Beckman Instruments, Inc.

Beckman Coulter, Inc.

Affymetrix, Inc.

Peter J Coassin

Jang B Rampal

Robert S Matson

Jack D McNeal

David B Helphrey

Edwin M Southern

Charles T Caskey

Kenneth D Konrad

Charles A Keenan

Ronald M Cook

Edward G Hanna

Stephen W Wunderly

William H Shope

Clement P Aime

Glenn C Sasaki

David E Helphrey

Jiunn-Jye Dih

Roger Winer

Carlton B Mc Kinney

An analytical biochemistry system featuring a substrate with reactants immobilized thereon at fixed, known locations, a holder supporting the substrate and a manipulator for transporting the holder to a fixed sample and to an inspection station. The reactants are binding agents for a target biomolecule in a sample which forms a bound substance having a detectable characteristic. The holder may be a standard pipettor, optionally carried by a robot arm or hand as the manipulator to contact the sample for detection of the presence of target biomolecules within the sample. In one embodiment, the holder is a pipette tip within which the substrate is housed, or it may be a pipette adapter which bears the substrate and fits within the sample wells of a standard microtiter plate. After appropriate incubation, the substrate and holder may be moved from contact with the sample, and the substrate may be exposed to any necessary development steps before being moved by the manipulator to a location for probing, such as by a beam. Probing of the substrate is performed to identify binding or complexing of target biomolecules of the sample with the reactants immobilized on the substrate, and may be accomplished via fluorescence detection, light scattering, autoradiography, or some other detection method.

Analytical biochemistry system with robotically carried bioarray

A system for detecting the presence of a target biomolecule in a sample where there is a robotic arm to move a pipette adaptor to the desired reagent locations to facilitate the detection.

A solid support based hybridization assay is provided which allows for the systematic and reproducible analysis of repeat and tandem repeat oligonucleotide sequences of DNA and RNA by hybridization to a reverse dot blot array comprising strings of such repeats complementary to those found in particular nucleic acid targets (e.g., analyte PCR product). An addressable library (i.e., an indexed set) of complementary repeats is synthesized on a suitable support. Preferably, the support comprises a low fluorescent background support, thereby facilitating the use of non-radioisotopic modes of detection (such as fluorescence or chemiluminescence); particularly suitable in this regard is an aminated polypropylene support or similar material. Preferred arrays permit screening of DNA and RNA samples for complete sets of particular types of nucleotide repeat sequences (e.g., all nucleotide doublet or triplet repeats).

Oligonucleotide repeat arrays

Disclosed herein are surface activated, organic polymers useful for biopolymer synthesis. Most preferably, aminated polypropylene is used for the synthesis of oligonucleotides thereto, and these devices are most preferably utilized for genetic analysis of patient samples.

Surface activated organic polymers useful for location - specific

Disclosed herein are surface activated, organic polymers useful for biopolymer synthesis. Most preferably, aminated biaxially oriented polypropylene is used for the synthesis of oligonucleotides thereto, and these devices are most preferably utilized for genetic analysis of patient samples.

Biopolymer synthesis using surface activated biaxially oriented

Inverse Linkage Oligonucleotides ('ILO') useful in enzymatic process are disclosed. Particularly preferred ILOs are amenable to enzymatic elongation from either, or most preferably, both termini. In a particularly preferred embodiment, each terminus of an ILO has an enzymatically functional 3' group. Accordingly, under appropriate conditions and in the presence of, e.g., dNTPs, enzyme, sample DNA, and ILO comprising a first region complementary to a first region of the sample DNA and a second region complementary to a second, different region of the sample DNA, exponential amplification of the sample DNA can be effectuated.

Inverse linkage oligonucleotides for chemical and enzymatic processes

The present invention makes use of a single detector to monitor several process functions, e.g. reaction efficiency, reagent flow rates, the presence of empty reagent reservoirs, the absence of a chemical reactor column in the system, blockage of flow system, etc., at a single location in the flow system. In accordance with the detection scheme of the present invention, only one detector is required to accomplish the same, if not more, functions as many detectors in the prior art instruments. In the described embodiment, an optical detector is positioned downstream of a chemical reaction chamber. This detector monitors the effluent from the reaction chamber to monitor the reaction efficiency. It also monitors the system functions upstream of the reaction chamber. System flow rate is monitored by detecting the presence of a gas bubble which has been introduced into the system at a known instance. Depletion of reagents in the reservoirs can be detected by monitoring the absence of the reagents at the detector at times when the reagents are expected. The flow system may be periodically diagnosed to check for flow blockage or missing flow component, by monitoring the flow past the detector which corresponds to a predetermined succession of reagents introduced into the system. Any deviation from a predictable succession of changes in the flow monitored by the detector indicates possible blockage of the flow delivery system or missing flow components.

