US3733179A - Method and apparatus for the quantitative determination of blood chemicals in blood derivatives - Google Patents
Method and apparatus for the quantitative determination of blood chemicals in blood derivatives Download PDFInfo
- Publication number
- US3733179A US3733179A US00756098A US3733179DA US3733179A US 3733179 A US3733179 A US 3733179A US 00756098 A US00756098 A US 00756098A US 3733179D A US3733179D A US 3733179DA US 3733179 A US3733179 A US 3733179A
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- US
- United States
- Prior art keywords
- blood
- container
- cholesterol
- optical density
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
- G01N33/528—Atypical element structures, e.g. gloves, rods, tampons, toilet paper
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/92—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving lipids, e.g. cholesterol, lipoproteins, or their receptors
Definitions
- the present invention relates to a method and apparatus for the quantitative determination of diagnostically significant chemicals in blood derivatives.
- Abnormally high or low concentrations of certain blood chemicals may signal the onset or presence of many body illnesses.
- abnormally low concentrations of cholesterol may signal a defective intestinal absorption of fats, liver disease, and overfunction of the thyroid gland.
- Increased abnormally high concentrations of cholesterol may foretell coronary thrombosis and may denote hereditary defects in fat metabolism, under-function of the thyroid gland, diabetes, and jaundice due to bile duct obstruction.
- Abnormal concentration of uric acid in blood are indicative of incipient gout and kidney stones.
- the method of the present invention comprises the sequential steps of (1) providing a first container of a solution capable of extracting a blood chemical from a blood derivative to form a component capable of reacting with a test material to form a colored fluid having an optical density dependent upon the concentration of said blood chemical in said blood derivative;
- FIG. 1 is a cross-sectional representation of the preferred apparatus of the present invention as viewed immediately prior to centrifugation;
- FIG. 2 is a cross-section view of the apparatus of FIG. 1 taken along line 22 of FIG. 1;
- FIG. 3 is a perspective exploded View of the apparatus of FIG. 1.
- blood chemical refers to cholesterol and to such other diagnostically significant chemical ingredients of blood as, for example, uric acid, bilirubin, protein, glucose, urea, etc.
- the reactants required for blood chemical analysis may be supplied in premeasured quantities in suitable containers to the laboratory technician who merely adds to one of the containers a sample of a blood derivative, joins the two containers together with the filter means, centrifuges the assembly, and measures the optical density of the resulting colored fluid, obviating the necessity of measuring and manually transferring the various reactants and thus reducing the human error associated with such manipulations.
- the method and apparatus of the present invention are adapted to be used for blood chemicals, the determinations of which may be reduced to the process of (1) preparing a liquid which contains the blood chemical to be analyzed in reactive form; that is, in a form capable of reacting with a test material to form a colored fluid having an optical density dependent upon the concentration of the blood chemical;
- the determination of total cholesterol by the procedure reported in Henry, supra, p. 855 may be carried out by the method of the present invention as follows:
- a measured sample of blood serum containing cholesterol is added to a first compartment, e.g. a glass vial, containing a premeasured amount of ferric chloride/ acetic acid reagent. This reagent precipitates protein and extracts cholesterol and cholesterol esters from the serum.
- a connector member having filter means is attached to the first compartment and this assembly is then attached to a second container, e.g. a second glass vial, containing a premeasured quantity of concentrated sulfuric acid.
- the filter means permits the assembly to be inverted during attachment thereof to the second container, preventing escape of the contents of the first container and avoiding spillage of the sulfuric acid from the second container.
- Centrifugation causes the contents of the first container to filter into the second container, forming two layers which, when subsequently mixed by gentle agitation, form a colored fluid.
- the optical density of the colored fluid is then measured and is correlated with the concentration of total cholesterol by known algebraic or graphic methods.
- a blood derivative containing cholesterol solely in ester form is substituted for the blood sample in the above example.
- a blood derivative may be prepared, for example, by precipitating free cholesterol from a sample of blood serum in an ethanol ether solvent by addition of digitonin, evaporating the solution to dryness, extracting cholesterol esters from the residue with petroleum ether, evaporating the petroleum ether and dissolving the remaining cholesterol esters in acetic acid. This procedure is more fully described in Henry, supra, pp. 857-858.
