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1 Introduction to BioMEMS & Medical Microdevices “Soft” Fabrication and Polymers Companion lecture to the textbook: Fundamentals of BioMEMS and Medical Microdevices, by Prof. Steven S. Saliterman, http://saliterman.umn.edu/ R012408 Steven S. Saliterman Biomaterials What is a biomaterial? Natural, synthetic and biological materials. Classes of biomaterials: Implanted or have other direct contact with living tissue (in vivo), Transport or containment function (in vitro), Process function (functionalized materials). Steven S. Saliterman Advantages of Polymers 1. Improved and easier machinability. 2. Optical transparency for certain detection strategies 3. Biocompatibility. 4. Acceptable thermal and electrical properties. 5. Ability to enclose high-aspect-ratio microstructures. 6. Ability for surface modification and functionalization.

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Page 1: Soft Fabrication and Polymers Handout · Natural Polymers Steven S. Saliterman Hydrogels Oosterbroek, R.E. and A. van den Berg, Lab-on-a-Chip: Miniaturized Systems for (Bio)Chemical

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Introduction to BioMEMS & Medical Microdevices

“Soft” Fabrication and PolymersCompanion lecture to the textbook: Fundamentals of BioMEMS and Medical Microdevices, by Prof. Steven S. Saliterman, http://saliterman.umn.edu/

R012408

Steven S. Saliterman

Biomaterials

What is a biomaterial? Natural, synthetic and biological materials.

Classes of biomaterials: Implanted or have other direct contact with

living tissue (in vivo),

Transport or containment function (in vitro),

Process function (functionalized materials).

Steven S. Saliterman

Advantages of Polymers

1. Improved and easier machinability.

2. Optical transparency for certain detection strategies

3. Biocompatibility.

4. Acceptable thermal and electrical properties.

5. Ability to enclose high-aspect-ratio microstructures.

6. Ability for surface modification and functionalization.

Page 2: Soft Fabrication and Polymers Handout · Natural Polymers Steven S. Saliterman Hydrogels Oosterbroek, R.E. and A. van den Berg, Lab-on-a-Chip: Miniaturized Systems for (Bio)Chemical

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Steven S. Saliterman

“Soft” Fabrication

1. “Soft” lithography.

2. Micromolding.

3. 3-D Photopolymerization.

4. “Smart” polymers and hydrogels.

5. Nanomedicine techniques.

6. Thick-film technologies.

7. Array patterning.

Steven S. Saliterman

Micro-Contact Printing (µCP)

Nguyen, N.T. and S.T. Wereley, Fundamentals and Applications of Microfluidics, Artech House, Boston, MA (2002).

Steven S. Saliterman

PDMS (Silicone) Stamp

PDMS (Silicone) Stamp

PDMS (Silicone) Monomer

Nguyen, N.T. and S.T. Wereley, Fundamentals and Applications of Microfluidics, Artech House, Boston, MA (2002).

Page 3: Soft Fabrication and Polymers Handout · Natural Polymers Steven S. Saliterman Hydrogels Oosterbroek, R.E. and A. van den Berg, Lab-on-a-Chip: Miniaturized Systems for (Bio)Chemical

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Steven S. Saliterman

Example: PDMS Microfluidic Device

Jaehoon Chung & Euisik Yoon

Steven S. Saliterman

PDMS Molding Station

Steven S. Saliterman

PDMS Castings

Page 4: Soft Fabrication and Polymers Handout · Natural Polymers Steven S. Saliterman Hydrogels Oosterbroek, R.E. and A. van den Berg, Lab-on-a-Chip: Miniaturized Systems for (Bio)Chemical

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Steven S. Saliterman

UV-Ozone Surface Treatment

Steven S. Saliterman

Inspecting the PDMS casting

Steven S. Saliterman

Alignment on Substrate

Page 5: Soft Fabrication and Polymers Handout · Natural Polymers Steven S. Saliterman Hydrogels Oosterbroek, R.E. and A. van den Berg, Lab-on-a-Chip: Miniaturized Systems for (Bio)Chemical

