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Microfluidics

Products & Applications

The Nano-Plotter is ideal to generate high-quality spots by non-contact microdispensing of sub-nanoliter volumes.

  • Array based Diagnostics
  • Organic Light Emitter Diodes (OLEDs)
  • Microdispensing of functional liquids is an essential step in
  • production of organic electronics
  • Reverse Phase Microarrays
  • Immunoassay for Allergy Diagnostics
  • Printing of Organic Field Effect Transistors
  • Arraying into 96-well Plates
  • Array Calibration for Antibody Spotting
  • Peptide Synthesis Project
  • Glycoprotein Arrays
  • Coating of Drug Eluting Stents

Nano-Plotter

BioSyntheSizer

Ink-Jet Printing of Organic Field-Effect Transistors

Low-cost flexible electronics with organic transistors calls for an easy and cost-effective patterning process. While contact printing, e.g. using reels, might be useful for large-scale production, ink-jet printing ensures high flexibility.

P3OT has been extensively studied as soluble organic semiconductor, but mostly in chloroform solutions. We tested the printing of organic field-effect transistors (oFETs) using different inks:

Semiconductor:

  • Commercial poly-(3-octylthiophene-2,5-diyl) (P3OT), 1 – 3 mg/ml in different solvents

Solvents:

  • Chloroform, chlorobenzene, trichloroethylene, xylene

Test vehicles:

  • Back side-metallized doped Si as gateBildschirmfoto 2014-09-02 um 16.09.26
  • 140 nm thermal oxide as gate dielectrics
  • 150 nm Ti/Au lift-off-patterned S/D-electrodes yielding 20-50 µm x 1-3 mm transistor channels
  • Rinsing in chloroform immediately before printing to obtain hydrophobic surfaces

 

Ink-jet printer:

  • Nano-PlotterTM , XYZ robotic stage with microwell plate for inks and washing solvents
  • Piezoelectrically driven Nano-Tip fabricated by Si-micromechanics with tip-outlet to reduce wetting
  • Camera system for function control of jetting and adjustment to substrate
  • Normal atmosphere (extendable to housed processing under nitrogen o.a.)Micro-Dosage of P3OT

Micro-Dosage of P3OT

  • Printing only possible from solutions with higher boiling points (not chloroform)
  • Line printing by overlapping of single dots
  • Problems (flake-like overlap) with trichloroethylene-based solution because of fast evaporation
  • Good printing from chlorobenzene and xylene solutions
  • Spot diameter ~ 150 – 180 µm, depending on concentration and jetting parameters

Bildschirmfoto 2014-09-02 um 16.11.02

Summary

We prepared oFETs with common Si/SiO2-Au bottom contact design using ink-jet printed semiconductor lines. To reduce evaporation, high-boiling solvents were used. We could print P3OT in trichloroethylene, chlorobenzene, and xylene. The printed oFETs revealed Ion/Ioff-ratios up to 20,000 and hole mobilities of up to 0.002 cm²/Vs (xylene solution). Although this does not represent ideal data, the ease of patterning offers a route to low-cost electronics. It also inspires to study patterning of other semiconducting materials with drastically decreased gate leakage.   Equipment: Nano-Plotter NP2.0

Development of a Pipetting Station for the Parallel Synthesis

Peptides are used by nature as active regulators and messengers in the human body. They combine high specificity with high affinity in molecular recognition processes, therefore they are ideally suited as drugs.   Peptide microarrays can be utilized for the identification of peptide sequences suitable for pharmaceutical or diagnostic applications as well as for the screening of enzymatic substrates or for enzyme inhibitors.   In a passed research project the Nano-Plotter is applied to the automated synthesis of peptide libraries on a variety of different solid supports such as glass microcapillary plates. The spatially addressable synthesis of different peptides on solid supports allows the subsequent screening of the peptide libraries by established assay techniques including optical screening by fluorescence methods. Only very few peptide sequences from a combinatorial library are typically suitable for the desired tasks, therefore it is highly desirable to produce only the minimal quantity of the candidate sequences necessary for screening. This saves costs and is environmentally friendly. For the realization of microreactions the Nano-Plotter is particularly suited, as it is capable to perform dosage steps in the microliter as well as in the nanoliter range. These dosage steps can be performed highly reproducibly at desired reaction coordinates in the nanoliter scale, a precondition which is indispensable for the generation of peptide arrays in the biochip format on glass surfaces. Bildschirmfoto 2014-09-02 um 14.20.34