- Determinations of bilirubin in blood serum by a modification of the Malloy-Evelyn procedure may be carried out by the method of the present invention by adding a measured sample of blood serum containing bilirubin to a first compartment containing a premeasured quantity of a methanol-water-hydrochloric acid solution, attaching thereto the connector member having filter means, attaching this assembly to a second container containing a diazonium salt capable of reacting with bilirubin to form colored azobilirubin, centrifuging to cause the contents of the first compartment to filter into the second compartment to cause formation therein of a colored azobilirubin solution, and correlating the optical density of the colored azobilirubin solution with the concentration of bilirubin in the blood serum sample by known means, as described above.
- the concentration of uric acid in blood serum may be determined by the method of the present invention by adding a blood serum sample to a tungstic acidphosphotungstic acid mixture in the first compartment, attaching this compartment by filter means to a second compartment of aqueous sodium carbonate, centrifuging the assembly to cause the contents of the first compartment to filter into the second compartment to form upon agitation, a colored fluid, and measuring the optical density of the colored fluid, which optical density may be correlated with the concentration of uric acid.
- the container in which the colored fluid is formed by transparent and adapted for use in standard spectrophotometers, as in the apparatus hereinafter described.
- the filter means of the present invention may be of any material which is resistant to the reagents employed in the desired determination; e.g. the filter means must not undergo significant chemical degradation nor significantly adsorb chemicals which pass therethrough during centrifugation.
- the filter means When connected to One container, the filter means must be sufficiently compact to prevent the flow of reagents therethrough under normal gravitational force (e.g., when assemblying the apparatus), and must be sufficiently porous to permit the passage of such reagents therethrough under a force substantially greater than the normal gravitational force (e.g. during centrifugation).
- Filters made from chemically-resistant polymers are useful in the method and apparatus of the present invention. Filters prepared from polyolefin fibers, especially polypropylene fibers, are preferred. It is desirable that such fibers have high surface/volume ratios. Fibers produced by the method described in U.S. Naval Research Laboratory Report No. 111,437, dated Apr. 15, 1954 and entitled Manufacture of Superfine Organic Fibers have been found to be especially useful and are preferred for filters of the present invention. Fibers produced by this method hereinafter are referred to as superfine fibers.
- the filters of the present invention are preferably capable of removing precipitated protein from fluids passing therethrough during centrifugation.
- Protein is precipitated from blood serum, for example, when blood serum is mixed into the ferric chloride-acetic acid reagent used in total" cholesterol determinations. Haziness caused by precipitated protein in the colored fluids obtained by the above-mentioned total cholesterol methods can noticeably but not seriously disturb accuracy.
- Polypropylene fiber filters may be provided which filter out precipitated protein, however, by treating the filters with tap water having an analysis such as that referred to in Example 1 below. By use of such treated filters in the total cholesterol method of the present invention, excellent accuracy and precision may be obtained.
- FIGS. 1-3 An apparatus for practicing the method of the present invention is shown in FIGS. 1-3 as assembled immediately prior to centrifugation.
- a pair of glass vials 10 and 12 are provided containing respectively, a premeasured solution 14 capable of extracting a blood chemical from a blood derivative to form therewith a component capable of reacting with a test material to form a colored fluid, and a pre-measured test material 16 capable of forming with said component a colored fluid having an optical density dependent upon the concentration of the blood chemical in the blood derivative.
- the open ends 18 and 20 of the vials 10 and 12 are provided with threaded outer diameters 22 and 24 respectively.
- the glass vials 10 and 12 containing the solution 14 and the test material 16 are provided with threaded vial caps (not shown) for storage. Prior to centrifugation, as shown in FIG.
- the vials 10 and 12 are connected by a connector member 26, the threaded ends 22 and 24 of the vials 10 and 12 threadingly engaging the threaded inner diameters 28 and 30 respectively of the open ends 32 and 34 of the connector member 26 to provide liquid-tight seals therewith.
