Hoffmann-la Roche Inc.

F. Hoffmann-la Roche Ag

Schott Glaswerke

Carl Zeiss Jena Gmbh

Carl-zeiss-stiftung

Cybio Ag

Christof Fattinger

Martin Heming

Tom Kissling

Thomas Zumstein

Volker Paquet

Ralf T Kersten

Johannes Segner

Remo Anton Hochstrasser

Peter Berndt

Dieter Voegelin

Hansj&ouml;rg Tschirky

Thilo Enderle

Roland Hochhaus

Jurgen Otto

Dieter Krause

Frank-Thomas Lentes

Burkhard Danielzik

Dieter Graefe

Martin Gluch

Patrick Iaiza

Hansjoerg Tschirky

Martin V&ouml;lcker

Roger Steiner

Richard Ameling

Hans-Peter Hirt

Gerhard Flury

Claudia Mcginnis

A device for use in the detection of binding affinities comprises a substrate, a planar waveguide arranged thereon and having an outer surface. The device further comprises a grating for coupling coherent light of a predetermined wavelength into the planar waveguide such that the coherent light coupled into the planar waveguide propagates through the planar waveguide in a predetermined propagation direction. An evanescent field of the coherent light propagates along the outer surface of the planar waveguide. The outer surface of the planar waveguide has receptor molecules arranged thereon capable of binding target samples to the receptor molecules such that light of the evanescent field is diffracted by the target samples bound to the receptor molecules. The receptor molecules are arranged along a plurality of straight parallel lines such that a portion of the light of the evanescent field is diffracted by the target samples bound to the receptor molecules.

Device for use in the detection of binding affinities

A method for the detection of binding affinities comprises providing a device having a planar waveguide () arranged on a substrate () and an optical coupler (). Coherent light () of a predetermined wavelength is coupled into the planar waveguide () such that the coherent light propagates along the planar waveguide (), with an evanescent field () of the coherent light propagating along an outer surface () of the planar waveguide (). Target samples () attached to binding sites () are arranged along a plurality of predetermined lines () on the outer surface () of the planar waveguide (). At a predetermined detection location, light of the evanescent field which is scattered by target samples () bound to binding sites () arranged along the predetermined lines () is detected. The light scattered by the target samples () bound to the binding sites () has, at the predetermined detection location, a difference in optical path length which is an integer multiple of the predetermined wavelength of the light.

Method for detection of binding affinities

A device for use in the detection of binding affinities, the device comprising a planar waveguide () arranged on a substrate (), and further comprising an optical coupler () having a predetermined length for coupling coherent light () of a predetermined wavelength into the planar waveguide () such that a parallel beam of coherent light propagates through the planar waveguide () with an evanescent field () of the coherent light propagating along an outer surface () of the planar waveguide (). The outer surface () of the planar waveguide () comprises binding sites thereon capable of binding target samples to the binding sites such that light of the evanescent field () is diffracted by target samples bound to the binding sites. The binding sites are arranged along a plurality of predetermined straight lines () running parallel to one another with a constant distance between adjacent straight lines.

A device () for use in the detection of binding affinities comprises a planar waveguide () arranged on a substrate (). The waveguide () has an outer surface () and a plurality of incoupling lines () for coupling a beam of coherent light into the waveguide () such that a parallel beam of coherent light () propagates along the waveguide (). The incoupling lines () are curved and have an increasing distance between adjacent incoupling lines (). A divergent beam of coherent light () of a predetermined wavelength is coupled into the waveguide () such that it propagates along the waveguide (). A plurality of binding sites () is attached to the outer surface () along at least one further plurality of diffraction lines arranged in an outcoupling section of the waveguide (). These diffraction lines comprise a plurality of curved outcoupling lines () having a decreasing distance between adjacent outcoupling lines. They decouple a diffracted portion of coherent light from the planar waveguide (), and the decoupled portion of coherent light () converges into a predetermined second focal location ().

A device for use in the detection of binding affinities comprises a planar waveguide () arranged on a substrate (), and an optical coupler () for coupling coherent light () of a predetermined wavelength into the planar waveguide. The coherent light propagates through the planar waveguide () with an evanescent field () propagating along an outer surface () of the planar waveguide. The outer surface () of the planar waveguide comprises binding sites () thereon capable of binding target samples () to the binding sites () such that light of the evanescent field () is scattered by target samples () bound to the binding sites (). The binding sites () are arranged along a plurality of predetermined lines () which are arranged such that the scattered light constructively interferes at a predetermined detection location with a difference in optical path length which is an integer multiple of the predetermined wavelength.

Sample handling system for handling samples contained in tubes (), each tube () having a hollow body, a closed bottom and an open top for accessing the sample contained in the tube (). The system comprises a micro-plate () comprising at least one grid insert () having a plurality of compartments. Each compartment comprises one or more side walls laterally confining a through-hole for receiving a said tube (). The through-hole has a top opening and a bottom opening and extends between the top opening and the bottom opening. A frame () to which the at least one separate grid insert () is to be attached to form the micro-plate (). The frame () laterally confines a through-opening which is dimensioned to allow for accessing each compartment () of the attached at least one grid insert () from above and from below. This allows for moving such tube () into and out of each compartment () through each of the top opening () and the bottom opening () of the through-hole ().

