Molecular Dynamics Limited

Amersham Biosciences (Sv) Corp

Amersham Biosciences Corp

Richard F Johnston

David John Roach

Stevan Bogdan Jovanovich

Robert T Loder, Jr

David L Barker

Dennis W Harris

Thomas M Armstrong

Eric Gifford Marason

Robert C Kain

John S Bashkin

Gregory J Ronan

Ezra Van Gelder

Siobhan C Pickett

Bee C Liang

Mary Trounstine

An apparatus for filling and cleaning channels and inlet ports of a microchip substrate is disclosed. A device of the apparatus comprising an array of tubes is inserted into each of the inlet ports of the microchip. The array of tubes of the device comprises a plurality of pressure tubes, surrounded by a plurality of vacuum tubes. In conjunction with this, pressurized solutions such as matrix or wash are introduced into common openings on the microchip that provide a passage to microchannels of the microchip with the use of pressure tip injectors of the apparatus. As matrix or wash solutions are pumped through the common openings and microchannels of the microchip substrate, wash solutions are pumped through the plurality of pressure tubes and everything is vacuumed through the plurality of vacuum tubes surrounding the plurality of pressure tubes. Various reservoirs of solutions are selected and allowed to flow by proper valve actuation. This process can be performed manually or easily automated by utilizing appropriate valves and control hardware/software.

Apparatus and method for filling and cleaning channels and inlet ports in microchips used for biological analysis

A substrate with a plurality of microchannels is movably deployed with other movable objects that will load sample into the microchannels, stimulate molecular migration, read the results of the migration, remove and replace the substrate, and prepare for a new run. The other objects include a gripper for engaging and moving the substrate, an electrode array of fine wires suitable for fitting into the microchannels for electromigration, and a scanning detector for reading migration results. A sequence of automatic operations is established so that one substrate after another may be moved into position, loaded with sample, stimulated for molecular migration, read with a beam, and then removed and replaced with a fresh substrate.

Robotic microchannel bioanalytical instrument

A capillary valve, connector and router where one or more cylindrical fibers, which may be capillaries, plugged capillaries, optical fibers, or the like, including at least one capillary tube are contained in a first bundle of fibers that terminates at a first face. A second cylindrical bundle of fibers also containing one or more fibers including at least one capillary tube terminates in a second face abutting the first face. A fastener or adapter holds the members together with faces in mutually biased alignment. Connection of a plurality of macroscale pumps enables push-pull fluid motion, with routing, in a capillary system formed by a plurality of fibers coupled by switches, connectors and routers. Chemical reactions, separations and analysis may be carried out with microliter volumes or smaller.

Method of merging chemical reactants in capillary tubes

A capillary valve, connector and router where one or more cylindrical fibers, which may be capillaries, plugged capillaries, optical fibers, or the like, including at least one capillary tube are contained in a first cylindrical bundle of fibers that terminates at a first face. A second cylindrical bundle of fibers also containing one or more fibers including at least one capillary tube terminates in a second face abutting the first face. A fastener or adapter holds the members together with faces in mutually biased alignment, allowing relative rotation of the two cylindrical bundles which terminate in rotatable ferrules. Various functions achieved by rotation include a zero dead volume slide valve, a fluid router and a manifold. The fibers in each sleeve are preferably of uniform size for close symmetrical packing, but could be of disparate sizes, allowing connection of macroscale tubes to capillary tubes. A single connector member may be attached by a fastener to a reservoir or other macroscale device to bring one or more capillary tubes into fluid communication with a macroscale device. A plurality of fibers in one ferrule could allow dispensing of fluid from a single fiber in the other ferrule so that a single fiber could feed a plurality of wells through the plurality of fibers. Connection of a plurality of macroscale pumps enables push-pull fluid motion, with routing, in a capillary system formed by a plurality of fibers coupled by switches, connectors and routers. Chemical reactions, separations and analysis may be carried out with microliter volumes and smaller.