- the connector member 26 is provided with an inner surface 35 having at a point 36 along its length a support means 38, such as a perforated transverse diaphragm,
- the filter 40 is air permeable and, when joined to one or both of the vials 10 and 12, is capable of preventing the passage therethrough of either the component formed in vial 10 or the test material 16 under the normal force of gravity and is further capable of permitting passage of the component or the material 16 therethrough under a force substantially greater than the normal force of gravity.
- the method of the present invention may be practiced as follows, the blood chemical to be determined being total cholesteroli
- the protective vial cap is removed from the vial 10 which contains 3.0 ml. of a 0.5% solution of ferric chloride in glacial acetic acid, and 0.020 ml. of blood serum is deposited therein.
- the end 32 of connector member 26, having therein a filter 40, is threaded snugly onto the open end of the vial 10.
- the assembly is inverted and is threaded onto the open end of a vial 12 containing 2.0 ml. of concentrated sulfuric acid.
- the total assembly is then placed in a centrifuge, the vial 10 being nearest the center of rotation thereof, and is centrifuged to cause the contents of the vial 10 to filter into the sulfuric acid.
- the two layers which are formed in the vial 12 are mixed by gentle agitation to form a colored fluid.
- the vial 12 (still connected to the vial 10 by the connector member 26) is placed in a standard spectrophotometer and the optical density (O.D.) is measured and is correlated with the concentration of cholesterol by comparison with a graph of D. versus cholesterol concentration, which graph had been prepared by performing this procedure with standard solutions containing known concentrations of cholesterol.
- EXAMPLE 1 Three acetic acid test solutions containing 100, 200 and 300 mg. of cholesterol per 100 ml. of solution, respectively, were prepared by dissolving known quantities of solid cholesterol (Matheson, Coleman and Bell Co.) in acetic acid. Each solution was tested in the illustrated apparatus as follows:
- test solution 0.020 ml. of test solution was added to 3.0 ml. of glacial acetic acid containing 0.05% (w./v.) of FeCl '6H O in a first threaded glass vial.
- Filter means identical to that illustrated in FIG. 1 was snugly threaded unto the glass vial, which filter means employed a filter pad which was prepared as follows:
- Superfine polypropylene fibers 95% of which were greater than 2.9 in diameter and 5% of which were greater than 17.5,u. in diameter, were formed into a mat which was treated successively with methyl ethyl ketone and with tap water of pH 8.2-8.7, the tap water (city water supply, St. Paul, Minn.) having an analysis essentially the same as that reported in Durfor and Becker, Public Water Supplies of the 100 Largest Cities in the United States, 1962, US. Government Printing Oflice, 1964, p. 222. Filter pads of the desired diameter were then cut from the treated mat.
- the glass vial-filter means assembly was then inverted and threaded onto a second transparent glass vial of 13.25 mm. average inner diameter which contained 2.0 ml. of concentrated sulfurc acid.
- the apparatus was then centrifuged at a speed of 2000 revolutions per minute for 3 minutes in an International Centrifuge Model CL (International Equipment Co.) centrifuge. During centrifugation, the filter pad assumed a position 2.75 inches distant from the axis of rotation of the centrifuge. The force on the filter pad was calculated to be 170 times the normal force of gravity.
- the filtrate which passed through the filter was transparent and formed a separate layer upon the sulfuric acid. The layers were mixed by gentle agitation of the apparatus, during which time the temperature of the resulting solution rose to about 60 C. and a red color developed therein.
- the second glass vial (still attached to the first glass vial by the filter means) was placed in the cuvette well of a Coleman Junion Colorimeter (Coleman Instruments Co.) using a simple adaptor, and the optical density of the colored solution was measured at 560 m as follows:
- EXAMPLES 25 By using the general procedure of Example 1, quantitative determinations of uric acid, protein, urea, and glucose may be obtained. Test parameters for these determinations are provided in Table II.
