Biosensor arrays and methods

• US 6,503,452 B1
• Filed: 08/04/2000
• Issued: 01/07/2003
• Est. Priority Date: 11/29/1996
• Status: Expired due to Term

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Kam, Lance, Boxer, Steven
• Primary Examiner(s): Snay, Jeffrey
• Application Number:
  US09/631,906
• Time in Patent Office: 886 Days
• Field of Search: 422/68.1, 422/82.02, 422/82.06, 436/71, 436/525, 436/527, 436/528, 435/287.2, 435/287.1, 427/2.11, 427/2.13
• US Class Current: 506/23
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00367 capillary
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00713 : Electrochemical synthesis
• CPC Class Codes: B01J 2219/00734 : Lipids
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/002 : Electrode membranes
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2405/04 : Phospholipids, i.e. phosphoglycerides
• CPC Class Codes: G01N 33/54373 : involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/544 : the carrier being organic
• CPC Class Codes: G01N 33/92 : involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743

Abstract

A surface detector array device suitable for use with a biosensor is disclosed. The device is formed of a substrate having a surface defining a plurality of distinct bilayer-compatible surface regions separated by one or more bilayer barrier regions. The bilayer-compatible surface regions carry on them, separated by a film of aqueous, supported fluid bilayers. The bilayers may contain selected receptors or biomolecules. A bulk aqueous phase covers the bilayers on the substrate surface.

Claims

1. A method for forming an array of biosensor regions, where each region has a different, known lipid bilayer compositions comprising the steps of:

providing a biosensor array having a plurality of lipid bilayer compatible regions, each compatible region being surrounded by one or more bilayer barrier regions,

providing a gradient forming device loaded with two or more different lipid bilayer compositions, the gradient forming device in fluid communication with a spot forming device for forming spots on a surface,

providing a multi-axis translation table for holding and translating a biosensor array workpiece,

placing a biosensor array workpiece that has a plurality of bilayer compatible regions surrounded by one or more barrier regions, and

forming spots of mixed lipid bilayer compositions resulting from the gradient forming device forming a gradient and translating the table in at least one axis while dispensing such composition mixture as it is formed, thereby dispensing to different, consecutive locations different ratios of each of the lipid bilayer compositions.

2. A method for making gradient biosensor array comprising the steps of:

mixing together first and second different lipid bilayer forming compositions contained from first and second sources by flowing in a substantially laminar flow, two different compositions from two different sources into one mixing chamber that substantially retains the laminar flow character of the two different compositions while flowing through the mixing chamber, where the facing edges of each different composition mix to form a gradient having a first edge and a second edge and further comprising composition combinations of different ratios beginning from the first edge of the gradient that faces the first composition, and ending at the second edge of the gradient that faces the other, second composition, and where the mixing chamber is adapted to dispense the gradient in a substantially laminar flow across the surface of the array, and

where the compositions contained in the gradient are captured and retained upon initial contact by bilayer-compatible regions of the array.