Capillary flow device

• US 5,300,779 A
• Filed: 08/18/1992
• Issued: 04/05/1994
• Est. Priority Date: 08/05/1985
• Status: Expired due to Term

• Current Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Original Assignee: Biotrack, Inc. (Novartis Ag)
• Inventors: Gibbons, Ian, Ostoich, Vladimir E., Allen, Jimmy D., Hillman, Robert S., Cobb, Michael E., Winfrey, Laura J.
• Primary Examiner(s): Dzierzynski, Paul M.
• Assistant Examiner(s): HANIG, RICHARD E
• Application Number:
  US07/931,719
• Time in Patent Office: 595 Days
• Field of Search: 250/341, 250/343, 436/69, 356/28, 73/55
• US Class Current: 250/341.1
• CPC Class Codes: B01F 21/00 Dissolving separating by dissolving B01D; dissolving to effect cooling F25D5/00
• CPC Class Codes: B01F 2101/23 Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
• CPC Class Codes: B01F 23/56 by introducing solids in liquids, e.g. dispersing or dissolving
• CPC Class Codes: B01F 25/4316 the baffles being flat pieces of material, e.g. intermeshing, fixed to the wall or fixed on a central rod
• CPC Class Codes: B01F 25/433 Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
• CPC Class Codes: B01F 25/4338 Mixers with a succession of converging-diverging cross-sections, i.e. undulating cross-section
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 35/7172 using capillary forces
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• 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 2400/0694 vents used to stop and induce flow, backpressure valves
• 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 3/502723 characterised by venting arrangements
• CPC Class Codes: B29C 45/00 Injection moulding, i.e. forcing the required volume of moulding material through a nozzle into a closed mould; Apparatus therefor injection blow-moulding B29C49/06
• CPC Class Codes: B29C 59/16 by wave energy or particle radiation , e.g. infrared heating B29C59/007 takes precedence
• CPC Class Codes: B29C 65/08 : using ultrasonic vibrations non-plastics element to plastics elements B29C65/645
• CPC Class Codes: B29C 65/4895 : Solvent bonding, i.e. the surfaces of the parts to be joined being treated with solvents, swelling or softening agents, without adhesives
• CPC Class Codes: B29C 66/30223 : said melt initiators being rib-like
• CPC Class Codes: B29C 66/54 : Joining several hollow-preforms, e.g. half-shells, to form hollow articles, e.g. for making balls, containers; Joining several hollow-preforms, e.g. half-cylinders, to form tubular articles
• CPC Class Codes: B29C 66/71 : characterised by the composition of the plastics material of the parts to be joined welding bar compositions B29C65/125
• CPC Class Codes: B29C 66/73921 : characterised by the materials of both parts being thermoplastics
• CPC Class Codes: B29C 66/9513 : characterised by specific vibration frequency values or ranges
• CPC Class Codes: B29K 2025/06 : PS, i.e. polystyrene
• CPC Class Codes: B29K 2025/08 : Copolymers of styrene, e.g. AS or SAN, i.e. acrylonitrile styrene B29K2055/02 takes precedence
• CPC Class Codes: B29K 2027/06 : PVC, i.e. polyvinylchloride
• CPC Class Codes: B29K 2055/02 : ABS polymers, i.e. acrylonitrile-butadiene-styrene polymers
• CPC Class Codes: B29K 2067/003 : PET, i.e. poylethylene terephthalate
• CPC Class Codes: B29K 2069/00 : Use of PC, i.e. polycarbonates or derivatives thereof, as moulding material
• CPC Class Codes: B29L 2031/756 : Microarticles, nanoarticles
• CPC Class Codes: G01N 2015/0092 : Monitoring flocculation or agglomeration
• CPC Class Codes: G01N 2015/1016 : Particle flow simulating, e.g. liquid crystal cell
• CPC Class Codes: G01N 2021/0346 : Capillary cells; Microcells
• CPC Class Codes: G01N 2035/00514 : Stationary mixing elements
• CPC Class Codes: G01N 21/47 : Scattering, i.e. diffuse reflection G01N21/25, G01N21/41 take precedence G01N21/55 takes precedence
• CPC Class Codes: G01N 21/49 : within a body or fluid
• CPC Class Codes: G01N 21/82 : producing a precipitate or turbidity
• CPC Class Codes: G01N 33/4905 : Determining clotting time of blood by chemical methods G01N33/86, C12Q1/54
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/86 : involving blood coagulating time or factors, or their receptors

Abstract

Novel methods and devices are provided involving at least one chamber, at least one capillary, and at least one reagent involved in a system providing for a detectable signal. As appropriate, the devices provide for measuring a sample, mixing the sample with reagents, defining a flow path, and reading the result. Of particular interest is the use of combinations of specific binding pair members which result in agglutination information, where the resulting agglutination particles may provide for changes in flow rate, light patterns of a flowing medium, or light absorption or scattering. A fabrication technique particularly suited for forming internal chambers in plastic devices is also described along with various control devices for use with the basic device.