- a method for the quantitative determination of a blood chemical comprising the sequential steps of (1) providing a first container of solution capable of extracting a blood chemical from a blood derivative to form a component capable of reacting with a test material to form a colored fluid having an optical density dependent upon the concentration of said blood chemical in said blood derivative;
- a method for measuring the concentration of cholesterol in a blood derivative comprising (a) providing a first container of premeasured solution of ferric chloride and acetic acid;
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- Life Sciences & Earth Sciences (AREA)
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- Immunology (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Urology & Nephrology (AREA)
- Analytical Chemistry (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Pathology (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
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Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US75609868A | 1968-08-29 | 1968-08-29 |
Publications (1)
Publication Number | Publication Date |
---|---|
US3733179A true US3733179A (en) | 1973-05-15 |
Family
ID=25042036
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US00756098A Expired - Lifetime US3733179A (en) | 1968-08-29 | 1968-08-29 | Method and apparatus for the quantitative determination of blood chemicals in blood derivatives |
Country Status (5)
Country | Link |
---|---|
US (1) | US3733179A (de) |
BR (1) | BR6911945D0 (de) |
DE (1) | DE1944246A1 (de) |
FR (1) | FR2016590A1 (de) |
NL (1) | NL6912626A (de) |
Cited By (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3884638A (en) * | 1973-08-01 | 1975-05-20 | Damon Corp | Method of determining cholesterol |
US4065358A (en) * | 1975-05-17 | 1977-12-27 | Kabushiki Kaisha Kyoto Daiichi Kagaku | Apparatus for producing reactions in colorimetric cells |
US4196085A (en) * | 1976-06-09 | 1980-04-01 | The United States Of America As Represented By The Department Of Health, Education And Welfare | Dialysis solution handling device |
US4230664A (en) * | 1979-01-23 | 1980-10-28 | Technion Research & Development Foundation Ltd. | Test pack kit for immunoassay |
US4234083A (en) * | 1979-11-13 | 1980-11-18 | Cohen Milton J | Mixing and filtering vial |
US4244916A (en) * | 1977-08-18 | 1981-01-13 | Jean Guigan | Device for conditioning a sample of liquid for analyzing with internal filter |
US4308347A (en) * | 1977-02-18 | 1981-12-29 | Hoffmann-La Roche Inc. | Device for detecting microorganisms |
US4369117A (en) * | 1980-05-12 | 1983-01-18 | American Hospital Supply Corporation | Serum separating method and apparatus |
US4534863A (en) * | 1984-05-22 | 1985-08-13 | Schleicher & Schuell, Inc. | Centrifugal filtering device and filter unit therefor |
US4735782A (en) * | 1986-10-22 | 1988-04-05 | Eli Lilly And Company | Extraction apparatus |
US4968432A (en) * | 1988-05-18 | 1990-11-06 | Cobe Laboratories, Inc. | Treatment of liquid including blood components |
US5057226A (en) * | 1988-05-18 | 1991-10-15 | Cobe Laboratories, Inc. | Treatment of liquid including blood components |
US5208142A (en) * | 1991-11-19 | 1993-05-04 | Miles Inc. | Method for separating erythrocytes from whole blood |
US5234840A (en) * | 1988-03-31 | 1993-08-10 | Porton Cambridge Limited | Assay with backwash |
WO1997001492A1 (en) * | 1995-06-28 | 1997-01-16 | Guild William C | Storing, mixing, and dispensing container |
US20020085270A1 (en) * | 2000-11-27 | 2002-07-04 | Bendett Mark P. | Apparatus and method for integrated photonic devices having add/drop ports and gain |
US20030185514A1 (en) * | 2002-03-29 | 2003-10-02 | Bendett Mark P. | Method and apparatus for tapping a waveguide on a substrate |
