E Y Laboratories, Inc.

Other

Albert E Chu

Peter K Chun

John L Lawless

Lian Tao

Siu Chin Yeung

A self-contained system uses light reflectivity to examine intensity of a dyed spot on a device membrane surrounded by background area to discern information about the specimen that produced the spot. In a preferred embodiment, a master clock alternatively drives one LED focussed upon the spot center, and then drives two LEDS focused on the background area. Light reflected from the spot and background is detected by preferably two photodetectors ('PDs') spaced-apart a multiple of 90&#xb0; azimuthal.

Reflectometry system with compensation for specimen holder topography and with lock-rejection of system noise

A device and method for filtering a biologically derived sample and for mixing the sample with a reagent, comprising a fluid container defining a reservoir compartment and including a container outlet, a filter and a fluid flow-through matrix disposed in a flow path between the reservoir compartment and the container outlet. Water-soluble, dried reagent is retained on the matrix. Means is provided for urging sample in an aqueous liquid in the reservoir compartment through the filter and matrix and out the container outlet. Pressure is applied to the sample in an aqueous liquid in the reservoir compartment to cause the sample to flow in liquid through the filter and matrix and out of the container for analysis.

Reagent delivery device and method of use

A self-contained system uses light reflectivity to examine intensity of a dyed spot on a device membrane surrounded by background area to discern information about the specimen that produced the spot. In a preferred embodiment, a master clock alternatively drives one LED focussed upon the spot center, and then drives two LEDS focused on the background area. Light reflected from the spot and background is detected by preferably two photodetectors (&ldquo;PDs&rdquo;) spaced-apart a multiple of 90&deg; azimuthal, a configuration discovered to minimize the effects of uneven membrane topography upon light intensity measurements. The PD outputs are average-summed together and are input to a phase lock-in amplifier system that enhances detected signal/noise by measuring signal voltage without producing noise. The lock-in system simultaneously positively and negatively amplifies the average-summed PD outputs, which amplified signal is then switched in synchronism with the LED drive signals. Only in-phase signals occurring during the active LED drive signal portion are sampled, and signal components present in the average-summed together PD output are essentially doubled in effective amplitude, thereby enhancing signal to noise ratios. The output of the switch is lowpass filtered to recover a noise-free DC level proportional to detected light intensity. A readout of the DC level provides an accurate measurement of the spot intensity.

An analytical device comprising a surfactant-treated porous reaction membrane having an exposed sample-contacting surface and at least one receptor area located in a limited region of the exposed sample-contacting surface. The limited region has a higher concentration of surfactant than areas of the sample-contacting surface that are peripheral to the limited region. To make the device, a surfactant-containing solution comprising at least 0.2% surfactant is added to the reaction membrane and allowed to dry. Then, a receptor reagent is added to a limited region of the reaction membrane. In the assay, the surfactant causes the liquid sample to flow faster through the portion(s) of the reaction membrane where receptor molecules are located.

Analytical assay device and methods using surfactant treated membranes to increase assay sensitivity

A method and system for automatic analysis of a testing substrate for an analyte in a liquid sample. The sample is applied to a testing substrate having an immobilized thereon, in a limited region of the testing substrate, a receptor capable of binding to the analyte. A labeled reagent, capable of binding to the analyte, is added to the testing substrate. If the analyte is present, a color is generated at the area of the testing substrate where the receptor is immobilized. The testing substrate is then illuminated and, using electronic equipment a digital image of the testing substrate is acquired and automatically scanned to locate an area of the testing substrate having the highest color density and generating a first measurement of color density. Next, an area peripheral to the area of highest color density is located and a second measurement of color density is generated. This peripheral area represents tho background density of the substrate, which can be considered to be the background &ldquo;noise&rdquo;. The presence or absence of the analyte in the liquid sample is calculated by adjusting the first measurement with said second measurement in accordance with a predefined mathematical function.

Optical specimen analysis system and method

An analytical device is provided. The device comprises a liquid-impervious top support layer that defines a rim around an open port. A porous reaction membrane having an upper surface and a lower surface is proximal to the top support layer, such that a portion of the reaction membrane upper surface and rim define a sample receiving well. The reaction membrane upper surface is sealed to the lower surface of the top support layer by water-insoluble adhesive so as to form a liquid-impervious seal therebetween. An absorbent body is proximal to and in liquid communication with the lower surface of the reaction membrane. The analytical device may further comprise a liquid-impervious bottom support layer which is attached to the lower surface of the absorbent body. The device can be used in immunoassays for the detection of a bindable substance in a liquid sample containing the target substance.