Using the Nano-Plotter two different approaches in the generation of peptide libraries on glass biochips are possible. On one hand “classical” replica peptide libraries can be generated by spotting solutions of preassembled peptides onto modified glass surfaces. Such peptide libraries for example are commercially available in microtiter plates, the peptides have to be equipped with special linker groups which allow their covalent attachment to the glass surface. Using this technique, the Nano-Plotter is capable of producing a high number of identical copies of given peptide libraries for screening purposes.
On the other hand, for the first time, the Nano-Plotter allows the sequential on-chip synthesis of peptides from activated amino acid building blocks utilizing the Fmoc-strategy. In this setup solutions of activated Fmoc amino acid building blocks are generated in situ by the Nano-Plotter and are spotted onto separate synthesis areas on glass microcapillary plates. This way, picomolar amounts of up to 900 different peptides are synthesized at specified positions on a glass microcapillary plate which can then directly  be used in optical screening experiments. The wash- and deprotection steps required in this procedure are performed automatically in a novel, chemically inert GeSiM synthesis chamber. With this approach it is possible to produce unique peptide libraries consisting of custom peptides, therefore it provides the highest flexibility concerning the diversity of candidate sequences.

Bildschirmfoto 2014-09-02 um 15.25.46

Equipment: Nano-Plotter NP2.0/E

Arraying of PEDOT:PSS for Organic Light Emitter Diodes (OLEDs)

Microdispensing of functional liquids is an essential step in production of organic electronics and organic light emitter diodes (OLED). Piezoelectric printing is widely used to build up circuits and arrays of transistors and of optical devices. The GeSiM drop-on-demand dispensers work well with a variety of organic and anorganic liquids. This application note outlines the results for: Poly(styrenesulfonate)/poly(2,3-dihydrothieno(3,4-b)-1,4-dioxin) 2.8 wt% in H2O [Aldrich 560596-25G], also known as PEDOT:PSS. PEDOT:PSS is required for the hole-injection and transportation layers of the OLED-pixels. Arrays of different formats, differently sized spots and different densities are available with the piezoelectric micropipetting system Nano-Plotter . The surface tension of the substrate affects the spot diameter. Bildschirmfoto 2014-09-01 um 12.19.49 Dispensing of multiple drops allows a wide range of spot diameters with each dispenser but the single-drop volume with PEDOT:PSS depends both on the dispenser type and the dispense settings. The diagrams show the single-drop volume for piezoelectric Nano-Plotter dispensers (Pico-Tip, Nano-Tip, Nano-Tip-A) and for the standalone dispenser SPIP. The new LD04 is still under development. Bildschirmfoto 2014-09-01 um 12.23.21 Equipment: Nano-Plotter NP2.1 with different piezoelectric dispensers

Testbild News

16. June 2014

Donut-shaped chambers

Lorem ipsum dolor sit amet, consetetur sadipscing elitr, sed diam nonumy eirmod tempor invidunt ut labore et dolore magna aliquyam erat, sed diam voluptua. At vero eos et accusam et, justo duo dolores et ea rebum. Stet clita kasd gubergren, no sea takimata sanctus est Lorem ipsum dolor sit amet. Lorem ipsum dolor sit amet, consetetur sadipscing elitr, sed diam nonumy eirmod tempor invidunt ut labore et dolore magna aliquyam erat, sed diam voluptua. At vero eos et accusam et justo duo dolores et ea rebum. Stet clita kasd gubergren, no sea takimata sanctus est Lorem ipsum dolor sit amet. Continue reading