US6636678B1 (en) | 1999-01-27 | 2003-10-21 | Teem Photonics, Inc. | Method and apparatus for waveguide optics and devices |
US20030196455A1 (en) * | 2002-04-17 | 2003-10-23 | Mccov Michael A. | Apparatus and method for photonic waveguide fabrication |
US20040208579A1 (en) * | 2002-03-29 | 2004-10-21 | Bendett Mark P. | Compact apparatus and method for integrated photonic devices having folded directional couplers |
US20040234321A1 (en) * | 2001-04-25 | 2004-11-25 | Breidenbach Diane C. | Dual cosmetic container |
US7354768B1 (en) * | 2004-04-28 | 2008-04-08 | Phase Dynamics, Inc. | Volume-differential assay using hydrophilic gel |
US7407625B1 (en) * | 2004-04-28 | 2008-08-05 | Phase Dynamics, Inc. | Volume-differential water assay system using hydrophilic gel |
US20110117673A1 (en) * | 2008-07-16 | 2011-05-19 | Johnson Brandon T | Methods and systems to collect and prepare samples, to implement, initiate and perform assays, and to control and manage fluid flow |
US8021873B2 (en) | 2008-07-16 | 2011-09-20 | Boston Microfluidics | Portable, point-of-care, user-initiated fluidic assay methods and systems |
US20180353952A1 (en) * | 2015-12-11 | 2018-12-13 | Siemens Healthcare Diagnostics Inc. | Specimen container and method for separating serum or plasma from whole blood |
US11090647B2 (en) * | 2017-04-28 | 2021-08-17 | U.S. Environmental Protection Agency | Double bottom test tube kit and method therefore |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3134611A1 (de) * | 1981-09-01 | 1983-03-10 | Boehringer Mannheim Gmbh, 6800 Mannheim | Verfahren zur durchfuehrung analytischer bestimmungen und hierfuer geeignetes mittel |
-
1968
- 1968-08-29 US US00756098A patent/US3733179A/en not_active Expired - Lifetime
-
1969
- 1969-08-19 NL NL6912626A patent/NL6912626A/xx unknown
- 1969-08-28 BR BR211945/69A patent/BR6911945D0/pt unknown
- 1969-08-28 FR FR6929433A patent/FR2016590A1/fr not_active Withdrawn
- 1969-08-28 DE DE19691944246 patent/DE1944246A1/de active Pending
Cited By (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3884638A (en) * | 1973-08-01 | 1975-05-20 | Damon Corp | Method of determining cholesterol |
US4065358A (en) * | 1975-05-17 | 1977-12-27 | Kabushiki Kaisha Kyoto Daiichi Kagaku | Apparatus for producing reactions in colorimetric cells |
US4196085A (en) * | 1976-06-09 | 1980-04-01 | The United States Of America As Represented By The Department Of Health, Education And Welfare | Dialysis solution handling device |
US4308347A (en) * | 1977-02-18 | 1981-12-29 | Hoffmann-La Roche Inc. | Device for detecting microorganisms |
US4244916A (en) * | 1977-08-18 | 1981-01-13 | Jean Guigan | Device for conditioning a sample of liquid for analyzing with internal filter |
US4230664A (en) * | 1979-01-23 | 1980-10-28 | Technion Research & Development Foundation Ltd. | Test pack kit for immunoassay |
US4234083A (en) * | 1979-11-13 | 1980-11-18 | Cohen Milton J | Mixing and filtering vial |
US4369117A (en) * | 1980-05-12 | 1983-01-18 | American Hospital Supply Corporation | Serum separating method and apparatus |
US4534863A (en) * | 1984-05-22 | 1985-08-13 | Schleicher & Schuell, Inc. | Centrifugal filtering device and filter unit therefor |
US4735782A (en) * | 1986-10-22 | 1988-04-05 | Eli Lilly And Company | Extraction apparatus |
US5234840A (en) * | 1988-03-31 | 1993-08-10 | Porton Cambridge Limited | Assay with backwash |
US4968432A (en) * | 1988-05-18 | 1990-11-06 | Cobe Laboratories, Inc. | Treatment of liquid including blood components |
US5057226A (en) * | 1988-05-18 | 1991-10-15 | Cobe Laboratories, Inc. | Treatment of liquid including blood components |
US5208142A (en) * | 1991-11-19 | 1993-05-04 | Miles Inc. | Method for separating erythrocytes from whole blood |