Sample handling system

A system for dispensing a sample into a buffer liquid includes a pressure chamber having pressure supply means for generating an overpressure within the pressure chamber. An inlet capillary supplies a buffer liquid to an outlet end arranged in the pressure chamber, and an outlet capillary discharges the buffer liquid from the pressure chamber. The outlet capillary has an inlet end in the pressure chamber facing the outlet end of the inlet capillary to form a capillary gap. A dispenser having a dispensing end is in the pressure chamber at the capillary gap to allow the sample at the dispensing end to be dispensed into the buffer liquid entering the outlet capillary inlet end. The pressure chamber includes a sample port that allows the dispenser to be moved into and out of the pressure chamber.

System for dispensing a sample into a buffer liquid

According to the invention there is provided a method for preparing the outer surface () of the planar waveguide () for binding target samples along the plurality of predetermined lines (). The method comprises the following steps. Providing a planar waveguide () with an outer surface () adapted for attachment of a head group () of a linker molecule () to the outer surface (). Sequentially applying at least one plurality of linker molecules () to the outer surface (). Each plurality of the at least one plurality of linker molecules () assembles to form an individual layer of linker molecules () with individual layers formed one above the other starting from the outer surface () of the planar waveguide (). Each linker molecule () comprises a functional group () and the head group () which is capable of attaching to the outer surface () of the planar waveguide () or to the functional groups () of the preceding layer of linker molecules (). The functional groups () of the plurality of linker molecules () of the uppermost layer are bound to photo-labile protecting groups () so that each functional group () bound to a said photo-labile protecting group () is incapable of attaching a complementary functional group of a further molecule. Exposing those photo-labile protecting groups () of the uppermost layer arranged along a plurality of predetermined lines () to light of a predetermined wavelength to remove the exposed photo-labile protecting groups () from the functional groups () to make these functional groups () capable of attaching a complementary functional group of a further molecule.

Method for preparing an outer surface of a planar waveguide to be capable of binding target samples along a plurality of predeterminded lines and a planar waveguide

A hanging droplet plate () comprises a predetermined number of droplet compartments () each being capable of receiving a droplet of a liquid. The respective droplet compartment () comprises a circumferential microfluidic wetting barrier () which is arranged to surround a respective cavity () and which prevents a droplet from spreading beyond the microfluidic wetting barrier (). The respective compartment () comprises a closed bottom () and at least one additional circumferential microfluidic wetting barrier (), each additional circumferential microfluidic wetting barrier () which is arranged to surround a preceding circumferential microfluidic wetting barrier (). A wettable area () is arranged between two adjacently arranged microfluidic wetting barriers ().

Hanging droplet plate

A robotic microplate storage system includes a freezer room having freezing units and a first robot for moving and removing microplates into and out of the freezing unit. The first robot can also transfer microplates to a processing station, where the microplates are stored in a microplate recipient within the freezing unit. The storage system may also include at least one processing room which is thermally separated from the freezer room. Each processing room may include a processing station having a tube transfer module and a second robot for moving the microplates between the microplate recipients and the tube transfer module. The first robot may be designed such that it is only capable of removing a microplate recipient from and moving it into a freezing unit as well as transferring it from a freezing unit to a processing station or vice versa.

System and method for robotic storage of microplates

A transport system for transporting and handling microtiter plates, for use in high throughput screening, diagnosis and/or combinatorial chemistry, comprising modules with devices for preparing specimens and/or introducing specimens, and/or for optical readout and/or for plate storage and/or devices for further processing steps or readout steps. The system includes an inter-modular transport system for transporting the microtiter plates between the different devices and at least one central transport system for asynchronous plate transfer between individual modules via input and output buffers.

Device for transporting and holding microtiter plates

Microtiter plate

A compound handling system handles a multiplicity of chemical or biological compounds or samples, and is especially adapted for high throughput screening of compounds that are stored and handled in aliquotted form. Aliquots are contained in individual containers and the containers are arranged in racks having holding spaces open at opposite ends. Insertion and removal of the containers is effected in either direction of movement, and each container may be sealed with foil to protect its integrity.

Compound handling system

The invention relates to an imaging system for optical automatic analysers, especially fluorescence readers. On the sample side, the imaging system contains a cylindrical lens array and a prism array, which is arranged upstream of the cylindrical lens array. The prismatic effect of the prisms of the prism array lies in the direction of the cylinder axes of the cylindrical lenses. Together with a telescopic imaging system, the inventive imaging system creates a number of parallel cylindrical focussing volumes between the cylindrical lens array and a detector array, these focussing volumes being slanted towards the optical axis of the telescopic system in relation to the vertical. The arrangement enables the detection of fluorescence with a large aperture in one direction, and at the same time enables depth selective analysis of the fluorescence signal, especially the discrimination of the fluorescent radiation originating from the solution above.

Imaging system with a cylindrical lens array

A microdispensing system is useful for the open-jet dispensing of liquids. A valve having a valve chamber is bounded by an impermeable elastic membrane and is filled with the liquid for dispensing. One or more liquid supply lines lead to the valve chamber. An outlet closed from the exterior by the membrane in the position of rest leads from the chamber to a dispensing nozzle. An actuator chamber is disposed on the other side of the membrane. In the actuator chamber, an electromechanical drive is connected to the membrane for the purpose of briefly lifting the membrane from the outlet. The actuator chamber is closed in such manner that it can be subjected to a pressure differing from atmospheric pressure.

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Blauen, Switzerland

Christof Fattinger