Testbild News

1 June 2014

Nanofair 2014

Nanofair 2014 will provide a forum for presenting current research and for the exchange of ideas and information between researchers, scientists and engineers from industry, research laboratories and academia. Contributions will cover fundamental scientific aspects as well as application oriented research and development. Furthermore successful implementations of new products using nanotechnology will be addressed as well. Continue reading

Ressourcen

Microarraying/ Liquid HandlingAbstractsAuthors/ Published
Advances in Lectin Microarray Technology: Optimized Protocols for Piezoelectric Print ConditionsWiley Online: Current ProtocolsKanoelani T. Pilobello, Praveen Agrawal, Richard Rouse, Lara K. Mahal, 2013
Antibody colocalization microarray: a scalable technology for multiplex protein analysis in complex samples. Mol. Cell. Proteomics, in pressMol. Cell Proteomics Pla-Roca, M., Juncker, D. et.al., 2012
Clinical utility of serum autoantibodies detected by protein microarray in melanoma.Int. J. Proteomics 2011Sabel, M.S., Liu, Y.,Lubman, D.M. et.al., 2011
Towards multiple readout application of plasmonic arraysBeilstein Journal of NanotechnologyCialla, D., Weber, K. et.al., 2011
The living microarray: a high-throughput platform for measuring transcription dynamics in single cells.BMC GenomicsRajan, S., Djambazian, H., Dang, H.C.P., Sladek, R., Hudson, T.J., 2011
Application of photonic crystal enhanced fluorescence to cancer biomarker microarrays.ACS analytical chemistryHuang, C.-S., Ruimin Tan, R., Zangar, R.C. et.al., 2011
Template-free structuring of colloidal hetero-monolayers by inkjet printing and particle floatingRSC Soft MatterRetsch, M., Dostert, K.-H., Nett, S.K., Vogel, N., Gutmann, J.S., Jonas, U., 2010
The identification of auto-antibodies in pancreatic cancer patient sera using a naturally fractionated Panc-1 cell line.IOS Cancer BiomarkersPatwa, T., Pal, M., Brand, R.E., Simeone, D.M., Lubman, D.M. et.al., 2010
Generation of Live-Cell Microarrays by means of DNA-directed immobilization of specific cell-surface ligands.WILEY Angewandte ChemieSchroeder, H., Ellinger, B., Becker, C.F.W., Waldmann, H., Niemeyer, C.M., 2007
Screening of Glycosylation Patterns in Serum Using Natural Glycoprotein Microarrays and Multi-Lectin Fluorescence DetectionACS PublicationsPatwa, T., Zhao, J., Anderson, Michelle A., Lubman, D., et.al., 2006
Generation of High Density Protein Microarrays by Cell-free in Situ Expression of Unpurified PCR ProductsThe ASBMAngenendt, P., Kreuzberger, J., Glökler, J., Hoheisel, J., 2006
Peptide microarrays for the detection of molecular interactions in cellular signal transductionNCBIStoevesandt, O,, Elbs, M., Köhler, K., Lellouch, AC., Fischer, R., André, T., Brock, R., 2005
Micro-Contact PrintingAbstractsAuthors/Published
Nanoimprint patterning of thin cadmium stannate films using a polymeric precursor routeRSC PublishingBenjamin Schumm, Philipp Wollmann, Julia Fritsch, Julia Grothe, Stefan Kaske, Journal of Materials Chemistry, Issue 29, 2011

Application Spotlights/ Customer Projects

The Nano-Plotter is ideal to generate high-quality spots by non-contact microdispensing of sub-nanoliter volumes.