On-line process flow and reaction monitor

An automated method and apparatus for performing biopolymer synthesis on a two-dimensional support surface whereby a two-dimensional matrix or array of biopolymers are obtained on the surface. An applicator in the form of a thick plate having in a surface at least one cavity in the form of an open chamber or channel is used for applying reagents to the surface of a solid phase support material. The applicator is positioned over the solid support material with the surface having the cavity sealed against the material surface. For each cavity, reagents for synthesis are introduced sequentially into one end of the cavity and collected from the other end of the cavity. A one-dimensional array of biopolymers are thus formed on the support material, where each element of the array contains a population of biopolymers having identical sequence. Further synthesis of additional biopolymers is performed by linearly moving or rotating the applicator relative to the support material and carrying out synthesis procedure so that another one-dimensional matrix or array of biopolymers are formed at an offset position to the previous array. At each overlapping region of the two arrays, a cell of biopolymers are formed which each comprises a strand from the first array and a strand from the second array. The result is a two-dimensional array of biopolymers of different sequences at each discrete cell. The arrays of discrete cell containing different biopolymers may be used to conduct hybridization reaction analysis of a biological sample.

Method and apparatus for creating biopolymer arrays on a solid support

The present invention is directed to a synthesis reaction column which can be conveniently implemented in post synthesis procedures. The reaction column is configured to allow easy connection to a syringe and post synthesis reagent container without requiring connection adapters. In one embodiment, the reaction column configured in the form of a cylindrical column containing the solid-phase support and having a narrow bore tube extending at one end. The tube functions as a piercing tip for accessing a septum sealed vial containing post synthesis reagent. In another embodiment, the reaction column is configured in the form of a cylindrical barrel enclosing the solid-phase support and having a threaded mount at one end. To complement the reaction column for post synthesis procedures, a vial having a complementary threaded mount at the opening is used for containing a reagent. This vial is conveniently threaded onto the end of the barrel without adapters. Consequently, post synthesis procedures can be implemented conveniently. Both embodiments may be conveniently connected to the reagent delivery system in an automated instrument for carrying out synthesis procedures, as well as post synthesis procedures.

Synthesis reaction column

The present invention is directed to the implementation of a multi-port rotary valve in an automated chemistry processing instrument which reduces chemical reagent cross contamination and simplifies system design and control. One or more multi-port rotary valves are used in conjunction with isolation valves which are each dedicated for an associated reagent in the system. According to one embodiment of the present invention, the instrument utilizes a multi-port valve which defines several fluid branches each associated with a reagent. The valve has a common inlet and common outlet which are selectively brought into fluid communication with the branches in a controlled sequence. At each branch, there is a two-way three-port isolation valve which controls introduction of an associated reagent into the branch. When a branch is selected by the rotary valve, the reagent introduced into the branch is delivered out of the common outlet by the flow from the common inlet. According to another embodiment of the present invention, the reagents are introduced through isolation valves between two multi-port rotary valves.

Fluid delivery system utilizing multiple port valve

A compact manifold for distribution of fluids (gas or liquid or combination thereof). The manifold has a block having fluid channels provided therethrough between two faces of the block. Against one face, a plate is fastened which swages ferrules between the plate and the block to tightly connect fluid conduits through the plate to the block. On the opposite face of the block, a manifold plenum is formed in a groove between a manifold plate and an o-ring. The o-ring is pressed against the manifold plate by a back plate and both plates are securely fastened onto the block such that the holes in the manifold plate are aligned with the fluid channels in the block. Checkvalves are positioned between the block and the manifold plate to prevent backflow. The above-mentioned components are positioned into their respective places and are secured upon the tightening of the fasteners. The manifold is configured with at least two plenums each having a group of distribution outlets. A checkvalve is provided at each outlet on the plenums. The plenums are connected to a single source in cascade, whereby the plenums are connected via a length of small diameter tubing which serves as a barrier against diffusion of fluid between the plenums. Thus, there are at least two checkvalves and a diffusion barrier tubing in the flow path between two reagent containers.

Growing community of inventors

San Juan Capistrano, CA, United States of America

Peter J Coassin