Devices and methods utilizing arrays of structures for analyte capture

• US 5,952,173 A
• Filed: 08/21/1997
• Issued: 09/14/1999
• Est. Priority Date: 09/30/1994
• Status: Expired due to Term

• Current Assignee: Abbott Laboratories Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Hansmann, Douglas D., Lowery, Michael G., Shain, Eric B., Oosta, Gary M., Schapira, Thomas G., Loomis, Neil W., Grace, John P.
• Primary Examiner(s): CHIN, CHRISTOPHER L
• Application Number:
  US08/917,012
• Time in Patent Office: 754 Days
• Field of Search: 422/55, 422/56, 422/57, 422/58, 422/101, 435/7.5, 435/7.9, 435/7.93, 435/7.92, 435/7.94, 435/810, 435/187.1, 435/287.2, 435/287.3, 435/288.2, 435/6, 436/514, 436/518, 436/527, 436/531, 436/164, 436/172, 436/804, 436/805, 436/809, 436/810, 156/625.1
• US Class Current: 435/6.11
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0825 Test strips
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: C08G 18/0866 the dispersing or dispersed phase being an aqueous medium
• CPC Class Codes: C08G 18/10 Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
• CPC Class Codes: G01N 33/5304 Reaction vessels, e.g. agglutination plates for solid-phase systems G01N33/543
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54393 Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
• CPC Class Codes: Y10S 435/81 Packaged device or kit
• CPC Class Codes: Y10S 436/804 Radioisotope, e.g. radioimmunoassay
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10S 436/809 Multifield plates or multicontainer arrays
• CPC Class Codes: Y10S 436/81 Tube, bottle, or dipstick

Abstract

The present invention relates to analytical devices for determining the presence or amount of an analyte in a test sample. The analytical devices comprise an inlet port, a vent, a channel, and an array of structures. The structures have immobilized reagent covalently or non-covalently attached to the surface of the structures. The immobilized reagent captures analyte in the test sample where it is detected by a detection system. The present invention also provides methods and reagents for performing assays utilizing the analytical devices of the present invention. The present invention also provides methods of manufacturing the analytical devices of the present invention.

Claims

1. A method for determining the presence or amount of an analyte present in a test sample comprising, in combination, the steps of:

providing an analytical device comprising a base layer, an inlet port, a vent, and an array of structures arising from said base layer,

each of said structures having a surface providing immobilized reagent, said immobilized reagent covalently or non-covalently attached to said surface of each of said structures, said immobilized reagent capable of binding a member selected from the group consisting of;

analyte, analyte-analog, ancillary binding member, and labelled reagent; and

a plurality of channels adjacent to said structures, wherein said test sample containing said analyte, analyte-analog, ancillary binding member, or labeled reagent flows through said channels, said analyte, analyte-analog, ancillary binding member, or labelled reagent diffusing across the width of said channels and binding to said immobilized reagent, wherein the ratio of the height of said structures to the average width of said channels is greater than 2;

1;

adding said test sample to said inlet port, said test sample being transported through said plurality of channels from said inlet port to said array of structures;

said test sample entering said channels, said analyte diffusing through the width of each of said channels wherein said immobilized reagent captures said analyte; and

detecting said analyte through an analyte detection system comprising a specific binding member conjugated to a detectable label, said detectable label capable of producing a signal at a capture site, said detection determining the presence or amount of said analyte present in said test sample.

2. A method of manufacturing analytical devices comprising the steps of:

providing a master having a base layer, an inlet port, a vent, and an array of structures arising from said base layer,

each of said structures having a surface capable of containing immobilized reagent, said immobilized reagent capable of being covalently or non-covalently attached to said surface of each of said structures, said immobilized reagent capable of binding a member selected from the group consisting of;

analyte, analyte-analog, ancillary binding member, and labelled reagent; and

a plurality of channels adjacent to said structures, through which channels a test sample containing said analyte, analyte-analog ancillary binding member, or labeled reagent is capable of flowing, said analyte, analyte-analog, ancillary binding member, or labelled reagent capable of diffusing across the width of said channels to bind to said immobilized reagent, wherein the ratio of the height of said structures to the average width of said channels is greater than 2;

1;

making a tool from said master; and

producing said devices from said master.

3. The method of claim 2 wherein said devices are manufactured by a process selected from the group consisting of:

lasering, LIGA, micromachining, photolithography, reactive ion etching, ion beam milling, embossing, electroforming, electroplating, injection molding, compression molding, casting and reaction injection molding.

4. A method for determining the presence or an amount of an analyte in a test sample comprising, in combination, the steps of:

providing an analytical device comprising a base layer, a test sample inlet port, an vent, and an array of structures arising from said base layer,

each of said structures having a surface providing an immobilized polycationic reagent, said immobilized polycationic reagent covalently or non-covalently attached to said surface of each of said structures, said immobilized reagent capable of capturing a polyanionic material; and

a plurality of channels adjacent to said structures, wherein said test sample containing said analyte, analyte-analog, ancillary binding member, or labeled reagent flows through said channels, said analyte, analyte-analog, ancillary binding member, or labelled reagent diffusing across the width of said channels and binding to said immobilized reagent, wherein the ratio of the height of said structures to the average width of said channels is greater than 2;

1;

providing a polyanionic material coupled to a first specific binding member which is specific for a first epitope of said analyte;

mixing said polyanionic material with said test sample whereby said first specific binding member binds said analyte;

adding said mixture to said inlet port, said mixture being transported through said plurality of channels to said array of structures;

providing an analyte detection system comprising a second specific binding member specific for an epitope of said analyte different from said first epitope, said second specific binding member conjugated to a detectable label, said detectable label capable of producing a signal at a capture site; and

determining the presence or amount of said analyte present in said test sample by said detection system.