Claims

1. A method for carrying out an assay that relies on measurement of coagulation time of a blood sample to determine presence or amount of an analyte in or property of said sample, which comprises:

a. selecting an enclosed capillary device for use in said assay, said device comprising a housing with a capillary passageway in said housing, said capillary passageway terminating at an inlet port at one end of said passageway and a vent at another end of said passageway, said housing further being adapted to fit into an electronic monitoring device that carries out said measurement, said passageway further containing a measured amount of dry reagent on a surface of said capillary pathway that induces clotting of said blood sample;

b. inserting said capillary device into said monitor;

c. applying said sample to said inlet port of said device, either before or after said capillary device is inserted into said monitor;

d. determining a time of coagulation of said sample using said monitor, wherein said monitor detects coagulation of said sample by detecting interaction of light with particles in said capillary passageway; and

e. relating said time to said presence or amount of said analyte in or property of said sample.

2. The method of claim 1, wherein said sample is whole blood or blood from which red blood cells have been removed.

3. The method of claim 1, wherein said reagent contains one or more components of a natural blood clotting mechanism.

4. The method of claim 3, wherein said reagent comprises thromboplastin.

5. A method for performing a prothrombin time assay on a blood sample which comprises:

a. adding said sample to an inlet port of an analytical device containing a capillary passageway used in a horizontal orientation for performing a prothrombin time assay on a blood sample, which comprises;

i. a housing;

ii. an inlet port in said housing;

iii. a reaction chamber enclosed in said housing;

iv. a capillary unit for transmitting, via capillary action, said sample from said inlet port to said reaction chamber, said inlet port, capillary unit, and reaction chamber together forming at least part of a horizontal capillary passageway when said housing is in its normal operating position;

v. a measured amount of a dry reagent in said reaction chamber, wherein said reagent induces clotting of said sample; and

vi. a vent for gases in said housing, said vent communicating with said reaction chamber to provide for exit of gases when sample enters said capillary passageway;

b. permitting said sample to flow via capillary action from said inlet port through the capillary unit of said device into the reaction chamber; and

c. detecting a change, if any, in viscosity of said sample by detecting interaction of light with particles in said capillary passageway as said sample reacts with the reagent in said capillary passageway, said change in viscosity occurring as a result of clotting of said sample.

6. An analytical system for performing a prothrombin time assay on a blood sample, which comprises:

a. an electronic monitor comprising;

i. means for emitting light;

ii. means for detecting interaction of said light with particles in a fluid;

iii. means for holding a capillary device containing a sample to be analyzed in a horizontal position so that said light interacts with said sample;

b. a capillary device adapted to fit into said monitor and be retained by said means for holding, said capillary device comprising;

i. a housing;

ii. an inlet port in said housing;

iii. a reaction chamber enclosed in said housing;

iv. a capillary for transmitting, via capillary action, said sample from said inlet port to said reaction chamber, wherein said inlet port, capillary, and reaction chamber together form at least part of a horizontal capillary passageway when said housing is in its normal operating position;

v. a dry reagent in said reaction chamber, wherein said reagent induces clotting of said sample; and

vi. a vent for gases in said housing, said vent communicating with said reaction chamber to provide for exit of gases when sample enters said capillary passageway.

7. The system of claim 6, wherein said monitor detects a change in interaction of light with particles from said sample or said reagent when said sample coagulates.

8. The system of claim 7, wherein said change is cessation of motion of said particles.

9. The system of claim 8, wherein said reagent contains one or more components of a natural blood clotting mechanism.

10. The system of claim 7, wherein said particles are red blood cells.

11. The system of claim 7, wherein said particles are metallic.

12. The system of claim 11, wherein said interaction of light is transmission, absorption, or scatter of light as light passes through said sample.

13. The system of claim 8, wherein said monitor detects when sample is applied to said capillary device and when said motion ceases.