  • Microarrays and Service
    • We offer a comprehensive service to evaluate your application before investing into an instrument. More…
  • Manufacturing of array based diagnostics
    • The manufacturing of state-of-the-art diagnostic kits requires more precise liquid handling than ever before. The Nano-Plotter is one solution to address these needs. More…
  • Arraying into 96-well plates
    • Micro titer plate based assays allow more complex analysis when the well bottom is prepared with different well aligned capture molecules. More…
  • Antibody arrays and tip cleaning
    • Sticky proteins/peptides can be a challenge for modern microarrayers. More…
  • Reverse Phase Protein Arrays (RPPA)
    • A simple, robust and highly parallel assay architecture for monitoring of protein expression and activation. More…
  • Glycoprotein arrays
    • Complementary to the popular antibody arrays, this application uses pre-separated proteins from cellular lysates or other biofluids. More…
  • Coating of coronar stents
    • This application notice shows how to dispense Nanoliter amounts on stain less steel made coronar stents. More..
  • Loading of Biosensors
    • Label free detection of biomolecules is an attractive solution for users, but challenges liquid handling technology. Small but exact sample aliquots needs to be tethered onto tiny areas of electronic chips. No problem for the Nano-Plotter camera system. More…
  • Dipensable Liquids
    • Here we present an overview of mechanically dispensable liquids. More…
  • Dispensing of Adhesives
    • Heatable piezoelectric dispensers emit Nanolitre volumes of high-viscous adhesives. More…
  • Collision of Droplets
    • The high kinetic energy of flying microdroplets supports mixing of mixable liquids. More…

BioScaffolder

BS31_app_notes

  • Introduction
    • General overview of applications and printable materials. More…
  • PCL-PEG Blends for Tissue Engineering
    • FAU Erlangen succeeded in improving the properties of PCL for tissue engineering by adding PEG. More…
  • Struts and Capsules
    • A group from the Friedrich-Alexander University in Erlangen added prefabricated capsules enriched with cells to hydrogel before printing. More…
  • Green Bioprinting
    • A team from the Technische Universität Dresden printed algae cells suspended in hydrogel together with mammalian cells. More…
  • Alginate/Methylcellulose Blends
    • Immediate cross linking of alginate after printing can be avoided – Accordingly to an approach of researchers at the Technische Universität Dresden. More…
  • Artificial Tissues from the Inkjet
    • To a certain extent inkjet dispensers can emit cell containing suspensions but special bioinks will be required. More…
  • As FAST as Possible
    • GeSiM has become part of an EU funded Consortium (Horizon 2020) to optimize bulk and surface properties of scaffold materials for implants. More…
  • Bioprinting: The Future of Surgery?
    • A scaphoid bone scaffold model was printed from Calcium Phosphate Cement. More…

Nano-Plotter

Platforms / Sizes

The modular non-contact Microarrayer

The Nano-PlotterTM NP2.1 is available in two sizes:

NP2.1 with a slide capacity of 55; NP2.1/E with a slide capacity of 120.

All Nano-Plotter versions come with the following common features:

  • 1 to 16 independent piezoelectric pipetting tips in any combination. Post sales upgrade is possible.
  • Sample aspiration from 96 well or 384 well micro plates
  • Array density > 3000/cm2
  • Dust cover
  • Automatic wash/dry station
  • Optical function test of each individual pipette tips after sample aspiration

 

 

Easy and superb arraying onto slides (For HD introduction video click here)

 

NP2.1 can be configured to a particular application. And… it can grow! It is easy to increase the number of pipetting channels after sales. Also, most accessories can be upgraded. Thus, this instrument might be your companion from research to production.

 

Process Control

Automatic Function Test for each Piezo Tip

A camera system with sophisticated image analysis inspects each piezoelectric pipettor after sample aspiration. The analysis is for:

  • Deflection of the main droplet from the vertical
  • Droplet size, count and speed
  • Deviation of satellite drops from the main jet

The checking function returns a result (Path/Fail) for each pipette. So if a tip fails to spot according to specification, the Nano-Plotter can either repeat sample aspiration, or continue printing with only the working pipettes and repair the missing spots afterwards.