Capillary valve, connector, and router

A sample substrate for use in a fluorescence imaging system includes a rigid base with a specularly reflective surface, typically metal, on which is deposited a transparent coating layer. The coating layer has a thickness selected so that a particular fluorescence excitation wavelength, corresponding to a specified fluorescent constituent to be sought in sample material, has an optical path from the top of the coating layer to the reflecting surface in the base of substantially an odd multiple of one-quarter wavelength, so that the standing wave of the fluorescence excitation wavelength of light incident on the substrate has an antinode located at or near where sample material would be disposed on top of the coating layer. This maximizes fluorescence excitation of the sample on the reflective substrate. The transparent coating layer may be a dielectric material (e.g. silica) or may be a multilayer structure with a top layer of biologically active material for binding a specified sample constituent.

Optical substrate for enhanced detectability of fluorescence

A microspot deposition system featuring a hollow cylindrical wall extending from a closed end, terminating in an open end and including a longitudinal gap extending from the open end toward the closed end to allow the rapid exhaustion of the atmosphere and efficient cleaning within the cylindrical wall. The cylindrical wall defines a lumen with both the lumen and the gap adapted to facilitate capillary action of liquid in fluid communication therewith to form a meniscus proximate to the open end. To facilitate deposition of liquid contained within the lumen, the gap may be tapered so that it is narrowest proximate to the open end. The narrowed portion of the gap results in a meniscus having a reduced area to ensure preferential fluid flow toward the open end, which facilitates deposition via capillary action between the liquid in the lumen and a working surface on which the liquid is to be deposited.

High-speed liquid deposition device for biological molecule array

A method for coupling DNA to a glass substrate by aminating the glass substrate with an aminosilane, reacting DNA with a carbodiimide/imidazole solution to create a 5'-phosphorimidazolide, and reacting the aminated glass substrate and phosphorimidazolide to couple the DNA to the substrate.

Aminosilane/carbodiimide coupling of DNA to glass substrate

A capillary electrophoresis separation matrix for single-stranded nucleic acids, along with methods for using and preparing the matrix, are disclosed. The separation matrix provides denaturing conditions and contains hydroxyethyl cellulose (HEC) in combination with urea, and preferably also includes formamide. The separation matrix may be used for DNA sizing and sequencing applications and provides a single-base resolution to approximately 500 base pairs. The separation matrix is inexpensive, easy to prepare, requires no polymerization steps, and is of low enough viscosity to be pumped easily into and out of capillary tubes for electrophoresis. The low viscosity allows for high throughput of samples and reuse of the capillary tubes for numerous separations.

Denaturing separation matrix having hydroxyethyl cellulose for nucleic

A fluorescence detection scanner and method employing a fiberoptic collector, positioned adjacent to the scanning plane of the excitation beam, with a light collecting surface which is oriented to reject back-scattered excitation light from the incident surface of the sample support. The scanning plane of the excitation beam is off normal relative to the incident surface of the sample support and the light collecting surface is located within the area defined by the resulting acute angle of incidence. The light collecting surface is angled away from the location at which the incident excitation beam intersects the surface of the sample support so that back-scattered excitation light does not enter the optical fibers. The orientation of the light collector results in a four to five-fold decrease in excitation-light background without attenuation of the fluorescence emitted by the sample. Long-pass interference filters, selected to reject the excitation wavelength, are located at the input and output surfaces of the fiberoptic light collector to further reduce background excitation light. Multiple fluorophores are discriminated by sequentially scanning the sample with a different interchangeable narrow bandpass filter for each fluorophore. Internal fluorescence standards in the sample are used to determine filter efficiencies for each label in each filter image and the quantity of each fluorophore is computed by linear analysis. Increased detector sensitivity allows linear quantitation of multiple fluorophores in the femto-mole range.

Apparatus for measuring spatial distribution of fluorescence on a

Using storage phosphor recording media, two exposures are made of a sample containing two target substances tagged with different radiative emitters, for example 32-P and 35-S. The first exposure, image 1, is of the sample directly on the phosphor screen. The second exposure, image 2, is made with the appropriate absorption material between the sample and screen. Both images are captured. By using simultaneous equations isotope contributions of each label can be determined. Quantitative assessment of the contributions of the isotopes, and hence the target substances, are made by calculating isotope efficiencies both with and without the absorption filter.

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Murphys, CA, United States of America

Richard F Johnston