The GeSiM Micro-Contact Printers are designed to simplify prototyping of microfluidic devices. Proven lithography-based patterning technologies are expensive. Micro casting tools for mass production of disposable fluidic chips and cartridges are even more expensive. On the other side, biological samples quickly clog microchannels.
Automatic micro patterning platform
The GeSiM micro-contact printers (µCPx.x) close the gap between microfluidic research and production. You will get two methods on one platform: Micro-contact printing for surface patterning down below 1 Micron and 3D imprinting for microfluidic devices. Click the tab Procedures for details. Each µCP accommodates at least five stamps with user specific patterns. An external casting station replicates consumed stamps for reasonable operating costs.
All GeSiM micro-contact printers features a proprietary stamping method based on pneumatic actuation. It delivers precision without the need of expensive granite beds and damping tables.
The smallest but versatile single-level µCP combines camera, stamp holder and UV lens head by one tool. The max. printing area is 20 x 20 mm.
The two-level µCP is suitable for UV transparent print targets. The UV source is arranged on the lower level, opposite to the print stamp on the upper level. A collimator combined with a photomask synchronizes the exposition frame perfectly to the stamp image field. This method allows multiple imprints on one target up to six inches without spacing between adjacent images (“Chessboard” style).
Same as before, a larger work tray adapts more targets for batch processing.
µCP4.1 is for single imprint NIL (Left); µCP6.1 replicates imprints (Right)
Automatic micro-contact printing
The platform design of all GeSiM instruments allows to equip the micro-contact printers with material handling tools for liquids, pastes, powders, UV-curable materials and much others.
Basically, each micro-contact printer comes with several modules on the work deck like a stamp rack, substrate holder and others.
Core components onboard of µCP4.1
The combination of tools is given by several individually lowering Z-axes. The basic setup offers:
- µCP print head for soft membrane stamps up to 20 mm by 20 mm, integrated alignment microscope and UV adapter for optical fibres (5 mm diameter)
- Pneumatic dispenser for the deposition of high-viscous liquids like photoresist SU8 and NOA 81 (Norland), respectively
- Syringe dispenser for the application of low-viscous inks for micro-contact printing
High-precision lithography with the bulged stamp
Polymer stamps are the heart of the GeSiM microcontact printers. The footprint of the stamp represents particular patterns for each customer and each application. GeSiM produces master chips for each particular design. Stamps are to be made by the user with the included casting station. Both PDMS and PTFE can be used for stamps.
The proprietary stamping method doesn’t require sophisticated mechanical setups. When the print head touches down the stamp gets bulged out by air pressure and connects smoothly and without artefacts to the substrate surface.
Fluidic “flow-through” stamps are a special version for applying grains or bead during the microcontact printing process.
Different Sizes of PDMS stamps for GeSiM micro-contact printers
Tools for material handling
Initially the process starts with a thin layer of liquid. The built-in spin coater works with photo resists for NIL as well as a protein solution for contact printing (Stamp inking).
Several material handling methods are available:
- Displacement pipet tips as you use it in your daily work flow
- Piezoelectric GeSiM dispensers for managing smallest volumes
- Piezoelectric valves (Third party) for making smallest drops of high-viscous media
- Pneumatic extruders for dispensing of pasty materials from disposable cartridge.
- Powder pipets for transfer of micrograms of granular materials.
µCP stamp (Left) and powder pipet (Right) above a reservoir
UV hardening during NIL on µCP4.1
Each GeSiM micro-contact printer allows two different applications:
This process transfers a sample liquid called “ink” onto a planar target surface. The PDMS stamp is inked with the sample, subsequently pressed onto the surface, thereby transferring the sample only from the high areas, as in letterpress printing.
Spinning of ink on target
Drying of Stamp
Stamp detached from target
Not just chemicals, also biomolecules, nanoparticles, beads, or cells can be printed. Patterns of proteins like fibronectin or laminin can serve as adhesive substrate to grow cells only on protein-covered areas.
GeSiM printers automatically use up to five stamps with different inks and different patterns for well aligned prints on the same substrate.
NIL – Nanoimprint Lithography
Nanoimprint Lithography (NIL) is a popular approach to make disposable microfluidic devices at low numbers. The GeSiM micro-contact printer has to be supplied with a curable photopolymer as well as with the printing substrate.
First, the target surface has to be coated with an appropriated material, e.g. a liquid, UV-hardened, polymer. Then, instead of transferring an ink, the elevated patterns of the PDMS stamp shape their reverse image into a homogeneous layer on the stamp target. µCP6.1 is capable of lining up several prints step-by-step without any spacing in between.
Spinning of photo resist
Stamp alignment/ Drying
Stamp detached from target
3D structures can be printed with SU8 photoresist or NOA (Norland). Heights of up to 150 microns are feasible. The aspect ratio height/width depends on the layout but can easily reach (3…5)/1.
After detaching the stamp the printed targets can be sealed by cover lids in order to achieve microfluidic devices.
