Alternative MicroFabrication and Applications
in Medicine and Biology
Massachusetts Institute of Technology
6.152 - Lecture 15
Fall 2003
These slides prepared by Dr,Hang Lu
MIT BioMEMS,Fall 2003
Outline of Today’s Materials
Intro
Alternative materials and fabrication techniques
Applications in biology and chemistry
Applications in medicine
A real MTL example of rapid prototyping
MIT BioMEMS,Fall 2003
Micro Systems for Bio / Med
Micro systems have characteristic length scale in the
order of microns,(Human hair width is ~100
microns.)
The applications of these systems span
– Biological analysis
– Medical diagnosis
– Chemical analysis and synthesis
– Drug discovery
– Drug Delivery
–…
MIT BioMEMS,Fall 2003
Immunoassay chip (Aclara)
Advantages of Micro Systems
Small length scale
Laminar flow (good and bad)
High surface-to-volume ratio
Small thermal mass
Close to some biological length scale
Shorter processing time
Less sample / reagent required
Disposable
Automation possible
Parallel operation possible – high throughput
Integration possible
Whitesides (Harvard U.);
Photo credit,Felice Frankel
MIT BioMEMS,Fall 2003
Alternative Materials
Materials requirement for bioMEMS is different from
that for MEMS,
Desired properties of bioMEMS materials
– Biocompatible
– Chemically modifiable
– Easy to fabricate
– Economic
– Soft and compliable
–Smart
If not Si and glass,what then?
Polymers (e.g,PDMS,PMMA) are good materials
especially for biological applications,
MIT BioMEMS,Fall 2003
Alternative Fabrication Methods
Soft lithography
Micro molding in capillaries
Replica Molding
Micro contact printing
(MIMC)
Y,Xia and G.M,
Whitesides (Harvard U.)
MIT BioMEMS,Fall 2003
Other Polymer Methods
Hot embossingHot embossing
Injection molding
Stamp (master)
Heat and pressure
Thermoplastic
Substrate
MIT BioMEMS,Fall 2003
Lab-on-a-chip (Caliper)
Examples of bioMEMS Systems
Detection and diagnosis
Synthesis and analysis
Interaction and interrogation
Treatment
MIT BioMEMS,Fall 2003
DNA electrophoresis I
PCR chip (A,Manz,Imperial College)
Etched glass
Continuous
Three T zones
Thermal insulation
MIT BioMEMS,Fall 2003
DNA electrophoresis II
Electrode insertion
scheme matching high
throughput need
Mathies (Berkeley)
High throughput
Etched glass
MIT BioMEMS,Fall 2003
Protein microarrays
Schreiber (Harvard U.)
Small molecule –protein interactions
High throughput screening of
compounds
Printed glass slide
Protein – protein interactions
Protein profiling
Derivatized glass slide
MacBeath (Harvard U.)
MIT BioMEMS,Fall 2003
MicroFAC
Fluorescence based sorting
PDMS molded from silicon master
Feedback controlling fluid flow
(electroOsmotic flow)
MIT BioMEMS,Fall 2003
DEP Cell Sorter
U,Texas – Houston
Rare cell detection
Field flow fractionation using
dielectrophoretic force
MIT BioMEMS,Fall 2003
Microfluidics on a CD
Gyros Inc,
Centrifugal forces
Metering
Fluid delivery
Protein analysis
Hematology
MIT BioMEMS,Fall 2003
Examples of bioMEMS Systems
Detection and diagnosis
Synthesis and analysis
Interaction and interrogation
Treatment
MIT BioMEMS,Fall 2003
Synthesis with Microreactors
Gas phase
reactor (MIT)
Multi-phase
reactor (MIT)
Liquid phase
reactor (MIT)
Microreactors for synthesis and chemical researches
Temperature and pressure sensors,heaters,heat
exchangers,valves,separators…
MIT BioMEMS,Fall 2003
Lab-on-a-chip (Caliper)
Examples of bioMEMS Systems
Detection and diagnosis
Synthesis and analysis
Interaction and interrogation
Treatment
MIT BioMEMS,Fall 2003
Max Planck Institute
Neuro implant
Neuro-circuit interaction – neuro recording
Prosthesis research
Chemical delivery – molecular probe
Issues with long term implant – bio compatibility
MIT BioMEMS,Fall 2003
Lab-on-a-chip (Caliper)
Examples of bioMEMS Systems
Detection and diagnosis
Synthesis and analysis
Interaction and interrogation
Treatment
MIT BioMEMS,Fall 2003
Drug-delivery
Santini (Microchips)
Controlled delivery
Dry chemicals packed in wells
Electrochemistry of gold film
with body fluid (erosion)
Quick response time
MIT BioMEMS,Fall 2003
Tissue Engineering
neoglyco-protein
neoglyco-protein
E,coli
E coli
microfluidics
contact printing
Patterning cells using
Patterning cells using micro
Patterning protein
Co-culture of cells
(hepatocytes and
BSA
erythrocytes
fibroblasts)
erythrocytes
MIT BioMEMS,Fall 2003
Small Materials – e.g,Hydrogel
Beebe (U Wisconsin)
Hydrogel
pH responsive
Sensing and regulating
In situ fabricated
MIT BioMEMS,Fall 2003
NEMS/nanofluidics
Craighead (Cornell U.)
