Biocept, Inc.

Puritan-bennett Corporation

Novatrix, Inc.

Jcs Biomedical, Inc.

Novartis Ag

Soonkap Hahn

Henry K Hui

Pavel Tsinberg

Charles S Bankert

Alan M Nelson

Monte Bennett

Roberto Fagnani

John Merritt

Xiaofan Dong

Tim Watanaskul

Pat Roycroft

Carl Frederick Edman

Jhobe Steadman

Jeffrey T Jackson

Tony Pircher

Yehudit Falcovitz-Gerassi

Sandra Matsumoto

Peter M Lloyd

Ron Yamamoto

Zhiyi Xie

Mingying Gai

Wei Pan

Steven T Saville

Yehudit Gerassi

A biochip is formed with a plurality of optically clear hydrogel cells attached to the top surface of a solid substrate in the form of an array. Each of the cells is formed of a hydrogel of polyethylene glycol, polypropylene glycol or a copolymer thereof having reactive isocyanate groups. Binding entities are immobilized in these cells, which entities are effective to selectively hybridize to or sequester a target biomolecule. Different binding entities are immobilized in different cells in an array to create a biochip that can be used to assay for a number of target biomolecules.

Three dimensional format biochips

Methods for detecting in a single assay any one of multiple chromosomal disorders that result from aneuploidy or certain mutations, particularly microdeletions, and kits for use therein. A polymerase chain reaction (PCR) is carried out to amplify eukaryotic genomic DNA using a plurality of primer oligonucleotide pairs wherein one primer of each pair has a detectable label attached 5' thereto. A plurality of the primer pairs are targeted to DNA segments of different chromosomes of interest which are indicative of potential chromosomal disorders, and one pair is targeted for a control gene. The amplified PCR products are purified, and single-stranded DNA having the detectable labels is obtained therefrom and hybridized with spots on a microarray that each contain DNA oligonucleotide probes having nucleotide sequences complementary to a nucleotide sequence of one strand of each segment. The microarray is imaged for presence of labels on its respective spots, and the absence or presence of chromosomal disorders as indicated by one or more of the targeted DNA segments of interest is diagnosed by first comparing the imaging results to the imaging of spots specific to the control gene and then to results obtained from imaging normal DNA.

Detection of chromosomal disorders

A novel hybridization device that improves the efficiency and consistency of microarray hybridization reactions by achieving a greater degree of internal mixing of target solution. The device provides a gasket-and-cover-type chamber wherein solution mixing is achieved by the creation of a multitude of microbubbles. One or more of the inner walls that define the chamber contain bubble-rupturing elements that extend into the chamber and terminate in sharp edges. They are typically located on opposite sides of a rectangular chamber and are pointed in a direction opposing bubble movement. Their interference with larger bubbles causes their breakup into microbubbles which travel separate and distinct paths as a result of external agitation and thereby provide improved solution mixing that results in a uniform distribution of target molecules to the probe molecules bound to the substrate. The sensitivity and consistency of the hybridization reaction is significantly increased.

Microarray hybridization device having bubble-fracturing elements

Microwell biochips () are formed from a thin flat plate () of polymeric material having a plurality of regularly spaced holes () that extend completely therethrough and create microwells. The lower end of each hole is closed by a microporous, hydrophobic, polymeric membrane () laminated to the undersurface of the plate which retains an aqueous test solution in the wells until a vacuum is applied to the undersurface thereof to effect draining of the solution and of any wash solution that might be subsequently added. A spot of polymerizing isocyanate-functional hydrogel is applied generally centrally to the porous membrane surface at the bottom of each well in a manner so as to cover only a minor portion of the surface and out of contact with the well sidewalls, thus leaving substantial surface area through which drainage can be readily effected. Biological capture agents are associated with the polymerizing hydrogel so as to become immobilized as a part thereof.

Microwell biochip

A method for encapsulating biologics within a hydrogel by using an aqueous solution of an isocyanate-functional hydrogel prepolymer which is mixed with an amount of biologics and an aqueous solution containing a dithiol crosslinking agent under physiological pH conditions. An additional bidentate crosslinking agent may be included. The product of such method may be a bioreactor or an assay device having a plurality or different biologics encapsulated at predetermined locations in a substrate. 

Methods and gel compositions for encapsulating living cells and organic molecules

Methods for preparing a biochip are provided herein wherein the biomolecular probe to be used with the biochip is alternatively bound to a hydrogel prepolymer prior to or simultaneously with polymerization of the prepolymer. In particularly preferred embodiments, a polyurethane-based hydrogel prepolymer is derivatized with an organic solvent soluble biomolecule, such as a peptide nucleic acid probe in aprotic, organic solvent. Following derivatization of the prepolymer, an aqueous solution, for example sodium bicarbonate, preferably buffered to a pH of about 7.2 to about 9.5, is added to the derivatized prepolymer solution to initiate polymerization of the hydrogel. Alternatively, a water soluble biomolecule, such as DNA or other oligonucleotide, is prepared in an aqueous solution and added to the polyurethane-based hydrogel prepolymer such that derivatization and polymerization occur, essentially, simultaneously. While the hydrogel is polymerizing, it is microspotted onto a solid substrate, preferably a silanated glass substrate, to which the hydrogel microdroplet becomes covalently bound. Most preferably the hydrogel microdroplets are at least about 30 &mgr;m thick, for example about 50 &mgr;m to about 100 &mgr;m thick. The resulting biochips are particularly useful for gene discovery, gene characterization, functional gene analysis and related studies.