WO1997001492A1 (en) * | 1995-06-28 | 1997-01-16 | Guild William C | Storing, mixing, and dispensing container |
US5634714A (en) * | 1995-06-28 | 1997-06-03 | Guild; William | Fluid mixing and dispensing system for the rapid mixing of a prestored substance with a fluid and the dispensing thereof |
US5863126A (en) * | 1995-06-28 | 1999-01-26 | Guild; William | Fluid mixing and dispensing system for the rapid mixing of a prestored substance with a fluid and the dispensing thereof |
US6970494B1 (en) | 1999-01-27 | 2005-11-29 | Teem Photonics, S.A. | Rare-earth doped phosphate-glass lasers and associated methods |
US6636678B1 (en) | 1999-01-27 | 2003-10-21 | Teem Photonics, Inc. | Method and apparatus for waveguide optics and devices |
US6690873B2 (en) | 1999-01-27 | 2004-02-10 | Teem Photonics | Method and apparatus for waveguide optics and devices |
US8545120B2 (en) | 2000-02-29 | 2013-10-01 | Diane C. Breidenbach | Dual cosmetic container |
US6954564B2 (en) | 2000-11-27 | 2005-10-11 | Teem Photonics | Apparatus and method for integrated photonic devices having high-performance waveguides and multicompositional substrates |
US20020085270A1 (en) * | 2000-11-27 | 2002-07-04 | Bendett Mark P. | Apparatus and method for integrated photonic devices having add/drop ports and gain |
US6493476B2 (en) | 2000-11-27 | 2002-12-10 | Teem Photonics | Apparatus and method for integrated photonic devices having gain and wavelength-selectivity |
US20040234321A1 (en) * | 2001-04-25 | 2004-11-25 | Breidenbach Diane C. | Dual cosmetic container |
US20030185514A1 (en) * | 2002-03-29 | 2003-10-02 | Bendett Mark P. | Method and apparatus for tapping a waveguide on a substrate |
US20040208579A1 (en) * | 2002-03-29 | 2004-10-21 | Bendett Mark P. | Compact apparatus and method for integrated photonic devices having folded directional couplers |
US6813405B1 (en) | 2002-03-29 | 2004-11-02 | Teem Photonics | Compact apparatus and method for integrated photonic devices having folded directional couplers |
US20030196455A1 (en) * | 2002-04-17 | 2003-10-23 | Mccov Michael A. | Apparatus and method for photonic waveguide fabrication |
US7354768B1 (en) * | 2004-04-28 | 2008-04-08 | Phase Dynamics, Inc. | Volume-differential assay using hydrophilic gel |
US7407625B1 (en) * | 2004-04-28 | 2008-08-05 | Phase Dynamics, Inc. | Volume-differential water assay system using hydrophilic gel |
US20110117673A1 (en) * | 2008-07-16 | 2011-05-19 | Johnson Brandon T | Methods and systems to collect and prepare samples, to implement, initiate and perform assays, and to control and manage fluid flow |
US8021873B2 (en) | 2008-07-16 | 2011-09-20 | Boston Microfluidics | Portable, point-of-care, user-initiated fluidic assay methods and systems |
US8846310B2 (en) | 2008-07-16 | 2014-09-30 | Boston Microfluidics | Methods of preparing and operating portable, point-of-care, user-initiated fluidic assay systems |
US20180353952A1 (en) * | 2015-12-11 | 2018-12-13 | Siemens Healthcare Diagnostics Inc. | Specimen container and method for separating serum or plasma from whole blood |
US10870110B2 (en) * | 2015-12-11 | 2020-12-22 | Babson Diagnostics, Inc. | Specimen container and centrifugation method for separating serum or plasma from whole blood therewith |
US11697114B2 (en) * | 2015-12-11 | 2023-07-11 | Babson Diagnostics, Inc. | Centrifugation method separating serum or plasma from whole blood using a specimen container having a cap to retain blood cells |
US11090647B2 (en) * | 2017-04-28 | 2021-08-17 | U.S. Environmental Protection Agency | Double bottom test tube kit and method therefore |
Also Published As
Publication number | Publication date |
---|---|
BR6911945D0 (pt) | 1973-03-13 |
FR2016590A1 (de) | 1970-05-08 |
NL6912626A (de) | 1970-03-03 |
DE1944246A1 (de) | 1970-03-05 |
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