Chemical apparatus and process disinfecting – deodorizing – preser – Analyzer – structured indicator – or manipulative laboratory... – Sample mechanical transport means in or for automated...
Patent
1994-06-20
1997-09-23
Pyon, Harold
Chemical apparatus and process disinfecting, deodorizing, preser
Analyzer, structured indicator, or manipulative laboratory...
Sample mechanical transport means in or for automated...
422 67, 422 8209, 436 43, 436 50, 436164, 356414, 356418, G01N 2164, G01J 342
Patent
active
056701136
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
This invention relates to methods and apparatus for assaying biological samples to which a reagent is added and particularly, to computer-controlled methods and apparatus for such assaying.
Assaying processes are well known in which a reagent is added to a sample, and measurements of the sample and reagent are made to identify sample attributes stimulated by the reagent. For example, one such assay process concerns determining in a chromogenic assay the amount of an enzyme present in a biological sample or solution. Such assays are based on the development of a colored product in the reaction solution. The reaction develops as the enzyme catalyzes the conversion of a colorless chromogenic substrate to a colored product.
In such assays it is often required to determine the enzymatic activity of a number of samples and at one or more dilutions. Enzymatic reactions characteristically proceed at a constant rate provided substrate is present in a large molar excess, i.e., the concentration of substrate does not limit the rate of reaction. With such kinetic parameters, it may be convenient to set up several reaction solutions separately in the wells of a microtiter plate, for example, carrying out each reaction for a predetermined constant amount of time and stopping the reactions while they are still in a linear range of the assay. With each of the so-called end-point reactions stopped, no further color development occurs and the reaction solutions in the separate wells of the microtiter may be read at any convenient time.
Plate readers which automatically read the intensity of a colored solution in an array of wells are known. Also, plate readers which measure the amount of fluorescence in a well of a microtiter plate are known.
Classically, assays of the above-described type are performed by a laboratory worker who prepares the sample, manually adds a precise amount of reagent to the sample, and then measures the result at one or more preselected times after the reagent addition. This classical approach is very time consuming for the laboratory worker and additionally, when the stimulated reaction yields time-varying results, precise timing on the part of the laboratory worker is required. If such timing is not properly performed, erroneous assay results may occur.
One known laboratory device for partially automating tests to detect fluorescence as a measurable attribute is the Fluoroskan II. The Fluoroskan II includes a plate carrier system to hold a sample-containing plate having a plurality, e.g., 96, of sample-containing wells. A laboratory worker places a portion of the sample into some or all of the wells of the plate, and then adds reagent to the sample-containing wells. The plate is then placed in the Fluoroskan II which automatically measures the fluorescence of the samples in the wells. Although this known apparatus has proven valuable for fluorescence testing, some problems, which were also inherent in the classical testing, still remain. For example, the addition of reagent by the laboratory worker still requires a large amount of laboratory work time. Also, since the measured results of reactions may be dependent on the time elapsed since reagent addition, the first samples to receive reagent may have progressed past the point of meaningful reaction results by the time all samples have received reagent. Further, some reactions complete so quickly that it is nearly impossible to add reagent to a sample, move the sample plate to the assay apparatus and move the sample to a measurement position before the reaction has run to completion.
A need exists to rapidly screen compounds to determine their effect on a protein's function such as cell surface proteins like ion channels and receptors, the regulation of which surface proteins can be important in treating certain disease states. Such cell surface proteins permit intracellular transduction of extracellular signals. These cell surface proteins, by transmitting information regarding extracellular stimuli via specific intr
REFERENCES:
patent: 3772154 (1973-11-01), Isenberg et al.
patent: 4234540 (1980-11-01), Ginsberg et al.
patent: 4681742 (1987-07-01), Johnson et al.
patent: 4908186 (1990-03-01), Sakamaki
patent: 5096807 (1992-03-01), Leaback
patent: 5104621 (1992-04-01), Pfost et al.
patent: 5108703 (1992-04-01), Pfost et al.
patent: 5125748 (1992-06-01), Bjornson et al.
patent: 5355215 (1994-10-01), Schroeder et al.
Wall et al. (1991) "Rapid Functional Assay for Multidrug Resistance in Human Tumor cell Lines using the Fluorescent Indictaro Fluo-3", J. Natl. Cancer Inst. 83:206-207.
van den Pol et al. (1990) "Glutamate, the Dominant-Excitatory transmitter in Neuroendocrine Regulation" Science 250:1276-1278.
Rijkers et al. (1990) "Improved Method for Measuring Intracellular Ca.sup.++ with Fluo-3" Cytometry 11:923-927.
Williams et al. (1992) "Structure and Functional Expression of an .omega.-Conotoxin-Sensitive Human N-Type Calcium Channel", Science 257:389-39.
Williams, et al. (1992) "Structure and functional expression of .alpha..sub.1, .alpha..sub.2 and .beta. subunits of a novel human neuronal calcium channel subtype," Neuron, 8:71-84.
Minta et al., "Fluorescent indicators for cytosolic calcium based on rhodamine and fluorescein chromophores," J. Biol. Chem., 264(14):8171-8178 (1989).
Kao et al., "Photochemically generated cytosolic calcium pulses and their detection by Fluo-3", J. Biol. Chem., 264(14):8179-8184 (1989).
Meyer et al., "Kinetics of calcium channel opening by inositol 1,4,5,-Triphosphate," Biochemistry, 29:32-37 (1990).
Cornell-Bell et al., "Glutamate induces calcium waves in cultured astrocytes: long-range glial signalling," Science, 247:470-473 (1990).
Brooker et al., "Calcium wave evoked by activation of endogenous or exogenously expressed receptors in Xenopus oocytes," Proc. Natl. Acad. Sci. USA, 87:2813-2817 (1990).
Jensen et al., "Fluorescence measurement of changes in intracellular calcium induced by excitatory amino acids in culture cortical astrocytes," J., of Neuroscience, 10(4):1165-1175 (1990).
Gutierrez et al., "Dihydropyridine-sensitive calcium channels from skeletal muscle," J. of Biol. Chem., 266(25):16387-16394 (1991).
Miller, "The revenge of the kainate receptor," TINS, 14(11):447-479 (1991).
ICN Biomedicals, Inc., "DIGIFLEX-TP.TM. Automatic Pipette (Model 33020), Operating and Service Manual" (1986).
Flow Laboratories "Fluoroskan II, Operating Instructions" (1988).
Bujo et al., "Different sensitivities to agonist of muscarinic acetylcholine receptor subtypes", FEBS Lttrs. 240:95-100 (1988).
Akong Michael Anthony
Brust Paul
Harpold Michael Miller
Velicelebi Gonul
Pyon Harold
Seidman Stephanie L.
SIBIA Neurosciences Inc.
LandOfFree
Automated analysis equipment and assay method for detecting cell does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Automated analysis equipment and assay method for detecting cell, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Automated analysis equipment and assay method for detecting cell will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1937786