Method of making biochips and the biochips resulting therefrom

The childbirth-assisting device uses an automatically synchronized expandable pneumatic girdle to externally augment the secondary force of labor. The girdle through which the pressure is applied is fitted around the abdomen of the woman. An inflatable bladder within the girdle is inflated to create a downward pressure on the abdomen upon detection of a contraction. An external pressure monitor is used to detect contractions to provide a signal for synchronizing inflation of the girdle. The external pressure monitor includes a solid state force sensor embedded within a pliable housing which is conformable to the patient's abdomen to improve accuracy.

Child birth assisting system

The childbirth-assisting device uses an automatically synchronized expandable pneumatic girdle to externally augment the secondary force of labor. The girdle through which the pressure is applied is fitted around the abdomen of the woman. An inflatable bladder within the girdle is inflated to create a downward pressure on the abdomen upon detection of a contraction. External pressure monitors which detect contractions may be attached directly to the girdle, and the girdle is configured to assure that the bladder is correctly positioned at all times. A member may be provided to prevent multiple uses of a girdle to assure the integrity of the girdle during use.

Child-birth assisting system

The childbirth-assisting device uses an automatically synchronized expandable pneumatic girdle-to externally augment the secondary force of labor. The pneumatic girdle is fitted around the abdomen of the woman and the girdle is inflated to create a downward pressure on the abdomen when a contraction occurs. The synchronization of the girdle's inflation and the contractions is provided by an electronic controller which receives a signal from an intra-uterine monitor indicating a contraction and causes the girdle to inflate at a certain rate until a preset intra-uterine pressure is attained. Once the intra-uterine pressure reaches the pre-set pressure, the girdle pressure is maintained until the offset of the contraction is detected, at which time the girdle is deflated.

The optical fiber pH microsensor includes an optical fiber having a portion of the surface of a light conducting core covered with a layer of a pH sensitive dye material. The dye material is covalently bonded to a polymeric matrix which is in turn covalently bonded to the optical fiber core to prevent leaching of the indicator dye material during extended use. The dye material is crosslinked in situ over the tip of the optical fiber to yield a hydrophilic, ion permeable pH sensor which can be used intravascularly to monitor blood

Optical fiber pH microsensor and method of manufacture

The carbon dioxide sensor includes a CO.sub.2 sensing matrix formed from a hydrophilic, gas permeable, cross-linked polyurethane. The polyurethane matrix is formed from a polyurethane pre-polymer mixture which cross links when mixed with an aqueous carbon dioxide buffer solution. The dye-buffer solution is physically entrapped as a homogeneous dispersion in the polymer matrix. The matrix is applied to the exposed glass core of an optical fiber, which may first be coated with a primer to allow the polyurethane matrix to bond firmly to the tip of the optical fiber. The hydrophilic polymeric matrix is preferably coated with a hydrophobic material to help avoid leaching of the dye from the matrix, and to prevent diffusion of hydronium ions into the sensing matrix. The hydrophobic polymer overcoat may thereafter be cured by heat treatment. The hydrophobic coating may also contain a light reflective material such as TiO.sub.2.

CO.sub.2 sensor using a hydrophilic polyurethane matrix and process for

The optical fiber pH microsensor includes an optical fiber having a portion of the surface of a light conducting core covered with a layer of a pH sensitive dye material. The dye material is covalently bonded to a polymeric matrix which is in turn covalently bonded to the optical fiber core to prevent leaching of the indicator dye material during extended use. The dye material is crosslinked in situ over the tip of the optical fiber to yield a hydrophilic, ion permeable pH sensor which can be used intravascularly to monitor blood pH.

The method of stabilizing a carbon dioxide sensor involves formulation of a bicarbonate buffer solution in the sensor with a bicarbonate ion concentration of from about 100 mM to about 200 mM bicarbonate. The method also involves treatment of the sensor to reduce the instability that may occur in carbon dioxide sensors when such sensors are exposed to either very low or very high carbon dioxide levels for extended periods of time. The sensor is treated by exposing the sensor to an aqueous solution containing at least 2 weight percent carbon dioxide, for from several days to several months. The solution may be prepared in advance, or may be dynamically infused with carbon dioxide to provide the desired carbon dioxide content.

Method of stabilizing a carbon dioxide sensor

The method of stabilizing a carbon dioxide sensor involves treatment of the sensor to reduce the instability that may occur in carbon dioxide sensors when such sensors are exposed to either very low or very high carbon dioxide levels for extended periods of time. This is accomplished by storing the sensor in an aqueous solution containing at least 2 weight percent carbon dioxide, for from several days to several months. The solution may be prepared in advance, or may be dynamically infused with carbon dioxide to provide the desired carbon dioxide content.

Growing community of inventors

San Clemente, CA, United States of America

Soonkap Hahn