Equipment

Lab-on-a-Chip, the miniaturized laboratory on a chip, is a complex system for the simultaneous query of several parameters of one specimen. The SPR measuring device, developed at the Fraunhofer IOF, presents the basis for the Lab-on- the- Chip development. It consists of a reading system and the corresponding SPR chips. In order to measure smallest amounts with the best possible signal-noise ratio, different approaches, such as dielectrophoresis, magnetrophoresis and hydraulic focusing were optimized per simulation. The realization of the corresponding micro-fluidic specimen handling system was done by a Rapid-Prototyping procedure.

Producer

• Fraunhofer IWS / Fraunhofer IOF

Principle

• surface plasmon resonance
• signal increase by using different physical effects during the specimen handling

Technical data

• specimen volume: < 60 µL
• measurement period: depending on the application from 2 min to up to 2h
• analytes numbers are dependent on the immobilization method (e.g. 17 measuring areas of 200 µm width during the functionalization by inverse Micro-Contact-Printing)

Applications

• detection of genetic mutations (DNA detection)
• detection of phytopathogen RNA viruses (RNA detection)
• immunological in-vitro test of substances with artificial humane lymph nodes (antibody detection)
• quick point-of-care diagnostics of bacterial infections (antibody detection)
• detection of various substances in water
• substance testing – detection of particular markers in cell culture supernatants
• substance testing – detection of interaction between receptor and ligant

Advantages

• disposables – polymer chips are suitable for mass production
• parallelism – up to 180 spots enable various applications without need of testing
• non-imaging SPR – angle-resolved measurement offers simple error detection and high measuring reliability
• open system – combination of SPR measurements and various microfluidic systems, depending on requirement
• robust – no moving mechanical parts

Due to the rapid prototyping 3D procedure it is now possible to process pasty materials into porous structures with defined, adapted geometries. To implement these constructs the IWS scientists use a dispense system, driven by compressed air – the 3D Scaffold-Printer. This printer enables the forming of defined strands from viscose material and their arrangement into a structured order.

Presently the 3D Scaffold-Printer is mainly applied in the fields of medical and biotechnological engineering. In addition to the generation of sensor and actor elements, based on conductive plot media, recent research activities focus on individually designed, porous 3D cell matrices, based on highly biocompatible substances. Theses scaffolds are used as base structure for the production of biological tissues.

By means of a multi-channel dosing system, up to three different dosing media can be processed and thus complex scaffolds can be designed.

Producer

• Fraunhofer IWS / GESIM

Technical data: 3D Scaffold-Printer

• main assembly: 3-artridge-dispense system and 3-axial motion system
• dispense pressure: 1-7 bar
• resolution (X Y Z): 2 x 2 x 10 µm
• working place (X Y Z): 100 x 346 x 40 mm
• cartridge temperature control: max. 100 °C
• needle sensor for automatic correction of positional deviations

Options

• fibre-linked UV-irradiation
• fibre-linked spectrometry
• surface treatment with PlasmaPen
• pipetting system

Materials

• biological hydro gel (e.g. collagen, agar, alginate)
• bioactive mineral compounds (e.g. bone cement paste)
• biocompatible non-absorbable polymer pastes 
  (e.g. PU, silicone)
• biodegradable polymer pastes (e.g. PCL, PLLA, …)
• wax, waxy materials (e.g. parafin)
• photopolymers
• conductive pastes, containing nano metal powder

Applications

• production of scaffolds for tissue engineering
• production of soft tissue implants
• printing of living cells (Organic Printing)
• development of perfusion-micro bioreactor systems, based on hollow fibers
• generation of conductive coatings for biotechnological applications
• production of sensors and actuators

The technological development increasingly turns to more and more compact and smaller components and structures. The technology of Nano-Imprint/µ-Contact-Printings (µ-CP) is an excellent alternative to the photolithography, not only because of the costs. Cost-efficient materials can be applied on substrates in an additive-and subtraction process, by the one-time production of an adapted silicone master and the casting of plastic replicas.

The applications range from spatially resolving chemical surface modifications, to the production of smallest geometries and sensor structures, such as the imprinting of light conducting cables, up to their usage as micro reaction systems.

Producer

• GESIM

Technical data

• printing and drying station for max. 4 stamps
• accuracy of 5 μm for repeated printing on the same substrate
• substrate size: 25 x 75 mm
• structured area: max. 10 x 10 mm
  (master chip: 15 x 15 mm)

Materials

• highly and low viscous media
• polymeres
• biological matrices
• modification of metals

Applications

• micro-contact-printing procedure for wet-chemical surface functionalization of smallest substrate amounts
• nano-imprint procedure for the reproducible replica production of structure geometries up to the nm range (Insertion of microfluidic structures in gel)

Flexible solutions for highly sensitive measuring processes of fluorescence signals are the basis for a successful monitoring of chemical and biochemical reactions, cell growth and differentiation. The modular fluorescence measuring system offers a perfect tool for these tasks, last but not least because of its small size of 90 x 100 x 25 mm³. Thanks to the module’s small focus size the fluorescence measurement becomes possible in very small volumes (up to 1 µL) and low concentrations (up to 6*10^-16 mol/mL for calcein).