 

strobocheck-camerastrobo_goodstrobo_bad
Stroboscope cameraValid droplet image. The jet angle is inside a user defined region, the number of satellite droplets is small enough.Invalid droplet image. The flight angle of one satellite droplet differs too much from the angle of the main jet.

A more accurate drop volume estimation is available with the optional micro flow sensor.

Volume Measurement

Unique Drop Volume for different Sample Species

NP21_Flow-Sensor

NP21_Flow-Sensor

Naturally, the dispense behaviour of the piezoelectric tips is affected by the sample. A highly sensitive flow sensor in the system liquid path of each tip measures the compensated volume of the ejected drops.

More than a Microarrayer

Customized Versions of the Nano-PlotterTM

Besides array spotting, GeSiM has the flexibility and capability to create custom instruments on request. The Nano-PlotterTM software comes with an open user interface for the development of liquid handling applications by the customer.

Third party dispensers and other tools on the Nano-Plotter print head

Third party dispensers and other tools on the Nano-Plotter print head

In addition, GeSiM develops and delivers OEM Versions of the Nano-PlotterTM to other instrumentation manufacturers.

- Heatable piezodispensers
- Dispensers with reservoir cartridges on top
- Dispensers for high-viscosity media
- Passive Microliter dispensers
- Plate hotel for large samples sets
- Vacuum tweezers
- Wash system for dedicated cleaning solutions
- Print head camera for process observation

As an example, microarray spotting can be accomplished by Microliter liquid handling or manipulation of mechanical parts like glass lids. For manufacturing of a large number of identical arrays with a limited set of samples we recommend piezoelectric tips with an integrated reservoir.

Benchtop lab automation exceeding liquid handling is available with the GeSiM BioSynthesizer.

 

Procedure

Basic Function of Target Camera

The fiducial pattern recognition camera allows both point-and-click definition of the spot layout in a live video image or automatic target recognition by image processing software.

 

The video shows how the alignment process works. The user needs to write a “spotting plan” in advance for each spot pooint.

1. Initially a precise offset measurement gives the exact distance between the camera axis and the drop trajectory of each dispenser.
2. Now the camera travels to each of the two alignment markers on each target substrate. Two pictures are taken of each target substrate.
3. The software calculates the coordinates for each spot point and completes the spotting run without any further user interaction.

Microarrays and Service

Customer Service is a Priority with us!

Fluorescence Image of a Microarray

Fluorescence Image of a Microarray

Microarraying applications are rather complex. The result depends on a lot of laboratory steps and many SOPs while all the necessary instruments are expensive.

Regarding the spotting part of each microarray experiment we will work with you towards your application goals. Don’t place an order on such instrument before you are sure it does the job. If available we can accept your printing material for free feasibility tests. Visits to our premises as well as phone/Skype conferences can also transfer our experience to you.

To a certain extent GeSiM also offers microarray spotting services providing non-commercially available reagents/samples/substances can be supplied to us.

We are often asked about throughput for production projects: It will very much depend on your array layout and other parameters. Please contact us with your particular idea.

 

Manufacturing of Array based Diagnostics

Multiplexing your Assay

Until now diagnostic kits for blood or patient serum are mostly based on nitrocellulose membrane. The analyte hybridizes against a limited set of test molecules and calibration standards, typically less than five.

By switching to the microarray format much more parameters can be tested. In recent years the Nano-PlotterTM NP2.1 has been proofen as reliable tool for the production of microarrays for diagnostic use.

Please download this pdf for selected reference installations.

 

Arraying into 96-well plates

Multi Parameter Analysis with 96 Well Plates

Nano-Plotter NP2.1 instruments can be configured for arraying on the bottom of 96-well microplates. On request special target decks and 2-row print heads are available, matching the 9 mm pitch. GeSiM has developed an optimized piezoelectric pipet (Nano-Tip AR-J) with slimmer design for this application. The highest achievable spot density is significantly dependent on sample type and surface properties of the plate.