Using entropic effect
of large DNA molecules
Near field fluorescence
detection
MIT BioMEMS,Fall 2003
MIT BioMEMS,Fall 2003
MIT BioMEMS,Fall 2003
MIT BioMEMS,Fall 2003
MIT BioMEMS,Fall 2003
MIT BioMEMS,Fall 2003
MIT BioMEMS,Fall 2003
MIT BioMEMS,Fall 2003
MIT BioMEMS,Fall 2003
MIT BioMEMS,Fall 2003
Our Process
MIT BioMEMS,Fall 2003
Process Flow - Overview
Si
Unexposed
SU-8 (50 μm)
Surface treatment &
casting PDMS
photolithography
UV light
mask
Si
PDMS
Si
removing elastomer from
master
development
PDMS
seal against glass after plasma
treatment and insert tubing
“master”
tubing
Si
MIT BioMEMS,Fall 2003
The Master Material - SU-8
Negative photodefinable epoxy
Capable of forming high-aspect
ratio (25:1) and thick (2mm)
structures
Used as electroplating template,in
microfluidic applications,and as
structure material for other
microfabrication techniques
100 μm
R,Jackman (MIT)
R,Jackman (MIT)
250 μm
Si
MIT BioMEMS,Fall 2003
Replica Material - PDMS
CH
3
CH
3
CH
3
Upon treatment in oxygen plasma,
CH
3
Si
O Si O Si CH
3
PDMS seals to itself,glass,silicon,
silicon nitride,and some plastic
CH
3
materials.
CH
3
CH
3
n
Plasma oxidation
(~ 1 min)
Air (~ 10 min)
contact PDMS
surfaces
irreversible seal:
formation of
covalent bonds
MIT BioMEMS,Fall 2003
Photolithography Steps
1,Define patterns on first layer
1.1 EML hotplate dehydrate wafer at 200C for 1 hr
1.2 EML hood spin coat SU-8
1.3 EML hotplate prebake 15 min at 105C (ramp up
from room temp slowly and cool to < 60C)
1.4 EML photo expose through the mask
1.5 EML hotplate postbake 15-20 min at 105C
1.6 EML hood develop SU-8 in developer (PGMEA)
1.7 EML hood dry wafers with nitrogen
1.8 EML hood silanize wafers (1 hr)
MIT BioMEMS,Fall 2003
Micromolding Steps
2,Molding SU-8 structures with PDMS
2.1 Mix prepolymer and initiator (10:1)
2.2 Degas the mixture
2.3 Cure PDMS at 65C for 2 hr
MIT BioMEMS,Fall 2003
Packaging
3,Making PDMS-based devices
3.1 Carefully remove PDMS from wafer
3.2 Cut devices out using a razor blade
3.3 Punch holes in PDMS
3.4 Clean PDMS and glass substrates
3.5 Plasma ash PDMS and glass substrates
3.6 Bond
3.7 Insert tubing
3.8 Test
MIT BioMEMS,Fall 2003
Our Mask
MIT BioMEMS,Fall 2003