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Steven S. Saliterman

Video Inspection of Alignment

Steven S. Saliterman

Inspecting the Final Device

Steven S. Saliterman

Test Apparatus

Page 6: Soft Fabrication and Polymers Handout · Natural Polymers Steven S. Saliterman Hydrogels Oosterbroek, R.E. and A. van den Berg, Lab-on-a-Chip: Miniaturized Systems for (Bio)Chemical

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Steven S. Saliterman Jaehoon Chung & Euisik Yoon

Steven S. Saliterman

Micromolding

Injection Molding

Reaction Injection Molding

Hot Embossing

Injection Compression Molding

Thermoforming

Atmospheric Molding

AMANDA

Steven S. Saliterman

Injection Molding

Left: Heckele, M. and W.K. Schomburg, Review on micro molding of thermoplastic polymers. Journal of Micromechanics and Microengineering 14(3), pp. 1-14 (2004).

Right: Image courtesy of Thermotech

Page 7: Soft Fabrication and Polymers Handout · Natural Polymers Steven S. Saliterman Hydrogels Oosterbroek, R.E. and A. van den Berg, Lab-on-a-Chip: Miniaturized Systems for (Bio)Chemical

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Steven S. SalitermanHeckele, M. and W.K. Schomburg, Review on micro molding of thermoplastic polymers. Journal of Micromechanics and Microengineering 14(3), pp. 1-14 (2004).

Variotherm Process

Steven S. Saliterman

Hot Embossing

Heckele, M. and W.K. Schomburg, Review on micro molding of thermoplastic polymers. Journal of Micromechanics and Microengineering 14(3), pp. 1-14 (2004).

Steven S. Saliterman

Thermoforming

Heckele, M. and W.K. Schomburg, Review on micro molding of thermoplastic polymers. Journal of Micromechanics and Microengineering 14(3), pp. 1-14 (2004).

Page 8: Soft Fabrication and Polymers Handout · Natural Polymers Steven S. Saliterman Hydrogels Oosterbroek, R.E. and A. van den Berg, Lab-on-a-Chip: Miniaturized Systems for (Bio)Chemical

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Steven S. Saliterman

3-D Photopolymerization

Three-dimensional photopolymerization is based on layer-by-layer assembly, and is used for rapid production of devices for modeling and prototyping: Stereolithography (SL)

Microstereolithography (MSL)

Dynamic Projection MSL

Steven S. Saliterman

Photopolymerization

UV curing occurs between 225 and 550 nm. Free radical curing:

When the photoinitiator is exposed to UV, they break down leaving components with an unpaired electron, or free radicals.

Propagation occurs with addition of monomers, and transfer of the free radical down the propagating chain to continue the process of addition of monomers.

Termination occurs when the growing chain stops. Acrylates are associated with free radical

polymerization.

Steven S. Saliterman

Ionic polymerization: Involves an attack on the π electron pair of a

monomer.

Cationic curing : Cationic polymerization occurs when the active site

has a positive charge (in contrast to anionic polymerization in which the active site has a negative charge).

Addition of monomers moves the charge down the chain until termination occurs.

Epoxies are associated with cationic curing .

Page 9: Soft Fabrication and Polymers Handout · Natural Polymers Steven S. Saliterman Hydrogels Oosterbroek, R.E. and A. van den Berg, Lab-on-a-Chip: Miniaturized Systems for (Bio)Chemical

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Steven S. Saliterman

Microstereolithography (MSL)

Suzumori, K. and et al., Microfabrication of integrated FMAs using stereolithography. Proceedings of IEEE MEMS, pp. 136-141 (1994)

Steven S. Saliterman

Dynamic Mask Projection MSL

Bertsch, A. et al., Microsterolithography using a liquid crystal display as dynamic generator. Microsystem Technology 3(2), pp. 42-47 (1997).

Steven S. Saliterman

Clips Car

Gear BoneBertsch A., 1998, 1999, 2001, Personal Correspondence.

MSL Fabricated Parts

Page 10: Soft Fabrication and Polymers Handout · Natural Polymers Steven S. Saliterman Hydrogels Oosterbroek, R.E. and A. van den Berg, Lab-on-a-Chip: Miniaturized Systems for (Bio)Chemical

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Steven S. Saliterman

Pipe Cup

Gear ScrewBertsch A., 1997, 1999, Personal Correspondence.