Array_in_96wellplate

64 spots of different size made with Nano-Tip AR-J368 spots
1 drop (250 pL)5 drops (1.25 nL)10 drops (2.5 nL)1 drop

This example was printed with fluorescine solution containing 10% glycerol.We used a 96 well plate from GreinerBioOne (Order #762070, Midbind ).

Slidedeck_for_MTPs

NP2.1/E tray for 12 standard format well plate

 

Antibody Arrays without Cross Contamination

Antibody Pipetting with Piezoelectric GeSiM Tips

  • 4 antibodies were assessed (IL6, EGF, PSA, C-RP)

    Rows of protein spots before and after tip washing

    Rows of protein spots before and after tip washing

  • Antibodies were spotted at 100ug/mL concentration
  • To evaluate carry over between each antibody two plain water samples were aspirated (Water Wash 1 and 2)
  • The GeSiM Nano-Tip was used at one drop (approx 350 pL) per spot
  • Arrays were spotted on GenTel PATHTM slides
  • The tip was washed with water (9 seconds), 0.2N KOH (2 seconds) then water (9 seconds). The piezo was activated during the  water washes
Bar graph quantifying signal intensities

Bar graph quantifying signal intensities

Bar graph quantifying percent CVs

Bar graph quantifying percent CVs


Courtesy of HTS Ressources, San Diego (USA)


 

Common Recommendations for Spotting of Antibodies:

  • Use protein concentrations of max. 1 mg/mL containing less than 1 M salt.
  • As proteins need higher piezo voltage, activate the stroboscope break in the standard NPL programs to adjust the parameters. In case of varying spotting parameters for different samples optimized values should be added to the well plate file (See manual for more instructions).
  • Carbohydrates like trehalose can help hydrate proteins and maintain their native structure even in a dry state. But you must prove that these viscous solutions can be spotted without problems.
  • If you have a large protein supply, ultrafiltration would remove aggregates. If you have only small volumes, centrifuge at least.
  • Avoid to suck particles into the pipettes by not using up the entire sample volume.
  • Added buffer should be sterile-filtered to prevent spoiling.
  • The first spot in a row of spots may be stronger than the following ones. If this is the case, define a “yellow paper object” near your first slide and dispense the first spots onto this target.
  • Adjust the piezo parameters for each pipette before each run until the droplet pattern in the stroboscope “looks good” for all of them. Your experience is needed here.
  • If you require low inter-tip CVs or need to know absolute droplet volumes, dispense labeled protein and quantitate spots in a scanner.

Cell Lysate Microarrays (Reverse Microarrays) – From Cells to Protein Profiles

Reverse Phase Protein Arrays

Microarrays with individual cell lysate spots of a 130 µm diameter, representing 1 to 10 cell equivalents each, are being produced using the robust piezo-electric non-contact deposition method of the Nano-Plotter. Signals are generated by fluorescently labeled antispecies antibodies. Due to the extremely low sample consumption of the spotting process large numbers of replicate arrays can be produced and thus allow the efficient determination of substantial numbers of proteins.  The simple, robust and highly parallel architecture of the assay yields precise quantitative information and allow time course monitoring of protein expression and activation.

From tissue to data (Source: Zeptosens AG)

From tissue to data (Source: Zeptosens AG)

 

From tissue to data: The procedure of Zeptosens Cell Lysate Microarrays

 

 

 

 

 

 

The applicability of the ZeptoMARK CeLyA approach has been demonstrated among others by

  • Identification of disease relavent marker proteins in cultured cells, tissues, microdissected material as well as depleted serum and urine
  • Determination of dose efficacy and IC50 of drug candidates
  • Quantification of cell signalling pathway activation / inhibition with a precision of better than 20%
  • Monitoring phosphorylation changes on multiple kinases

More information on this technology ist available from Bayer Technology Services, Leverkusen (German)


 

Glycoprotein Arrays

Protein Microarrays

to study Post Translational Modification Changes as a Function of Disease (Tasneem et.al.)

