Category Archives: Biosynthesizer

BioSyntheSizer

Concept of the BioSyntheSizer

Introduction

Introduction video (720p) on Youtube

Introduction video (720p) on Youtube

The compact GESIM BioSyntheSizer manifests a new instrumentation concept for robots for complex laboratory automation on low-volume scale. It is a new, very compact lab automation platform whose goal is utmost flexibility. In the standard configuration it masters several different chemical syntheses simultaneously, as long as they fit in a liquid handling scheme. This, on the other hand, allows parallelization without having to make a new setup for each synthesis.

 

20 years of experience in the field of microfluidics and lab automation sets the BioSyntheSizer apart from common pipetting robots. Hard- and software follow a strictly modular approach and makes the platform open for application specific configurations. We will be pleased to learn about your requirements in chemical synthesis!

 

BSyS 3.1

A Dream comes true in Chemical Synthesis

The BioSyntheSizer relies on a gentle but accurate robotic stage with a cascadable tool head with up to seven independently moving Z-axes.

Micro work flows for customer specific configurations

Micro work flows for customer specific configurations

 

From an application perspective the platform allows to define synthesis work flows consisting of different material handling steps/micro work flows (Right side, to be completed). Very different tools, vessels and reactors connect and work together for a specific application. The instrument software always reflects the current setup and quickly adapts to changing requirements when new hardware gets onboard.

 

The instrument has been designed for but not limited to the synthesis of biopolymers, e.g. collagen, hydrogels, radiopharmaceutical tracers. Click here for an overview of already realized applications.

 

 

 

Multi-Function Head for Free Choice of Tools

Interchangeable Tools for up to 7 Z-Axes

Individually lowering Z-axes allow to synchronize multiple tools with different dimensions. The head of the instrument connects to the F-box (Media control unit for compressed gas, power, vacuum).

 

Example of a BSyS print head with seven Z-axes: (1) camera, (2+3) twin tool vaccum gripper + 3-lumen pipet, (4) FlipTube cap opener, (5) heatable piezo pipet +Z-Sensor on one axis, (6+7) nozzle/needle adapter (From left)

Example of a BSyS print head with seven Z-axes: (1) camera, (2+3) twin tool vaccum gripper + 3-lumen pipet, (4) FlipTube cap opener, (5) heatable piezo pipet +Z-Sensor on one axis, (6+7) nozzle/needle adapter (From left)

 

Liquid Handling

  • Conical receptacle to load/ eject disposable pipet tips and Luer needles
  • Needle tips for penetration of antiseptic lids
  • Piezoelectric Picolitre pipettes
  • Twin-tip Piezoelectric pipet: Two piezo pipets can be swivelled to mix up drops in flight
  • Solenoid dispense valves for the Nanolitre range
  • Pneumatic/ piezo dispense valves for more viscous drops

Mechanical tools

  • Vacuum gripper for crimp vials and 3-lumen pipette for inert gas, solvent, vacuum, e.g. for azeotropic drying of solutes
  • Tool for cap opening/closing of FlipTube microcentrifuge tubes
  • Z-sensor to measure height profiles of substrates

Others

  • Powder pipettes for the Microgram range
  • Cartridge dispensers for high viscous media
  • Titration pipette for automatic adjustment of pH
  • Camera for pattern recognition and QR code identification
  • UV lamp for crosslinking

 

 

Racks and Reactors

Components for the Work Area of the Instrument

BSys3.1 with application specific kit plates onboard (right)

BSys3.1 with application specific kit plates onboard (right)

 

On the work deck you find easily mountable and removable holders for disposable pipette tips, needles, microtitre plates, glass slides, storage and reaction vessels (e.g. crimp vials with septum, microcentrifuge tubes with cap) and other freely definable objects that can be heated or cooled on request. A time-controlled connection to extraction or cleaning columns, an HPLC or a photometric analysis can be done via tube adapters.

 

  • Trays for micro well plates/ slides
  • Racks for microcentrifuge tubes, septum vials, disposable pipette tips, Luer-lock needles
  • Racks  with tube adapters to connect nozzles to tubes/columns etc.
  • Racks with filter cartridges for ion separation
  • Application specific microfluidic manifolds
  • Reactors with antiseptic lid, temperature up to 150°C, pressure up to 8 bar
  • Magnetic stirrers
  • Wash/Dry stations, optical tools for tips alignment and droplet measurement (stroboscope)

 

 

 

Accessories

Covers, Chillers and Others

  • Enclosure for dust protection, N2 pressure excess
  • Humidification
  • Chilling and temperature control
  • Radioactivity sensors
  • Separate F-Box with pumps, valves etc.

 

 

Synthesis of PET-Tracers

Proof-of-concept for automated synthesis of PET-Tracers

This tab outlines the result of a cooperative development of ABX GmbH and GESIM mbH, initiated by a BMBF supported joint research project (FKZ: 13N10271).

To conduct a PET scan, a short-lived radioactive tracer isotope is injected into the living subject (usually into blood circulation). The tracer is chemically incorporated into a biologically active molecule in order to fit a particular medical indication.

The tracer isotope cannot be produced in advance but must be synthesized shortly before the PET scan. On the other hand, the manipulation of radioactive components requires stringent work protection measures for the clinical staff.

MSRP3.1 with with reactor (left) and ABX kit plates (right)

BSys 3.1 with with reactor (left) and ABX kit plates (right)

BSyS 3.1 allows the unattended synthesis of multiple radioactive tracers for different medical indications. It brings up productivity of the PET facility to a new level:

  • Up to eight validated synthesis per day
  • Novel synthesis procedure established for [18F]FDG, [18]FLT, [18]FMISO, [18]FNaF, [18]FES, [18F]FET, [18]FSB-peptides and [68Ga]GA-peptides
  • 8 Kit plates featuring reactor, reagent and SPE purification and separate canulla reservoirs

This version of BSyS 3.1 still needs to be evaluated and certified for use with PET scanners in a clinical environment. Research groups from Roskilde and Copenhagen, Denmark, have used the BSyS 3.1 to develop Ti-containing cytotoxic compounds without cisplatin cross-resistance. However, at present no protocol exists that is working out of the box.

 

 

Synthesis of Hydrogels

The Promise of Water containing Hydrogels

Hydrogels are widely used in regenerative medicine. The soft and water containing polymers are well appropriated as cell culture media but keep cells “in shape”: 3D printing arranges the hydrogel in a spatial manner or allows combined printing with other polymers.

In collaboration with the Leibniz Institute for Polymer Research Dresden a configuration for Hydrogel synthesis was developed. It starts with the conjugation of Polyethylene Glycol (PEG) with crysteine-containing peptides such that the conjugate contains a terminal thiol group. At the same time, heparin is coupled with reactive groups, all in an automated way. The PEG-peptide-thiol polymer is then linked to the heparin via a sulphur bridge, and other components (cells, adhesive peptides) are added. Star-hydrogels are possible.


The GeSiM BioScaffold printer is well appropriated for 3D prints with hydrogels. Please visit the related product site for BS3.1.