Transcript uTAS04_poster - Carnegie Mellon School of Computer Science

Microdialysis
Patient Monitoring
Doctors usually monitor physiology on a
real-time basis such as heart rate, blood
pressure, etc.
SUSPENDED, POROUS CELLULOSE ACETATE
MEMBRANES FOR MICRODIALYSIS USE
George C. López1
Gary K. Fedder1,2
In vitro microdialysis setup with close-up of semi-permeable
membrane interface
Physiological salt solution
is pumped through the
microdialysis probe.
Microdialysis setup
A more direct indicator of a patient’s
status is using microdialysis
Institute, 2Electrical and Computer Engineering Dept.
Carnegie Mellon University Pittsburgh, Pennsylvania, USA
Glass
beaker
1Robotics
Micro Total Analysis System (mTAS) 2004
Malmö, Sweden
Microdialysis is a real-time technique to
monitor the chemistry of the extracellular
space in living tissue.
Probe Interior
Assessing chemistry in a tissue’s vicinity should provide more
accurate data on biochemical and pharmacological events occurring in
a patient.
Conventional Microdialysis Probe
MEMS-based Device Concept
Concentration gradient develops across
semi-permeable membrane interface.
Sampled molecules diffuse into probe.
Fabrication Process Flow
Mask
Microdialysis
Membrane
Buffer
Inlet
Silicon
(a) Film patterning
Silicon Substrate
Advantages of silicon-based
(b) Silicon etch
 Semiconductor fabrication technology
 Miniaturization, Multiplicity, and Microelectronics
 Standard processes, no assembly required
Microchannel
(c) Porous polymer spin-on
Phase Separation Process
Variables in the procedure
5
 Choice of polymer
6
7



3
2

Step 2
Desired polymer is chosen, in my case it was cellulose
acetate powder.
Step 4
Solution is spin cast onto a silicon substrate at a specific
rotational speed.
Polymer is dissolved in a miscible solvent at a desired
concentration. N,N-dimethylacetamide (DMAc) solvent used.
Step 5
Substrate is then immersed into a room temperature
water bath overnight.
Step 6
Step 3
Cellulose acetate film
Silicon
substrate
 Acquisition, fractionated collection, and sensing on-chip
4
Step 1
process step.
 Able to span up to 75 micron wide
silicon trench.
 Polymer’s wetting characteristics are
largely responsible for its ability to fill
or span across a cavity.
Porous
Polymer
 Integrated approach
Phase Inversion Process
1
 Deposition of polymer is final
Microchannel
Porous Polymer Fabrication
Porous Polymer Fabrication
Sampled solution
Semi-Permeable
Membrane
Output fractionation and sensing
Disadvantages
 Probes are hand assembled
 Limited lifetime
 Large fluid dead volume
 Affects temporal
resolution
Collected dialysate will
contain a representation of
tissue’s chemistry
Polymer-solvent mixture is created (Rotating arm,
mixing takes overnight). Viscous solution is created
Solvent and non-solvent are immiscible. Cellulose
acetate precipitates from solution with void regions.
Substrate allowed to air dry. A thin, porous cellulose
Step 7 acetate film is formed.
Characterization of Polymer Film
Design of Experiments


Cellulose Acetate
Choice of solvent
N,N-Dimethylacetamide
Polymer concentration
---Variable--Spin speed
---Variable--Evaporation time
---Variable--Composition of coagulation bath 100% deionized water
Temperature of coagulation bath Room temperature
 Factorial experiment designed for three variables.
 Visual confirmation of results using SEM, AFM, and light
microscopy.
Optimal Settings for Porous Film
SEM imaging of cellulose acetate
Polymer Concentration
(max)
(min)
Optimum conditions:
Polymer Conc. 10% (w/v)
Spin Speed
2.5 kRPM
Evap. Time
< 5 seconds
Low speeds caused considerable peeling of
polymer
Set of 15 different runs
performed to determine
optimum processing
conditions
At high polymer concentrations, rough
surface texture and small density of pores
(max)
Evaporation Time
Close-up magnification
(max)
Spin Speed
At low polymer concentrations, film is too
thin, coverage issues
Polymer Concentration (w/v) 5%, 10%, 15%
Spin Speed 1 kRPM, 2.5 kRPM, 4 kRPM
Evaporation Time <5 sec., 30 sec., 1 min.
Microdialysis Chip: MWCO Determination
Polymer Spanning Long Channels
Longer channels
50 um wide channel. Bridges: 5 um width, 50 um spacing
Inlet/Outlet tubing
Fluidic interconnect was attached to the
inlet/outlet ports to interface with the
microchannels.
The cellulose acetate showed
permeability to myoglobin (MW=17 kDa)
and soybean trypsin inhibitor (20 kDa)
plane shrinkage of the film during drying. Considerable amount of
film stress causes delamination.
 Long channels provide less support, therefore polymer tears and
delaminates. Series of spaced bridges offer structural support as
shown on right.
 A porous cellulose acetate film was suspended over a silicon
channel using a standard fabrication process of spin coating.
 Although the polymer undergoes considerable stress during
drying, a 75 micron wide cavity was spanned.
Microbridges
 Stress in these phase separation films are from constrained in-
Conclusion
Polymer Film
Photograph of Chip
SEM micrograph showing
microchannels
Permeability tests indicate the ability of low molecular weight
molecules to pass through the 20 micron thick cellulose acetate.
References
[1] Bergveld, P. , Olthuis, W., Sprenkels, A.J., Pijanowska, D.,
Linden, H.J. van der, Bohm, S. Integrated Analytical Systems,
Comprehensive Analytical Chemistry Series, 39, pp. 625-663,
2003
[2] Mulder, M., Basic Principles of Membrane Technology,
Kluwer Academic Publishers: The Netherlands, 1996.
[3] Vaessen, D., McCormick, A., Francis, L., Polymer 43(8) 22672277 (2002)