Background

Complementary to the popular antibody arrays, this application uses pre-separated proteins from cellular lysates or other bio-fluids. The resulting arrays are probed with agents that can specifically detect certain post translational modifications. Differences in modifications between different disease states can therefore be highlighted.

Method

Glycoproteins from serum samples can be enriched and separated by nonporous reversed-phase HPLC. Separated proteins are then arrayed on nitrocellulose slides and probed with multiple types of lectins using a biotin-streptavidin platform to detect glycan structures present in the glycoprotein.

Dilution series of standard glycoproteins to study lectin specificity.

Dilution series of standard glycoproteins to study lectin specificity.

 

Printed glycoproteins were probed with biotinylated lectin followed by streptavidin conjugated to green florescent Alexafluor.

 

Comparison of different glycan structures in sera from healthy patients and those diagnosed with pancreatic cancer using multi-lectin detection.

Comparison of different glycan structures in sera from healthy patients and those diagnosed with pancreatic cancer using multi-lectin detection.

Each vertical panel of spots represents a unique peak from the reversed-phase HPLC separation. Each separated glycoprotein was printed in 9 replicates to monitor variations due to printing. Within 10% variation was found for most fractions studied.

 

 

 

 

 

 


Courtesy of: Tasneem Patwa
University of Michigan Medical Center
Department of Surgery
MSRB I, A510B
1150 W. Medical Center Drive
Ann Arbor, MI 48109-0650
USA


Patwa TH, Zhao J, Anderson MA, Simeone DM, Lubman DM.: Screening of glycosylation patterns in serum using natural glycoprotein microarrays and multi-lectin fluorescence detection. Anal Chem. 2006 Sep 15;78(18):6411-21.

 

 

Stent Coating

Coating of Drug Eluting Stents

The GeSiM Nano-PlotterTM has been extended by a motor controlled rotor for the application of Micrograms of solved polymer on cylindrical microstructures. This application notice shows how to dispense Nanoliter amounts on stain less steel made coronar stents. Basically a “stent” is a tiny mesh or scaffold for insertion into coronar vessels of the human body. Orginally stents were developed to prevent blood vessels from collapsing after ballon angioplasty. A resistent problem was that bar metal stents still experienced reblocking as a body’s response to the “controlled injury” of arterial vessels during insertion of the stent. The controlled drug release requires to embed the drug into a soluble polymer. For a reproducible release rate an exact amount of drug solution has to be applied to the scaffold structure of the stent. Dipping the stent into a reservoir is no appropriated approach. The rather high viscous drug solution simply bridges meshes of the stent structure which leads to an unpredictable amount of remaining drug after levering the stent out of the reservoir. Placing the stent onboard of the micropipetting system Nano-Plotter brings up several advantages:

  • Less waste of material by controlled aspiration of sample into the dispenser nozzle
  • Applying of single drops below one Nanoliter avoids bridges between and tears on the stent structure
  • The programmable number of microdrops ensures exact and reproducible drug deposition solely on the stent structure
  • The camera based alignment of the dispenser above the stent ensures that no stent will be missed
  • The rotating stent holder allows homogenous coating of all sides of the cylindrical stent
The rotating stent holder can be moved to any position between 0° and 360°

The rotating stent holder can be moved to any position between 0° and 360°

A single drop volume is about 250 Pikolitres

A single drop volume is about 250 Pikolitres

 

The GeSiM Nano-PlotterTM has been extended by a motor controlled rotor for the application of Micrograms of the operation software of the Nano-Plotter allows two different modes for dispensing on the stent structure: a) Continuous line dispensing emitting drops at a fixed frequency (faster) b) Step-by-step dispensing, the nozzle stops before ejecting a drop (more accurate).


The development of the rotating stent holder was initiated by

UoG-logo.gifUniversity of Greenwich, School of Sciences, Medway Campus, Central Avenue
Chatham Maritime, Kent, ME4 4TB, UK
We thank Dr. Dionysios Douroumis and his group

 

Loading of Biosensors

Electrical Biochips – The comfortable Way of detecting Biomolecules

Eight channel head over biochip wafer

Eight channel head over biochip wafer

 

The department “Biotechnical Microsystems (BTMS)” of the Fraunhofer ISIT is one of the worldwide leading groups in the field of electrical biochip technology. The electrical biochips offer intrinsic advantages because of particle tolerance and mechanical robustness by the direct transduction of biochemical reactions into electrical current.

