Method for quantitative analysis of body fluid constituents

• US 5,087,556 A
• Filed: 05/17/1989
• Issued: 02/11/1992
• Est. Priority Date: 05/17/1989
• Status: Expired due to Fees

• Current Assignee: ActiMed Laboratories, Inc.
• Original Assignee: ActiMed Laboratories, Inc.
• Inventors: Ertinghausen, Gerhard
• Primary Examiner(s): Rosen, Sam
• Assistant Examiner(s): Chin, Christopher L.
• Application Number:
  US07/352,985
• Time in Patent Office: 1,000 Days
• Field of Search: 435/7.9, 435/808, 435/291, 436/514, 436/807, 436/518, 422/56
• US Class Current: 435/7.9
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/028 Graduation
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0825 Test strips
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: C12Q 1/00 Measuring or testing processes involving enzymes, nucleic acids or microorganisms measuring or testing apparatus with condition measuring or sensing means, e.g. colony counters, C12M1/34; Compositions therefor; Processes of preparing such compositions
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/558 using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• CPC Class Codes: Y10S 435/81 Packaged device or kit
• CPC Class Codes: Y10S 435/975 Kit
• CPC Class Codes: Y10S 436/807 Apparatus included in process claim, e.g. physical support structures

Abstract

The invention is a self-contained, chromatic quantitative analyzer that quantitatively detects an analyte in a biological fluid. The invention includes a base having a first open reservoir for receiving the biological fluid. A means for separating solids from the biological fluid is provided in the first open reservoir. A channel is provided which draws, by capillary and/or wicking action, the biological fluid from the first open reservoir to a second open reservoir. The second open reservoir draws the biological fluid from the channel and, when the second open reservoir is full with the biological fluid, the capillary and/or wicking action terminates. A membrane is provided in the channel which is permeable to the biological fluid. There is at least one chromatic chemical indicator immobilized in the membrane in a predetermined concentration. The membrane enables the biological fluid to interact with the chromatic chemical indicator.

Claims

1. A method for quantitatively analyzing a biological fluid for an analyte comprising the following steps:

depositing a biological fluid sample in a first open reservoir of an analytical device, said first open reservoir having means for separating solids from a fluid sample, whereby solids in said biological fluid sample are substantially retained in said first open reservoir;

drawing said biological fluid sample through a channel from said first open reservoir to a second open reservoir to fill said second open reservoir with said biological fluid sample, said second reservoir being configured so as to draw a precise predetermined volume of biological fluid sample through said channel;

said channel including a permeable membrane having at least one reagent specific for the analyte to be determined, said reagent including a chromatic indicator immobilized in said membrane in a predetermined amount to quantify the analyte in said biological fluid, whereby analyte in said biological fluid sample reacts with said reagent to produce a color change in said channel;

said channel being provided with calibration means related to said color change to quantify the amount of analyte present in said biological fluid sample.

2. The method according to claim 1 wherein said reagent is selected form the group consisting of enzymes, labeled antibodies, unlabeled antibodies, antigens, and a dye.

3. The method according to claim 1 wherein said analyte is selected from the group consisting of cholesterol, glucose, HDL cholesterol, triglycerides, hormones, drugs, infectious agents, and antibodies.

4. The method according to claim 2 wherein said chromatic indicator comprises cholesterol esterase, cholesterol oxidase, ascorbic acid oxidase, sodium cholate, a surfactant, peroxidase, 4C1-1-naphthol, and a buffer.

5. The method according to claim 2 wherein said chromatic indicator comprises cholesterol esterase, cholesterol oxidase, ascorbic acid oxidase, sodium cholate, a surfactant, peroxidase, 3,3'"'"',5,5'"'"'-tetramethyl benzidine, and a buffer.

6. The method according to claim 2 wherein said chromatic indicator comprises glucose oxidase, peroxidase, 4C1-1-naphthol and a buffer.

7. The method according to claim 2 wherein said chromatic indicator comprises glucose oxidase, peroxidase, 3,3'"'"',5,5'"'"'-tetramethyl benzidine, and a buffer.

8. The method according to claim 2 wherein said chromatic indicator comprises glycerol kinase, lipase, glycerol phosphate oxidase, ATP, a surfactant, 4C1-1-naphthol and a buffer.

9. The method according to claim 2 wherein said chromatic indicator comprises glycerol kinase, lipase, glycerol phosphate oxidase, ATP, a surfactant, 3,3'"'"',5,5'"'"'-tetramethyl benzidine, and a buffer.

10. The method according to claim 1 wherein said reagent is selected from the group consisting of labeled drugs, labeled hormones, and labeled antibodies.

11. The method according to claim 10 wherein said reagent comprises peroxidase labeled conjugate of theophylline, an antibody against theophylline, urea peroxide, and a buffer.

12. The method according to claim 11 wherein said reagent comprises a labeled antibody, an antigen to the antibody to be analyzed.

13. The method according to claim 11 wherein aid biological fluid sample is whole plasma.

14. In a method for quantitatively analyzing a biological fluid for an analyte by contacting said biological fluid sample with a membrane having immobilized thereon at least one reagent specific for the analyte to be determined, said reagent including a visually observable chromatic indicator, the improvement comprising:

drawing said biological fluid sample from a first open reservoir through a channel including a permeable membrane having a reagent immobilized in said membrane to a second open reservoir wherein said biological fluid sample is substantially completely reacted with the reagent immobilized in the membrane, such that said second reservoir is configured to meter the volume of the biological fluid sample through said channel.