SUSPENDED, POROUS CELLULOSE ACETATE MEMBRANES FOR MICRODIALYSIS USE

1
Patient Monitoring
Microdialysis
In vitro microdialysis setup with close-up of
semi-permeable membrane interface
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 1Robotics Institute, 2Electrical and
Computer Engineering Dept. Carnegie Mellon
University Pittsburgh, Pennsylvania, USA Micro
Total Analysis System (mTAS) 2004 Malmö, Sweden
Collected dialysate will contain a representation
of tissues chemistry
Physiological salt solution is pumped through the
microdialysis probe.
Microdialysis setup
A more direct indicator of a patients status is
using microdialysis
Glass beaker
Microdialysis is a real-time technique to monitor
the chemistry of the extracellular space in
living tissue.
Probe Interior
Sampled solution
Assessing chemistry in a tissues vicinity should
provide more accurate data on biochemical and
pharmacological events occurring in a patient.
Semi-Permeable Membrane
Concentration gradient develops across
semi-permeable membrane interface. Sampled
molecules diffuse into probe.
Conventional Microdialysis Probe
MEMS-based Device Concept
Fabrication Process Flow

• Deposition of polymer is final process step.
• Able to span up to 75 micron wide silicon trench.
• Polymers wetting characteristics are largely
  responsible for its ability to fill or span
  across a cavity.

Mask
Output fractionation and sensing
Microdialysis Membrane
Buffer Inlet
Silicon
(a) Film patterning
Silicon Substrate

• Advantages of silicon-based

Cellulose acetate film
(b) Silicon etch

• Semiconductor fabrication technology
• Miniaturization, Multiplicity, and
  Microelectronics
• Standard processes, no assembly required

Disadvantages
Porous Polymer

• Probes are hand assembled

Microchannel

• Integrated approach
• Acquisition, fractionated collection, and
  sensing on-chip

Microchannel

• Limited lifetime

Silicon substrate

• Large fluid dead volume
• Affects temporal resolution

(c) Porous polymer spin-on
Porous Polymer Fabrication
Phase Separation Process
Porous Polymer Fabrication
Phase Inversion Process

• Variables in the procedure

• Choice of polymer
• Choice of solvent
• Polymer concentration
• Spin speed
• Evaporation time
• Composition of coagulation bath
• Temperature of coagulation bath

• Cellulose Acetate
• N,N-Dimethylacetamide
• ---Variable---
• ---Variable---
• ---Variable---
• 100 deionized water
• Room temperature

5
6
4
7
1
2
3

• Solution is spin cast onto a silicon substrate
  at a specific rotational speed.

• Desired polymer is chosen, in my case it was
  cellulose acetate powder.

Step 4
Step 1
Substrate is then immersed into a room
temperature water bath overnight.
Step 5

• Polymer is dissolved in a miscible solvent at
  a desired concentration. N,N-dimethylacetamide
  (DMAc) solvent used.

Step 2

• Factorial experiment designed for three
  variables.
• Visual confirmation of results using SEM, AFM,
  and light microscopy.

Solvent and non-solvent are immiscible.
Cellulose acetate precipitates from solution with
void regions.
Step 6

• Polymer-solvent mixture is created (Rotating
  arm, mixing takes overnight). Viscous solution
  is created

Step 3
Substrate allowed to air dry. A thin, porous
cellulose acetate film is formed.
Step 7
Characterization of Polymer Film
Optimal Settings for Porous Film
Design of Experiments

• SEM imaging of cellulose acetate

Polymer Concentration
Optimum conditions Polymer Conc. 10 (w/v)
Spin Speed 2.5 kRPM Evap. Time lt 5 seconds
(max)
Set of 15 different runs performed to determine
optimum processing conditions
(max)
(min)
Evaporation Time
Close-up magnification
(max)
Spin Speed
Polymer Concentration (w/v) 5, 10, 15 Spin
Speed 1 kRPM, 2.5 kRPM, 4 kRPM Evaporation Time
lt5 sec., 30 sec., 1 min.
Microdialysis Chip MWCO Determination
Polymer Spanning Long Channels
Conclusion
Longer channels

• 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.
• 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) 2267-2277 (2002)

50 um wide channel. Bridges 5 um width, 50 um
spacing
Fluidic interconnect was attached to the
inlet/outlet ports to interface with the
microchannels. The cellulose acetate showed
permeability to myoglobin (MW17 kDa) and soybean
trypsin inhibitor (20 kDa)
Inlet/Outlet tubing
Microbridges
SEM micrograph showing microchannels
Polymer Film

• Stress in these phase separation films are from
  constrained in-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.

• Photograph of Chip