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coreshellscaffold

Advanced Tools for BS3.1

Dec. 2016: We are proud to annouce new printing tools for the BioScaffold Printer BS3.1. Melt Electrospinning Writing allows the accurate deposition of polymer fibres below 20 Micrometer diameter.

The Pneumatic Core/Shell Extruder combines biopolymers of different characteristics, e.g. e soft polymer hosting living cells in the core lane with a more rigid biopolymer in the shell lane.

iba-flow-through-cell

Enridgement and Manipulation of Microorganisms

Oct 2016: In collaboration with IBA Heiligenstadt e.V. GeSiM developed a customized MicCell to investigate microorganisms in drinking water. This MicCell comprises three fluidic channels. Cell manipulation is achieved by interdigital electrodes with sizes from 20…100 Micrometers. We embedded up to 12 different IDEs for

  • Dielectrophoretic enridgement
  • Pulsation based perforation of cell membranes
  • Measurement of conductivity changes

Schieke.pdf

 

3d-insect

Meet us at upcoming events!

Sept. 2016: There are a few events coming up dealing with state-of-the art aspects of tissue engineering and 3D printing:

  • The annual conference of the German Society for Biomaterials will take place on 29th September to 1st October in Aachen. We will demonstrate the latest BioScaffold printer BS3.1
  • A bioprinting and 3D printing conference to be held in Cambridge, UK (13/14 October). Our UK distributor, Analytic Ltd., will man a booth.

Don’t miss these opportunities to meet up with GeSiM, We look forward to fruitful talks with you.

 

Neutec

We welcome Neutec Group Inc!

May 2016: GeSiM is proud to announce the partnership with Neutec Group Inc., Farmingdale, NY.

The established sales company will start to promote the new GeSiM BioScaffoldprinter BS3.1 within the territory of North America. It allows customers in the US and Canada to purchase Bioprinter products and accessories from a local source.

Turtle_Thumbnail

New Demo Lab in Shanghai

May 2016: GeSiM is now preparing new lab space in one of Asia’s leading Biotech Hotspots. It will allow local prospects to see and try GeSiM instruments before doing an investment.

The lab is supposed to open mid July and will be managed by our Asian Sales Manager. It is located in the Baoshan District of Shanghai. Please contact us for detailed information.

 

Currently there are no vacant positions at GeSiM mbH. Please revisit this page from time to time.

 

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)