µArray + liquid handling    µContact + NIL

Picoliter fabrication liquid handling platform

The Nano-PlotterTM is not just another microarray spotter. Modular hardware and an open software guarantee utmost flexibility to tackle even the most demanding print job. The piezo dispensers handle a wide range of liquids, not only protein and DNA, and eject droplets as small as 50 picoliters.

Microscope-based image processing makes printing onto microelectrodes or other tiny elements easy. Customized Nano-Plotter versions, e.g. for integration into automated production lines, are available on request.

Application examples
  • Microarrays for research, diagnostics and drug discovery (DNA, proteins, carbohydrates, lipids etc.)
  • Spotting of beads and living cells
  • Spotting into 96-well plates and onto many other substrates
  • Pipetting of miniaturized assays
  • Coating of biosensors, usually aided by automatic image processing
The Nano-PlotterTM comes in two different sizes with the following common features:
  • Small footprint
  • Includes dust cover
  • Z-sensor for height profile measurement of targets
  • 1 – 16 independent piezoelectric pipetting tips with full fluidic control
  • Sample aspiration from 96-well or 384- well microtiter plates (MTPs)
  • Array density up to 3000/cm2
  • XY repetition accuracy ± 10 µm, encoder-controlled, step width 2 µm. Travel speed up to 500 mm/s. Spotting on the fly (spotting while travelling) possible
The piezoelectric tips are made of silicon and glass by micromachining (reactive ion etching, anodic bonding etc.). Samples come only in contact with silicon dioxide (the Si surface is oxidized). Each tip is individually actuated; sample uptake and washing are done by syringe pumps. The minimum dead volume (additional sample) is approx. 1 µl. Unused sample can be returned to the well after spotting. Various arrangements on the pipette head are possible.

Tips are thoroughly rinsed on the inside and the outside to avoid contamination. DNA solutions (e. g. 0.1 mg/ml oligos) are washed away in seconds. Proteins and peptides may need longer, and in special cases additional wash fluid (detergent, acid, base etc.) is taken from a reservoir, a well or a second wash bowl

Solids dissolved in organic solvents are spotted by putting a solvent “plug” and an air gap between sample and system water.

Stroboscope check of the piezo tips Each piezoelectric tip is tested by analysing the stroboscope image of the flying droplets before and after spotting. If no droplet is detected, maybe caused by an empty well, the pipette is switched off and the array is repaired later. (If dry spots are visible, a microscope can search for missing spots!) Droplet volume and speed depend on the sample, mainly viscosity. Computing a body of rotation from the droplet contour gives a rough volume estimation; the speed is measured by analysing the droplet pattern at two time points. You can thus optimize pipette parameters so that all samples are spotted with the same speed.

If GesiM’s microfluidic flow sensor is placed in the tube system, it can measure the flow during the stroboscope test, This provides a very accurate droplet volume determination.
For more info, please see product page
Click image to expand view

Non-contact spotting of picoliter droplets ensures utmost flexibility and quality for the fabrication of complex biochips. For many years, Nano-Plotters have been reliable companions for both research and production

The area inside the hood can be varied. Various removable slide trays (also tailor-made) and trays for MTPs are available so that one can trade in slide capacity for source MTPs. NP2.1: Standard layout for 5 x 11 slides (up to 26mm x 76 mm) and one sample plate

NP2.1/E: Configurations for 5 x 23 slides with one sample plate (top) and 3 x 23 slides with four sample plates (bottom). More layouts are available.

Wash cycle in the normal (top) and the optional extra wash station

Stroboscope image (left), 8-fold flow sensor on a syringe pump unit (center) and flow sensor graph (right). A flow rate of 1.7 µl/min at a frequency of 100 Hz corresponds to a droplet volume of 280 pl

Special dispensing systems from GeSiM. Left, heatable piezo tip that is compatible with microtiter plates, with additional temperature sensor cable in a Nano-Plotter. Center, heatable bulk piezo dispenser with reservoir (without fluidics). It can deliver droplets as small as 10 pl. Right, glass capillary dispenser with solenoid valve for higher viscosity and volumes of > 50 nl. Needs a fluidic system with overpressure

Spots on a membrane (2.5 nl, 0.4 mm pitch) and in a 96-well MTP at 0.3 mm pitch. The Z-height sensor measures all target Z-positions for automatic adjustment of spotting heights

Production site for specially designed FDA cleared diagnostic chips

Viscous samples and large volumes Manufactured using a variety of other dispense heads. Viscous media can be delivered by our heatable piezo dispensers. We also offer heatable systems for bulk piezo pipetting with large sample reservoirs. And finally there is a solenoid valve dispenser for nanolitre volumes.

Spotting onto tiny structures It is not easy to dispense a 50 µm droplet exactly onto a target of similar size. A microscope camera on the print head helps: first target positions are identified (typically via alignment marks), then the X/Y position of the droplet is measured to correct even the smallest deviations.

Arrays for DNA, proteins and more This piezo technology provides high spot homogeneity and allows different spot sizes simply by varying the number of drops per spot. Different samples can be spotted by adjusting pipetting parameters, mainly voltage. For higher viscosity, special tips (“HV-J”) and heatable tips are available.

Large-scale chip production Of course, the rather small Nano-PlotterTM is ideal for research and chip development, but this does not mean that it is incapable of high-volume chip production.