Steven S. Saliterman

Smart Polymers and Hydrogels

“Smart” polymeric materials exhibit significant changes in their characteristics with small changes in their environment.

These external stimuli include pH, calcium, magnesium, organic solvents, temperature, magnetic field, electrical potential, and IR and UV radiation.

Some materials respond to dual stimuli such as calcium and PEG, calcium and temperature, calcium and acetonitrile, pH and temperature, and light and temperature.

Electroactive polymers (EAPs) respond to electrical stimulation.

Steven S. Saliterman

Smart polymers are either reversible soluble-insoluble (SIS) in aqueous media or cross-linked in the form of hydrogels.

SIS polymers include synthetic polymers such as poly (N-isopropylacrylamide) (PNIPAAm) and methyl-methacrylate polymers; and natural polymers such as alginate and chitosan (polysaccharides).

CH

H2C

C

CH CH3O

NH

*

*

H3C

n

Poly(N-isopropylacrylamide) (PNIPAAm)

Page 11: Soft Fabrication and Polymers Handout · Natural Polymers Steven S. Saliterman Hydrogels Oosterbroek, R.E. and A. van den Berg, Lab-on-a-Chip: Miniaturized Systems for (Bio)Chemical

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Steven S. Saliterman

O

OO

OO OOH OH

O

OH

OH

O

HO

HO

*

*

HO

COO-

-OOC

-OOC

COO-

H2N

n

Alginate

O

O

OH

O

OHO

**

NH2

NH

C

OH3C

HOH2C

CH2OHn

Chitosan

Natural Polymers

Steven S. Saliterman

Hydrogels

Oosterbroek, R.E. and A. van den Berg, Lab-on-a-Chip: Miniaturized Systems for (Bio)Chemical Analysis and Synthesis, 1st ed. Amsterdam, Elsevier (2003).

Steven S. Saliterman

When a stimulus is applied at a critical level, both SIS and hydrogels increase or decrease their overall hydrophilicity and either swell or shrink respectively.

Physical hydrogels are held together with noncovalent forces and have hydrophilic and hydrophobic domains.

Chemical hydrogels are held together by crosslinking, and have regions of high and low crosslinking. Areas of low crosslinking allow higher swelling.

Page 12: Soft Fabrication and Polymers Handout · Natural Polymers Steven S. Saliterman Hydrogels Oosterbroek, R.E. and A. van den Berg, Lab-on-a-Chip: Miniaturized Systems for (Bio)Chemical

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Steven S. Saliterman

Synthesis

OH

O

Acrylic Acid (AA)

O

OH

O

2-hydroxyethyl methacrylate (HEMA)

O

O

O

H2O

Ethyleneglyco dimethacrylate (EGDMA)

O

OCH3

Ph

OCH3

2,2'-dimethoxy-2-phenyl acetophenone (DMPA)

Steven S. Saliterman

Synthetic Hydrogels

Steven S. Saliterman

Hydrogel Applications

Controlled drug delivery.

Thermo-responsive microfluidic actuator.

Ultrasensitive microcantilever sensor.

Combined with optically active nanoparticles, light frequency-dependent optical switching can be accomplished.

Optical control by fiberoptics at a distance.

Tissue scaffolding devices with selective diffusion.

Page 13: Soft Fabrication and Polymers Handout · Natural Polymers Steven S. Saliterman Hydrogels Oosterbroek, R.E. and A. van den Berg, Lab-on-a-Chip: Miniaturized Systems for (Bio)Chemical

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Steven S. Saliterman

Summary

Biomaterials for medical diagnostics and therapeutics include natural, synthetic and biological materials that have contact with humans or human products such as blood, urine, cerebral spinal fluid, organs and other tissue.

“Soft Fabrication” includes: “Soft” lithography. Micromolding. 3-D Photopolymerization. “Smart” polymers and hydrogels. Nanomedicine techniques. (see textbook) Thick-film technologies. (see textbook) Array patterning (to be covered later).