Introduction to Soft Lithography


This is the second part to my first post about Hard Lithography (Wafer Fabrication). I’m going to just briefly cover soft lithography techniques.


Polymer Materials vs. Glass for BioMEMs

Glass has well known surface and electro-osmotic properties for microfluidic applications. Polymers also have some similar properties, such as optical transparency and biocompatibility, but also have a few advantages and disadvantages.

Advantages of polymers include:

  • Improved and easier machinability
  • Modifiable thermal and electrical properties
  • The ability to form high-aspect-ratio microstructures
  • Amicability to incorporation of more surface modification and functionalization than glass alone
  • Polymers can be designed to be degradable

Disadvantages of polymers can include:

  • Optical aberrations
  • Sensitivity to certain solvents
  • Absorption of detection frequencies during fluorescence
  • Electrophoretic polymer materials might not hold up to electric fields or dissipate heat
  • Some polymers might not be able to handle the bonding temperatures required to make enclosed channels.


Ionic, Covalent, and Metallic bonding and Biomaterials

Ionic bonding is when atoms exchange electrons and are then electrically attracted to each other due to the resulting ionization.

A Covalent bond is a weaker bond in which electrons are shared between molecules, reducing overall energy of both molecules and thus inducing a favorable state.

In metallic bonding large numbers of valent electrons prefer to non-specifically drift around protons, this constant transfer of electrons creates a sea of electrons around proton cores.

Bonding relates to biomaterials in that any functionalization or polymerization will rely on these bonds. Traditionally ionic bonds are the strongest, followed by covalent bonds. Metallic bonds result in an electrically conductive (and generally also thermally conductive) component. Depending on the biomaterial properties needed, the bond types must be considered.


Soft Lithography

In soft lithography, generally a PDMS stamp is made by casting PDMS over a silicon wafer master mold and then peeling the PDMS off after it is cured. The wafer is made with hard lithography techniques.

Microcontact printing (μCP) entails the PDMS stamp being coated with the liquid material that is intended to be patterned. The raised part of the PDMS is coated much like on a stamp pad, and the patterned material, including biologically active molecules, is applied to a surface in a well defined pattern.

Microtransfer molding (μTM) is the opposite of microcontact printing in that the lowered areas of the PDMS stamp are filled with patterning substance.

Molding in capillaries (MIMIC) is when the empty PDMS stamp is placed on the substrate, then prepolymer liquid is applied at the end of the channels. Electro-osmotic forces to carry the prepolymer into the channels where they are then cured in the shape of the PDMS mold. The mold is removed and the relief sections of the stamp are left.

Decal-transfer microlithography (DTM) allows elastomeric detail patterns to be transferred using engineered adhesion and release properties of a specific PDMS patterning tool.


Injection Molding

In injection molding, thermoplastic pellets are melted down and transported by a screw to the injection mold. The melted plastic is injected into a steel or aluminum mold under high pressure, allowing the entire mold to fill. The plastic then takes on the shape of the mold, which is removed after the system has cooled.

Reactive injection molding is also an option, in which two liquid polymers are injected and allowed to polymerize in the mold. This way non-thermoplastic materials can be injection molded.


Hot Embossing

Hot embossing is a method used with thermoplastic materials. A thick piece of material is inserted between two mold plates, and formed into a shape under pressure and heat. Nickel and silicon molds can be used, and pressure from 5-10 tons is applied.

The advantages of using hot embossing include low polymer flow, the ability to use high-MW polymers (which have better mechanical and thermal properties) and the ability for continuous cycle.

Micro and nano scale features can be made this way. However, it is more difficult to make structures with high aspect ratios.


AMANDA Processing

AMANDA is short for “surface micromachining, micromolding, and diaphragm transfer.” A flexible diaphragm is of a structural material (like polyimide) is deposited and patterned on a silicon substrate. Then, a housing structure is molded to house the diaphragm and the diaphragm is stuck to the housing with an adhesive. Additional parts can then be added. This method is used to make pressure sensors. Below is an excerpt from a paper that uses the method.


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Schematic design of the micro valve in the closed state (left) and the open state (right).

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Manufacturing step: component bonding.


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Manufacturing step: filling the transmission medium.


3D Features with Photopolymerization

Photopolymerization is an additive manufacturing technique often used for rapid prototyping. Generally Stereolithography and microstereolithography are categorized as photopolymerization techniques, both of which use UV light to build 3D solid structures from a liquid resin bath.

UV light is used to initiate polymerization in liquid polymer resin between 225 and 550 nm wavelength spectrum.

There are two types of polymer curing in photopolymerization that use UV light, free radical and cationic curing. In free radical polymerization, when the photoinitiator is exposed to UV it breaks down and generates a free radical. This radical can then initiate polymerization and propagate polymer chains until another radical terminates the processes. Generally acrylates are used in this curing process.

With ionic polymerization, a pi electron pair in a monomer is attacked. Cationic polymerization occurs when the active site has a positive charge, and anionic polymerization occurs when the active site has a negative charge. In both types, the charge is moved down along the polymer as new mers are added until termination occurs. Epoxies are generally associated with this cationic curing.