Producer

• Fraunhofer IWS / IOF

Principle

• fluorescence measurement

Technical data

• wavelength characteristics:
  activation 1: 467 nm / emission 1: 517 nm,
  activation 2: 590 nm / emission 2: 602 nm
• light output is gradually adjustable to 1 W
• period depending on application from 100 ms min to 10 s
• detection limit for calcein at 6*10-16 mol/mL
• detection limit for EGFP at 1.8*10-16 mol/mL
• multiple measurement is possible with defined intervals
• activation via LabVIEW or C + +

Applications

• monitoring of fluorescence-stained or self-fluorescent cell cultures
• monitoring of fluorescence-based reporter gene assays
• reaction kinetics measurements of fluorescent reactance

The NP 2.1 Nano Plotter™ is a universal micro-pipetting system. It consists of a basic model with removable dust cover, a diluter block, an equalizing tank, an ultrasonic humidifier as well as reservoirs for liquids and effluent. The left side of the basic Nanoplotter™ contains the target rack, while the right side contains what is referred to as the functional block with micro-titer plate holder, wash station, drying block, stroboscopic camera and function test sensor.The core of the system: the piezoelectric micro-pipettes that are able to individually or simultaneously meter liquids in parallel using the drop-on-demand process.

This fluid stream is devoid of any direct contact and can precisely and reproducibly immobilize tiny spots on any fixed surface. The droplets produced are always the same size, achieving uniform spotting results.

Producer

• GESIM

Principle of operation

• dispensing of nanodroplets devoid of direct contact via piezo pipettes
• simultaneous or individual metering using the drop-on-demand process

Technical data

• sample quantities: 0.35 nL per drop
• spot life: Up to 20 min per chip, depending on the number of lines
• up to eight pipette channels

Applications

• functionalization of SPR chip
• production of fluorescence patterns for calibration purposes
• production of micro-arrays of proteins

Particle image velocimetry (PIV) allows stream velocities to be determined even in the micro-channels. This facilitates temporally and spatially resolved descriptions of complex circulation of fluid streams, such as in cell cultures or lab-on-a-chip systems for example.

Producer

• Fraunhofer IWS

Principle of operation

• specialized tracer particles are dissolved in the medium
• image recorded using high-speed camera on modified microscope mount
• calculation of stream velocity via cross-correlation (IWS software)

Technical data

• stream velocities up to 500 mm/s can be measured
• statistical presentation of data signals (temporal display of average flow)
• triggerable data logging

Applications

• characterization of micro-pumps
• measurement of shear forces in cell culture systems
• capture of stream profiles in two dimensions
• description of particle distributions

Lab-on-a-chip, the miniaturized laboratory on a single chip, is a complex system for parallel investigation of multiple experimental parameters in a single sample.

A multi-portal system is available for automated pick-and-place, monitoring, and analysis of lab-on-a-chip systems. This includes a temperature-controlled support plate for biochips that can be accessed from above and below using a three-axis gantry with interchangeable heads. The robotic portal system facilitates conduct of complex, precise, fully-automated, user-defined processes spanning many months at high throughput levels with continuous monitoring and logging.

Producer

• Fraunhofer IWS

Technical data

• support plate with up to 10 supports for biochips
• integrated pipette changer
• dispenser for two pipettes
• sealable support plate for 96-well titer plate
• camera system and fluorescence measurement module for real time monitoring of several spectral regions
• can be operated under sterile conditions (in a sterile cabinet for example)

Universal control software

• can automatically execute a protocol consisting of a chronological sequence of doses and data measurements for every chip
• maintenance and test functions
• standard software interface for integrating with laboratory information management systems (LIMS)

Applications

• carrying out long-term toxicity tests on human multi-organ chips
• real-time monitoring of cell vitality and oxygen concentration in biochips

A system for non-invasive measurement of oxygen concentrations was developed at the Fraunhofer IWS based on the OPAL System from Colibri Photonics GmbH in order to ascertain the uptake and consumption of oxygen in chemical, biochemical, and biological processes. Thanks to the compact 90 x 100 x 25 mm³ sensor head, the system can be adapted to operate as a stand-alone module or be employed as a measurement unit in a robotic portal. Automated, spatially-resolved measurement of oxygen content is possible by coupling it to the robotic portal system.

Producer

• Fraunhofer IWS

Principle of operation

• measurement of oxygen content via fluorescence lifetime

Technical data

• optical output power adjustable up to 1 W
• data capture interval from 1 s to continuous, depending on the application
• spatial resolution down to 500 µm
• multiple measurements at programmed time intervals

Applications

• spatially resolved monitoring of oxygen content in cell cultures
• transducers in biosensors involving oxygen consumption
• measurement of reaction kinetics for reactions using