Selection of applications already done:
- Selective printing of self-assembled monolayers (SAM) by µCP, or microstructuring by NIL, on metal (Cu) and electroplating on the unprotected areas
- Fabrication of silver micro- and nanopatterns by µCP of SAM on glass and electroless metallization
- Direct (nano)imprinting of microfluidic structures into photoresist
- Microcontact printing of extracellular matrix proteins to direct cell adhesion to certain spots (see below…)
- Fine-structuring of surfaces via NIL for cell growth studies (e.g. flat vs. grooved surface)
- Printing of patterned thermoresponsive microgel coatings to study adherent cells (Uhlig et al., 2016)
Micro-Contact-Printing: Fibronectin patterns for cell growing
Human Umbilical Cord Blood Neural Stem Cells (HUCB-NSC) were grown on microcontact printed fibronectin squares for a differentiation study.
The squares were printed using PDMS stamp on a cell repellent, plasma polymerized poly-ethylene-oxide (PEO) like surface using fibronectin solution in an acetate buffer as an ink.
HUCB-NSC cells on micro-contact printed Fibronectin squares – Phase contrast image
Fluorescence Image – Green: β-tubulin-II neuronal marker; Red: GFAP; Blue: Cell nuklei
The cells do not adhere to the PEO coated regions, but are attached to the printed 100 µm fibronectin squares. After the culturing period the cells were fixed and immunostained for glial and neuronal differentiation markers.
Courtesy of EC Joint Research Centre, Nanobiosciences Unit, Ispra, Italy (Dora Mehn)
Nano-Imprint Lithography: Micro needle arrays
Vacuum containment on the print head of µCP4.1
Functionalized micro needle arrays gain increasing interest for subcutaneous drug delivery without injection needles. Development of a cost-effective manufacturing technology for controlled drug release is still challenging. Here we present an approach for low-volume manufacturing of micro needle arrays with the GeSiM micro-contact printers. Nano-Imprint-Lithography allows much better spatial resolution than conventional 3D-SLA.
Microneedle arrays with high-aspect ratio are achieved by evacuating the space around the PDMS stamp. GeSiM microcontact printers are available with a containment ring surrounding the stamp. Thus a sealed volume allows evacuation when the stamp touches down on the print target.
Master structure for stamp casting
PDMS print stamp
Final micro needle array
The master structure for multiple stamp casting (left(top) image) was done by 2-photone-lithography using a stiff synthetic material. The µCP4.1 stamp was than made from PDMS Sylgard 184, Dow Chemicals Europe GmbH) as usually (middle). Finally the micro needle array (right (bottom)) consists of a UV-hardened resist (NOA-63, Norland Products Ltd.).
The geometry of the NOA-63 needle array supports usability: The height is 1,200 µm, both bottom diameter and spacing between adjacent needles are 200 µm.
For more details please download the µCP4.1 microneedle array application note.
Nano-Imprint Lithography: Nanoplasmonic sensor structure
Surface plasmon resonance (SPR) sensors allow label-free, real-time biomolecule detection with high sensitivity. Classical SPR sensors utilize a gold film on a prism, which cannot be scaled down. To overcome this, a nanostructured gold layer is used to excite plasmons without bulky optics. The nanoplasmonic sensor structure detects diclofenac in wastewater using immobilized diclofenac in the presence of diclofenac antibodies (Steinke et al., 2018) or measures ethanol concentration during fermentation processes with an ethanol-sensitive hydrogel (Kroh et al., 2019).
Central to this method is the reproducible fabrication of nanostructured surfaces by nanoimprint lithography (UV-NIL) using a GeSiM µCP 4.1 and a UV-cross linkable photoresist.
Nanopillar arrays made by UV-NIL on a glass wafer with a GeSiM µCP4.1, SEM image inline
Nano-Imprint Lithography: Picolitre wells for cell biology
Picowells, 25 µm wide, printed by UV-NIL, empty
Picowells filled with cells
In cooperation with M. Deutsch’s lab from Bar-Ilan University and others, picowell arrays have been printed by UV-NIL in UV-curable adhesives such as NOA81 for the activity measurement, e.g. by multiparametric enzymic assays, of individual cells (Deutsch et al., 2010; Afrimzon et al., 2010; Markovitz-Bishitz et al., 2010).
NIL made honeycomb Picowells with single cells
One application was toxicology testing of nanoparticles that the GeSiM Nano-Plotter had spotted into the picowells, another the formation and study of organoids from cancer cells in honeycomb structures (Zurgil et al., 2014), also with electrodes.
Courtesy of Matti Deutsch, Bar-Ilan University
Nano-Imprint Lithography: In vitro neurotoxicity assay development
Electrodes on the well bottom of a MEA chip, each well 100 x 100 x 50 µm
Scanning electron microscopic image of one well of the microarray (by Cesar Pasqual Garcia)
Primary (rat) neurons grown forming a network in the microwells; Green: β-tubulin-II neuronal marker, Blue: cell nuclei. (by Jakub Nowak)
Microelectrode array chambers (MEA chips) were applied as a support to generate 3D microwell environment for neural cells in electrical activity measurement studies.
The printer with UV illumination and the 24 well stamps were used to generate imprints with 100 µm sized wells and interconnecting channels aligned to the electrodes of the multi-electrode arrays. The matrix of PEG based hydrogel was polymerized by 60 s UV exposition.
Courtesy of EC Joint Research Centre, Nanobiosciences Unit, Ispra, Italy (Dora Mehn)