Analytical device for membrane-based assays

A method and system for automatically analyzing the presence of an analyte in a liquid specimen of biological origin are described. The liquid specimen is added to a testing substrate that has a receptor immobilized on a portion of its surface. If analyte is present in the specimen, it will specifically bind to the receptor. A labeled reagent is added to the testing substrate which will bind to the analyte, if present, and generate a color on the testing substrate. The testing substrate is then illuminated and, using electronic equipment, a digital image of its surface is acquired and automatically scanned to locate an area that has the highest color density, which corresponds to the presence of labeled reagent. A measurement of color density, corresponding to pixels per unit area, is generated. An area peripheral to the area of highest color density, which represents background density, is also located and a measured. The presence or absence of analyte in the liquid sample is determined by adjusting the measurement of labeled reagent with the background density measurement in accordance with a predefined mathematical function. In some cases, the result of the test will be interpreted as a binary, positive/negative result according to whether the measurement taken is above or below a given threshold. In other cases, a continuous range of values may be generated from different samples that correspond to the concentration of the analyte present in each tested sample.

An apparatus is provided for use in assays for the detection of a bindable target substance in a liquid sample. The apparatus comprises an elongate reaction membrane strip which is porous and liquid-permeable, the upper surface of the membrane strip having receptors thereon capable of binding to the target substance; an absorbent material located adjacent to the lower surface of the reaction membrane strip; and a container means for the reaction membrane strip and absorbent material, including a top wall defining a fluid port in the form of an elongate slot adjacent the membrane strip and including a fluid seal means disposed at the periphery of the fluid port defining a seal between the container top wall and reaction membrane strip. In one embodiment, the receptors on the membrane strip correspond to Western blot proteins. An assay for the detection of bindable target antibody in a liquid sample employing the apparatus is also described.

Elongated membrane flow-through diagnostic device and method

Immunoassay devices and methods that employ non-antibody control substances are disclosed. A non-antibody substance, such as Protein A, that specifically binds to the Fc portion of IgG is used to determine whether patient sample is properly added to the device during the assay procedure.

Immunoassay device having an internal control of protein A and methods

A specimen containing N. lactamica, N. meningitidis, N. gonorrhoeae or B. catarrhalis is incubated simultaneously with a first substrate for beta-galactosidase and a second substrate for gamma-glutamyl aminopeptidase to form reaction products with one or the other Neisseriae which yields a detectible first or second signal distinct from each other depending upon the presence of the enzyme. Signals may comprise distinct colors which emit either in the absence or presence of diazo dye coupler. A third substrate specific for prolyliminopeptidase in N. gonorrhoeae may be added to form a detectible third signal of the same type. The third substrate may be incubated simultaneously with the first two substrates or later. The absence of all of the first three signals is a positive indication that the specimen contains B. catarrhalis. Also, a diagnostic test kit for performing the above tests with or without lectin or antibody for agglutination based upon specific recognition.

Neisseria detection system

Am improved device and method for analyte assay in liquid samples, wherein a porous membrane with an immobilized receptor which is capable of directly or indirectly binding to the analyte is separated from a body of absorbent material capable of absorbing the liquid sample by a septum capable of substantially separating the porous membrane from the absorbent body while substantially directing the flow of the liquid sample from the porous membrane to the absorbent body.

Directed flow diagnostic device and method

A lectin is covalently bonded to an immunological conjugate such as an antibody-antigen or its equivalent. Then, the lectin-conjugate is isolated from the reaction product mixture by one of a number of alternative techniques involving one or more of the following types of reaction; (1) reversible reaction of the lectin with an insolubilized sugar to isolate lectin from the remainder of the mixture, (2) reaction of one immunological component (e.g., antibody) bonded to the lectin with an insolubilized corresponding component (e.g., antigen) to separate the antibody components from the remainder of the reaction mixture, and (3) filtration of the reaction components to separate on the basis of product molecular weight, size and/or shape of the components.

Soluble immunoassay reagent comprising lectin covalently bonded to

Method for forming an isolated lectin-immunological conjugate

A method for the determination of one or more components of an immunological conjugate, e.g., antigens, of a fluid sample in a competitive or sandwich technique in which the conjugate is labelled and separated from its reactive mixture by reversible attachment to a solid surface. In a preferred embodiment, the solid surface comprises insolubilized sugar which reversibly bonds to a lectin covalently bonded to one member of the conjugate. After separation of such solid surface from the remainder of the reaction mixture, the insolubilized sugar-lectin bond is broken by contact with a sugar solution which displaces the labelled lectin compound. The immunological components including label and lectin may be preincubated in a homogeneous solution prior to reversible attachment to the sugar solid surface. For a competitive system, a sample containing antigen is incubated with a known quantity of labelled antigen and lectin-bound antibody. In the sandwich technique, the sample antigen is incubated with lectin-bound antibody and further with labelled antibody and this reaction mixture is contacted with insolubilized sugar. Either the competitive or sandwich technique are adaptable to a sequential flowthrough system with sufficient residence time to eliminate the preliminary incubation steps.

Growing community of inventors

Hillsborough, CA, United States of America

Albert E Chu