The use of gold electrode arrays combined with integrated reference and auxiliary electrodes along with sensitive, selective measurement techniques like “Redox-Cycling” enables powerful sensor systems. These arrays are useful for the detection of a variety of analytes within one sample simultaneously. User-friendly operability is realized by integrating the biochips into cartridges. In combination with micro-fluidic components and integrated electronics, these electrical microarrays represent the basis of rapid and cost-effective analysis systems. They can be used to identify and quantify DNA, RNA, proteins, whole cells as well as haptens.

 

Droplets on a biochip

Droplets on a biochip

The used array chips consist of 16 gold electrodes for immobilizing capture molecules and the final electrochemical read out. These positions are 350 µm in diameter and therefore the capture molecules have to be deposited position specific by a piezodriven nanodispensing device. In our case we use the nanospotter technology from GeSiM (Left image). The chips are spotted directly on a diced wafer with 316 biochips glued on a dicing frame. Each chip will be picture recognized by the nanoplotters head camera before dispensing. Then the chips are spotted individually by 4 or 8 nanotips with a dispensed amount of 10 nl on each chip position. Afterwards the head camera takes a picture of each freshly dispensed chip for quality control (Right image). Then the chips are incubated, blocked, dried and are ready for assembling.


FhG-ISIT

FhG-ISIT

 

With Courtesy of Dr. Eric Nebling, Fraunhofer Gesellschaft Germany (ISIT)
Fraunhoferstrasse 1, D-25524 Itzehohe

 


–     L. Blohm et. al.: “Rapid detection of different human anti-HCV immunoglobulins on electrical biochips”, Antibody Technology Journal, 2014:4 23–32

–      S. Kraus et. al.: “Quantitative measurement of human anti-HCV Core immunoglobulins on an electrical biochip platform”, Biosensors and Bioelectronics 26 (2011) 1895 – 1901

 

 

 

Piezoelectric

 

Dispensers

Piezos and Pulses

How does the Drop come out?

Deflection of a piezoelectric ceramics on a GeSiM dispenser

Deflection of a piezoelectric ceramics on a GeSiM dispenser

The dispensers (also called “pipettes” or “jets”) follow the drop-on-demand principle, i.e., a drop is released exactly when the piezo ceramic actuator is triggered. This results in the bending of a silicon diaphragm behind the actuator and this in turn leads to a compression of the liquid inside the “pump chamber” and hence to the ejection of a droplet from the nozzle. After this, the ceramic returns to its initial state and the dispenser is refilled with liquid from the inlet. No valve is involved in this process.

Basically this process only works for low-viscous liquids up to a viscosity of about 5 mPa*s (5 cP). Liquids with lowering viscosity at elevated temperature may be used with our heatable dispensers.

 

Specs and Sizes

Which Dispenser works best for me?

Baiscally GeSiM offers piezoelectric microdispensers for two different drop volumes: The standard type SPIP emits drops between 0.6 and 1.1 Nanolitres. The other one is called PicPIP for drops of 0.1…0.2 Nanolitres. Basically the larger one has a wider viscosity range and is therefore easier to manage.

Two operation modes are available for the GeSiM dispenser: Drop bursts and continuous flow at frequencies up to 500…1000 Hz, depending on the liquid properties.

Bent Steel Capillary

Bent Steel Capillary

HPLC Bushing 1/16 inch

HPLC Bushing 1/16 inch

Stainless Steel Connector

Stainless Steel Connector

PEEK Capillary

PEEK Capillary

 

 

 

 

 

 

Both types of dispensers are available with different housings.


 

Please download the product brochure for more details and ordering information.