule detection. Annual Review of Analytical Chemistry, 2009, 2, 77-98.
Microfabrication
used to manufacture integrated circuits and MEMS
Minaturise for
enhanced performance
scalable fabrication and quality
cheaper at larger volumes
Positives
Force effects required for pzieoelectric effect as close together High surface to volume ratio - good thermal dissipation Quick Response Lower Power Consumption reduced footprint -array dynamic range electrical integration minimally invasive
Negatives
High frictional forces
Manufacturing inaccuracy can be higher
strong surface effects- aggregate due to charges
Piezolelectric l
ceramic and crystalline display linear electromechanical response to stress or electric field
Piezoelectric used in MEMS
actuate mechanical movement
transduce mechanical response to discernible electrical response
Piezoresistive effect
semi-conductor material (doped silicon) undergoes mechanical stress which resistance properties
transduce mechanical event into an electrical response see change in resistance
temperature sensitive, compensate with Wheatstone bridge
Electrostatic effect
decreases with the square of the distance
actuation - attractive/repulsive force between moving and fixed plates as voltage applied between them
Sensing - capacitance (energy store) changes as distance between plates changes
Pressure sensors
blood pressure
intracranial/cerebro spinal fluid/intraocular/endoscopes for organs
BioMEMs
biological sensor - recognition element in contact with transducer —> electrical signal
MEMS functionalised with a recognition biomolecule that can pull down a specific target molecule and lead to a physical mechanical change that can be observed
Deliver drugs topically
microfabrication of microneedles - no pain, not long enough to reach nerve endings, also continuous extraction
shallow penetration - reduce infection
deliver where most effective, larger molecular
Ideal Bio-MEMS (3)
dynamic range
low limit of detection
quick analysis time
Advantages of Bio-MEMS
Could show excellent LOD due to scaling
Microfabrication - low cost mass production
Label free
Array format for multiplexing (different markers)
Cantilever
Beam anchored at one point
Microneedles cantilever
stiff to penetrate skin - short thick and wide
Diagnostic cantilever
flexible - long thin and narrow
transduction through mechanical deflection or or dynamic mechanical motion
Properties of microcantilever dependent on
geometry and material properties
stiffness Kspring = EWTcubed/4Lcubed
Static mode of detection/stress mode/deflection mode
mechanical compliance of cantilever increases with uniform reduction in size (smaller LOD) (when binding analyte) (surface stress not weight)
Static mode cantilever action
bend up or down
similar to bimetallic strip on heating (one metal expands more)
Static mode mechanism
biomolecules bind - surface stress developed electrostatic repulsion/attraction conformational change hydration change steric interaction
Probe coating contracts relative to cantilever
creates tensile surface stress - bends up
Probe coating expands relative to cantilever
creates compressive surface stress - bends down
Recognition molecule bind one side
and not the other
Activate - thiol chemistry
Passivate - silane chemistry
Measure/Record microcantilever detection
beam deflection/optical lever detection - reflective gold
recorded on position-sensitive photodetector
Advantage of optical lever detection
sensitive - 0.1nm resolution
Disadvantage of optical lever detection
bulky external optical equipment with two alignments
Piezoresistive Readout
embed piezoresistive material on cantilever
as cantilever deflects - change resistance - electronic readout
Advantages of piezo
Miniaturised
simple readout
Disadvantages of piezo
resolution not as good ~1nm
Static mode considerations (5)
- in real time in aqueous environment
- temperature sensitive
- change buffer composition –> deflection
- Differential reference sensors needed to remove unwanted background
- unpredictable when protocol developed
Dynamic mode/resonant mode: resonance
F0= (1/2pi) x (squareroot spring constant/mass)
tendency of a mechanical system to oscillate with greater amplitude at a certain frequency
depends on geometry (mass) +spring constant
Dynamic mode mechanism
Apply voltage to piezoelectric actuator to drive to resonance
(external or deposited onto cantilever)
Add mass to the cantilever
reduce resonant frequency
minimal detectable mass added proportionate to total mass
Advantage of dynamic mode
very low LOD
Disadvantage of dynamic mode
viscous damping (liquid) dissipated to fluid as thermal energy solution - carry out within cantilever long analysis time
Biointerface
Border between aqueous environment and physical devices - addition of recognition molecules
DNA/RNA apatamers
single stranded, form secondary structures
peptide apatamers
artificial antibodies
recognition molecules should
have affinity/ dissociation constant in nM to pM
streptavidin and biotin 10x-15
SAMs
Self assembling monolayers
basis of bio-interface assembly
SAMs - gold thiol chemistry
Sulphur Base (thiol (SH)) - spontaneous covalent bond with gold aliphatic Carbohydrate chain - hydrophobic - pack densely Headgroup - add functionality - cross link further molecules
SAMs - silicon base
(alkyl)silane molecule forms covalent bond also
Head Groups (5)
Amino - NH2 Carboxy - COOH Aldehyde - CHO Thiol - SH Hydroxyl - OH
Physisorption mechanism and groups
Charged Group (NH3+, COO-)
Chemisorption mechanism and groups
Cross-linking (ALL)
Physisorption Advantages (2)
simple cheap fast
non-covalent bonding improved using tags
Physisorption Negatives (3)
random orientation
changes to pH etc cause leaching
Physical contact could unfold protein
Physisiorption solution
tag head group and target molecule with biotin and use streptavidin (tetramer) to bind the two
Chemisorption Advantages (3)
Covalent bonding stable over time (amide bond)
Specific cross-linking fairly simple
Small physical contact with interface - no unfolding
Chemisorption Disadvantage
Orientation is random
Oriented Chemisorption
suitable for receptors, protein aptamers , synthesised DNA/RNA
if adding cysteine (mutagenesis), must be no other cysteines - could have receptors pointing away
Antibody chemisorption
bind constant region via carbohydrate group etc
could biotinylate
Blocking layers
eliminate non-specific binding of proteins - bio-inert
e.g. bovine serum albumin
polyethylene glycol - block physisorption
Blocking layer mechanism
densely form hydrogen bonds with water - create thick layer - molecules flow over
Efficient Sensing Surface/bio-interface (4)
Optimal density recognition molecule
absence non-specific binding (not too many biotin etc.)
stability
excessive high density cross-linker - steric interference and reduced recognition molecule immobilisation
Clean gold with
Hydrogen peroxide and sulphuric acid
Require smooth surface
SAMs not line up
Site specific immobilisation
soft lithography - microcontact printing
microcapillaries
microspotter
dip pen nanolithography
Microcontact printing
create master stamp by inking with cells/proteins on cast PDMS
soft nature protects ink and substrate
Microcontact considerations
PDMS modified make it hyrdrophilic for biomolecules
swelling in aqueous solvents - poor marking
stamp may degrade
requires skilled operator
MEMS mechanically sensitive
Microcontact printing positives
simple direct write
submicron resolution
Functionalise microcantilevers with
microcapillaries
microspotters
simple write, but poor resolution
Dip pen nanolithography
AFM tip - 0.1nm
molecular ink thioalkane 15nm
protein in liquid ink 250nm
Dip pen positives
high resolution
direct write
potential for registration - exact positions
Dip pen negative
expensive
slow processing
limited parallelisation capabilites