Stereolithography is a layer by layer linear process. For additive manufacturing to make a 3D structure, acrylate resin is poured into a container and cured into a solid when UV light is shined on various points. 3D parts are drawn layer by layer with UV light on a flat staging surface, slowly creating a 3D solid part. The part is then removed from the liquid resin bath and cleaned, leaving only the cured resin structure.

Microstrerolithography can achieve layers of 1-10 microns in thickness and uses a mask rather than x-y scanning as in stereolithography. The mask is dynamically generated using an LCD displayer and rapid layer by layer polymerization.

Both types make use of machine code generated from a CAD 3D model (.stl) conversion, usually using software that comes with the machine.


“Smart” Polymers

A smart polymer will respond to characteristics (such as pH, temperature, calcium, magnesium, organic solvents, magnetic field, electrical potential, IR radiation and UV radiation) in its environment. Some even respond to dual stimuli such as calcium and PEG, calcium and temperature, calcium and acetonitrile, pH and temperature, and light and temperature.

I just wrote a post about these polymers, which you can find in my article “Smart Polymers and their Stimuli”.


Reversible SIS Polymers vs Crosslinked Smart Polymers

SIS polymers are reversible soluble-insoluble in aqueous media. The other type of smart polymer is crosslinked in the form of hydrogels. Examples of reversible SIS polymers are poly(N-isopropylacrylamide) (PNIPAAm), methyl-methacrylate, chitosan, and alginate.

Both types of polymers change their hydrophobicity and change volume when exposed to their stimulus trigger. A polymer with an increase in hydrophobicity will swell according to literature, however, it seems more likely that it would shrink.



Hydrogels may be selectively polymerized using a UV light (365 nm), a colliminating microscope, and photolithography masks. To make a hydrogel, precursor molecules are linked in various ways and exposed to water. All hydrogels have water as a main bulking agent.



Nanomedicine involves medical techniques that require sub 100nm feature sizes. This can include drug delivery mechanisms, sensor and diagnostic technologies, and genetic manipulations.

Nanoimprint lithography (NIL) can include either thermal or ultraviolet. Thermal NIL is similar to hot embossing in that a lowviscosity polymer is heated past its glass transition temperature and pressed into its final shape with nano-sized features. UV-NIL is performed at a low pressure, at room temperature. A thin resin layer or resin droplets are stamped with a mold and cured inside the mold with UV light.

Self-assembling monolayers (SAMs) self assemble through numerous weak noncovalent bonds. These can be Van der Waals, Ionic, or hydrogen bonds to assemble the molecules in a well defined hierarchical structure. A common SAM structure is a thiol or disulfide on a gold substrate. Silane can be used on nonmetallic oxide surfaces like SiO2 and Ta2O5. Alkyl chains are then assembled on the surface of the thiol mounts as tail groups. Finally, the ends of the tails can be functionalized with –OH or –NH3 to modify hydrophobicity or bonding properties.

A side note for thin film formation is the use of a Langmuir-Blodgett process for the formation of a monolayer of molecules on a substrate.

AFM can be used to measure topography. It can also be used for nanolithography by tipping the tip in organic and inorganic material or immobilizing an enzyme on the tip and inciting enzymatic activity.

STOMP is process of compressing malleable metal film on a rigid support (i.e. gold on mica) with a proper stamp, then using chemical etch to remove areas while under compression from the stamp.

Thick film technologies use a gravure or screen-printing process to apply material paste in patterns. Generally materials used are not high-purity. Sol-gel techniques have chemical precursors suspended in a colloidal solution (sol) and brought by dehydration or chemical reaction to the point at which gelatinous phase occurs (gel). These can be applied using thick film processes. Ceramics can be applied this way and then sintered.


Self-Assembling Monoloayers (SAMs)

Self-assembling monolayers (SAMs) self assemble through numerous weak noncovalent bonds. These can be Van der Waals, Ionic, or hydrogen bonds to assemble the molecules in a well defined hierarchical structure.

A common SAM structure is a thiol or disulfide on a gold substrate. Silane can be used on nonmetallic oxide surfaces like SiO2 and Ta2O5. Alkyl chains are then assembled on the surface of the thiol mounts as tail groups. Finally, the ends of the tails can be functionalized with –OH or –NH3 to modify hydrophobicity or bonding properties.

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From Milan Mrksich and George M. Whitesides. Representation of a self-assembled monolayer (SAM) of alkanethiolates on the surface of gold. (Left) Hexagonal coverage scheme of thiols coordinated to the gold (111) surface; the sulfur atoms (shaded circles) fill the hollow three-fold sites on the gold surface (open circles). (Right) The alkyl chains are close-packed and tilted approximately 30″ from the normal to the surface. The properties of the SAM are controlled by changing the length of the alkyl chain and the terminal functional group X of the precursor alkanethiol. The missing row represents a common defect present in SAMs. The detailed structures of point and line defects have not been established.

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Gold thiolate monolayer (Top Left), funtionalized Doublelayer (Top Middle), MPC (Top Right), and Protein immobilization of His-tag labeled proteins (Bottom) from An Introduction to SAMs.

SAMS can be stamped on or applied in solution.

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Here a PDMS stamp is used to transfer alkanetiolates to a gold substrate, where the sulfur groups stick.